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

Scientific Programme(Day 2 : Aug-28-2015)

Cancer Cell Biology
Session Chair:
Yoshiaki Omura
New York Medical College, USA


Session Introduction

Yoshiaki Omura
New York Medical College, USA
Title: New method of detecting various cancers & their biochemical information from ECGs was found. In addition to information on the heart, we can also screen cancers and evaluate the effects of any cancer treatments
Biography:
Professor Yoshiaki Omura received Oncological Residency Training at Cancer Institute of Columbia University & Doctor of Science Degree through research on Pharmaco-Electro Physiology of Single Cardiac Cells in Vivo and in Vitro from Columbia University. He published over 260 original research articles and 8 books. He is currently 1) Adjunct Prof. of Family & Community Medicine, New York Medical College; 2) Director of Medical Research, Heart Disease Research Foundation, New York; 3) President and Prof. of International College of Acupuncture and Electro-Therapeutics, New York; 4) Editor in Chief, Acupuncture & Electro-Therapeutics Research, International Journal of Integrative Medicine,which is indexed by 17 major international Indexing Periodicals. Currently he is also 5) Executive Editor of Journal of Integrative Oncology. Formerly he was also Adjunct Prof. or Visiting Prof. in universities in USA, France, Italy, Ukraine, Japan& China. His main research is on "Non-invasive, safe, quick diagnostic method & safe effective treatment of cancer & other intractable medical problems" and he developed several diagnostic methods & safe effective treatment of cancers which saved many lives.

Abstract:
Introduction: During the past 10 years, the author successfully detected biochemical changes, bacterial and viral infections, and identifying the exact location of the infections of different part of the heart by ECGs. Similar findings were found at different parts of the brain by EEGs. Recently the author found that using electrocardiogram not only information on the different part of the heart but also can detect various cancers existing in the rest of the body. Method: Cancers existing at outside of the heart from rest of the body were able to be detected from part of QRS complex as well as rising part of T-wave of every recorded 12 lead ECGs by detecting maximum Electromagnetic Field (EMF) Resonance Phenomenon between 2 identical molecules with same amount using simple method which received a U.S. patent in 1993. From recorded ECG, EMF Resonance Phenomenon between specific cancer microscope tissue slides and ECG were only detected from rapidly changing part of QRS complexes of ECGs& a part of rising part of T-waves where information on cancer exists.Results:Strong EMF resonance was found between not only rapidly changing dV/dt at QRS complex of ECGs, but also the author found even at rising part of the T-wave where change of dV/dt is insignificantly small. The author was able to detect cancer of various organs including lung, esophagus, breast, stomach, colon, uterus, ovary, prostate gland, common bone marrow related malignancies such as Hodgkins Lymphoma, Non Hodgkins Lymphoma, Multiple Myeloma as well as Leukemia. In addition the author was also able to find when the patient has more than one different cancer at different parts of the body. In addition, most of medicine taken within 8-10 hours before taking ECG can be detected from part of QRS complex & rising part of T-waves. Discussion: Thus, by comparing the same lead of ECGs before and after any treatment, the therapeutic effect of specific cancers can be evaluated. In addition, if electrocardiogram is taken periodically we can find approximately when cancer information starts appearing in the electrocardiogram. Maximum information from cancer can be found in QRS complex where dV/dt is relatively large. This new concept and method can be applied any recorded ECGs for detection and screening of the cancer. Thus, electrocardiogram can provide not only information on the heart but also can provide any single cancer or multiple cancers which exist in the outside of the heart of the same individual.

Guang Zhu
The Hong Kong University of Science and Technology, China
Title: Mechanistic study of human proteins that regulate cell proliferation and differentiation
Biography:
Dr. Guang ZHU is a Professor of Division of Life Science, The Hong Kong University of Science and Technology. He obtained his BSc and MSc in physics. He studied for his Ph.D degree at University of Maryland and National Institutes of Health, USA, specialized in biomolecular NMR spectroscopy. Currently Dr. Guang ZHU’s research focuses on structure-functional study of human proteins in DNA replication. Studies on the molecular mechanisms of proteins involved in DNA replication provide basis for structure-based drug design against cancer. He has published more than 78 peer-reviewed reports. He has served on the editorial boards of International Journal of Spectroscopy and Chinese Journal of Magnetic Resonance.

Abstract:
Proper organ development requires the precise regulation of both the total number of cells (cell proliferation) and the types of cells (cell differentiation). During cell proliferation, Cdt1 mediated loading of DNA helicase (Mcm2-7) to replication origins is required for DNA replication. And Hox gene activation is necessary for embryonic cell differentiation. It has been shown that these two processes are linked through the cell cycle-regulator Geminin and the homeodomain-containing transcription factors Hox. To understand the molecular mechanism involved, we determined the solution structures of Geminin-Hox, Orc6-DNA, G-quadruplex and Cdt1-Mcm6 complexes by nuclear magnetic resonance (NMR) spectroscopy and conducted biochemical study to delineate the structural basis of this mutual regulation. In addition, we found that histone H4-K20 methyltransferase SET8 is a new cell-cycle regulator and plays an important role in the developmental program of metazoans. (These works are supported by RGC, NSFC, and AoE/M-06/08)

Domenico Mastrangelo
University of Siena, Italy
Title: High doses of sodium ascorbate as a new frontier in Ocular Oncology
Biography:
Domenico Mastrangelo, MD has completed hid degree in Medicine and Surgery on October 26, 1979, at the age of 24 . He then specialized in hematology (1983), Oncology (1987), Clinical Pharmacology (1990), Ophthalmology (2010). His experience is in the fields of hematological/oncological epidemiology and laboratory, cell biology, molecular biology. He published more than 100 papers in reputed scientific journals, including chapters in highly reputed scientific books, in the fields of ocular oncology and clinical oncology.

Abstract:
An improved understanding of the role of oxidative stress in cancer, has recently led to a completely new approach to the systemic therapy of cancer, and modulators of the oxidative balance, such as sodium ascorbate (ASC), have already entered advanced phases of preclinical and clinical development. As demonstrated in two recent papers published by our group, both retinoblastoma (Y79) and uveal melanoma (C918, and OCM1) cell lines, are extremely sensitive to high concentrations of sodium ascorbate, in vitro. In particular, retinoblastoma (Y79) cell lines shows a reduction of viability of up to 90%, in vitro, when exposed to increasing concentrations of sodium ascorbate, for one hour. The same apply to both the uveal melanoma cell lines tested in these experiments, thus indicating a marked sensitivity of uveal melanoma to high doses of ascorbate. Given the lack of toxicity of high doses of sodium ascorbate for normal cells, the potential toxicity of chemotherapeutic approaches in retinoblastoma, and the lack of a systemic treatment for uveal melanoma, the Authors suggest that the results of their laboratory experiments be quickly translated into routine approaches to the systemic treatment of ocular tumors, including retinoblastoma and uveal melanoma.

Arun Dharmarajan
Curtin University, Australia
Title: Targeting cancer stem cells Via Wnt/Beta-Catenin antagonist, secreted frizzled related protein-4 (SFRP4)
Biography:
Arun Dharmarajan was educated at the University of Madras, India, and the University of Western Australia, Perth, Australia (PhD;1985). He did his postdoctoral training at Johns Hopkins University School of Medicine, Baltimore, USA. On completion of his postdoctoral training, he was appointed as an instructor in the department of Gynecology and Obstetrics and subsequently was promoted to Assistant and Associate Professor in the same department. Professor Dharmarajan, moved back to UWA late 1994 having spent 10 years at Johns Hopkins, Baltimore USA. He has been a Professor in the School of Anatomy and Human Biology, University of Western Australia, Perth since 2001. Currently Professor Dharmarajan is at the Faculty of Health Sciences in a role as a Co-ordinator of South Asia Research Initiatives for the School of Biomedical Sciences. Professor Dharmarajan has carried out pioneering studies in apoptosis (Physiological Cell Death) and cell signaling mechanisms in several Endocrine Organs such as corpus luteum, placenta, uterus, and ovary etc. His laboratory has cloned several apoptosis-associated genes. In late 1990, Professor Dharmarajan along with Professor Bob Friis, University of Bern, Switzerland discovered Secreted Frizzled Related Protein-4 (sFRP4), a wnt anatagonist. Professor Dharmarajan’s group has published extensively on the role of sFRP4 and apoptosis and cancer and more recently its role in blocking angiogenesis. He has US, India and Australia patent for this work. His group also has a shown that sFRP4 can cause the cancerous ovarian cells to become more sensitive to chemotherapy treatments in laboratory studies. Professor Dharmarajan’s current research interest is cancer stem cells and ways to specifically target cancer stem cells. Professor Dharmarajan’s international standing as a scientist is evidenced by his publication record, his experience as a student supervisor and mentor, his extensive collaborations both overseas and within Australia, and his invited attendance at over 90 international/national meetings. Professor Dharmarajan has published over 125 refereed papers/reviews and book chapters. He has supervised more than 80 Hons, M.Sc and PhD students. Professor Dharmarajan has received numerous awards and invitations to present his work both at national and international conferences

Abstract:
Malignant tumours have a highly tumourigenic subpopulation, termed cancer stem cells (CSCs), which drive neoplastic formation and proliferation. Unlike the bulk of tumour cells, CSCs are chemo- and radio-resistant and hence are the major reason for treatment failure. CSCs are genetically diverse and their frequency and phenotype varies between tumour types and during the course of disease. The existence of CSCs has been confirmed in many tumour types including gliomas, breast, lung, prostate, head and neck, and colon cancers. Wnt/β-catenin signalling plays a key role in the proliferation of tumour cells. Frizzled-4, a member of the Wnt signaling family, governs both the stemness and invasiveness of glioma stem cells. We recently demonstrated that a naturally occurring Wnt antagonist, secreted frizzled-related protein 4 (sFRP4), was able to chemosensitize and inhibit the growth of glioma and head and neck stem cells by reducing their capacity for self-renewal and by inducing differentiation. We have since investigated whether sFRP4 would have a similar effect on breast, prostate, mesothelioma, and ovary. Our data demonstrated a synergistic effect when sFRP4 was used in combination with clinically used therapeutics after 24 h of treatment. Our exciting results have driven us to explore the possible use of this naturally occurring protein as an adjunct to normal chemotherapeutic treatment of cancer.

Ammu K Radhakrishnan
International Medical University, Malaysia
Title: Delta- and gamma-tocotrienols induce apoptosis in K562 human chronic myeloid leukaemia cells through intrinsic and extrinsic pathways
Biography:
Ammu K Radhakrishnan obtained a First Class Honours Bachelor of Science degree in Biochemistry from the University of Malaya, Kuala Lumpur. Following this, she was appointed as a research fellow at the Department of Biochemistry, Faculty of Medicine, University of Malaya for two-years. During this fellowship, she pursued her post-graduate studies and obtained her Master of Science Degree. In 1989, she was awarded the prestigious Shell-Cambridge Commonwealth Trust Scholarship and the British ORS Award to read for her Doctor of Philosophy at the Department of Pathology, University of Cambridge, Britain. After obtaining her PhD, she pursued post-doctoral research work at the Sir William Dunn School of Pathology, University of Oxford, Britain. Her area of specialisation is therapeutic immunology. She joined the International Medical College (IMC), now the International Medical University (IMU) in 1997 as a lecturer. Currently, she is a Professor of Pathology at this university. Ammu is involved in teaching and is an avid researcher. Her research areas include immune regulation and modulations in cancer (breast cancer and leukaemia), development of immune-based therapeutics as well as identification of novel natural products against cancer, genomics of autoimmune disease and role of nutrition in immunity. She has successfully supervised many post-graduate students at the doctoral and masters levels as well as final year under-graduate research students. Ammu has many publications in Tier 1 and 2 ISI and peer-reviewed indexed journals. She is a Fellow of the Cambridge Commonwealth Trust and the Cambridge Philosophical Society.

Abstract:
Introduction:Vitamin E are fat soluble micronutrients that have important physiological functions. The vitamin E family consist of two main sub-families, tocopherols and tocotrienols (T3); each with four isoforms (, ,  and ). Among the tocotrienols the delta- (T3) and gamma- (T3) isoforms is reported to possess exceptional anticancer activities using various cell-based and animal models. The K562 cells are derived from a chronic myeloid leukaemia (CML) patient. To date, the anti-cancer effects of T3 or T3 have not been well characterised in leukemic cells. Methods: The anti-cancer effectsof palm oil-based T3 andT3 were evaluated on the K562 cells using two cell proliferation assays (MTT and BrDU). For gene expression studies, the K562 cells were cultured in the presence of T3 of T3 at their respective IC50 values for 72 hours. Then, RNA was extracted from these cells and purified. The RNA was analysed using a commercial quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) arrays to identify differentially regulated genes involved in apoptosis in the K562 cells. Some of the differentially regulated genes were selected for validation by real-time PCR and ELISA. Results:The results from the cell proliferation assays showed that T3 and T3exerted dose- and time-dependent anti-proliferative effects on the K562 cells. However, we found that T3 was more cytotoxic compared to T3 [p<0.05]. The T3 and T3 isoforms differentially regulated 24 genes in the human apoptosis array. Most of the genes regulated by tocotrienols were from the (i) BCL-2 family, (ii) CARD domain members, (iii) Caspases, (iv) GADD family, (v) P53 family and (vi) TNF receptor and (vii) the TNFR ligand super-families. The data from the real-time PCR and protein analysis correlated very closely with the gene expression of these proteins. Conclusion: Palm oil based T3 and T3exert potent anti-cancer effectson K562 cells through regulation of a number of genes that are involved in apoptosis.

Rami I. Aqeilan
Ohio State University, USA
Title: Metabolic reprograming in cancer
Biography:
Born in East Jerusalem, Dr. Rami Aqeilan is an Associate Professor at The Lautenberg Center for Immunology and Cancer Research, Hebrew University-Hadassah Medical School of Jerusalem. He began his academic career at the University of Jordan where he received a B.Sc. in biology, followed by a M.Sc. and Ph.D. from the Hebrew University-Hadassah Medical School. Following his graduation, he started a post-doctoral fellowship at the laboratory of Dr. Carlo M. Croce in the Kimmel Cancer Center at Thomas Jefferson University, Philadelphia-Pennsylvania working on a newly discovered gene named the WW domain-containing oxidoreductase (WWOX). During his post-doctoral tenure, Dr. Aqeilan identified WWOX as a tumor suppressor gene and characterized its biochemical interacting ability with several partners that mediate WWOX tumor suppressor function. In 2005 assumed his first faculty position as a Research Assistant Professor in the Department of Molecular Virology, Immunology and Medical Genetics at the Comprehensive Cancer Center in Ohio State University (Columbus, Ohio). In 2008 he joined the Medicine faculty at The Hebrew University of Jerusalem. In 2010, he founded the Palestinian Forum for Medical Research (PFMR). Since late 2013, He serves as a research consultant for Augusta Victoria Hospital (AVH) in East Jerusalem. Dr. Aqeilan has had a long-term interest in the genetic and molecular basis of cancer development. As a cancer biologist, he believed that the best approach against disease is to obtain a better understanding of its molecular basis. Therefore, the ultimate goal of his research is to discover the genes and to elucidate the pathways that represent targets for the development of rational, specific and effective therapeutic approaches to cancer. His research has taken advantage of mouse models, tissue culture and human clinical samples. Most recently, Dr. Aqeilan has been studying the early events contributing to breast cancer and pediatric osteosarcoma initiation and progression. His main focus is to study genomic instability and metabolic reprograming in cancer development. Dr. Aqeilan serves as an editorial board member of the Cell Death and Disease, Journal of Cellular Biochemistry, Frontiers in Genetics, and American Journal of Cancer Research and has served as an external reviewer for many peer-reviewed journals including Proceedings of the National Academy of Sciences-USA, Cancer Research and more. He has authored or co-authored more than 85 original articles. He is the winner of several awards among which is the Kimmel Award for Cancer Research, Ma’of Fellowship and the Bergman Memorial Research Award. He is the president of the Palestinian Forum for Medical Research (PFMR) and an active member of the American Association for Cancer Research (AACR), European Association for Cancer Research (EACR), and has spoken nationally and internationally about his own research.

Abstract:
During malignant transformation cancer cells undergo significant metabolic changes. The change in glucose metabolism is the best-known example of metabolic reprogramming in cancer cells. Under aerobic conditions, normal cells process glucose, first to pyruvate via glycolysis in the cytosol and thereafter to carbon dioxide in the mitochondria yielding ATP; under anaerobic conditions however, glycolysis is favored and relatively little pyruvate is dispatched to oxygen-consuming mitochondria. In cancer cells, the main source of cellular energy is glycolysis, even in the presence of abundant oxygen. This shift to aerobic glycolysis or “Warburg effect” is a hallmark of malignant cells. The reliance of cancer cells on aerobic glycolysis for ATP production results in high glucose consumption (to compensate for the low efficiency of glycolysis). Identifying the molecular mechanisms responsible for the shift to aerobic glycolysis is important for understanding the basic biology of malignant transformation and for designing targeted therapies. The hypoxia-inducible factor 1 (HIF1α) is a transcription factor that regulates many genes responsible for this switch. We recently demonstratethat loss of tumor suppressor WWOX (WW domain-containing oxidoreductase) is associated with enhanced level and function of HIF1α resulting in rewiring of cell metabolism and cancer transformation. Indeed, WWOX deficiency is associated with enhanced glycolysis and diminished mitochondrial respiration, conditions resembling the ‘Warburg effect’. Importantly, WWOX expression is inversely correlated with that of glucose transporter 1 (GLUT1), a direct target of HIF1α, in human breast cancer patients. Our study provides evidence that the tumor suppressor WWOX acts as a safeguard mechanism to inhibit HIF1α activity under normoxic conditions, to guarantee glucose flux into mitochondria and TCA cycle hence preventing the Warburg effect and contributing to tumor suppression.

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 completed his Ph.D. from Bose Institute, India (1989). He did his post-doctoral research in US including NIH from 1989-98. Currently, he is Scientist-G (Professor) at NCCS, India. He has received several awards including FARE, NIH; National Bioscience Award; Bhatnagar Prize; International Awards from Greece and USA. He is Fellow of National Academy of Sciences and Indian Academy of Sciences. He has published 73 papers including Nature Medicine, Science, PNAS, Cancer Research, JBC, TCB, Oncogene etc and one US patent. He serves as Editorial Board Member of Current Molecular Medicine, Molecular Medicine Reports, American Journal of Cancer Research and Associate Editor of JCMT and Molecular Cancer.

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.

Domenico Mastrangelo
University of Siena, Italy
Title: High doses of ascorbate in acute myeloid leukemia: New hopes from in vitro studies
Biography:
Domenico Mastrangelo, MD has completed hid degree in Medicine and Surgery on October 26, 1979, at the age of 24 . He then specialized in hematology (1983), Oncology (1987), Clinical Pharmacology (1990), Ophthalmology (2010). His experience is in the fields of hematological/oncological epidemiology and laboratory, cell biology, molecular biology. He published more than 100 papers in reputed scientific journals, including chapters in highly reputed scientific books, in the fields of ocular oncology and clinical oncology.

Abstract:
Acute Myeloid Leukemia (AML) is a heterogeneous group of diseases, for what concerns cell morphology, immunophenotype, cytogenetics, gene expression and treatment outcome. Although with modern chemotherapeutic regimes, a considerable number of patients achieve the first hematological remission, and are possibily cured, AML still represent a serious health problem, and new therapeutic approache are highly desirable. In a recent paper, we have been able to demonstrate that HL60 cell lines are extremely sensitive to concentrations of sodium ascorbate (ASC) ranging from 1 to 3 mM. The present investigation has been undertaken in order to investigate the role of high doses of ASC in inducing apoptosis/necrosis in cancer cells belonging the myeloid lineage (Nb4, K562, U937) in vitro. The results of this study indicate that esposing human myeloid cells to high doses of ascorbate (1 – 7 mM), in vitro, results in apoptosis/necrosis of the great majority of cells, within concentrations of ASC ranging from 1 to 5 mM. These results indicate that the whole myeloid lineage is sensitive to high doses of ASC and warrant further in vivo and clinical investigation on the role of high doses of ASC in the treatment of AML

Madhulika Singh
CSIR-Indian Institute of Toxicology Research, India
Title: Muc1 is a functional and targetable marker of cancer stem cells in human breast cancer cases
Biography:
Dr. Madhulika Singh completed her Ph.D. degree in year 2003 from Department of Zoology, Lucknow University (India). She accomplished her postdoctoral studies from CSIR-Indian Institute of Toxicology Research (CSIR-IITR, India) and started her career in cancer research. Presently she is working as Women Scientist (DST) at CSIR-IITR, India. So far she has published more than 30 original research papers in peer reviewed journals and presented at national and international conferences. Her current research interest embraces the role of breast cancer stem cells in cancer pathogenesis and drug resistance.

Abstract:
Mucin 1 (Muc1) is a secreted oncogenic mucin that is aberrantly overexpressed in breast cancers but its potential uses to target breast cancers stem cells (BCSCs) have not been explored. Here, we report that Muc1 expression may identify cells with characteristics of breast cancer stem/progenitor cells (BCSCs). Upon Muc1(+) selection, we have found rare subpopulation of undifferentiated cells expressing Muc1 in 70% BC tissue samples. These cells were growing indefinitely (~28 weeks) as mammospheres in serum-free cell culture medium and also shown high ALDH activity and Muc1, EpCAM, CD49f, and CD44+/CD24- expression in comparison to Muc1(-) subpopulations (p<0.05). Muc1(+)BCSCs give rise to ~3.8-fold larger number of colonies and were more tumorigenic in Nude mice as compared with Muc1(-) cells. These cells expressed high levels of peculiar gene signatures consisting of stem cell and drug resistance (p<0.05). Upon differentiation in serum containing media Muc1(+) BCSCs acquired the specific luminal lineage markers (Muc1, CK 8,18 and 19). Further, differentiated progenies was dedifferentiated into parental BCSCs subpopulations with significantly increased mammospheres formation capabilities suggesting bidirectional interconvertibility and high grade of cellular plasticity potential in Muc1(+) BCSCs (p<0.05). GO-201 (Muc1 inhibitor) depleted established tumor in vivo, but did not affected engraftment of Muc1(-) BCSCs. Our results establish that Muc1 is highly expressed in BCSCs and define the Muc1 subunit as a valid target for therapeutic eradication of BCSCs. Additionally; dedifferentiation assay reflects the process of cancer relapse via conversion of non cancer stem cells to cancer stem cells under favourable tumour microenvironments.

Cancer Therapies
& Clinical Cancer Research
& Cancer Management and Prevention
Session Chair:
Maciej Jóźwik
Medical University of Białystok, Poland


Session Co-Chair:
Arig Ibrahim-Hashim
H. Lee Moffitt Cancer Center and Research Institute, USA


Session Introduction

Maciej Jóźwik
Medical University of Białystok, Poland
Title: Levonorgestrel-releasing intrauterine systems for the primary prevention of endometrial adenocarcinoma and other malignancies in women
Biography:
Dr. Maciej Jóźwik, MD, PhD, is a full Professor of Obstetrics-Gynecology at the Department of Gynecology and Gynecologic Oncology, Medical University of Białystok, Białystok, Poland. He has completed his PhD at the age of 30 years from the Medical University of Białystok. In 1994, he publicly defended a thesis awarding him the title of Foreign Assistant of the University of Montpellier, France. Later, he was a long-term Postdoctoral Research Fellow at the University of Colorado Denver, CO, USA. He has published more than 40 papers in reputed journals, has 14 review articles and chapters in text books, and has been serving as an editorial board member of several international journals and a grant reviewer for the European Commission.

Abstract:
The wide-spread use of the levonorgestrel-releasing intrauterine system (LNG-IUS) has just reached 25 years of duration and the scientific data on its long-term efficiency has become available. The subject was explored systematically using computed search of electronic medical databases supplemented with hand-searching and cross-referencing. Quality of the evidence was assessed using the Canadian Task Force on Preventive Health Care ranking. The vast majority of the data referred to Mirena® (Bayer). When released into the uterine cavity, LNG exerts mainly paracrine action via the topical suppression of the endometrium due to epithelial thinning, glandular atrophy and pseudodecidual transformation. Yet, molecular biology studies identified a variety of important antiproliferative mechanisms in the endometrium evoked by the LNG-IUS, such as a substantial down-regulation of sex hormone receptors, decreased proliferation and a strong proapoptotic effect, coupled with the suppression of IGF-I mRNA and upregulation of IGFBP-1 expression. Consequently, the risk of developing endometrial adenocarcinoma in Mirena® users is lowered by as much as 50% compared with the general population risk. Importantly, this reduction is pronounced with continued use. A small proportion of the released LNG enters the bloodstream and thus the extra-endometrial actions are endocrine. LNG promotes differentiation, cell cycle arrest, and apoptosis, and reduces inflammation and the invasion associated with metastasis. A pooled analysis of observations from over 20 000 women indicated the protective effect of Mirena® on the prevalence not only of cervical adenocarcinoma, but also squamous cell carcinoma. Moreover, the use of the LNG-IUS at reproductive age was found to significantly decrease the risk of developing ovarian (by 40%), pancreatic (by 50%), and lung (by 32%) carcinomas at later age. In contrast, in one study, the risk for breast carcinoma increased by 19%, whereas a number of other studies failed to demonstrate such a hazard. In the current era of the increased occurrence of hormone-dependent carcinomas at earlier age, a broad application of hormone-releasing intrauterine devices may become a particularly important component of primary prevention of malignancies in women. Obese and overweight patients seem perfect candidates for such an intervention.

Arig Ibrahim-Hashim
H. Lee Moffitt Cancer Center and Research Institute, USA
Title: Targeting tumor microenvironment acidity to enhance immunotherapy
Biography:
Dr. Ibrahim- Hashim has completed her Medical degree from Comenius University in Bratislava, Slovakia. She was trained in the USA for over 10 years as a Cancer Biologist, and immunologist. She serves as the coordinator of the tumor microenvironment group at the Department of Cancer Imaging and Metabolism at The Moffitt Cancer Center in Tampa, Florida.She has over 20 peer-reviewed publications in addition to oral presentations at international conferences, chapter book and two patents. She is a member of American Association for Cancer Research (AACR), and a member of Women in Cancer Research.

Abstract:
The extracellular pH of solid tumors is acidic due to a combination of high rates of lactic acid production (a consequence of fermentative glycolytic metabolism) and poor perfusion. This extracellular acidity has been shown to promote tumor progression and metastases. Importantly, we have developed a therapeutic strategy (buffer therapy) to specifically neutralize tumor acidity. Bicarbonate therapy has no effect on the growth of primary tumors in immunocompromised mice, or in immunocompetent mice inoculated with a weakly antigenic (B16) tumor. In contrast, we have observed reduced tumor growth of antigenic tumor xenografts in immunocompetent or transgenic (TRAMP) mice. We have investigated the effect of pH on anti-tumor immunity both in vitro and in vivo. In melanoma, we observed that tumor acidity inhibits antitumor immunity by preventing T-cell activation, promoting an M1 to M2 macrophage phenotype switch, and increased infiltration of myeloid-derived suppressor cells, MDSCs. In addition reversal of acidity with buffer therapy synergized with checkpoint blockade (anti-CTLA4 and anti-PD1) and adoptive T-cell therapy, which resulted in cures. Furthermore the growth of Panc02 in a PDAC model was inhibited with buffer monotherapy, which increased T cell infiltration in to tumors, decreased MDSCs in tumor and spleen, and decreased tumor weight when combined with a dendritic cell (DC) vaccine. Thus the low pH generated by tumors has a significant role in inhibiting general anti-tumor immune responses. Manipulating the micro-environmental acidity using buffers in combination with immunotherapy improve outcomes by promoting effective anti-tumor T cell activity and regression of established melanoma and pancreatic cancers.

Oliver Szasz
St. Istvan University, Hungary
Title: Immune-modulation of cancer by nanothermia
Biography:
Dr. Oliver Szasz is bioengineer, associate professor of Biotechnics Department of St. Istvan University (Hungary). He has over 40 published articles, owns several patents. He has essential contribution of inventing of nanothermia technology.

Abstract:
Introduction – Hyperthermia in oncology has a long but rather controversial history from the dawn of human medicine. Discovery of the electromagnetic heating had shown numerous advantages of hyperthermia in oncology, but despite of these it is far from the wide acceptance among professionals. The present hyperthermia trend in oncology focuses on the emerging nanotechnology. Our objective is to show a special nano-heating without artificial particles in the tumor, named nanothermia, and show its vaccination-like effect. Method – The nanothermia technology selects and heats the cluster of transmembrane proteins, the membrane rafts of the malignant cells. It is an impedance controlled capacitive coupling at 13.56 MHz carrier frequency with time-fractal modulation. The nano-heating mechanism is proven in silico, in vitro and in vivo experiments, evaluation histomorphologic and immunohystochemical methods. Results – Model-systems in silico and in vitro show heating effect which is similar to the artificially inserted and heated nano-particles in the tumor. The damage associated molecular pattern (DAMP) is observed during the apoptotic cell-death. The released HMGB1 calreticulin, HSP70 and HSP90 in the extracellular matrix together with the massive appearance of apoptotic bodies form immunogenic cell-death which could be certainly the basis of the in-situ natural immune vaccination of the tumor [1]. Conclusion – Nanothermia shows its definite advantages in local cell-killing and in possible tumor-vaccination too. It is a feasible method for the reliable and controllable basic of the modern hyperthermia demands in oncology [2]. Reference – [1] Szasz O, et al. Tumor vaccination International patent pending , 2013, PCT/EP 2013/067653 [2] Szasz A, et al. (2010) Oncothermia, Springer, Heidelberg

Norikatsu Miyoshi
Osaka University, Japan
Title: Prognostic prediction models for colorectal cancer patients after curative surgical resection
Biography:
After Miyoshi completed his MD, he has done his Ph.D when he was 24 years old from Osaka University and postdoctoral studies from Harvard Medical School / Massachusetts General Hospital, Cancer Center. He is a surgeon for colorectal cancer and chief director of Osaka Medical Center for Cancer and Cardiovascular Diseases. He has published more than 50 papers in reputed journals and have gotten more than 10 grants and awards. He also has been serving as 3 editorial board members of repute.

Abstract:
To develop a prediction tool for recurrence and survival in colorectal cancer (CRC) patients following surgically curative resections. Methods: Between January 2004 and December 2007, 376 CRC patients were investigated at the Osaka Medical Center for Cancer and Cardiovascular Diseases. Patients with at least one of the following criteria were excluded: preoperative treatment, synchronous distant metastasis, non-curative resection, and incomplete follow-up after operation. All patients were retrospectively analyzed. A Cox proportional hazards model was used to develop a prediction model for disease-free survival (DFS) and cancer-specific survival (CSS). In univariate and multivariate analyses of clinicopathological factors, the following factors had significant correlation with DFS and CSS: tumor location, preoperative serum CEA, pathologically defined tumor invasion, and lymph node metastasis. Using these variables, novel prediction models were constructed by the Cox model with a c-index of 0.841 and 0.876 for DFS and CSS, respectively. The prediction models were validated by external datasets in an independent patient group. This study showed novel and reliable personalized prognostic models, integrating not only TNM factors but also tumor location and preoperative serum CEA to predict the patients’ prognosis. These individualized prediction models could help clinicians in the treatment of postoperative CRC patients.

Dana Haddad
Memorial Sloan-Kettering Cancer Center, USA
Title: A novel vaccinia virus carrying the human sodium iodide symporter facilitates longterm deep tissue image monitoring of virotherapy and targeted radiotherapy of pancreatic cancer
Biography:
Dana Haddad, MD, PhD obtained her medical degree from the University of Auckland, New Zealand, and subsequently completed her PhD at the University of Wuerzburg in Germany and Memorial Sloan-Kettering Cancer Center in New York. Her research focuses on the treatment and imaging of cancer via PET imaging, which involves genetic engineering of a “cancer-specific” virus expressing the human sodium iodide symporter. This virus is now a candidate for several phase I clinical trials. Dr. Haddad is in her final year of radiology training and will begin her fellowship in Breast and Women’s Imaging at Memorial Sloan Kettering in July 2016.

Abstract:
Introduction: To assess therapeutic response and potential toxicity of oncolytic virotherapy, a noninvasive modality is needed. This study aimed to assess the feasibility, parameters, and determining factors of serial imaging and longterm monitoring of virotherapy and tumor response of pancreatic cancer xenografts treated with GLV-1h153, a vaccinia virus carrying the human sodium iodide symporter (hNIS). Methods: Pancreatic cancerxenografts (PANC-1) in nude mice were treated systemically or intratmorally with GLV-1h153 and serially imaged using 124I and positron emission tomography (PET) 1, 2, 3, and 5 weeks post viral injection. Signal intensity was compared with tumor therapeutic response and optical imaging, and tumors histologicaly analyzed for morphology and presence of virus. Autoradiography was performed utilizing technecium-pertechtenate and gamma-scintigraphy to assess determining factors for radiouptake in tumors. Combination therapy with GLV-1h153 and systemic radioiodine was then explored. Results: GLV-1h153 successfully facilitated serial long-term imaging of viral therapy with PET signal intensity correlating to tumor response. GLV-1h153 colonization of tumors mediated uptake of potentially therapeutic doses of radioiodine. Successful radiouptake required presence of virus, adequate blood flow, and viable tissue, while loss of signal intensity was linked to tumor necrosis. Finally, combining systemically administered GLV-1h153 and 131I lead to enhanced tumor kill when compared to virus or 131I alone (P<0.01). Conclusion: GLV-1h153 is a promising oncolytic agent for the treatment, long-term imaging, and monitoring of therapeutic response of cancer. GLV-1h153 provided insight into tumor biological activity and facilitated enhanced tumor kill when combined with systemic targeted radiotherapy. Further investigation into parameters and potential synergistic effects of combination therapy is warranted.

Suzanne L. Topalian
Johns Hopkins Kimmel Cancer Center, USA
Title: Antibodies blocking the PD-1 pathway: A new age for cancer therapy
Biography:
Topalian received her medical degree from the Tufts University School of Medicine. She trained in surgery and was a research fellow and subsequently a Senior Investigator in the National Cancer Institute, NIH. She then joined the Johns Hopkins faculty in 2006 to direct the Melanoma Program in the Kimmel Cancer Center. Dr. Topalian is a physician-scientist whose studies of human anti-tumor immunity have provided a foundation for the development of cancer vaccines, adoptive T cell transfer, and immunomodulatory monoclonal antibodies. Her current research focuses on manipulating immune checkpoints such as PD-1 in cancer therapy, and discovering biomarkers predicting clinical outcomes. Named one of Nature’s 10 in 2014, her work has established immunotherapy as a treatment modality in oncology.

Abstract:
The PD-1 pathway, composed of the immune cell co-receptor Programmed Death 1 (PD-1) and its ligands, PD-L1 (B7-H1) and PD-L2 (B7-DC), mediates immunosuppression within the tumor microenvironment. Several different monoclonal antibodies designed to “release the brakes” on anti-tumor immunity by blocking PD-1 or PD-L1 have demonstrated significant and durable activity against multiple types of advanced cancers in the clinic, validating this pathway as a target for cancer therapy and ushering in a new age for cancer immunotherapy. Following regulatory approvals in 2014 for nivolumab (Japan and US) and pembrolizumab (US) to treat advanced melanoma in the second- or third-line setting, first- and second-line approvals for additional cancer types are anticipated. The generally manageable safety profile of PD-1/PD-L1 blocking antibodies is consistent with the development of synergistic combination therapies, which are predicted by preclinical models to have increased efficacy. Studies identifying tumor PD-L1 protein expression as a factor associated with enhanced responsiveness to PD-1 pathway blockade are only scratching the surface of potential biomarkers which might guide patient selection. Such biomarkers hold promise for further enhancing the risk:benefit profile for PD-1/PD-L1 antagonists and for increasing our understanding of the mechanistic underpinnings of this key pathway in tumor biology. Supported by the National Institutes of Health R01 CA142779, the Melanoma Research Alliance, the Barney Foundation, the Laverna Hahn Charitable Trust, Moving for Melanoma of Delaware, Stand Up 2 Cancer-Cancer Research Institute grant SU2C-AACR-DT1012, and Bristol-Myers Squibb.

Gautam Sethi
National University of Singapore, Singapore
Title: Identification of gamma-tocotrienol as a novel chemosensitizer in xenograft mouse model of human gastric cancer
Biography:
After completion of his Ph.D research in Cellular Immunology from India, Dr. Sethi joined University of Texas MD Anderson Cancer Center, and worked in the area of inflammation and cancer research for his post-doctoral studies. The focus of his research over the past few years has been to elucidate the mechanism (s) of activation of pro-inflammatory transcription factors by carcinogens and inflammatory agents and the identification of novel inhibitors of these oncogenic molecules for prevention of and therapy for cancer. So far the results his research work have so far resulted in more than hundred scientific publications in high impact factor peer reviewed journals and several international research awards.

Abstract:
Gamma-tocotrienol, a member of Vitamin E superfamily has attracted great attention of late for its anti-proliferative and anti-carcinogenic potential against different cancers. For example, our group has recently reported that anti-proliferative and chemosensitizing effects of -tocotrienol are associated with its ability to suppress activation of signal transducers and activator of transcription 3 (STAT3), a pro-inflammatory transcription factor that plays a pivotal role in the survival, proliferation, angiogenesis and chemoresistance of hepatocellular carcinoma. However, the potential of gamma-tocotrienol to overcome chemoresistance in gastric cancer, which is one of the deadliest cancers in Asia-pacific region, has never been explored before. Hence, we investigated the efficacy of gamma-tocotrienol in combination with capecitabine to modulate tumor growth and survival in xenograft mouse model. Cell proliferation and apoptosis assays indicated that gamma-tocotrienol potentiated capecitabine induced programmed cell death in various gastric cancer cell lines. Gamma-tocotrienol also inhibited expression of Bcl-2, Bcl-xL, cyclin-D1, COX-2, ICAM-1, VEGF, CXCR4, MMP-9 proteins, induced PARP cleavage and inhibited constitutive and capecitabine-induced NF-κB activation in gastric cancer cells. In vivo studies using xenograft model of human gastric cancer demonstrated that gamma-tocotrienol alone suppressed tumor growth and this effect was further potentiated in conjunction with capecitabine. Also the markers of proliferation index Ki-67 and the micro vessel density CD31 were significantly downregulated in tumor tissues by the combination of capecitabine and gamma-tocotrienol. As compared to the vehicle control, gamma-tocotrienol further suppressed the NF-κB activation and expression of cyclin D1, COX-2, ICAM-1, MMP-9 and survivin in tumor tissues obtained from treatment groups. Overall our results suggest for the first time that gamma-tocotrienol can potentiate the effects of capecitabine through modulation of multiple markers of proliferation, invasion, angiogenesis and metastasis in gastric cancer.

Bassam Janji
Laboratory of Experimental‐Hemato‐Oncology, Luxembourg
Title: Hypoxia‐induced autophagy in the tumor microenvironment: A new regulator of the antitumor immune response
Biography:
Bassam Janji is an associate head of the laboratory of Experimental Hemato-Oncology at the Luxembourg Institute of Health (LIH). He holds a PhD from the University of Pierre and Marie Curie in 2000 and he performed a post doc at the prestigious Curie institute in Paris. He joined the LIH in 2004 as a researcher and 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 in the regulation of the anti-tumor immune response. Dr Janji has been promoted senior researcher after obtaining his HDR degree (Habilitation to lead Research) in 2011 from the University of Paris 11 and nominated in 2015 associate head of lab. The expertise of the Bassam Janji in the field of tumor microenvironment has been internationally recognized through several research and review papers.

Abstract:
Hypoxia, a common feature of the tumor microenvironment, is associated with tumor resistance to anti‐cancer therapies. Recently, it has been reported that hypoxic tumor microenvironment also plays a significant role in shielding tumor cells from immune attack either by promoting immune suppression, or by inducing many other oncogenic events in cancer cells, allowing tumors to escape immune surveillance. Natural killer (NK) cells are effectors of the innate immune system, able to kill cancer cells through the release of the cytotoxic protease granzyme B. It has been reported that hypoxic tumor microenvironment interferes with the antitumor function of NK cells by mechanisms that are not fully understood. Here, we provided evidence that hypoxia decreases breast cancer cell susceptibility to NK‐mediated lysis by a mechanism involving the activation of autophagy in cancer cells. Targeting autophagy was sufficient to restore NK‐mediated tumor cell killing under hypoxia. Furthermore, we showed that the resistance of hypoxic tumor cells to NK cell attack was neither related to a defect in their recognition by NK cells, nor to a defect in the cytolytic function of NK cells toward hypoxic cells. We demonstrated that autophagy activation degrades NK‐derived granzyme B in the lysosomes of hypoxic cells making them less sensitive to NK‐mediated killing. Inhibition of autophagy restored granzyme B levels and reverted the resistance of hypoxic cells in vitro. Our results highlight autophagy as a critical factor in modulating NK‐mediated anti‐tumor immune response. We have validated this concept in vivo by showing that targeting autophagy significantly improved NK‐mediated tumor shrinking in breast and melanoma models. This study provides a cutting‐edge advance in our understanding of how hypoxia‐induced autophagy impairs NKmediated lysis and paves the way for formulating more effective NK‐based antitumor therapy by combining autophagy inhibitors.

Abdulhamid Chaikh
Grenoble University Hospital, France
Title: Clinical evaluation of lung and heart toxicity prevention using respiratory gating in patients with left sided breast cancer
Biography:
Dr.Abdulhamid Chaikh, has completed his Ph.D at Joseph Fourier University (Grenoble-Alpes) - France. He was qualified for assistant professor position in French University. He is working as scientist for Medical Physics & Radiation Oncology and teaching in master degree at the medical school of Grenoble-Alpes University. He is also the local manager for the French National Research Agency project (ANR-11-TECS-0018) at Department of Radiation Oncology and Medical physics, University Hospital of Grenoble. He has published more than 15 papers in international journals and participated to over 15 national and international conferences. He is carrying out peer reviewed articles and serving as an editorial board member of the Journal of Case Reports in Oncology and Therapy. He is a member of American Association of Physics in Medicine.

Abstract:
Purpose: we evaluated the benefit to protect the lung and decrease the risk of cardiovascular diseases using radiotherapy with respiratory gating for left breast cancer treatment. Material and methods: 10 cases with left sided breast cancer were studied. For each case, 2 treatment plans were generated. Plan 1 was generated using free breathing and Plan 2 using the gating method. An global analysis based on 2D and 3D gamma maps was made to evaluate the under-overestimated dose. Clinical evaluation was carried out using linear quadratic model to calculate Tumour Control Probability (TCP) and Lyman Kutcher-Burman model to calculate Normal Tissue Complication Probabilities (NTCP) for heart and lung. Wilcoxon test was used to check the significance of the differences and the correlation coefficient (r) was calculated using Spearman’s rank test. Results: using the gating technique, the maximum doses to heart and lung were significantly decreased by a dividing factor ranging from 1.03 to more than 5. Gamma maps showed a reduced radiation dose to heart and the surrounding tissues, and an increased delivered dose for breast targets. Therefore, TCP was significantly increased while decresing the NTCP for pneumonitis and long term cardiac mortality. A strong correlation was observed with, r > 0.9, due to increased distance between target and surrounding healthy tissues and increasing lung density. Conclusion: we assessed the protection of heart and lung for breast radiotherapy using the parameters of the radiobiological models. Delivering the prescribed dose with respiratory gating will significantly decreasing NTCP for heart and lung and may also increasing the TCP for targets.

Feng Yan
Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital, China
Title: Analysis of the UHRF1 expression in serum and tissue for gastric cancer detection
Biography:
Feng Yan, is the vice director of Department of Clinical Laboratory in Nanjing Medical University Cancer Hospital. The research works of Feng Yan focus on the bioanalytical chemistry in laboratory medical diagnostics, particularly in detection of tumor markers and tumor cells. She has published 74 papers in SCI journals.

Abstract:
Objective: To analyze the Ubiquitin-like with PHD and ring finger domains (UHRF) 1 expression in gastric cancer (GC) serum and tissue. Methods: The concentrations of UHRF1 DNA in serum were compared between 187 GC patients and 56 healthy controls using real-time PCR. Immunohistochemical analysis using tissue microarrays was performed. Results: UHRF1 DNA levels were significantly higher in GC patients compared to healthy controls (p<0.001) and have associations with age and lymph node metastasis (LNM). The UHRF1 expression was significantly higher in tumor tissue than matched normal tissues (p<0.001). Conclusions: The UHRF1 expression in serum and tissue may represent a novel biomarker for GC diagnosis and prognosis.

Jun Yu
The Chinese University of Hong Kong, China
Title: MicroRNA in colorectal cancer: From benchtop to bedside
Biography:
Jun YU is a professor in Department of Medicine and Therapeutics, Faculty of Medicine CUHK. She completed her MD and PhD at Tongji Medical University. She undertook postdoctoral research in Department of Gastroenterology at the University of Dresden and University of Magdeburg, Germany, and subsequently in Department of Medicine and Therapeutics, The Chinese University of Hong Kong (CUHK)in 1998-2002. She worked as a Senior Research Officer at Westmead Hospital at University of Sydney, Australia in 2003-2005. She returned to Hong Kong in 2005 and currently as a Professor at Department of Medicine and Therapeutics,Director of the Research Laboratory of Institute of Digestive Disease, and Associate Director of State Key Laboratory of Digestive Disease, CUHK. She has published over 240 peer-reviewed papers (38 papers with impact factor > 10) and 7 book or book chapters particularly in the areas of gastrointestinal cancers. She has obtained 11 research-related prizes/awards.

Abstract:
Colorectal cancer (CRC) is the third most common cancer worldwide. Both the incidence and death rates from CRC are increasing rapidly in Asian countries. CRC screening allows the detection and removal of early stage lesions, and has been demonstrated to reduce both CRC morbidity and mortality.Testing for molecular aberrations in CRC has emerged as a promising non-invasive approach for CRC screening and treatment. microRNAs are short non-coding RNAs that regulate gene translation. Most tumor types, including CRC, are found to have altered microRNA expression profiles. Studies have begun to examine the association of up-regulated microRNA and their association with CRC incidence and prognosis as well as the possibility of using circulating microRNAs or fecal microRNA expression as noninvasive early detection biomarkers. We are among the first to report the detection of miRNA-92 as non-invasive biomarker for the diagnosis of CRC (Gut 2009). Since colonocyts constantly shed into the lumen, molecular alterations in CRC tumor or even in adenoma might be detected in stool samples. We consequently demonstrated that stool-based miRNA were stable with highly reproducible detection and stool miRNAs are useful for screening CRC and polyps (Gut 2012; Clin Cancer Res 2014).Bio-functional characterization of the dysregulated miRNAs in CRC can function as tumor suppressor or oncogenic factors. These data suggest that microRNAs may be potential molecular classifiers, early detection biomarkers, and therapeutic targets for CRC. Thus microRNAs appear to represent an emerging class of biomolecule being utilized as biomarkers for CRC diagnosis and treatment.

Sanjay P. Bagaria
Mayo Clinic, USA
Title: Hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis activation of immune populations of peritoneal surface: Implications into prognosis and therapy
Biography:
Sanjay P. Bagaria is as an Assistant Professor of Surgery at Mayo Clinic in Jacksonville. He completed surgical training at New York Presbyterian Weill-Cornell Medical College and surgical oncology training at the John Wayne Cancer Institute in 2010. His translational research interests are in sarcoma, melanoma, and hyperthermic intraperitoneal chemotherapy. In particular, he focusses on the role of immunotherapy in the setting of surgical resection.

Abstract:
Peritoneal carcinomatosis (PC) is the dreaded sequelae of many gastrointestinal cancers that is uniformly fatal. Aggressive medical and surgical management have not produced long-term survivors and there remains a critical need for more effective therapy for PC. Cytoreductive hyperthermic intraperitoneal chemotherapy (CR-HIPEC) is a surgical oncologic procedure that involves the removal of all macroscopic PC and the treatment of residual microscopic PC with heated chemotherapy. Direct intraperitoneal administration and circulation of cytoxic agents at high concentrations in the operating theater is able to eradicate disease and simultaneously avoid the systemic absorption and toxicity observed with intravenous chemotherapy. In addition, delivering chemotherapy at 42 degrees Celsius increases the cytotoxic effects of the drug by increasing tissue penetration and inhibiting cellular mechanisms of replication and repair. Yet despite advances in CR-HIPEC surgery, median life expectancy remains less than 3 years. Thus, there is a critical need to expand and build on CR-HIPEC surgery with additional therapies. Immunotherapy has recently transformed the landscape of oncology; however their value in the treatment of PC remains unknown. This talk is designed to present an overview of CR-HIPEC surgery and present data that shows how CR-HIPEC stimulates the immune system of the peritoneal surface, and how augmentation of this immune response with immunotherapy is an attractive mechanism to improve eradication of PC.

Wahid Khan
National Institute of Pharmaceutical Education and Research, India
Title: Therapeutic nanocarriers to combat cancer drug resistance
Biography:
Dr. Wahid Khan did his Master’s and Ph.D from National Institute of Pharmaceutical Education and Research (NIPER), Mohali, Punjab, India. Thereafter, he was associated as Postdoctoral Associate for 2 years at School of Pharmacy and Center for Nanoscience and Nanotechnology, The Hebrew University of Jerusalem. Currently, he is working as Assistant Professor in Department of Pharmaceutics, NIPER, Hyderabad. He is having experience of working in areas of drug delivery, drug targeting, nanomedicine and biodesign of implantable medical devices. He has filed 2 patents, edited one book and has 55 international publications to his credit. He is recipient of various nation and international awards, fellowships and and research grants.

Abstract:
Multidrug resistance (MDR) is one of the most significant obstacles in cancer chemotherapy. One mechanism involved in the development of MDR is the over expression of P- glycoprotein. P-gp efflux transporter has a major impact on the pharmacological behavior of most clinically used drugs, critically affecting drug absorption, disposition and elimination in the body. A majority of anticancer drugs possess P-gp substrate properties leading to poor oral bioavailability and efficacy. Nanocarriers have gained a substantial attention in improving the oral bioavailability of anticancer drugs. The principle advantage of nanocarriers include their increased solubilisation potential, superior encapsulation, altered absorption pathway, prevention from metabolic degradation, chemical versatility of materials eligible for nanomedicines and targeting potential. Thus, transmembrane efflux of drugs can be tackled by co administration of P-gp modulators or inhibitors along with the anticancer drug in nanocarriers. Co administration of natural compounds like naringin, geniestein, morin, biochanin A, schisandrol B, myricetin, silymarin, baicalein and curcumin has been reported to substantially increase the oral bioavailability of anticancer agents such as paclitaxel, docetaxel, doxorubicin, etoposide. Recently, we have reported co-delivery of Rapamycin (RPM) and Piperine (PIP) loaded polymeric nanoparticles for breast cancer and this suggested improved efficacy of RPM loaded nanoparticles in killing breast cancer cells and a 4.8 fold increase in the bioavailability of RPM in presence of PIP was seen. Thus the use of anticancer drug in combination with a P-gp inhibitor co-delivery in nanocarriers would be a promising approach in cancer chemotherapy especially to combat cancer drug resistance.

Amal Hussain Al Haddad
United Arab Emirates University, UAE
Title: Whole transcriptome analysis in muscle and fat biopsies from patients with cancer cachexia reveals novel mechanisms
Biography:
Dr. Amal Al Haddad is currently a researcher at the college of medicine at the United Arab University since 2010. Amal has a unique interest in oncology in general and palliative oncology in particular. Amal is working on different cancer-related projects including understanding the molecular basis of cancer-related cachexia being one of the most under-studied end-of-life complications. Amal has a PhD in cancer biology and a master degree in management. She worked for nursing department in both adult and pediatric oncology at SKMC and Tawam Hospitals. Amal is a presenter in many oncology, hematology, and palliative care conferences and meetings. She recently presented her work in cancer cachexia at the "2nd Cancer Cachexia" conference in Montreal, Canada.

Abstract:
Background: Cachexia is responsible for one third of cancer deaths. However, its underlying mechanisms are not fully revealed. Purpose: To shed light on the mechanisms of cachexia in skeletal muscle and fat. Methods: Samples of rectus abdominis muscle and visceral fat were collected from cachectic patients vs. stable weight controls. Gene expression was analyzed using next generation sequencing, and confirmed with RT-PCR. Results: In muscle, 30 genes showed highly significant change in expression. Downregulated genes included 7 that are involved with metabolism (5 of which are mitochondrial); 4 with signaling; 4 with ubiquitination; and 3 with intracellular trafficking. There was marked downregulation of multiple genes involved in glycogen metabolism which correlates with the lack of glycogen, muscle weakness, and fatigue; characteristic of cachexia. The 5 upregulated genes include 2 involved with calcium signaling and 2 with cell matrix interactions. Expression of genes previously thought to be important in cachexia was not significantly different. Atrogin-1, upregulated in an in vitro cachexia model, was downregulated. Expression of myostatin and its receptor were significantly decreased, possibly reflecting end organ adaptation. In visceral fat, expression of 6 genes were downregulated and 10 upregulated. Several of these encode metabolic enzymes. Of genes in fat previously implicated with cachexia, such as hormone sensitive lipase and adipose tissue triglyceride lipase, were unchanged. While leptin was significantly downregulated and zinc-α-2-glycoprotein was significantly upregulated as expected. Conclusions: These studies explain some documented evidence in cachexia pathogenesis, highlight ambiguous data, and reveal unexpected changes in the pathophysiology of the cachexia.