World Congress on
Cancer and Prevention Methods
August 27-29, 2015, Dubai, UAE

Scientific Programme(Day 3 : Aug-29-2015)

Workshop on, "Cancer Biomarker Development and Validation"
Session Chair:
Upender Manne
University of Alabama at Birmingham, USA


Session Introduction

Upender Manne
University of Alabama at Birmingham, USA
Title: Development of patient population-specific molecular biomarkers
Biography:
Dr. Upender Manne is a Professor of Pathology and a Senior Scientist at the Comprehensive Cancer Center and the Minority Health Disparity Research Center of the University of Alabama at Birmingham. He received his doctoral degree from Osmania University, Hyderabad, India, and postdoctoral training at University of New South Wales, Sydney, Australia. For more than 20 years, his scientific career has been dedicated to translational research on human cancers. He has published more than 85 peer-reviewed scientific papers and review articles in high-impact national and international journals. He is an expertise and leader in the field of Cancer Biomarkers Development and Validation.In 2009, he was invited by the US Presidents Cancer Panel to address how racial/ethnic admixtures affect the findings of molecular biomarker studies relating to cancer outcomes. Till now, Dr. Manne has mentored more than 45 undergraduate, medical, and graduate students; residents; clinical fellows; and postdoctoral fellows. In 2009, his mentoring skills were recognized by a Sir Charles Barkley Mentoring Excellence Award.

Abstract:
Colorectal cancer (CRC), the third most common cancer, is found predominately in countries that practice the Western diet. The pathologic stage, most commonly used for prognosis, may not be the best indicator of outcome, since patients with tumors of identical stage have different treatment responses and outcomes. Thus, there is a need to identify predictors of therapy efficacy, disease recurrence, and patient survival.Due to contradictory results, no marker has achieved acceptable clinical utility. These differences may be due to technical discrepancies, under-powered study populations, an admixture of different proportions of racial/ethnic/geographic groups, or to different tumor sites within the colorectum, tumor stages, and/or patient demographics. For example, abnormal nuclear accumulation of p53 in CRC cells is a strong indicator of poor patient survival of non-Hispanic Caucasians (CAs) with proximal colon tumors. In African-American (AAs), but not CAs, the Pro/Pro phenotype correlates with a higher incidence of missense p53 mutations, nodal metastasis, and higher mortality due to CRC.p53, however, has no prognostic value for AAs or CAs with distal or rectal tumors. Establishment of race-based differences in p53 may aid in identifying patients with aggressive phenotypes. Several similar molecular (p27kip-1, Bax, Bcl-2, and miRNAs) evidences will be presented. To establish personalized medicine, research should focus on identification of individual differences based on race/ethnicity; on the discovery of molecules (genes, mRNA transcripts, and proteins) relevant to these differences; and on development of therapies to target these molecules. Such strategieshave the potential of reducing the personal and socio-economic burden of cancer.

Hassan Ashktorab
Howard Univeristy Cancer Center, USA
Title: Targeted cancer gene sequencing identifies potential causative novel candidate mutations in colon carcinogenesis
Biography:
Dr. Ashktorab has completed his Ph.D at the age of 28 years from Utah University and postdoctoral studies from Indina University and University of Florida, School of Medicine. He is the director of Microarray lab, a member of Gastrointestical Research group. He has published more than 100 papers in reputed journals and has been serving as an editorial board member of many Journal including DDS, GUT, PlosOne and others.

Abstract:
Colorectal cacner is the second cause of death in the world and genomic alteration palys an importan role in this desase. Much of the underlying genetic ‘cancer driver’ mutations in sporadic colorectal cancer (CRC) have not been characterized by race. Here, we report the identification of distinct novel variants from CRC patients in mismatch repair (MMR) genes MHS3 and MSH6, and APC. We developed a panel of 20 frequently altered colon cancer genes for targeted sequencing in 138 colon tissues using next generation sequencing to examine 98.8% of the targeted exons and splice junctions at a depth of sequencing that allowed for high confidence variant calling. After alignment and variant calling, we annotated the variants with information from the 1000 Genomes Project, COSMIC, Polyphen2, and PFAM domain and transcription factor motifs. Excluding synonymous SNVs, 212 deleterious variants in adenoma, 760 in advanced adenoma, and 2624 variants in tumors were detected. Novel variants (1591 and 1363) were found in MMR genes (MSH6 and MSH3) and APC gene, respectively. These findings further highlight the relevance of APC gene in CRC onset but also the potential underestimation of the MSI-H in sporadic CRC as many of the novel mutations in MMR genes detected here were of a deleterious nature with an thraputic interst.

Corinne E Griguer
University of Alabama at Birmingham, USA
Title: Mitochondrial biomarkers in cancer
Biography:
Dr. Corinne E Griguer has completed her Ph.D. from University of Montpellier (France) and postdoctoral studies from University of Washington School of Medicine. Currently, she is an Associate Professor in the Department of Neurosurgery and a member of the Neuro-oncology group of the Comprehensive Cancer Center at the University of Alabama at Birmingham. Herresearch is focused on mechanistic studies of glioma initiation and progression, especially the contributions from the molecular alterations of mitochondria. She identified Cytochrome c Oxidase as a key player in the regulation of chemo-resistance, and a novel prognostic biomarker of aggressive glioblastoma multiform.

Abstract:
Cancer cells exhibit changes that allow them to escape from cell death, sustain their proliferative trait, and divert their metabolism toward glycolytic energy production. Mitochondria play a central role in many metabolic and biosynthetic pathways, and the adaptation of mitochondrial function has been recognized as crucial to the changes that occur in cancer cells. In this talk, an overview will be given to demonstrate how mitochondrial markers aid in diagnosing, staging and identifying aggressive phenotypes of human cancers using our findings of brain cancer as example.

Esther Azungwe Suswam
University of Alabama at Birmingham, USA
Title: Validation of tumor suppressor function of tristetraprolin in brain and colorectal cancers
Biography:
Dr. Esther Suswam is an Assistant Professor of Pathology at the University of Alabama at Birmingham (UAB). Her research goals are to identify and validate molecular markers of cancer risk, progression, and outcomes, and the regulation of cancer growth via these pathways and the implications for racial/ethnic disparities. Efforts in her laboratory provided understanding on the impact of the RNA stabilization pathway on tumor progression, and elucidated the tumor suppressor role of tristetraprolin in brain cancer.

Abstract:
Posttranscriptional mechanisms play a critical role in the regulation of cancer growth. Tristetraprolin (TTP), a CCCH-tandem zinc finger protein, is a negative regulator of growth pathways utilized in cancer. TTP is a direct target of p53 and may complement p53 function through down-regulation of oncogenes and induction of tumor suppressor genes. However, the tumor suppressor function of TTP is lost or suppressed in many cancers, apparently, via distinct mechanisms. In malignant gliomas, we observed that TTP was expressed but it was extensively phosphorylated, thus we postulate that TTP is suppressed through hyperphosphorylation. We tested this hypothesis by analyzing the phenotypic effects of a mutated form of TTP (mt-TTP) in which 8 critical phosphoserine residues were converted to alanines by site-directed mutagenesis. Activation of TTP protein via inhibition of phosphorylation resulted in enhanced negative effect on growth factor production at both transcriptional and posttranscriptional levels, in enhanced antiproliferative effects and cancer cell killing.In contrast to malignant glioma, TTP expression was suppressed or lost in colorectalcancers (CRCs) and we observed concomitant upregulation of IL-8. We hypothesized that loss of negative regulation by TTP controls the aggressive phenotype of CRC through up-regulation of growth factors and tumor progression. We analyzed the mRNA expression of TTP and its targets and assessed its subcellular localization in primary CRCs as well as in cultured colon cancer cells. TTP mRNA was downregulated in tumors [31 of 45 CRCs (69%)], and low TTP levels correlated with advanced tumor stages (III and IV) and degree of differentiation. There was an inverse correlation between TTP and IL-8 expression in relation to tumor stage. These results were confirmed by immunohistochemistry. In cultured colon cancer cells, TTP mRNA levels inversely correlated with levels of IL-8, VEGF, and cIAP2 mRNAs, suggesting interactions of TTP with these cell survival factors. These findings suggest that the tumor suppressor mechanisms of TTP vary in brain and colorectal cancers.

Chandrika J Piyathilake
University of Alabama at Birmingham, USA
Title: Diet-related epigenetic biomarkers of cervical cancer risk
Biography:
Dr. Chandrika Piyathilake is a Professor/Director of the Molecular Epidemiology Laboratory at the University of Alabama at Birmingham (UAB). Her research goals are to systematically develop promising dietary interventions for prevention of cancer while understanding the underlying molecular mechanisms of action and discovery of biomarkers for early detection of cancer. She has taken a systematic approach to address the importance of nutritional factors for cancer prevention and control and have demonstrated that methyl donor micronutrients as well as overall dietary patterns are associated with cancer-protective levels of DNA methylation in the genome of the host and cancer causing viruses.

Abstract:
Infections with oncogenic or high-risk human papillomaviruses (HR-HPVs) are the causative agents for developing cervical intraepithelial neoplasia (CIN) and cervical cancer (CC). Prophylactic vaccines against the most carcinogenic HPV genotypes, HPV 16 & 18 have proven to be beneficial in lowering the development of HPV 16/18 associated CIN, particularly when the vaccine is received prior to acquiring the infections. Prophylactic vaccines are, however, ineffective in millions of women already infected with such HPV types. Therefore, the predominant mechanisms for prevention of HPV-associated CIN/CC for the foreseeable future will continue to be screening and treatment of CIN lesions or other non-vaccine based approaches such as micronutrients. Micronutrient-based approaches are particularly important for the prevention and control of CIN/CC because HR-HPVs are classified as human carcinogens and micronutrients such as folate and vitamin B12 have anti-carcinogenic functions via their effects on immune response, integration and proliferation of HPVs or methylation of the host and HPV DNA. We have previously reported that higher circulating concentrations of folate are associated with a lower likelihood of becoming HR-HPV positive and of having persistent HR-HPV infections, and when infected, a greater likelihood of clearing HR-HPVs. Our studies have also demonstrated that women with lower folate status and positive for HPV-16 were 9 times more likely to have CIN 2+, strongly suggesting a specific effect of folate on HPV-16, the most commonly found and most carcinogenic type of HPV. Our recent studies have demonstrated that a higher degree of methylation in the long interspersed nucleotide element 1 (L1) in peripheral blood mononuclear cells (PBMCs), a folate and vitamin B12- related epigenetic alteration is associated with a lower risk of developing CIN 2+. Further, we also demonstrated that a higher degree of methylation of CpG sites in the promoter and enhancer of HPV 16 was associated with a lower likelihood of being diagnosed with HPV 16-associated CIN 2+ and folate and vitamin B12 play an important role in maintaining a desirably high degree of methylation at these specific CpG sites. Our observations indicate that interventions with folate and vitamin B12 are likely to be effective in reducing the risk of developing CIN/CC and the degree of L1 or HPV methylation are useful markers to assess the efficacy of such interventions.

Sunil Sudarshan
University of Alabama at Birmingham, USA
Title: Therapeutic implications of oncometabolite-driven kidney tumors
Biography:
Dr. Sudarshan received his medical degree from Duke University School of Medicine. After training in Urology, he went onto to receive advanced training in Urologic Oncology from the National Cancer Institute at the NIH. He is associate professor of Urology at the University of Alabama at Birmingham where he also serves as Director of the Renal Cancer Biology Program. His laboratory is focused on elucidating the role of metabolism in renal carcinogenesis.

Abstract:
Renal cell carcinoma (RCC) is among the 10 most common malignancies in both men and women. Unfortunately, progress in the treatment of patients with advanced disease has been incremental, and new treatment approaches are warranted. Altered metabolism, an established hallmark of malignancy, may provide novel therapeutic opportunities. Oncometabolites, small molecules with putative transforming properties, represent one of the clearest links between metabolism and cancer. A unifying theme amongst the oncometabolites identified to date is their ability to alter the epigenome via inhibition of enzymes involved in DNA and histone demethylation. In the context of RCC, there is increasing recognition of the role of epigenetics to the pathogenesis of this malignancy. However, the drivers of the RCC epigenome remain poorly characterized. Studies by our laboratory and others have identified elevations of the putative oncometabolite (L)-2-hydroxyglutarate (L-2HG) in RCC as well as brain tumors. Elevations of L-2HG in RCC are due to genetic loss of L2HGDH (L-2HG dehydrogenase) which is located on chromosome 14q. Intriguingly, 14q loss is associated with a DNA hypermethylation phenotype and worsened outcomes in RCC patients. This talk will focus on the mechanisms that promote L-2HG accumulation in RCC as well as the impact of L-2HG on the epigenome and tumorigenesis. Collectively, the data presented will provide novel insight into the metabolic basis of the epigenetic landscape of RCC. Moreover, the data presented have biomarker implications for therapeutic approaches to advanced RCC.

Cai Wanpei
National University of Singapore, Singapore
Title: Characterization of a novel modulator of Wnt/β-catenin signaling in triple Negative Breast Cancer
Biography:
Cai Wanpei is currently a third year Ph.D student at The National University of Singapore (NUS). She obtained her bachelors (with honours) in Life science from the National University of Singapore (NUS) in 2009. After graduation, she was was recruited into Thermo Scientific as a system engineer, from 2009 to 2012. During her time at Thermo Scientific, she was involved in the research and development of new PCR and real-time PCR products such as ViiA™ 7 and QuantStudio™ 12K Flex. In 2012, she left her vocation in Thermo Scientific to join NUS after receiving a 4-year direct Ph.D scholarship from NUS Yong Loo Lin School of medicine.

Abstract:
Breast cancer is a principle cause of death in women globally and a diverse malignancy. Despite recent advances in breast cancer therapeutics, mortality of highly metastatic triple negative breast cancer (TNBC) subtype remains high; due to their lack hormone receptors expression for targeted therapy. Therefore, there is a pressing need to identify new prognostic markers and therapeutic targets for this group of breast cancers. Aberrant activation of Wnt/β-catenin signaling has been associated with breast cancers; where 40% of total breast cancers have elevated β-catenin levels and/or Wnt activity. Herein, we identify DEAD-box RNA helicase DP103 as a novel prognostic biomarker and metastasis-driving oncogene; highly expressed in TNBC subtype. High DP103 expressing TNBC cells correlated with increased Wnt activity, leading us to hypothesize a role of DP103 in modulating Wnt/β-catenin pathway. Furthermore depletion of DP103 in metastatic TNBC cells decreases Wnt/β-catenin activity and expression of downstream Wnt target genes while overexpression of DP103 increased Wnt activity. This suggests DP103 to play a role in regulating Wnt/β-catenin signaling. Interestingly, induction of Wnt/β-catenin signaling in Wnt responsive TNBC cells also significantly increased Dp103 expression, indicating a possible positive feedback loop. Collectively, our data suggest a novel regulatory role of DP103 in the Wnt/β-catenin signaling pathway, and presents itself as a potential drug target for inhibition of Wnt/β-catenin pathway in TNBC patients. In breaking the Achilles’ heel of this positive feedback loop and thereby weaken Wnt/β-catenin activity, we hope to achieve a much favorable outcome in TNBC patients.

Wang Chao
National University of Singapore, Singapore
Title: RNA helicase DDX20, a biomarker of statin activity in invasive breast cancer
Biography:
Wang Chao is a PhD Student in the school of Medicine in National University of Singapore (NUS). Her current research interest is chemotherapy drugs for breast cancers and she is doing research in Cancer Science Institute, Singapore. Before her PhD, she obtained her bachelor degree in the school of Basic Medical Sciences from Peking University, China, where she focused her research on the effects of statins on bone formation. She was one of the top students in Peking University, and was awarded National Scholarships consecutively. Currently, she is offered research scholarship and Medicine Top-Up scholarship to further her study in NUS.

Abstract:
Statins, used for the treatment of hypercholesterolemia, inhibit the rate-limiting enzyme of the mevalonate pathway, 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Interestingly, cancer cells are dependent on the sustained availability of this pathway and habor dysregulated expression of HMGCR. In several prospective studies, simvastatin use was associated with reduced risk of breast cancer. It is reported that statins inhibit proliferation and metastasis in a variety of cancers, including breast cancer by interfering with activation of NF-κB. Our group recently reported a novel oncogene, DDX20, as a crucial positive regulator of NF-κB activation and its target genes. In the present study, we first assessed correlation between 17 mevalonate pathway genes and expression of DDX20 in a cohort of 1325 breast cancer tumors. Among the 17 genes evaluated, positive correlation with DDX20 expression was observed in eight of them, with HMGCR having the most significant positive correlation. Our in vitro experiments show exposure of breast cancer cells to statins lead to a Rho A-dependent decrease in expression of DDX20, leading to decreased tumor proliferation in a mevalonate pathway-dependent manner. Conversely, overexpression of DDX20 significantly abrogated the effects of statins. A similar observation was seen in a mouse model, where simvastatin fed mice show significantly decreased DDX20 and lung metastases, corroborating our observations in vitro. A long term implication of our findings is the possibility of an effective combinatorial therapeutic intervention using statins (to suppress DDX20 expression) and a suitable first-line agent for the treatment of invasive breast cancer.

Advances in Nanoparticle Technology for Cancer Imaging &
Epidemiology and prevention
Session Chair:
Swadeshmukul Santra
University of Central Florida, USA


Session Introduction

Swadeshmukul Santra
University of Central Florida, USA
Title: Quantum dot probes for bioimaging and biosensing appications
Biography:
Swadeshmukul Santra is an Associate Professor of NanoScience Technology Center, Department of Chemistry, Materials Science & Engineering and Burnett School of Biomedical Sciences at the University of Central Florida. He received his Doctor of Philosophy degree in chemistry from the Indian Institute of Technology Kanpur, India in 1998. He did his postdoctoral studies at the University of Florida, USA. Prior to joining the UCF in 2005, he was appointed as a Research Assistant Professor at the UF - Department of Neurological Surgery. He has published more than 60 peer-reviewed articles. He is a member of ACS, AVS, MRS and AAAS.

Abstract:
Over the past decade, Quantum dot (Qdot) nanotechnology has provided sophisticated tools for sensitive imaging of biological systems and sensing of biomolecules. In comparison to traditional organic dyes and fluorescent proteins, Qdots are much brighter and highly photostable. Real-time intracellular tracking of biological molecules and multiplexed imaging of intracellular organelles with high resolution have been possible using Qdot probes. In recent years, a number of Qdot based biosensing probes have been reported which could tremendously advance cancer drug discovery research by confirming release of therapeutic cargoes and possibly quantifying the released cargo amount within a single cell. Despite of these outstanding biological applications, wide-spread use of Qdot nanotechnology in nanomedicine has been limited primarily due to undesirable intrinsic heavy-metal induced cytotoxicity issues and poor understanding of Qdot pharmacokinetics. In this talk, I will present an overview of Qdot research in cancer imaging and sensing.

Munir Abu-Helalah
Mutah University, Jordan
Title: Delay in presentation, diagnosis and treatment for colorectal cancer patients in Jordan
Biography:
Dr Abu-Helalah completed his medical degree from Jordan University of Science and Technology (JUST) 2001. He moved in 2002 to the United Kingdon (UK) where completed a master degree in Public Health (MPH) from the University of Dundee in 2004 and a PhD in epidemiology and preventive medicine from the University of London in 2009. While he was in the UK, he worked as a Research Fellow in epidemiology and preventive Medicine at the St Bartholomew’s Hospital, London-UK, in 2007/2008. In 2009, he joined King Hussein Cancer Center in Jordan as a Senior Officer for the cancer control program. In 2011, he joined the National Guard Health affairs as an Assistant Professor of Epidemiology and Preventive Medicine. In February 2012, he returned to work in Jordan at the Faculty of Medicine, Mutah University. He was selected in 2013 as the regional director for Middle East and North Africa for the Global Center for Public Health and Disease Control, Ohio, USA. He also works as a consultant and technical expert for several regional and international organizations. Dr Abu-Helalah has special expertise and interest in chronic diseases control and prevention particularly cancer, diabetes, thyroid disorders, cardiovascular diseases, and smoking cessation. This is in addition to his experience in medical research and in applying evidence based medicine in clinical practice. He has conducted more than ten workshops in the above fields over the last two years and he has had important publications in these fields in peer-reviewed journals. On 9 April 2014, Dr Abu-Helalah was honoured by HRH Prince of Easter Region, KSA as the “Winner of the First place in the Prince of Easter Region Award for the Best Cancer Research in the Arab World” in the first round of this prize.

Abstract:
Introduction Colorectal cancer (CRC) ranked first among cancers reported in males and second among cancers reported in females in Jordan in 2010. There has been no specific CRC-control programme in Jordan. Additionally, there has been no published study from Jordan or its neighbours on patient delays in presentation, diagnosis or treatment. Therefore, we conducted this study to assess these important quality indicators aiming to improve prognosis for CRC and to provide baseline data for future health-promotion programmes for CRC in Jordan. Methods This project was a cross-sectional study on CRC patients at Al Bashir Hospital, Ministry of Health, and at the Military Oncology Center of the Jordanian Royal Medical Services. Results The total number of participants was 189. The proportion of patients with presentation delay, diagnosis delay or treatment delay was 33.9%, 68.1% and 32.6%, respectively. The main reasons reported for delay in presentation were lack of knowledge that symptoms were suggestive of cancer (58.5%), misdiagnosis by physicians or pharmacists (38.4%) or the patient did not want to visit a doctor (3.1%). Predictors of delay and mean time for presentation, diagnosis and treatment were identified. Conclusion Our results revealed that CRC patients in Jordan experience delays in presentation, diagnosis and, to a lesser degree, in treatment. This could justify the advanced stages at diagnosis and poor outcomes for CRC patients. Our findings provide baseline information for future CRC-control programmes in Jordan. We recommend that CRC-prevention programmes in Jordan focus on early detection of CRC, and target both patients and physicians.

Roland Sennerstam
Karolinska Institutet, Sweden
Title: Mammography screening in a follow of patients from the nineties up to year 2010
Biography:
Dr Roland Sennerstam began his academic studies at the University of Stockholm. He completed a Bachelor of Arts Degree with Mathematics, Genetics and Chemistry. Soon thereafter he started to study medicine at the Karolinska Institute and became early linked to the Institute of Medical Cell Research and Genetics, Medical Nobel Institute. There he was involved in cell research under the leadership of professor Torbjörn Caspersson . Dr Sennerstam completed his thesis at the Department of Tumour Pathology, Karolinska Hospital and Institute, where professor Caspersson entered as retired professor. The title of his thesis was Cell Growth and Cell Division in relation to Embyonic Differentiation and Tumour Dedifferentiation. Dr Sennerstam has combined research with clinical work in various clinical positions in medicine and oncology from head of units to Staff Medical Officer. In research he has focused on the cell cycle and published in 1995 a cell cycle model based on the relation between the DNA-Division Cycle and the Cell Growth Cycle. Lately he has pointed out in two recent publications the importance of the tumor tetraploid position as an important intermediate position between low malignant diploid tumors to highly malignant aneuploid tumors. Dr Sennerstam now works as associate professor at the Department of Oncology and Pathology Karolinska Hospital and Karolinska Institutet.

Abstract:
Mammography screening has been proven to reduce mortality among breast cancer (BC) patients. These results are due to that screening discovers the tumors in a smaller size having not yet reached the higher level of malignancy potentials. The discussion that nowadays has become the current is whether we detect BC tumors at such a small size that they never will interfere with the patients health during their lifetimes. It is however hard to prove because the growth rates of the tumors vary much within broad limits for BC tumors. Furthermore some reports have found breast tumors in particular in the tumor stage-II A-B having a size between 10-20 mm to go into spontaneous regression. In this presentation we have made a follow up among 1660 patients diagnosed from 1991 to 1998 up to year 2010 registering tumor size at diagnosis, tumor stage, proliferation indeces, lymph node metastases, distant metastases appearing during the follow up period, Cyclin-A, Ki_67 and survival rates. We started focusing on following the change in mean tumors size per year from start of screening to elucidate how soon the percent of small tumors became substantial in comparison to the unscreened age groups. Mammography screening was introduces in our Stockholm Gotland county in 1989 for the age group 50-69 years by inviting women to screening every other year. The increase of small tumors in relation to the unscreened population appeared first in the years 1997 and 1998. The attendance to the mammography screening has been found to be high at our county up to 90%. The suggested regression of tumors of particular size and tumor stage was found to be due to a redistribution of size over time along with the progress of screening starting the first years to reduce tumors mainly in the size interval >20 mm and several years later an effect of screening upon the percent of increasing small tumors < 10 mm. This shift in tumor size over time increased the tumor size interval 10-20 mm and tumor stage-II A-B during 1992-1994 but in later years to be equalized in size until the increase in small tumor became obvious. In the screened age 50-69 the effect of screening was strongest in the age decade 60-69 years having reached up to five mammography screening since its introduction in 1989. We found in comparison to the unscreened age group < 50 years a significant reduction in proliferation index, Cyclin-A, Ki_67 and lymph node metastases The rate of distant metastases was reduced from 35.9% to 20.1% for the optimal screened age decade 60-69 years old The death rate was reduced from 35.4% to15,5% in a similar comparison.

Munir Abu-Helalah
Mutah University, Jordan
Title: Breast cancer screening in Jordan: Limitations and furture recommendations
Biography:
Dr Abu-Helalah completed his medical degree from Jordan University of Science and Technology (JUST) 2001. He moved in 2002 to the United Kingdon (UK) where completed a master degree in Public Health (MPH) from the University of Dundee in 2004 and a PhD in epidemiology and preventive medicine from the University of London in 2009. While he was in the UK, he worked as a Research Fellow in epidemiology and preventive Medicine at the St Bartholomew’s Hospital, London-UK, in 2007/2008. In 2009, he joined King Hussein Cancer Center in Jordan as a Senior Officer for the cancer control program. In 2011, he joined the National Guard Health affairs as an Assistant Professor of Epidemiology and Preventive Medicine. In February 2012, he returned to work in Jordan at the Faculty of Medicine, Mutah University. He was selected in 2013 as the regional director for Middle East and North Africa for the Global Center for Public Health and Disease Control, Ohio, USA. He also works as a consultant and technical expert for several regional and international organizations. Dr Abu-Helalah has special expertise and interest in chronic diseases control and prevention particularly cancer, diabetes, thyroid disorders, cardiovascular diseases, and smoking cessation. This is in addition to his experience in medical research and in applying evidence based medicine in clinical practice. He has conducted more than ten workshops in the above fields over the last two years and he has had important publications in these fields in peer-reviewed journals. On 9 April 2014, Dr Abu-Helalah was honoured by HRH Prince of Easter Region, KSA as the “Winner of the First place in the Prince of Easter Region Award for the Best Cancer Research in the Arab World” in the first round of this prize.

Abstract:
Introduction Breast cancer is the most common type of cancer in Jordan. Current efforts are focused on annual campaigns aimed at increasing awareness about breast cancer and encouraging women to conduct mammogram screening. In the absence of regular systematic screening for breast cancer in Jordan, there is a need to evaluate current mammography screening uptake and its predictors, assess women’s knowledge and attitudes towards breast cancer and screening mammograms and to identify barriers to this preventive service. Methods This cross-sectional study was conducted in six governorates in Jordan through face-to-face interviews on a random sample of women aged 40 to 69 years. Study questionnaire: A structured questionnaire was designed to cover the study objectives using the Health Belief Model. It was tested and piloted in study areas. Results A total of 507 participants with mean age of 46.8±7.8 years were interviewed. There was low participation rate in early detection of breast cancer practices. Breast self-examination, doctor examination and periodic mammography screening were reported by 34.9%, 16.8% and 8.6% of study participants, respectively. Additionally 3.8% underwent breast cancer screening at least once but not periodically, while 87.6% had never undergone mammography screening. Reported reasons for conducting the screening were: perceived benefit (50%); family history of breast cancer (23.1%); perceived severity (21.2%); and advice from friend or family member (5.8%). City residents have shown higher probability of undergoing mammogram than those who live in towns or villages. Results revealed negative perceptions and limited knowledge of study participants on breast cancer and breast cancer screening. The most commonly reported barriers for women who never underwent screening were: fear of results (63.8%); no support from surrounding environment (59.7); cost of the test (53.4%); and religious belief, i.e. Qadaa Wa Qadar (51.1%).

Alisher Agzamov
Kuwait Cancer Control Center, Kuwait
Title: The use of Robot Physician’s (RP) in unstable ICU Oncology patients
Biography:
Dr. Alisher Agzamov has completed his MD in 1981 from Tashkent University and postdoctoral PhD studies from Moscow University School of Medicine in 1991. During 1992 – 1998 He was a Senior Consultant Cardiac Anaesthesioligst of the Europen Cardiac Surgery Programme and Professor of Anaesthesiology of the University of Zambia and University Teaching Hospital, Lusaka, Zambia; From 1998 till up to date He is the Senior Consultant Anaesthesiologist fo the Department of Anaesthesiology & ICU, Kuwait Cancer Control Center ( KCCC). Ministry of Health, Kuwait City, Kuwait. He has published more than 550 papers in reputed journals and has been serving as an editorial International board member of reputable Anaesthesia and Intensive Care Journals. His main Scientic interest in fileds fo Anaesthesia and ICU Management Surgical and Medical ICU Oncology Patients. His using extensively Robots Physians in ICU Management of Oncology ICU patients.

Abstract:
BACKGROUND: The timely assessment and treatment of ICU Surgical and Medical Oncology patients is important for Oncology surgeons and Medical Oncologists and Intensivists. We hypothesized that the use of Robot Physician’s (RP) in ICU can improve ICU physician rapid response to unstable ICU Oncology patients. METHODS: This is a prospective study using a before-after, cohort-control design to test the effectiveness of RP. We have used RP to make multidisciplinary ICU rounds in the ICU and for Emergency cases. Data concerning several aspects of the RP interaction including the latency of the response, the problem being treated, the intervention that was ordered, and the type of information gathered using the RP were documented. The effect of RP on ICU length of stay and cost was assessed. RESULTS: The use of RP was associated with a reduction in latency of attending physician face-to-face response for routine and urgent pages compared to conventional care (RP: 10.2 +/- 3.3 minutes vs conventional: 220 +/- 80 minutes). The response latencies to Oncology Emergency (8.0 +/- 2.8 vs 150 +/- 55 minutes) and for Respiratory Failure (12 +/- 04 vs 110 +/- 45 minutes) were reduced (P < .001), as was the LOS for patients with AML (5 days) and ARDS (10 day). There was an increase in ICU occupancy by 20 % compared with the prerobot era, and there was an ICU cost savings of KD2.2 million attributable to the use of RP. CONCLUSION: The use of RP enabled rapid face-to-face ICU Intensivist - physician response to unstable ICU Oncology patients and resulted in decreased ICU cost and LOS.

Abdul Hameed
Lasbella University of Agriculture, Balochistan
Title: Various aspects, patterns and risk factors in breast cancer patients of Balochistan
Biography:
Dr. Abdul Hameed, did Ph.D in Biotechnology, title of his research was Mutational Analysis of Gene CHEK2 in Breast Cancer Patients from Balochistan. He is presently working as Assistant Professor, Faculty of Veterinary and Animal Sciences, Lasbella University of Agriculture, Water and Marine Sciences (LUAWMS), Uthal, Balochistan, Pakistan.

Abstract:
Purpose: Breast cancer is the commonest malignancy of females throughout the world with one million new cases each year. In Pakistan, the burden of breast cancer disease is high with late stage presentation being a common feature, more than half being stage III or stage IV. The objective of this study was to study various aspects, patterns and risk factors in breast cancer patients of Balochistan. Method: Present study was performed on 134 patients of breast cancer who were registered in CENAR. The patients were interviewed by providing a questionnaire. Informed consent was taken from all the patients who took part in this study after explanation of the study aims. Body mass index (BMI) was calculated and biopsy reports were obtained from patients files. All the cases were classified with respect to age, gender, ethnic group (Baloch, Pashtoon, Punjabi, Afghani, Hazara) BMI, cancer type, cancer grade, hormonal status, side of the cancer, fertility and marital status. Results: Out of 134 patients, the most common ethnic group was Pashtoon with a total of 42 and the common age group was 41-50 years with a total of 51. Invasive ductal carcinoma (IDC) was the most common type, accounting for in 128 patients (95.5%) followed by invasive lobular carcinoma (ILC). Conclusion: Pashtoon was the most common ethnic group, IDC was common type and most of the patients had an ER/PR positive hormonal status.

Mohammad Alam Saeed
Universiti Teknologi Malaysia, Malaysia
Title: Synthesis of aqueous suspension of iron oxide nanoparticles without any surface modification for MRI imaging and in-vivo drug delivery
Biography:
M A Saeed completed PhD work in Experimental High Enery Physics at BaBar Experiment (as a member of Babar Collaboration), Standord Linear Accelerator Center (SLAC) California, as a member of Albany High Energy Physics Group, University at Albany, NY, USA. Currentaly he is working as a faculty member at Physics department, Universiti Teknologi Malaysia (UTM). He has contributed more than 450 papers in reputed journals (Impact Factor) and has been serving as an reviewer as well as a member of editorial board of journal. His h-Index is more than 58.

Abstract:
This study describes a very simple method to synthesize aqueous suspension of iron oxide nanoparticles (IONPs) Fe3O4 that can be used for an anticancer drug delivery agent and Magnetic resonance imaging (MRI) contras agent. The work aims to synthesize aqueous suspension of iron oxide nanoparticles (Fe3O4) without any surface modification and to load with anticancer drug. The aqueous suspension of IONPs was synthesized by a reformed version of co-precipitation method while drug was loaded by rotary shaker and the characterization of resultant particles were carried out by XRD, EDS, TEM, VSM, FTIR, UV-vis. Peaks of XRD indicate that the particles are magnetite with an average diameter of 8 nm determined by TEM. The magnetic properties of the particles (loaded & unloaded) analyzed by VSM at room temperature indicate that particles are super-paramagnetic. The nanoparticles of this size and magnetic properties are believed to be excellent for targeting a cancerous tumor and for MRI contras agent, where the water based suspension of IONPs may be an option for in-vivo drug delivery.

Dean G. Tang
The University of Texas, USA
Title: Prostate cancer stem cells: Molecular regulation and clinical relevance
Biography:
Dr. Dean Tang is currently a professor in the Department of Epigenetics & Molecular Carcinogenesis at The University of Texas MD Anderson Cancer Center. He is also an adjunct professor in the College of Pharmacy, University of Texas at Austin. He obtained Ph.D. in cancer biology in 1994 at Wayne State, and joined the MD Anderson Cancer Center in 2000. As an expert with national and international recognition, He has worked on cancer research for over 30 years with >130 publications, many of which are in top-tier peer reviewed journals such as Cell, Science, Nature Medicine, Cell Stem Cell, Cancer Research, PNAS, and Oncogene. Dr. Tang’s research has been continuously funded by the National Institutes of Health (NIH), Department of Defense (DOD), American Cancer Society (ACS), Cancer Prevention and Research Institute of Texas (CPRIT), and many other agencies.

Abstract:
Most human tumors harbor self-renewing stem cell-like cancer cells functionally termed cancer stem cells or CSCs. There is strong evidence that CSCs are relatively quiescent and intrinsically resistant to stand-of-care anti-cancer therapies. Our lab has been employing prostate cancer as a model to elucidate the basic principles that govern CSC development. Our work (2-8) has revealed that human prostate CSCs (PCSCs) largely reside in the undifferentiated (i.e., PSA-/lo) PCa cell population, and are intrinsically resistant to androgen-deprivation therapy as well as chemotherapeutic drugs. The PSA-/lo PCSC pool is heterogeneous containing many subsets of more tumorigenic cells. Unbiased miRNA library screenings have uncovered multiple tumor-suppressive microRNAs, including miR-34a (5), let-7 (8), miR-128 (9), and miR-141 in different subpopulations of PCSCs. Systemic delivery of some of these miRNAs inhibited tumor regeneration as well as metastasis. These results suggest that several key tumor-suppressive miRNAs are coordinately downregulated in CSCs to regulate their biological properties and these tumor-suppressive miRNAs can be explored as novel replacement therapeutics targeting CSCs (5).

Azzam Falak
Mohammed V University, Morocco
Title: Ion proton next-generationsequencingfor identificationof clinically relevent mutationsin moroccan colorectal cancer cases
Biography:
Falak AZZAMwas born in Rabat, Morocco, in 1987. She is a Ph.d student on Onco-genetics and Epigenetics at Mohammed V University Faculty of Sciences of Rabat, Morocco. She got her bachelor and master degree on biology and Biotechnology at the same university. Miss Falak Azzam animated several seminars on molecular Biology and new generation sequencing. In addition, she is a regular contributor on Onco-genetics research with different national laboratory in Morocco. She presented her research in many international conference on Onco-genetics and Epi-genetics.

Abstract:
The identification of gene variants plays an important role in the diagnosis of genetic diseases. In effect, diagnostic laboratories are confronted with new challenges: costs, turn- around-time and small amount of input DNA for testingwillincreasewith the number of tests performed on a sample using semi conductor sequencing. As other solid tumors, colorectal cancer (CRC) is a genomic disorder in which various types of molecular alterations (MA), such as point mutations, genomic re-arrangements, gene fusions, or chromosomal copy number alterations, can contribute to the initiation and progression of the disease.The aim of this study is to identify mutation variants from CRC Moroccan patients using massive-parallel sequencing for clinical analysis. Methods:DNAsampleswere isolated from80 solid tumors FFPE tissue biopsy specimens using the MagMaxTMFFPE DNA Isolation kit (Invitrogen™, Thermo Fisher Scientific). Ten ng of sample were processed using the Ion AmpliSeq™ Colon and Lung panel v2 developed by Onco Network Consortium targeting 87 hotspotregionsin 22 genes that are of clinical interest for colorectal and lung cancer following the Ion AmpliSeq™ Library Kit ™ (Ion Torrent™, Thermo Fisher Scientific). After emulsion PCR, spheres were loaded on Ion PI™ Chip v2 for sequencing using Ion Proton system. Results were analyzed using the Ion Reporter™ Software. Results: The primary results analysis of New Generation Sequencing testing, shown 81% were pre-tested for KRAS. The most frequent currently non-actionable MAs were identified in TP53 and APC. The majority of cases harbored ≥1 actionable MAsand the most commonly are KRAS, BRAF, PIK3CA, SMAD 4 and FBX7. Actionable MAs characterized by gene amplifications were detected in FGFR1, EGFR, and MET. Conclusions: For the most part, the availability of fast bench top sequencers such as the Ion Proton (Semi conductor sequencing) show that approachto stratify colon and lung cancer patients is feasible in a clinical setting. Results point to the potential of KRAS, BRAF, NRAS, ERBB2 and EGFR targeted therapies for a significant subset of patients.

Xiaofeng Dai
Jiangnan University, China
Title: WDR5 over-expression is prognostic of poor breast cancer outcome
Biography:
Dr. Xiaofeng Dai, Ph.D. (Bioinformatics, Quantitative Methods in Economics), now is an Associate Professor at the National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, JiangNan University, China. She got her B.Sc. in Biology, M.Sc. in Biochemistry & Molecular Biology, and M.Sc. in Bioinformatics. She received her Ph.D. in Computational System Biology at Tampere University of Technology, Finland, and Ph.D. in Quantitative Methods in Economics at Aalto University, Finland. She conducted her postdoctoral researches at the Department of Obstetrics and Gynecology in Helsinki University and Institute for Molecular Medicine Finland, where she started her career in cancer. Dr. Dai got the “Chinese Government Award for Outstanding Self-financed Students Abroad” in 2009, “Best Paper Award” from “the international conference BIOTECHNO”, Bucharest, 2009, and received a research financial support of 800000¥ from “National Natural Science Foundation of China” in 2014. Currently Dr. Dai’ researches focus on breast cancer subtyping and heterogeneity, cancer stem cell signaling network and its association with immune response in basal breast cancer. She has published 15 papers as the first author in reputed journals.

Abstract:
WDR5 is a core component of the human mixed lineage leukemia-2 complex, which plays central roles in ER positive tumour cells and is a major driver of androgen-dependent prostate cancer cell proliferation. Given the similarities between breast and prostate cancers, we explore the potential prognostic value of WDR5 gene expression on breast cancer survival. Our findings reveal that WDR5 over-expression is associated with poor breast cancer clinical outcome in three gene expression data sets and BreastMark. The eQTL analysis reveals 40 trans-eQTL SNPs which are mapped to 38 genes that are enriched with “cell death and survival, cell cycle, cancer” signallings. Knocking down WDR5 in MCF7 dramatically decreases cell viability, but does not alter tumour cell response to doxorubicin. Our study reveals the prognostic value of WDR5 expression in breast cancer which is under long-range regulation of genes involved in cell cycle and carcinogenesis, and anthracycline could be coupled with treatments targeting WDR5 once such a regimen is available.

Bashair Ali Al-Zahrani
King Abdullah Medical City, Saudi Arabia
Title: Metallic stent insertion for palliation of esophageal cancer: Single center experience from Saudi Arabia
Biography:
Bashair is an Intern at Umm Alqura university ،medical college .Interesting in research , She did research in epidemiology of gastrointestinal cancer .The role of black seed and honey in relieving the degree of symptoms associated of breast cancer. She participated in 3rd students scientific research forum.

Abstract:
Background: Expandable metal stents are increasingly used as a non-surgical alternative for palliation of advance colorectal cancer .However, most data on this originates from western world where the incidence is low. There is scarcity of data from high incidence region like Asia. The aim of this study is to evaluate the efficacy of self expanding metallic stents (SEMS) in inoperable colorectal cancers in the western region of Saudi Arabia. Methods: This is a retrospective review of SEMS placed in a single tertiary referral hospital for histological proven inoperable colorectal cancer from 2012 till 2015. Apart, from demographics data the success of stent placement, complication, re-intervention and mortality were collected. Results: 23 SEMS were placed in 23patients, and all were placed for palliation of obstruction. Median age of patients was 52 years (range 39-84) with 56.5% (13) of the colorectal cancer involving the sigmoid and39% (9) involving Rectum and4..3%(1) involving the splenic flexure. The SEMS was placed successfully in all the cases with symptomatic improvement in obstruction. There was stent related complication in form of4.3%(1)migration , 8.7%(2) perforation. However, .The mortality was 39% (9) with a median survival of 90 days (range 30 – 365). no significant difference in re-intervention rates (p = 0.05) of tumor in-growth or migration. Chemo and/or radiotherapy were given to 73.9% (17) of the patients without any significant benefit on survival (p =.48). Conclusion: SEMS was effective in palliating obstruction in inoperable colorectal cancer without major complications. The rates of tumor in-growth and migration were comparable to other studies and SEMS provided long term palliation

Kamis Gaballah
Kings College London, UK
Title: Novel therapies for oral cancer and precancer
Biography:
Kamis Gaballah is currently Associate Professor in Oral and Maxillofacial Surgery at Ajman University, UAE. Since graduationon 1993 Dr. Gaballah showed a great interest in the field of Oral and Maxillofacial Surgery for which he was extensively trained andpracticed in many countries including Libya, Egypt, Ireland, United Kingdom, Norway and UAE. During his surgical training he wasawarded with the fellowship of the Royal College of Surgeons in both England and Ireland . Dr. Gaballah was also formally trainedin Oral Medicine at the Trinity College Dublin of the Ireland. Up on his completion of the professional surgical training andpracticing for several years in the field, he has joined the University of London for intensive and novel research on the cancer genetherapy. His research work focused on the use of the tissue engineering, virus-mediated gene therapy for head and neck cancer andoral potentially malignant lesions and also the inhibition of angiogenesis to prevent the recurrence of head and neck cancer insurgically treated patients. He has published his novel research outcome in highly-ranked journals and his papers were cited bysignificant number of authors all over the world. His academic interest was expanded to include the higher education teaching andlearning for which he was formally trained at the University of London and warded with membership of the UK council of highereducation before joining the King’s College London as a Clinical Lecturer in Oral Surgery.

Abstract:
Head and neck cancer is the eighth most common cause of cancer death worldwide with nearlyhalf million new cases are diagnosed annually. The vast majority of this disease affect the oralcavity in form of squamous cell carcinoma. Despite all advances in the epidemiological studies,identification and verification of potential risk factors, diagnostic technologies and improvement ofsurgical and radiotherapy techniques, the survival rate of patient with head and neck cancer didnot witnesses a substantial improvement over the last 5 decades. The latter is reflected in the factthat Approximately 50-60% of patients have local disease recurrence within 2 years and 20-30% ofpatients develop metastatic disease. This made this cancer being the subject of intensive researchto establish alternative effective treatment modalities. In this talk the speaker will share withaudiences his and others research experience to develop novel therapies including targetedoncolytic viruses and anti-angiogenesis. These attempts were not limited to the treatment ofestablished lesion but also focused in prevention of emergence new lesions and to control loco-regional recurrence by tackling the residual disease.