HPV and Cervical Cancer Which Is Focused Mainly on Early Detection of Cervical Cancer and HPV Vaccine Will Be a Meeting of First of Its Kind in India
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PREFACE The Institute of Cytology & Preventive Oncology (ICMR) is honored to host the 24th Annual Convention of the Indian Association for Cancer Research (IACR) and an International Symposium on "Human Papillomavirus and Cervical Cancer" in the ICPO's new premises at Noida, India. Cervical cancer being the major cancer in Indian women, the Symposium is to focus mainly on cervical cancer and its principal causative agent, human papillomavirus (HPV) while IACR Convention will cover all aspects of human cancer. The meeting will have a special emphasis on clinical cancer research including early detection, pharmacological interventions, genomics and proteomics, prevention and management of cancer. The highlights of this four day meeting include sessions on molecular epidemiology, molecular mechanisms of carcinogenesis, bioinformatics, HPV Vaccine and a special session of panel discussion on early detection of cervical cancer, an interface between basic scientists and clinicians in oncology that will be moderated by Prof. Usha Luthra and Dr. John Sellors. Besides, there will be several plenary talks by renowned experts from India and abroad and special public talks by Prof. Harald zur Hausen, Prof. Inder M. Verma, Dr. P.B. Desai and Prof. Indraneel Mittra. Besides, there will be product exhibition by industries under a banner "Technology Against Cancer - 2005". The Symposium on HPV and Cervical Cancer which is focused mainly on early detection of cervical cancer and HPV Vaccine will be a meeting of first of its kind in India. This meeting has a special significance as it is being organized at a critical juncture when Indian Government has agreed to start trial of the HPV Vaccine against cervical cancer in India and ICPO has been recognized as a national co-coordinating centre for this vaccine programme. In this Conference about 250 abstracts will be presented. There will be ample opportunity for young scientists to win awards both in oral and poster sessions. The Conference Secretariat has created additional Ten Special Appreciation Awards for good poster presentations. We hope that this abstract book would serve as a knowledge house which will enthuse many young researchers to present their work in the future IACR meetings. The future of cancer research in India would set for an encouraging growth both in quality as well as quantity. I thank all young research students and the staff of Molecular Oncology Division and other staff of ICPO who worked tirelessly to categorize, edit and organize these abstracts. Special thanks are also to Prof. Neeta Singh of AIIMS and Dr. K. Satyanarayana, Editor of IJMR, New Delhi for their unstinted support and help in printing this book of abstracts. B.C. Das Organizing Secretary 24th Annual Convention of IACR & International Symposium on "HPV and Cervical Cancer" Indian J Med Res (Supplement) February 2005, pp 1-3 PRESIDENTIAL ORATION POL-1 Molecular Biomarkers in Oral Cancers Dhananjaya Saranath* Reliance Life Sciences Pvt. Ltd., Sir H.N. Hospital & Research Centre, New Tower Building, Raja Ram Mohan Roy Road, Mumbai, 400 004, India. *[email protected] Globally, over a quarter million new cases of cancers of the oral cavity were diagnosed in the year 2000, with 80,000 (30%) being Indian oral cancer patients and 47,000 oral cancer related deaths in India. The poor survival and high mortality rates are due to presentation in advanced stages, recurrence of the primary and development of second primary tumors. Hence, efforts to understand the mechanism of oral carcinogenesis and the biology of oral cancer are imperative, and may define the pathology and processes involved in initiation and progression of the disease, as also indicate biological behaviour of the cancer cells. Development of predictive biomarkers of high oral cancer risk individuals, as well as biomarkers of radio-chemo resistance, may result in better patient management. Hence, we investigated molecular genetic and epigenetic events in oral carcinogenesis. In our studies, transcriptional silencing of multiple regulatory genes – p16, MGMT, DAPK and GSTP1, by hypermethylation at the promoter regions, was observed as an early event occurring in 88% of the tumor tissue samples and 75% corresponding tumor adjacent mucosa. Further, multiple genes were hypermethylated in 56% malignant cancers and 46% tumor adjacent mucosa. It was interesting to note that a majority of buccal scrapings from premalignant oral lesions and long term tobacco users were also hypermethylated in the genes. On the other hand, hypermethylation was not observed in buccal scrapings of normal healthy individuals with no tobacco/alcohol habits. Additional biomarkers including p53 and H.ras mutations and consequent over-expression, EGF-R amplification and overexpression, microsatellite instability and loss of heterozygosity on chromosomes 3 and 9, were observed as early events occurring in a certain proportion of premalignant oral lesions. Telomerase activity was observed in 88% oral cancer samples and 25% premalignant oral lesions. Our data indicates that a judicious selection of a panel of biomarkers may indicate useful predictive biomarkers in individuals with higher risk of progressing to oral cancers. These would constitute important objective markers in selection of high risk individuals for preventive chemotherapeutic trials, and objectives assessment of the efficacy of the chemo- and radio- therapy. Molecular aberrations including activation of oncogenes by amplification, point mutations and restriction fragment length polymorphisms of c.myc/N.myc, K.ras/N.ras, Bcl-2/Bax, erbB-1 and ERK3, were observed in oral cancer tissues. Several of these biomarkers viz p53, H.ras and BclXL, may indicate inherent resistance of the cancer cells to chemo-radioresistance The specific alterations in an individual would also be useful in objective monitoring of efficacy of therapy, using buccal scrapings of the individual, post therapy, and in aggressive follow-up protocols. The aberrant expression of specific genes in oral cancers and premalignant oral lesions, would be useful in determining novel therapeutic targets in prevention and treatment of oral cancers. 1 2 INDIAN J MED RES (SUPPL) FEBRUARY 2005 KEYNOTE / PUBLIC LECTURES KPL-1 Papillomaviruses in Human Cancers Harald zur Hausen* Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. *[email protected] KPL-2 Gene Therapy: Medicine of 21st Century Inder M. Verma* Laboratory of Genetics, The Salk Institute, La Jolla, CA 92037, USA. *[email protected] At the beginning of the third millennium, man has an opportunity to fulfill the cherished goal of improving the lot of humankind. Newer modalities of medicine are being practiced and daily new breakthroughs are being reported. I would like to talk about gene therapy, a form of molecular medicine, which will have a major impact on human health. At present, gene therapy is being contemplated for both genetic and acquired diseases. These include hemophilia, cystic fibrosis, diabetes, cancer, Parkinson’s, Alzheimer’s, etc. In the former case, a wide variety of somatic tissues are being explored for the Introduction of foreign genes with a view towards gene therapy. A prime requirement for successful gene therapy is the sustained expression of the therapeutic gene without any adverse effect on the recipient. A highly desirable delivery vehicle will be the one that can be generated at high amounts, integrate in non-dividing cells and have little or no associated immune problems. We have recently generated vectors based on the AIDS virus that have the ability to introduce genes into both dividing and non-dividing cells. The vectors (lentiviral) also have a very expanded host range and can introduce genes in a variety of cells. We have recently generated third generation of lentiviral packaging constructs that contain only the gag/pol, VSV G envelope and the sin vector. Thus our current lentiviral vectors are devoid of six viral genes and therefore we consider them to be safe vectors. Using third generation lentiviral vectors we can introduce genes directly into brain, liver, muscle, hematopoietic stem cells, and more recently retina and a number of tumor cells. Our data shows that lentiviral vectors can not only efficiently deliver genes, but also have long term sustained production of the foreign protein. We have not observed any untoward immunological consequences due to the vector. My talk will discuss in detail the use of vectors for a wide variety of genetic and acquired diseases. Additionally I will discuss the use of lentiviral vectors for transgenesis, and uses in studying complex biological systems. I will also discuss the social and ethical implications of genetic approaches to human health. KPL-3 Cancer Causes and Prevention I Mittra* Bhopal Memorial Hospital & Resaerch Centre (BHMRC), Bhopal. *[email protected] 24th Annual Convention of IACR & International Symposium on “HPV and Cervical Cancer” KEYNOTE / PUBLIC LECTURES 3 KPL-4 Is Cancer Curable? – Future of cancer therapy P.B. Desai* 307, Samuder Mahal, Dr. Ani Basent Road, Worli Mumbai-400018. *[email protected] KPL-5 An Overview on Cancers in India K.T. Dinshaw* Tata Memorial Centre, Department of Radiation Oncology, Dr. Ernest Borges Marg, Parel, Mumbai – 400012. *[email protected] Indian J Med Res (Supplement) February 2005, pp 4-31 PLENARY ORAL PRESENTATIONS PO-1 Convergence of Information Technology and Cancer Surveillance in the Descriptive epidemiology of cancer