2nd World Congress on

Cancer and Prevention Methods

November 07-09, 2016, Furama RiverFront, Singapore

Scientific Programme(Day 1 : Nov-07-2016)

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Keynote Speaker

Mathew L. Thakur
Thomas Jefferson University, USA
Title: Translating Genomic Fingerprints For Early, Accurate and Non-invasive Diagnosis

Biography: Dr. Thakur is a highly respected, renowned investigator, nationally and internationally, for his pioneering research, scholarly activities, and leadership. He has published 221 peer reviewed original articles in prestigious journals, 4 books, 51 book chapters and several editorials. He has given 254 invited presentations both nationally and internationally, in addition to 180 presentations at Universities and commercial organizations throughout the world. He has 20 granted or pending patents in the development of radiopharmaceuticals and molecular imaging. He has received ten highly prestigious national and international awards, a testimony to recognition by his peers of his outstanding contributions.

Abstract: INTRODUCTION: Human lifespan is increasing worldwide. In 2020, there will be more than 23 million males over the age of 65 yrs. living in the USA alone. With the lifelong risk of 17% for developing prostate cancer (PCa), nearly 4 million males in the USA will face the risk of developing PCa. Although great strides have been made in the management of PCa, the need is compelling for its early, accurate and non-invasive diagnosis. OBJECTIVES: Our goal is to develop a simple, reliable, non-invasive and inexpensive urinary assay that shall detect, with high sensitivity, malignant PCa cells, shed in voided urine. METHOD: With a IRB approved exempt protocol, a portion of voided urine, collected as a standard of care from 235 male and female patients (18 to 75 yrs. M=190, F=45) presented in the urology clinic. Urine was cytospun, cells were fixed and incubated with a biomolecule TP4303, developed in our laboratory that consists of a fluorophore. TP4303 a high affinity, kd=1.3x10-9M, for VPAC genomic receptors that are expressed in high density on PCa cells at the onset of oncogenesis. On normal epithelial cells, VPAC receptors are minimally present. Excess of TP4303 was washed, cell nuclei were stained with DAPI and cells were then observed under a microscope. The normal cells, in the absence for VPAC, show only blue nucleus where as the malignant cells expressing VPAC has orange fluorescence ring around the nucleus. Results were analyzed and validated. RESULTS: Out of 131 PCa patients 129 (98.4%) had malignant cells. One was negative (0.1%) and one slide (0.8%) was technically unclear. None of the 4, BPH had any VPAC positive cells (100%). There were 4 patients with renal cancer, all of whom had malignant cells (100%). From 43 subjects (M=29, F=14) with urothelial bladder cancer, 41 (95.3%) were positive for malignant cell, 1 (2.3%) was negative and 1 (2.3%) was unclear due to excess of RBC. The status of fifty three subjects (M=22, F=31) was unclear and were considered “normal”. In this group, 11 (20.7%) had malignant cells, 32 (60.4%) were negative and 10 (18.8%) were unclear for technical reasons. Validation of results concluded that TP4303 was truly targeting VPAC receptors and that malignant cells were over expressing PCa specific encoded genes. CONCLUSION: The method is simple, rapid and non-invasive and detects PCa with high sensitivity.


Diagnosis and Therapy

Session Introduction

Dezső Tóth
Kenézy Teaching Hospital, Hungary
Title: Individualized, stage-adapted surgery in gastric cancer.

Biography: Dezső Tóth MD, PhD is an Associate Professor in the Department of General Surgery at the Kenézy Teaching Hospital in Debrecen, Hungary. He is a founder member of the County’s Breast Center. He graduated from University of Debrecen, Medical School in 1997 and in Medical Economics in 2001. He is certified in General Surgery and Clinical Oncology and he received his Ph.D. in "Examination of lymph node involvement in solid neoplasms – Sentinel lymph node biopsy“ with summa cum laude in 2012. His research area is in surgical oncology, especially in the field of gastric and breast cancer. He is author and co-author of over 20 peer-reviewed publications (original article, review, chapter and case reports) published in prestigious scientific journals, such as Gastric Cancer, The Breast, Molecular Cancer, Pathology and Oncology Research and World Journal of Gastrointestinal Oncology.

Abstract: Approximately, one-third of patients with gastic cancer have an unnecessarily extended lymph node dissection with a higher rate of morbidity and mortality. Preoperative diagnostic tools have a low sensitivity and specificity determining lymph node involvement. The Maruyama computer program (MCP) can estimate the lymph node involvement preoperatively and the sentinel lymph node (SLN) biopsy may help to reduce the number of redundant lymphadenectomy intraoperatively. 74 patients were investigated by the Maruyama computer program and 58 patients were labelled with blue dye for SLN mapping. All patients underwent open gastric resection and D2 lymphadenectomy. Twenty patients were marked submucosal by an endoscopist and in 38 patients injection was performed by the surgeon subserosal. The staining method and the lymphadenectomy were supervised by the same surgeon. To measure the probability calculations by MCP, we had to define a ‘cut-off level’, with using the calculation of the receiver-operating characteristics analysis. The Maruyama computer program had a 90.2% of sensitivity, 63.3% of specificity and 78.4 % of accuracy. The positive predictive value was 75.5% and the negative predictive value was 84%. The false negative rate was 9.8%. The sensitivity of sentinel lymph node mapping was 96.6%, the false negative rate was 3.4% and the specificity was 100%. The accuracy of SLN mapping was 98.2%. The positive predictive value was 100% and the negative predictive value was 96.6%. The intraoperative sentinel lymph node examination is superior to the preoperative estimation by the Maruyama computer program. However, using these two methods in a parallel fashion could be useful in decision-making for determining the appropriate extent of lymphadenectomy. The individualized stage-adapted surgery can guarantees the best outcome for the patients with gastric cancer.


Uday Mukherjee
Apollo Gleneagles Hospital, India
Title: Dysplasia and oral pre-cancer

Biography:

Abstract: With approximately 80,000 new cases of oral cancer diagnosed each year in India, and 46000 Oral cancer related deaths annually, India tops the figures in Oral Cancer globally and thus oral cancer is an important public health issue. Majority of oral cancers arise from longstanding premalignant lesions. Lack of awareness about oral cancer and its risk factors, are the primary reason for delayed presentation. This presentation is specifically for the health care provider, as it focuses on the major contributions in the field of oral cancer health care delivery. The presentation will highlight and review the various diagnostic tools in the market , proven preventive methodologies and other support activities for early detection which is an important part of comprehensive treatment of oral cancer.


Reyaz M Singaporewalla
Khoo Teck Puat Hospitial, Singapore
Title: Clinicopathological Correlation of Thyroid Nodule Ultrasound and Cytology Using the TIRADS and Bethesda Classifications

Biography:

Abstract: Background: Clinico-pathological correlation of thyroid nodules is not routinely performed as until recently there was no objective classification system for reporting thyroid nodules on ultrasound. Aim: To compare the Thyroid Imaging Reporting and Data System (TIRADS) system of classifying thyroid nodules on ultrasound with the findings on fine needle aspiration aspiration cytology (FNAC) reported using the Bethesda System. Methods: A retrospective analysis of 100 consecutive cases over 1 year (Jan – Dec 2015) was performed comparing single surgeon-performed bedside thyroid nodule ultrasound findings based on the TIRADS classification to the FNAC report based on the Bethesda Classification. TIRADS 1 (normal thyroid gland) and TIRADS 6 (biopsy proven malignancy) were excluded. Benign appearing nodules were reported as TIRADS 2 and 3. Indeterminate or suspected follicular lesions were reported as TIRADS 4 and malignant appearing nodules were classified as TIRADS 5 during surgeon performed bedside ultrasound. All the nodules were subjected to ultrasound-guided FNAC and the results were compared to the Bethesda FNAC classification. Results: Of the 100 cases, 74 were considered benign, 20 as suspicious for malignancy and 6 were indeterminate on ultrasound. Overall concordance rate with FNAC was 83% with sensitivity and specificity of 70.6% and 90.4%, respectively. The negative predictive value was 93.8%. Conclusion: It is essential for clinicians performing bedside ultrasound thyroid and guided FNAC to document their clinical impression of the nodule in an objective fashion and correlate with the gold standard cytology to improve their learning curve and audit their results.


Gurmeet Singh
Cipto Mangunkusumo Hospital, Indonesia
Title:

Biography: Gurmeet Singh obtained his medical degree in 1997 at Universitas Kristen Krida Wacana, Jakarta, Indonesia. In 2001, he worked in Wamena, Papua. He moved back to Jakarta in 2006, having spent 5 years in the eastern part of Indonesia, to start his post-graduate in Internal Medicine, Universitas Indonesia. Graduated as an internist in 2010, he took his sub-specialist in Pulmonology, and finished as a Pulmonologist in 2016. Currently Gurmeet Singh is a staff at the Respirology and Critical Illness division, Internal Medicine, Universitas Indonesia. Currently, he is a lecturer, student supervisor, and mentor at Faculty of Medicine Universitas Indonesia; Board Staff Member of National Health Insurance Regional Central Jakarta; and honorary editor for Indonesian Journal of Chest Critical and Emergency Medicine. Gurmeet Singh’s current research interest is pulmonary infection in critically ill patients and pleural diseases. Gurmeet Singh has published over 40 research papers published in National and International Journals.

Abstract: Cytomegalovirus (CMV), one of the known members of the human ß herpes virus, is an important cause of morbidity and mortality in immunosuppressed patients. The infection is usually latent and reactivation can occur when cell-mediated immunity is disturbed. CMV infection often remains unrecognized in critically ill patients, resulting in prolonged ICU stay and increased mortality [1,2]. The incidence of CMV is between 0 to 36% in critically ill patients. Potential risk factors for CMV reactivation include hospitalization in ICU with sepsis, mechanical ventilation for more than 21 days, and multiple blood transfusions. Infection can occur between 4 to 12 days [3]. Rapid and accurate diagnosis of the etiology of pneumonia is needed to improve the outcome especially in critically ill patients [4]. CMV can be detected by tissue biopsy and rapid PCR CMV cultures of urine and bronchoalveolar lavage fluid with shell vial method [5].


Epidemiology and Prevention

Session Introduction

Redhwan Ahmed Al-Naggar
Universiti Teknologi MARA (UiTM), Malaysia
Title: Malaysian adolescents: Do they know enough about cancer?

Biography: Redhwan Ahmed Al-Naggar has completed his Ph.D at the age of 33 years from National University of Malaysia and fellowship from National Cancer Institute, Maryland, USA. He is currently working as a medical research coordinator at Faculty of Medicine, UiTM, Malaysia. He has published more than 300 papers in reputed journals and has been serving as an editorial board member of many reputed journals.

Abstract: Background: Few studies have investigated the information and states of teenagers toward cancer prevention and treatment. The aim of this study was to assess the knowledge of secondary school student about cancer. Materials and Methods: A cross-sectional study was conducted among secondary school students. Results: The findings of our quantitative analysis suggest that Malaysian youth generally possess a moderate knowledge about cancer. Quantitative analyses found that socioeconomic inequalities and bias in education present as important factors contributing to cancer awareness, prevention, and treatment among Malaysian adolescents. Conclusions: The findings indicate that Malaysian youth generally possess a moderate knowledge about cancer but the current deficiencies in initiatives directed to cancer awareness continue to hinder the improvement in prevention of cancer among Malaysian adolescents.


Aisha Mukhtar Dodo
Cardiff Metropolitan University, United Kingdom
Title: Knowledge, attitude, perception, and barriers to breast and cervical cancers screening among women in northern Nigeria

Biography: Aisha Mukhtar Dodo is a PhD student in the department of Health Sciences at the Cardiff Metropolitan University. She holds a BSc in Biomedical Science, and a Masters of Public Health. Aisha completed her undergraduate studies at Cardiff Metropolitan University, and Post graduate at Cardiff University. Her research interests lie in the area of medical anthropology with a focus on improving breast and cervical cancers health behaviours. Presently, she is working towards understanding the factors that influence screening uptake in Northern Nigeria, and designing a guideline to support service providers in developing appropriate programmes.

Abstract: Background: Breast and cervical cancers are major causes of female cancer deaths. Prevention, early detection and treatment decrease this burden. Various demographic and sociocultural factors influence knowledge, attitude and practice of preventive methods in developing countries. Aim: Explore the level of awareness, perception and attitude towards breast and cervical cancers in Kaduna, a state in Northern Nigeria. Methods: Self-administered questionnaires were developed based on the constructs of Social Cognitive Theory and Theory of Planned Behaviour. Purposive non-random sampling was used to recruit 238 adult women, visiting the National Eye Centre in Kaduna state. Fisher’s exact and Mann Whitney tests were employed to test for association between appropriate variables, with p value of 0.05 as measure of statistical significance. Findings: Women had better knowledge of breast cancer (71.4%) than cervical cancer (58.8%), although screening uptake was poor for the two cancers. Wearing iron bra, putting money in bra; and inserting herbs were stated as causes of breast and cervical cancers respectively. Barriers to screening included lack of interest, gender of doctors/nurses, absence of cancer symptoms, and belief in divine treatment. Others reported positive attitude to screening provided their families and spouses were supportive. These findings would be explored in a future qualitative study. Conclusion: For effective cancer management, programmes that address the sociocultural beliefs and practices in the developing world are needed.


Huda Basaleem
University of Aden, Yemen
Title: Current challenges on the breast cancer control strategy in Yemen

Biography: Huda Ba Saleem holds a PhD in Community Medicine and Public Health (National University of Malaysia). She is the director of Aden Cancer Registry and Research Center, the head of the Community Medicine department (Aden University, Yemen) and a member of several international professional organizations. She serves on the editorial board of international medical journals and functions as consultant and principal investigator for international organizations. She has many published articles in international peer reviewed journals. In 2013, Huda received the Elsevier Foundation Award in life sciences for early career women scientists in the developing world for the Arab region.

Abstract: In Yemen, breast cancer is a leading cancer. Nevertheless, the current efforts in approaching its burden appear to be patchy and fragmented due to the lack of a comprehensive national breast cancer control strategy (NBCCS). The present paper aimed at describing the actions needed to develop the NBCCS based on registry data and portraying the challenges for such strategy. Breast cancer data from the population based Aden Cancer Registry (2002-2013) were used to estimate the needed resources regarding raising awareness, early detection, diagnosis, treatment, rehabilitation and palliative care services. A qualitative participatory approach for the roles and responsibilities of the developing partners and the needs of the development process were critically analyzed. The paper details the context through which the strategy could be developed starting from the purpose of providing a framework for an integrated, comprehensive set of activities covering all aspects related to breast cancer control, passing through the characteristics of the NBCCS, the guiding principles and steps of development, the process of development and the possible related challenges. Finally, the need for NBCCS to guide the existing and future actions with a set of evidence–based, cost–effective priority actions while being sensitive and realistic to resource opportunities and constraints was highly focused. To conclude, population based registry data are important resources to develop cancer control strategies. NBCCS cannot be achieved successfully by any single organization and its development should be consortium–based. The necessary partnerships of many partners and their responsibilities were indicated within a comprehensive NBCCS.


Huda Basaleem
University of Aden, Yemen
Title: Trends of breast cancer in aden cancer registry, Yemen (1997 – 2011)

Biography: Huda Ba Saleem holds a PhD in Community Medicine and Public Health (National University of Malaysia). She is the director of Aden Cancer Registry and Research Center, the head of the Community Medicine department (Aden University, Yemen) and a member of several international professional organizations. She serves on the editorial board of international medical journals and functions as consultant and principal investigator for international organizations. She has many published articles in international peer reviewed journals. In 2013, Huda received the Elsevier Foundation Award in life sciences for early career women scientists in the developing world for the Arab region.

Abstract: According to GLOOCAN 2012; breast cancer is the second most common cancer in the world and the most frequent cancer among women. In Aden Cancer Registry, breast cancer is a frequently reported cancer. The present paper aimed at determining the trend of breast cancer over 15 years period (1997-2011) based on in Aden Cancer Registry data; the only population-based cancer registry in Yemen. Data were collected from the main public and private hospitals, abroad treatment registry at Ministry of Aden Health Office and diagnostic centers in the governorates covered by the Registry. The collected data were entered and analyzed using Canreg-4 software with duplicate entry checking by name, age, sex, morphology, topography and residence.. The World Standard Population and the local population of the four Governorates were used in the analysis. There were 1227 registered breast cancer patients; 95.5% of them were females. They represent 16% of all cancers and 35% of female cancers. The median age was 47 years (minimum 18; maximum 88) with 21.8% of cancers reported in those younger than 40 years. Around half of registered patients were from Aden (55.5%). Carcinoma not otherwise specified was the diagnosis found in 48.6% whereas 39.9% was infiltrating duct carcinoma. There is a rising trend in the registered patients and age standardized incidence rate per 100.000 inhabitants during 1997-2011. We concluded that breast cancer is the most incident cancer among all cancers in both sexes. The steady rising incidence indicates that efficient breast cancer control strategy is mandatory.


Khaled Al-Sakkaf
University of Aden, Yemen
Title: Cancer as a rising health problem in Yemen (2007 – 2011)

Biography: Khaled Al-Sakkaf holds a PhD in Community Medicine and Public Health (National University of Malaysia). He is an epidemiologist in Aden Cancer Registry and Research Center and the Department of Community Medicine (Aden University, Yemen) and a member of several international professional organizations. He is a consultant and principal investigator for international organizations. He has many published articles in international peer reviewed journals.

Abstract: Cancer is a major killer throughout human history and appears to change its grasp as human kind advanced industrially and technologically. In Yemen, there is evidence of rising trend of cancer incidence. This paper aimed at describing the pattern of cancer over five years (2007-2011) in Aden Cancer Registry, Yemen. Data from Aden Cancer Registry, a population-based cancer registry covers around three million inhabitants were collected (2007-2011). These include cancers from main hospitals, public and private clinics, diagnostic centers, and abroad treatment registry at Ministry of Public Health and Population. Canreg-4 was used for data entry and analysis. The World Standard Population and the local covered population were used in the calculation process. A total number of 3500 cancer cases were reported with an increment of 98% from the first five-year report (1997-2001) and 73% from the second one (2002-2006). Fifty four percent of patients were females. The mean age in male patients was 49.5±3.5 years and in females 48.6±2.5 years. In order, the most leading sites were the digestive system (19.1%), followed by breast, lymphomas, head and neck, and leukemias (17.6%, 14.3%, 9.9% and 9.7% respectively). The age standardized rate per 100.000 inhabitants was 31.1 and 32.9 for males and females respectively. Females share a higher burden of cancer compared to males. The current report shows increased incidence of most cancers compared to previous ten years. The need to investigate cancer–related community risk factors is highly recommended.


Cancer Cell Biology

Session Introduction

Hyeong-Reh C. Kim
Wayne State University, USA
Title: PDGF signaling and prostate cancer bone metastasis

Biography: Hyeong-Reh C. Kim, Ph.D. is Professor in the Department of Pathology, School of Medicine, Wayne State University in Detroit, Michigan USA. Dr. Kim conducts cancer research focusing on tumor-stromal interactions critical for tumor cell invasion and metastasis. Of particular interest is the serine protease and platelet-derived growth factor signaling network for prostate cancer bone metastasis. She received her Ph.D. in Biochemistry, Molecular Biology and Cell Biology at Northwestern University in Evanston, IL and post-doctoral training at Washington University in St. Louis, MO.

Abstract: The ‘seed and soil’ hypothesis is often invoked to address cellular and molecular mechanisms underlying the tendency of prostate cancer (PCa) to metastasize to bone. Cancer cells, upon their arrival in the bone marrow, perturb the delicate homeostatic balance of the bone marrow microenvironment by activating proteolytic cascades and growth factor signaling networks. Tumor-mediated bone responses include increased osteoclast differentiation, leading to bone destruction and new bone formation. Growth-promoting factors released from the metabolized bone matrix during osteoclastic bone resorption are thought to provide a favorable microenvironment for tumor cell proliferation, creating a positive feedback signaling loop. Thus, it is important to identify PCa cell-initiated signaling axes critical for tumor--bone stromal interactions for more indepth understanding of PCa bone metastasis. Recently, we uncovered a platelet-derived growth factor D (PDGF D)-initiated, novel protease/growth factor signaling network, critical for intraosseous PCa growth. Secreted as a latent homodimer, PDGF D contains a N-terminal CUB domain and a C-terminal growth factor domain (GFD). The proteolytic removal of the CUB domain is required for the growth factor domain dimer (PDGF D GFD-D) to activate its cognate receptor, β-PDGFR. We demonstrated that the serine protease matriptase processes latent PDGF D into its active form in a 2-step manner. This involves the generation of a hemidimer (PDGF D HD), an intermediate form consisting of one full-length PDGF D chain and a single GFD subunit. We made novel findings that PCa-derived PDGF D is capable of preparing a metastatic niche within the bone by inducing osteoclast activation via PDGF D HDspecific signaling and by promoting human mesenchymal stem cell (hMSC) differentiation into osteoblasts through both PDGF D HD and GFD-D signaling. PDGF D-initiated bone remodeling is critical for intraosseous PCa growth, and thus PDGF D and its proteolytic activator matriptase are potential therapeutic targets. In conclusion, our study uncovers novel functions of PDGF D in bone remodeling critical for PCa bone metastasis and provide valuable information for the development of PDGF inhibitors based on PDGF ligand-specific biology.


Bassam Janji
Luxembourg Institute of Health, Luxembourg
Title: Improving cancer immunotherapy by targeting autophagy

Biography: Dr Bassam Janji is the deputy director of the laboratory of Experimental Cancer Research and principal investigator of the tumor microenvironment group operating in the Department of Oncology at the Luxembourg Institute of Health (LIH). In 2000, Dr Janji obtained his PhD Diploma in Oncology from the University of Pierre and Marie Curie in Paris and joined the prestigious Curie institute in Paris. During his Post Doc, he investigated the involvement of protein tyrosine phosphatases in the control of the Epithelial-Mesenchymal Transition of tumor cells. In 2004, he moved to the Public Research Center of Health, in Luxembourg, and appointed as a researcher, where he studied the role of the actin cytoskeleton remodeling in tumor resistance, progression and metastasis. In 2007 he integrated the laboratory of Experimental Hemato-Oncology in order to set up a research program dedicated to the role of the tumor microenvironment, notably the hypoxic stress, in regulation of the anti-tumor immune responses. After obtaining his HDR degree (Habilitation to lead Research) from the University of Paris in 2011, Dr Janji was promoted as senior researcher and appointed in 2015 as a deputy director of the laboratory of Experimental Cancer Research. Currently, his lab contains more than 17 people including 8 researchers and 4 PhD students. The expertise of the Dr Janji in the field of tumor microenvironment and tumor immunity is internationally recognized through several research and review papers as well as book chapters.

Abstract: Hypoxia is a common characteristic of solid tumor. It is now well established that hypoxic stress in the tumor microenvironment is a major contributor of tumor escape from immune surveillance. In addition to its role in damping the cytotoxic function of immune cells, hypoxia contributes to the emergence of resistant tumor cells able to evade fully functional host immune system by activating autophagy-dependent intrinsic resistance mechanism. We have recently showed that hypoxic stress upregulates the expression of the Programmed Death-Ligand 1 (PD-L1) on the surface of tumor cells thereby inhibiting the anti-tumor immune response. While immune checkpoint inhibitors including PD-1/PD-L1-based therapy result in remarkably durable clinical remissions in some patients with melanoma, others reap a short-term benefit or no benefit at all. It appears that durable clinical remission using immune checkpoint inhibitors is likely dependent on the expression of PD-L1 on the surface of tumor cells and the presence of tumor-infiltrating lymphocytes in the patient’s tumor. Therefore, understanding the molecular mechanisms underlying the expression of immune checkpoint inhibitors and those regulating the infiltration of immune cells into the tumor bed represents a major challenge to improve current immunotherapies in non-responsive cancer patients. Thus, it stands to reason that switching the hypoxic immune-suppressive microenvironment to an immune-supportive one is a prerequisite to achieve successful PD-1/PD-L1 based immunotherapy. We provided evidence that inhibition of autophagy by knocking down Beclin1 using CRSPR/Cas9 technology, induced a massive infiltration of functional immune cells into the tumor core. In keeping with this, we strongly believe that targeting autophagy improves the efficacy of immune checkpoint inhibitors by regulating the temporal dynamic of immune cells in the tumor microenvironment, leading to the modulation of the immune landscape of hypoxic tumors. This study could provide cutting-edge approaches to improve the efficacy of immune checkpoint inhibitors in non-responsive cancer patients.


Hina Bhat
Sher-e-Kashmir University of agricultural sciences and technology of Kashmir,India
Title: Alpha 1 syntrophin protein plays a suspicious role in cell migration and carcinogenesis

Biography:

Abstract: We have studied the expression of alpha-1-syntrophin (SNTA1) protein in histologically confirmed human breast cancerous tissue samples. Our results suggest a significant increase in the expression of SNTA1 adaptor protein as compared to its expression in the corresponding normal tissue samples. No significant difference in expression of SNTA1 protein was observed in stomach, lung, colon and rectal cancers. Our results suggested a role for SNTA1 in carcinogenesis and its possibility as a novel diagnostic or prognostic marker in breast cancers. Taking a lead from here and the earlier works on these proteins, we learnt that SNTA1 has also been implicated in the activation of RhoGTP'ase Rac1 protein. However, the underlying mechanism has not yet been explored. We used Co-immuno precipitation assays to show a complex formation involving SNTA1, GRB2 proteins that was shown to significantly increase the active Rac1 levels within human breast cancer cell lines (HBL 100, MCF 7), while siRNAs and shRNAs were used to down regulate expression of these proteins. Various Rac1 activation assays and functional assays, such as cell migration assays, in vitro wound healing assays, were also performed. Our results showed a significant increase in activation of Rac1 when SNTA1 and P66shc were over expressed, whereas their depletion not only effectively reduced the levels of active Rac1 but also showed a negative effect on the migratory potential of human breast cancer cells. Taken together we propose a possible mechanism of Rac1 activation and cell migration involving SNTA1 and emphasize its role in breast cancer cell migration, and carcinogenesis.


Adhip P.N. Majumdar
Wayne State University, USA
Title: Gut Microbiome Regulation of Colon Cancer Stem Cells and Carcinogenesis

Biography: Dr. Adhip P.N. Majumdar, received his MS and Ph.D. degrees from the University of London, England, and D.Sc (Doctor of Science) degree in Gastroenterology from the University of Aarhus, Denmark. Dr. Majumdar has been a Professor at Wayne State University since 1992. He also holds the post of Senior Research Career Scientist at the Detroit VA Medical Center. Over the past several years Dr. Majumdar’s work has been streamlined to uncover the biochemical and physiological pathways governing the growth of gastrointestinal (GI) tract. He has published over 195 original scientific articles in peer-review journals and a multitude of book chapters and review articles. As reflected by the literature published from Dr.Majumdar's lab, he is particularly interested in elucidating the patho-physiology of age-related changes in the GI mucosa specifically those that lead to malignancy. To this end, Dr. Majumdar has begun to investigate the role of pluripotent, self-renewing CSCs in the development and progression of GI malignancies. Dr. Majumdar has been continually funded by the VA and NIH and is considered one of the nation’s leading investigators in gastrointestinal aging and cancer.

Abstract: Colorectal cancer (CRC), an age-related disease, whose incidence increases markedly after the age of 50 years, is a multi-step process resulting from accumulation of mutations during progression from normal epithelium to carcinoma. Loss or inactivation of the tumor suppressor gene in adenomatous polyposis coli (Apc) initiates genomic instability that is thought to produce the phenotypic appearance of an adenoma. Increasing evidence suggests that pluripotent cancer stem cells (CSCs) are involved in the development and progression of many types of malignancies, including CRC. Earlier, we reported that patients with ≥3 adenomas (High-risk for CRC) exhibit a marked increase in CSCs in the colon than those without adenomas. Although the regulatory mechanisms for this increase in CCSs are poorly understood, we have suggested a role for secondary bile acids in the intestine, specifically deoxycholic (DCA) and lithocholic (LCA) acids, bio-transformed by gut microbiota, in regulating this process. Indeed, we observed a marked rise in Fusobacterium nucleatum and Enterobacterium (both are associated with CRC) in High-risk CRC patients. An opposite phenomenon was noted for the anti-inflammatory Bifidobacteria and for probiotic Lactobacillus acidophilus. Among the secondary bile acids, DCA and LCA are thought to be the most significant with respect to the development of CRC. Interestingly, we found the levels of DCA and LCA in the colon of High-risk (HR) CRC patients to be markedly higher than those at lower risk (LR) for CRC. Interestingly, we found DCA and/or LCA to induce not only mutations of CRC initiating genes such as β-catenin but also CSCs in normal human colonic epithelial cells, as evidenced by increased colonosphere formation and elevated expression of several CSC markers as well as MMP-2, accompanied by an induction in drug exclusion and increased expression of multiple drug resistance (MDR) transporters ABCB1 and ABCG2. Our observations suggest that alterations in specific gut micro-organisms resulting in increase in DCA and LCA that induce stemness in colonic mucosal cells where CRC-initiating genes are mutated are responsible for the development of sporadic CRC.


Thejaswini Venkatesh
University of Kerala, India
Title: MCPH1 functions as a tumor suppressor in oral squamous cell carcinoma

Biography:

Abstract: MCPH1 (microcephalin 1), a protein of 835 amino acids is ubiquitously expressed in human tissues and its deficiency leads to several cancer, a neurodevelopmental disorder primary microcephaly and otitis media. It is shown to have functions in DNA repair, apoptosis and cell cycle checkpoints. Additionally, MCPH1 possesses BRCT domains that are harbored by tumor suppressors like BRCA1 and BRCA2. Currently, its functions as tumor suppressor is well established. Our research study tested the possibility of MCPH1 as a tumor suppressor in oral squamous cell carcinoma (OSCC). Loss of heterozygosity and mutations of MCPH1 were observed at a frequency of 19.72% (14/71) and 6.6% (1/15) in oral cancer specimens. MCPH1 promoter methylation was also observed in 4/40 (10%) tumor samples. Also, downregulated expression of MCPH1 was seen in tumor tissues and cell lines both at mRNA and protein levels. Overexpression of MCPH1 decreased cellular proliferation, anchorage-independent growth in soft agar, and tumor size in nude mice, indicating its tumor suppressive characteristics. Using bioinformatic approaches and luciferase assay, we elucidated that miR-27a which negatively regulates the MCPH1 levels. To conclude, MCPH1 functions as a tumor suppressor gene and is regulated by miR-27a in OSCC (Plos One, 2013).


Suresh PS
Mangalore University, India
Title: Phosphatase and ER crosstalk in augmenting tamoxifen response in breast cancer

Biography: Dr Suresh PS is an UGC Assistant Professor at Dept of Biosciences, Mangalore University since Jan 2015. With successful completion of Ph. D. from Indian Institute of Science, Bangalore in 2010, he relocated from India to work as a post doctoral research scientist at the Department of Pharmacology and Toxicology, Medical College of Wisconsin, USA where he initiated study on Endocrine pharmacology and begin to understand how signaling pathways can affect anti-estrogen therapy in breast cancer. His work as a post doctoral research scientist in Ohio Medical centre, Ohio state University for a brief period focused on liver cancer and miRNA therapeutics. He has authored more than 20 research articles in various international reputed journals including Nature Medicine, Journal of Biological Chemistry, Molecular Cancer therapeutics, European Journal of Cell Biology etc., and presented papers in national and international conferences. He is one among the specially selected faculties by UGC, India through a competitive centralized recruitment and selection for his exceptional creativity, zeal and commitment to research and teaching. He has got several awards, fellowships and honors and serves as an editorial board member in many journals related to his research and also a member in various international science societies. Broadly, current research projects in his lab at Mangalore University focus on endocrine cancers, signal transduction and reproductive and Molecular endocrinology.

Abstract: Breast cancer is a global health problem and strategies to treat breast cancer are evolving and there is a need to identify proper molecular targets. Tamoxifen is being used for the effective treatment of ER positive breast cancer for more than three decades. Acquired tamoxifen resistance in human breast cancer is a major stumbling block in the treatment of breast cancer. Therefore, it is important to identify novel molecular factors that mediate or improve drug sensitivity. In this study, we have identified protein tyrosine phosphatase H1 as a novel phosphatase for phospho-tyrosine 537-ERalpha (Mol Cancer Ther. 2014 13:230-8). Overexpression of this protein sensitized ER positive cancer cells to tamoxifen treatment along with nuclear translocation of ER. RNAi mediated attenuation of phosphatase in T47D, MCF7 and ZR75-1 cells decreased sensitivity to tamoxifen treatment and decreased nuclear translocation. Furthermore, the tumor xenograft of T47D cells stably transfected with phosphatase formed tumors in response to estradiol treatment and showed increased sensitivity to the tamoxifen therapy over the control. Our data suggests that phosphatase H1 contributes to increased tamoxifen sensitivity by increasing nuclear translocation of ERalpha through dephosphorylation of phospho-tyrosine 537 (Mol Cancer Ther. 2014 13:230-8). These findings and future prospects of the work will be discussed.


Cancer Therapies

Session Introduction

Gopal C. Kundu
National Center for Cell Science, India
Title: Osteopontin, a chemokine like protein acts as therapeutic target covering all hallmarks of cancer

Biography: Dr. Gopal Kundu has obtained his Ph.D. in chemistry from Bose Institute, Kolkata, India (1989). He did his post-doctoral research work at the Cleveland Clinic Foundation, University of Colorado, University of Wyoming, and the National Institutes of Health from 1989 to 1998. He has performed work in the area of cardiovascular biology, inflammation and immunomodulation during that period. In 1998, he joined as Scientist-D at National Centre for Cell Science (NCCS), India and at present he is Scientist-G. His area of research at NCCS is tumor biology, regulation of gene expression, cell signaling, cancer stem cells, angiogenesis, cancer therapeutics, biomarker studies and nanomedicine. He has received several awards including Fellows Award for Research Excellence from NIH, USA; National Bioscience Award, Govt. of India; Shanti Swarup Bhatnagar Prize, Govt. of India; International Award in Oncology, Greece; International Young Investigator Award, USA and 7th National Grassroots Innovation Award, Rashtrapati Bhavan, India. He is Fellow of National Academy of Sciences and Indian Academy of Sciences. He has published 74 papers including Nature Medicine, Science, PNAS, Cancer Research, JBC, TCB, Oncogene, Nanomedicine etc and one US patent. He serves as Editorial Board Member of Current Molecular Medicine, Molecular Medicine Reports, The Open Cancer Journal and American Journal of Cancer Research.

Abstract: Substantial advances in breast cancer treatments have resulted in a significant decrease in mortality. However, existing breast cancer therapies often result in high toxicity and nonspecific side effects. Therefore, better targeted delivery and increased efficacy of drugs are crucial to overcome these effects. Osteopontin (OPN), a pro-inflammatory and chemokine like protein plays crucial role in regulating the oncogenic and angiogenic potential of various cancers. Several groups have demonstrated the role of OPN in regulating the cell signaling that ultimately controls tumor progression and metastasis covering all the hallmarks of cancer. During last several years, we have demonstrated that both tumor and stroma-derived OPN regulate tumor growth and angiogenesis through induction of COX-2, uPA and VEGF expressions and activation of matrix metalloproteinase (MMP) in breast and other cancers. Our data revealed that OPN regulates p70S6 kinase dependent ICAM-1 expression and JAK/STAT3 signaling leading to tumor growth in breast cancer. Our recent data showed that OPN controls HIF-1alpha dependent VEGF expression and breast tumor angiogenesis. In addition, we have demonstrated that OPN activated macrophages play crucial role in melanoma progression and angiogenesis. Thus targeting OPN and its regulated signaling network could be novel therapeutic strategy for the management of cancers.


Zhi-Xiu Lin
The Chinese University of Hong Kong, China
Title: Brucein D sensitizes pancreatic cancer to gemcitabine/5-FU via inhibiting PI3K/Akt/Nrf2 and NF-κB pathways

Biography:

Abstract: Gemcitabine (GEM) and Fluorouracil (5-FU) are currently the first-line drugs for the treatment of advanced pancreatic cancer (PanCa). However, the poor response rate, various side effects and development of chemoresistance have compromised their marginal benefit. Hence, novel strategies are in urgent need for the management of this deadly disease. The aim of this study was to evaluate whether Brucein D (BD), a quassinoid isolated from the fruits of Brucea javanica (L.) Merr. (family Simaroubaceae), has potential effect in the treatment of PanCa when used either alone or in combination with GEM/5-FU. Our in vitro results showed that BD significantly inhibited the proliferation of four different human PanCa cell lines and potentiated the GEM/5-FU-induced growth inhibition and apoptosis in PANC-1 and Capan-2 cells, which correlated with the down-regulation of constitutive as well as GEM/5-FU-induced activation of NF-κB and Nrf2, and their-regulated gene products. In addition, the BD-induced inactivation of Nrf2 was found to be dependent on the PI3K/Akt signaling pathway. Most importantly, using an orthotopic nude mouse model of human PanCa, we found BD alone significantly suppressed tumor growth and augmented the antitumor activity of GEM/5-FU. These effects were also due to the down-regulation of NF-κB and Nrf2 activity and their target genes, decreased proliferation (PCNA and Ki-67), and increased apoptosis (TUNEL) in tumor tissues. Overall, our results demonstrate that BD can suppress the growth of human pancreatic tumors and potentiate the antitumor effects of GEM/5-FU through the inactivation of NF-κB pathway and inhibition of the PI3K/Akt/Nrf2 pathway, and the findings render BD as a promising naturally occurring compound for further development into anti-PanCa treatment.


Gautam Sethi
National University of Singapore, Singapore
Title: Potential use of pharmacological inhibitors of STAT3 for cancer therapy: Novel data with agents derived from mother nature

Biography: After completion of his postdoctoral training at University of Texas MD Anderson Cancer Center, Prof. Gautam Sethi joined Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore in 2008 as an Assistant Professor and was promoted to Associate Professor in 2015. The focus of his research over the past few years has been to elucidate the mechanism (s) of activation of oncogenic transcription factors such as NF-kB/STAT3 by carcinogens and inflammatory agents and the identification of novel inhibitors of these proteins for prevention of and therapy for cancer. From traditional Chinese and Indian medicinal plants, his group has identified numerous small molecules that can suppress various pro-tumorigenic signaling cascades involved in cancer initiation and promotion. The novel findings of his research work have so far resulted in more than one fifty scientific publications in high impact factor peer reviewed journals and several international awards. He currently serves as an Academic Editor for prestigious PLOS One journal and ad-hoc reviewer for several other international

Abstract: Signal transducers and activators of transcription (STATs) comprise a family of cytoplasmic transcription factors that mediate intracellular signaling that is usually generated at cell surface receptors and then transmitted to the nucleus. Numerous studies have demonstrated constitutive activation of STAT3 in a wide variety of human tumors, including hematological malignancies (leukemias, lymphomas, and multiple myeloma) as well as solid tumors (such as head and neck, breast, lung, gastric, hepatocellular, colorectal and prostate cancers). However, the development of novel drugs for the targeting STAT3 that are both safe and efficacious remains an important scientific and clinical challenge. We will present recent data from our group that shows that novel small molecule inhibitors (garcinol/butein) can suppress STAT3 activation through diverse molecular mechanisms and modulate the expression of genes involved in cancer progression. Overall, our findings have identified two promising STAT3 inhibitors with significant anticancer effects.


S.Arunachalam
Bharathidasan University, India
Title: Synthesis, aggregation behaviour, intercation with proteins and DNA and anticancr activites of some surfactant–ruthenium(ii) complexes

Biography: Dr. S. Arunachalam has completed his Ph.D., at the age of 30 years from the University of Madras, India and postdoctoral studies from university of Canada. He is the retired professor of chemistry, Bharathidasan University. He is published 72 papers in reputed journals. He has attended more than 25 conferences and presented papers. He has served as Chairman, Board of studies in chemistry, at Bharathidasan University. He has guided 13 Ph.D., scholars and currently 2 Ph.D., scholars are working under him. He has guided many M.Phil., and M.Sc., students. He has operated many research project in chemistry funded by various funding agencies like UGC, DST and CSIR. He has visited several countries like USA, Canada, Germany, Spain, Belgium and Japan under various capacities such as visiting researcher, visiting scientist, DST-FRG fellow, visiting professor etc. He is a Ph.D., examiner to various Universities in India including IITs.

Abstract: In this work, bipyridine and phenanthroline based double chain surfactant–ruthenium(II) complexes with alkylamine ligands of different chain length have been taken into account to analyse the impact of structural modification of surfactant metal complexes on their aggregation behaviour, DNA and protein binding and anticancer properties. The results have shown that the aggregation process is effectively induced by increasing the size of the head group as well as alkylamine chain length. These aggregates are vesicles in nature, and spherical, monodisperse and narrow size distributed in shape. The interaction of surfactant−ruthenium(II) complexes and their precursor ruthenium(II) complexes, with biomacromolecules (DNA, BSA and HSA) generally resulted that the precursor- and surfactant−ruthenium(II) complexes are likely to involve electrostatic and hydrophobic binding, respectively. Also their extent of interaction with the biomacromolecules is enhanced upon increasing the size of the head group as well as alkylamine chain length. Further BSA has more binding affinity with all the complexes compared to HSA. This kind of increase of hydrophobicity of surfactant–ruthenium(II) complexes enhances the cell wall penetration, thereby improve the anticancer properties against A549 lung cancer cell line. Thus the present findings will create new avenue towards the development of surfactant based metallodrugs for various anticancer applications.


Cancer Management and Prevention

Session Introduction

Masahiro Tsubaki
Yuai Memorial Hospital, Japan
Title: Outcomes of fecal occult blood testing in one local hospital in Japan

Biography: Masahiro Tsubaki M.D, Ph D graduated from Hirosaki National University, School of Medicine in 1983. He worked in First Department of Surgery, Tokyo Medical and Dental University (TMDU) from April, 1983 to March, 1998. He was an expert of JICA, Instituto Chileno-Japones, Santiago CHILE from January,1994 to December, 1994. He worked as an Assistant Professor and leader of the unit for Colorectal surgery from April, 1998 to June, 2011. He acted as Vice President of Yuai Memorial Hospital from July 2011. He worked as a Project Professor of Latin American Collaborative Research Center of TMDU from 16th of September, 2014 to 12th of October, 2015.

Abstract: Introduction: Fecal occult blood tests (FOBT) are used in screening for colorectal cancer. Recently, over 48000 deaths per year were recorded due to colorectal cancer in Japan. Clearly, the early detection of colorectal cancer is of utmost importance. Purpose: The purpose of this retrospective study was to review the outcomes of the FOBT in a local hospital in Japan Materials and Methods: From January 2008 to December 2014, the immunological FOBT was used in screening 52703 people in our hospital. Two stool samples were taken one day apart. When one or two positive samples were found, the results were mailed to the patients. Further examinations to detect colorectal cancer with colonoscopy or barium enema were performed for the patients who opted for those studies. Clinico-pathological findings were described according to the General Rules for Clinical and Pathological Studies on Cancer of the Colon, Rectum and Anus. Results: Of the 52703 screened, 2923 or 5.54% were positive by FOBT. Further examination was performed in 1361 cases, or 46.5% to detect the disease. Colorectal cancers were confirmed in 37 (or 2.9%) of those who had colonoscopies. Of the 37 colorectal cancers, 25 ( 71.4%) were diagnosed as stages 0 or 1. Conclusions: The percentage of early colorectal cancers identified by FOBT was high. FOBT was useful in screening for colorectal cancers.


Sundardas D. Annamalay
Sundardas Naturopathic Clinic, Singapore
Title: Correlations between homoeostatic reserve and mortality in cancer: A literature review

Biography:

Abstract: This paper reviews the literature regarding the correlations between homoeostatic reserves and mortality for cancer. In the 1920’s and 1930’s, a distinguished researcher at Yale University School of Medicine, Harold Saxon Burr, suggested that diseases could be detected in the energy field of the body before physical symptoms appear. Moreover, Burr was convinced that diseases could be prevented by altering the energy field. These concepts were ahead of their time, but are now being confirmed in medical research laboratories around the world. However what he was actually measuring was the energetic field that was being generated by the movement of red blood cells carrying their respective charges that gave rise to electric and then magnetic fields. This was one measure of assessing the functional reserve of the organism. We know that in the pre-cancer stages the functional reserves change for the worse. During the treatment and after the treatment of cancer the level of the functional reserve is a measure of morbidity and mortality. One valid way of measuring the functional reserves of the body is using the heart rate variability assessment and bio-impedance assessment. Both heart rate variability analysis and bio-impedance assessment are independent markers for functional reserves as well as morbidity and mortality.


Agboola Oluwaseun Abosede
University Teaching Hospital Nigeria
Title: Single Visit approach to cervical cancer prevention at The Obafemi Awolowo University Teaching Hospital,Nigeria

Biography: Mrs Agboola Oluwaseun in an oncology nurse per excellence; had her nursing training at the Osun State School of Nursing in Nigeria 1993, got her first degree in Health Education at the Lagos State University Oojo Nigeria in 2001. She was sent for a training in oncology by the International Network for Cancer Training and Research Belgium in 2005 and has since been practicing as an oncology nurse. She has presented papers in many international conferences on challenges facing Africa in cancer prevention and control especially gynaecological cancers. She has attended many conferences including the 2nd International Cancer Control Conference in Brazil in 2007, 7th Aortic Cancer Conference held in Da re Salaam Tanzania in 2009, 5th International Cancer Control Conference in Seoul South Korea November, 2011. She also had training in colposcopy technique at the Christian fellowship Health Centre India, Multi-professional palliative care training at the famous St. Christopher’s Hospice London United Kingdom in September 2014. She is presently a Chief Nursing Officer at the Obafemi Awolowo University Teaching Hospital, Ile-Ife, Osun State, Nigeria working at the gynaecological oncology unit where screening and treatment of gynaecological cancers is her major task. She loves travelling, meeting people and educating women on the risks, prevention and treatment of cancers, happily married with children.

Abstract: Introduction : Cervical cancer burden is the highest in low and middle income countries that have about 80% of all the new cases a year worldwide,resulting in 300,000 deaths a year.Less than 6% of these women have ever had a screening test in yheir life time because of non avalability of screening centers,awareness on preventive measures for cervical cancer in developing countries and extreme poverty of most of the women,whose source of livelihood and income are inadequate thus are not able to afford the conventional cytology screening programme. Materials and Mehods : Cervical screening is designed to identify women in their reproductive age with pre invasive leisions in the cervix,( CIN ) that when treated with local ablative or excision procedures will prevent progression of CIN to invasive cervical cancer. In developing countries like Nigeria alternative screening tests like visual inspection with acetic acid and lugol’s iodine are employed because it is cheap,affordable, easily preapared with sensitivity of 70-90% and specificity 50-90%.The test results of VIA/VILI are available immediately and treatment with cryotherapy with cure rate of 80% are given thus losing patient to follow up care is minimised as treatment is offered as ‘’Single Visit’’. RESULTS : Women that came in for screening with positive cervical VIA/VILI screening were treated same day with cryotherapy thus treating them at single visit. CONCLUSION : For countries in low and middle income categories ‘’single visit’’ cervical cancer screening has been tested and found acceptable to women and health providers.


Clinical Cancer Research

Session Introduction

Fouad Al-Dayel
Alfaisal University, Saudi Arabia
Title: Loss of PTEN expression is associated with aggressive behavior and poor prognosis in middle eastern triple negative breast cancer

Biography:

Abstract: Objective: To explore the significance of the role of PTEN in middle eastern triple negative breast cancer Methods: We analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Results: Loss of PTEN immunostaining was observed in 77% of the cases. PTEN loss was significantly associated with large tumor size (p=0.0030), high grade (p=0.0281), tumor recurrence (p=0.0333) and Triple negative breast cancers (p=0.0086). PTEN loss in Triple negative breast cancers was significantly associated with rapid tumor cell proliferation (p=0.0396) and poor prognosis (p=0.0408). PTEN deletion was found only in 60 cases (6.4%) of cases. Conclusion: Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation.


Sergey N Rumyantsev
Department of Evolutionary Immunology, USA
Title: Susceptibility to Cancer among Various Groups of Human Populations

Biography:

Abstract: This article develops the results of a recent pioneered investigation of the population differences in human susceptibility to Cancer. The focus of current investigation was based on the integration of recent achievements in evolutionary immunology, epidemiology, and anthropology of cancerous diseases. Main focus was on the origin of differences in hereditary immunity against the disease which has resulted in different population indexes of mortality among 124 populations from across the globe united in four groups of population according to their differences in susceptibility to cancer: a group of the 43 most susceptible populations, a group of Indigenous Australians, a group of the 32 most resistant populations, and a group of 48 less resistant populations. Intriguing differences in geographic disposition of the groups have been revealed and interpreted. The issues of origin, evolution, geographic disposition, and dating of discovered features are discussed.


Cancer Biomarkers

Session Introduction

Ali Fendri
Institute of Molecular and Cellular Biology of CNRS, France
Title: Quantitative expression analysis of BCL2L12, BCL2 and the BCL2-associated X mRNA expression : A novel biomarker for the prediction of short-term relapse in nasopharyngeal carcinoma

Biography: Dr. Ali Fendri has completed his Ph.D in 2010 at the age of 30 years from the University of Tunisia working of the molecular aspect of Nasopharyngeal carcinoma. From 2010-2012 he performed his first postdoc at the IBMC of Strasbourg –CNRS- France. Then he obtained the graduation of Lecture at the Center of biotechnolgy in Tunisia from 2012-2014. By the beginning of 2014 Ali joined again the IBMC of Strasbourg for a researcher position. During his research activity he published several papers in reputed journals mainly in the field of oncology.

Abstract: Nasopharyngeal carcinoma (NPC) is a highly metastatic epithelial malignancy showing high prevalence in Southeast Asia and North Africa. BCL2-like 12 (BCL2L12) is a new member of the apoptosis-related BCL2 gene family, members of which are implicated in various malignancies. BCL2 (Bcl-2) is an anti-apoptotic gene with marked up-regulation in various malignancies, such as breast cancer, in which expression of the BCL2 protein has been proposed as a prognostic tumor biomarker. The BCL2-associated X (BAX) gene encodes the most important pro-apoptotic member of the BCL2 family. The objective of the current study was to analyze BCL2L12, BCL2 and BAX mRNA expression in nasopharyngeal biopsies of NPC patients, and to assess its prognostic potential in this disease. Total RNA was isolated from 88 malignant and 9 hyperplastic nasopharyngeal biopsies, resected from Tunisian patients. After cDNA synthesis by reverse transcription of polyadenylated RNA, BAX mRNA expression was analyzed using a highly sensitive quantitative real-time polymerase chain reaction (qRT-PCR) method. GAPDH served as an endogenous control gene. Higher BCL2L12 mRNA levels were detected in undifferentiated carcinomas of the nasopharynx, rather than in nonkeratinizing nasopharyngeal tumors (P = 0.045). BCL2L12 expression status was also found to be positively associated with the presence of distant metastases (P = 0.014). High BCL2 mRNA levels were detected in advanced-stage nasopharyngeal tumors (p = 0.030). Furthermore, BCL2 mRNA expression was strongly associated with lymph node involvement (p = 0.009) and presence of distal metastases (p = 0.013). On the other side, lower BAX mRNA levels were detected in NPC biopsies than in hyperplastic nasopharyngeal samples. BAX mRNA expression status was associated with low tumor extent, negative regional lymph node status, and absence of distant metastases. Kaplan-Meier survival analysis demonstrated that patients with both BCL2L12- and BCL2 positive NPC tumors have significantly shorter disease-free survival (P = 0.020, P = 0.011) respectively. Contrariwise, patients with BAX mRNA-positive NPC have significantly longer disease-free survival. The major contribution of the current study is the quantification and evaluation, for the first time, of the prognostic significance of the BCL2L12, BCL2 and BAX mRNA expression in nasopharyngeal carcinoma patients. Our results suggest that the expression these three proteins may constitute a novel and independent tumor biomarkers for nasopharyngeal carcinoma.


Rahma AIT HAMMOU
University Hassan II-Mohammedia, Morrocco
Title: Development of nano-technological biosensors from tumor markers for early diagnosis of gynecological and breast cancers: Viral etiology in Morocco

Biography:

Abstract: Breast and gynecologic cancers (cervical cancer, ovarian cancer ...) represent a real public health problem in Morocco. In 2011 these cancers accounted for 60% of all cancers among women and 50% of cancer among women treated at the National Institute of Oncology. These cancers are often diagnosed at an advanced stage of the disease, especially in rural areas where the awareness and education of the population still represent real obstacles. In spite of significant advances in research on these cancers, with the new tools of molecular biology, viral etiopathology of these cancers is often associated and reported to HPV (human papilloma virus), EBV, MMTV, HBV, and the most affected virus is often the HPV. Therefore their diagnosis is frequently performed late to the metastatic stage. In Africa more than 30% of cancers are caused by infection, and several studies are oriented towards the search of a viral etiology in gynecologic and breast cancers. Similarly, in the context of the prevention of cancer, one of the current approaches is the identification of specific biomarkers that allow early diagnosis of these cancers. Among these, the identification of MicroRNAs (miRNAs), which are epigenetic biomarker able to regulate promoters of genes of cancer cells and which are released early in the general circulation, thus providing potential targets for diagnosis. It is in this context that our research project proposes to locate and identify a molecular profile of miRNAs specific to each type of breast and gynecological cancers in the moroccan population, seek the involvement of viral etiology in these cancers from biopsies, and develop a nano-biosensor in order to establish an early diagnosis, better prognosis and improved therapeutic monitoring for patients.


Cancer Detection and Imaging

Session Introduction

Veronica James
ANU College of Physical and Mathematical Sciences
Title: See It Come - Watch It Go

Biography:

Abstract: Text The cancers that have been investigated by Fibre Diffraction(FDD)all send out a notice of their arrival to every point in the body. This message is passed either through the blood or via collagen. FDDcan pick up this signal and interpret it. Treatment can start early to remove this new unwanted arrival and if it is totally removed, there will be no further signals - thus providing reassurance to the patient that their cancer is cured