December 27-28, 2011 The 1 Annual Meeting Tanta University

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st
The 1 Annual Meeting
The Middle-Eastern Association for Cancer Research
December 27-28, 2011
Tanta University
Egypt
1
The 1st Annual Meeting of the Middle-Eastern
Association for Cancer Research (MEACR)
“Cancer Research from Bench to Clinic”
‫اﻟﻤﺆﺗﻤﺮ اﻟﺴﻨﻮى اﻷول ﻟﻼﺗﺤﺎد اﻟﺸﺮق اﻷوﺳﻄﻰ ﻷﺑﺤﺎث اﻟﺴﺮطﺎن‬
”‫“اﻟﺠﺪﯾﺪ ﻓﻰ أﺑﺤﺎث اﻟﺴﺮطﺎن ﻣﻦ اﻟﺒﺤﺚ إﻟﻰ اﻟﺘﻄﺒﯿﻖ اﻟﺴﺮﯾﺮى‬
Tanta University, Egypt (December 27 – 28, 2011)
ORGANIZED BY
TANTA UNIVERSITY
MEACR
UNDER THE PATRONAGE OF
MINISTER OF HIGHER EDUCATION
PROF. DR. HUSSAIN KHALID
VICE-PRESIDENT OF POSTGRADUATE STUDIES
PROF. IBRHAIM A. SALEM
2
HONORARY CHAIRS
Prof. Mostafa El-Sheikh
Dean, Faculty of Science, Tanta University
Prof. Ayman EL-Saied
Dean, Faculty of Medicine, Tanta University
EXECUTIVE CHAIRS
Egyptian-CHAIR
Prof. Mohamed L. Salem
Tanta University
MEACR-CHAIR
Prof. Ala-Eddin Al Moustafa
CEO, MEACR
3
GENERAL SECRETARY
PROF. YOUSRY AL-SENOOSY
VICE-DEAN, FACULTY OF MEDICINE
TANTA UNIVERSITY
PROF. TAREK FAYED
VICE-DEAN, FACULTY OF SCIENCE
TANTA UNIVERSITY
PROF. ASHRAF BARAKAT
HEAD, ONCOLOGY DEPARTMENT
FACULTY OF MEDICINE
COORDINATORS
PROF. MAHMOUD ABDEL AZIZ
PROF. OF OTORHINOLARYNGOLOGY
TANTA UNIVERSITY
PROF. SAID HAMAD
PROF. OF CLINICAL PATHOLOGY
TANTA UNIVERSITY
DR. MOHAMED ALM ELDIN
LECTURER OF ONCOLOGY
TANTA UNIVERSITY
INTERNATIONAL COMMUNICATION
MEDICAL SCIENCE SECTION
DR. MOHAMED EL-SHANSHOORY, MD, PHD
PROF. OF PEDIATRICS, TANTA UNIVERSITY
BASIC SCIENCE SECTION
DR. EHAB TOUSON, PHD
FACULTY OF SCIENCE, TANTA UNIVERSITY
DR. ELSAYED SALEM, PHD
FACULTY OF SCIENCE, TANTA UNIVERSITY
4
Welcome
6
Scientific Program
7
Plenary Session 1 (day 1, 27th)
8
A- Special Session 1 (Prof. General Omar heikal)
8
B- Plenary Session 1
9
Parallel Sessions 1 (Oral presentations, day 1)
14
Poster Session 1 (poster abstracts, day 1)
34
Plenary Sessions 2 (day 2, 28th)
46
A- Special Session 1 (Prof. Mostafa Elsayed)
47
B- Plenary Session 2
49
Parallel Sessions 2 (Oral presentations, Day 2)
53
Poster Session 2 (Poster abstracts, Day 2)
78
5
It is our great pleasure that the Middle Eastern
Association for Cancer Research (MEACR) and the
University of Tanta, Egypt host the first Annual meeting
from December 27th to 28th, 2011 at the Conventional
Center of the Medical campus of Tanta University. Tanta
is the capital of Al-Gharbiah provience which is located
about 80 km north to Cairo, the capital city of Egypt and
is famous with the great mosque of sidi Ahmed ElBadawi and magnificent traditional and country side
surroundings. The burden of cancer has
rapidly
increased in Egypt and the in the Middle East. The
MEACR
conference
2011
will
focus
on
sharing
experiences of cancer research activities from different
resource
settings.
collaboration
are
Regional
challenges
and
to
be
international
forced.
The
conference will offer a good opportunity to exchange
knowledge, form networks and also discover the culture,
cuisine and scenic surroundings in dynamic Egypt
starting from Tanta. We take this opportunity to welcome
all participants and invite them to enjoy fruitful
interpretations in cancer esearch.
Chair of the MEACR conference
6
7
Day 1:
December 27, 2011
A. Special Session 1
Hepatocellular Carcinoma in Egypt
Dr. Omar Heikal, General, MD
President of Military Medical Academy
Prof. of Medicine, G.I.T and Hepatology
Tel. (202) 2620371 – 22615943 (Office)
Fax :(202)2613421, Mobile: +2 – 010 -1721265
E-mail: [email protected]
Biography
Prof. Omar Heikal (MD) is the Prof. of Medicine, GIT and Hepatology, at Military Medical Academy,
Cairo, Egypt since 1999. He has been a Fellow at Royal Free Hospital (GIT, HEPTO) since 1990 School of
Medicine London University. He Is the Chief of Military Medical Academy since July 2007 till now. He was
graduated (MB Bch) from Faculty of Medicine, Ain Shams University in 1971. He was then spent his
Residence of Internal Medicine (1973 – 1976) at Kobry El-Kobba Military Medicine Hospital and Master
Degree (MSc; General Medicine) from Faculty of Medicine, Ain Shams University in 1979.
Prof. Omar served as the Chairman of Internal Medicine Department, Hepatology unit in Air Force
Hospital, 1993, and Chairman of Internal Medicine and GIT Unit, Ghamra Military Hospital, 1994-1995,
Chairman of Internal Medicine in Kobry Elkobba Military Hospital, 1996 – 2001. He has also served as a
Commando of Specialized Medical Hospital in K.K 2002 – 2006, Chairman of Internal Medicine Council,
Military Medical Academy, Cairo, Egypt.
Prof. Omar is a member in the Egyptian Society of Hepatology, Member of Medical Sector of High
Supreme Council since 2007, Kasr Ainy, Faculty of Medicine council, Ain Shams, Faculty of Medicine
council, the Egyptian Medical Council – EMC, Higher Committee for Organ Transplantation. He is the
Vice president of the Egyptian Society of Hepatology Gasroenerology and Infectious Diseases and Vice
president of the Egyptian group for study of GIT and Hepatology and the Dean of Arab Society of Proper
use Antimicrobial from 2002 – 2005. Dr. Omar research focuses on hepatocellular carcinoma and the role
of hepatitis virus C infection in the development of this disease.
Abstract: Liver cancer is the fifth most common cancer worldwide and the third most common
cause of cancer mortality. Hepatocellular carcinoma (HCC), which accounts for 80% - 90% of
primary liver malignancy, is characterized by a very poor prognosis and is associated with high
mortality. Nowadays, more than half a million cases are diagnosed every year on a worldwide
basis. The peak age of incidence is 50-70 years, with a male predominance of 4:1. There has been
a remarkable increase of the proportion of HCC among chronic liver disease patients from 4.0%
8
to 7.2% over a decade. For patients at risk of developing HCC, the aim of imaging is lesion
detection, lesion characterization and determination of the stage. The European Association for
the study of the Liver has documented the diagnostic criteria for HCC. Nodules larger than 2 cm
with an arterial hypervascular pattern by two imaging techniques or by imaging technique
associated with an AFP level higher than 400 ng/ml was considered to be HCC in cirrhotic
patients without needing confirmation by a positive biopsy. The epidemiology of HCC in Egypt
and the world will be presented.
B. Plennary Session 1
(Cancer Research from Bench to Clinic)
01
From bench to bedside: The use of arabinoxylan rice bran (MGN-3/Biobran) in
cancer medicine
Mamdooh Ghoneum, Ph.D.
Faculty Executive Board (FEB), Charles Drew University of
Medicine & Science, Department of Otolaryngology, Associate
Professor III, Chief of Research, Department of Neurobiology,
UCLA, School of Medicine, USA
Contact: Phone (323) 563-5953, [email protected]
Biography
Dr. Ghoneum is currently Associate Professor and Chief of Research
at Charles Drew University of Medicine and Science, Department of Otolaryngology, Head and Neck
Surgery, Los Angeles, CA. He is also Research Associate at Department of Neurobiology, School of
Medicine, University of California Los Angeles (UCLA). Dr. Ghoneum earned his Ph.D. at the University
of Tokyo, Japan in the field of radioimmunology (1976-1980) and did his postdoctoral at UCLA, School of
Medicine (1983) in the field of cellular and molecular immunology. He has published 90 articles and 130
abstracts, including 8 books in Japanese and in English related to cancer immunology. He holds 3 patents
for inventing 3 biological response modifiers for the treatment of cancer. He currently serves on the
Editorial Board of the International Journal of Occupational Medicine, Immunology and Toxicology and
Ejorsa "Egyptain Journal of Radiation sciences and Application.” In addition to his expertise in immune
suppression by chemical carcinogens, aging and stress, Dr. Ghoneum is an internationally recognized
immunologist who is an expert in the area of Cancer Immune therapy.
Dr. Ghoneum’s contribution to immunotherapy is introducing and patenting several new nontoxic biological response modifiers (BRMs) that activate NK cells and induce apoptosis of cancer cells.
These BRMs include: arabinoxylan rice bran (MGN-3), marina crystal minerals (MCM), active
hemicellulose compound (AHCC), gross thymic extract (Thymax) etc. Results of his studies have been
published in several peer review journals and are currently applied in major clinical trials around the
world. He received several international awards from; The American Cancer Society. 1993. Japan
Functional Food Research Association (JAFRA) Tokyo, Japan. 2002. The Filipino-Chinese Medical
Society. Manila, Phillipines, 2005. In 2007 he was nominated for the annual $1 million prestigious
Gotham Prize in Cancer Research. He created a video to educate the public about a new cancer therapy.
The video was created in collaboration with Dr. Susan Kelly and Dr. Keith Norris. He had special
accelerated promotion. He has been awarded numerous research grants from NIH-MBRS and major
9
research institutions in Japan. He has been a reviewer for the NIH Study Section Member. He has been an
organizer for annual workshops between the Japanese Immunology Society and Drew University since
1990. He is a member of several Scientific Societies, including the American Association for Cancer
Research (AACR).
Abstract: This study describes how bench research on arabinoxylan rice bran (MGN-3 /Biobran)
has translational potential. Although conventional therapeutics for cancer have proven to be
initially effective, many patients relapse over time. Tumor relapse may be due to the development
of therapeutic resistance, motivating the need to study novel treatments that target drug resistant
cells. The current study explains the potential of MGN-3 as a chemo-sensitizer and as a novel
adjuvant for the treatment of cancer. MGN-3 is an arabinoxylan with a xylose in its main chain
and an arabinose polymer in its side chain. MGN-3 has attracted the attention of many scientists
and health professionals from around the globe for its ability to fight cancer.
In a recent study, a three-year randomized clinical trial of the anticancer activity of MGN-3
against hepatocellular carcinoma (HCC) was carried out in the Military Central Hospital,
Vietnam. 68 patients with HCC (stages I and II) were divided into two groups: 38 patients were
treated with conventional therapy (CT) plus MGN-3, and 30 patients were treated with CT alone.
CT included transarterial oily chemoembolization (TOCE) and pericutaneous ethanol injection
therapy (PEIT). Results showed a synergistic effect of CT and MGN-3. Patients in the MGN-3
group showed: i) reduced tumor size, ii) lower alpha fetoprotein (AFP) level, iii) lower alanine
transaminase (ALT) level, iv) less recurrence of cancer, and v) higher survival rate.
In a major clinical study that was conducted at Sano Clinic, Japan, 205 progressive and partially
metastasized cancer patients were treated with chemotherapy plus MGN-3 or chemotherapy
alone. Patients in the MGN-3 group demonstrated: i) prolonged life expectancy, ii) an improved
quality of life (QOL) as characterized by a decrease in pain, nausea, and malaise and an increase
in appetite. In another study at the Mayo Clinic, Florida, doctors described a case report as
follows: “the lung masses steadily decreased in size, and at 34 months after the initiation of
[MGN-3] therapy, the tumor was undetectable.”
Extensive basic research examined the mechanisms by which MGN-3 synergized with
chemotherapy and exerted anti-cancer activity. Results demonstrated that MGN-3 sensitized
cancer cells to chemotherapy by modulating drug transport. In addition, MGN-3 modulated host
immune responses by i) activating dendritic cells, NK cells, and T cells, and ii) inducing the
production of cytokines such as interleukin-2 and interferon-gamma. We conclude that MGN-3
may be useful for the treatment of HCC and needs to be studied in clinical trials.
10
02
Id Genes and Proteins as Novel Therapeutic Targets for Metastatic Cancer
Pierre-Yves Desprez, Ph.D
Senior Scientist, California Pacific Medical Center, Cancer Research Institute,
475 Brannan Street, San Francisco, CA 94107, USA
E-mail: [email protected]" <[email protected]
Biography
Dr. Pierre-Yves Desprez joined the University of California at Berkeley at the
end of 1991 after completion of his doctoral thesis at the University of Lyon in
France. Dr. Desprez has been a Principal Investigator and a Staff Scientist at
the California Pacific Medical Center Research Institute in San Francisco
since 1996. The main focus of his laboratory is the regulation of tumor cell
behaviors by transcriptional regulators. Dr. Desprez¹s laboratory was one of the pioneer groups to show
that the expression of Id-1 protein was upregulated in multiple types of cancer and that it may therefore
represent a new marker that indicates the progression of some cancers on their way towards their final,
untreatable stages. Moreover, the laboratory was the first one to show that Id genes and proteins were
promising targets for the suppression of breast invasive and metastatic cancers. Recently, the discovery by
Dr. Desprez and his colleague Dr. McAllister that a cannabinoid compound represented the first nontoxic
agent that decreased Id-1 expression, and consequently breast tumor aggressiveness and metastasis, was
reported worldwide by several news agencies.
Abstract: During normal development and embryogenesis, helix-loop-helix Id proteins regulate
the differentiation programs of many tissues. Moreover, recent studies have shown that
dysregulated Id expression contributes to cancer progression and metastasis. Specifically, we
found high levels of one of the Id family members, Id-1, in breast, prostate and brain tumor
biopsies from human patients with aggressive cancer and low levels of Id-1 in non-invasive
tumors. Ectopic expression of Id-1 in non-aggressive human cancer cells rendered them highly
proliferative and invasive, and induced high levels of matrix metalloproteinase (MMP)
expression. Conversely, human metastatic cancer cells became significantly less proliferative and
invasive in culture when Id-1 protein expression was decreased by antisense RNA directed
against the Id-1 gene. Next, we asked whether Id-1 could be exploited as a therapeutic target to
treat metastatic cancers. Using tumor-bearing animals and non-viral systemic gene targeting
technique, we showed that reduction of Id-1 levels, and consequently MMP expression, could
significantly decrease the metastatic spread of cancer cells. These results suggested that Id-1
gene and/or protein could be a promising target for development of therapeutic strategies to
reduce cancer metastasis. Since Id-1 expression is scarce in most mature adult tissues, a majority
of normal cells would not be affected by systemic therapy targeting this gene. We recently
determined that cannabinoid compounds could specifically inhibit the expression of the Id-1 gene
and, as a result, cancer cell proliferation and invasion in culture and tumor metastasis in vivo.
11
03
Nanodiagnostic Assays for In Vitro Detection of Cancer
Hassan M. E. Azzazy, PhD, DABCC, FACB
Professor of Chemistry
Leader, Novel Diagnostics & Therapeutics Research Group
Yousef Jameel Science & Technology Research Center
The American University in Cairo, Egypt
E-mail: [email protected]
Biography
Dr. Hassan M. E. Azzazy received his B.Sc. and graduate diploma in Biochemistry from Alexandria
University, Egypt. In 1994, he received his PhD in Biochemistry and Molecular Biology from University of
North Texas Health Science Center at Fort Worth, TX, USA. He was a postdoctoral fellow then an
assistant professor at the Pathology and Medical & Research Technology departments at University of
Maryland School of Medicine in Baltimore, MD. He is also an adjunct professor with the Graduate School
of Management and Technology, University of Maryland University College, Adelphi, MD. He has board
certifications in Clinical Chemistry and Molecular Diagnostics from the American Board in Clinical
Chemistry, Washington DC. Dr. Azzazy currently serves as professor of Chemistry at the American
University in Cairo. In 2009, he has founded the Novel Diagnostics and Therapeutics group at Yousef
Jameel Science & Technology Research Center, AUC. He is interested in developing novel
bionanotechnology-based diagnostics and identifying therapeutic candidates. He actively collaborates with
researchers in Japan, the Netherlands, Qatar, Portugal, and USA. Recently, Dr. Azzazy has received
Excellence in Research & Creative Endeavors Award, Excellence in Teaching Award from AUC and the
State Prize in Advanced Technological Sciences from the National Academy for Scientific Research &
Technology. He has over 120 publications including journal articles, conference abstracts, book chapters,
and monographs.
Abstract: Current cancer detection techniques are costly, time-consuming, often unable to
distinguish between benign and malignant tumors, and have variable sensitivity and specificity.
Nanoparticles have been proposed as promising tools to address these limitations. They have
unique optophysical properties which enable sensitive detection of cancer, and are easily
amenable to modification for use in different assay formats. Additionally, their synthesis and
functionalization are relatively simple and inexpensive and their detection methods are quite
versatile. This presentation serves as a guide for utilization of nanoparticles to develop assays for
detection of cancer cells and biomarkers in biological fluids. The following assay prototypes will
be discussed: (1) conjugation of magnetic and fluorescent nanoparticles to high affinity aptamers
for collection and detection of acute leukemia cells in mixed cells and whole blood samples; (2)
immobilization of epidermal growth factor peptide on nanoparticles for detection of circulating
tumor cells in peripheral blood of patients with squamous cell carcinoma; (3) employing
magnetic and gold nanoparticles in a bio-barcode assay for ultrasensitive detection of prostatespecific antigen after radical prostatectomy; (4) employing positively charged gold nanoparticles
to develop a colorimetric assay for measuring hyaluronidase activity in urine of patients with
bladder cancer; (5) using magnetic nanoparticles conjugated to antibodies for mixing reagents and
detection of tumor markers in microfluidic ELISA; (6) using gold nanorods as biosensors for
label-free detection of tumor markers based on antibody-antigen interaction and the resonant
Rayleigh scattering spectrum of individual gold nanorods; (7) using gold nanoparticles labeled
with antibody and luminal to develop a chemiluminescent immunoassay for detection of
carcinoembryonic antigen in serum; and (8) conjugating gold nanoparticles to telomere strand
primers for detection of telomerase activity and initial screening of telomerase inhibitors.
12
04
Gene Expression profile of Egyptian hepatocellular carcinoma
Abdel-Rahman N. Zekri, PhD
Prof Molecular Virology and Immunology
Head of Virology and, Immunology Department
National Cancer Institute, Cancer Biology Unit, Cairo University, Cairo, Egypt
E-mail: [email protected]
Biography
Dr. Zekri is the Prof. of Molecular Virology and Immunology at Cancer Biology
Department, National Cancer Institute, Egypt. He obtained his B.Sc. in
Microbiology in May 1982, M.Sc. in Microbiology in October 1987 and Ph.D. in
Virology and Immunology from National Cancer Institute, Cairo Univ in
November 1991. He was granted a Doctoral Fellowship from National Institute
of Health, Centers of Disease Control, USA in 1990 and a 2-year (1992-1993) Post Doctoral Fellowship
from University of Amsterdam, The Netherlands and from the National Institute of Health, USA (19951996) and a visiting scientist fellowship from the Fox Chase Cancer Center, USA (1996-1998). Dr. Zekri
research focuses on the development of novel cell-based therapy against hepatitis C virus-induced liver
cancer. He has been using stem cells and mesenchymal stem cells to treat patients with HCC who fail the
standard therapy. He has published several articles that indicate to the beneficial effects of such treatment
regimen. His research also focuses on the development of novel immunotherapeutic approaches against
HCV.
Abstract: The incidence rate in Hepatocellular carcinoma (HCC) has increased worldwide
leading to high mortality among cancer patients. This situation calls for more studies at the
molecular level. In continuation of our previously published preliminary work, we performed
cDNA microarray on 15K to give an insight on the genetic profile of Egyptian HCC using 25 K
c-DNA microarray as a confirmatory study. The study included 31 patients with HCC who were
studied for gene expression profile by 25 K c-DNA microarrays. In addition, another set of 30
HCC patients were used to confirm the array data. Those were tested by RT-PCR for selected 7
genes involved in immunoregulation and lipid metabolism pathways. Out of the 25,000 studied cDNAs, 958 transcripts were differentially expressed; 503 were up regulated and 455 were down
regulated. Only 19 pathways were specifically up regulated (P<0.05) by 27 genes and 13
pathways are specifically down regulated (P<0.05) by 19 genes. Thrity seven genes showed
significant difference in their expression between HCC cases with high and low AFP. The
confirmatory HCC cases showed down regulation of the following genes: PPP3CA (75%), ATG5 (85%), BACE (62%), and up regulation of ABCG2 (90%), RXRA (80%), ELOVL2 (65%),
CXR3 (80%) genes. This is the first study on the global gene expression profile in Egyptian HCC.
The identified genes could provide a panel of new diagnostic, prognostic as well as for molecular
target therapy for HCC in the future.
Contributing authors: Abeer A. Bahnassy1, Hanaa M Al-el-Din2 Mohamed Abouelhod3 Mohamed M
Hafez3, Zeinab K Hassan1, Ahmed Ali4
1
Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo University,
Cairo, Egypt, 2Center of Informatics Sciences, Nile University, 3Clinical Pathology Department, Faculty of
Medicine, Beni-Suef University, 4Biostatistic and Epidemiology Department, National Cancer Institute,
Cairo University, Cairo, Egypt.
13
14
Session 1: Therapy (Human studies):
O 1.1
Therapy (Human studies)
Bryostatin-1, Fenretinide and 1α,25(OH)2D3 induce growth inhibition, apoptosis and
differentiation in T and B cell-derived Acute Lymphoblastic Leukemia cell lines
Ali M. Ardekani1*, Shahrzad Soleymani Fard1, Mahmoud Jedi Tehrani2, Ramin
Ghahremanzade3
1Reproductive Biotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IRAN; 2.
Monoclonal Antibody Research Center, Avicenna Research Institute, ACECR, Tehran, IRAN.
3Nanotechnology Research Center, Avicenna Research Institute, ACECR, Tehran, IRAN
Corresponding Author: Dr. Ali M. Ardekani. Editor-in-Chief: Avicenna Journal of Medical Biotechnology,
Reproductive Biotechnology Research Center, Avicenna Research Institute
Tel/Fax: 66409980- 6649365; E-mail: [email protected]
Abstract
Background: In much acute leukemia, normal differentiation does not occur. However,
in many cell lines derived from hematologic malignancies, differentiation or apoptosis
can be induced by variety of agents. Despite advances in the treatment of acute
lymphoblastic leukemia (ALL), in most patients long-term survival rates remain
unsatisfactory, especially in T-cell derived ALL. Aim: Thus we studied the anti-cancer
effects of fenretinide, 1α,25(OH)2D3, and bryostatin-1 in CCRF-CEM (T-cell derived)
and Nalm-6 (B-cell derived) ALL cell lines. Methods: MTT proliferation assay was used
to assess proliferative response of the tumor cell lines under the effects of the studied
compounds. Results: Using MTT assays, both cell lines were shown to exhibit increased
inhibition of proliferation at micro and nanomolar concentrations and induce apoptosis
via activation of caspase-3 pathway. Furthermore, for the first time we are reporting
consistent anti-proliferative and apoptotic effects of Bryostatin-1 in ALL T-cell derived
cell line with the lowest ED50. To evaluate the differentiation induction by fenretinide,
1α,25(OH)2D3, and bryostatin-1 in ALL cell lines, we assayed for the expressions of
CD19, CD38 markers on Nalm-6 and CD7 marker on CCRF-CEM cell line. The flow
cytometric analysis showed a significant increase in expression of CD markers in
response to anticancer drug treatments. Conclusion: Overall results demonstrate that the
anticancer agents used in this study are strong inhibitors of ALL cell proliferation and
inducers of apoptosis and differentiation in vitro. These findings may be quite significant
if these drugs are to be used for differentiation therapy of ALL patients in the clinic in the
future. Further studies are warranted to establish the in vivo effect of these drugs
particularly in patients with T-cell derived ALL.
Key words: Acute lymphoblastic leukemia, anti-cancer compounds, apoptosis, differentiation
15
O 1.2
Therapy (Human studies)
Concurrent radiotherapy and chemotherapy for locally advanced squamous cell
carcinoma of the head and neck
1-Elsayed Mostafa Ali 2-Ahmad Gaber Abdelraheem
1-Lecturer of Clinical Oncology, Faculty of Medicine, Sohag University, Sohag
2-Lecturer of ENTsurgery, Faculty of Medicine, South Valley University, Egypt
Correspondence: Dr. Elsayed Mostafa Ali
E-mail: [email protected], Phones: 0101638744 / 0932308901
Abstract
Background: Concurrent chemoradiation is the standard of treatment for patients with
advanced head and neck squamous cell carcinoma (HNSCC). Aim: The present study
was carried out with objective of assessing the feasibility and efficacy of low dose
gemcitabine as radiosensitizer when used during radical therapeutic management of
patients with locally advanced HNSCC. Patients and methods: From July 2008 to
December 2010, 52 patients with locally advanced HNSCC (stage III 50%, stage IVa
50%) were enrolled. All received course of radiotherapy (70 GY over 7 weeks)
concurrent with weekely infusions of gemcitabine at 50 mg/m2. Results: All patients
were available for toxicity and response. Severe mucositis (grade 3-4) was observed in
76% of patients. Severe hematological toxicity was uncommon. Xerostomia was the most
common late toxicity in 34 patients (65.4%). The rate of complete and partial response
rate was 67.3% and 21.1% respectively, with an overall response rate of 88.45%. 2 years
disease free survival was 38.46%. Conclusion: using low dose gemcitabine concurrent
with radiotherapy is maintaining high response rate with low systemic toxicity, in spite of
severe mucositis in a high percentage of patients.
Key words: chemoradiation, gemcitabine, head and neck cancer, locally advanced, radiotherapy,
squamous cell carcinoma
O 1.3
Therapy (Human studies)
Role of chemotherapy in the treatment of uterine leiomyosarcoma:
About ten cases and literature review
Imane Ouafki, H.El Yacoubi, M.Benameur, S.Boutayeb, H.M’Rabti, H.Errihani
Department of Medical Oncology, INO, CHU Rabat, Morocco E-mail: [email protected]
Abstract
Introduction: Uterine leiomyosarcoma is a rare malignancy, developed at the expense of
mesenchymal components of myometrium. It represents 1.3% of all cervical cancers and
40 to 50% of uterine sarcomas. Materials and methods: This is a retrospective study of
ten cases treated in the Nationnal Institute of Oncology in Rabat (Morocco), from 2004 to
2011, and review of the literature focuses on uterine leiomyosarcomas. Results: The
average age of patients at diagnosis was 50 years. The circumstances of discovery were
pelvic pain, abdominal distention, and bleeding. The diagnosis rarely discussed before
16
surgery, is usually made on histological examination of the operative specimen. The
outcome is related to the mitotic activity of the tumor and to the infiltration of nearly
structures. Treatment was multidisciplinary based on surgery, radiotherapy and
chemotherapy for metastatic patients. Discussion: The uterine leiomyosarcoma is a rare
entity, occurring in middle-aged women between 45 and 55. Its absolute frequency is
0.67 per 100 000 women per year aged over 20 years. Clinically it is manifested by pelvic
pain, abdominal mass or vaginal bleeding. On CT, large areas of necrosis or cystic
transformation may suggest the diagnosis which is often made on the part of
hysterectomy performed for uterine fibroids. Treatment is primarily surgical and should
be complete at the outset, consisting of a hysterectomy with annexectomy. Radiotherapy
reduces the incidence of local recurrence but does not improve survival. Chemotherapy is
indicated in locally advanced or metastatic uterine leiomyosarcoma. The most active
drugs are doxorubicin, ifosfamide, docetaxel and gemcitabine. The recurrence rate varies
from 35 to 70%. The 5-year survival is 25 to 40%. The presence of metastases influence
survival: 19 months for lung metastases and 12 months if multiple metastases.
Conclusion: Uterine leiomyosarcoma is a rare cancer with poor prognosis. Preoperative
diagnosis is rarely made . Management of locally disease remains surgical.Chemotherapy
improves progression-free survival and quality of life in metastatic patients.
O 1.4
Therapy (Human studies)
A case of primary pleural leiomyosarcoma treated by chemotherapy
Imane Ouafki, H.El yacoubi, T.Sghiri, S.Boutayeb H.M’Rabti, H.Errihani
Department of Medical Oncology, INO, CHU Rabat; Morocco E-mail: [email protected]
Abstract
Introduction: Primary sarcomas of the thorax are rare. They occur in the lung,
mediastinum,
pleura,
and
chest
wall.
Angiosarcoma,
leiomyosarcoma,
rhabdomyosarcoma, and mesothelioma (sarcomatoid variant) are the most common
primary intrathoracic sarcomas. Primary leiomyosarcoma of the chest wall is a rare
neoplasm and is reported to occur in approximately 1-4 % of the patients with primary
soft tissue sarcomas of the chest wall.We here present a case of locally advanced pleural
leiomyosarcoma. Case report: We report a case of a 64-year-old man with locally
advanced primary pleural leiomyosarcoma which was treated by chemotherapy in
October 2011. The circumstance of discovery was an intrathoracic mass, gradually
increasing in volume, operating in a context of fever and altered general condition.
Abdominal computed tomography showed a huge lesional process thickened wall and
pseudo-necrotic center, substernal seat, occupying the right thoracic base, measuring 14 x
9 cm long axis, forcing the heart cavity with discrete pericardial effusion. This tumor has
a bottom development exerting a mass effect on segment VIII and IV of liver. Surgical
exploration revealed a very locally advanced pleural tumor invading the mediastinum. A
simple biopsy was performed. In the histological study, the tumor was diagnosed as a
high-grade leiomyosarcoma. Our patient received a doxorubicin-based chemotherapy at a
dose of 60 mg / m², administered every 21 days. Evaluation after 6 cycles of
17
chemotherapy found a clinical benefit and a radiological partial response estimated at
30%. Currently, he is in good control. Discussion: The pleural leiomyosarcoma is an
exceptional disease. It usually occurs in the sixth decade or later with a male
predominance. Clinically, it is characterized by a painful retrosternal mass, as may be
asymptomatic in early stages. Radiologically it appears as a necrotic process exerting a
mass effect on adjacent structures. The initial diagnosis is often difficult because the
clinical and imaging are not specific. The diagnosis is confirmed by biopsy and
pathological study with immunohistochemistry. For which is the surgical treatment, in
many previous reports, it is recommended that the resection should include all of the
involved soft tissues and bones with an adequately ensured margin of normal tissue
around. Indeed such wide chest wall resection contributes to decreasing local recurrences,
but it does not lead to prolonged survival. Also Gordon et al. mentioned that the factors
affecting prognosis were histological tumor grade and development of metastasis, but not
margin status. To the contrary, Perry et al. reported that the most important factor
affecting overall survival was margin status. Whichever may be true, at least it is
important that resected margins are tumor-negative. Chemotherapy is indicated for
locally advanced or metastatic pleural leiomyosarcoma. It is essentially based on
doxorubicin at a dose of 60 mg / m² on day 1 and ifosfamide 5 g / m² on day 1
administered every 21 days . Metastatic disease is transmitted by the blood and is mostly
liver and lung. Conclusion: Pleural leiomyosarcoma is an extremely rare entity. Its
diagnosis is pathological. Extended surgery with clear margins remains the treatment of
choice. Chemotherapy has its place before surgery, or in case of metastatic disease.
O 1.5
Therapy (Human studies)
Bladder leiomyosarcoma: A case report
Imane Ouafki, H.El Yacoubi, M.Benameur, S.Boutayeb, H.M’Rabti, H.Errihani
Department of Medical Oncology, INO, CHU Rabat; Morocco
E-mail: [email protected]
Abstract
Introduction: The bladder leiomyosarcoma is a rare tumor. The clinical characteristics
and the methods of therapeutic management remain uncodified. The treatment is
essentially surgical excision often associated with adjuvant chemotherapy. The poor
prognosis of this tumor appears to be related to high grade of the tumor, with rapid local
recurrence and the occurrence of distant metastases. Case report: We report a case of a
52-year-old man who consulted for intermittent terminal hematuria with urinary
frequency. Clinical examination was normal. Renal and vesico-prostatic ultrasound
objectified a right lateral bladder process with a right.
18
O 1.6
Therapy (Human studies)
Comprehensive management of peritoneal carcinomatosis as a new emerging
specialty
Ayman Elnemr, MD, PhD1, Yutaka Yonemura, MD, PhD2
1
Surgical Oncology Unit, Tanta University, Tanta, Egypt
NPO Organization to support Peritoneal Surface Malignancy Treatment, Osaka, Japan,
Correspondence: Ayman Elnemr, M.D,Ph.D
Head of Surgical Oncology Unit, Department of Surgery, Tanta University,
mobile: +20(10)624-5403; home: (040)536-0910, E-mail: [email protected]
2
Abstract
In this presentation we will provide the full description of the comprehensive
management of peritoneal carcinomatosis (PC) as a new emerging specialty. Approaches
to this malignancy differ completely form those used for the treatment of cancers
affecting the individual organs in the peritoneal cavity. The current state-of-the-art
treatment for PC consists of a cytoreductive surgery (CRS) and perioperative
intraperitoneal chemotherapy (PIC). The complete cytoreduction rate depends on the
selection criteria for the CRS and the ability and experiences of the surgeons. This
cytoreductive approach may require six peritonectomy procedures to resect or strip
cancer from all intra-abdominal surfaces. These are greater omentectomy-splenectomy;
left upper quadrant peritonectomy; right upper quadrant peritonectomy; lesser
omentectomy-cholecystectomy with stripping of the omental bursa; pelvic peritonectomy
with sleeve resection of the sigmoid colon; and antrectomy. No survival benefit has been
reported by cytoreductive surgery alone. In contrast, CRS plus hyperthermic
intraoperative intraperitoneal chemotherapy (HIPEC) confers a prolonged survival
period. In this work, the current investigational modalities, quantitative estimators of PC,
our surgical techniques for the complete CRS and hyperthermic intraoperative
intraperitoneal chemotherapy (HIPEC) will be presented.
Session 2: Anti-tumor Immunity
O 2.1
Anti-tumor Immunity
Improvement of conventional cancer therapies by
immunological microenvironment
manipulating
tumor
Shengdian Wang, MD, PhD
Professor/Deputy Director; CAS Key Lab of Infection and Immunity Institute of
Biophysics, Chinese Academy of Sciences
Tel +86-10-64888493(Office); 64886603(Lab), Fax: +86-10-64846538, E-mail
[email protected]
19
Biography
1998, Ph.D. degree from Chinese Academic Medical Science and Beijing Union Medical College; 19982003, postdoctoral fellow in Department of Immunology, Mayo Medical School, Mayo Clinic, Rochester,
MN, USA; 2003~2005, Research Associate in Mayo Medical School, Mayo Clinic and Johns Hopkins
University; 2005, Professor, Institute of Biophysics, CAS., supported by CAS Hundred Talent Program. T
lymphocytes play critical roles in host immune response against viral infection and cancer and are
involved in the progression of autoimmune diseases. Activation and differentiation of lymphocytes are
regulated by co-signaling pathways. We combined our basic study with clinical resource and requirement
to mainly study the cellular and molecular mechanisms of co-signaling pathways, trying to elucidate the
regulation of T cell responses during viral infection and in the progression of cancer and autoimmune
diseases, to develop new approach for immunotherapy. In recent years, we established a series of mouse
models of chronic hepatitis B, tumor metastasis and the transplant of human cancer tissue. We found that
co-signaling molecules of CD24, B7-H1/PD-1, CD137/CD137L have a important roles in initiation and
development of chronic hepatitis B and hepatocellular carcinoma. Our study demonstrated that T cell
responses are important for the anti-HER2/neu antibody-mediated tumor therapy, and B7-H1/PD-1
inhibitory co-signaling pathway play critical role in dysfunction of anti-tumor immune responses in tumor
microenvironment, which will promote the tumor therapy.
Abstract: Although it has been well known that the immune system plays a critical role in
occurrence and development of cancer, the contribution of immune system has been neglected in
conventional cancer therapies. Accumulating evidence indicates that the innate and adaptive
immune systems make a crucial contribution to the antitumor effects of conventional chemo- and
radio-therapies. We have recently demonstrated that the therapeutic effect of anti-HER2/neu
antibody also depends on both innate and adaptive immunity. Antibody mediated blockade of
HER2/neu signaling and induction of ADCC cause tumor cell death and the release of danger
signals, such as HMGB1, that initiate tumor specific CTL responses by triggering an innate
MyD88-dependent pathway. Intriguingly, the addition of chemotherapeutic drugs shortly after
anti-HER2/neu antibody, although capable of enhancing the reduction of tumor burden, could
abrogate antibody-initiated immunity leading to decreased resistance to rechallenge or earlier
relapse. Although the antitumor T cell responses could be induced by immunogenic death of
cancer cells, and really made crucial contributions to therapeutic effects in conventional cancer
therapies, combination of immunotherapies aimed to promoting specific antitumor T cell
responses could not dramatically improve the conventional therapies. Our analysis on the tumor
microenvironment showed that tumor tissues were heavily infiltrated by tumor-associated
macrophages with M2 phenotypes and CD8+ T cells highly expressing inhibitory co-signaling
receptor PD-1 with the development of tumor. Amelioration of tumor immunosuppressive
microenvironment dramatically improves the therapeutic effects of anti-HER2/neu.
O 2.2
Anti-tumor Immunity
Genetic engineering of poorly immunogenic cancer cells with a xenogenic antigen
ncreases their responses to chemotherapy and formation of anti-tumor immunity
1*
1
Mohamed Labib Salem, 1Sabr Ali EL-Naggar and 2Abeer Hasan
Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Egypt
Zoology Department, Faculty of Science, Cairo University, Egypt
*
Correspondence: Prof. Mohamed Labib Salem, Prof. of Immunology
E-mail: [email protected], Tel. (+20) 01274272624
2
20
Abstract
Background: Although some cancers can respond to chemotherapy, several types of
cancers do not. Moreover, the growth of the cancer that responds to tumor recurs
resulting in failure of treatment and tumor progression due to the lack of anti-tumor
immunity. Therefore, this failure poses a challenge toward cancer treatment. Aim: The
main aim behind designing this study was to determine whether poorly immunogenic
tumor that fails to respond to chemotherapy can be genetically engineered to be
immunogenic and respond to chemotherapy and form immunity. Methods: The EL4
thymoma cancer cell line on C57BL/6 (H2 b) background was used. This cell line is
known to be poorly immunogenic and does not respond in vivo to treatment with the anticancer drug cyclophosphamide (CTX). This cell line was genetically engineered to
express and secrete ovaalubmin (OVA), which is a xenogenic antigen to C57BL/6 mice.
The OVA-transfected EL4 cell line was termed EG7. As control, the B16 melanoma cell
line, also on C57BL/6 (H2b) background, was used and transfected with OVA gene to
form B16-OVA cell line, which express, but not secrete, OVA protein. The cell lines
were injected (2 x 105/mouse) via subcutaneous injection into the left flank of wild type
or splenectomized mice and then treated once with intraperotoneal injection of
4mg/mouse CTX. The mice were re-challenged with the tumor 1-2 months after the
primary tumor challenge. The tumor size was monitored by measuring the length and
width of the tumor using Caliper twice a week. The tumor surface area was calculated by
multiplying the two diameters and expressed as mm 2. Results: Treatment of EL4-bearing
mice at any time point after tumor challenge did not affect the tumor growth rate and the
mice succumbed the tumor and dies after 3 weeks. Treatment of EG7-bearing mice with
CTX, however, resulted in cure of the tumor even when the treatment was delayed until
the tumor reached an advanced size (about 100mm 2). Interestingly, these tumor-free mice
immediately rejected the second and the third challenge with EG7, but not the B16-OVA
or EL4, tumor injected 1 month after the 1ry prior tumor injection. Finally, the absence of
spleen (using spelenctomized mice) had no effect on the responses of EG7 to CTX and
the formation of anti-tumor immunity. Conclusion: Engineering poorly immunogenic
tumor to secrete xenogenic antigen is a reliable means to increase its immunogenicity and
responses to chemotherapy. The data also indicate to the importance of secretion but not
expression of the antigen. These data has potential implication in cancer chemotherapy
and immunotherapy.
Keywords: Cyclophosphamide, Cancer, B16, Chemotherapy, EL4, EG7, Thymoma
O 2.3
Anti-tumor Immunity
Immunotoxicity investigation of representative heterocyclic drugs
Mohamad A. Fararjeh PhD.
Department of immunology and Medical Laboratory Technology, Hashemite University. Zarqa, Jordan
Fax: +962 5 3750573. Mobile +962 79 5590491; E-Mail: [email protected]
21
Abstract
Heterocyclic drugs are a group of antiprotozoal and antibacterial agents. These drugs are
widely used and are used repeatedly because of reinfections. The bone marrow
suppression by metronidazole has been previously shown in different studies. The
objective of this study was to determine the immunomodulatory effects of MTZ at
plasma concentration and higher in vitro and in vivo using animal model. Doses were
selected according to plasma concentration of drug in human. For in vitro studies,
parenteral solution of drug was used, and different concentrations of MTZ (5, 10, 50, and
200 μg/ml) were used. For in vivo study, immunotoxicological screening tests were
conducted, we examined the effects of subtheraputic, therapeutic and high dose exposure
to intraperitoneally (i.p.) administered MTZ at doses of 14, 28, 42, 57, and 114 mg/kg
body weight which were equals to (0.5x, 1.0x, 1.5x, 2.0x, and 4.0x) human therapeutic
dose respectively, using healthy female Balb/c mice (6-8 weeks old; 19-21g weights) for
14 days. At the end of treatment, peripheral blood samples from the retro-orbital plexus
were collected, and then animals were sacrificed by cervical dislocation. Spleen, thymus,
liver, lymph nodes, and kidneys were collected and weighed. Functional tests including,
percent body weight gain, organ body weight ratio, spleenocytes phenotypes
determination by flow cytometry were performed to assess the effect of the drug on the
cell mediated immune response. In order to test innate immune response, in vitro TNF-α
production by activated peritoneal macrophages were determined. IFN-γ and IL-2
spleenocytes production in vitro were also tested using sandwich ELISA. Results showed
that high as well as therapeutic doses of MTZ suppressed humoral as well as cell
mediated immune responses. MTZ at low dose (14 mg/kg) showed significant changes in
humoral immune system. It seems that MTZ has suppressive effects on mice immune
system. The effectiveness of MTZ in the treatment of diseases should be counterbalanced
by the increasing evidence of its immunotoxicity. Statistical analysis was done using oneway analysis of variance (ANOVA). All analyses were made using GraphPad Prism 4.03
statistical software package.
O 2.4
Anti-tumor Immunity
The toll-like receptor 3 agonist polyinosinic-cytidylic acid (poly(I:C)) targets natural
killer cells with NK1.1+CD11b+CD11c+Ly6G-B220+ phenotype
1, 3
Mohamed L. Salem, 1,2Sabry A. EL-Naggar, and 3David J. Cole
1
Immunology and Biotechnology Unit, Department of Zoology, Faculty of Science, Tanta University, Tanta,
Egypt
2
Department of Biology, Faculty of Science, Al-Jouf University, Sakakah, KSA; 3Department of Surgery,
Medical University of South Carolina, Charleston, SC 29425, USA
Correspondence: Pof. Mohamed Labib Salem, Prof. of Immunology;
[email protected]; [email protected]
Tel: +20-01274272624, Fax: +20-40-3350804
22
Abstract
Background: Natural killer (NK) cells are traditionally considered to be one of the major
arms of the innate immune system. These cells are capable of killing virally infected and
tumor targets while spare most normal cells. We have reported recently that in vivo
administration of the TLR3L poly(I:C), a synthetic double stranded RNA (dsRNA) that
mimics viral dsRNA, into naïve mice induces rapid increases in the frequencies of NK
cells mainly in the liver. Aim: In order to get more insight into the phenotype of the NK
cells targeted by poly(I:C), we performed a detailed phenotypic analyses on the NK cells
in blood, spleen and liver after treatment with poly (I:C). Results: We found that
poly(I:C)
targeted
NK
cells
expressing
the
phenotype
NK1.1highCD11bhighCD11chighLy6Glow B220low. These cells did not express the typical costimulatory molecules CD40 and CD80. Using CR3 -/- knockout mice and NK-depleted
mice (by injection of anti-asialo GM1 polyclonal antibody) demonstrated absolute
requirement of CD11b and NK1.1 molecules, respectively to mediate the effects of
poly(I:C) on NK cells. We further found that the effects of poly(I:C) on NK cells is
partly mediated by the presence of its specific TLR3. Conclusion: Taken together, our
data show that a subset of NK cells expressing the myeloid markers CD11b and CD11c
are the target of the TRL3L poly(I:C) under partial effect of TLRs. These results are of
paramount significance for the rationale clinical application of this biological response
modifier toward viral infection and cancer diseases.
Keywords: Poly(I:C), TLR3 agonist, TLR3 ligand, natural killer cells, attrition, PBL, expansion, Liver.
O 2.5
Anti-tumor Immunity
Intermittent prolonged fasting during Ramadan attenuates proinflammatory
cytokines and immune cells in healthy subjects
Mo’ez Al-Islam” E. Faris1*, Ref’at A. Al-Kurd1, Mohamed L. Salem2, Safia T. Kacimi3,Yasser
K. Bustanji2, Mohammad K. Lahham2, Mohamad K. Fararjeh4
1
Department of Nutrition, Faculty of Pharmacy and Medical Sciences, Petra University, Amman, Jordan
Zoology Department, Faculty of Science, Tanta University, Egypt
3
Dept of Clin. Pharmacy and Biopharmaceutics, Fac. of Pharmacy, University of Jordan, Amman, Jordan.
4
Faculty of Medical Laboratory and Technology, Hashemite University, Zarka, Jordan.
Corresponding author: Dr. Moez Faris <[email protected]>
2
Abstract
Inflammation has long been associated with carcinogenesis, especially in the promotion
phase. Intermittent fasting has been shown to extend life expectancy and reduce
inflammation and cancer promotion in animal models. In the holy month of Ramadan,
adult healthy Muslims are refrained for 29-30 days from eating and drinking from down
to sunset (about 14-15 hours a day). This makes Ramadan fasting a unique model of
prolonged intermittent fasting. The current study aimed to investigate the impact of
Ramadan intermittent fasting (RIF) on selected inflammatory cytokines. Fifty healthy
volunteers (21 males and 29 females), were recruited for the investigation of circulating
proinflammatory cytokines (IL-1β, IL-6, and TNF-α), immune cells (total leucocytes,
monocytes, granulocytes, and lymphocytes), anthropometric and dietary assessments.
23
The investigations were conducted one week before Ramadan fasting, on the third week
of Ramadan, and one month after the cessation of Ramadan. The proinflammatory
cytokines IL-1β, IL-6, and TNF-α, systolic and diastolic blood pressures, body weight,
and body fat percentage were significantly lower (P< 0.05) during Ramadan as compared
to before Ramadan or after the cessation of Ramadan fasting. Immune cells significantly
decreased during Ramadan but still remained within the reference ranges. Conclusion:
These results indicate that RIF attenuates inflammatory status of the body by inhibiting
proinflammatory cytokine expression and decreasing body fat and circulating leucocytes.
Further, these data showing that the anti-inflammatory effect on RIF are expected to be of
a paramount significance to patients with inflammatory diseases that have been found to
progress into cancer with the increase of inflammation. As such, Ramadan fasting can be
considered as adjuvant regimen during anti-cancer treatment
Key words: Interleukin-1β, Interleukin-6, Leucocytes, Prolonged Intermittent Fasting, Ramadan,
Tumor Necrosis Factor-α.
O 2.6
Anti-tumor Immunity
Survivin expression increases during aging and enhances the resistance of aged
human fibroblasts to genotoxic stress
1Huda H. Al-Khalaf and 2Abdelilah Aboussekhra
1 The Joint Centre for Genomics Research, King Abdulaziz City for Science and
Technology, Riyadh 11211, KSA. 2 King Faisal Specialist Hospital and Research Centre,
Department of Biological and Medical Research, MBC # 03, PO BOX 3354, Riyadh
11211, KSA
Correspondence: Dr. Huda H. Alkhalaf: Tel: 996-1-4647272 Ext: 32962; Mobile: 996-50350-7881; email: [email protected]
Abstract
Background: Cancer is principally an age-related disease. Survivin, an important antiapoptotic protein is highly expressed in most cancers. Aim: We examined age-related
modulation of survivin level. Results: We have shown accumulation of surviving and
phospho-survivin (Thr34) in aged normal human skin fibroblasts and mice organs. This
age-related accumulation of survivin was due to protein stabilization through association
with the molecular chaperone Hsp90 protein, which was also up-regulated during aging.
Interestingly, Hsp90 binds preferentially to phospho-survivin, which explains its higher
stability. In addition, we provide clear evidence that aged cells exhibit apoptosis
resistance when challenged with UV light, cisplatin, γ-rays or H2O2 as compared to their
younger counterparts. In response to γ-rays and H2O2, the levels of Bcl-2 and both forms
of survivin were upregulated in old cells, but not in their corresponding young ones. This
repression of survivin and phospho-survivin in young cells is p53-dependent.
Importantly, surviving inhibition/down-regulation with flavopiridol or specific shRNAs
increased the apoptotic response of old fibroblasts to various genotoxic agents, and
restored the pro-apoptotic Bax/Bcl2 ratio and the increase in the levels of cleaved
capsase-3 and PARP in old cells. Conclusion: These results show the role of survivin in
24
the age-dependent resistance of human fibroblasts, and provide new insights into the
molecular mechanisms that underlie the complex relationship between aging, apoptosis
and cancer.
Session 3: Tumor Markers
O 3.1
Tumor Markers
Comparison of gross cystic dosease fluid
primary and metastatic breast carcinoma
protein 9 (GCDFP-15) expression in
Imrana Basher, Samina Mansoor; Shaukat Khanum
Cancer Hospital and Research Centre, Lahore Pakistan.
<[email protected]>
Correspondence: Dr. Imrana Tanvir
Abstract
Aim: The objectives of the study is to evaluate the concordance of staining pattern of
Gross cystic disease fluid protein -15 (GCDFP-15) in primary and metastatic breast
carcinoma as to assess its utility as a diagnostic marker for unknown primary breast
cancer. Method: Between 17 June 2006 to 19 December 2006, Fifty cases of cancer
breast found suitable by inclusion criteria were invited for the study. An informed
consent was obtained from all of them. The data regarding age, socio-economic status,
duration and symptoms of illness, clinical examination and investigation were collected
from the hospital record. The received mastectomy specimens were fixed in 10%buffered
neutral formalin. Representative sections were processed and stained with hematoxylin
and eosin to see the tumor morphology. The immunohistochemical stain GCDFP-15 was
performed simultaneously on primary and metastatic tumors. Two pathologists assessed
the immunohistochemical stains independently. Information obtained was recorded on
the performa. The expression of (GCDFP-15) in primary tumors was compared with the
expression of this biomarker in metastatic carcinoma. Results: GCDFP-15 Expression
was compared and positivity was observed in 92% of primary tumors which was reduced
to 88% in metastatic. Gross cystic disease fluid protein showed 96% concordance in
primary and metastatic tumor. Conclusion: GCDFP-15 showed significant concordance
of staining pattern between primary and metastatic tumors. 96% concordance is observed
in primary and metastatic tumors, which proves its utility as a diagnostic marker.
Keywords: CYSTIC DISEASE; 9GCDFP-15; METASTATIC; BREAST CARCINOMA
25
O 3.6
Tumor Markers
Clinical evaluation of spermidine andsSpermine in breast cancer patients and follow
up the progress of disease
Alaa K. Jabbar and Raad K. Muslih
College of Pharmacy , Al- Mustansiryia University, Baghdad , Iraq
Correspondence: Prof. Alaa K. Jabbar; E-mail: [email protected]
Abstract
Practical evidence was suggested an important role of Spermidine and Spermine
concentration levels in breast cancer development. Spermidine and Spermine have been
determined in human serum samples of 25 primary invasive breast cancer patients and 9
serum samples from breast cancer patients ( stage three) in different ages .Statistical
analysis was performed in order to determine the concentration level values in different
ages . The concentration levels of Spermidine and Spermine in breast cancer patients
were significantly higher than the primary invasive breast cancer patients. They
correlated especially with markers of tumor of high stages of cancer patients. Spermidine
and Spermine concentration levels were identical between cancer patients controls. The
knowledge of the Spermidin and Spermine concentration levels pattern in breast cancer
become importance in clinical practice particularly of Spermidine and Spermine is target
as a therapeutic approach.
O 3.3
Tumor Markers
Plasma analysis of non-smokers, smokers and lung cancer patients for patternbased differentiation profiling of proteins and peptides by magnetic bead technology
with MALDI-TOF MS
Syed Ghulam Musharraf *a, b, Naghma Hashmi b, Muhammad Iqbal Choudhary
Rizvic, Ahmed Usmanc, and Atta-ur-Rahman a,b,
a,b
,
Nadeem
a. Dr. Panjwani Center for Molecular Medicine and Drug Research, University of Karachi, Karachi,
Pakistan; b. H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological
Sciences, University of Karachi, Karachi-75270, Pakistan; c. Jinnah Postgraduate Medical Center
(JPMC), Karachi-75510, Pakistan
*Corresponding author. Tel.: +92 213 4824924-5; 4819010; fax: + 92 213 4819018-9.
E-mail address: [email protected]
Abstract
Lung cancer is among the most lethal diseases accounting for millions of death, and
smoking is the major contributor. Current study focused on the correlation between the
proteomic profiling of lung cancer patients, healthy nonsmokers and smokers. Patternbased diagnostic peptide profiling of 186 plasma, comprising lung cancer (LC) patients,
healthy non-smokers (NS) and smokers (S) was performed through RPC-18 magnetic
bead fractionation with MALDI-TOF-MS analysis. Statistics were investigated by
ClinProTools (CPT) software in four groups, I (NS vs. LC), II (S vs. LC), III (NS vs. S),
and IV (NS vs. S vs. LC). Support vector machine (SVM) algorithm was employed for
26
groups I, II and III, while supervised neural network (SNN) was used for group IV. 100%
recognition capability and 96.70, 94.30 % cross validation were found for groups I and II,
while groups III and IV showed 85.60, 87.80 % cross validation and 96.70, 94.90 %
recognition capability, respectively. Unique peptides at m/z 1760, 5773, and 5851 Da
were expressed only in cancerous subjects while peaks at m/z 2940 and 7172 Da showed
gradual decrease in intensity from NS < S < LC. Developed diagnostic model was
externally validated with 100 % sensitivity and 71-77 % specificity. Pattern based
diagnostic profiling of plasma peptides in lung cancer patients, smokers and non-smokers
by above mentioned technique have been developed. Up- or down-regulated biomarker
peaks with high diagnostic capability were identified and can serve as a potential tool for
the detection and the screening of lung cancer. Details will be discussed in the oral
presentation.
O 3.4
Tumor Markers
Lymphatic invasion as a possible route for peritoneal dissemination: a new concept
Ayman Elnemr MD, PhD1,4, Yutaka Yonemura MD, PhD1, Masahiro Miura MD, PhD, Eisei
Nishino MD, PhD3
1
NPO Organization to Support Peritoneal Surface Malignancy Treatment, Japan
Department of anatomy, Oita Medical University, Oita, Japan
3
Department of Pathology, Kishiwada Tokushukai hospital, Kishiwada, Osaka, Japan
4
Department of Surgery, Faculty of Medicine, Tanta University, Egypt
Correspondence: Ayman Elnemr, M.D,Ph.D
Head of Surgical Oncology Unit, Department of Surgery, Tanta University,
mobile: +20(10)624-5403; home: (040)536-0910, E-mail: [email protected]
2
Abstract
Background: It is well known that cancer cells disseminate inside the peritoneum by
seeding and direct attachment to peritoneal mesothelium closer to blood vessels, followed
by angiogenic switch and neovascularization. This is the first study to demonstrate the
lymphatic invasion in peritoneal dissemination using the monoclonal antibody (Mab) D240 to identify the lymphatic endothelium. Methods: A total of 10 consecutive patients
with 90 resected peritoneal specimens of the different zones in cases of peritoneal surface
malignancy were investigated. Expression of D2-40 in lymphatic endothelial cells was
examined immunohistochemically in the formalin-fixed and paraffin-embedded
specimens. D2-40-positive lymphatic vessel distribution and density (LVD) at the
different peritoneal zones were quantitatively evaluated. CEA Mab was used to
identifying the invading cancer cells. Results: Lymphatic endothelial cells in all
examined tissues expressed D2-40. Its positive staining delineated flattened channels or
open spaces lined by a single layer of endothelial cells. Lymph vessels lined with D2-40
were visualized just below the mesothelial layer of the peritoneum especially in the area
of falciform ligament, followed by the right subdiaphragmatic peritoneum and paracolic
gutters. Clusters of cancer cells were identified in the lymph vessels of the submesothelial
layer. The frequency of the invasion to the submesothelial layer lymph vessels correlated
27
with presence of microscopic invasion. Conclusion: There were lymph vessels in the
submesothelial layer of the peritoneum, and cancer cells can spread through these
channels, and permeate to the deep large lymph vessels. We conclude that our concept of
lymphatic invasion as possible route for peritoneal dissemination could be supported by
using Mab D2-40, as a new selective marker of lymphatic endothelium.
O 3.5
Tumor Markers
A step in new tumor markers for HCC
Mohamed Fathey Elgazzar M.D. Internal Medicine; Tawhid Mohamad Mowafy, Professor of
Internal MedicineNabil Atia Khatab Professor of internal medicine; Abd elaziz Zydan
Professor of clinical Pathology; Magda Hamed Bakr Professor of pathology
Corresponding author: Mohamed Fathey Elgazzar M.D. Internal Medicine.
Consultant of Internal medicine, Banha University, 3Kornish st., Stad area, Tanta, Egypt
[email protected], Telephone: 01000128881
Abstract:
Background: AFP is considered as the reference biological marker for HCC; however
the lack of increase of AFP in some cases justifies the search for new markers. Hepatic
tumor cells produce and release t-PA, fibrinogen and PAI-1. Aims: to determine the
reliability of t-PA, fibrinogen and PAI-1 in detection of primary liver cancer as compared
to or combined with the established tumor marker AFP. Patients and methods: We
performed a comparative study of plasma level of PAI-1 antigen, t-PA antigen,
fibrinogen antigen and alpha fetoprotein in twenty cirrhotic patients of post viral
hepatitis, 45 HCC patients with a history of pre-existing cirrhosis with only one focal
lesion without metastasis, divided into subgroup A tumor size <5cm and subgroup B with
tumor size >5cm. Group III consists of 10 normal control persons. Results: PAI-1 was
significantly increased in HCC patients than cirrhotics and normal control groups. t-PA
level was significantly elevated in cirrhotics than normal group. Fibrinogen level was
significantly elevated in HCC than cirrhotic and normal groups. Alpha fetoprotein level
was significantly elevated in HCC than cirrhotic and control groups. Plasma levels of
PAI-1, fibrinogen and t-PA antigens were higher in patients with tumor size >5cm than
<5 cm tumor sized patients. Conclusion: PAI-1, AFP and fibrinogen can be used as
markers for detection of HCC especially when combined with each others and they have
competitor cost effectiveness. Plasma PAI-1antigen, t-PA, fibrinogen and AFP can be
used in follow up of HCC progression, its response to treatment and its relapse.
Key words: HCC, tumor markers, PAI-1, t-PA, fibrinogen.
28
Abstract 5.1
O 3.6
Tumor Markers
Cancer Genetics
Correlations of genetic mutations of Fibroblast Growth Factor Receptor 3 in
schistosomal bladder cancers with the expression profile of Epidermal Growth
Factor Receptor
Elsayed I. Salim, Ph.D. (D.M.Sc.)
Ass. Professor of Toxicological Pathology & Molecular Carcinogenesis. Zoology Department, Faculty of
Science, Tanta University, Tanta-31527- Egypt
Asian Pacific Organization for Cancer Prevention (APOCP). E-mail: [email protected];
[email protected] Telefax: (+20) 040 3350804; Cell: (+20) 01220177760
Abstract
We have recently proposed a molecular mechanism of induction of Schistosomal bladder
cancer due to increased levels of oxidative stress accompanied by DNA damage and
repair (Salim et al., Int. J. Cancer, 1;123(3):601-8.2008). The present study analyzed the
possible prognostic value of the fibroblast growth factor receptor (FGFR3) genetic
mutations in bladder cancer accompanied or not with Schistosomiasis in Egyptian
patients. FGFR3 belongs to a family of structurally related tyrosine kinase receptors, the
FGFR family, which are regulating cell proliferation, differentiation, migration and
angiogenesis. A FGFR3 mutation, evaluated by a PCR-single-stranded conformation
polymorphism (PCR-SSCP) analysis was found in 6 out of 17 (35.3%) Schistosomal
squamous cell carcinomas (SCCs), all had G→A transition in exon 7. Also one out of
four tumors (25%) of superficial urothelial carcinomas (UCs) had a mutation of A→G
transition in exon 15. In addition, the immunohistochemical expression status of FGFR3
and EGFR-1 were significantly higher in superficial Schistosomal SCCs and UCs in
comparison to invasive UCs and bilharzial cystitis cases. In conclusion, the results show
that Schistosomal SCCs and Papillary UCs have higher prognostic levels than invasive
tumors and bilharzial cystitis in bladder cancer patients.
Session 4: Stem cells
O 4.1
Apoptosis from Basics to Therapy
Stem Cells
Faris Q. Alenzi, PhD
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University,
AlKharaj, Saudi Arabia
Tel: 00966 1 5454518, Fax: 966 1 5454586, E-mail: [email protected]
Abstract
It is increasingly clear that apoptosis plays a central role in the pathogenesis of several
human diseases. For instance, an increase in apoptosis leads to cell loss accompanied by
29
neurodegenerative diseases, whereas we know that genetically determined defects of
apoptosis result in deregulated cell proliferation, typical of cancer. Hence, apoptosis
may be relevant as therapeutic targets for many human diseases. M y t a l k reviews
briefly the regulation and the clinical relevance of apoptotic mechanisms in several
different human diseases.
O 4.2
Stem cell origin of gastric cancer
Stem Cells
Sherif M. Karam
Department of Anatomy, Faculty of Medicine and Health Sciences, UAE University, PO Box 17666, Al-Ain,
United Arab Emirates; E-mail: [email protected]
Abstract
In the stomach, the epithelial stem cells undergo perpetual proliferation and
differentiation to maintain the steady state of four main cell lineages secreting mucus,
acid, pepsinogen and various hormones. Alteration of the gastric stem cell differentiation
program in genetically engineered mouse models induced some events that occur during
gastric carcinogenesis, e.g. loss of parietal and zymogenic cell lineages. In addition, the
gastric epithelial stem/progenitor cells were amplified. These hyperplastic stem cells
expressed glycoconjugates specific for adhesins of Helicobacter pylori. With age, these
mice developed gastric adenocarcinoma suggesting a role for stem cells in the origin of
cancer. To examine whether the stem cells also play a similar role in the human stomach,
we have recently assembled an array of gastric mucosal tissues obtained from informed
patients undergoing endoscopy (due to upper gastrointestinal symptoms) and gastrectomy
(for gastric adenocarcinoma). Tissues were processed for histological and
immunohistochemical analysis. Some tissues were frozen and later processed for Western
blotting using stem cell-specific antibodies (anti-Oct4). Eighty nine biopsies were
examined and categorized as: normal (33%), mild superficial gastritis (34%) and severe
atrophic gastritis (33%). About 5% of the latter exhibited evidence of intestinal
metaplasia. Cancer tissues obtained from three patients were examined in three regions:
safe resected margin, tumor edge and tumor center. Progressive changes in mucosal
thickness, dysplasia and cellular transformation were observed, and when compared with
alterations in biopsies, all appeared to represent a continuum of progression toward
invasive adenocarcinoma. Interestingly, epithelial stem/progenitor cells were amplified
during the early stages of gastric carcinogenesis. In conclusion, our studies on mice and
humans provide some evidence in support of the stem cell origin of cancer and would
help in designing new modalities for early detection and/or prevention of gastric cancer.
(Funded by Terry Fox Foundation for Cancer Research).
30
O 4.3
Stem Cells
The CD34+ blood stem cells in the umbilical cord: cell aging, chromosomal
instability, telomerase, and telomerase functions
Akram M. Abouzied
Zoology Dept., Faculty of Science, Suez Canal University, Ismailia, Egypt. E-mail: [email protected]
Abstract
Stem cells refer to the cells that have a capacity to divide, self renewal and multipotency.
Umbilical cord blood is attractive as a stem cell source for the following reasons: (a) it is
a resource that is usually being discarded; (b) it is rich in stem cells of fetal origin with
considerable proliferative potential; (c) the stem cells have reduced immuno-competence
making them permissible; (d) the cells are usually more readily available. However, the
disadvantages of using cord blood include the relatively small size and a longer time of
collection causing an increase risk for infections, cell viability and genomic instability.
Hematopoietic stem cells (HSCs) give rise to lineage restricted stem cells, which can
further differentiate into numerous blood cell types. Chromosomes are essential for cell
viability and directly involved in shaping the karyotypes of stem cells. Therefore,
structures, numbers and chromosome ends are required for chromosome stability. Stem
cells require active telomere elongation mechanisms to grow indefinitely. On the basis of
our experimental data, this could vary with respect to the source (e.g. bone marrow
peripheral blood, cord blood, age, pathology, treatment, processing procedure and so on).
Our objective in this review is to summarize the knowledge about CD34+ cells isolated
from umbilical cord and focus mainly on cell aging, chromosomal instability and
telomerase functions. The status of CD34+ cells from umbilical cord may show the same
number but could give unsatisfactory results in a promising stem cell research and
clinical practice.
Key Words: Human; CD34+; Umbilical cord; Stem cells; Chromosome ; Telomerase; Cell aging;
Chromosome instability
O 4.4
Stem Cells
Brief in vitro triggering of toll-like receptor signaling in fresh bone marrow cells
induces acquisition of dendritic cell-like phenotype and effective antigen
presentation capability
Mohamed Labib Salem and Sabry EL-Naggar
Immunology and Biotechnology Unit, Zoology Department, Faculty of Science, Tanta University, Egypt
Correspondence: Prof. Mohamed Labib Salem (PhD): e-mail: [email protected]
Tel. 0127 427 2624
Abstract
Background: Stem cell based therapy has been explored as a promising means to
overcome obstacles that meet the conventional therapy. Bone marrow (BM) is one of the
main sources of the adult hematopoietic stem cells. Treatment with chemotherapeutic
31
drug, in particular cyclophosphamide (CTX), alone or in combination with mobilizing
growth factors is known to increase the numbers of stem cells in the circulation. We have
reported recently the effectiveness of CTX to induce BM to yield higher numbers of
dendritic cell in vitro upon treatment the fresh cells in vitro with granulocyte-macrophage
colony stimulating factor (GM-CSF) and interleukin-4 (IL-4) for 7 days. Although this
beneficial effect of CTX to yield high numbers of dendritic cells is considered as a
significant advantage, the technology of the generation of dendritic cells in 7-10 days in
vitro is laborious and expensive. Aim: In this study we aimed to generate cells expressing
dendritic cell phenotype from BM after brief stimulation with toll-like receptor ligands
(TLRLs). Methods: Naïve mice were treated with an intraperitoneal injection of a single
dose of PBS or 200mg/Kg (4mg/mouse) of CTX. Mice were sacrificed after 2 days, the
time point we have reported to mobilize stem cells, and bone marrow was harvested and
cultured overnight after lysis of RBCs. The cultured cells were left alone or stimulated
with 5-10ug/mL of TLR2/6L (zymosan), TLR3L (poly(I:C)), TLR4L (lipopolysaccharide; LPS) , TLR6L (pam3), TLR7/8L (imiquimod) or TLR9L (unmethylated
ODN DNA; CPG) alone or in combination. The cells were harvested and analyzed by
flow cytometry for surface markers. The antigen presenting function of the harvested
cells was assessed in vitro after their pulsing with the MHC class-I OVA peptide
(SIINFEKL) after co-cultured with OT-1 CD8+ T cells that are genetically engineered to
specifically recognize this antigen. Results: BM harvested from CTX-treated mice should
higher numbers of cells expressing the myeloid markers CD11c, Ly6G and CD11b than
PBS-treated mice. Stimulating BM cells with different TLRLs induced much higher
numbers of the cells to co-express CD40, CD80, and CD86, the typical markers of the
activated dendritic cells. The TLR9L showed the highest effect, followed by the tLR3L
and TLR7/8L in particular in combination. Of more interest, the BM from CTX treated
mice conditioned with TLRLs showed superior antigen presenting function as evidenced
by their capability to induce OT-1 cells to proliferate in vitro and produce IFN-g.
Conclusion: BM cells from a host treated with chemotherapeutic drug can function as
antigen presenting cells upon brief stimulation with TLRls. These data have a significant
implication in immunotherapy against cancer and viral diseases.
O 4.5
Stem Cells
The differentiation of mesenchymal stem cell derived from the human umbilical
cord blood into heptocyte-like cells
Khalil A. Elhalfawy1, Medhat S. Hdwidy2, Ezzat A.El-Drieny3, Ehab M.M. Ali4, Batoul M.
Izzularab5
1. Professor of Genetic Engineering, Iinstitute of Genetic Engineering, Minoufiya University, Egypt
2. Professor of Obstetric and Gynacology, Faculty of Medicine, Tanta University, Egypt
3. Professor of Histology, Faculty of Medicine, Tanta University, Egypt
4. Professor of Biochemistry, Faculty of Science, Tanta University, Egypt
5. PHD student (Biochemistry Division), Faculty of Science, Tanta University, Egypt
Corresponding author: Batoul M. Izzularab: E-mail: [email protected]
32
Abstract:
The capacity of mesenchymal stem cell (MSCs) in the differentiation into specific cell
type make them very promising in tissue regeneration and repair. In this study
characterization of hepatocyte cell differentiated from human umbilical cord blood
(HUCB) mesenchymal stem cell in relation to their molecular expression and
morphological structure .MSCs were isolated from the cord blood by easy step
technology. Cultured cells were treated with fibroblast growth factor (FGF-4), hepatocyte
growth factor (HGF), Oncostain M (OSM), leukemia inhibitory factor (LIF) and stem cell
factor (SCF). Approximately 90%of cells were differentiated into hepatocyte on day 28
by immunostaining with CK8-18.Conventional and real time PCR showed that the
differentiated cells expressed number of hepatocyte specific genes. Electron microscopic
examination showed that the differentiated cells are structurally similar to hepatocytes.
HUCB-derived MSCs are a new source of cell type for cell transplantation and therapy.
Key words: Mesnchymal stem cell, Human umbilical cord blood, Differentiation, Hepatocyte
33
34
1. Therapy (Human Studies)
P 1.1
Therapy (Human Studies)
Paratesticular rhabdomyosarcoma of the young adult in a case report
Imane Ouafki, H. El yacoubi, T.Sghiri, S.Boutayeb , H.Mrabti , H.Errihani
Department of Medical Oncology, INO, CHU Rabat, Morocco.
[email protected]
Abstract
Introduction: The paratesticular rhabdomyosarcoma (RMS) is a rare tumor, observing
at any age, but especially in children and young adult. It develops from the mesenchymal
tissues of spermatic cord, epididymis and testicular tunics. It is characterized by its rapid
evolution with a poor prognosis. Case report: We report a case of embryonal
paratesticular rhabdomyosarcoma, in a young adult of 19 years, treated with
chemotherapy at the National Institute of Oncology (INO) in Rabat in 2010. The fact
discovery was a spontaneous right large purse, having gradually increased in
volume,accompanied by severe pain radiating along the spermatic cord.Clinical
examination revealed a painful scrotal lobed mass of 6 cm in diameter,with inguinal
extension and seems independent of the testicle. The testicular ultrasound showed a
homogenous echotexture of right testicle with a large heterogeneous mass fluid
measuring 58mm x 56mm in diameter and lateralized to the right, pushing back the right
testicle, the left testicle is normal. Abdominal ultrasound showed no deep pyelocaliceal
expansion. Cystoscopy confirmed the presence of a tumor occupying the entire right side.
Transurethral resection of bladder tumor was incomplete. Pathological examination was
in favor of a bladder leiomyosarcoma. The uroscan showed a process of bladder filling
peri-vesical fat and invading the right ureteral meatus, measuring 39.7 x 27.6 x 39 mm.
The treatment consisted of a radical cystoprostatectomy with urinary diversion type
Briker and bilateral ilio-obturator lymph node dissection. Pathological examination of the
specimen revealed the presence of a high-grade bladder leiomyosarcoma. The limits of
resection were healthy. Lymph nodes were invaded.Our patient had adjuvant
chemotherapy based on six cycles of doxorubicin and ifosfamide. It is in good control
with a decline of 6 months. Discussion: The bladder leiomyosarcoma is a relatively rare
tumor, representing less than 1% of bladder cancers. It occurs in patients between the
sixth and eighth decade with a male predominance. Its prevalence is higher among
patients treated with cyclophosphamide with an increased risk x 9. The mode of
revelation is a macroscopic hematuria in 80% of cases, less frequently on the occasion of
obstructive symptoms or abdominal mass. Diagnosis is based on pathological
examination with immunohistochemical study. A review of the experience of the MD
Anderson study reported 14 patients with bladder leiomyosarcoma. They had undergone
35
radical cystectomy with urinary diversion Briker type, followed by adjuvant doxorubicin
and dacarbazine or vincristine, doxorubicin and cisplatin. The overall survival at 5 years
was 59% with a median survival of 6 years. Conclusion: The bladder leiomyosarcoma is
a rare disease .His prognosis seems increasingly improved with the advent of
chemotherapy, ensuring completion of surgery in advanced or metastatic tumors, and
reducing the risk of local recurrence or metastatic disease after adjuvant therapy
lymphadenopathy, the tumor markers (hCG, LDH, α FP) was normal. The scans of the
chest, abdomen and pelvis were without abnormalities.He underwent an inguinal
orchiectomy with ligation of the spermatic cord. Histological examination of the
specimen was in favor of an embryonal rhabdomyosarcoma confirmed by
immunohistochemical study. The patient was reoperated 10 days later, a right
hemiscrotectomy is performed, histologic examination showed no scrotal
invasion.Chemotherapy Based on six cycles of doxorubicin 60 mg / m² and Ifosfamide 9
mg / m² is established one month postoperatively. The patient is in good control.
Conclusion: The paratesticular RMS is a rare tumor, which requires early diagnosis and
accurate staging. The treatment is now well codified and thanks to the combination
surgery, chemotherapy and radiotherapy the prognosis has improved significantly.
Adequate long-term monitoring must be introduced to detect relapses which are generally
fatal.
P 1.2
Therapy (Human Studies)
Tamoxifen resistance in breast cancer: cCytochrome p450 2D6 gene copy number in
Iranian patients
Keivan Majidzadeh-A, MD, MPH, Ph.D; Rezvan Esmaeili, Ph.D candidate; Mahta Mazaheri,
MD, Ph.D; Leila Farahmand, Pharm D., Ph.D; Sahar Motamedi, Msc
Cancer Genetics Research Group (CGRG), Iranian Center for Breast Cancer (ICBC), Academic Center for
Education, Culture and Research (ACECR), Iran
e-mail: Dr. Keivan Majidzadeh <[email protected]
Abstract
Background: Tamoxifen is one of the most effective adjuvant breast cancer therapies
available. The rate of metabolism of this medicine is mainly determined by the amount of
cytochrome p450 2D6 (CYP2D6) enzyme expressed in the liver, which is highly variable
due to its extensive genetic polymorphisms and copy number variation. So copy number
variation maybe one of the most important mechanisms of resistance to Tamoxifen. Aim:
Since there is limited information about CYP2D6 in resistant patients, we aimed to
determine copy number of this gene in Tamoxifen resistant Iranian breast cancer patients.
Materials and Methods: Samples: A total of 23 unrelated Iranian Tamoxifen resistant
and 56 sensitive breast cancer patients as the control group were obtained from Iranian
Center for Breast cancer Bio-Bank (ICBC-BB). DNA extraction was done using phenol
chloroform method and the extracted DNA concentration was quantified using
spectrophotometery. Copy number analysis: Establishment of standard curves for copy
number determination was done by cloning of CYP2D6 fragment as the gene of interest
36
and albumin gene as a copy number control in TA cloning vector. PCR Primers were
designed using primer express V.3.0 software. Real-time PCR was performed using the
ABI 7500 system apparatus. Amplification reactions (20 ul) were carried out in triplicate
with 40 ng of template DNA, SYBR Green Master Mix buffer (PrimerDesign Ltd, UK)
and 300 nM of each primer. Each sample was run triplicate with 4 fold serial dilutions in
the same plate. Samples with standard deviation greater than 0.5 from the mean threshold
cycle of the triplicates were excluded from the analysis. Copy number calculation was
done using applied biosystems SDS software ver2.0. Result: Primer efficiency for
CYP2D6 and Albumin was 104 % and 97% respectively. The copy number range was
0.4 to 3 and no significant difference was seen between resistance and nonresistance
group in this phase of study. Conclusion: Although no significant difference was
detected between two groups in this phase of the study, it does not mean that copy
number variation play no role in resistant group in the samples. Further analysis including
genotyping and multivariate analysis considering other factors for tamoxifen resistance
and also increasing sample size must be done in order to decide about CYP2D6 status in
tamoxifen response in Iranian samples.
Key words: CYP2D6, copy number, tamoxifen
P 1.3
Therapy (Human Studies)
A case of orbital rhabdomyosarcoma in adults
Imane Ouafki, H.El Yacoubi, T.Sghiri, S.Boutayeb ,H.M’Rabti, H.Errihani
Department of Medical Oncology, INO, CHU Rabat, Morocco. E-mail: [email protected]
Abstract
Introduction: Rhabdomyosarcoma is a malignant mesenchymal tumor, the most
common. It represents 60-70% of mesenchymal tumors and 5% of all malignancies. It is
the primary malignant orbital tumor most common in children, but it can occur at any
age. This is an emergency diagnostic and therapeutic care that is based on a
multidisciplinary approach. The originality of our case is related to patient age and tumor
histology. Case report: We report the case of a patient of 26 years, presented in August
2009 with a unilateral right rapidly progressive proptosis. Radiological assessment
showed an intraorbital expansive process of the lacrimal gland without invasion of the
optic nerve. A biopsy of the tumor was performed. Pathological examination was in favor
of embryonal rhabdomyosarcoma. Neoadjuvant chemotherapy (VAC) was administred
which allowed a reduction in tumor size by 40%. After six cycles the patient underwent
right exenteration, but the surgical limits were invaded. Two months later, he relapsed
locally and bone. He received first line chemotherapy: etoposide plus cisplatin with
stabilization after six cycles. Three months later, brain CT has objectified a right large
intraorbital tumor process with intracranial extension and significant lesion progression
by 114.2 x79, 9 mm long axis (vs. 37 x 25).A second-line chemotherapy (high dose
ifosfamide) was administered, with a complement of local radiotherapy.Discussion:
Rhabdomyosarcoma is a rare malignant tumor with an average age of discovery of 8
37
years, with a slight male predominance:sex ratio of 1,4. Its occurrence in adults is
exceptional. The clinic is non-specific. This may be a unilateral exophthalmos, not axial,
irreducible and rapidly progressive, with local inflammatory signs, an ophthalmoplegia or
swelling of eyelid. The MRI and CT allow oculo-orbital study of the anatomical
relationship of the tumor and staging. The CT scan appearance is fairly limited tissue
mass, making the contrast; if tumor extended, we have a total filling of the orbit. The
tumor extension is towards the ethmoid, nasal cavity and the cavernous sinus. However,
the CT is limited by the fact that it does not differentiate between tumor and sinus
retention. In addition, MRI can properly analyze periorbital extensions. Histologically,
the embryonal type is the most common and usually occurs in young children. After 10
years, the alveolar type is most often found. In addition to the atypical age of our patient,
histological type is unusual. The diagnosis of rhabdomyosarcoma is based on
pathological examination. The local expansion is specified mainly by CT, MRI
secondarily. The treatment is based on chemotherapy with or without radiotherapy.
Monitoring is done by the clinic and imaging. It allows early detection of possible local
recurrence in 70 to 80%, or metastatic in 30%. The risk of recurrence decreases over 3
years to become lower after 6 years.Conclusion: Although exceptional in adults, the
diagnosis of rhabdomyosarcoma should be considered in orbito-palpebral rapidly
progressive swelling. The diagnosis and treatment of this disease should be initiated early
to improve prognosis. The frequency of metastases and / or recurrence requires a
prolonged clinical and radiological surveillance.
P 1.4
Therapy (Human Studies
Assessing the response of radiotherapy in treating the patients with lung cancer
Yasha Makhdoumi1, Mehrdad Soltani Delgosha2, Amir Houshang Youssefi3, Isa Bilejani3
Mashhad university of Medical science1, Reza Oncology Centre2, Tabriz University of Medical science3,
IRAN. Correspondence: Dr. Mehrdad Soltani Delgosha. [email protected]
Abstract
Introduction: Lung cancer is the deadliest type of cancer. Each year, more people die of
lung cancer. Lung cancer is more common in older adults. There are many different types
of treatment like surgery, chemotherapy and Radiotherapy. Treatment depends on the stage
of cancer. One of the main ways of treatment is radiotherapy. Aim: In this study, we
investigate the effect of radiotherapy on survival rate of patients with lung cancers.
Material& Methods: in this retrospective study, we assessed 111 patients with lung
cancers who were admitted in Imam Khomeini hospital in Tabriz. All the patients got
radiotherapy as main treatment. For each patient total radiotherapy dosages, fractions,
duration of therapy and survival were determined and analyzed. Results: the mean age of
patient was 60. 80.2% patients were male and 19.8% were female. 25.2% were operated,
18% were got chemotherapy.Total dosages were used from 1000CGy to 9000CGy.The
range of fractions was between 2 and27 in which the mean was 19. Duration of
radiotherapy was 4 to 5 weeks.The survival rate of patients was 0 to 48 months in which
38
there wasn't significant difference between SCLC and NSCLC (p=0.05,t-test).By
correlation test we found out there was significant correlation between radiotherapy
dosage and survival rate of patients. There was no significant relationship between the
fractions of radiotherapy and survival rate. Conclusion: increasing the dosages and
fractions in the appropriate range will significantly improve the survival rate of patients
with lung cancers, in our study the mean of survival was 6.32 months which 8.8% of
patients survived more than 1year.
Key words: Radiotherapy, lung cancer, survival.
P 1.5
Therapy (Human Studies
Protective effect of carvedilol on Adriamycin-induced left ventricular
dysfunctionvin children with Acute Lymphoblastic Leukemia
Nagla A. El-Shitanya,Osama A. Tolbab, Mohamed R El-Shanshoryc, EslamE. El-Hawaryc
a
Department of Pharmacology and Toxicology, College of Pharmacy, Tanta University, Tanta, Egypt
Pediatric Department, College of Medicine, Cardiology Unit, Tanta University, Tanta, Egypt.
c
Pediatric Department, College of Medicine, Hematology and Oncology Unit, Tanta University, Tanta,
Egypt.
Correspndence: Dr. Nagla Fouad El-Shitany; Asociate Prof of Pharmacology And Toxicology (e-mail:
[email protected]
b
Abstract
Adriamycin (ADR) is a potent chemotherapeutic agent widely used in the treatment of
childhood acute lymphoblastic leukemia (ALL); its clinical use is limited for its marked
cardiotoxicity. The present study aimed to investigate the possible protective role of
carvedilol on ADR-induced left ventricular dysfunction in children with ALL.Fifty newly
diagnosed ALL children were included in this study. They were divided into two equal
groups; 1- ADR group, 2- carvedilol + ADR group. Patients were evaluated with
conventional 2-dimensional echocardiographic examination (2-D), pulsed tissue Doppler
(PTD), and 2-D longitudinal strain echocardiography (2-DS) before and after therapy.
Plasma troponin I, LDH and CPK levels were also determined before and after
therapy.ADR treatment induced left ventricular systolic dysfunction as assessed by
significant decrease in fractional shortening (FS) (2-D) and global peak systolic strain
(GLPSS) (2-DS). In addition, ADR treatment significantly increased plasma troponin I
and LDH. Pretreatment of ADR-treated patients with carvedilolresulted in significant
increase in FS (2-D), and GLPSS (2-DS). Alsocarvedilolpretreatment inhibited ADRinduced increase in the plasma troponin I and LDH.These results suggested that,
carvedilolcould be used to protect the heart against the cardiotoxic effect of ADR. Large
scale studies are recommended, to allow further assessment of the protective role of
carvedilolin ADR-induced cardiotoxicity in cancer patients.
39
2. Anti-Tumor Immunity
P 2.1
Anti-tumor Immunity
Dendritic cell-based vaccine in cancer: total RNA vs cancer testis chimeric antigens
RNA in esophageal squamous cell carcinoma
Mohammad Reza Abbaszadegan, Ph.D.1, Mehran Gholamin, Ph.D.1, Mohammad Mahdi
Forghanifard, Ph.D.1, Omeed Moaven, M.D.1, Moein Farshchian, M.Sc.1, Bahram Memar,
M.D.4, Mohammad Naser Forghani, M.D.3
1
Division of Human Genetics, Immunology Research Center, Avicenna Research Institute, Mashhad
University of Medical Sciences (MUMS), Mashhad, Iran
2
Department of Pathology, Omid Hospital, MUMS, Mashhad, Iran
3
Department of Surgery, Omid Hospital, MUMS, Mashhad, Iran
Correspondence: Dr. Mohammad Reza Abbaszadegan (PhD); [email protected]
Abstract
Introduction: Esophageal cancer is the seventh most common cause of cancer deaths
worldwide and the fifth leading cause of cancer-related death in Iran. Squamous cell type
of the cancer (ESCC) consists 95% of all cases. The high incidence areas of Iran include
Golestan and Khorasan Provinces in northeastern Iran with incidence rate of ASR of 43.4
per 100,000 for men and 36.3 for women. These regions of Iran are located in a high risk
area designated as “Central Asian Esophageal Cancer Belt”. Most cases of ESCC are
diagnosed in advanced stages. Surgical treatment and adjuvant therapeutic modalities
such as chemo- and radiotherapy have only a minimal effect on patient outcome and the
overall 5-years survival rate is less than 25%. Development of vaccines against ESCC
may improve the therapeutic modality as a neo-adjuvant. Methods: We evaluated the
capability of autologous Dendritic cells (DCs) transfected with total tumor and normal
RNA as compared with mRNA of chimeric tumor antigen epitopes (ChiTA) to induce
cytotoxic CTL as the preliminary step to design a DC-based vaccine in the ESCC.
Monocytes-derived DCs were electroporated with either total tumor or normal RNA or
ChiTA mRNA. T cells were then primed with tumor or ChiTA RNA transfected DCs and
lytic effects of the generated CTL were measured with Calcein-AM cytotoxicity assay
and IFN-γ Release Elispot assay. Results: Cytotoxicity was induced against DCs loaded
with tumoral RNA (%24.8 ± 5.2 SEM) while in normal RNA- loaded DCs, it was
minimal (%6.1 ± 2.4 SEM) and significantly lower (p < 0.05). INF-γ secretion was more
than 2-folds higher in tumoral RNA-loaded DCs when compared with normal RNAloaded DCs (p < 0.05). Significantly higher differences were obtained in lyses of cells
loaded with chimeric mRNA vs Mock cells by ChiTA-stimulated lymphocytes, using
cyotoxicity test, %65 vs %4 (P < 0.05). Conclusion: Stimulation of immune system
using pulsed DC with ChiTA mRNA which has tumoral antigens epitopes as compared to
total tumoral RNA may have a better advantage to develop DC-vaccine as a new
therapeutic modality against ESCC.
Key words: Dendritic Cell, Vaccine, Chimeric, Tumor antigen, Esophageal cancer, RNA
40
P 2.2
Anti-tumor Immunity
In vivo generation of splenic dendritic cell subsets by Berberis Vulgaris extract
Doaa A. Ghareeb1, Eiman H. El-Wakeel2, Maha A. El-Demellawy3, Marwa Abo Sariaa3,
Mohamed Abd El Sallam4, Mina Saad1, Noha Habachi1, Amel Abd Elmagied1, Hend M.
Hussein5
1Biochemistry Department, Faculty of Science, Alexandria University, Egypt
2 Microbiology and Botany Department, Faculty of Science, Alexandria University, Egypt
3 Biomedical technology Department, City of Scientific Research and Applied Technology, Egypt
4 Pharmacognosy Department, Faculty of Pharmacy, Alexandria University, Egypt
5 Faculty of Pharmacy, Faros University, Alexandria, Egypt
Correspondence: Dr. Doaa A. Ghareeb, e-mail: [email protected]
Abstract
Dendritic cells (DCs) are unique antigen presenting cells that are immature prior to their
encounter with an antigen. The efficient capacity of DCs to initiate and regulate
lymphocyte-mediated immunity has led to the study of DCs as cellular vaccine. In this
study, we demonstrated a novel approach for implementing and characterizing an
efficient DCs-base immunization. DCs were expanded in vivo by intraproteneal and
intravenous injection of mice with Berberis vulgaris crude ethanolic extract (BRB) at
dose of 30 and 60 mg/kg for IV and at 100 and 200 mg/kg for IP administration route.
Spelenocytes were isolated then splenic DCs were purified with magnetic micro beads.
Our results showed that IP BRB administration increased enriched DC population by 10
and 15 % while IV injection increased it by 18 and 25% respectively that combined with
a significant increase in Interleukin 12 (IL12) secretion by four fold at IV BRB injection
(60 mg/kg), in comparison to a negative control. Therefore, BRB can be used to
increased DC production that will open a new hope in HCV treatment as it is well known
that DC and IL 12 are progressively decreased in HCV patients.
P 2.3
Anti-tumor Immunity
Recombinant human anti – ALCAM (Activated leukocyte cell adhesion molecule)
antibody scFv fragment production in bacterial host
Leyla Farahmand, Ph.D Candidate; Keivan Majidzadeh-A, MD, MPH, PH.D; Alireza M. Ansari, Ph.D
Candidate; Nasrin Abdoli, MSc
Cancer Genetics Research Group (CGRG), Iranian Center for Breast Cancer (ICBC), Academic Center for
Education, Culture and Research (ACECR), Iran
E-mail: Kkeivan Majidzadeh" <[email protected]>
Abstract
Background: Recent studies demonstrated that cancer may arise from stem cells known
as cancer stem or tumor initiating cells (TICs) which might be in charge of primary and
metastatic tumor growth. So stem cells are considered as potential therapeutic and
diagnostic targets for many types of cancers such as breast cancer. Cancer stem cell
marker profiles have been suggested for many tumors, with several markers such as
41
Activated leukocyte cell adhesion molecule (ALCAM) (CD166). ALCAM is a cell
adhesion molecule which play critical role in cell migration and cancer progression.
Aim: The molecular methods developments and the evaluation of the structure and
function of the antibodies have made it possible to create new generation of antibodies,
known as recombinant human antibodies. These antibodies and their derivatives have
emerged as an important targeted therapy and diagnostic agents and fast growing group
within biotech-pharma research. Materials &methods: DNA fragments encoding the
light and heavy variable (VL, VH) regions were obtained by amplification of germ line
antibody variable segments using polymerase chain reaction (PCR). Amplified sequences
were mutated to encode the anti – ALCAM (VL, VH) regions. VL and VH were
operatively joined together by a linker to generate scFv (single-chain variable fragment)
and inserted into a dicistronic expression vector. Expression cassette transformed to the
bacterial host and was cultured in LB medium. Produced antibody was assayed by
conventional methods. Results: Dicistronic expression vectors were constructed for the
antibody scFv fragment and Expression of antibody fragment was processed successfully.
Whole cell harvested from induced cultures electrophoretically separated by Laemmli
gel. Assembled antibody was observed under Non-reducing condition. Other
conventional assays showed other related results, respectively. Conclusion: ALCAM is
classified as an adhesion molecule so anti ALCAM antibodies can suppress cell
migration, cancer growth and metastasis. Despite vital role of antibodies in therapeutic
regimens, cost of producing recombinant antibodies at large scale is a big problem.
Bacterial hosts, such as Escherichia coli, are an alternative route and potentially more
economical expression system for production aglycosylated antibodies and their
fragments.
P 2.4
Anti-tumor Immunity
Molecular immunological studies on a novel zymosan-binding protein (ZBP-240)
Soha Gomaa1, Miki Nakao2
1
Labortory of Biotechnology and Immunity, Tanta University Egypt,
Biotechnology, Kyushu University, Japan
Correspondence: Soha Gomaa; E-mail: [email protected]
2
Division of Bioscience and
Abstract
C3 has been recognized as a major serum protein with binding ability to zymosan, crude
yeast cell wall component. Unlike zymosan-binding proteins (ZBPs) of other vertebrates
tested to date, tilapia ZBPs contained a novel major polypeptide with molecular mass of
240 kDa, designated as ZBP-240, in addition to the iC3b fragment. ZBP-240 was purified
from tilapia serum by three chromatographic separations on Q-Sepharose HP, Superdex
200, and hydroxylapatite and digested chemically using CNBr or enzymatically by lysyl
endopeptidase releasing 2-3 digested peptides which are separated by RP-HPLC. On the
Superdex 200 column, ZBP-240 migrated as a ~400 kDa protein, suggesting that it is
42
present as a dimer in serum. ZBP-240 was also characterized for its binding ability to
various microbial targets like (gram-positive and gram-negative bacteria, different yeasts,
YCW and zymosan). Furthermore, ZBP-240 was demonstrated to show a significant
opsonic activity, like complement C3, for tilapia kidney phagocytes enhancing
phagocytosis. ZBP-240 also enhanced binding of C3 to the microbial targets, probably
resulting in further increase of C3-mediated target opsonization. More over, functional
assays of C3 and a novel ZBP-240 at the protein level demonstrated their binding and
opsonization of microbial targets, suggesting their unique coordination in pathogen
recognition and elimination. Based on the previous study, we may use this novel ZBP240 in cancer immunotherapy by studying its receptors on different cells as this protein
may enhance phagocytic cells through toll like receptors (TLR), how it activates different
cells like dendritic and T-cells and finally anti-tumer immunity.
3. Tumor Markers
P 3.1
Tumor Markers
Assessment of ki67 frequency in breast cancer patients without axillary lymph
nodes involvement and its relation with disease free survival condition
Fatemeh Homaei Shandiz, M.D.*1; Nourieh Sharifi, M.D.2; Monavar Afzalaghaee, M.D.3;
Emane Roshanzamir, M.D.4; Hossein Shabahang, M.D.5; Alireza Tavasoli, M.D.6; Shadi
Emami, M.D.; 7Javad Aghamohammadian
1Associated professor of Radiation Oncology, Cancer Research Center of Mashhad University Medical of
Sciences, Omid and Ghaem Hospitals, Iran;
2 Associated Professor of Pathology, Mashhad University Medical of Sciences;
3Assistant professor of Epidemiology, Mashhad University Medical of Sciences;
4 Mashhad University of Medical Sciences;
5 Associated professor of Surgery, Mashhad University of Medical Sciences;
6 Associated professor of Surgery, Mashhad University of Medical Sciences;
7Mashhad University of Medical Sciences;
7Assistant professor of Pathology, Mashhad University of Medical Sciences
*
Corresponding author: Dr. Fatemeh Homaei Shandiz, Associated professor of Radiation Oncology,
Cancer Research Center, Omid Hospital, Alandasht Sq., Mashhad, Iran, Tel: +98-511-8428621 / 8445647
, Fax: +98-511-8428622 , E-mail: [email protected]
Abstract
Introduction: The aim of this study was to assess ki67 frequency in breast cancer
patients without axillary lymph nodes involvement and evaluating of its prognostic value
in disease free survival and relation with other prognostic factors such as age, size of
tumor, pathologic subgroup, ER, PR, P53 and HER-2. Methods: Ki67 levels were
measured by IHC and compared with prognostic factors of tumor in lymph node negative
43
invasive breast cancer and its effect on disease free survival. Results: We assessed 106
women with the mean age 49. 94.3% of patients were invasive ductal carcinoma of breast
and mean of tumor size at diagnosis was 2.8 centimeter. 50.9% of patients were ER
positive and 47.2% of them were PR positive and P53 was positive in 48.1% cases.
According to IHC methode, only 8.5% of our patients were Her2/neu positive. Ki67 by
IHC method was positive in 66 (62.3%) patients. There was a meaningful relation
between ki67 positive cases and age (p=0.0229) and positive Her2/neu status
(KAPPA=0.043) and positive P53 cases (KAPPA=0.265). In positive ki67 cases, the
mean of age was less than negative ki67. After mean of 40 months follow up 13 patients
(12.3%) had recurrence. The most common kind of recurrence was systemic and in the
relapsing cases, 10 patients (77%) were Ki67 positive (p=0.0235) that was significance.
The 3 year disease free survival in Ki67 positive and negative patients were 89% and
85% (p=0.556). Conclusion: It is suggested to carry out survival study on more cases to
find out the relation between Ki67 positivity and cancer recurrence.
Key words: breast cancer; ki67 proliferative factor; negative Axillary lymph node;
disease free survival; Iran
P 3.2
Tumor Markers
A comparative immunohistochemical study of benign prostate hyperplasia (BPH)
and prostate cancer (PCa) in Sulaimani province using Prostate- Specific Antigen
(PSA) as a tumour marker
Sirwan Mustafa Muhammad*; Intissar Numman Waheed **
*Department of Biology\ College of Science\ University of Sulaimania; **School of Pharmacy\ Faculty of
Medical Sciences\ University of Duhok, Iran
Correspondence: Dr. Intissar Numman Waheed E- mail: [email protected]
Abstract
Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are two common diseases
in aging males and their prevalence increases exponentially with age. The current study
was applied to evaluate the significance of serum Prostate- Specific Antigen (PSA) as a
screening tool for the PCa and the role of percent free - to- total PSA ratio in the
discriminating between BPH and PCa as well as to experience immunohistochmical
expression of PSA in human prostate tissue specimens and scoring the staining intensity.
Prostatic biopsies and blood were collected from (62) patients aged between (50-89)
years. Also eleven healthy men with negative digital rectal examination, (median age,
60.6yr) were enrolled in this study as a control group. The commonest diseases
encountered were BPH (59.7%), BPH with prostatitis (19%), adenocarcinoma (17.7%),
and transitional cell carcinoma (3.2%). The intensity of PSA staining was scored as (0, 1,
2, and 3). 27% of BPH cases demonstrated strong staining scores of (3) and 47% of them
showed scores of (1), whereas 50 % of PCa cases showed scores of (1) with no cases of
PCa and prostatitis revealed staining scores of (3). 54% of BPH cases had tPSA level < 4
ng/ml as well 13.5% of them having tPSA>10, while 15.3% of Malignant cases had tPSA
44
level < 4 ng/ml and 84.7% of them having tPSA>10. The statistical analysis showed a
significant difference between (BPH and PCa ); (PCa and control cases) and (prostatitis
and control) in regard to tPSA. Regarding to % cPSA the entire cases of PCa showed
levels >60% aligned with only 75%, 27%, 16% in prostatitis, control and BPH groups
successively. The mean comparison showed statistically significant differences between
the PCa patients and control cases and between prostatitis and control cases, while no
significant differences between BPH and control group. Regarding to % FPSA, 53.8 % of
PCa cases showed ≤15, along with 16.6 % of prostatitis showed ≤15, while no cases of
both BPH and control revealed FPSA ≤15. Comparison of the means showed a
statistically large difference between the (PCa and BPH), (PCa and control) and
(prostatitis and control) cases. While no significant differences between (BPH and
control) cases. In conclusion PSA staining intensity was increased and expressed in a
strong and uniform pattern in BPH tissue sections in comparison with the PCa tissue
sections, in which the staining intensity was decreased. Combinational use of tPSA with
other molecular forms of PSA especially proportion of FPSA provide higher diagnostic
and differentiative accuracy than the tPSA alone.
45
46
Day 2
December 28, 2011
A- Special Session
Beating cancer cells to death with gold nanoparticles in more than one
way
Mostafa E l-Sayed, PhD
Professor, Juilius Brown Chair and Regent Professor, Director,
Laser Dynamics Lab, Georgia Institute of Technology
(http://ldl.gatech.edu), Atlanta, Georgia,, USA, E-mail:
[email protected]
Biography
Mostafa El-Sayed was born in Egypt where he received his B.Sc. He received his Ph.D.at Florida State
University with Professor Michael Kasha. After doing postdoctoral work at Yale, Harvard and Caltech, he
joined the faculty at UCLA. In 1994, he moved to Georgia Tech and became the Julius Brown Chair,
Regent Professor and Director of the Laser Dynamic Lab. El-Sayed and his group (over 70 Ph.D. students
and over 40 Postdoctoral Fellows) have contributed to many areas of physical and material chemistry
research. They have been involved in the development of new techniques such as magneto photo selection,
picoseconds Raman spectroscopy and phosphorescence microwave double resonance spectroscopy. Using
spectroscopic techniques, they have been able to answer fundamental questions regarding ultra-fast
dynamical processes involving molecules, solids and photo biological systems. Since he moved to Georgia
Tech, El-Sayed and his group became active in the study of the physical, chemical and photo thermal
processes of metallic and semiconductor nano structures of different shapes and compositions. The shape
dependent applications of the metallic nanoparticles in nano catalysis, nano motors as well as nano
medicine (in Cancer diagnoses and photo-thermal therapy) have been demonstrated.
El-Sayed has published over 520 peer-reviewed papers, gave over 45 special named lectures and over 250
invited talks at National and International meetings. He has served on numerous international and national
committees such as the Advisory Boards of NSF and Basic Energy Sciences of DOE and the National
Research Council Board of Chemical Sciences. Prof. El-Sayed has served as the Editor-in-chief of the
47
Journal of Physical Chemistry (1980-2004) and as the U.S. Editor of the International Reviews in Physical
Chemistry.
El-Sayed is an elected member of the U.S. National Academy of Science, and elected Fellow of the
American Academy of Arts and Sciences, the AAAS and the American Physical Society. He has also
received the 1990 King Faisal International Prize in Science and an Honorary Doctor of Philosophy
degree from the Hebrew University. He has received a number of national awards such as the Fresenius,
the Tolman, the Richard's medal, as well as other numerous local ACS section awards. In 2002, he
received the ACS-APS Langmuir National Award in Chemical Physics. In 2007, he was named the
Distinguished Professor of the year at Georgia Tech and was offered the Miller Visiting Professorship at
the University of California at Berkeley.
Abstract: Gold nanoparticles have a number of properties that are used in cancer
diagnosis and therapy: 1) they can scatter light very strongly and if bound to cancer cells
they enable us to detect cancer (used in diagnosis). 2) Depending on their size and shape,
they can also absorb light very strongly and convert it into localized photothermal heat
that can melt attached cancer cells (used for photo-thermal therapy). 3) Because of their
large size compared to molecules, each can carry thousands and thousands of drug
molecules, transport them to sick cells and enhance drug effectiveness (used in drug
delivery). 4) Because of their small size compared to the size of the cell components, we
can bind them to its nucleus which stops cell division and convinces the cancer cells to
commit suicide (apoptosis). 5) Using the strong scattering and toxic properties of silver
nanoparticles, the interesting behavior of community of dying cancer cells was captured
in time on vedio.
References:
1. Xiaohua Huang; Ivan H. El-Sayed; Wei Qian and Mostafa A. El-Sayed, “Cancer Cell
Imaging and Photo thermal Therapy in Near-Infrared Region by Using Gold
Nanorods,” Journal of American.
2. Chem. Soc., 128, 2115-2120, (2006) [most cited paper in the field of chemistry,
Sept-Oct 2007, most cited paper in JACS in 2007]
3. Xiaohua Huang, Prashant K. Jain, Ivan H. El-Sayed, Mostafa A. El-Sayed, “Gold
nanoparticles: interesting optical properties and recent applications in cancer
diagnostics and therapy,” Invited Review, Nanomedicine, 2(5), 681-693, (2007). #1
most cited Nanomedicine article to date (Oct 27, 2009)
4. Dreaden, E. C.; Mwakwari, S. C.; Sodji, Q. H.; Oyelere, A. K.; El-Sayed, M. A.,
Tamoxifen-PEG-Thiol Gold Nanoparticle Conjugates: Enhanced Potency and
Selective Delivery for Breast Cancer Treatment. Bioconjugate Chemistry, 20, 2247–
2253 (2009).
5. Kang, B.; Mackey, M.A.; El-Sayed, M.A., Nuclear Targeting of Gold Nanoparticles
in Cancer Cells Induces DNA Damage, Causing Cytokinesis Arrest and Apoptosis.
Journal of the American Chemical Society Communication, 132, 1517–1519 (2010)
6. L Austin, B Kang And El-Sayed, J. Am. Chem. Soc., Comm , 2011 , 133 (44), pp
17594–17597
48
B- Plennary Session 2
01 Role of plasminogen activators (PAs) system in hormone dependent
malignancies: diagnostic, prognostic and therapeutic implications
Shafaat A. Rabbani, MD
Professor, McGill University Health Centre
Department of Medicine , 687 Pine Avenue West, Montreal, Quebec, Canada
H3A1A1. Tel: 1-514-843-1632, Fax: 1-514-843-1712
E. mail: [email protected]
Biography
Dr Shafaat A. Rabbani received his medical degree from KingEdward Medica, College, Lahore, Pakistan.
He did his research fellowship at McGill University, Montreal, Canada, where he was awarded the Medical
Research Council of Canada Fellowship. His research interests include skeletal metastasis in hormone
dependent malignancies, role of proteases in tumor progression and epigenetic regulation of gene
transcription in cancer. Studies carried out in the laboratory of Dr Rabbani led to invitations to national
and international conferences, scientific panels and patents related to his area of research. Over the years
he served as a consultant and scientific advisor to several biotechnology and multinational pharmaceutical
companies in the area of oncology. He was also awarded the Medical Research Council of Canada and
Canadian Cancer Research Society Scholar award. More recently he received the Outstanding Achievement
Award from the Society of American AsianScientists in Cancer Research (SAASCR). Dr Rabbani is a Full
Professor in the Department of Medicine and is an Associate Member in the Departments of Physiology and
Oncology at McGill University Health Centre in Montreal, Canada.
Abstract: Hormone dependent malignancies (breast, and prostate) are unique due to their
propensity to develop skeletal metastases, which results in a high incidence of tumor associated
morbidity and mortality. In the multi-step process of tumor progression, a number of growth
factors and proteases play a crucial role in promoting tumor cell invasion, migration and
metastasis to non skeletal and skeletal sites. Members of the PA system; urokinase type
plasminogen activator (uPA), its receptor (uPAR) and PA inhibitors 1 and 2 (PAI-1, 2) are
expressed by several tumors including breast and prostate cancer. uPA is a member of the serine
protease family and plays a key role in tumor progression due to its ability to break down different
components of the extracellular matrix to promote tumor invasion and metastasis. These
proteolytic effects of uPA are localized via uPAR, which is anchored to the tumor cells via its
glycophosphatidylinositol (GPI) anchor and can also form a complex with integrins and
vitronectin. While PAIs regulate the activity of uPA and tissue type plasmingon activator (tPA),
high levels of PAI-1 is associated with the progression of several malignancies including breast
cancer. Long term studies in patients with different cancers have shown increased expression of
uPA, uPAR, and PAI-1 with advanced stage cancer. Determination of the levels of expression of
uPA, uPAR, and PAI-1 in these patients by immunohistochemistry and ELISA can serve as useful
clinical tools to predict disease status and response to therapy. We have shown that uPA
49
and PAI-1 are abundantly expressed in highly invasive, hormone insensitive breast and prostate
cancer cells. This selective expression of uPA and PAI-1 at late stages of cancer was shown to
occur via the epigenetic regulation by DNA methylation of these pro-metastatic genes.
Determination of the promoter methylation status of these key genes in patients with various
cancers, including breast and prostate cancer, was shown to correlate with their expression and
disease stage, where they can serve as a reliable and early method to predict disease progression.
Using current molecular and cell biology techniques and our established in vivo models of breast
and prostate cancer associated with skeletal metastasis, we have developed and validated various
therapeutic strategies to block uPA, uPAR transcription, expression and activity. Results from
these studies, which show the effectiveness of these approaches and their current state of clinical
development, will be presented and discussed.
02
Prostate-Specific Antigen: Where we are and where we are going
Kailash C. Chadha, PhD
Associate Member & Associate Professor of Oncology
Department of Molecular & Cellular Biology, State University of New York at
Buffalo, Roswell Park cancer institute, Buffalo, NY, USA
Tel: 716-845-3101, Fax; 716-845-1275
e-mail:[email protected]
Biography
Kailash Chadha is the Associate Member and Associate Professor of Oncology in the Department of
Molecular and Cellular Biology at Roswell Park Cancer Institute, and Department of Medicine, State
University of New York at Buffalo, NY, USA. He got his Ph.D. degree in Virology from the University of
Guelph, Guelph, Ontario, Canada. After his graduation he spent two years as a fellow of National
Research Council of Canada. Following that he joined Roswell Park Cancer Institute in Buffalo, New York
as a Cancer Research Scientist in the Department of Medical Viral Oncology. His research interests are in
the area of cell and molecular biology of Herpes viruses, interferon and prostate cancer. He has published
well over 125 publications, written several book chapters and currently holds four U.S. patents. He has
been invited to participate in numerous national and international scientific meetings and has often chaired
sessions on several international meetings. He is currently on the editorial board of J. Medicine and Indian
J. Medical Microbiology, The Open Prostate Cancer Journal, International J Nephrology & Urology,
World Journal of Clinical Urology and member of several professional organizations including New York
Academy of Sciences; American Association for the Advancement of Science; Society for Experimental
Biology & Medicine; American Association for Cancer Research; International Society for Interferon &
Cytokine research and The Society of Basic Urologic Research etc. Recently, he has completed editing a
book on interferons entitled “Interferons: Current Status, published by Research Signpost (ISBN 81-7736256-9). His immediate research interest is in developing new ”biomarkers” for early detection and
management of prostate cancer and in studying physiological role of prostate-specific antigen (PSA) in
regulating prostate tumor growth and in-particular role of PSA in “angiogenesis”. His research is being
supported by National Cancer Institute, American Cancer Society, National Multiple Sclerosis Society, and
EMD Serono Inc.
Abstract: Prostate cancer has the highest incidence of any non-cutaneous malignancy in the
western world and is the second leading cause of cancer related deaths in men. Prostate-Specific
50
Antigen (PSA) is an androgen regulated serine protease of the tissue kallikrein family, and a well
recognized biomarker for the early diagnosis and management of prostate cancer. However, PSA
test is neither disease specific nor tissue specific and test results are >70% false positive and 30%
false negative. Therefore, one of the major goal is to identify additional circulating biomarkers
that will either alone or in combination with PSA test will significantly improve the sensitivity
and specificity in the early diagnosis and in management of prostate cancer. At present, we are
investigating the relevance of IL-8, TNF-α and sTNFR1 etc as potentially new biomarkers. Our
data strongly suggests that serum levels of IL-8, TNF-α and sTNFR1 will provide powerful tools
in differentiating between the benign and malignant tumors; which is the major disadvantage of
currently available PSA test.
PSA has been documented to have anti-tumorigenic and anti-angiogenic activities. We have
shown that intact PSA has anti-angiogenic activity in vitro based on inhibition of tube formation
by human umbilical vein endothelial cells (HUVEC) in Matrigel. PSA is also known to regulate
expression, in endothelial cells and in prostate cancer epithelial cells of pro-angiogenic growth
factors/cancer genes/proteins including VEGF, IL-8, EphA2, CYR61, Bcl2, Pim-1 oncogene,
uPA, and up regulate expression of anti-angiogenic genes/proteins, including interferons and
interferon related genes. Furthermore, exogenously administered PSA inhibited growth of PC-3M
prostate tumor xenografts in nude mice. In preliminary studies, we have shown that PSA
significantly decreased micro vessel density (MVD) in xenografts of human prostate cancer tissue
harvested from animals treated with PSA; compared to animals treated with vehicle. These
observations validate both the potential therapeutic importance of PSA and the utility of primary
xenograft model for evaluation of anti-angiogenic therapeutics.
Impact of our research: The physiological role of PSA in prostate tissue microenvironment, in
prostate tumor growth and progression, and in prostate cancer metastasis is not known.
Attenuation of PSA levels with age, disease progression, or during androgen deprivation therapy,
however, removes this important regulator of angiogenesis, and by extension results in tumor
progression. Re-introduction of human PSA into the prostate tissue microenvironment may
suppress tumor angiogenesis through either the inhibition of expression of pro-angiogenic genes
or induction of expression of anti-angiogenic genes, or via inhibition of signaling mechanisms
associated with angiogenesis that are independent of gene transcription. Validation of an antiangiogenic effect of PSA on the human tissue vasculature in a pre-clinical model of primary
xenografts of human prostate and prostate cancer tissue will provide compelling evidence that
PSA has therapeutic potential against prostate cancer.
Precursor Lesions & Predictive markers of Oral Cancer
Shahid Pervez, PhD
Professor & Consultant Histopathology, Department of Pathology &
Microbiology, Aga Khan University Hospital, Stadium Road P.O. Box 3500,
Karachi 74800, Pakistan
Phone: 92 21 4861554; [email protected]
51
Biography
Dr Shahid Pervez obtained M.B., B.S. from Pakistan in 1982, Diploma in Clinical Pathology, University of
London and Ph.D. in histopathology, University of London in 1990, and the F.C.P.S (fellowship in
Histopathology), Pakistan, 1993. He currently works as a Professor and Consultant Section of
Histopatholgy, Department of Pathology and Microbiology, Faculty of Health Sciences, Medical College,
the Aga Khan University Hospital, Karachi, Pakistan. His major research interests are in Head & Neck
cancer, Breast Cancer and Lymphomas. He is Vice President of the ‘Middle Eastern Association for
Cancer Research (MEACR)’ and supervised several PhD students. He published over 160 research papers,
contributed several chapters and edited a Histopathology Atlas. He is also on the editorial board of several
international journals.
Abstract: In southern Pakistan ‘Oral Cancer (OC)’ is 2nd most common malignancy in both
males and females with highest reported incidence in the world. In contrast to Europe, Australia,
South America and Africa where smoking and alcohol are the prime risk factors, in subcontinent
including Pakistan alternate chewing habits along with smoking are the main culprits. A common
precursor lesions in our practice therefore is ‘Oral submucosal fibrosis’ aetiologically strongly
associated with chewing of areca nut, which is recently being categorized by IARC as a human
carcinogen. Biopsies usually are characterized by epithelial atrophy, keratosis & fibrosis.
Dysplasia may or may not be associated. Other common precursor lesion encountered includes
‘Leukoplakia’.
Recently it has been shown that ‘Human papillomavirus (HPV’ plays a significant role in
carcinogenesis of OC and incidence of HPV association in white Americans is 9 times higher
than black Americans. Interestingly HPV association with OC has been shown to be associated
with good response to chemotherapy and radiation and prolonged overall survival, hence
disparity in survival of white & black Americans. A similar study was conducted in Karachi,
Pakistan however we did not find survival advantage although 2/3rd of the 140 cases contained
predominantly HPV 16 genome. In view of the evidence from US studies that HPV status may be
used as a prognosticator & predictor to stratify patients for treatment options, there is a
compelling need for better understanding of the molecular pathogenesis in a large cohort of
patients who are particularly at great risk.
Preparing Scientific Manuscripts for Publication – Focus on the APJCP
Malcolm Moore Ph.D
Prof., Head, UICC Asian Regional Office, Chief Editor, Asian Pacific Journal of Cancer Prevention, Chief
Editor APJCP, Head UICC Asian Regional Office, [email protected]
Abstract: It is essential for the success of cancer control programs in the Middle East for
scientists to be able to publish their research findings in the international literature, where they
can be accessed though PubMed and other citation systems. To help younger scientists in
particular, the Asian Pacific Organization of Cancer Prevention, and its official journal the Asian
Pacific Journal of Cancer Prevention, have tried to promote a skeleton approach to writing papers,
focusing on essential principles to maximise the ease of writing and hopefully impact of research
results. Whether destined for submission to the APJCP, Clinical Cancer Investigation or any other
international journal, it is of the essence that research projects and manuscripts are well designed,
following instructions to authors and avoiding obvious pitfalls. My own 30 years experience of
helping German, Japanese and now other Asia scientists write papers is here condensed to
hopefully provide clues to acceptance by reputable journals specialising in the cancer field.
52
53
Day 2: Oral Presentations
Session 1: Infection and Cancer
O 1.1
Infection and Cancer
Skin cancer and cutaneous blastomycosis
Azhar A.F. Al-Attraqhchi*, Husam Hasson, Hiba Thamer
Address: Al-Kadhimiyah/Baghdad/Iraq/College of medicine/Al-Nahrain University, Iraq
Correspondence*:[email protected]
Abstract
Background: Blastomycosis is a pulmonary disease caused by inhaling spores of the
dimorphic fungus Blastomyces dermatitidis, occasionally, the fungi spread
hematogenously, causing extrapulmonary disease. Cutaneous blastomycosis are common
on the face, extremities neck and scalp as the infection spreads from the lungs to other
parts of the body. Skin neoplasms are skin growths with differing causes and varying
degrees of malignancy. Basal-cell carcinoma is the most common type of skin cancer.
Aim: This study was conducted to relate between cutaneous blastomycoses and skin
cancer, we found that there were two cases of blastomycoses with basal cell carcinoma.
Materials and methods: Skin biopsies were obtained from one hundred patients with
verrucous, ulcerative and noduler lesions. Controls included skin debris of 10 apparently
healthy individuals. Bbiopsies were processed for histopathology or cultivated in agar.
Results: According to the type of lesion, the patients distributed into three groups of
clinical presentations which are: 1) verrucous lesions; 2) ulcerative lesions; and 3)
noduler lesions. According to histopathology only eight samples (8%) out of 100 were
positive, revealed (budding yeasts), which were the same of that culture results. A 51 and
75 years old males with verrucous and ulcerative lesions, respectively, one in the face and
the other on his leg, both showed skin cancer (basal cell carcinoma) superimposed with
blastomycosis.
Key words: Blastomycosis, skin cancer
O 1.2
Infection & Cancer
Studies on the genomic association between Schistosomiasis and HCV infection
Akram M. Abouzied1, Rasha H. Soliman2, Tarek M. El-Beltagy1, Hekmat M. Tantawy1.
1
Zoology Department, Faculty of Science, Suez Canal University, Ismailia, Egypt
Department of Parasitology and Laboratory Medicine, Faculty of Medicine, Suez Canal University,
Ismailia, Egypt
2
Correspondence: Dr. Akram K. Abouzied
Faculty of Science, Suez Canal University, Ismailia, Egypt, e-mail: [email protected]
54
Abstract
Background: Hepatitis C virus (HCV) infection and schistosomiasis are major public
health problems in the Nile Delta of Egypt. Studies done in Egypt found the highest risk
of HCV infection in whom infested with schistosomiasis. Moreover, HCV-Ab prevalence
reported to be more than 70% in adults suffering from schistosomiasis. HCV is a leading
stage cause of end-stage liver disease. Co-infection with schistosomiasis leads to faster
progression to cirrhosis, liver failure and hepatocellular carcinoma (HCC). Aim: The
overall aims of the studies described in this work were: 1) to gain knowledge of whether
HCV infections could be trasmitted by Schistosoma mansoni to human and 2) to assess
whether or not a genomic association between schistosomiasis and HCV infection.
Methods: We screened the genomic DNA libraries of Schistosoma mansoni based on
PCR by using two oligonucleotide specific primers of HCV RT-PCR diagnostic kits.
Results and Conclusion: This work increases our knowledge of the existence of HCV
genome in the genomic DNA of Schistosoma mansoni. In addition, it highlights the
genomic association between schistosomal infestation and HCV infection.
O 1.3
Infection & Cancer
Hepatitis B and C viral forms in a group of patients with hepatocellular carcinoma
in hepatitis C hyper endemic region, Egypt
Abdel Raouf Abou El Azm MD1, Hassan El-Batae MD 1, LobnaAbou Ali MD 1, Maali
MabroukMD 2, Hussien Ghorabah PhD3 , Amr El Badry MD 4.
Department of Tropical Medicine and Infectious Diseases 1, Clinical Pathology 2, Pathology3, Radiology4,
Faculty of Medicine, Tanta University, Egypt
Corresponding author: Prof. Dr Abdel RaoufAbou El Azm. E-mail: [email protected]
Abstract
Background: The rate of hepatocellular carcinoma (HCC) is increasing worldwide. The
major risk factors are chronic hepatitis B and C (HBV and HCV). Co-infection and
occult-B are generally believed to be factors favoring progression of liver fibrosis
towards cirrhosis and HCC. Occult HCV infection is a new form of HCV. Egypt is highly
endemic with HCV. Aim: to investigate the incidence of HBV, and HCV viral forms
associated with HCC and their carcinogenic potential in our area. Patients and methods:
Sixty three consecutive patients with HCC and 54 with cirrhosis were selected in addition
to 54 apparently healthy controls. Sera were tested for HBsAg and HCV-antibodies by
ELISA, HCV-RNA and HBV-DNA for patients negative for HBsAg using(PCR) and
occult-C by liver biopsy. Results: HCC patients proved 100% HCV infection (positive
serum RNA in 85.7% and 14.3% occult-C), HBV co-infection 38.1% of which 28.57%
occult-B. Cirrhotic patients showed 11.11% non-viral cirrhosis, 88.89% HCV (positive
serum RNA 77.77%, and Occult-C 11.11%), of which 16.66% co-infection while occultB 11.11%. Controls showed 5.56% HCV RNA. There was an insignificant increase in coinfection, occult-C and occult-B in HCC patients as compared to cirrhosis and significant
increase in HCC and cirrhosis as compared to control. Conclusion: HCV infection alone
or in co-infection is the main cause of HCC in our region. Occult-B seemed higher
55
prevalence andamplify HCC risk than occult-C. HBV is under estimated. The study can
give a better strategy for primary, secondary prevention of HCC and control of both
viruses.
O 1.4
Infection & Cancer
Hepatocellular carcinoma is it a preventable disease?
Abdel RaoufAbou El-Azm
Department of Tropical Medicine and Infectious Diseases, Faculty of Medicine, Tanta University, EGYPT
Prof. Abdel RaoufAbou El-Azm, e-mail: [email protected]
Abstract
Liver cancer incidence rates have been rising rapidly in the past decade. There are several
reasons for this spike in prevalence, many of which are preventable.HCC has a poor
prognosis. Itcauses death 6 months-1 year from diagnosis and is considered a preventable
disease rather than a curable one. It can be prevented by public health measures that
reduce exposure to known risk factors for this disease.HCC prevention appears to be a
cost-effective public health strategy in at-risk populations and is preferable to HCC
surveillance as a cancer control. HCC is a disease of multi-factorial etiology and
developed in multistep process. It is the result of an accumulation of risks which will be
discussed.
O 1.5
Infection and Cancer
Increases in the frequency of myeloid-derived immunosuppressor cells in Egyptian
patients with chronic hepatitis C virus
1
2
Mohamed Labib Salem (PhD), 2Abdel Raouf Abou Al-Azm (MD), 3Maha Aldemelaawy (PhD),
Hasan Albate (MD), 4Mohamed Attia, 1Mohamed Abou Senna (BSc)
1,4
Zoology Department, Faculty of Science, Tanta University, Egypt
Department of Tropical Medicine, Faculty of Medicine, Tanta University, Egypt
3
Biomedical technology Department, City of Scientific Research and Applied Technology, Egypt
4
Department of Clinical Pathology, Faculty of Medicine, Tanta University, Egypt
Correspondence: Prof. Mohamed L Salem, [email protected] (01274272624)
2
Abstract
Background: Clearance of hepatitis C virus (HCV) infection depends on functional
immune cells, including myeloid cells. Suppression of immunity results in progression of
the disease and the development of liver cancer. We have reported recently that cancer
progression correlate with the emergence of an immunosuppressive population called
myeloid-derived suppressor cells (MDSC). Similarly, HCV infection may also induce
expansion of MDSC from myeloid precursors. Aim: the main aim of this study was to
etermine whether the failure of chronic HCV patients to IFN-α therapy correlates with
increases in the numbers of MDSC. Methods: about 25 patients were recruitedin this
study in addition to 5 healthy controls. The patients were selected among those admitted
at Tropical Medicine & Infectious Diseases, Tanta University, Tanta, Egypt. Patients
were determined positive for HCV by measuring the HCV RNA level in their plasma
56
using commercial kit. A clinical protocol was approved by the Protocol Review
Committee of the Faculty of Medicine, Tanta University Institutional Review Board and
a written consent was obtained from subjects. Peripheral blood samples were collected
from the patients before treatment with IFN-α or at multiple time points during the
treatment. The frequency of the MDSCs in the PBMCs was analyzed by flow cytometry
and characterized as Lin-HLA-DR-CD11b+CD22+ after staining with anti-human Lin,
HLA-DR, CD11b, and CD33 mAbs. Results: The results clearly showed increases in the
number of MDSCs in the PBMCs of about 8 patients. The increases in the numbers of
these cells were independent of the number of weeks after IFN- α treatment. Conclusion:
These data indicate to the role of MDSCs in the failure of the HCV patients from the
treatment with IFN-α. These results open a new avenue to target these cells to improve
the efficacy of IFN-α treatment.
Keywords: HCV, IFN-a, MDSC, myeloid suppressive cells.
O 1.6
Infection & Cancer
High-risk HPV/Oncogene interaction & cancer progression
Amber Yasmeen1,2, Andrew Darnel1,2, Amal Kassab1, Pierre-Yves Desprez3 & Ala-Eddin Al
Moustafa*1,2,4,5
1
Segal Cancer Centre, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec,
Canada; 2Department of Oncology, McGill University, Montreal, Quebec, Canada; 3California Pacific
Medical Center Research Institute, San Francisco, CA 94115, USA; 4Department of Mechanical
Engineering, Concordia University, Montreal, Quebec, Canada; and 5Syrian Research Cancer Centre of
the Syrian Society against Cancer, Aleppo, Syria
*Correspondence: DR. Ala-Eddin Al Moustafa; E-mail: [email protected]
Abstract
Human papillomaviruses (HPVs) are a group of host-specific DNA viruses, with more
than 120 different types identified to date. HPVs are classified as high or low risk (HR or
LR) depending on their potential to provoke cancer. Persistent infections with HR types
of HPVs could present a major risk factor for the development of a variety of human
cancers including cervical, colorectal, head and neck as well as breast cancers. However,
HPV infection alone, with one type of HR-HPV, is not sufficient to induce neoplastic
transformation of normal human cells; HPV-infected cells must undergo additional
genetic alterations. Therefore, we investigated the association between E6/E7 oncoproteins of HR-HPVs and several oncogenes such as ErbB-2, Id-1 and Src in human head
and neck, breast and cervical cancer. Our data showed that E6/E7 cooperate with these
oncogenes to enhance tumor progression of these human carcinomas. Moreover, we
reported the E-cadherin/catenin complex, which is an important regulator of normal
adhesion in epithelial cells, is a major target of E6/E7/ErbB2, Id-1 and Src cooperation.
Thus, in my presentation, I will talk about the interaction between E6/E7 of HR-HPV and
57
ErbB-2, Id-1 as well as Src and their outcome on the E-cadherin/catenin complex in
human head and neck, breast and cervical cancers.
Key words: HPV, ErbB-2, Id-1, Src, E-caderin/catenin complex, head and neck cancer, breast cancer, and
cervical cancer
Session 2: Theray (Preclinical Studies)
\\\
O 2.1
Therapy (Prelinical Studies)
In vitro and in vivo antitumor activity of novel 3D-organotin supramolecular
coordination polymers based on CuCN and pyridine bases
Safaa El-din H. Etaiw*(1), Ahmed S. Sultan (2) and Mohamed M. El-bendary (1)
Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt (1)
Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt (2)
*Corresponding author. Dr. Mohamed M. El-bendary. E-mail address: [email protected],
[email protected] Tel: +01008043708
Abstract
Two novel organotin supramolecular coordination polymers (SCP), namely,
[Me3SnCu(CN)2.(EN)2], 1 and [Ph3SnCu(CN)2.(3-mpy)2], 2 are obtained by the reactions
of K3[Cu(CN)4], ethyl nicotinate (EN) or 3-methylpyridine (3-mpy) and Me3SnCl or
Ph3SnCl in H2O/acetonitrile solution at room temperature. 2D-layers are constructed via
H-bonds between the parallel 1D-puckered chains which contain nanometer-sized [CN(R3Sn)NC-] spacers connecting the tetrahedral (T-4) copper sites. The network
structures of 1 and 2 consist of infinite layers connected by interlayer H-bonds forming
3D-framworks. 2 is the first compound in this family containing the Ph 3Sn cation. The
electronic absorption spectra of 1 and 2 reveal a broad band at 320 nm due to CT
transition while the emission spectra exhibit high energy bands at 400-460 nm due to
metal-centered (MC) transitions and low energy bands at 485-530 nm corresponding to
MLCT. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay
was used to determine the in vitro antitumor effects of the SCP 1 and 2 on human breast
cancer cell line, ZR-75-1. Cell cycle analysis revealed that the SCP 1 and 2 induced
apoptosis in ZR-75-1 breast cancer cell line through activating caspase-3. Moreover, in
vivo model, the compound SCP 2 suppressed tumor growth developed mammary
carcinoma by 52.3%. Taken together, our novel compounds selectivity exhibit specific in
vivo and in vitro antitumor effects.
Key words: Organotin supramolecular coordination polymer, Copper Cyanide, pyridine bases,
Hydrogen bonds, in vitro/ in vivo antitumor activity.
58
O 2.2
Therapy (Prelinical Studies)
Targeting Clusterin by small interference RNA sensitizes cervical cancer cells to
hyperthermia
1
1
Mohamed K. Hassan,1 Ali Hussein Abo-Almaati, 2Hidemichi Watari, 2Noriaki Sakuragi.
Biotechnology program, Zoology Department, Port Said University, Egypt
Department of Obstetrics and Gynecology, Graduate School of Medicine, Hokkaido University Sapporo,
Japan. Correspondence: E-mail: [email protected]
2
Abstract
The cytoprotective chaperone protein, Clusterin (CLU), has been reported to be involved
in carcinogenesis and tumor growth, including apoptotic cell death, cell cycle regulation,
DNA repair, cell adhesion, tissue remodeling, lipid transportation. Here, we investigated
how human cervical cancer cells escaped from hyperthermia. Treating Hela cell line with
hyperthermia (42.5oC) induced cytostatic arrest in the G2/M phase without prominent
apoptosis. Hela cells, which have negative P53, expressed quite large amounts of wild
type Bax which up-regulated after hyperthermia. Western blotting analysis indicated that
Clusterin expression was up-regulated upon hyperthermia treatment and that upregulation was maximum one-day after hyperthermia treatment. Transfection of siRNA
specifically targeted CLU into Hela cells resulted in Bax-induced apoptosis by
hyperthermia 2-3 times more than control siRNA transfectant as detected by FACS and
Annexin V staining independent of P53. Interestingly CLU-KD cells did not show the
same cytostatic arrest as well as control cells but were directed into cytotoxic G1 arrest
followed by apoptosis. Taken together, our data indicate that CLU-based cellular
protection from heating is cell cycle dependent. Disturbing this protection mechanism is a
possible approach to enhance the therapeutic efficacy of hyperthermia.
Abstract 2.3
Therapy (Prelinical Studies)
Vitamin C and diallyl sulfide as chemo-sensitizers to cisplatin in treating
hepatocellular carcinoma
Abdel-Hamid, NM *1, Nazmy, MH 1and Nazmy, WH 2
1
Biochemistry Department, Faculty of Pharmacy and 2Physiology Department, Faculty of Medicine, Minia
University, Egypt
Correspondence: Prof. Abdel-Hamid,Nabil Mohie.PhD , Department of Biochemistry, Faculty of
Pharmacy, Minia Univ, Egypt.. Mobiles: +201006426998, +201227300491 and +201121830691. Land
Phone: +20506913997. E-mail: [email protected]
Abstract
Background: The resistance to chemotherapy is a major obstacle in the treatment of
hepatocellular carcinoma (HCC), necessitating the discovery of additional agents. The
use of natural products in this respect is extensively under investigation. Aim: This work
aims to check if naturally occurring materials can help in improving response to CP
chemotherapy and if ploylol profile can assist in more accurate HCC detection.
Materials and Methods: Two hundred and ten male albino rats were used, divided into
14 groups. Selected groups were pre-treated with vitamin C (ascorbic acid, AA) and/or
diallyl sulphide (DAS). Hepatocarcinogenesis was initiated by a single intra-peritoneal
59
(IP) injection of diethyl nitrosamine (DENA), diabetes was induced by a single IP
injection of Streptozotocin (STZ). Other groups were treated with cisplatin (CP) alone or
combined with AA and/or DAS for 14 weeks. Results: The results revealed that DENA
significantly increased relative liver weight, serum ALT, AST and GGT activities, AFP,
TNF-α and IL-6 levels, expression of aldose reductase (AR), sorbitol dehydrogenase
(SDH) and Bcl2 proteins in the liver with decrease in body weight, expression of Bax
protein and Bax/Bcl2 ratio in the liver. These effects were more pronounced in
DENA+STZ group. These parameters showed relative correlation to AFP levels in HCC,
in response to AA and/or DAS treatment except for SDH. Treatment with CP and/or AA
and/or DAS significantly modulated most of these parameters except for SDH which
showed no significant change in response to the suggested treatment. Conclusion: In
conclusion, AA and/or DAS showed apparent chemo-sensitizing, anti-inflammatory, AR
inhibitory, apoptotic inducing and anti-diabetic activities, indicating new aspects for use
as adjuvant to chemotherapy. Induction of diabetes in hepatoma-bearing rats showed
higher resistance to chemotherapy. The suggested biomarkers are useful prognostic tools
in HCC patients with diabetic background.
Keywords: Ascorbic acid, Chemo-sensitization, Diabetes, Diallyl sulphide, Hepatocellular carcinoma,
Diethyl nitrosamine.
O 2.4
Therapy (Prelinical Studies)
Phosphonopeptides synthesis using α-aminophosphonates and their antimicrobial
and anticancer activities
Mohamed F. Abdel-Megeeda,*, Badr E. Badrb, Mohamed M. Azaama
a
Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
Department of Botany, Faculty of Science, Tanta University, Tanta, Egypt.
Correspondence: Dr. Mohamed F. Abdel-Megeed: Tel.: +20104694523; Fax: +23344352
E-mail address: [email protected]
b
Abstract
A series f novel phosphenopeptides using α-aminophosphonates derivatives has been
synthesized. The antimicrobial activities against Escherichia Coli (NCIM2065) as gramnegative bacteria, Bacillus Subtitles (PC1219) and Staphylococcus aureus
(ATCC25292) as gram-positive bacteria, Candida albicans and Schccaromycies
cerevisiae as fungi showed high activities at low concentrations (10, 50, 100µg/ml).
Furthermore, anticancer activity against human colon carcinoma cell line (HCT116) was
also carried out and all compounds showed significant cytotoxicity (IC50:13.7, 7.5, 5.9,
15.9, 9.1, and 9.4 µg/ml). The lethal dose of the synthetic compounds was also
determined (1000, 843, 100, 67, 175 and 100µg/ml) which indicated that some of these
compounds are safe and less toxic.
60
O 2.5
Therapy (Prelinical Studies)
Anti-tumor activity of some 1, 3, 4-thiadiazoles and 1, 2, 4-triazine Derivatives
against Ehelishs Ascites Carcinoma
Ahmed EL-Barbary, L-Naggar and Shaimaa Talat
Chemistry Department and Zoology Department, Faculty of Science, Tanta University, Tanta, Egypt
Correspondence: Prof. Ahmed EL-Barbary, Prof. of Organic Chemistry, Chemistry Department, Faculty of
Science, Tanta University, Tanta, Egypt. E-mail: [email protected]
Abstract
Recently, identifying new chemo-preventive agents to replace the current chemotherapies
consider one of the most important approaches which could be crucial for cancer
treatment. The present study was conducted to evaluate the anti-tumor activity of some
newly synthesized heterocyclic 1, 3, 4-thiadiazoles and1, 2, 4-triazine derivatives.
Different groups of mice were inoculated with Ehrlish Ascetic Carcinoma cells (EAC)
intra-peritoneal (i.p) (2x10^5 cells mouse -1). After one day of inoculation, mice were
treated either with cisplatin (reference drug) or with twenty five different new derivatives
of 1, 3, 4-thiadiazoles or1, 2, 4-triazine. The anti-tumor activities of these derivatives
against EAC-bearing mice were monitored through he changes in the total body weight.
Total ascetic volume, the number of live and dead tumor cells, median cervical time
(MST) and some biochemical parameters. The results showed that only five compounds
of1, 3, 4-thiadiazoles significantly inhibited the tumor progression after 14 days of the
treatment. Interestingly, two of these compounds increased the life span of tumored mice
by 34 and 40% when compared with the untreated group.incontrast, all 1, 2, 4-triazine
derivatives did not show any potential anti-tumor activity against EAC-model. In
conclusion, screening of1, 3, 4-thiadiazoles derivatives did not show any marked antitumor activity.
O 2.5
Therapy (Prelinical Studies)
The curative effect of Cymbopogon citrates volatile oil against chlorambucil drug
toxicity
Islam M. El Garawani
Researcher of Molecular Biology and Genetic Engineering, PhD.
National Organization for Drug Control and Research, MHP
e-mail: [email protected]
Abstract
Chlorambucil (CLB) is a bifunctional alkylating drug widely used as an anticancer agent
and as an immunosuppressant. Its chemical structure and clinical experience indicated its
mutagenicity, teratogenicity and carcinogenicity. The aim of this study is to investigate
the curative effect of oral treatment with lemongrass (Cymbopogon citratus) essential oil
(75 mg/kg) against damage induced by chlorambucil (7.5 mg/kg) administration in rats.
The results of our study revealed that the presence of good improvement in spleen
genomic DNA and total protein evaluated by SDS-PAGE after 15 days. In addition, the
excellent improvement also was evaluated by alkaline single cell gel electrophoresis
61
(SCGE)/comet assay for lymphocytes from rats' blood after 48 hours of treatments with
the same doses of chlorambucil and Cymbopogon citratus. Our findings indicated that
lemongrass essential oil provided a good curative effect against chlorambucil possible
hazardous effects.
Session 3: Medicinal Plants
O 3.1
Medicinal Plants
Gene profiling cDNA microarray analysis of rat colon carcinogenesis treated with
crude Nigella sativa oil
Elsayed I. Salim, Ph.D., D.M.Sc.
Ass. Professor of Toxicological pathology & MolecularCarcinogenesis, Zoology Department, Faculty of
Science, Tanta University, Tanta-31527- Egypt
Asian Pacific Organization for Cancer Prevention (APOCP)
E-mail: [email protected], [email protected]
Telefax: (+20) 040 3350804, Cell: (+20) 01220177760
Abstract
It was recently shown that Nigella sativa (N. Sativa) extracts can exert significant
modulatory effects on different pathological, toxicological and cytotoxic protocols in
vitro and in vivo. Studies from our laboratory and others have also shown inhibitory
effects on tumor formation by N. sativa in different animal carcinogenesis bioassays
including colon cancer. The present experiment was designated to evaluate the candidate
genes possibly involved with N. sativa inhibitory effects on colon carcinogenesis in post
initiation phase. 20 male rats were administered two consequent injections of 1,3dimethylhydrazine (DMH) (20 mg/kg b.wt) subcutaneously, once a week at the
beginning. The first group (10 rats) received 200 mg/kg of fresh N. sativa oil daily by i.g.
for eleven weeks after cessation of the carcinogen administration, while the second
control group (10 rats) had no treatment after DMH administration. Repeated genetic 3DcDNA microarray analysis pointed out mainly to 19 genes to be significantly changed in
the colonic mucosa after N. sativa treatment either by up or down-regulation.
Interestingly, these genes encoding transcription factor activity, regulation of cell cycle,
signal transduction, xenobiotic metabolism, apoptosis, DNA repair and lipid transport
and metabolism. Real-time reverse transcription-PCR (RT-PCR) analysis confirmed the
altered expressions of some dedicated genes after N. sativa treatment. These data point
out to the involvement of N. sativa oil in many genetic pathways particularly those
concerning cell cycle, apoptosis, DNA repair and xenobiotic metabolism in response to
oxidative stress. These results could explain the genetic mechanism of action of N. sativa
oil in inhibiting colon carcinogenesis in rats.
62
O 3.2
Medicinal Plants
Cytotoxic effects of aqueous , methanolic and secondary metabolites extracts of
Capparis spinosa fruit on tumor cell lines in vitro
Asaad Abdulwahed, Bader, AL-Asady, Khesar, Husen, Khalil and Sa’adi Saleh Mohammed
Barwari
University of Duhok ,Faculty of Medicine , School of Medicine, Dept.of Anatomy Duhok, Iraq
Correspondence: Dr. Asaad Abdulwahed aabal_f[email protected]
Abstract
The present study aims to prepare two types of extracts; (methanolic and aqueous) crude
extracts and (polyphenol and rutin) secondary metabolite extracts of immature fruit of
Capparis spinosa to evaluate the cytotoxic effects of all these extracts on Human larynx
carcinoma (Hep-2) and Human cervix adenocarcinoma (HeLa) tumor cell lines in vitro.
The results of present study showed that the yield of extraction % of methanol and
aqueous crude extracts;16.1% and 15%,respectively,whereas that of polyphenol and rutin
secondary metabolite extracts were 12.7% and 12.1% ,respectively. The results revealed
that the more effective extracts against the proliferation of Hep-2 tumor cell line was
aqueous extract after 24 hrs treatment. After 48hrs treatment each of methanol, aqueous
,and rutin was more effective than polyphenol extract. All types of immature fruit
extracts had CC50 values on Hep-2 cell line > 10000μg/ml for both periods of exposure.
The present study revealed that the effect of both methanol and rutin on proliferation of
HeLa cell line after 24 hrs treatment were more than that of aqueous and polyphenol
extracts. After 48hrs treatment the activity of methanolic extract and aqueous against the
proliferation of HeLa cell line more than that of polyphenol and rutin, the values of
CC50 on HeLa cell line treated with methanol extract after 48hrs was 9700 μg/ml.
Aqueous extract was more effective after 48hrs than 24 hrs. The present study shows that
HeLa tumor cell line was more effective than Hep-2 tumor cell line.
O 3.3
Medicinal Plants
Oxidative stress biomarkers in young male rats fed with stevioside
Hala A. Awney
Lab. Environmental Toxicology, Department of Environmental Studies, Institute of Graduate Studies &
Research, Alexandria University, 163 Horreya Ave., El-Shatby 21526, P O Box 832, Alexandria, EGYPT.
Email: [email protected]
Abstract
Stevioside is a natural non-caloric sweetener refined from Stevia rebaudiana Bertoni
leaves. The introduction of stevioside as a sugar substitute in the diets of diabetics and
others on carbohydrate-controlled diets has been suggested, but safety issues have
prevented implementation. The aim of this study was to examine antioxidant status
changes in the sera, livers, kidneys and brains of young male rats fed with low doses of
stevioside (SL) or high doses of stevioside (SH) for 12 weeks. We investigated oxidative
stress biomarkers such as the levels of total antioxidant capacity (TAC), reduced
63
glutathione (GSH) and thiobarbituric acid reactive substances (TBARS) and the activities
of superoxide dismutase (SOD), catalase (CAT) and glutathione reductase (GR). Our
results show that SH treatment causes significant induction of TBARS in liver, kidney
and brain, accompanied by a significant reduction in TAC, SOD, CAT, GR and GSH
levels in the same organs. SL treatment causes insignificant changes in TAC, SOD and
CAT, but significant reduction was observed in GR, GSH and TBARS in serum and all
tested organs when compared with the control. In conclusion, features of oxidative stress
were detected in the liver, kidney and brain of young male rats treated with SH for 12
weeks, whereas no significant changes in TAC, SOD and CAT were detected after SL
treatment.
Keywords: Stevioside; safety, sweeteners; food safety; oxidative stress biomarkers
O 3.4
Medicinal Plants
Berberis vulgaris new extract: A new solution for HCV genotype 4 infection
Doaa A. Ghareeb1, Eiman H. El-Wakeel2, Maha A. El-Demellawy3, Marwa Abo Sariaa3
1Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
2 Microbiology and Botany Department, Faculty of Science, Alexandria University, Alexandria, Egypt.
3 Biomedical technology Department, City of Scientific research and Applied Technology, Egypt
Correspondence: Dr. Doaa A. Ghareeb, e-mail: [email protected]
Abstract
Hepatitis C virus (HCV) infection is a global public health problem that affects almost
3% of the world's population with a morbidity and mortality that are second only to HIV
among the emerging infections. The conventional antiviral regimen is a combination
therapy of pegylated Interferon (INFα) and the nucleoside analogue ribavirin, but only
40% to 50% of patients who can complete the 6- to 12-month treatment have a sustained
virologic response. Also, it is too expensive for use in most underprivileged countries.
Because, Berberis vulgaris has shown a number of beneficial effects including
immunostimulation and macrophage activation, we screened Berberis vulgaris new
extract (BCE) anti HCV activity in vitro comparing to its active ingredient Berberine
chloride (BRB). Peripheral blood lymphocytes (PBLs) of healthy donors were isolated by
Ficoll gradient centrifugation. Purified PBLs were co-cultured with HCV-infected serum
in RPMI culture medium for 24 hours. To investigate in vitro interactions, BER or BCE
was added at serial dilutions of 1-300 ug/ml. INFᵧ and interleukin 12 (IL12) levels in
culture supernatants were measured by ELISA. Also, RNA was detected in PBLs lysates
by nested HCV RT-PCR and the products were resolved on 2% agarose gel. The PBLs IC
50 of BRB and BCE were 600 ug, and 900 ug, respectively, after 24 hours incubation.
Significant alterations in PBLs distribution were identified; where BRB and BCE
enriched the PBLs count by 2, and 3 folds, at a dose of 100ug/ml. At the same dose in
culture supernatants, BCE activated INFᵧ by 2 fold, and induced IL-12 secretion by 3
fold, while BER did not. mRNA expression revealed similar patterns. Furthermore, BCE
treatment led to 174 bp band disappearances, which is an indication for viral RNA, while
BER treatment did not.These findings suggest that BRB does not account as anti HCV,
64
while BCE successfully blocks viral entry into PBLs, which was indicated by 174 bp
band disappearance. The mechanism by which BCE works,, is that it functions as a part
of the host innate immune defense mechanisms Thus, further studies are needed to define
the precise mechanisms of viral clearance.
O 3.5
Medicinal Plants
Interrelation of anticancer and antioxidant effects of some Egyptian plants and their
phenolic constituents
N. M. Abdel-Hady, Gouda T.M. Dawoud* and **A. A. El-Hela
Pharmacognosy Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, Egypt
* Phytochemistry Dept. Medicinal Plant Center, NODCAR
**Pharmacognosy Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo, Egypt
Correspondence: Dr. Nevein Abdelhady: E-mail: [email protected]
Abstract
Cancer is a dreadful human disease, increasing with changing life style, nutrition, and
global warming while current available potent anticancer drugs cause serious side effects
in most instances. Plants are considered to be the most potential resource of anticancer
agents; they are diverse, largely productive, biologically active and chemically unique
offering great scope for discovery of new anticancer drugs. Several reports suggested that
the relationship between their anticancer effect and their antioxidant character; they
suggested that most of them act through promoting host resistance against various
diseases, restabilizing body equilibrium and conditioning body tissues as well.
Polyphenolic content of such plants is a determinant factor in evaluating their
pharmacological effects as they displayed an array of pharmacological properties as
antioxidant, immunostimulant and antitumour activities. This paper is conducted on this
aspect with a view to provide more information about the anticancer effect of a chosen
twenty-three Egyptian medicinal plants interrelated with their antioxidant effect and
polyphenolic content screening for cheaper, safer and potent natural anticancer to
challenge this dreadful human disease.
O 3.6
Medicinal Plants
The mushroom extract from Pleurotus ostreatus inhibits cell proliferation of HepG2
cells and protects rats from liver damage induced by dimethylnitrosamine
carbontetrachloride
Nihad Abdelmoneim1, Muhammad El-Saadani1, Eiman Aleem2, Ayman Daba3, Samar Saleh1
1
Alexandria University, Faculty of Science, Department of Biochemistry, 2Alexandria University, Faculty
of Science, Department of Zoology, Division of Molecular Biology, Moharram Bey 21511, Alexandria,
Egypt, 3City for Scientific Reseasrch and Technology Application (MuCSAT), Genetic Engineering and
Biotechnology Research Institute, New Borg El Arab, Alexandria, Egypt
Correspondence: Dr. Eiman Abdel Aleem, Department of Zoology, Division of Molecular Biology, Faculty
of Science, Alexandria University, Alexandria, Egypt, E-mail: [email protected]
Abstract
Medicinal mushrooms have been shown to improve cardiovascular health and stimulate
immune function. The oyster mushroom Pleurotus ostreatusis one of the widely
cultivated edible mushrooms. The aim of the present study was to investigate the
protective effect of polysaccharide-protein (PSP) complexes isolated from the oyster
mushroom against Diethylnitrosamine/Carbon tetrachloride-induced hepatotoxicity in
65
vivo and its antiproliferative effects in vitro using HepG2 cells. We isolated and partially
purified PSP from the culture broth of P. ostreatus mushroom and determined its
chemical and physico-chemical properties Treatment of HepG2 cells with PSP inhibited
cellproliferationwith an IC50 of 0.54 µg / ml.We induced liver injury in rats using
DENA/CCl4 for 14 weeks. The rats were divided into the following groups and received:
(I) only DENA/CCl4, (II) DENA/CCl4+PSP 30 mg/kg for 14 weeks, (III) DENA/CCl4
followed by PSP only at the last four weeks of the experiment, (IV) PSP only for 14
weeks, (V) PSP for the last 4 weeks, (VI) only saline. PPP protected and treated the rats
against hepatic injury induced by DENA/ CCl 4and induced an increase in superoxide
dismutase and glutathione-S-transferase, decrease in hepatic lipid peroxidation, and in the
activity of liver enzymes, as well as total cholesterol in comparison to the group with
liver toxicity. Furthermore, PSP treated the histopathological changes induced by DENA/
CCl4(fibrosis, necrosis, macrosteatosis and inflammation). We conclude that PSP extract
from the oyster mushroom isanatural and inexpensiveway to improve the body’s defence
against oxidative stress.
Session 4: Epidemiology
O 4.1
Epidemiology
Is cancer a major problem in Egypt?
Nadira Mansour
Professor of Public Health and Community Medicine,
Faculty of Medicine ,Tanta University
Epidemiology can answer this question. It helps us in knowing the magnitude, distribution and
determinants of this problem. Also, it is the first step that paved the way for the health planner to
take the correct actions to solve the problem. The National population Based Cancer registry for
Egypt and Gharbiah population based cancer registry are good efforts that can be used as guides
in dealing with cancer problem in Egypt.
O 4.2
Epidemiology
Brief overview cancer epidemiology in the Middle-East – pointers to research
priorities
Malcolm Moore
PhD, Head, UICC Asian Regional Office, Chief Editor, Asian Pacific Journal of Cancer Prevention; Chief
Editor APJCP, Head UICC Asian Regional Office. Correspondence: Prof. Malcolm Moore
<[email protected]>
66
Abstract
South-West Asia, stretching from Lebanon and Syria in the north, through to Yemen in
the south and Iraq in the east, and the North-Western and Central region of Asia, from
Turkey through Iran to the Central Asian republics, are home to more than 500 million
people. Cancer is already a major problem and will only become heavier over time,
especially with aging of what are now still youthful populations. There are a number of
active registries in the region and population-based data are now available for a
considerable number of countries, highlighting both similarities and variation in the
different cancer types. In males, the most prevalent cancers vary, with lung, urinary
bladder or liver in first place in the Arab world and Turkey, but stomach in most of Iran
and Central Asia, followed by the oesophagus. For females throughout the region breast
cancer is the major problem, with cervical cancer relatively rare. In both sexes, nonHodgkins lymphomas and leukemias are important in Arabia. General tendencies for
increase in adenocarcinomas but decrease in squamous cell carcinomas and gastric cancer
point to change in environmental influence over time. Variation in risk factors depends to
some extent on the level of economic development but also different cultural influences
which have obvious interest for cancer epidemiology research. Overall the countries of
the region face similar challenges in achieving effective cancer control, underlying the
necessity for cooperation. Conclusion: Although the demographics and clinical
characteristics of children with ALL are similar to those reported elsewhere but the
outcome even at this early phase appears suboptimal.
O 4.3
Epidemiology
Lung cancer incidence in the Arab league countries: perspectives of risk factors and
control
Elsayed I. Salim1,2 Malcolm Moore2, Abdulrahman Jazieh3,
1
Ass. Professor of Toxicological Pathology & Molecular Carcinogenesis, Zoology Department, Faculty of
Science, Tanta University, Tanta-31527- Egypt
Asian Pacific Organization for Cancer Prevention (APOCP)
E-mail: [email protected]; [email protected]
Telefax: (+20) 040 3350804, Cell (+20) 01220177760
2
Asian Pacific Organization for Cancer Prevention (APOCP), UICC-ARO regional Office,
[email protected]
3
Oncology Dept., Cancer Center, King Abdulaziz Medical City-Riyadh. Saudi Arabia,
[email protected]
Abstract
Lung cancer incidence, the most common cancer worldwide, is gradually increasing in
the Arab world, 15 out of 22 Arab countries have lung cancer as the most common cancer
in males. Also the forthcoming prediction of estimated numbers of new lung cancer cases
in the Arab world shows a gradual increase every year. Population growth, aging,
increased smoking prevalence particularly in youth and women, as well as increased
67
exposures to environmental pollutants in the region may play a critical role. Also the
frequency of different histological types of lung cancer shows a shift towards squamous
cell carcinomas in males and adenocarcinomas in females. This histological trend has
changed in the last two decades in USA and Eastern Europe reflecting changes in patterns
of tobacco consumption, the latter is increasing in the Arab world. The comparison
between the tobacco prevalence and lung cancer incidences in the Arab populations
reveals an obvious risk in most Arab countries for example in Bahrain, Tunisia, Algeria,
Morocco and Libya for males, and Lebanon for both sexes, however, some Arab
countries with high smoking prevalence had either low lung cancer incidence rates
(Yemen, Sudan and Djibouti), or moderate incidence rates such as Egypt, Syria and most
of the Gulf Cooperation Council (GCC) countries except Bahrain. In contrast to the high
incidence and mortality rates of lung cancer in African Americans over Caucasians in the
USA, the African Arabs in Mauritania, Somalia, Djibouti and Comros besides Yemen
show the lowest incidence and mortality rates in the Arab countries. The underlying
mechanisms for this trend warrant interest. There is a great need for networking all the
cancer research data in the Arab region. This will be certainly of high advantage to the
region and the world.
O 4.4
Epidemiolog
Health in the West Bank, occupied Palestinian Territory: Cancer mortality pattern
assessment, 1999-2000
Niveen Abu-Rmeileh, PhD1, Emilio Antonio Luca Gianicolo, MS2, Suzan Mitwali, MPH1,
Maurizio Portaluri3, Antonella Bruni, MS2, Jawad Bitar, MD4, Mutaem Hamad4,Maria Angela
Vigotti2, Rita Giacaman1
1. Institute of Community and Public Health- Birzeit University, Occupied Palestinian Territory.
2. Institute of Clinical Physiology of the National Research Council, Italy.
3. Radiotherapy Dept. "Perrino" General Hospital, Brindisi, Italy
4. Health Information Management Centre- Ministry of Health, Occupied Palestinian Territory
Correspondence: Dr. Niveen Abu-Rmeileh [[email protected]]
Abstract
Background: The burden of cancer is increasing worldwide, both in developed and
developing world. The situation in the occupied Palestinian territory is not different. This
study aims to study mortality patterns of cancer types in the different governorates in the
West Bank. Methods: The study is based on death certificates collected for Palestinians
living in the West Bank, occupied Palestinian territory for the period between 1999 to
2009 by the Palestinian Ministry of Health Information Centre. Results: The quality of
data was judged based on the completeness and proportion of ill-defined diseases as
cause of death. The most common cause of death out all cancer types was lung cancer
among males and breast cancer among females followed by colo-rectal cancer in both
males and females. There were regional variation in cancer specific causes of death. The
central governorates had the lowest standardised mortality rate for most cancer types for
both men and women. Lung cancer standardised mortality rate was highest in the north
among men, prostate cancer standardise mortality rate was highest in north and south.
Breast cancer standardized mortality rate was highest in the south, as was female genital
organs standardized mortality rate. Conclusion: The study documents regional variation
in deaths due to cancer. The observed variation might be explained by personal,
68
contextual and environmental factors that need to be investigated in depth to correctly
inform policy maker.
O 4.5
Epidemiology
Is risk malignancy index a useful tool for predicting malignant ovarian masses in
developing countries?
Dr. Aliya Aziz, Dr. Nida Najmi
Department of Obstetrics & Gynecology, Aga Khan University Hospital, Karachi, Pakistan
Correspondence: Dr. Aliya Aziz, E-mail: [email protected]
Abstract
Introduction: Risk of malignancy index has been widely studied for prediction of
malignant pelvic masses in western population, however, little is known regarding its
implication in the developing countries. The objective of this study is to determine how
accurately the RMI can predict the malignant pelvic masses. Materials & Methods:
This was a retrospective review of charts conducted at The Aga Khan University
Hospital, Karachi, Pakistan. Those patients who came to the Gynecological clinic
between January 2004 to December 2008 with adnexal masses were identified by means
of IDC-9CM coding system. The files of these patients were reviewed for collecting
information related to demographic characteristics, ultrasound findings, menopausal
status, CA 125 and histopathology. Patients with advanced stage disease were excluded.
The RMI for each of these patients were calculated based on the standard formula.
Results: A total of 283 women were included in the analysis. When analyzing the
individual parameters of RMI, the best predictor for malignancy was ultrasound with the
sensitivity, specificity and positive likelihood ratio of 78.3%, 81.5% and 4.2
respectively. The positive likelihood ratio of RMI at the standard cut off value of 250
was 8.1 while at the cut off of 200; it was 6.8 with comparable sensitivity and
specificity. Conclusion: RMI is a sensitive tool in predicting malignant adnexal masses.
A cut off of 200 may be suitable in developing countries for triaging and early referrals
to tertiary care centers.
O 4.6
Epidemiology
Fertility preservation in young female cancer patients
Mohamed Salama Gad
Professor of Obstetrics and Gynecology Menoufiya University, Egypt
E-mail: [email protected]
Abstract
For some patients, especially young women, loss of fertility after cancer treatment is
almost as painful as facing the disease itself. Variables to be considered before treatment
include patient’s age, cancer type and stage, proposed treatment regime and time before
it is initiated, availability of partner sperm. All these data along with fertility
preservation strategies, ovarian protection, and ovarian preservation will be discussed.
69
Session 5: Cancer Genetics
Abstract 5.1
O 5.1
Cancer Genetics
Cancer Genetics
Molecular Mechanisms of Liver Cancer
Mehmet Ozturk, PhD
Prof., Department of Molecular Biology and Genetics
Mehmet Ozturk, Department of Molecular Biology and Genetics, Bilkent
University, Ankara, Turkey
INSERM-UJF Centre de Recherche U832, InstitutAlbert Bonniot, Grenoble,
France
Phone: (90)(312) 266 50 81 Fax: (90)(312) 266 50 97,
Emails:[email protected],, [email protected]
Biography
Mehmet Öztürk, Professor of Molecular Biology and Director of Bilkent University Bilgen Genetics and
Biotechnology Research Center in Ankara, is jointly affiliated with INSERM-UJF U832 Research Center
as a Research Director. Profesor Öztürk, after graduating from Gazi University Faculty of Pharmacy,
obtained a PhD degree in biochemistry from Paris XI University in 1985. From 1995 to 1992, he
performed research on liver cancer in Harvard Medical School affiliated Massachusetts General Hospital
in Boston. He became Assistant Professor of Biochemistry at Harvard Medical School in 1989. Profesor
Öztürk was invited to create a molecular oncology unit Leon Berard Cancer Center in Lyon in 1992. He
worked as an INSERM Research Director at this institution between 1992-1995. Upon invitation from
Bilkent University, he moved to Ankara to create the Department of Molecular Biology and Genetics at this
university. He worked as department head at Bilkent University until 2007, when he decided to take his
present joint appointment position. The department he created was awarded in 2004 by Koc Foundation
for its outstanding contributions to life sciences in Turkey. Profesor Öztürk is a molecular biologist
working on genetic and biological foundations of cancer. He was awarded TUBITAK-TWAS Science
Award, and elected as a member to Turkish Academy of Sciences, European Molecular Biology
Organization and TWAS, The Academy of Sciences for the Developing World. He served as a UNESCO
International Bioethics Committee Member between 1998-2001.
Abstract: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancers.
Worldwide, most HCCs are etiologically linked to chronic hepatitis due to Hepatitis B (HBV) and
Hepatitis C (HCV) viruses. Chronic liver injury caused by viral infections or other factors such as
alcohol appears as the driving cellular mechanism of hepatocellular carcinogenesis. Chronic liver
injury is associated with different forms of cellular stress causing excessive hepatocyte death, and
increased proliferation as a compensatory response. Chronic hepatitis, when it takes tens of years,
drives liver tissue into a fibrotic process leading to cirrhosis. Cirrhotic hepatocytes display several
landmark features of senescent cells such as shortened telomeres, increased levels of cyclindependent kinase inhibitors (CDKIs) and senescence-associated beta-galactosidase (SA-β-gal).
More than 80% of liver cancers occur in cirrhotic patients. This suggests that liver cirrhosis is the
primary cause of HCC. Tumor cells emerging from cirrhotic nodules display features indicative
of their escape from senescence-mediated cell cycle arrest. Re-expression of telomere reverse
transcriptase, inactivating mutations of p53, epigenetic silencing of CDKI p16, and lack of SA-βgal activity are the major indicators of senescence escape in HCC cells. Mechanisms of
70
uncontrolled proliferation of HCC cells are ill known. Oncogenic mutations of β-catenin gene
associated with excessive cell proliferation are observed in a subset of HCCs. Increased
phosphorylation of Akt suggests that tyrosine kinase receptors may also be activated. Therapeutic
efficacy of Sorafenib, a protein kinase inhibitor drug, also suggests that tyrosine kinase signaling
is overactive in these tumors. However, it is presently unknown whether this overactivity is due
to a genetic mutation or not. Recent investigations aiming at finding additional mechanisms are
being expanded to non-genetic mechanisms such as epigenetic aberrations. Experimental
induction of liver cancer by methyl-deficient diet is a well-established concept. Recent
investigations identified aberrant DNA methylation and histone changes in HCC. Most recently,
inactivating mutations of ARID2, a chromatin remodeling gene, have been reported in one fifth of
HCCs associated to HCV infection. Our unpublished data provide additional support for the
implication of multiple epigenetic aberrations in liver cancer. Some of such epigenetic regulatory
genes may serve as potential tumor markers, as well as drug targets for better management of
liver cancer.
O 5.2
Cancer Genetics
Cellular and molecular analysis of human non-Hodgkin lymphoma subtypes
Nasser Parsa, M.D., Ph.D.
National Institutes of Health (NIH), Bethesda, MD. USA. Email: [email protected]
Abstract
Background: Non-Hodgkin’s Lymphomas (NHLs) are heterogeneous group of
malignant tissues which originated from the lymphoid system. To evaluate the molecular
and cellular alterations in malignant tissues, micro-array technology has been developed
to provide us with a better understanding of pathogenesis of human cancers. Aim:
Burkitt’s lymphomas (high grade) and Diffuse Large B-Cell Lymphomas (intermediate
grade) were analyzed by microarray genomic profiling which led to an accurate reclassification of these Non-Hodgkin’s Lymphomas subtypes. Methods and Materials:
Microarray based expression profiling was employed to examine approximately 100
Burkitt’s lymphoma specimens. With this technique, we can study the expression of
thousands genes in one experiment. These tumors were already analyzed and reported by
the conventional and pathological methods as high grade Burkitt’s lymphomas. Results:
With the help of microarray which involves the hybridization of mRNA molecule to its
cellular DNA (cDNA) template on a microchip, we were able to show a different gene
expression which is only associated with DLBCL-lymphomas. After careful analysis of
molecular and translational profiling of these tumors, we were able to demonstrate a
different diagnosis which eventually will have an impact on the prognosis. Results:
Specific genetic alterations associated with their protein expression led to the
identification of several molecular markers to re-classify 75 out of 100 tumors from high
grade Burkitt’s to intermediate grade of DLBCL-lymphomas. BCL2 and BCL-6 genes
were two of the targeted genes that showed an over expression which is associated with
DLBCL-lymphomas. DLBCL- patients respond to treatment remarkably and have a
much better prognosis than the Burkitt’s lymphoma patients. Conclusions: Our
knowledge of human cancers has originated from the developmental discoveries in
cancer biology. The advanced molecular technology helped us to recognize the basic
mechanisms of most molecular processes that govern the formation of a malignant tumor.
71
The RNA-microarrays and protein profiling of NHLs have revealed to us a better
understanding of molecular pathogenesis of human lymphomas. Consequently, it
provided us with an accurate diagnosis and followed by more specific and effective
treatment.
O 5.3
Cancer Genetics
Application of interphase Flourescence In Situ Hybridization (FISH) in the
aneuploidies studies of the spontaneous miscariages products
Sarah Mellali (1), Latifa. Mohamadi (1), K. Haoud (1,2), S. Moulessehoul
(1), Biotoxicology laboratory, Biology department, Science Faculty, University Djillali liabes Sidi bel
abbes , Algeria.
(2)Medical cytogenetic service, Medical University, Clermont-Ferrand; France
Dr. Mohamdi Latifa: [email protected]; [email protected]
Abstract
The spontaneous miscarriage is one of the most common complications of pregnancy;
actually this type of loss represents 10 to 20% of all recognized pregnancies. The genetic
causes explain 2/3 of these pregnancies failures. Indeed the fetus karyotype
abnormalities, mainly numerical, are present in nearly 70% of first trimester spontaneous
abortions. This number drops to 20% in the second trimester. On account of the frequent
culture failures and the long delays that reach 3 weeks, the molecular cytogenetic,
specially hybridization in situ fluorescent (FISH) on Interphase nuclei, allowed as to
study the karyotypes of miscarriages products in order to identify the chromosomal
abnormalities that are the most often linked to this fetal losses. Our experimental works is
based on the chorionic villi molecular cytogenetic analysis of curettage products of 15
patients suffering from spontaneous miscarriage, with gestation ages between 8 and 18
weeks. Interphase FISH technique has been applied to our samples in order to detect the
most frequent aneuploidies that could be at the origin of these spontaneous miscarriages.
We detected the presence of three pathological cases represented by two cases of
Turner’s syndrome and one case of Down's syndrome. The other results was balanced for
the chromosomes 13, 18, 21, X and Y however the probes used didn't allow as to exclude
the involving possibility of other chromosomal abnormalities. Interphase FISH technique
afford us a reliable, efficient and quick result (within 24 H), however this technique
remains an exam of second intention (after the conventional Karyotype) since it is
expensive and can only detected the targeted chromosomal abnormalities. A statistical
study has been achieved on 946 patients having spontaneous miscarriages for the year
2009, at the Maternity center of Sidi Bel Abbes. The maternal age, first risk factor,
showed a peak between 35 and 39 years. The frequency of spontaneous miscarriages was
about 10% out of the total number of registered pregnancies, in which 2/3 occurring late.
4% of the recruited women experienced three successive miscarriages, which it is
extensively over to the average recorded previously in published studies that is situated
between 0.4 and 1% only.
Keywords: Spontaneous miscarriage, Chromosomal abnormalities, Chorionic villi, Interphase FISH.
O 5.4
Cancer Genetics
Probing the methylation status of different tumor suppressor genes from bladder
cancer patients of Pakistani origin
Shumaila Bilgrami1, Shahid Pervez2, Sohail Qureshi3and Farhat Abbas4*
72
Office of Research and Graduate Studies1, Department of Microbiology and Pathology2, Department of
Biology, School of Science and Engineering, Lahore University of Management Sciences, DHA, Lahore,
Pakistan3 Department of Surgery4, Aga Khan University, Stadium Road, Karachi 74800, Pakistan
*Correspondence: Farhat Abbas, MD
E-mail: farhat.abbas @aku.edu ; Tel: +92-213-4402/4409; Fax: + 92-213-493-4294;
Abstract
Background: Bladder cancer is the second most common urological malignancy in men,
with a high recurrence rate in superficial disease and a bad prognosis associated with the
muscle invasive cancer at initial diagnosis. Promoter methylation induced silencing of
tumor suppressor genes has been implicated for various genes in bladder cancer. Aim:
We analyzed the promoter methylation in a panel of tumor suppressor genes involved in
apoptosis, DNA repair, cell cycle control and progression in non-invasive and invasive
bladder cancer. Methods: Promoter hypermethylation was investigated in the gene
promoters of RASSF1a, APC, MGMT, p16 and p15 in 43 non-invasive and low grade, 33
invasive and high grade bladder cancer and 10 cases with normal bladder mucosa/benign
urologic disease using real-time methylation-specific PCR with SYBR green. In addition
to the 86 tissue samples, DNA methylation analyses were also carried out in 16 plasma
samples from patients with invasive high grade bladder cancer. Results: Promoter
hypermethylation was frequently observed in RASSF1a, APC and MGMT genes (pvalue<0.001) and was prominent in the invasive high grade bladder cancer tissues as
compared to the non-invasive low grade group (p<0.001) and normal bladder mucosa (pvalues 0.040, 0.000 and 0.003 for RASSF1a, APC and MGMT, respectively). When the
data from16 plasma samples were compared to the corresponding tissue samples, only
APC (p-value 0.006) and p16 (p-value 0.011) showed significance in paired-T test.
Conclusions: Our results suggest that promoter methylation analysis can serve as a
valuable tool for monitoring progression of bladder cancers and assessing their spread.
Although the data on plasma samples is preliminary, it has encouraged us to interrogate
the DNA methylation status of an expanded panel comprised of oncogenes and tumorsuppressor genes in a larger number of samples.
O 5.5
Cancer Genetics
Methylation profile of cancer related genes in Tunisian patients with breast,
gastrointestinal and nasopharyngeal carcinomas
Raja Mokdad-Gargouri, Imen Miladi-Abdennadher, Dorra Ben Ayed-Guerfali, Sondes Karray-Chouayekh,
Ali Fendri and Ali Gargouri
Centre of Biotechnology of Sfax, University of Sfax Tunisia; [email protected]
Abstract
Epigenetic modification is one of the mechanisms leading to gene silencing in neoplastic
cells. By methylation-specific PCR, we analyzed the promoter methylation profile of
cancer-related genes in Tunisian patients with breast, gastrointestinal and nasopharyngeal
carcinomas. These genes are involved in crucial cellular functions such as the tumor
suppressor (RASSF1A), cell cycle control (P16INK4a), DNA repair (hMLH1), cell
signalling (RARb2) and apoptosis (DAPKinase). The MSPCR was performed on tumor
DNA as well as normal tissues. We showed that RASSF1A gene promoter is highly
methylated in breast and nasopharyngeal carcinoma. However, the percentage of
methylated RASSF1A is lower in colorectal (35%) and gastric (45%) adenocarcinomas.
Moreover, we showed that aberrant methylation of p16INK4a and hMLH1 promoters
73
occur more frequently in colorectal than in breast carcinoma (47% vs 19 % for p16INK4a
and 53% vs 24% for hMLH1). Significant associations were revealed between aberrant
methylation status and clinico-pathological parameters. In fact, hypermethylation of
hMLH1 is predictive of poor prognosis in breast and colorectal carcinomas while the
methylated RASSF1A correlated with advanced TNM in nasopharyngeal carcinoma of
Tunisian patients. Altogether, our data supports that the methylation profiles of CpGisland hypermethylation vary with tumour types.
O 5.6
Cancer Genetics
Centrosome-associated Nuak2 kinase regulates centrosome amplification and cell
cycle progression of cancer cells
Doaa H Zineldeen1,2 and Makoto Nakanishi 2
1
Department of Medical Biochemistry, Faculty of Medicine, Tanta University, Egypt,
Department of Biochemistry & Cell Biology, Graduate School of Medicine, Nagoya City University,
Nagoya, Japan. Correspondence: Dr. Doaa Zineldeen, e-mail: [email protected]
2
Abstract
Centrosomal amplification is a common phenomenon in various human malignancies and
may play a dominant role in tumor initiation and progression. Here, we report a novel
function of the mammalian Nuak2 kinase by demonstrating that human Nuak2 directly
contributes to centrosome amplification. A subpopulation of endogenous Nuak2 localized
to the centrosomes in a cell-cycle dependent manner. Overexpression of Nuak2 resulted
in centrosome overduplication in a kinase-activity dependent manner, while
overexpression of its kinase- dead mutant negatively affected centrosome duplication and
resulted in fragmented pericentriolar material and mitotic defects. Additionally,
overexpressed wild type Nuak2 caused polyploidy and stabilization of the microtubules.
Targeting Nuak2 kinase by its specific small interfering RNA (siRNA duplexes) arrested
the cells at metaphase. Those cells showed defective centrosomal duplication together
with variable spindle polar abnormalities and chromosomal misalignment. Furthermore,
our data indicate that at interphase Nuak2 is required for duplication of centrosomes,
thereafter centrosomal maturation, bipolar spindle assembly and normal mitotic
progression. Overall, considering that centrosome overduplication is linked to cellular
transformation, our observations may also provide a molecular link between mammalian
Nuak2 kinase and cancer and provides a multimodal therapeutic target in a subset of
malignancies.
74
Session 6: Tumor Markers
O 6.1
Tumor Markers: Thyroid
Screening of TPO gene c.1708C>T and c.1978C>G mutations in Iraqi patients with
hypothyrodism and thyroid cancer
Abdul-Hassan, I.A.1 , Al-Ramahi, I. J.2 , Al-Faisal, A.H.M.1 and Barusrux, S.3
1
Genetic Engineering and Biotechnology Institute(GEBI), Baghdad, Iraq.
Al-Razi Centre for Medical Diagnostic kits Production, Ministry of Industry, Iraq.
3
Center for Research and Development of Medical Diagnostic Laboratories (CMDL) ,Faculty of
Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Correspondence: Dr. Ismail A. Abdul-Hassan, Tel : +9647700011410, E-mail: [email protected]
2
Abstract
Thirty seven patients (hypothyroidism, n=20 and thyroid cancer, n=17) and twenty five
healthy individuals (control) were used in this study. These patients who attend the
endocrinologist in Nuclear Medicine Hospital and Al Yarmouk Nuclear Medicine
Department in Baghdad, were selected during a period from July to October 2009.
Modified specific locked nucleic acid (LNA) primers were used for the detection of TPO
gene mutations which include c.1708 C> T and c.1978 C>G. Seven mutations were
found in TPO gene. Mutations involved transition cytosine by thymine at position 1708
of the exon 10 (c.1708C>T) were found in four thyroid cancer patients, while,
transversion of cytosine by guanine at the position 1978 of exon 11 (c.1978C>G) were
found in one thyroid cancer and two hypothyroidism patients. It can be conclude that the
c.1708C>T and / or c.1978C>G mutant TPO in hypothyroidism and thyroid cancer
patients studied is very likely to be properly expressed but lacks enzymatic activity.
Key Wards: TPO, c.1708C>T, c.1987C>G, Mutations, LAN primers.
O 6.2
Tumor Markers
Histo-pathological study of mammary glands of benign tumors in the female rats
Abdul –Hadi sallal Mohammad; Tawfeeq Jawad Ali; Atheer kadhim ibadi
College of Health and Medical Technology; Community Health Department Kufa
Technical Institute of Kufa; Iraq
Correspondence: Prof. Abdul-Hadi Mohammad ([email protected])
Abstract
The present study revealed the type of the benign tumours in the female albino rats at age
(4) months, the common type of benign tumours in mammary glands was fibro adenoma
which arise from connective tissue and epithelium, histologically, the fibro adenoma
appear as duct like structure and thinner in ductular structure of mammary gland which
occurred and over growth in the connective tissue masses. The female rats with benign
breast tumour showed epithelial hyperplasia had a definitive increased risk of developing
75
mammary gland cancer, and the epithelial and connective tissue hyperplasia was related
to mild increased risk. The complications of connective tissue can occur in the mammary
glands such as lipomas and haemangiomas.
Keywords: Histo-pathology; Mammary glands; Breast Tumors; Rats
O 6.3
Tumor markers
High Ezrin immunoreactivity is an indicator of poor survival in squamous cell
carcinoma of uterine cervix
Tahany M. Shams, M.D*; Hanaa O. Badr- El- Din, M.D** and Iman Loay, MD
The Departments of Pathology* Faculty of Medicine, Suez Canal University; Obstetrics and
Gynecology**, Faculties of Medicine, Al-Azhar University and Department of Pathology***, Cairo
University, National Cancer Institute, Egypt
Correspondence: Dr. Tahani Shams: E-mail: [email protected]
Abstract
Background and Aim: Ezrin; the membrane-linking protein is highly expressed in
several types of human cancers and correlations between its immunoreactivity and
histopathological data as well as patient outcome have previously been shown. However,
such studies have not yet been done on cervical cancer. So the aim of our study was
investigate the expression of Ezrin in cases of cervical squamous cell carcinoma then
correlate the data with disease specific survival and metastasis survival and also with
other clinicopathological variables as age, grade, stage, lymph node or distant metastasis,
tumor size and type. Material and Methods: We carried out Immunohistochemical
analysis of Ezrin in 64 cases of cervical cancer and correlated it to clinicopathologic
variables and disease outcome. Ezrin was scored as absent (0), weak (1), intermediate (2)
and marked (3) staining. Results: Ezrin was identified in 50(78.1%) of 64 cervical cancer
studied cases which classified as weak, moderate and marked in 16%, 28% and 56%
respectively. In contrast to the predominantly membranous immunoreactivity in normal
cervical epithelium, it was cytoplasmic in cancer cells. Ezrin expression significantly
correlated with lymph node metastasis and distant metastasis at diagnosis (p <0.001), also
there is significantly correlation with tumor grade and stage (p= 0.02 and 0.005
respectively but not correlated with other variables as (age, tumor size, histological type).
For statistical analysis, we classified Ezrin expression into two group as (-&1) and (2&3);
the last is considered as high Ezrin expression. Regarding outcome, high Ezrin expression
was associated with short disease specific survival (DSS) and poor metastasis survival
MS (P <0.001). In univariate analysis the patients with (-&1) Ezrin score had a
significantly longer DSS and MS (P <0.001) so high Ezrin immunoreactivity can predict
both 5 year DSS and MS but this prediction was lost in multivariate analysis. conclusion:
Our results suggested that Ezrin expression may represent an effective prognostic marker
and a potential target for treatment of invasion and metastasis in cervical cancer.
Keywords: Ezrin, immunohistochemistry, squamous cell carcinoma, cervical cancer,
clinicopathological, patient surviva
76
O 6.4
Tumor markers
Detection of circulating tumour cells in prostatic cancer patients using polymerase
chain reaction
Ola Sharaki(1),Seif Elislam Mahmoud(2), Abla abou zeid(1), Nermine Hossam(1) and Rasha
Nour(1)
Clinical Pathology Department (1), Surgical Urology (2) Faculty of medicine, Alexandria University
Correspondence: Dr. Nermine Hossam Eldin Zakaria
Assistant Professor of Clinical Pathology
Technical Manager of AUHL, Faculty of Medicine, Alexandria University, Egypt
[email protected], Mob: 01223374277
Abstract
The aim of this study was to determine the presence of hematogenous neoplastic cells in
patients with prostate cancer. We used a reverse transcription (RT) polymerase chain
reaction (PCR) of prostate- specific antigen (PSA) mRNA to detect the presence of
circulating tumour cells in 34 clinicopathologically proven prostatic cancer patients, 19 of
them were proven to have locally malignant tumour and 15 were diagnosed with
metastatic prostate cancer. 26.3%(5/19) of patients with locally malignant tumour were
positive for CTCs and 80%(12/15) of patients with metastatic disease were positive for
CTCs . There was a statistically significant positive correlation between CTCs and tPSA, Gleason score and imaging studies. We recommend searching for CTCs to be done
as a routine in all newly diagnosed non metastatic prostate cancer patients for the early
detection of metastasis.
Key words: prostate cancer, prostate specific antigen, PCR and circulating tumour cells.
Abbreviations: RT reverse transcriptase, PCR polymerase chain reaction, PSA prostate
specific antigen, CTCs circulating tumour cells.
O 6.5
Tumor markers
Quality Care Nursing: Educational issues in genetic testing
Manal Tawfiq
Deapartment of Obstetritcs and Gyencology, Faculty of Nursing, Tanta University, Egypt
Abstract
Fifteen years a major scientific revolution started with the establishment of the human
genome project. Since that time a comprehensive sequence of the human genome has
been defined. Individual, family and social goals conflict with current health care
practices and polices when genetic testing is done. Current health polices do not fully
address their concern. Unresolved issues include protection and privacy of individuals
while considering genetic information needs family members, determination of a
properiate monitoring of genetic test, assressing generic health care descripancies, and
assuring appropriate nursing workforce preparation. Introducing genetic testing into
health care requires that providers are knowlegable regarding ethical, policies, and
practices, issues in order to minimize risk for any harm, protect the right of individuals
and family and considered social context in the management of genetic test results. The
understanding of these issues is a component of the gentic nursing competency that must
be addressed at all levels of nursing education.
77
Day 2: Poster Session 2
1. Infection and Cancer
O 1.1
Infection and Cancer
Anti-schistosomal and anti-tumor responses to mutual interaction between cancer
and infection
Mohamed Labib Salem1, Afrah Fathi Salama2, Mohammed Mahmud Ali El-said3 Afnan
Hamdy El-gowily4
Immunology and Biotechnology Unit, Zoology Department 1* and Biochemistry Department, Faculty of
Science, Tanta University3, Biochemistry Department, Faculty of Science, Alexandria University, Egyp 4,
*Corresponding to: Dr. Mohamed Labib Salem, Prof. of Immunology,
[email protected]]; [email protected]
Tel: +20-01274272624, Fax: +20-40-3350804
Abstract
Background: Tumor can be developed in schistosoma-infected patients. Alternatively,
patients with tumor can be subjected to schistosoma infection. It is not clear, however,
whether there is a mutual effects of these diseases with or without treatment with the
choice drugs. Aim: Determine the host responses to mutual interaction between cancer,
represented by Ehrlich ascites, and infection, represented by Schistosomiasis.Method:
For schistosmiasis infection, mice were infected with 70 cercariae by tail immersion. For
tumor challenge, mice were injected with 1 million cells of Ehrlich ascites carcinoma cell
line. The anti-schistosomal drug prazequintal (PZQ) and the anti-tumor drug cisplatin
were used for intraperitoneal treatment at the indicated time points. Results: Mice
infected with schistosoma and challenge wit tumor 4-5 weeks later showed the same
antischistosomal (worm and egg burden) and antitumor (total tumor cell count and mouse
survival) parameters when compared to mice infected with schistosoma alone group or
challenged with tumor cells alone. As expected, combinatorial treatment with PZQ and
cisplatin of schistosoma-infected mice that were challenged 4-5 weeks later with tumor
cell line decreased the tumor burden as wells as the worm and egg burden after treatment
as compared to the non-treated controls. Interestingly, however, the worm and egg
burden in mice challenged with schistosoma alone or schistosoma and tumor cells
showed more decreases after treatment with both cisplatin and PZQ. Conclusion: The
results of this study showed that there is no mutual interaction between schistosomiasis
infection and tumor burden. It also showed that PZQ has no effect on antitumor
parameters while cisplatin even at low doses has anti-schistosomal effects.
Keywords: Schistosomiasis, Breast Cancer, Ehrlich ascities; Prazequintel; Fibrosis; Worm
Burden
78
O 1.2
Infection and Cancer
Association of hepatitis virus on acute and chronic myeloid leukemias: A
preliminary report
A . Movafagh*1 ,N.Varma2 , F.Shaveisi Zadeh
*1
For correspondence PhD; Associate Professor and Head Department of Medical Genetics,Shahid Beheshti
University of Medical Sciences ,Tehran, Iran, Fax +98(21) 2240067 +98-21-23872572; E mail
[email protected]
2
Postgraduate Institute of Medical Education and Research (PGI), Chandigarh, India
Correspondence: Movafagh Abolfazl Head Department of Medical Genetics, Associate Professor,Department of
Medical Genetics. Shahid Beheshti Medical Sciences University., Chamran Highway,EVIN AVE.Tehran Iran
0098 21 23872572, 0098 09121307881, Email [email protected]
Abstract
Background: More than 15% of human cancers can be attributed to virus infection. In
this connection, Hepatitis B Virus (HBV) increases the risk of leukemia, especially acute
myeloid leukemia. Materials and Methods: This prospective sectional study was
conducted from 1996 to 2010 among patients with acute and chronic myeloid leukemia
and controls. Cytochemical staining, immunophenotyping, cytogenetic /molecular
cytogenetics, Elisa, enzyme immunoassay and Western blot, were the main subject of
laboratory manipulation. Results: Hepatitis B virus was diagnosed in one control patient
(%0.004) and four infected with leukemic patients (%3). The differences of leukemic
patients revealed statistical significant when compared with controls (P=0.0047).
Conclusion: In the preliminary results, the prevalence of HBV infection was higher in
patients with leukemias than in patients as non malignant controls, but the number of
cases is not large enough to draw firm conclusion. We suggest that this issue warrants
further investigation by large consortium studies.
Keywords: Leukemia, AML, CML, HBV, Association
2.Theray: Preclinical Studies
P 2.1
Therapy (Preclinical Studies)
Anti-angiogenic and apoptotic effect of novel synthetic Europium(III)-Acridine
carboxylate complex against Ehrlich ascites tumor cells
Abdullah I. El-Faloujia, Mona F. El-Azabb, Belal H. M. Husseinc and Hassan A. Azab c
a
Biotechnology Research Center, bDepartment of Pharmacology and Toxicology, Faculty of Pharmacy,
c
Chemistry Department, Faculty of Science. Suez Canal University, Ismailia 41522, Egypt.
Correspondence: Dr. Abdullah I. El-Falouji
Biotechnology Research Center, Suez Canal University , Ismailia 41522 , Egypt .
Tel.: +20-01115990299; fax: +2064-3200452., E-mail: [email protected]
79
Abstract
New organometallic complex europium(III)-acridine-9-carboxylate complex was
synthesized and characterized. Invivo anti-tumor and anti-angiogenic potencies of
europium(III)-acridine-9-carboxylate complex against ehrlich ascites carcinoma (EAC)
cells are described. The newly synthesized complex resulted in inhibition of proliferation
of EAC cells and ascites formation. The anti-tumor effect was found to be through antiangiogenic activity as was evident by the reduction of microvessel density in EAC solid
tumors. Their anti-angiogenic effect is mediated through, at least in part, the downregulation of VEGF receptor type-2 (Flk-1). Capillary electrophoresis (CE) method was
used to monitor the progress of complexes to induced apoptosis of EAC cells by analyze
DNA fragmentation. It was found that EAC cells had distinct DNA fragmentation
patterns analyzed by CE.
Keywords: Lanthanum complex, Antitumor activity, anti-angiogenesis, Apoptosis, DNA fragmentation.
P 2.2
Therapy (Preclinical Studies)
Discovery of carbon-nanotube genes’ target in human normal bronchial epithelial
cells model
Anas Alazzam1,2, Etienne Mfoumou1,2, Ion Stiharu1, Narayanswamy Sivakumar1 & Ala-Eddin Al
Moustafa1,2,3
1
Department of Mechanical Engineering, Concordia University, Montréal, Quebec, Canada. 2Montréal
Centre for Experimental Therapeutics in Cancer, Lady Davis Institute for Medical Research of the Sir
Mortimer B. Davis-Jewish General Hospital, McGill University, Montréal, Canada; and 3Department of
Anatomy, Faculty of Medicine/University of Aleppo, Aleppo, Syria
Corresponding Author: Ala-Eddin Al Moustafa, email: [email protected]
Abstract
Carbon nanotubes (CNTs) offer exciting opportunities for science and applications. In
recent years, CNTs research has been established as a highly interdisciplinary field to
exploit their outstanding features. Great interest has been generated in fullerenes in
general, but especially in CNTs and carbon nanohorns as biologically compatible
materials and drug carriers mainly because of their distinct architecture, hollow interior
and cagelike structures. However, the small size, large surface area, and high reactivity of
these materials are the main factors for potential toxicity. Moreover, CNTs will have
wide-spread applications in many technological fields, thus worker/consumer exposure is
likely to occur, posing emerging health concerns. Initial toxicological studies
demonstrated that pulmonary deposition of CNTs causes acute pulmonary inflammation
as well as chronic responses such as fibrosis. However, the mechanisms by which CNTs
provoke susceptibility to toxicity and pulmonary inflammation is not clear. Thus,
genome-wide monitoring of gene expression is important to understand the extent of
CNTs effect. To this end, we have carried out a cDNA array analysis using Affymetrix
probe-sets complementary to approximately 54 675 human genes, to monitor the levels of
expression within aggregates of human normal bronchial epithelial cells treated with
80
CNTs and their wild type cells. We identified a comprehensive list of genes that are
differentially expressed between CNTs-treated and their control cells, the majority of
them have been identified for the first time as targets of CNTs-effect. In addition to
revealing the complex nature of the genetic changes after the accumulation of CNTs in
human normal lung cells; we believe that our data can provide the possibility to use
modified forms of CNTs as a potential therapeutic agent to treat lung cancer.
Key words: Carbon Nanotubes, Human Bronchial Epithelial Cells, cDNA Microarray, Gene Expression.
This work was published in the Nanomedicine journal (Alazzam et al., 2010)
O 2.3
Therapy (Preclinical Studies)
Anticancer peptides derived from animal venoms
Mohamed A. Abdel-Rahman a* and Peter N. Strong b
a
Zoology Department, Faculty of Science, Suez Canal University, Ismailia 41522, Egypt
b
Biomedical Research Centre, Biosciences Division, Sheffield Hallam University, Sheffield S1 1WB, UK
Correspondence: Dr. Mohamed A. Abdel Rahman, PhD
Lecturer of Molecular Physiology & Toxinology, Editor of the Journal of Venom Research (JVR)
Zoology Dept., Faculty of Science, Suez Canal University, Ismailia, 41522, Egypt, Mobile: +20120862886,
e-mail: [email protected], [email protected]
Abstract
Natural products have a rich history in the development of anti-cancer drugs. Venomous
animals use their venoms, both to subdue prey and as defense mechanisms, and as a
consequence these venoms contain a pharmacopeia of biologically active molecules
which have been proven to either be of direct use as novel therapeutic agents or to
provide a critical template for the design of others. Venoms of several animal species
(such as snakes, scorpions, spiders, frogs, bees, wasps and ants) and specific proteins and
peptides isolated from these venoms have shown therapeutic potential as anti-cancer
agents. Several cytotoxic venom peptides have been shown to possess several distinct
mechanisms of action including (i) ion channel blockade (ii) matrix metalloproteinase
inhibition and (iii) induction of apoptosis. The first clinical trials of synthetic peptides
derived from animal venoms are beginning to show positive results and the field is
looking very promising. In this review, we present research highlights characterizing
peptides of animal venoms which have anticancer activity. Our recent findings of the
anticancer efficacy of Conus venom will also be discussed.
Keywords: Venom, Cytotoxic Peptides, Cancer, Anti-tumor therapy.
O 2.4
Therapy (Preclinical Studies)
Combined effect of Cerastes cerastes snake venom and magnetic waves on Ehrlich
tumor bearing mice
H. M. SAYED AHMED 1, F.M. ALI2, H.A. ABD EI TAWAB3, E.M. ABD EL-KADER4 AND
C. R. SHAKER 5
Department of Pharmacology1, Faculty of Pharmacy, Cairo University, Cairo, Egypt, Department of
Biophysics 2, Faculty of Science, Cairo University,
81
Department of Pharmacology3, Faculty of Pharmacy, Cairo University, Cairo, Egypt , Department of
Pharmacology4, Faculty of Pharmacy, Modern University for Technology and information, Cairo, Egypt
and Holding company of biological products and vaccines VACSERA 5 ,Cairo, Egypt.
Dr Nevein Abdel hady [email protected]>
Abstract
The use of chemotherapy for cancer treatment is a successful modality. However, this
treatment has its side effects, which limits its applicability. This work was done to study
the effect of snake venom and/or of exposure to extremely low frequency magnetic
waves (ELF- MW) on liver of normal mice, and of Ehrlich carcinoma bearing mice. A
total of 122 mice were used, divided into two groups, "A" and "B". Group A: normal
mice were subdivided into 3 subgroups: A 1: control, was given saline 0.2 ml: A2: was
given (0.75 μg / g b.w) snake venom; A3: was whole body exposed to 4.5 Hz square wave
magnetic field of intensity 2 Gauss for a period of 7 days (d) at a rate of 2h/d. Group B:
tumor bearing mice, were subdivided into 5 subgroups: B 1: was received no treatment;
B2: was given (0.75 μg / g b.w) snake venom; B3: was whole body exposed to 4.5 Hz
square wave magnetic field of intensity 2 Gauss for a period of 7 days (d) at a rate of
2h/d; B4: was given snake venom and exposed to MWs; B 5: was given 2.8 mg/kg
methotrexate as standard chemotherapy. Histological examination of liver using
hematoxylene and eosin (H& E), as well as blood analysis were performed. Results
showed that crude snake venom did not satisfactorily control tumor growth; while
exposure to ELF- MWs at resonance frequency 4.5 Hz, 2G was quite effective in limiting
tumor growth and proliferation, with minimal effect on non- involved tissues. The use of
magnetic waves at resonance frequency 4.5 Hz, 2G proves to be much safe for treatment
of primary tumor site and to secondary sites.
O 2.5
Therapy (Preclinical Studies)
A novel hydrogen bonded bimetallic supramolecular coordination polymer
[Me3Sn(bpe).Ag(CN)2.2H2O] as anticancer drug
Safaa El-din H. Etaiw1, Ahmed S. Sultan2, Ahmed S. Badr El-din1
1
Chemistry Department, Faculty of Science, Tanta University, Tanta, Egypt
Biochemistry Department, Faculty of Science, Alexandria University, Alexandria, Egypt
Correspondence: Dr Ahmed Samara Ahmed Badr El-din
Lecturer of Inorganic Chemistry, Chemistry Department, Faculty of Science, Tanta University, Egypt
E-mail: [email protected]; [email protected]; Mobile: 002/0104363172
2
Abstract
The reaction of Me3SnCl, K3[Ag(CN)4] and 1,2-bis(4-pyridyl)ethane (bpe) in
water/CH3CN solution at room temperature affords the novel bimetallic supramolecular
coordination polymer (SCP) [Me3Sn(bpe).Ag(CN)2.2H2O], 1. The structure of 1 consists
of cationic {-Sn(Me3)-bpe-}+ chains that are neutralized by [Ag(CN)2]- anions. The
dicyanoargentate(I) anions present discrete uncoordinated fragments between the cationic
chains. The water molecules bind the cationic chains and the anions forming 3Dsupramolecular structure through hydrogen bonds. 1 exhibits strong fluorescence in the
82
solid state at room temperature. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium
bromide (MTT) assay was used to determine the in vitro antitumor effects of the SCP 1
on human breast cancer cell line, T-47D. Cell cycle analysis revealed that the SCP 1
induced apoptosis in T-47D breast cancer cell line. Moreover, in vivo, the SCP 1
suppressed tumor growth in rats model developed mammary carcinoma by 44.8%
compared to the vehicle treated control. Thus, the SCP 1 exhibits specific in vivo and in
vitro antitumor effects.
Keywords: Silver cyanide, Trimethyltin, 1,2-bis(4-pyridyl)ethane, Supramolecular Coordination polymer,
Hydrogen bonds, Fluorescence, Antitumor activity.
O 2.6
Therapy (Preclinical Studies)
Synthesis, antimicrobial, and anticancer activities of new α- aminophosphonate
derivatives using 3-acetylpyridine
Mohamed F. Abdel-Megeeda,*, Badr E. Badrb, Mohamed M. Azaama
a
Department of Chemistry, Faculty of Science, Tanta University, Tanta, Egypt.
Department of Botany, Faculty of Science, Tanta University, Tanta, Egypt.
Correspondence: Dr. Mohamed M. Azaam: Tel.: +20104694523; Fax: +23344352
E-mail address: [email protected]
b
Abstract
A series of novel α-aminophosphonate derivatives using 3-acetyl pyridine has been
synthesized. The antimicrobial activities against Escherichia coli (NCIM2065) as gramnegative bacteria, Bacillus subtilis (PC1219) and Staphylococcus aureus (ATCC25292)
as gram-positive bacteria, Candida albicans and Schccaromycies cerevisiae as fungi
showed high activities at low concentrations (10, 50, 100 μg/ml). Furthermore, anticancer
activities against two cancer cell lines [liver carcinoma cell line (HepG2) and human
breast adenocarcinoma cell line (MCF7)] were also carried out and all compounds
showed significant cytotoxicity (IC 50: 17.3, 15.8, 13.3, 17.1, and 17.6 μg/ml for HepG2
and 18.2, 17.6, 20.2, 19.6, and 19.4 μg/ml for MCF7 respectively). The lethal dose of the
synthesized compounds was also determined (915, 38, 83, 1000, and 843 μg/ml) which
indicated that some of these compounds are safe and less toxic.
Keywords: α-Aminophosphonate, 3-acetyl pyridine, anticancer, antimicrobial, lethal dose.
P 2.7
Therapy (Preclinical Studies)
Marine sponges: A potent source of anticancer metabolites
Haiam M. Aboul-Ela
The National Institute of Oceanography and Fisheries. Alexandria, Egypt
e-mail: [email protected]
Absract
The search for pharmaceutically active compounds from natural sources is well
established. With oceans covering 70% of the surface of the earth, coupled with the large
and varied biodiversity of the marine environment, the oceans remain a largely
unexplored, but extremely promising source of new drug candidates. Approximately half
of the novel marine natural products reported in the literature are biologically active. This
83
occurrence can be contributed to the reliance of sessile, soft-bodied marine invertebrates
on chemical defense for survival, as many lack the physical defense mechanisms of
movement and camouflage. Among the most promising sessile marine organisms in this
aspect are marine sponges. More than 15.000 marine products have been described up to
now in which sponges are champion producers, concerning the diversity of products that
have been found. They are responsible for more than 5300 different products and every
year hundreds of new compounds are being discovered. Most bioactive compounds from
sponges can be classified as antiinflammatory, antitumour, immuno- or neurosurpressive,
antiviral, antimalarial, antibiotic or antifouling. The chemical diversity of sponge
products is remarkable. In addition to the unusual nucleosides, bioactive terpenes, sterols,
cyclic peptides, alkaloids, fatty acids, peroxides, and amino acid derivatives (which are
frequently halogenated) have been described from sponges. A number of isolated sponge
compounds are inhibitors of protein kinase C (PKC). PKC inhibitors have attracted
interest worldwide, as there is evidence that too high levels of PKC enzyme are both
involved in the pathogenesis of arthritis and psoriasis (due to regulation of phospholipase
A2 activity), and in tumour development. The marine sponges continue to attract attention
as rich sources of structurally novel anticancer secondary metabolites.
P 2.8
Therapy (Preclinical Studies)
Marine derived Fungi through the drug discovery and application in treatment of
cancer and neurological disorders
Asmaa N. Ali1, Nehad M. Abdel-Moneim2 and Ahmed M. Abdel-Azeem3
1
National Institute of Oceanography and fisheries, [email protected]
Department of Biochemistry, Faculty of Science, Alexandria University
3
Department of Botany, Faculty of Science, Suez Canal University
2
Abstract
Fungi derived from marine sources are considered to represent a huge reservoir of secondary
metabolites, many of which are biologically active and have application. Marine fungi are highly
potent producers of bioactive substances with antifungal, anti-cancer, anti-inflammatory and
antioxidant activity. Tyrosine kinase inhibition, antioxidant and anti-inflammatory effect,
indicate the powerful effect of fungal extract as a protective against many types of cancer and
neurological disorder such as Alzheimer's disease (AD), Parkinson's disease (PD) and
Huntington's disease (HD). Our result recorded highly inhibition ratio by 91.98%, 91.09%,
93.55% of tyrosine kinase, in-vitro lipid per oxidation (TBARS inhibition assay) and
acetylcholinestrase inhibition respectively.
84
3. Medicinal Plants
P 3.1
Medicinal Plants
Comparison of antitumor effects of garlic extracts against human laryngeal
carcinoma
Ahmad Ghorbani1,2, Jalil Tavakkol-Afshari3, Moosa-Alreza Hadjzadeh4, Mohammad Taghi
Shakeri5, and Heydar Parsaei6
1
Neyshabur Faculty of Medical Sciences, Neyshabur, Iran
Pharmacological Research Center of Medicinal Plants, Faculty of Medicine, Mashhad University of
Medical Sciences, Iran
3
Immunology Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Iran
4
Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
5
Department of Social Medicine, Faculty of Medicine, Mashhad University of Medical Sciences Iran
6
Department of Pharmacology, Faculty of Medicine, Mashhad University of Medical Sciences, Iran
Correspondence: Dr. Ahmad Ghorbani: [email protected]
2
Abstract
Experimental studies provide evidences that garlic (Allium sativum) is effective inhibitor
of the tumor growth. In this study, we compared the antitumor effects of two types of
garlic extracts, aqueous and ethanolic, against human laryngeal carcinoma (Hep2) cells.
The cells were cultivated and incubated with concentrations of 0.5, 1, 4, 8 and 12 mg/ml
of the extracts. They were assessed microscopically for signs of death such as
morphological changes, granulation and anchorage independency from 24 to 72 h after
treatment. Also, the antiproliferative properties of the extracts were determined by MTT
colorimetric assay. After 24 h, the cytotoxic effect of garlic was started from
concentrations of 4 and 8 mg/ml for ethanolic and aqueous extracts, respectively. For
both extracts, the effect became more pronounced with time and with increase of
concentration. According to MTT assay, the viability of Hep2 cells decreased to 10 and
80% of control with the addition of 12 mg/ml of ethanolic and aqueous extracts,
respectively. Therefore, it seems that ethanolic extract of garlic had more potent
antitumor property against human laryngeal carcinoma than its aqueous extract.
P 3.2
Medicinal Plants
Sophora pachycarpa and Salvia chorassanica: as promising antitumor medicinal
plants
Seyed Hadi Mousavi*, Mahsa Hossini Motaez, Hojat Soufi, Seyed Ahmad Emami, Zahra
Tayarani-Najaran,
* Seyed Hadi Mousavi, M.D., Ph.D., Pharmacological Research Centre of Medicinal Plants, School of
Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Email: [email protected], [email protected] . Mobile: + 98-9155199598, Work: 0511 8002258
85
Abstract
Here, we investigated the cytotoxic effects of methanol extract and obtained fractions
from S. pachycarpa and Salvia chorassanica root extract as Iranian medicinal plants on
different cancer cell lines including A549, HeLa, HL60, MCF-7, and PC3 cells, and
lymphocytes as non-malignant cells. Meanwhile the role of apoptosis was explored in
this toxicity. Malignant and non-malignant cells were cultured in RPMI 1640 medium
and incubated with different concentrations of plant extracts. Cell viability was quantified
by MTT assay. Apoptotic cells were determined using PI staining of DNA fragmentation
by flow cytometry (sub-G1 peak) and activity of caspase 3,8 and 9. The degree of DNA
fragmentation was analyzed using agarose gel electrophoresis based on the formation of
internucleosomal units. S. pachycarpa inhibited the growth of malignant cells in a dosedependent manner and the CH2Cl2 fraction showed the lowest IC50 values ranged from
30 to 50 μg/mL in various cell lines. The IC50 for methanol extract, n-hexan, CH2CL2
fractions for S. chorassanica were calculated 8.8, 5.45 and 2.38 µg/ml in HeLa cells. S.
pachycarpa and S. chorassanica induced a sub-G1 peak in flow cytometry histogram of
treated cells, DNA fragmentation and activation of caspase 3 and 8 acivity indicating
apoptotic cell death is involved in S. pachycarpa and S. chorassanica -induced toxicity.
In conclusion, S. pachycarpa and S. chorassanica exert cytotoxic effects in different
cancer cell lines in which apoptosis plays an important role. IC50 values show both
plants could be considered as a potential and promising chemotherapeutic agent in cancer
treatment.
Keywords: apoptosis, Sophora pachycarpa, Salvia chorassanica, cytotoxicity
P 3.3
Medicinal Plants
Potential in vitro and in vivo antitumor effects of polyphenolic compounds on
experimental tumor ascites
1
Mohamed Labib Salem, 2Abdel-Halim Abdel- Hady Mostafa, 3Ehab M. Mohamed, and 3Abeer
Abdel-Hamid Ahmed Khamis
1
Zoology Department, Faculty of Science, Tanta University; 2Biochemistry Department, Faculty of Science,
Ain Shams University; 3Biochemistry Division, Chemistry Department, Faculty of Science, Tanta
University, Egypt. Correspondence: Pof. Mohamed Labib Salem, Prof. of Immunology;
[email protected]; [email protected]; Tel: +20-01274272624, Fax:
+20-40-3350804
Abstract
Background: Although several conventional anti-cancer drugs are available, most of
them are toxic and intolerable after long-term use. Therefore, there has been a global
increased interest to identify novel agents that can possess anti-tumor effects by itself or
maximize the anti-tumor effects of low doses of conventional anti-cancer drugs. Aim:
The primary aim of this study was to purify phenolic compounds from widely used
medicinal plants extracts, including Camellia Sinensis, Nigella Sativa,Triticum Aesativum
and Matricaria Chamomilla. The secondary aim was to investigate the anti-tumor effects
86
of a single or combinatorial treatment with extracts from these plants in vitro and in vivo.
Methods: Ehrlich ascities carcinoma (EAC) cells were used as a breast cancer tumor
model. For in vitro studies, 1 million EAC cells in PBS were incubated with varying
concentration of phenolic extracts at 37 ◦C for 4h in CO2 incubator. The viability of the
cells was determined by trypan blue exclusion method. For in vivo studies, was EAC cells
were injected into Swiss albino mice followed by oral administration of the phenolic
extracts at a dose of 100 mg/kg body weight every other day for 14 d. After 24h of the
last treatment dose, the mice were left to monitor their survival or sacrificed to assess the
tumor cell numbers. Results: The phenolic extracts from C. Sinensis, N. Sativa, T.
Aesativum and M. Chamomilla caused significant (P<0.01) increases in the mean survival
time (MST) and prolonged the life span of EAC tumor-bearing mice. The enhanced
survival o was associated with decreases in the total numbers of tumor cells as well as the
numbers of viable and dead tumor cells. Interestingly, the anti-tumor effects of
combinatorial treatment of the extracts showed higher effects than treatment with single
estract. Furthermore, addition of either of these phenolic extract with cisplatin, the drug
of choice for EAC, induced higher anti-tumor responses than treatment with the extract or
cisplatin alone. The phenolic extract of green tea showed the highest the anti-tumor
effects as compared to the other extracts. Conclusion: The phenolic extracts of the
studies plants have potential anti-tumor effects when used in combination and can
enhance the anti-tumor effects of the conventional anti-cancer drugs.
P 3.3
Medicinal Plants
Outcome of Teucrium polium plant extract on human prostate and lung cancer
Mustapha Kandouz1, Khadidja Haïdara1, Amal Alachkar2, Amber Yasmeen1 & Ala-Eddin Al
Moustafa1,2,3,4
1
Segal Cancer Centre, Lady Davis Institute for Medical Research, McGill University, Montreal, Quebec,
Canada; 2Syrian Research Cancer Centre of the Syrian Society Against Cancer & Aleppo University,
Aleppo, Syria; 3Oncology Department, McGill University, Montreal, Quebec, Canada; and 4Department of
Mechanical Engineering, Concordia University, Montreal, Quebec, Canada
Correspondence: Dr. Ala-Eddin Al Moustafa, email: [email protected]
Abstract
Teucrium polium (TP) is a medicinal plant that has been used for more than two thousand
years for treating many diseases such as abdominal pain, indigestion and diabetes in the
Middle East. On the other hand, human prostate and lung metastatic cancers are the two
major causes of cancer-related deaths especially in western countries. Nevertheless, the
effect of TP plant extract on human metastatic cancer cells especially prostate and lung
cancers has not been investigated yet. Hence, we examined the effects of TP extract on
selected parameters in human prostate and lung cancer cell lines, PC3, DU145, H322 and
A549. We found that TP plant extract induces cell death and provokes S cell cycle arrest
and reduction of G0-G1 phase in these cell lines. We also reported that TP extract induces
differentiation to an epithelial phenotype “mesenchymal-epithelial transition” which is an
important process in cell invasion and metastasis; consequently TP plant extract provokes
a dramatic decrease in cell invasion of PC3 and DU145 cancer cells in comparison with
87
untreated cells. These alterations are accompanied by a re-localization of the expression
patterns of E-cadherin and catenins which can be induced by the conversion of
catenin’s role from a transcriptional regulator to a cell-cell adhesion molecule via Src
dephosphorylation. Our data reveal that TP plant extract regulates signaling pathways of
cell death and cell adhesion, suggesting that this plant extract has therapeutic promise in
the treatment of several human carcinomas including prostate and lung.
Key words: Teucrium polium plant, prostate & lung cancers, cell death, cell invasion, E-caderin/catenin
complex, Src
P 3.4
Medicinal Plants
Cytotoxic and apoptogenic properties of Sophora pachycarpa and Salvia chorassanica
in human cancer cell lines
Seyed Hadi Mousavi*, Mahsa Hossini Motaez, Hojat Soufi, Seyed Ahmad Emami, Zahra
Tayarani-Najaran,
* Seyed Hadi Mousavi (Pharmacological Research Centre of Medicinal Plants, School of Medicine,
Mashhad University of Medical Sciences, Mashhad, Iran) Email: [email protected],
[email protected]; + 98-9155199598, Work: 0511 8002258
Abstract
Here, we investigated the cytotoxic effects of methanol extract and obtained fractions
from S. pachycarpa and Salvia chorassanica root extract on different cancer cell lines
including A549, HeLa, HL60, MCF-7, and PC3 cells, and lymphocytes as non-malignant
cells. Meanwhile the role of apoptosis was explored in this toxicity. Malignant and nonmalignant cells were cultured in RPMI 1640 medium and incubated with different
concentrations of plant extracts. Cell viability was quantified by MTT assay. Apoptotic
cells were determined using PI staining of DNA fragmentation by flow cytometry (subG1 peak) and activity of caspase 3,8 and 9. The degree of DNA fragmentation was
analyzed using agarose gel electrophoresis based on the formation of internucleosomal
units. S. pachycarpa inhibited the growth of malignant cells in a dose-dependent manner
and the CH2Cl2 fraction showed the lowest IC50 values ranged from 30 to 50 μg/mL in
various cell lines. The IC50 for methanol extract, n-hexan, CH2CL2 fractions for S.
chorassanica were calculated 8.8, 5.45 and 2.38 µg/ml in HeLa cells. S. pachycarpa and
S. chorassanica induced a sub-G1 peak in flow cytometry histogram of treated cells,
DNA fragmentation and activation of caspase 3 and 8 acivity indicating apoptotic cell
death is involved in S. pachycarpa and S. chorassanica -induced toxicity. In conclusion,
S. pachycarpa and S. chorassanica exert cytotoxic effects in different cancer cell lines in
which apoptosis plays an important role. IC50 values show both plants could be
considered as a potential and promising chemotherapeutic agent in cancer treatment.
Keywords: apoptosis, Sophora pachycarpa, Salvia chorassanica, cytotoxicity
88
P 3.5
Medicinal Plants
Quantitation of the antitumor Activity of Some Natural Compounds
Afrah Fatthi Salama, Ahmad Ahmad ABarbary, Saad Mohamed El-Gendy, Shabaan El-Sayed Abdel-Azez
Division of Biochemistry, Chemistry Department, Faculty of Science, Tanta University, Egypt and
Department of Cancer Biology, National Cancer Institute, Cairo university, Egypt
Corresponding author: Dr. Afrah Salam, [email protected]
Abstract
Background: There is a growing interest in investigating the anti-tumor effects of
thymoquinone (TQ), the bioactive constituent of the volatile oil of black seed, and garlic.
It is not known, however, whether their anti-tumor effects are due to apoptotic or necrotic
effects. Aim: The goal of this study was to investigate the anti-neoplastic, cytotoxic or
apoptotic effects using the hepatoma (Hep-G2 cells) and lung cancer (H460) cell lines.
Methods: The anti-tumor effects of TQ and garlic were measured using sulphorodamine
B (SRB) cytotoxicity, MTT, and flow cytometry assays. Results: Treatment of Hep-G2
and H460 cells with TQ (50, 100, 200, 300 and 400ug/ml) or garlic extracts (1, 2, 3 and 4
%) resulted in significant decreases in the proliferation and survival rates of Hep-G2 and
H460 cells after 48 hours and completely inhibited the cell growth after 72 h of treatment
as compared to the effect of cisplatin. Interestingly, the anti-tumor effects of these agents
were found to be mediated though induction of potent apoptotic effects as compared to
cisplatin, which induced both cell apoptosis and necrosis. Conclusion: Supplementation
of TQ and garlic could be used as an adjuvant therapy during anticancer treatments.
Keywords: Thymoquinone; Garlic extract; Apoptosis; Cell cycle; Anti-cancer; Hep-G2 cells; H460 cells
P 3.6
Medicinal Plants
Protective effect of Crocus sativus stigma extract and Crocin (trans-crocin 4) on
methyl methanesulfonate–induced DNA damage in mice organs
Elham Asadpour, Hamid R. Sadeghnia
Neuroscience Research Center (NRC), Department of Pharmacology, Department of New Sciences and
Technology, School of Medicine, Mashhad University of Medical Sciences (MUMS), Mashhad, Iran
Tel: +98 511 882 8566, Fax: +98 511 882 8567, E-mail:[email protected]
Abstract
This study was designed to examine the effect of aqueous extract of Crocus sativus
stigmas (CSE) and crocin (trans-crocin 4) on methyl methanesulfonate (MMS)-induced
DNA damage in multiple mice organs using comet assay. Adult male NMRI mice in
different groups were treated with either physiological saline (10 mL/Kg, intraperitoneal
[ip]), CSE (80 mg/Kg, ip), crocin (400 mg/Kg, ip), MMS (120 mg/Kg, ip), and CSE (5,
20, and 80 mg/Kg, ip) 45 min prior to MMS administration or crocin (50, 200, and 400
mg/Kg, ip) 45 min prior to MMS administration. Mice were scarified about 3 h after each
different treatment, and the alkaline comet assay was used to evaluate the effect of these
compounds on DNA damage in different mice organs. The percent of DNA in the comet
tail (% tail DNA) was measured. A significant increase in the % tail DNA was seen in
89
nuclei of different organs of MMS-treated mice. In control groups, no significant
difference was found in the % tail DNA between CSE- or crocin-pretreated and salinepretreated mice. The MMS-induced DNA damage in CSE pretreated mice (80 mg/Kg)
was decreased between 2.67-fold (kidney) and 4.48-fold (lung) compared to those of
MMS-treated animals alone (p<0.001). This suppression of DNA damage by CSE was
found to be depended on the dose, which pretreatment with CSE (5 mg/Kg) only reduced
DNA damage by 6.97%, 6.57%, 7.27%, and 9.90% in liver, lung, kidney, and spleen,
respectively ( p>0.05 as compared with MMS-treated group). In the same way, crocin
also significantly decreased DNA damage by MMS (between 4.69-fold for liver and
6.55-fold for spleen, 400 mg/Kg), in a dose-dependent manner. These data indicate that
there is a genoprotective property in CSE and crocin measured by comet assay in vivo.
Key Words: Crocus sativus, Crocin, Genotoxicity, Comet assay, DNA damage
P 3.7
Medicinal Plants
Biological and therapeutic effects of Berberis vulgaris and its active constituent,
Berberine: antioxidants, anti-cholinergic, anti-diabetic and anticancer effect
Doaa A. Ghareeb 1, Abeer ES Abd El Wahab 2, Eman Sarhan 1, Marwa M Abu-Serie 2, Maha
A. El Demellawy 2.
Biochemistry Department, Faculty of Science, Alexandria University 1, Medical Biotechnology
Department, Genetic Engineering & Biotechnology Research Institute, City for Scientific Research &
Technology Applications, Egypt 2
Correspondence: Prof. Maha A. El Demellawy, City for Scientific Research & Technology Applications,
Phone: +203-459-3422, Fax: +203-459-3407, [email protected]
Abstract:
Berberis vulgaris is a well known plant with traditional herbal medical history. The aims
of this study was to bioscreen and compare the in vitro biological activity (antioxidant,
anticholinergic, antidaibetic and the anticancer) of barberry crude extract and berberine
active compound. The effect of B. vulgaris extract and berberine chloride on
thiobarbituric acid reactive substances (TBARS) and diphenyle –α-picrylhydrazyl
(DPPH) radical scavenging), nitric oxide scavenging activity, superoxide dismutase
(SOD) and glutathione peroxidase activity (GPx), acetylcholinesterase (AChE) and αgulcosidase activities were spectrophotometrically determined. On the other hand, the
effect of extract and berberine as anticancer was estimated on three different cell lines
which were MCF-7, HepG-2, and Caco-2 cells by using neutral red uptake assay. Our
results showed that barberry crude extract contains 0.6 mg berberine/mg extract. Barberry
extract showed potent antioxidative capacity through a decrease in thiobarbituric acid
reactive species (TBARS) and NO and the oxidation of DPPH that associated with GPx
and SOD hyper activation. Berberis crude extract α-glucosidase stimulatory effect was
more potent than berberine chloride effect. Besides, different concentrations of both
berberine chloride and barberry ethanolic extract showed to have no growth inhibitory
effect on normal blood cells (PBMC). Otherwise, both berberine chloride and barberry
ethanolic extract showed to have inhibitory effect on the growth of breast, liver and colon
cancer cell lines (MCF7, HepG2 and CACO-2 respectively) at different incubation times
90
starting from 24 hrs up to 72 hrs and the inhibitory effect increased with time in a dose
dependant manner. This work demonstrates the potential of the bioactive ingredients of
barberry on suppressing lipid peroxidation, suggesting a promising use in the treatment of
hepatic oxidative stress, Alzheimer and idiopathic male factor infertility. Beside, Berberis
vulgaris ethanol extract can induce cancer cell death that could return to its powerful
antioxidant activity.
Keywords: Berberis vulgaris, berberine chloride, antioxidant, anticancer, α-glucosidase
P 3.8
Medicinal Plants
Evaluation of hepatoprotective and anticancer properties of aqueous olive leaf
extract in chemically induced hepatocellular carcinoma in rats
1
1
Abdel-Hamid, NM, 2El-Moselhy, MA, 1Abdel-Baky, AE and 1Fawzy, MA
Biochemistry Department, Faculty of Pharmacy, Minia University, Egypt.
Pharmacology and Toxicology Department, Faculty of Pharmacy, Minia University, Egypt.
Correspondence: Dr. Mohammed Ahmed M. El-Moselhy, PhD
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Minia University
Tel: Mob.: 0101748182, Work: +2 086 2347759, Fax: +2 086 2369075
E-mail: [email protected]
2
Abstract
Objectives: Hepatocellular carcinoma (HCC) is the fifth most common cancer
worldwide. The study aimed to investigate the role of aqueous olive leaf extract (AOLE)
in modulating metabolic disorders occurring in hepatic malignancy induced by
trichloroacetic acid (TCA). Design: Eight groups of rats were assigned as follows: First,
untreated normal control. Second, treated with 5-fluorouracil (5-FU), (75 mg/kg),
intraperitoneally (IP) once weekly for 3 weeks. Third, treated with oral AOLE (500
mg/kg) once daily for 28 days. The 4th group co-treated with AOLE and 5-FU as
mentioned above. The 5th group treated with oral daily doses of TCA (500mg/kg) for five
days. The 6th group treated with TCA for 5 days, from the sixth day with 5-FU for 3
weeks. Group 7 given TCA then, with AOLE. Group 8 received TCA, 5-FU and AOLE.
Blood samples were collected by decapitation after 28 days. Liver tissues were
histologically studied. Results: TCA showed neoplastic tissue features, greatly improved
by treatment with AOLE and 5-FU combination. TCA significantly increased blood
ALT, AST, alkaline phosphatase (ALP) and acetyl CoA synthase (fatty acid synthase,
FAS) activities, total bilirubin (T Bil), triglycerides (TG), total glycosaminoglycans
(TGAGs), alpha-fetoprotein (AFP), reduced serum total lipoprotein lipase (TLPL)
activity. AOLE, combined with 5-FU produced a pronounced improvement in most of
studied parameters. Conclusion: AOLE showed promising hepatoprotective and adjuvant
anticancer properties if combined with 5-FU.
Key word: HCC, 5-FU, Olive Leaves, Acyl Co Synthase, Lipase, Adjuvant Herbal.
91
P 3.9
Medicinal Plants
Immunohistochemical changes in mouse liver infected with Schistosoma mansoni
and the protective role of milk thistle extract
Doha M. Beltagy1 and Ehab Tousson2
1
Biochemistry, Department of Chemistry, Faculty of Science, Damanhour University (e-mail:
[email protected]); 2Department of Zoology, Faculty of Science, Tanta University (e-mail:
[email protected]), Egypt. Correspondence: Dr. Doha M Beltagy: [email protected]
Abstract
Schistosomiasis is one of the major human parasitic diseases in many developing
countries and is one of the causes of morbidity and mortality in the human population.
The present work has been planned to study the histopathological and
immunohistochemical expression of P53 and CD68 in mouse liver tissues experimentally
infected with Schistosoma mansoni, in addition to the ameliorating role of milk thistle
extract (silymarin). Fifty adult male mice were divided into five groups (10 animals
each). First and second groups were the control and silymarin groups respectively while
the third group was the infected group in which mice were infected with Schistosoma
mansoni live cercariae for 6 weeks. The fourth and fifth groups were the co- and post
treated groups in which mice were infected with Schistosoma mansoni cercariae and
treated with silymarin during and after Schistosoma infection respectively. The major
histopathological lesions were variable numbers of perioval granulomas, diffuse
infiltration of inflammatory cells, mainly eosinophils and small mononuclear cells, and
fibrosis of portal areas and interlobular septa. Treatment with silymarin led to a
significant reduction in granuloma area in all treated infected mice compared to nontreated infected mice. Immunohistochemical observations of the liver tissues showed a
significant increase of the apoptotic protein P53 and CD68 after infection with the
cercariae of schistosoma, comparing with the control one. The expression of the
cytoplasmic P53 and CD68 were very low in the control liver sections. A significant
decrease in the expression of the cytoplasmic P53 and CD68 were observed after
silymarin treatment.
Key words: P53; CD68; immunoreactivity; Schistosoma; Mice; Liver; silymarin
92
3. Epidemiology
P 4.1
Epidemiology
What do know Iranian women about breast cancer?
Roghaiyeh Nourizadeh*1, Fatemeh Bakhtariagdam2, Leila Sahebi 2
1
PhD candidate in reproductive health, Shahid Beheshti University of Medical sciences; 2Academic
member of Health and Nutritin Faculty, Tabriz University of Medical sciences, Iran
Correspondence: Roghaiyeh Nourizadeh ([email protected]); mobile No. 09144131729
Abstract
Background: Breast cancer is the most common cancer among women in Iran and the
worldwide. It is the second cause of death due to women’s cancer after lung cancer. Early
detection in improvement of outcomes and survival rates is very crucial. Aims: The
purpose of this study was to determine women’s health knowledge, beliefs and
population needs in order to design appropriate educational programs in promotion of
breast cancer screening behaviors. Methods & Materials: The study design was a
descriptive cross- sectional one, in which 219 women referring to Health Centers of
Tabriz (one of the five biggest cities of the country) were selected through cluster random
sampling. Data were collected by using a self-administered questionnaire consisted of 4
sections: demographic characteristics, knowledge of breast self examination, health
beliefs and behaviors of breast cancer screening. Health beliefs questions derived from
Champion’s Health Belief Model Scales. logistic regression, independent t-test, pearson
correlation and Chi square test were used for statistical analysis using SPSS 17. Results:
5% of participants had adequate knowledge regarding breast cancer and breast self
examination (BSE). The percentage of women who performed BSE was 41.6%, while
regular performance was 8.2%. 16% and 8.5% of eligible people reported having had a
clinical breast exam and mammogram respectively. Severity perceptions of women who
had a screening mammogram was significantly higher than those who had not had
(p=0.008). Conclusions: Low rates of knowledge and breast cancer screening behaviors
of participants in this study show importance of continues education and focus on early
detection. Educational programs should be designed in the ways that improve early
detection performance in the population.
Key words: Breast Cancer, Screening, Health Belief Model
93
O 4.2
Epidemiology
The role of health belief model in promotion of beliefs and behaviors of breast
cancer screening in women referring to health care centers of Tabriz, 2010
Fatemeh Bakhtariagdam1, Roghaiyeh Nourizadeh *2, Leila Sahebi3
1Academic member of Health and Nutrition Faculty, Tabriz University of Medical Sciences; 2Shaheed
Beheshti University of Medical sciences; 3Academic member of Health and Nutrition Faculty, Tabriz
Tabriz University of Medical Sciences, Iran
Correspondence: Roghaiyeh Nourizadeh ; E-mail: [email protected]; Tel. 09144131729
Abstract
Background: Breast cancer is the most common cancer among women in Iran and the
worldwide. It is the second cause of death due to women’s cancer after lung cancer. Early
detection in improvement of outcomes and survival rates is very crucial. Aim: The
purpose of this study was to determine to what extent educational program based on
HBM can change women’s health beliefs and behaviors of breast cancer screening.
Methods & Materials: The study design was quasi experimental, in which 219 women
referring to Health Care Centers of Tabriz selected through cluster random sampling
divided into case and control groups. Data were collected by using a self-administered
questionnaire consisted of 4 sections: demographic characteristics, knowledge of breast
cancer and its screening methods, health beliefs and behaviors of screening. 3 months
after the intervention, 2 groups sat for posttest. Logistic regression, Paired t test,
Wilcoxon, t-test, Man-Whitney U, McNemar, Pearson Correlation and Chi-square test
were used for statistical analysis using SPSS. Results: Post intervention, there was a
remarkable increase within the experimental group in perceived seriousness (p=0.02),
threat (p=0.01) and benefit (p<0.001), while within control group there was a meaningful
decrease in perceived sensitivity (p=0.01) and an increase in perceived seriousness
(p=0.01). Also it was seen an increase of 15.4% in frequency of BSE in experimental
group. Overall, post intervention was found a significant difference in screening
behaviors between groups (p=0.03). Conclusion: The culturally-sensitive educational
intervention based on HBM was to some extent effective in change of health beliefs and
screening behaviors. In future educational programs, it seems focus on inducing
perceived sensitivity and also reducing perceived barriers would have an important effect
on mammography practice in long time follow up.
Key words: Breast cancer, Cancer screening, Health Belief Model
94
P 4.3
Epidemyology
Women with breast cancer in North East of Iran are obese 3
1
Fatemeh Homaei-Shandiz, M.D., Associated professor of Radiation-Oncology, cancer
Research Center, MUMS, Iran; 2Mohammad-Reza Ghavam-Nassiri, M.D, Associate Professor
of Radiation-Oncology,
1,2
Department of Radiation-Oncology, Faculty of Medicine, Omid Hospital, Mashhad University of Medical
Sciences, Iran; 3Mommamad Khaje-daloee, M.D, Associate Professor of Epidemiology,3Social Medical
Center; 4Elham Esmaelee-Shandiz, MD, General Practitioner, Omid Hospital, Mashhad University of
Medical Sciences, Iran; 5Marzyeh Razban, MD, General Practitioner, Omid Hospital, Mashhad University
of Medical Sciences, Iran; 6Abdolreza Norouzy PhD, MRCP, Assistant Professor of Clinical Nutrition;
7
Mohsen Nematy *, MD, PhD, Assistant Professor of Clinical Nutrition
; 6,7
Department of Nutrition and Biochemistry, Faculty of Medicine, MUMS, IRAN
Dr. Fatemeh Homaei Shandiz <[email protected]>
Abstract
Background: Breast cancer is the most frequent cancer among women worldwide. It has
been the most common cancer (%32) and the second cause of cancer mortality (19%)
among Iranian women in 2004, affecting women at least one decade younger than their
counterparts in developed countries. Epidemiological studies have shown that obesity is a
risk factor for post-menopausal breast cancer. Objectives: The aim of this study was to
determine obesity prevalence in patients with pre and post menopausal breast cancer and
controls. Methods: A case control study was performed to determine the body mass
index (BMI) in 231 patients with either pre or post menopause documented breast cancer
using excisional biopsy in both Omid and Ghaem teaching hospitals (Mashad, Iran)
between June 2007 and June 2008. . Patients were compared with five hundred and
sixteen healthy women. Results: Results showed that 27.7%, 37.7%, and 34.6% of
patients regardless of being in pre or post menopause were obese or severely obese,
overweight, and normal or underweight respectively. In control group this data was
significantly different and only 19.4% of controls were obese or severely obese (p-value
= 0.022). Considering menstruation status with BMI, overweight and obesity ratio was
higher in cases in both premenopausal status than controls (25.7 kg/m 2 vs. 18.3 kg/m2 p =
0.17) and postmenopausal status than controls (30.8 kg/m 2 vs. 21.3 kg/m2 p = 0.11).
Conclusion: Results from this study showed that overweight and obesity may predict risk
of breast cancer in both pre and post menopausal north east Iranian women.
Key words: Breast Cancer, Body mass index, Obesity, Pre menopause, Post menopause.
Source of founding: Mashhad University of Medical Sciences
95
P 4.4
Epidemiology
The relationship of diabetes, body shape and breast cancer
Samira Ebrahimzadeh Zagami, M.Sc. 1, Nahid Golmakani, M.Sc. 1, Azadeh Saki, PhD2, Dr.
Fatemeh Homaii Shandiz, MD.3
1
Lecturer and faculty of midwifery, School of nursing and midwifery, Mashhad University of Medical
Science, Mashhad, Iran; 2Mashhad University of Medical Science, Mashhad, Iran; 3Omid Hospital,
Mashhad University of Medical Science, Mashhad, Iran.
Corresponding author: Samira Ebrahimzadeh Zagami; Email: [email protected]
Abstract
Background: Breast cancer is the most common malignancy among women in the
world. So, it is important to identify high risk women. It is thought that the body size and
shape may have a key role in increasing breast cancer. There are controversial studies
about it. Aim: The purpose of this study was to determine the relationship between the
size and shape of the body and breast cancer. Methods: In this case control study, 400
women participated (200 were diagnosis for breast cancer and 200 were healthy women).
The study was done in Omid Hospital and Ghaem Hospital (Mashhad, Iran) in 20102011. After completing the interview form, it was measurement the weight, height, breast
size and waist, hip, arm and chest circumference. Body shape questionnaire was used.
The data were analyzed using t- test, correlation and Chi-square test. Results: The cases
had higher weight, and waist, hip, and chest circumference compared to the controls (the
difference was statistically significant in women aged ≥50 years) and significant lower
height and arm circumference in total cases. Thyroid and android bodies were higher in
case group and gynaeoid and lymphatic bodies were higher in healthy women. This
difference was statistically significant (P <0.001). Conclusion: Our findings
demonstrated that a few body size factors and body shape influence the risk of breast
cancer. Age appears to affect the relationships.
Key Words: Body circumferences, body shape, breast cancer
P 4.5
Epidemiology
The relationship of diabetes, body shape and breast cancer
Samira Ebrahimzadeh Zagami, M.Sc. 1, Nahid Golmakani, M.Sc. 1, Azadeh Saki, PhD.2,
Masoumeh Bagheri, B.Sc.3
1
Lecturer and faculty of midwifery, School of nursing and midwifery, Mashhad University of Medical
Science, Mashhad; 2Mashhad University of Medical Science, Mashhad; 3Ghaem Hospital, Mashhad
University of Medical Science, Mashhad, Iran.Correspondance: Nahid Golmakani; Email:
[email protected]
Abstract
Introduction: Incidences of breast cancer and diabetes have increased over the past
decades with the obesity. Insulin resistance is associated with breast cancer risk and is
characteristic for type 2 diabetes. More than 16% of patients with breast cancer have
96
diabetes, and old age and obesity are two major risk factors for type 2 diabetes and also
are associated with breast cancer. On the other hand, few studies have shown that there
may be a correlation between breast cancer and body shape. Aim: So this study was
performed to evaluate the relationship of diabetes, body shape and breast cancer.
Methods: In this case control study, 400 women (200 were diagnosis for breast cancer
and 200 were healthy women) participated. The study was done in Omid Hospital and
Ghaem Hospital (Mashhad, Iran) in 2010-2011. The Samples filled a questionnaire
included demographic characteristics, reproductive and body shape questionnaire. Data
were analyzed using Chi-square and regression.Results: In this study, 17.7% of patients
with breast cancer had diabetes. Women with diabetes had an increased incidence of
breast cancer (2.64; 95% CI 1.41– 4.92) compared with women without diabetes. Body
shapes were android in 30.6% and lymphatic in 29.4% of women with both diabetes and
breast cancer. There was significant difference between diabetes, body shape and breast
cancer (p=0.004). Conclusion: It seems that diabetes together with the body shape may
be a predictive of breast cancer in women. More studies are needed to do with larger
sample in this regard.
Key Words: Diabetes mellitus, body shape, breast cancer.
P 4.6
Epidemiology
Are Asian breast cancer patients younger? An age-period-cohort analysis of data
from International Agency for Research on Cancer (IARC).
Alireza Mosavi-Jarrahi, Ph.D.
Associate Prof. of Epidemiology Dept. Social Medicine, Medical School Shahid Beheshti University of
Medical Sciences, The Cancer Institute Research Center, Tehran, Iran
Correspondence: Alireza Mosavi-Jarrahi, Ph.D., Tel: +98-912-114-5572 Fax: +9821-66428655; E.Mail:
[email protected] or; URL:http://sites.google.com/site/epiamosavi/
Abstract
Introduction: Breast cancer is the most frequent cancer among females almost in all
population of the world. There is a good volume of literature that patients of Middle East
and Asia are in average one decade younger than their counterpart in developed and
European countries. This study aimed to utilize the data from cancer in five continent
volumes I through XIII to examine if a younger age is, in fact, a through phenomenon of
breast cancer natural history in Asian populations. Material and methods: Data from
cancer in five continent volume I through XIII were obtained from IARC data repository
for 8 populations; four from Asia (Singapore, China-Honking, Japan-Ozaka, ChinaShanghai), and four from developed countries (Denmark, Australia, Germany, Norway).
Under the assumption that age specific incidence is a function of age specific risk plus a
risk acquired due to exposure to risk factors in a period and an underlying risk acquired
due to a cohort effect, data were prepared to fit an age-cohort-period analysis. A Poisson
regression model were fitted to the data for each population, the age specific incidence
was obtained after taking into account the period and cohort effect. Result: The adjusted
age specific cohort indicated no difference in terms of magnitude between countries of
97
Asia and Europe before age 50 years (premenopausal) however, significant difference
was observed post menopausal age. In the European countries incidence increased as age
increased but in Asian population incidence plateau after age 50-60. Conclusion: It was
concluded that a younger age among Asian population is in fact an artifact of
identification Bias.
P 4.7
Epidemiology
Cancer overview in Iran comparing Middle East global problem and regional
solutions
Ali Motlagh*, Payam Azadeh**, Abdolah Fazalizadeh, Mohamad Esmaeil Akbari, Rashid
Ramezani, Fatemeh Nadali
*Radiation Oncologist, MD, MPH, Cancer Research Center, Shahid Beheshti University of Medical
Sciences, Tehran, Iran
Radiation Oncologist, MD, Jorjani Cancer Center, Imam Hossein Hospita, Shahid Beheshti University of
Medical Sciences, Tehran, Iran
President of Iranian Cancer Society, Tehran, Iran
Professor of Surgery, Head of Cancer Research Center, Shahid Beheshti University of Medical Sciences,
Tehran, Iran
Cancer Office, Ministry of Health, Tehran, Iran
Abstract
Based on WHO estimation the incidence of cancer will rise from 10 million in 2000 to 20
million in 2020 and nearly 70% of this increase will occur in developing countries. The
last report of pathology based cancer registery program show the age-standardized rate
(ASR) is 148 and 135 in men and women respectively. The incident case are more than
80,000 each year that is estimated increase two to three fold in 10 to 15 years. The main
cause of this raising is increasing life expectancy that has reached from 58.9 in 1979 to
71.7 in 2009. The most common incident cases are breast, stomach, colorectal and
bladder cancer in both sexes. In Iranian men, stomach, bladder, prostate and colorectal
are most common while breast, colorectal, stomach and esophagus are common in
women. The five years survival is not available in national level but there are some
institutional reports. For example, cancer research center of Shahid Beheshti Medical
University organized some research project for estimation of survival of prevalent cancer
in Iran using follow up of patients that were registered in national cancer regitery
program before. Bsed on these studies the five years survival of breast cancer were 71%
in Iran. Recently Iranian Cancer Society has planned to start a data rgistery for collection
of clinical, pathologic characteristics and routine practices in seven main cancer centers
around the country. The registration will do using web-based software named
CRABCARE that prepared for this purpose. There are some similarities between Middle
East country regarding population pyramid and most of them are categorized as low
prevalent area for cancer in the world but seems with increasing the life expectancy the
incidence of cancer more dramatically increase comparing developed countries. The ASR
of cancer has some diversity in Middle East and differs from 76.6 in Syria and 177.8 in
Lebanon for men and 69.3 in Syria and 162.1 in Lebanon for women. In contrast, of most
98
of the western countries, some countries in Middle East have more incident case in
women than in men and majority of them are categorized as high and low income
countries. Control of cancer need to a comprehensive program and each program cannot
be planned without valid data. Such data including clinical, pathology, stage at
presentation and routine practice. One of the opportunities of mutual program between
Middle East countries can be registration of cancer data in cancer centers via a web based
program like program that have be designed for this purpose in Iran.
5. Cancer Genetics
P 5.1
Cancer Genetics
Micronucleus frequency among Iraqi thyroid disorder patients
AL-Ramahi I.J.1 , AL-Faisal A.H.M2, and Abudl-Hassan I.A. 1
1
Genetic Engineering and Biotechnology Institute (GEBI; [email protected]), Baghdad, Iraq.
Ministry of Industry, Baghdad, Iraq
Correspondence: Dr. Intesar Jawad Kadhm
The A1-Razi Center for Research & Medical Diagnostic Kits Production Ministry of Industry & Minerals,
Baghdad, Iraq. E-mail: [email protected] Mobile: 009647702731130
2
Abstract
Background: Micronucleus assay has been extensively used in detection of DNA
damage and instability in cancer and genetic disorders. Aim: This study was aimed to
investigate the micronucleus frequency among Iraqi thyroid disorder patients.Materials
and Methods: In the current study, Micronucleus, binucleated cells and nuclear division
index (NDI) were investigated in Iraqi patients with thyroid disorders. Results: The
results indicated that significantly (p<0.05) increased BN Micronucleus frequencies in
thyroid cancer group (37.58±3.07) versus other thyroid disorder groups (6.60 ± 1.29,
14.90 ± 1.69, 15.56 ± 1.76). While the frequency of micronucleus per 1000 and the NDI
were significantly (p<0.05) decreased in hypothyroidism (Micronucleus 1.55±0.36) (NDI
0.009±0.001) versus other thyroid disorder groups (MN: 6.05 ± 0.97, 6.09 ± 0.53, 5.34 ±
0.56) (NDI: 0.049±0.003, 0.032±0.002, 0.025±0.002), with no difference versus healthy
group (0.0±0.0). The number of BN Micronucleus and micronucleus are parallel to the
severity of thyroid disorders which were 6.60±1.29, 14.90±1.69, 15.56±1.76 and 37.58 ±
3.07 for hypothyroidism, thyroid toxic goiter, thyroid non toxic goiter and thyroid cancer,
respectively. The number of BN Micronucleus and Micronucleus are parallel to the
severity of thyroid disorders which were 6.60±1.29, 14.90±1.69, 15.56±1.76 and 37.58 ±
3.07 for hypothyroidism, thyroid toxic goiter, thyroid non toxic goiter and thyroid cancer,
respectively. Conclusion: The results indicated that there were no significant differences
among age and sex groups as related with BN Micronucleus formation within each
thyroid disorder groups and healthy control group.
Key words: Micronucleus; Thyroid; Cancer; DNA
99
P 5.2
Cancer Genetics
Aberrant methylation of hMLH1 and p16INK4a in Tunisian patients with sporadic
colorectal adenocarcinoma
Imen MILADI-ABDENNADHER, Rania ABDELMAKSOUD-DAMAK, Lobna AYADI,
Abdelmajid KHABIR, Foued FRIKHA, Lamia KALLEL, Mounir FRIKHA, Tahia SELLAMIBOUDAWARA, Ali GARGOURI and Raja MOKDAD-GARGOURI
Centre de Biotechnologie de Sfax – Tunisia
e-mail: "imen miladi" <[email protected]>
Abstract
Background: The methylation of CpG islands in the promoters is associated with loss of
protein via repression of gene transcription. Several studies have demonstrated that
tumour suppressor and DNA repair genes are often aberrantly hypermethylated in
colorectal cancer. Aim: The present study was conducted to examine whether the
methylation profile of p16INK4a and hMLH1 (human mutL homologue 1) promoters
was associated with clinical features and patients’survival in CRC (colorectal carcinoma).
Results: Aberrant methylation of p16INK4a and hMLH1 promoters was found in 47.2
and 53.4% of tumours respectively. For adjacent non-tumoral mucosa, p16INK4a was
fully unmethylated in 30% of the cases, whereas hMLH1 was predominantly
unmethylated (76%). Methylation of p16INK4a correlated with gender and tumour size
(P=0.005 and 0.035 respectively), whereas those of hMLH1 significantly correlated with
overall survival (P log rank = 0.007). Concomitant methylation of p16INK4a and
hMLH1 was associated with TNM (tumour, lymph node and metastases) stage and
tumour size (P=0.024 and 0.021 respectively). Conclusion: Our data show that loss of
hMLH1 expression through aberrant methylation could be used as a marker of poor
prognosis in CRC.
Keywords: Methylation; hMLH1; p16INK4a; Tunisian patients; sporadic colorectal adenocarcinoma
P 5.3
Cancer Genetics
Molecular analysis of the RET proto-oncogene in patients with medullary thyroid
carcinoma
El Annas Abdessamad1, Charaibi Abdelmjid2, Iraqi Hind2, El Mzibri Mohammed3, Hilal
latifa1,4
1
Laboratoire de Génétique et de Physiologie Neuroendocrinienne – Bases Moléculaires de Maladies
Génétiques, Faculté des Sciences, Université Ibn Tofail, Kénitra 14 000, Morocco, [email protected]
2
Service d’Endocrinologie Diabétologie et Nutrition, Ibn Sina Hospital, Rabat, Morocco
3
CNESTEN BP1382 RP10001, Rabat, Morocco
4
Laboratoire de Biochimie et Immunologie, Université Mohammed V – Agdal, Faculté des Sciences, Rabat,
Morocco
Abstract
Objective: Germline mutations of RET proto-oncogene are the known cause of
hereditary medullary thyroid carcinoma (MTC), which account for approximately 25% of
100
all MTC cases and occur as multiple endocrine neoplasia type 2 (MEN2) syndromes.
Here, we present the contribution of RET proto-oncogene to MTC in Moroccan patients
with different form of MTC. Patients and Methods: A total of 31 patients with MTC,
from 31 separate families constitute the case study of this research. All patients were
referred to the endocrine department for a post-operative management, 27 of them were
clinically characterized as apparently sporadic cases, 3 patients with NEM2B and one
with MEN2A. RET genetic screening was performed by direct sequencing RET exons 5,
8, 10, 11 and 13–16. Results: Sequence analysis revealed that 10 (37%) of the apparently
sporadic cases carried an RET germline mutation who were reclassified as hereditary
form. We have identified seven different mutations: 7 patients with MEN2A syndrome,
all with mutation in codon 634, 4 patients with FMTC syndrome, 2 of them with
mutation in codon 891 and 2 in codon 804, 3 patients with MEN2B syndrome all with
mutation in codon 918. Conclusions: This is the first comprehensive genetic screening
and analysis of MTC among Moroccan families. Our study confirm that C634R having
the highest prevalence among the afflicted families . The results further confirm the
necessity and advantages of DNA sequencing for identification of hereditary MTC cases.
This will contribute to the definition of a national policy of this cancer control. Key
words: Multiple endocrine neoplasia type 2, proto-oncogene RET, genetic screening.
* This study has been supported by the CNRST Morocco (PROTARS/P12-20)
P 5.4
Cancer Genetics
Analyzing of new mutations in Iranian families with breast and ovarian cancer
Sadr-Nabavi Ariane1&4, Dastpak Mahtab1, 2, 1, 4,*, Homaei-Shandiz Fatemeh 5, Bahrami Ahmad-Reza1, 2, 3,*,
Bidkhori Hamid-Reza1, 2, Raeesolmohaddeseen Mahmood 1,
1
Cellular and Molecular Biology Research Department, ACECR- Mashhad Branch, Mashhad, Iran
2
Department of Biology, Faculty of Sciences, Ferdowsi University of Mashhad, Mashhad, Iran
3
Institute of Biotechnology, Ferdowsi University of Mashhad, Mashhad, Iran
4
Department of Medical Genetics, Mashhad University of Medical Sciences, Mashhad, Iran
5
Department of Radiation Oncology, Cancer Research Center, Mashhad University of Medical Sciences,
Mashhad, Iran
Correspondence: Dr. Sadr-Nabavi Ariane1 (PhD); [email protected]
Tel;00985118002226; 00989155570305
Abstract
Background: The most common malignancy among females in the world, is Breast
cancer. In Iran, Breast cancer is the first malignancies among women. Familial history
and Age are the significant risk factors for the progress of this disease in Iran. The
majority of hereditary breast cancers can be associated with inherited mutations in
BRCA1 and BRCA2 genes. Some new studies demonstrated that BRCA1 mutations are
seen in high-risk women with positive family history of breast cancer. Methods: Two
patients were included in this study. The first one was a 41 years old woman who
developed bilateral cancer in two different ages of 24 and 41. The second patient was one
of the monozygotic twins at the age of 24. The pathological characteristics of the studied
tumors were different. 10 families were also included in this study as control group, who
101
showed no cancer in three generations. BRCA1 gene was screened for all exons by PCR
and sequencing methods. The data was analyzed with ABI Sequencing Analysis Seq
Scap 2.5 software. The sequencing data was compared with the NCBI/GenBank data base
using BLAST and with our data base using BioEdit and Mega software. Results: We
found some polymorphisms and a novel mutation (Arg762Ser) in exon 11F for BRCA1
gene. DNA samples of 10 control families and one pair twin reanalyzed for new mutation
on exon-11F by direct sequencing. The results confirmed that new mutation is not the
case in the controls and twins. Conclusion: We conclude that this mutation is a missense
mutation and unclassified variant (UV). This mutation could be used as a predictive
factor in Iranian families with familiar breast and ovarian cancer. However, this needs to
be further analyzed by functional tests. GenBank accession number: These sequence
variant have already been submitted to GenBank: accession number BankIt1473921
JN686490
Key words: Breast cancer, BRCA1, unclassified variant, Iran
P 5.5
Cancer Genetics
Secondary chromosomal abnormalities of de novo acute meyloid leukemia: the first
report from Middle East
Abolfazl Movafagh 1*, Maryam HajiSeyed Javadi1, Abbas Hajifathali2
*1
For correspondence; Department of Medical Genetics,Shahid Beheshti University of Medical Sciences
(SBMU) , Tehran Iran, Fax +98(21) 2240067- +98 -21 - 23872572, E mail: [email protected]
2-Department of Internal Medicine, Oncology, Hematology, Cancer research Centre,Shahid Beheshti
University of Medical Sciences
3-Department of Paramedical and Proteomics, Shahid Beheshti University of Medical Sciences
Abstract
Background and Aims: The secondary chromosome aberration in de novo Acute
Meyloid Leukemia (AML) is less specific and occur in addition to the primary
chromosome abnormalities. Secondary chromosome aberration in acute nonlymphocytic
leukemia has been recognized for many years as the most serious long – term
complication malignant disease. Our aim of this study was one that focused on patients
with ANLL associated with secondary chromosomal abnormalities in an Iranian
populations following conventional and High Resolution Cell Synchronization technique.
Methods: We analyzed 127 consecutive patients with AML using Methotrexate cell
synchronization and 24h un-stimulated cultures of bone marrow cells to determine the
incidence of chromosomal aberrations and association of specific primary and secondary
chromosome anomalies according to French American British (FAB) morphological
subtypes. Results: The distribution of the secondary changes was clearly nonrandom.
The most frequent numerical changes were –X,- Y, -7, +8, -10 and +22 and the most
common structural aberrations were i(17q), 9q-, dicentric and marker chromosome.
Conclusion: We believe this report is the first of de novo ANLL patients showing
secondary chromosomal abnormalities presented here. These findings could contribute to
widen the knowledge of the related chromosomal abnormalities to ANLL patients being
102
reported here. The information provided in this study, demonstrated that the distribution
of secondary chromosomal changes in our ANLL patients is quite nonrandom.
Key Words: Abnormality, Chromosome, Iran, Leukemia, Secondary
P 5.6
Cancer Genetics
Genotoxicity of anticancer drug Azathioprine (Imuran): Role of omega-3 (ω-3) as
protective agent
Elelaimy I.A*; Elfiky, S.A.**; Hassan, A.M.**; Ibrahim, H.M.*Alsayad; R.I**.
Faculty of Science Monoufia University* Shebin Elkom, Egypt& National Research Centre NRC**, Dokki,
Egypt. Correspondence: Dr. Ibrahim Elaimy: [email protected]
Abstract:
Omega-3 (ω-3), is long-chain, polyunsaturated fatty acids (PUFAs) of plant and marine
origin. The present study was conducted to evaluate the protective effect of omega-3
against cytotoxicity and genotoxicity of anticancer drug; Azathioprine (Imuran). Male
levels; therapeutic (5mg|kg) and double therapeutic (10mg|kg) doses. Azathioprine was
intraperitonealy injected with the previous doses in 0.1 ml of 0.9% NaCl for 3 times at 48
hour interval. Omega-3 was orally administered with 0.05 ml per head for ten
consecutive days either before or after Azathioprine treatments. At the end of
experimentation period, samples of bone marrow were collected from five mice within
each group for micronucleus assay. The liver and testis tissue samples were removed and
stored at – 80 C until use for DNA extraction, and determination of glutathione contents.
Another animal group was treated at the same regimen and were used for the
determination of sperm abnormalities and sacrificed after 35 days. Epididymis were
removed for the sperm abnormality study. The results indicated that oral administration
of omega-3 either before or after treatment of Azathioprine was effective in reduction of
the frequencies of Mn-PCEs, decreased the DNA fragmentation, total sperm
abnormalities and significantly increased sperm count, percentage of PCEs, enhanced the
ratio of PCEs to NCEs. However, random amplified polymorphism of DNA (RAPD)
showed distinct differences in animal groups intoxicated with Azathioprine before and
after omega-3 treatment, which reflected DNA protective effect of omega-3. Depletion
in glutathione content in testis was also observed in Azathioprine treated mice, which
was improved by oral administration of Omega-3 either before or after treatment with
Azathioprine.
Keywords: Omega-3, micronucleus test, sperm abnormalities, RAPD, Genotoxicity.
103
P 5.7
Cancer Genetics
Studies on a new novel detoxification-related gene
Mohamed Nassef1, Yuji Oshima2
1
Labortory of Biotechnology and Immunity, Tanta University Egypt,
Division of Bioscience and Biotechnology, Kyushu University, Japan
Correspondence: Dr. M. Nassef; E-mail: nas[email protected]
2
Abstract
Full-length cDNA sequence of tributyltin-binding protein type1 in Japanese medaka
(Oryzias latipes) (Olat.TBT-bp1) was determined by means of rapid amplification of
cDNA ends (3´/5´-RACE) of liver tissue. Genomic analysis of the structure of the gene
encoding Olat.TBT-bp1 protein revealed that the exon–intron organization of this gene
corresponded to that of the genes encoding lipocalin superfamily proteins, suggesting that
Olat.TBT-bp1 can be categorized as a member of the lipocalin superfamily, which plays
an important role as a detoxification-related gene for carcinogenic components.
Additionally, intraperitoneal injection with tributyltin-d27 (TBT-d27) fish–1. Blood
samples were then collected on day 7 after injection and BT-bp1 in the blood sera were
purified and quantified by western blotting analysis. As a result, a positive relationship
between the concentrations of TBT-bp and TBT was observed. We suggest that TBT-bp
may play an important role in detoxification cycle of carcinogenic components. More
studies are required to confirm this point.
6. Tumor Markers
P 6.1
Tumor Markers
Tumor safe margin ambiguity: different expression of CCND1 in normal adjacent
and normal tissues in breast cancer
Rezvan Esmaeili, Ph.D candidate; Keivan Majidzadeh-A, MD, MPH, Ph.D; Asieh
Olfatbakhsh, MD; Leila Eini, MSc; Ali akbar Zare, MSc
Cancer Genetics Research Group (CGRG), Iranian Center for Breast Cancer (ICBC), Academic Center for
Culture, Education and Research (ACECR); Iran
E-mail: Dr. Keivan Majidzadeh" <[email protected]
Rezvan Esmaeili <[email protected]>
Abstract
Background: The safety of tumor margin in breast cancer surgery is one of the most
important issues affecting prognosis and survival of the patients. Some observations have
showed that pathologically confirmed tumor free tissues around the excised tumor may
have some differences with normal tissue. Aim: To help to confirm possible differences
between normal tissue adjacent to the tumor and normal tissue, we compared the gene
expression in “normal tissue adjacent to the tumor”,” tumor tissue” and “absolute normal
tissue obtained from non-affected women”. Method: mRNA was extracted from 195
104
breast tissues ( 90 tumors, 90 normal adjacent and 15 normal breast tissues from cosmetic
reductive surgery) using RNXplus (cinagen, Iran), cDNA was prepared using 1ug of total
RNA (Qiagen, GmbH ).mRNA expression of ki67, CDKN1B, CDKN1A, CCND1,
CCNE was measured by Real- Time PCR (ABI7500) using ACTB and TFRC as
endogenous control. Raw data was analyzed by Applied Bio Systems SDS software v.2.
Gene expression analysis was done with REST 2009 software (Qiagen, GmbH). Results:
Comparison of gene expression between tumor and normal adjacent reveal that KI67 is
up-regulated in tumors by mean factor of 3.025 with P (H1) =0. Same analysis between
tumor and normal breast tissue shows up-regulation in Ki67 and down-regulation in
CDKN1B by mean factor of 6.192 and 0.131 and P (H1)= 0.001 and 0.014 respectively.
At last CCND1 is up regulated in normal adjacent in comparison with normal breast
tissue by mean factor of 4.687and P(H1)= 0.039. Conclusion: Although differences in
gene expression profile of the tumor tissue vs. normal tissue are obvious, those of normal
adjacent vs. normal breast tissue may spot to the fact that molecular analysis of surgical
normal adjacent tissues can help to detect non-clear adjacent tissues which may change to
tumor in the future. Obviously Excision of these tissues will reduce recurrence and
improve prognosis and survival of the patients.
P 6.2
Tumor Markers
Survey efficacy of polymorphism LEPR (Lys109 Arg) in susceptibility to breast
cancer
Fatemeh Homaei Shandiz, M.D. 1;Jalil Tavakkol Afshari, PhD; *2; Parvaneh Sanglakh1; Azam Brook1;
Rashin Ganjali1; Monavar Afzalaghaee, MD3; Mohsen Nematy, MD, PhD.4; Shadi Emami, M.D.3; Javad
Aghamohammadian.
1
Associated professor of Radiation Oncology, Cancer Research Center of Mashhad University Medical of
Sciences, Omid and Ghaem Hospitals, Iran;
2*
Immunology research center, Buali Institute, Mashhad University of Medical Sciences;
3
Mashhad University of Medical Sciences;
4
Department of Nutrition and Biochemistry, Faculty of Medicine, MUMS, IRAN
*
Corresponding author: Dr. Jalil Tavakkol Afshari, Associated professor of Immunology, Immunology
Research Center, Buali Institute, Mashhad University of Medical Sciences
Abstract:
Introduction: Breast cancer is one of the most frequent malignancies among Iranian
women. The most obvious character of this cancer is young age susceptibility. The
prevalence of this affliction in Iran has been reported 17.44 cases per100000in 2007 [1].
Having strongly confirmed the relation between Leptin receptor as a mediator in obesity
and breast cancer, we evaluated the gene polymorphism of leptin receptor [2]. The aim of
this study was to assess the gene polymorphism of leptin receptor (109 codon) in breast
cancer patients and comparison with control group. Material and Methods: In this study
we compared 89 patients of breast cancer with 94 cases as control group. Having
extracted the DNA from blood leucocytes by salting out method, the gene polymorphism
of leptin receptor in 109 codon was assessed by PCR-SSCP method. Results: The results
105
of our survey revealed no meaningful relation between breast cancer and gene
polymorphism of LEPR109 (p=0.54). Also, there was not a meaningful relation between
allele's frequency and induction of breast cancer among our patients. No significant
relation between this gene polymorphism and BMI was also observed (p=0.722).
Conclusions: The results of this study showed that LEPR (Arg 109 Lys) mutation did not
have any role in our breast cancer patients. It was also proved that our cases did not have
higher BMI compared to control group.
Key Words: breast cancer –PCR-SSP- LEPR109
P 6.3
Tumor markers
PIVKA II, cytokeratin 19, and glypican as biomarkers for Hepatitis C virus related
hepatocellular carcinoma
Rasha A. Alm El-Din, M.D. 1, Mohamed M. El-Bedewy, M.D. 2, Mohamed A. Alm El-Din,
M.D.3
Department of Medical Microbiology and Immunology 1, Internal Medicine2, and Clinical Oncology3 ,
Tanta University Hospital, Tanta Faculty of Medicine, Tanta, Egypt
Correspondence: Dr. Mohamed Alm El-Din [[email protected]]
Background: PIVKA-II, cytokeratin and glypican-3 (GP3) have been investigated in
several setting as new biomarkers for diagnosis of Hepatitis C virus (HCV) related
hapatocellular carcinoma (HCC). Aim of work: To evaluate the serum level of PIVKAII, cytokeratin and GP3 as new biomarkers for diagnosis of HCV related HCC. Materials
and Methods: Two groups of patients were studied; the first group consisted of 30
patients with radiologically-diagnosed or biopsy-confirmed HCC with underlying HCV
cirrhosis and the second group included 30 patients with HCV cirrhosis Serum samples
were assessed by specific ELISA assay for PIVKAII, cytokeratin and Glypican-3. Results
were compared to that of the established biomarker, alpha-fetoprotein (AFP). Results:
The mean serum level of AFP was significantly higher in patients with HCC
complicating HCV cirrhosis as compared to those with HCV cirrhosis (91.62 ng/ml vs.
5.41 ng/ml, respectively, p value <0.0001). Similarly, the serum of patients with HCC
showed significantly higher level for both PIVKA-II and cytokeratin (41.72 ng/ml and
167.38 ng/ml, respectively), when compared to patients with HCV (8.56 ng/ml and 94.97
U/L, respectively p value <0.0001). There was no significant difference in the serum
level of GP3 between the study groups. Conclusion: PIVKAII and cytokeratin 19 are
good biomarkers for diagnosis of HCC in HCV cirrhotic patients with comparable
specificity and sensitivity to AFP.
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