Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 4th World Congress on Cancer Science & Therapy Chicago, USA.

Day 1 :

  • Special Session on Bioactive Natural Products for Cancer Prevention and Therapy
Speaker

Chair

Anupam Bishayee

California Northstate University, USA

Session Introduction

Anupam Bishayee

California Northstate University, USA

Title: Breast cancer prevention and treatment with oleanane triterpenoids

Time : 09:25- 09:45

Speaker
Biography:

Anupam Bishayee has 25 years of combined experience in pharmaceutical and biomedical research, teaching, administration and service. His research focuses on elucidation of the cancer preventive and therapeutic effects of medicinal plants, natural products, dietary, and synthetic agents using several pre-clinical models of cancer. His various other projects are funded by the National Institutes of Health as well as private pharmaceutical/biotechnological companies. He has published more than 102 original research papers and authoritative review articles in high-impact, peer-reviewed journals, 10 book chapters, and presented nearly 40 papers at various national and international scientific events.

Abstract:

Breast cancer is one of the most frequently diagnosed malignancies and main causes of death in women worldwide. Current treatment options, including surgery, radiotherapy, adjuvant chemotherapy and hormone therapy, may not be adequate to signifi cantly reduce the current morbidity and mortality of breast cancer. Th e value of natural products and dietary phytochemicals, including triterpenoids, in the prevention and treatment of breast cancer has been established. Oleanolic acid, an oleanane-type pentacyclic triterpenoid, is present in various dietary and medicinal plants. Emerging studies indicate that oleanolic acid and other oleanane triterpenoids modulate multiple intracellular signaling pathways and exhibit chemopreventive and antitumor properties in various cancer models. Several oleanane triterpenoids have been prepared by chemical modifi cation of oleanolic acid moiety, and some of these compounds are considered to be the most potent antiinfl ammatory and anticarcinogenic triterpenoids known to mankind. Th is lecture will critically examine the potential role of oleanane triterpenoids in chemoprevention and treatment of mammary cancer. Th e available preclinical studies using these agents and underlying molecular mechanisms will be presented. Our laboratory has undertaken an extensive research program to investigate mechanism-based chemopreventive eff ect of a novel oleanane triterpenoid, namely methyl amooranin (AMRMe), employing dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumorigenesis, a classical animal model that resembles human breast cancer. Th is lecture will present our results on the eff ects of AMR-Me on mammary tumor incidence, tumor burden, and tumor histopathological indices during DMBA-induced rat mammary carcinogenesis. Mechanistic results demonstrating the regulatory infl uence of AMR-Me on cell proliferation, apoptosis, proapoptotic protein Bax, antiapoptotic protein Bcl-2, estrogen receptors, Wnt/-catenin signaling, and nuclear factor-kappaB-mediated infl ammatory cascade during experimental mammary tumorigenesis will be analyzed. Several challenges and future directions of research to translate already available impressive preclinical evidence on oleanane triterpenoids to clinical practice of breast cancer prevention and therapy will also be discussed.

Keith I Block

Block Center for Integrative Cancer Treatment, USA

Title: Clinical research on herbs and supplements for cancer: An integrative medicine perspective

Time : 09:45-10:05

Speaker
Biography:

Keith I Block, MD, is an internationally recognized expert in integrative oncology. In 1980, he co-founded the Block Center for Integrative Cancer Treatment in Skokie, Illinois, and serves as its Medical and Scientifi c Director. He is the founding Editor-in-Chief of the peer-reviewed journal, Integrative Cancer Therapies. He has served on the National Cancer Institute’s Physician Data Query (PDQ) Cancer CAM Editorial Board since 2005. He has more than 90 publications in scientific journals relevant to nutritional and integrative oncology. He is also the author of Life Over Cancer, published by Bantam Hardcover Books, in April, 2009

Abstract:

Integrative medicine incorporates herbs and supplements, plus lifestyle interventions such as exercise, bio behavioral and dietary therapies into comprehensive treatment plans alongside conventional treatments, such as chemotherapy for cancer patients. Th e integrative medicine paradigm is evidence-based, and considers clinical trial data as primary in making treatment decisions, in addition to preclinical and traditional medicine perspectives. Treatment protocols exist that aid us in making decisions about supplementation when clinical trial evidence is less than optimal However, a surprising number of clinical trials now exist to inform us about the potential usefulness of herbal therapies and other dietary supplements in cancer treatment. Th is lecture will review trials in 6 areas, as follows: basic nutritional support to normalize parameters such as omega-3 intake; countering biochemical disruptions such as glycemic disorders, excessive oxidation and inflammation; countering disease specific molecular targets; mitigating disease-related symptoms such as fatigue and weight loss; mitigating treatment-related adverse eff ects; and enhancing treatment effi cacy. We will also examine herbs that have been tested specifi cally as cancer treatments, such as green tea and curcumin. While many trials have limitations in study design, many examples of natural substances that are promising or already clinically useful in the integrative setting can be cited.

Speaker
Biography:

Hossein Tavana has developed robotically operated, high throughput microtechnologies to expedite compound screening against breast cancer cells. These technologies enable identifying compounds that block the growth and compromise the viability of cancer cells in 3D tumor spheroid models, and inhibit the migration of metastatic breast cancer cells. He was selected as one of Top 20 Young Investigator Frontiers in Bioengineering in 2013 and as a Young Innovator in Cellular and Molecular Bioengineering in 2014. He has published fi ve book chapters, over 30 peer-reviewed journal articles, and fi led fi ve US patents. His research is funded by NIH and NSF.

Abstract:

Metastatic triple negative breast cancer (TNBC) is an aggressive malignancy that comprises 15-20% of breast cancers in the US but claims disproportionately high patient mortality. Migration of cells is an essential process toward metastatic progression of the disease; however, existing chemotherapeutic compounds do not eff ectively inhibit cell migration. We explored the potency of a series of natural compounds, phytochemicals, to block the motility of TNBC cells. We used a novel, high throughput cell migration assay technology to robotically generate a migration niche of well-defi ned size within each well of standard microwell plates. Th is approach enabled screening a collection of phytochemicals, each compound at a wide range of sub-lethal concentrations, on the migration of two metastatic TNBC cells. Our screening showed that phytochemicals can eff ectively interfere with deregulated cell motility. Specially, fi setin and quercetin potently blocked migration of both MDAMB- 231 and MDA-MB-157 TNBC cells. Our results suggested that the anti-migratory property of these compounds is in pat due to the scavanging of intracellular reactive oxygen species (ROS) and interference with MAPK signaling pathway.

Colleen Huber

Naturopathic Medical Doctors of Arizona, USA

Title: Glycemic restriction in cancer patients: A 7-year, controlled interventional study

Time : 10:45-11:05

Speaker
Biography:

Colleen Huber is a Naturopathic Medical Doctor in private practice in Tempe, Arizona. She is Co-Founder and Secretary of the American Naturopathic Research Institute/Naturopathic Oncology Research Institute (ANRI / NORI). She is a Fellow of the Naturopathic Oncology Research Institute. She is a credentialed physician at Plaza Healthcare in Scottsdale, AZ, a 179-bed in-patient, sub-acute facility, where she practices up to the full-scope of practice for naturopathic physicians licensed in Arizona. She graduated from Southwest College of Naturopathic Medicine in Tempe. Her academic writing has appeared in The L ancet and other medical journals.

Abstract:

Previous research has shown a correlation between blood glucose or glycemic load and cancer growth for a number of types of cancer. Th ose studies were retrospective and/or studies of fewer than 20 human subjects and/or studies on mice. In this controlled interventional study, we followed the diets and outcomes of all 317 cancer patients who came to our clinic with a diagnosis of cancer, and who stayed at least two weeks in our care. Th e patients were all treated naturopathically, with antineoplastic nutrients and herbs, plus the recommended dietary intervention of abstention from sweetened foods. We analyzed the clinical signifi cance (mortality) of sweetened food consumption among those cancer patients.Since 2006, this clinic has collected data on sugar consumption in cancer patients, and has actively recommended, but never enforced in any way, avoiding sweetened foods (except with the sweetener Stevia rebaudiana, which has no sugar content or sugar alcohol content. All results are reported in this paper.Comparing all patients who were steadfast in our recommended naturopathic treatments with the sweetened food eaters who were steadfast in all but dietary recommendations, 151 / 183 = 83% of all totally steadfast patients went into remission, but only 9 / 25 = 36% of the steadfast sweetened food eaters went into remission.Consuming sweetened foods (other than stevia sweetened foods) made a signifi cant diff erence in patient outcome across all stages and all types of cancer. We therefore recommend that the diet of cancer patients not contain sweetened foods other than stevia.

Break: Coffee Break 11:05-11:20 @ Versailles Foyer

Gary D Stoner

Medical College of Wisconsin, USA

Title: Chemoprevention of gastrointestinal tract cancers with berries

Time : 11:20-11:40

Speaker
Biography:

Gary D Stoner completed his PhD at the University of Michigan in 1970, conducted Post-doctoral studies at the University of California-San Diego and, in 1992, joined the Department of Preventive Medicine at Ohio State University as Lucius Wing Chair in Cancer Etiology and Prevention. He has Chaired the NIH Chemo/ Dietary Prevention and the ACS Nutrition and Environment Study Sections. He is Professor of Medicine at the Medical College of Wisconsin and is conducting additional clinical trials of berries for the prevention of esophagus and colon cancer. He has more than 300 peer-reviewed publications. 55 book chapters and has edited 4 books.

Abstract:

We examined the ability of freeze-dried berries to prevent G.I. tract cancers in animals and humans. Most studies used black raspberries (BRBs), due to their high antioxidant potential and high content of anthocyanins and fi ber. In rodent studies, the consumption of BRB powder, at 2.5, 5 and 10% of a synthetic diet, resulted in a 40-70% inhibition of carcinogeninduced cancer in the rat esophagus and colon, and the spontaneous development of intestinal tumors in mice. Mechanistically, BRBs inhibit proliferation, infl ammation and angiogenesis and stimulate apoptosis and diff erentiation, and protectively modulate genes in multiple signaling pathways. Th e most active inhibitory constituents in BRBs are the anthocyanins. A Phase I trial showed that BRBs are well tolerated in humans at oral doses that elicit chemopreventive eff ects in rodents. Th e oral administration of BRB powder (45g/day) to 20 Barrett’s esophagus patients for 6 months led to reductions in oxidative stress, but minimal eff ects on the lesion. Oral administration of strawberry powder (60g/day) to 37 Chinese patients with esophageal dysplasia led to histologic regression of ~80% of mildly dysplastic lesions and reduced levels of iNOS, COX-2, and phospho-NF-κB-p65 proteins. Treatment of 20 colorectal cancer patients with BRB powder for an average of 3 weeks led to reduced cell proliferation and demethylation of suppressor genes in the Wnt signaling pathway. Treatment of patients with familial adenomatous polyposis with rectal BRB suppositories caused a 36% regression of rectal polyps. Th ese trials indicate that berries have signifi cant promise for chemoprevention of esophageal and colon cancer in humans.

Sanjay Gupta

Case Western Reserve University, USA

Title: Modifi cation of the epigenome by green tea polyphenols: Role in cancer prevention

Time : 11:40-12:00

Speaker
Biography:

Sanjay Gupta has authored some 130 publications, including book chapters, research articles and reviews, and has spoken at several occasions in cancer prevention symposium, seminars and meetings. He has obtained funding from National Cancer Institute (NCI), National Center for Complementary and Alternative Medicine (NCCAM) and National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). He has also received his funding support from various private foundations including Cancer Prevention Foundation, Ohio Board of Reagents and The Gateway for Cancer Research. He has been serving in various study sections at NCI and Department of Defense (DOD) and reviewer for several prestigious scientifi c journals. His innovative research on basic and translational aspects has led to publications in several peer-reviewed high-impact scientifi c journals including Cancer Research, Clinical Cancer Research, Oncogene, Proceedings of the National Academy of Sciences, USA, Journal of Clinical Oncology, FASEB Journal and has been featured on NBC-5 news and highlighted in the Plain Dealer, and American Association for Cancer Research press release.

Abstract:

Diet and lifestyle factors contribute to cancer development by inducing both epigenetic and genetic changes that, in combination with genetic make-up, result in the disruption of key cellular processes leading to neoplastic process. Dietary polyphenols have been reported to demonstrate many interesting biological activities, including induction of epigenetic changes and cancer prevention. We recently demonstrated that green tea polyphenols has ability to modify the epigenome resulting in upregulation of various tumor suppressor genes in breast and prostate cancers through epigenetic modifi cation(s) at various levels. Th e presentation will discuss various epigenetic mechanisms elicited by green tea polyphenols resulting in its anticancer activity in breast and prostate cancers. Understanding the mechanism(s) of epigenetic regulation and its reversibility by dietary polyphenols will result in the identifi cation of novel targets that may be useful in developing new strategies for the prevention and treatment of cancer.

  • Track 1: Cancer Cell Biology, Diagnostic and Prognostic Cancer Biomarkers
    Track 2: Organ-Specific Cancers, Cancer Genetics, Drug Development & Diagnostics
    Track 4: Tumor Science
Speaker

Chair

James R Mansfield

PerkinElmer, USA

Session Introduction

Mine Yarim

Yeditepe University, Turkey

Title: Synthesis and anticancer screening studies of benzothiazole-based piperazine derivatives

Time : 12:00-12:20

Speaker
Biography:

Mine Yarim has studied anticancer drug design and authored several peer-reviewed reports. She has served on numerous review committees for the National Science Foundation in Turkey. She has served on the editorial boards for the Pharmacologia. She is a member of the QSAR Society.

Abstract:

This lecture will cover our study on benzothiazole-based piperazine derivatives and their cytotoxic activities. Target compounds were synthesized according to reactions shown below in reaction scheme. Structures of compounds were clarifi ed with IR, 1H-NMR, 13C-NMR, mass spectroscopies and elemental analyses. In vitro cytotoxic activities were screened in comparison with camptothecin (positive control) and 5-fl uorouracil (reference) by sulphorhodamine B assay against breast cancer (MCF-7), hepatocellular carcinoma (HUH-7) and colorectal carcinoma (HCT-116) cell lines. Th e most potent compound against HUH-7 and MCF-7 cell line was compound 1d; IC50 = 3,1 μM and IC50 = 9,2 μM, respectively. Th e most potent compounds against HCT-116 cell line were compound 1a; IC50 = 4,8 μM and compound 2a; IC50 = 4,5 μM.

Alvaro Macieira-Coelho

French National Institute of Health (INSERM), France

Title: The suppressive effect of organism senescence on cancers

Time : 12:20-12:40

Speaker
Biography:

Alvaro Macieira-Coelho completed an MD at the University of Lisbon, Portugal, was an intern at the University Hospital, and completed a PhD at the University of Uppsala, Sweden. He was appointed Head of the Department of Cell Pathology, Cancer Institute, Villejuif, France and Research Director at the French National Institute of Health. He has authored 150 peer-reviewed articles and published nine books. Awards: Fritz Verzar prize, University of Vienna; Doctor Honoris Causa, University of Linköping; Johanan of International visiting Professor, Mario Negri Institute, Milan; Seeds of Science Career prize, Lisbon.

Abstract:

Most of the scientifi c literature reports that aging favors the development of cancers. However, more than half of the cancers become clinically manifest during the second half of the human life span and their frequency increases with age, but their natural history starts way back at earlier ages. Th e incidence of each type of cancer is related inter alia to the developmental stages of the human life span. Th ere are cancers characteristic of the early and late post-natal developmental stages, others of maturity, others of the stage of sexual involution, and fi nally during human senescence the incidence declines for all cancers. In general the progression of cancers is also slower in the old. Th ere are several possible explanations for this decline, which will be described. Th e idea that aging favors the development of cancers is so ingrained that even when the data point against this view, investigators do not accept it. Th e evolution of neoplastic disease is the result of pre- and postnatal aggressions suff ered by the organism, individual susceptibility, and developmental events that evolve continuously from beginning to the end of the human life span. One has to stop accepting the dogma that aging favors neoplastic growth and ask why tumors are characteristic of the diff erent developmental periods and why the incidence declines during senescence. Th ese questions should be solved before the origins of cancers can be understood.

Biography:

WenYong Chen is an Associate Professor, Department of Cancer Biology, Beckman Research Institute. His research interest focus on Cancer Biology.

Abstract:

Acquired resistance through genetic mutations is a major obstacle in targeted cancer therapy, but the underlying mechanisms are poorly understood. Using chronic myeloid leukemia (CML) as a disease model, we studied mechanisms of CML acquired resistance to tyrosine kinase inhibitors. By examining genome-wide gene expression and Exome sequencing of CML cells before and after developing genetic resistance, we identified key changes in cellular differentiation status when CML cell acquired genetic resistance. Forced differentiation overcame CML acquired resistance by altering CD38 expression and cellular NAD metabolism, which led to inhibition of SIRT1 functions and error-prone DNA damage repair in CML cells and blocking mutation acquisition. Our study sheds novel insight of cancer acquired resistance and has clinical implication of using differentiation agents to overcome drug resistance to tyrosine kinase inhibitors.

Anton Amann

Innsbruck Medical University, Austria

Title: Lung cancer screening by analysis of exhaled breath

Time : 13:00-13:20

Biography:

Anton Amann is Head of the Breath Research Institute of the University of Innsbruck. He has worked on volatiles released through exhaled breath, skin emanations and urine and has studied volatile compounds released by cell and bacterial cultures. A specifi c focus of his work is on real-time analysis of exhaled breath. He has coordinated the EU-project BAMOD and was awarded the Marie-Curie medal of the Polish Chemical Society in 2010. He is Editor-in-Chief of the Journal of Breath Research and Chairman of the International Association for Breath Research (IABR).

Abstract:

Volatile compounds released through exhaled breath, the nasal cavity, oral cavity, urine or sweat play an important role in the human metabolism. Typical techniques used for their analysis are gas chromatography with mass spectrometric detection (GCMS) and proton-transfer-reaction time-of-fl ight mass spectrometry (PTR-TOF). A most interesting possibility is real-time analysis of exhaled breath, during exertion of an eff ort on a stationary bicycle or during sleep. Th is has been done for a few compounds like isoprene, acetone, 2-pentanone or dimethylsulfi de. Th e investigation of exhaled breath of cancer patients is a particular focus of research. Some compounds (e.g., pentanal, hexanal, octanal and nonanal) appear in higher concentrations in cancer patients as compared to healthy volunteers, whereas other compounds (like isoprene) show lower concentration in exhaled breath of cancer patients. During the past decade about 115 diff erent volatile biomarkers have been published in regard to cancer. For all these compounds careful validation studies will be necessary. Cancer cell culture investigations reveal that diff erent cell types can release or consume diff erent volatile compounds. Compounds released are hydrocarbons (e.g. 2, 3, 4-trimethylpentane, octane or 4-methylheptane), alcohols (e.g., 3-methyl-1-butanol, ethanol or 2-methyl-1-propanol), esters, acetone and 2-pentanone. Th e use of endogenously produced volatiles in diff erent fi elds of research is still at its very beginning. Th e use of isotopically labeled compounds for measurement of enzyme activity with breath tests based on exhaled 13CO2 is already very near to clinical application. Th is off ers the possibility of non-invasive phenotyping, thereby complementing genetic tests and opening up the way to a “personalized” medicine.

S V Rana

Post Graduate Institute of Medical Education and Research (PGIMER), India

Title: Imperative effect of wheatgrass on tumor marker and histology of experimentally induced colon cancer in rats

Time : 13:20-13:40

Speaker
Biography:

S V Rana is working as Faculty in the fi eld of Clinical Biochemistry related to Gastroenterology since 1988. Throughout her career; she has worked on non-invasive diagnostic tests for various gastrointestinal diseases. Her fi eld of specialization is colorectal cancer, gall bladder cancer and pancreatic cancer. She is actively involved in the research studies related to pathological, risk factors and preventive aspects of cancer. Her expertise is also in oxidative stress and antioxidants in different gastrointestinal diseases, hepatotoxicity and its prevention, role of non-invasive hydrogen breath in different gastrointestinal diseases. She has published various research papers and review articles in national and international journals.

Abstract:

Colorectal cancer (CRC) is most common forms of gastrointestinal cancer. Diff erences in colon cancer incidence are attributed to environmental & dietary factors. Wheatgrass is powerhouse of nutrients & vitamins for human body. It is believed to treat number of conditions like common cold, cough, eczema, etc. Total Sialic acid (TSA) level in serum is sensitive marker for early diagnosis of colorectal cancer. Th us, aim of study was to determine eff ect of wheatgrass in experimentally induced colon cancer in rats. Twenty four adult Sprague Dawley rats were divided into 4 groups. Group1: Rats were fed on normal diet and administered with normal saline subcutaneously. Group2: 1,2 dimethylhydrazine (DMH) was administered subcutaneously at 30 mg/Kg b.wt dose once/week for 16 weeks. Group 3: Wheatgrass was administered orally 100mg/100g b.wt dose in drinking water along with DMH injection. Group 4: Wheatgrass was administered orally 100mg/100g b.wt dose in drinking water. Wheatgrass treatment was started 2 weeks prior to administration of DMH. TSA level was measured in serum and histological studies were also conducted. A signifi cant increase (P<0.001) in levels of TSA was observed following DMH treatment at 8 (47.5±5.1 mg/dl) and 16 weeks (66.4±7.5 mg/dl). However, wheatgrass supplementation reduced TSA levels at 8 and 16 weeks but decrease was signifi cant (P<0.001) only at 16 weeks. Histologically, rats treated with DMH showed carcinoma with variably sized irregular glands. In wheatgrass supplemented group, dysplasial changes were reduced with focal crypt distortion and mild to moderate mononuclear infl ammatory cells in lamina propria. Th e present study indicated that supplementation of wheatgrass in colon carcinogenesis has positive benefi cial eff ect, reducing adverse eff ects of DMH.

Break: Group Photo
Lunch Break 13:40-14:25 @Athens
Biography:

James R Mansfi eld is a scientist with over 25 years of experience in spectral imaging, in-vivo spectroscopy and applied data analysis, directed towards fi nding of novel optical methods for the diagnosis and monitoring of medical conditions. He is currently the Director of Quantitative Pathology Applications at PerkinElmer where he is the senior application scientist for their multispectral and digital pathology product lines, which are being used in a wide range of fl uorescence and brightfi eld microscopy applications. Before PerkinElmer he worked at Cambridge Research & Instrumentation, where he helped develop their multispectral imaging systems. Prior to that he worked at the National Research Council of Canada as a research scientist and at several small companies developing non-invasive spectroscopic methodologies. His research has included projects ranging from the objective classifi cation of skin cancer spectra using mid-infrared spectral imaging, to developing methods for the non-invasive determination of the severity of rheumatoid arthritis, to the development of the fi rst of several spectral imaging systems able to map out skin oxygenation levels. He is an Associate Editor of the American Journal of Nuclear Medicine and Molecular Imaging, holds 6 patents, has over 50 publications and has served as an invited speaker, session chair and organizer at a variety of international conferences.

Abstract:

There has been a rapid grown in the fi eld of tumor immunobiology in recent years as a result of recent successes in cancer immunotherapies, and it is becoming clear that immune cells play many sometimes confl icting roles in the tumor microenvironment. However, obtaining phenotypic information about the various immune cells that play these roles in and around the tumor has been a challenge. Existing methods can either deliver phenotypic information on homogenous samples (e.g., fl ow cytometry or PCR) or morphologic information on single immunomarkers (standard IHC). We present here a methodology for delivering quantitative per-cell marker expression and phenotyping, analogous to that obtained from fl ow cyt ometry, but from cells imaged in situ in FFPE tissue sections. Th is methodology combines: Th e sequential multi-marker labeling of up to 8 antigens using antibodies all of the same species in a single section; automated multispectral imaging (MSI) to remove the typically problematic FFPE tissue autofl uorescence and correct cross-talk between fl uorescent channels; and an automated analysis that can quantitate the per-cell marker expression, determine the cellular phenotype, count these cells separately in the tumor compartment and in the stroma and provide high-resolution images of their distributions. We present here three examples of this new methodology: Th e simultaneous labeling, analysis and validation of CD3, CD8 and FOXP3 multiplexed staining in follicular lymphoma; a CD4, CD8, CD20, pan-CK TH, TC and B cell panel in breast cancer; and PD-L1, CD8, CD34 and FOXP3 phenotyping and quantitation in melanoma. Each example will show the application of the multiplexed staining, per-cell quantitation and cellular phenotyping from multispectral images of FFPE tissue sections.

Speaker
Biography:

Patrick A Singleton received his BSc degree from Niagara University, Niagara Falls, New York, USA and his PhD from the University of Miami, Miami, Florida, USA in 2003. He was a Post-Doctoral Fellow at the University of California, San Francisco (UCSF), Johns Hopkins University (Baltimore, Maryland, USA) and the University of Chicago (Chicago, Illinois, USA) from 2003-2006. He became an Instructor of Medicine at the University of Chicago in 2006 and an Assistant Professor of Medicine at the University of Chicago in 2009. His major areas of research are related to vascular integrity in acute lung injury and lung cancer. He currently holds a Scientist Development Grant from the American Heart Association, a Biomedical Research Grant from the American Lung Association and an NHLBI R01 grant from the NIH. He is an author in over 50 peer reviewed papers. He is a member of several Special Emphasis Panels for the NIH and also a manuscript reviewer and editor for numerous major journals.

Abstract:

This lecture will address the identifi cation and characterization of the extracellular serine protease, HABP2, in lung cancer progression. Lung cancer is a devastating disease with limited treatment options. Many lung cancers have changes in their microenvironment including upregulation of the extracellular matrix glycosaminoglycan, hyaluronan (HA), which we and others have demonstrated can regulate the activity of HABP2. We have utilized a variety of techniques to study HABP2 oncogenic potential including immunohistochemical analysis on lung cancer patient samples using anti-HABP2 antibody. Stable control, shRNA and HABP2 overexpressing human lung adenocarcinoma cells were evaluated using immunoblot analysis, proliferation, invasion and urokinase plasminogen activator (uPA) activation assays with or without high molecular weight HA (HMW-HA) or low molecular weight HA (LMW-HA). In human lung cancer xenograft models, primary tumor growth rates and lung metastasis were analyzed using consecutive tumor volume measurements and nestin immunoreactivity in nude mouse lungs. Our results indicate that HABP2 expression is increased in several subtypes of non-small cell lung cancer patient samples. Further, HABP2 overexpression increased LMW-HA-induced uPA activation, proliferation and invasion in human lung adenocarcinoma cells. Overexpression of HABP2 in human lung adenocarcinoma cells increased primary tumor growth rates in nude mice by ~4 fold and lung metastasis by ~10 fold compared to vector control cells (n=5 per condition). Our data suggests a possible direct eff ect of HABP2 on uPA activation and lung cancer progression. Our observations suggest that exploration of HABP2 in non-small cell lung carcinoma merits further study both as a diagnostic and therapeutic option.

Speaker
Biography:

Simone Chevalier completed her PhD in Biochemistry at “l’ Université de Montréal”, Montréal, Canada, and did her Post-doctorate training in Biochemistry and Endocrinology at the University of British Columbia (Vancouver, B.C.) and Maisonneuve-Rosemont Research Centre (Montréal), respectively. She is Associate Professor in Surgery (Urology) at McGill University and holds affi liations in Medicine and Oncology. She is the McGill Urology Director of Research and Director of the PROCURE Québec Prostate Cancer Biobank. Her career has been devoted to prostatic proliferative diseases. She published more than 90 papers in reputed journals and 350 presentations at national and international meetings.

Abstract:

Prostate cancer (PCa) ranks fi rst among malignancies in incidence in North American males and second as a cause of mortality by cancer. Beside age, etiologic and progression factors are still not fully identifi ed. A turning point in disease progression is when patients who failed surgery or radiation therapies develop castration-resistance (CRCP) while receiving androgen-deprivation therapy (ADT). Underlying mechanisms are not elucidated. Accumulating evidence, including from our team, suggests that tumor cell heterogeneity contributes to PCa progression. In fact, the androgen-dependency/sensitivity of tumor cells expressing the androgen receptor (AR) appears to gradually shift into insensitivity even if AR remains a functionally active transcription factor. Concomitant to this adaptive process, subsets of AR negative(-) and androgen-independent tumor cells of the neuroendocrine (NE) and stem-like phenotypes progressively emerge. We and others have obtained evidence that irrespectively of AR, PCa cells grow and movein response to diverse growth factors (GFs, such as EGF and IGF-1), cytokines (IL-6), and NE-products present in their microenvironment. A novelfeature of the IL-6 drivensignaling pathway in PCa cells is the intervention of the non-receptor Fer tyrosine kinase (TK) which we showed essential for STAT3 activation, nuclear translocation and transcriptional activity of IL6-dependent genes.Of signifi cance, Fer also intervenes in the AR axis and allows IL-6 to control the transcriptional activity of genes that are normally driven by androgens. Moreover, Fer contributes but to a lesser extent to growth elicited by EGF, IGF-1, and androgens. In the latter case, Fer forms similar complexes with AR but STAT3 is not involved. Altogether Fer appears to promote PCa progression by integrating cross-talks involving STAT3 and AR as its substrates and binding partners up to the PCa cell nuclei.

Renata Dobrila-Dintinjana

Clinical Hospital Center Rijeka, Croatia

Title: Circulating cancer cells and their use in the real life

Time : 15:25-15:45

Speaker
Biography:

Renata Dobrila-Dintinjana is engaged in fi eld of gastrointestinal cancers and Supportive Cancer Care for 20 years and she has authored more than 50 peerreviewed articles and over 100 reports. She is author of ten book chapters, reviewer for couple of international journals (J of Supportive Cancer Care,) and international projects in fi eld of Cancer Research. She is also invited speaker in Postgraduated Courses regarding abdominal malignancies (Hong Kong, Moscow) and in many International Congresses and Symposia. She is member of several National Scientifi c Committees regarding Gastrointestinal Cancer and Supportive Cancer Care. She is serving as co-editor of Journal of Hepato-Gastroenterology and is Coordinator for Oncology section of IASGO.

Abstract:

CTC’s are cancer cells of solid tumor origin found in the peripheral blood of patients with advanced stages of most types of solid cancers. CTC’s are very rare and represent a surrogate biomarker of hematogenous metastases. Disseminated cancer cells (DTC’s) represent post-extravasation phase and can be found in bone marrow . DTC/CTC detection therefore can be used as a strong prognostic factor, so called minimal residual disease. CTCs have procoagulant phenotypes and strongly determine local thrombin concentration leading to risk of developing thrombosis. CTCs also interfere with host immune cells and platelets which release angiogenic and growth factors (VEGF, PDGF, TGF-beta) what lead to tumor growth and establishment of metastatic tumor sites . CTCs express hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor (VEGF), and VEGF receptor (VEGFR2), associated with angiogenesis and tumor progression. CTCs detection is an independent, strong prognostic factor for Overall Survival (OS) and predictor of Progression Free Survival (PFS) in patients with metastatic breast cancer, prostate cancer and advanced colorectal cancer . Th e standardized method for detection CTC in blood is an automated immunomagnetic enrichment and staining system for CTCs (the CellSearch® system). It performs automated immunomagnetic epithelial cell adhesion molecule (EpCAM)- based enrichment followed by CK staining of CTCs in blood samples. Th e main target organ for the metastatic process in colon cancer is liver. Th erefore the portal fl ow can represent a “post-intravasation highway” for CTC’s. Meta-analysis of nine studies that used molecular detection (646 patients) concluded that CTC’s detection in portal fl ow correlate with nodal invasion, and that CTC’s status during surgery for primary tumor correlate with further liver metastatic relapse, neverthless of tumor stage. Also, in other gastrointestinal carcinomas, presence of CTCs means worse prognosis. CTCs can estimate the risk of metastating disease (prognostic information), and identifi cating therapeutic targets (diagnostic information) and resistance mechanisms. CTCs is perfect alternative to invasive biopsies for early detection of metastatic tumor tissue, and to better assess responses to treatment (liquid biopsy). Molecular profi ling of CTCs has the potential to provide individualisation of cancer therapy. Most of the current strategies for detecting CTC are based on the epithelial markers, epithelial cell adhesion molecule and keratin; however, in certain tumor types, these epithelial markers are downregulated during tumor cell dissemination, hampering the detection of CTCs. Th e optimal cut-off for the number of CTCs associated with worse prognosis is still not established. Low number of CTCs is also restriction for proper evaluation of therapy response. Th e fact that described patients with breast cancer dormancy who had detectable CTCs had not relapsed even aft er a follow-up of >20 years makes the potential benefi t of this tool questionable. Also, if patient has two cancers (breast, colorectal), one or both can be metastatic; than the interpretation of CSCs results is regardless of origin of the disease. CTC’s presence during treatment also means that it’s a cancer with primary resistency for therapy. Shall we stopp harmfull and unusefull therapy? Can we defi ne subpopulation of patients with the highest treatment benefi t trough the CTCs measurements? Does procoagulant nature of CTCs has impact on cancer progres ? Is cancer-response on anticancer therapy also related to antithrombotic therapies? Key to answer these and many other questions is in the incorporation of CTCs into prospective clinical trials to test their clinical utility and there is no doubt that CTCs can become usefull diagnostic and prognostic tool for patients with cancers. We can conclude that CTCs will provide new insight into the biology of cancer and the process of metastasis.

Julie Sesen

Cancer Research Center of Toulouse, France

Title: Int6/eIF3e is essential for proliferation and survival of humanglioblastoma cells

Time : 15:45-16:05

Speaker
Biography:

Julie Sesen is a PhD applicant at the Paul Sabatier University in Toulouse, France. She completed a Master degree in Oncology and is now in her 2nd year of PhD. She works in the team of Pr. Elizabeth Moyal under the direction of Dr. Nicolas Skuli and Dr. Cathy Seva within the Cancer Research Center of Toulouse. Her research was awarded fellowships from the Ligue Contre le Cancer, Cancéropôle GSO and Association pour la Recherche contre le Cancer, and should allow us to identify new therapeutic options to improve the treatment of glioma patients. Her work was recently published in the International Journal of Molecular Sciences.

Abstract:

Based on the World Health Organization classifi cation, Glioblastoma Multiforme (GBM) are grade IV astrocytic brain tumors and are one of the most deadly human cancers. GBM are very aggressive, with frequent relapses despite an appropriate treatment combining surgery, chemotherapy and radiotherapy. In GBM, hypoxia is a characteristic feature and activation of Hypoxia Inducible Factors (HIF-1α and HIF-2α) has been associated with resistance to anti-cancer therapeutics. Int6, also named eIF3e, is the “e” subunit of the translation initiation factor eIF3, and was identifi ed as novel regulator of HIF-2α. Eukaryotic initiation factors (eIFs) are key factors regulating total protein synthesis, which controls cell growth, size and proliferation. Th e functional signifi cance of Int6/eIF3e and the eff ect of Int6/EIF3E gene silencing on human brain GBM has not yet been described and its role on the HIFs is unknown in glioma cells. In the present work, we show that Int6/ eIF3e suppression aff ects survival of various GBM cells. We highlight that Int6 inhibition induces decreased proliferation through cell cycle arrest and increased autophagy and caspase-dependent and capase-independent cell death. Surprisingly, these phenotypes do not correlate with decreasedglobal cell translation, but could be, in part, explained by the decrease of HIF and HIF target expression in GBM cells. Indeed, isolation of polysome-bound mRNA reveals modulation of specifi c mRNA translation, such as HIF mRNA, when Int6 is silenced. Although a deeper understanding of the molecular mechanisms involved in this Int6/eIF3e-HIFs pathway is necessary, Int6 could become a new therapeutic option for these aggressive tumors.

Fawzi Aoudjit

CHU de Québec Research Center, Laval University, Quebec, Canada

Title: Role of the alpha 2 beta 1 integrin in leukemia chemoresistance

Time : 16:05-16:25

Speaker
Biography:

Fawzi Aoudjit is a Professor in the Department of Microbiology-Immunology; Faculty of Medicine at Laval University (Québec, Canada). He attended Laval University in Quebec, where he received a PhD in Molecular Endocrinology and Physiology (1996). He completed Post-doctoral fellowships at the Institute Armand-Frappier in Montreal and at the Sanford-Burnham Research Institute in La Jolla California, after which he was appointed as an Assistant Professor at Laval University in Quebec (2001). His research interests focus on the functional role of integrin-extracellular matrix interactions in the regulation of normal and malignant cells, with a focus on T cells. His previous studies have been central in understanding how integrins regulate anoikis and death-receptor-mediated apoptosis. He is now a full Professor at Laval University and his current research focuses on how extracellular matrix regulates the chemoresistance and dissemination of leukemia, and the development of autoimmune diseases.

Abstract:

This lecture will address a novel pathway involved in leukemia chemoresistance. Previous studies have identifi ed alpha4beta1 integrin, which binds to the extracellular matrix fi bronectin, as a major pathway in cell adhesion-mediated drug resistance of myeloma, B cell and myeloid leukemia. However, the integrin pathways promoting chemoresistance in acute T cell lymphoblastic leukemia (T-ALL) were not defi ned. Our recent fi ndings showed that the collagen-binding integrin alpha2beta1 promoted the resistance of T-ALL cells to drug-induced apoptosis and enhanced clonogenic growth. Th is occurred via activation of the MAPK/ERK pathway, which upregulated the antiapoptotic protein Mcl-1 and the Mutidrug Resistanceassociated Protein-1 (MRP-1). In addition, we found that alpha2beta1 signaling is implicated in the chemoresistance of leukemic T cell blasts from T-ALL patients. However, fi bronectin, which binds to alpha4 and alpha5beta1 integrins had no eff ect. Th e role of alpha2beta1 integrin in chemoresistance is also seen in myeloid leukemia. Together these studies identifi ed alpha2beta1 integrin as new pathway in cell adhesion-mediated drug resistance and suggest that leukemic cells in contact with collagen, which is an abundant matrix protein in the bone marrow, could escape chemotherapy and lead to the appearance of drugresistant cells. Th e clinical importance of alpha2 vs. alpha4 integrin in chemoresistance will be discussed.

Break: Coffee Break 16:25-16:40 @ Versailles Foyer

Bernard Friedenson

University of Illinois, USA

Title: Genomic data to predict breast cancer invasive potential

Time : 16:40-17:00

Speaker
Biography:

Bernard Friedenson is a PhD Research Scientist with nearly 60 publications. He received an NIH Research Career Development Award and an Innocentive Award in competition with nearly 400 other scientists. He received a BA in honors chemistry-mathematics at the University of Minnesota Duluth and a PhD in biochemistryorganic chemistry at the University of Minnesota. During Post-doctoral work at Roswell Park Memorial Institute, he rose to senior cancer research scientist specializing in immunology. At UIC he acquired 13 years additional training in medical sciences, genomics, and molecular biology. He is a member of the American Society of Preventive Oncology, the American Society of Clinical Oncology and an Editorial Board Member of BMC Research News.

Abstract:

Breast cancer genomes have acquired mutations in essential immune defense genes. Although damage to the immune system favors cancer associated infections such as cancer viruses, there are still dense extracellular and intracellular structures that remain to physically block infection. Are these barrier defenses also damaged in invasive breast cancer? Cervical cancers caused by human papilloma viruses (HPVs) were used as a working model for cancer due to viral infection. Functional eff ects of ~6000 gene mutations in 14 cervical cancers were researched in depth. Functions damaged in this model viral cancer were then compared to functions damaged by ~3000 mutations in 21 complete breast cancer genomes and by ~5000 mutations in 103 breast cancer exomes. DNA sequences were from public databases. Mutations in breast and viral cancers occurred in nearly 1000 identical or closely related genes. Many mutated genes that were shared normally prevent infection, provide physical barriers against infection and prevent the spread of cancer. Loss of some genes in breast cancers can lead to loss or enzymatic digestion of structures surrounding and confi ning breast duct cells. Mutations in other genes damage cell membranes, allow abnormal cell shapes and interfere with normal cell adhesion, also favoring cancer spread. Additional gene damage opens routes for cancer cells and prevents removal of infection. Mutations aff ecting cell cycle control add to damage to immune and barrier defenses. Infections may play a larger role in breast cancer than previously believed. Variable damage to barrier defenses may explain variations in ductal carcinoma in situ biopsy results and may be useful in deciding on treatment options.

Biography:

Ramziya Kiyamova is a memer of National Academy of Sciences of Ukraine, Kiev with expertise in Oncology, Molecular Biology, Cancer Research is on ResearchGate

Abstract:

Over the last few years emerging evidence suggests that tumor-associated antigens (TAAs) and their cognate autoantibodies serve as molecular markers of human malignancy. The principle of the immunological detection of molecular changes in tumor cells by autoantibodies which was the main conception of this work allowed us to identify 41 autoantigens from medullary breast carcinoma (MBC) tumor by modifi ed SEREX (serological analysis of recombinant tumor cDNA expression libraries) approach. Preliminary phage based allogenic screening followed by large-scale ELISA based allogenic screening of MBC antigens with sera of breast cancer patients of different histological grades revealed 6 TAAs with highest immunogenicity in sera of breast cancer patients compared with sera of healthy individuals. Combination of these 6 TAAs in a single panel may differentiate cancer patients and healthy individuals with 70% of sensitivity and 91% specifi city. This panel of 6 TAAs can be considered as the base for creating of serological test-system for non-invasive breast cancer diagnostics in future.

Speaker
Biography:

Mona Zaky Nasser has obtained her Master and MD degree from Cairo University. She has spent one year (2008-2009) as a Postdoctoral Researcher in Washington University in ST Louis, USA. She has been involved in the establishment of the molecular diagnostic unit in Beni-Suef University. Moreover, she is the Director of the quality assurance program in the clinical chemistry unit in Misr University for Science and Technology. She has supervised many Post-graduate candidates and participated in number of conferences where she has presented few posters and oral presentations. Her research interest includes molecular diagnostics and genetic background of human cancer.

Abstract:

Introduction/Aim: Increasing evidence suggests thatseveral pathological hepatic diseases have been related to alterations of miRNAs expression.Th e present study was designed to assess the signifi cance of serum miR-21, miR-223, and miR-885-5p as potential biomarkers in diff erent clinico-pathological sequalae of HCV-related chronic liver disease. Patients and Methods: Serum miR-21, miR-223, and miR-885-5p were quantifi ed by real-time quantitative PCR in 60 Egyptian patients with HCV-related liver disease in addition to 25 healthy controls. HCV patients were classifi ed into: chronic HCV (n=15), liver cirrhosis (n=15), and hepatocellular carcinoma (HCC) (n=30). Results: Serum levels of miR-885-5p in cirrhotic patients (with or without HCC) were signifi cantly higher than the noncirrhotic patients; p=0.007 and healthy control; p=0.001. However, no such signifi cance was detected between HCV patients with and without HCC; p=0.12. Serum miRNA-885-5p was able to discriminate cirrhosis ± HCC from healthy controls using ROC analysis: AUC 0.85, 87% sensitivity and 80% specifi city. As regards serum miR-21, HCC patients had signifi cantly higher levels than non-HCC patients (non-cirrhotic and cirrhotic groups); p=0.048 and the control group; p=0.002. ROC could diff erentiate HCC from control group; AUC 0.89, 80% sensitivity, 80% specifi city. Serum albumin and bilirubin were signifi cantly correlated with miRNA-885-5p(r=-0.27, p=0.04) (r= 0.42, p=0.001) respectively, but such correlation was not observed with serum miRNA-21. In contrast, mi RNA 223 showed no signifi cant diff erence across the studied groups. Conclusion: Along the spectrum of HCV-related chronic liver disease, miR-885-5p could be a potential marker for advanced liver damage while miR-21 could be a helpful diagnostic marker for HCC.

Speaker
Biography:

Sylvestre Bonnet obtained his PhD in Inorganic Photochemistry in 2005 in Strasbourg, France. After moving to The Netherlands as a Postdoctoral Fellow he obtained a NWO-Veni grant in 2008 at Utrecht University, and a Tenure Track position at Leiden University in 2009. He recently obtained a NWO-Vidi grant (2012) and an ERC Starting Grant (2013) to build his inorganic chemical biology research group in Leiden. His expertise lies at the crossing point between inorganic chemistry, photochemistry, and lipid bilayers, with a strong focus on anticancer research and light-activated anticancer metallorugs. He has authored more than 35 peer-reviewed reports.

Abstract:

This lecture will build a bridge between cisplatin-like therapies and photodynamic therapy by addressing the light activation of anticancer metallodrugs. A rather vast family of new compounds, based notably on ruthenium(II), change their chemical structure upon visible light irradiation. It is possible to use these structural changes to trigger toxicity, i.e., achieving minimal toxicity in the dark but maximal toxicity aft er light irradiation. In the dark a sulfur- or nitrogen-based ligand serves as a protecting group that prevents the metal compound interacting with biological ligands. Once irradiated, the protecting ligand is substituted by water and the metal compound becomes able to bind to biological ligands such as DNA, small molecules, or proteins, and kill cancer cell. Th e author will show how the protecting ligand can also be used to link the metal-based prodrugs to a targeting vector such as a liposome, from which the metal-based prodrug detaches upon light activation. Supported and non-supported light-activatable metallodrugs remain activatable even in absence of dioxygen, which diff erentiates them from conventional dyes used in photodynamic therapy. Finally, diff erent strategies will be addressed that allow for tuning the light absorption properties of metal-based compounds and bring them into the photodynamic window.

Speaker
Biography:

Antonis E Koromilas holds a BSc in Chemistry and a PhD in Biochemistry from the Aristotelian University of Thessaloniki, Greece. He pursued his Post-graduate studies in Immunology (Stockholm University, Sweden), Molecular Immunology (Kyoto University, Japan) and Biochemistry (McGill University, Canada). He is Professor in the Department of Oncology, Faculty of Medicine, McGill University and Senior Scientists and Group Leader at Lady Davis Institute-Sir Mortimer B. Davis Jewish General Hospital, Montreal. He has won many Canadian and international research grants and personal awards, and he has served as an Editorial Board Member in international journals.

Abstract:

The lecture will address the function of the translation initiation factor eIF2 in stressed-induced tumorigenesis as well as in anti-tumor treatments with chemotherapeutic drugs. eIF2 is a master regulator of stress through its ability to control protein synthesis in response to various forms of stress including DNA damage, oxidative stress, oncogenic stress as well as stress in the tumor microenvironment. Cells respond to stress by inducing the phosphorylation of the alpha (α) subunit of eIF2 at serine 51 (S51) (herein referred to as eIF2αP), a modifi cation that leads to the inhibition of global protein synthesis. eIF2αP is mediated by four kinases, namely HRI, PKR, PERK/PEK and GCN2 each of which becomes activated to distinct form of stress. Despite the general inhibition of protein synthesis, specifi c mRNAs can bypass the blockade, and in fact, be effi ciently translated under stress. Such mRNAs encode for proteins that facilitate cell adaptation to stress as shown for transcription factors ATF4 and ATF5 in mammalian cells or GCN4 in yeast. Our work focuses on eIF2αP function as a cell fate decision maker through its ability to induce either cell survival or death in stressed tumor cells. We investigate how the dual but opposing function of eIF2αP relates to the activation of the MAPK and Akt/PKB-mTORC1 pathways in stressed cells. Our work suggests that inhibition of eIF2αP is a powerful approach to disarm cell survival and induce death in tumor cells treated with pro-oxidant drugs or drugs targeting the PI3K-Akt/PKB-mTORC1 pathway.

Marijan Dintinjana

General Practice Ambulance, Croatia

Title: Supportive Cancer Care: The Role of General Practitioner

Time : 18:20-18:40

Biography:

Marijan Dintinjana is a member in General Practice Ambulance, Croatia.

Abstract:

Most of the 11 million new cases of cancer annually presents with the clinical picture of disseminated malignant disease. Th e goal of treating these patients is not to cure, but prolonging life and maintaining quality of life. Malignant disease is now considered a chronic disease and the range of symptoms that occur during the life of cancer patients is extremely wide. Th e most common symptoms are pain, infections, respiratory disorders, emesis, anemia, anorexia-cachexia syndrome, diarrhea, jaundice, and psychosocial problems. Pain is the most common and most unpleasant distress symptom that occurs in cancer patients. It is defi ned as an unpleasant sensory and emotional experience that is primarily linked to tissue damage or described in terms of such damage. Th e pain is usually mixed type (nociceptive pain and neuropatic pain). As many as 50% of cancer patients will be anemic during their illness. Lower hemoglobin level inevitably implies poorer treatment outcome. Th e incidence of anemia in malignant disease is variable and depends on the type and stage of malignancy, chemotherapy regimens and intensity of treatment, infections and surgical interventions. Fatigue or unusual tiredness syndrome occurs in a large percentage (80-96%) of patients with malignant diseases, but is not recognized enough and its importanceis underestimated. Treatment options are scarce. Dyspnea is a bad prognostic sign. Th e etiology is unknown and therefore even treatment is diffi cult. Th ere is still no defi nitive statement about the therapeutic approach to patients with malignant dyspnea; to what extent and when to use opioids and oxygen. Tumor syndrome anorexia-cachexia means loss of appetite, weight loss> 10%, loss of muscle mass and hypoproteinemia. Th e syndrome occurs from 8-88% of cancer patients depending on the tumor site. Response to chemo/radiotherapy is lower, side eff ects are more pronounced and survival is shortened. Th e goal of treatment is adequate and timely application of pharmacotherapy preparations in order to avoid unintended consequences and treatment failure. In patients with malignant diseases common are respiratory and intra-abdominal infections. Th ey are a refl ection of the disease itself or as a result of the application of anti-tumor therapy (febrile neutropenia). From the patient’s point of view nausea and vomiting caused by chemotherapy are the most stressful component of treatment that may even lead to the rejection of potentially curative treatment. During the life, cancer patient express average about 10 of this and many other distress symptoms. Th e role of General Practitioner (GP) is early diagnostic of distress symptomatology, assessment of its intensity and early management. Altough GP are mostly prescribing the oncologists recommendations, GP are following their patients trough the whole course of their disease, and therefore are the cornerstone of support of cancer patient and his/hers famillies and caregivers. Furthermore, cancer destroys all components of life and thus signifi cantly reduces the quality of life of patients. Th is oft en leads to the occurrence of psychosocial problems which according to some studies are even more frequent compared to the pain and other physical symptoms. GP is the only doctor who deeply know the patients and familly needs and therefore its important part of medical care for oncology patients.

Vienna
Track 1: Cancer Cell Biology, Diagnostic and Prognostic Cancer Biomarkers
Track 2: Organ-Specific Cancers, Cancer Genetics, Drug Development & Diagnostics
Track 4: Tumor Science

Session Chair:
Clodia Osipo
Loyola University, USA

Jin Su

The Fourth Military Medical University, China

Title: Discoidin domain receptor 2, an anti-cancer target against both tumor cells and tumor stroma

Time : 12:00-12:20

Speaker
Biography:

Jin Su is a faculty in Fourth Military Medical University, China.

Abstract:

Accumulating evidences indicate that collagen matrix play an important role in disease progression, including cancer. Discoidin domain receptors (DDRs), consisting of DDR1 and DDR2, are collagen receptors as well as receptor tyrosine kinases (RTKs). By use of breast and oral cancer models, we found that DDR2 facilitates tumor cell metastasis and the mechanisms involve control of MMP expression and EMT. In addition, we also demonstrated that DDR2 is highly expressed by tumor endothelial cells (ECs) and enhances endothelial angiogenic activities. By use of a spontaneous Ddr2 mutant mouse colony, it was shown that DDR2 defi cient stroma is refractory to induction of xenograft tumor growth and angiogenesis. Notably, our newly developed chemical compound that blocks the phosphorylation of DDR2 reduces tumor growth, angiogenesis and metastasis. Th us, DDR2 may represent an anti-cancer target against both tumor cells and tumor stroma.

Stefan Ståhl

AlbaNova University Center, Sweden

Title: Affi body technology targeting cancer: Imaging and therapy applications

Time : 12:20-12:40

Speaker
Biography:

Stefan Ståhl is a faculty in AlbaNova University Center, Sweden.

Abstract:

Affi body molecules constitute a class of engineered affi nity proteins with potential in biotechnological, diagnostic and maybe also biotherapy applications. Affi body molecules are small (6.5 kDa) single domain proteins that can be isolated for high affi nity and specifi city to given protein targets. Fift een years aft er its discovery, the affi body technology is gaining use in many groups with an interest in small affi nity proteins. Th e generation and use of affi body molecules binding with high affi nity to the human epidermal growth factor receptors, EFGR, HER2 and HER3 and their use for medical imaging applications as well as eff orts towards future tumor biotherapy applications will be addressed. High contrast PET and SPECT imaging in mouse xenograft s as well as data on complete eradication of small HER2-expressing tumors in mice will be shown. Th e fi rst human studies for affi body-mediated imaging of HER2-expressing metastatic lesions in recurrent breast cancer patients will be presented. A picomolar HER3-binding affi body molecule has been generated that shows antiproliferative capacity in cell assays, and therapy applications can thus be considered. Th e small affi body molecules are also well suited for creating bispecifi c tumor targeting reagents, and our eff orts in this area will be described.

Clodia Osipo

Loyola University Chicago, USA

Title: Role of Jagged-1 in HER2-mediated notch inhibition in breast cancer

Time : 12:40-13:00

Speaker
Biography:

Clodia Osipo is an Associate Professor of Pathology/Oncology Institute and the Co-Leader of the Breast Cancer Translational Program at the Cardinal Bernardin Cancer Center of Loyola University Chicago. The focus of her research career has been to elucidate critical mechanisms responsible for drug resistant breast cancer. The goal of the research laboratory is to identify these critical survival and proliferative pathways to provide novel targets for new therapeutic interventions. Currently, the laboratory is focused on the role and contribution of the Notch signaling pathway in drug resistance to anti-hormonal and anti-ErbB-2 therapies. The critical research objective is to identify, validate, and test novel therapeutics targeting Notch signaling with the expectation of preventing breast tumor resistance, recurrence, progression, and ultimately death-associated with Notch-mediated drug resistance.

Abstract:

We have demonstrated that Notch1 is required for trastuzumab resistance in ErbB2 positive breast cancer. Th is indicates that ErbB2 suppresses Notch1 in breast cancer and therapeutic intervention targeting ErbB2 might have an unintended consequence which is aberrant up regulation of Notch1 which is a breast oncogene.However, the mechanism of action by which ErbB2 restricts Notch1 activation is unknown. In this current study, we investigated the role of cis- and trans-activation of Notch signaling by Notch ligands which are developmentally conversed to tightly regulate Notch activation. To address this hypothesis, we performed co-culture studies using fi broblasts expressing no Notch ligands or over-expressing human Jagged1 or Deltalike1 and ErbB2 positive breast cancer cells. We performed fl ow cytometry to isolate breast cancer cells aft er co-culture and extracted RNA to measure expression of Notch gene targets as a measure of Notch activity. Th e results showed that trastuzumab, Lapatinib, or ErbB2 knockdown increased overall Notch activation. Similarly, Co-culture with Jagged1- expressing fi broblasts increased overall Notch activation. However, Knocked down of Jagged1 in the breast cancer cells had little eff ect on ligand-induced Notch activation relieving the possibility of cis-inhibition. In contrast, Jagged1 knocked down abrogated trastuzumab-induced Notch activation in the breast cancer cells. Th ese results suggest that ErbB2 might restrict Notch activation by preventing Jagged1-mediated trans activation of Notch and not by promoting cis-inhibition. Confocal immunofl uorescence showed that Jagged1 is localized with Notch1 when ErbB2 is hyperactive but is traffi cked to the cell surface in response to trastuzumab. K44ADynamin abrogated Jagged1 expression on the cell surface as measured by IF and surface biotinylation studies. Furthermore, K44ADynamin expression abrogated trastuzumab-induced Notch1 activation. Importantly, we measured growth consequences of Jagged1-mediated Notch activation in response to trastuzumab and found that Jagged1 is necessary for survival of ErbB2 positive breast cancer cells and trastuzumab resistance as measured by cell cycle analysis and Annexin V staining. Th ese results taken together indicate that ErbB2 restricts Notch by limiting Jagged1-mediated trans-activation.

Biography:

Hulya Akgun has studied on anticancer drugs as well as other several new and active compounds. She has served on numerous reviews for the National Science Foundation in Turkey and also has authored several peer-reviewed reports. She is on the editorial boards of Anti-Infl ammatory Anti-Allergy Agents in Medicinal Chemistry

Abstract:

In this study, twenty six novel derivatives of 3-{2-[4-(substituted)piperazin-1-yl]-2-oxoethyl}quinazoline-2,4(1H,3H)-dione (compound 7-34) have been synthesized to screen their biological activities. Target compounds were synthesized according to the reactions shown in reaction scheme. Structures of compounds were clarifi ed with IR, 1H-NMR, 13C-NMR, mass spectroscopy and elemental analyses. In vitro cytotoxic activities were screened in comparison with camptothecin (positive control) and 5-fl uorouracil (reference) by sulphorhodamine B assay against breast cancer (MCF-7), hepatocellular carcinoma (HUH-7) and colorectal carcinoma (HCT-116) cell lines. Synthetized compounds generally showed moderate cytotoxic activity. 3-{2-[4-(4-Chlorobenzyl)piperazin-1-yl]-2-oxoethyl}quinazoline-2,4(1H,3H)-dion presented the highest activity against hepatoma (HUH-7), breast cancer (MCF-7) and colorectal cancer cell line (HCT-116) with the IC50 values of 2.5, 6.8 and 4.9 μM, respectively. 6,7-Dimethoxy derivatives seems to be selectively eff ected on HCT-116 cell lines whereas the compounds having R3 as diphenylmethyl structure showed selectivity on MFC-7 cell lines.

Speaker
Biography:

Shin Aoki graduated from the University of Tokyo and received PhD from the same University in 1992. After working as an Assistant Professor at the University of Tokyo, a Postdoc at the Scripps Research Institute, USA and an Assistant Professor in Hiroshima University, he became a Professor at the Faculty of Pharmaceutical Sciences, Tokyo University of Science in 2003. He is a recipient of several awards including the Pharmaceutical Society of Japan Award for Young Scientists (2002). His research interests include bioorganic chemistry, supramolecular chemistry, photochemistry, and medicinal chemistry.

Abstract:

8-Hydroxyquinoline (8HQ or oxine) and its derivatives are potent metal chelating agents and oft en used as fl uorescence sensors of Zn2+ and other metal cations. Recently, 8HQ have also been proposed as potential candidates for enzyme inhibitors and drugs to treat cancer, HIV, neurodegenerative diseases, and so on. In this paper, we present (i) the design and synthesis of 8HQ-based radioprotective agents for radiation therapy and (ii) the application of the photochemical cleavage reaction of 8-quinolinyl sulfonates (8QS) to the isolation of intact ligand-receptor complexes or living target cells. (i) In radiation therapy, adverse side eff ects are oft en induced due to the apoptosis that occurs in radiosensitive normal cell mainly caused by apoptosis-induction by the p53 protein. Th erefore, radioprotective drugs that can protect normal cells from radiation by temporary inhibition of p53 functions are be highly desirable. We have screened some zinc (II) chelators for the inhibition of radiation-induced p53-dependent apoptosis in MOLT-4 cells and found that N,N’-bis(2-pyridylmethyl)-1,2-ethanediamine and some 8HQ derivatives have the potent radioprotective activity, accompanied by a low cytotoxicity. (ii) We previously discovered the photochemical S-O bond cleavage reactions of 8QS in aqueous solution at neutral pH. Its application to QSbased photocleavable biotin-linkers for the isolation and recovery of the intact ligand-receptor complexes or living cells such as specifi c tumor cells will be presented.

Break: Lunch Break 13:40-14:25 @ Athens
Speaker
Biography:

Yeu Su is currently working in the Institute of Biopharmaceutical Sciences of NYMU. After getting his PhD from the University of Wisconsin-Madison, he went to the Johns Hopkins Oncology Center for his Post-doctoral training. He has studied the molecular mechanism of colorectal carcinogenesis for almost 15 years and his recent research has focused on understanding the origin of colorectal cancer stem cells as well as identifying novel agents capable of selectively eradicating them. Besides being the reviewers of a number of international journals, he now also serves on the editorial board for the World Journal of Biological Chemistry.

Abstract:

This lecture will fi rst address the functional roles of CD44 in the initiation and/or maintenance of human colorectal cancer stem cells (CRSCs) present in several established human colorectal carcinoma (CRC) cell lines. Th e author will present the results showing that much higher soft agar colony-forming ability and in vivo tumorigenicity are associated with the CD44+ HCT-15 CRC cells than their CD44- counterparts. In addition, signifi cant upregulation of Snail protein and marked downregulation of miR-203, a well-known stemness inhibitory microRNA, are found in CD44+ HCT-15 cells. Accordingly, the expression levels of Snail (other EMT inducers as well) and miR-203 in both HCT-15 and HCT-116 cells can be positively and negatively modulated by CD44 overexpression, respectively. Further analyses show that Snail suppresses miR-203 expression by binding directly to a specifi c E-box in the miR-203 promoter and c-Src activity stimulated by the interaction between CD44 and hyaluronan (HA) appears to be crucial for the activation of Snail. Further supporting the importance of miR-203 in diminishing the stemness of these CRSCs, signifi cant increases of their respective stemness are observed aft er the function of this microRNA in HCT-116 and HT-29 cells being disrupted. Besides above fi ndings, attendees of this lecture will learn the utility of Connectivity map (CMap) analysis in accelerating the identifi cation of agent(s) capable of selectively eradicating CRSCs. Using this novel bioinformatics approach, several “old” drugs with such activity wee identifi ed and the eff ect(s) as well as the molecular mechanism(s) of one compound will be discussed thoroughly in this meeting.

Biography:

Qin Shu Shao is a Professor of Surgery, Chief Physician, and Director of Gastrointestinal Surgery of Zhejiang Provinical People’s Hospital. He has published morn than fi fty articles in important national journals, 8 articles in SCI. He is a Standing Committee of Zhejiang Provinical Surgery Branch of Chinese Medical Association, a member of the National gastric Professional Committee of Chinese Anti-Cancer Association, a Professional Committee of hepatobiliary and pancreatic tumors surgery of Zhejiang Province and in magazine editorial of “Chinese Journal of Gastrointestinal Surgery” and “Chinese Journal of Digestive Surgery”.

Abstract:

This lecture will address a variety of topics related to the use of middle gastrectomy with regional lymph node resection as a new therapeutics in early gastric cancer in the middle one-third of the stomach. and will include discussion of: the therapeutics for gastric cancer in recent years; compare the advantage and disadvantage of these therapeutics; compare the diff erence of surgery time, lymph node resection, aerating time, hospitalization time postoperation, feed aft er 3 months and Visick graded index between group A (middle gastrectomy with regional lymph node resection), B(total gastrectomy with D1 lymph node resection) and C (endoscopic mucosal resection). We found that middle gastrectomy with regional lymph node resection in early gastric cancer will not increase the risk and time of surgery, and it can reduce the risk of lymph node migrating, complication related to surgery, and improve the quality of life.

Speaker
Biography:

Naglaa Zayed has obtained her Master and MD degree in Endemic Medicine and Hepato-gastroenterology, Faculty of Medicine, Cairo University. Her research interests include HCV infection and its consequences in addition to screening of colo-rectal cancer and the possible detection of genetic markers that may help in in the early detection of GIT malignancy. She has attended several national and international conferences w here she had presented few oral and poster presentations. She has published several papers in reputed journals and has been serving as a reviewer for few journals.

Abstract:

Introduction: Th e identifi cation of biomarkers in the presence of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) has the potential to improve patient outcomes through earlier diagnosis and treatment. Aim: To evaluate the esophageal tissue expression of glutathione S-transferaseP1 (GSTP1) and matrix metalloproteinase-9 (MMP-9) in patients with refl ux esophagitis, BE and EAC. Methods: Tissue expression of both GSTP1 and MMP-9 were analyzed in 120 paraffi n-embedded esophageal samples by immunohistochemistry obtained from 60 Egyptian patients; gastro-esophageal refl ux disease (GERD) (n=15), BE (n=15), EAC (n= 15) in addition to a control group with normal gross and histologic esophageal tissue (n= 15). Immunostaining was determined semi-qualitatively in all groups. Results: Normal esophageal mucosa demonstrated the lowest MMP-9 and highest GSTP1 tissue expression compared to all other groups; p<0.001. In contrast, the tissue expression of MMP-9 was signifi cantly higher and GSTP1 was signifi cantly lower in EAC and dysplastic BE than other groups; p value<0.001. Dysplastic BE demonstrated a signifi cant higher MMP-9; p<0.04 and lower GSTP1 tissue expression; p<0.003 compared to patients with non-dysplastic BE and GERD, however, no major changes were observed between non-dysplastic BE and GERD. Th e signifi cant down-regulation of MMP-9 was coupled by upregulation of GSTP1 expression along the whole spectrum of the disease, p value <0.001. Conclusion: Th e imbalance between tissue GSTP1 and MMP-9 in BE and EAC could be considered as potential markers that might be useful to identify patients at higher risk for progression to cancer.

Speaker
Biography:

Andrzej Lange is a Professor of the Institute of Immunology and Experimental Therapy, and the Founder and Head of the Lower Silesian Centre for Cellular Transplantation, Wrocław, Poland. He was a Research Fellow and lectured at several European and American universities. His pioneering work on immunological and genetic consequences of asbestos and aromatic hydrocarbons exposure earned him international recognition. He published 212 papers in peer-reviewed journals, mostly devoted to immunogenetic and clinical aspects of leukaemia treatment, including Hematopoietic Stem Cell Transplantation. Recently he has been involved in a study on regenerative medicine and cellular therapy post HSCT.

Abstract:

The current description of leukemia and lymphoma is based on molecular analysis of the neoplastic cells. Mutation of some genes increases the activity of serine/threonine and tyrosine (T/S) kinases, which drives the proliferation potential of malignant cells. In clinical practice several small-molecules are in use to block the enhanced kinases activity. Th e immune system plays a role in the surveillance of leukemia, providing the recognition of leukemic cells by lymphocytes what facilitates the administration to patients kinases inhibitors able to moderate tumor burden to avoid high-dose antigen tolerance. Th is will be discussed in some detail based on the model situations: (i) Flt-3 + acute myeloid leukemia, (ii) bcr/abl+ acute lymphoblastic leukemia relapsing post alloHSCT and (iii) JAK2 V617F + myelofi brosis. Th e use of T/S kinases inhibitors helped in the induction of remission. Th e role of the immune system surveillance including the graft -versus-leukemia eff ect in maintaining the remission will be discussed on the basis of the analysis of lymphocytes colonizing the marrow spontaneously or as an eff ect of donor lymphocytes infused intravenously or directly to the leukemic bone lesions in a relapsing patient. Th e data presented support the view that the use of some T/S kinases inhibitors by slowing down the expansion potential of leukemia facilitates the initiation of a spontaneous or induced graft -versus-leukemia eff ect.

Wilma A Hofmann

University at Buffalo, USA

Title: The role of a novel myosin in the development of prostate cancer

Time : 15:45-16:05

Speaker
Biography:

Wilma A Hofmann is an Assistant Professor in the Department of Physiology and Biophysics at the University at Buffalo. Her research interest focuses on structural components of the cell, their role in establishing and regulating cellular functions, and how this regulation translates into physiological consequences in health and disease. As a PI over the past 6 years, she has studied members of the myosin I family and their role in the development of various diseases with a particular focus on the role of cytoskeletal proteins in prostate cancer metastasis.

Abstract:

The majority of death from cancer is caused by metastasis, the spreading of cancer cells from the site of a primary tumor to other body parts followed by formation of metastatic tumors at these new sites. Despite the importance of metastasis in the clinical setting, little is known about the cellular mechanisms that are involved in this process. We recently discovered a previously unknown isoform of a class I myosin. Our data show that this isoform is selectively expressed in prostate cancer tumor tissues and in prostate cancer cell lines with high metastatic potential but not in normal prostate tissues or in prostate cancer cells with low metastatic potential. Furthermore, our data strongly suggest that this new myosin is critically involved in the acquisition of a metastatic phenotype in prostate cancer cells by enhancing the ability of cancer cells to invade surrounding tissue.

Break: Coffee Break 16:05-16:20 @ Versailles Foyer
Biography:

Rudolf Wank has focused on problems in immunogenetics and immunology for nearly four decades. After receiving the license to practice medicine in Munich, Germany, he spent fi ve years in the USA as scientist at the University of Madison, Wisconsin and at the Sloan Kettering Cancer Institute. He became Professor of Immunology at the University of Munich and concentrated on the genetics of the immune response. Eight years ago, he established the Immunotherapy Research Center in Munich, which undertakes to combine the treatment of patients with the best of science.

Abstract:

The CAPRI therapy is a novel adoptive cell therapy (ACT). It surpasses other ACT methods by its technical simplicity, the effi cacy and broad applicability. Th e priming procedure employs solely peripheral blood monocytic cells (PBMC) of the respective cancer patient without isolation of sub populations. Aquartette of immune cells, namely monocytes, dendritic cells, helper T cells and cytotoxic T cells remain in contact with each other during all activation steps. Th e cancer-immunogenic information for naïve T cells comes from monocytes. Monocytes need to be activated to display the specifi c cancer information. For this T cells were activated in the PBMC cultures with OKT3 antibodies to activate the monocytes. However, OKT3/CD3- stimulation induces downregulation of the antigen (αβ)-TCR of the OKT3-stimulated T cells. Th erefore, PBMC with naive/ unstimulated T cells have to be added. Already aft er 24h, the priming procedure is fi nished and yields highly effi cient CAPRI cells, probably for each type of cancer. A fi ve-year survival analysis showed that breast cancer patients with distant metastases (M1, N=42), treated with CAPRI cells in an adjuvant fashion, survived on average 53months whereas breast cancer patients from the Munich Tumor center in the same tumor stage without CAPRI cell treatment survived 31 months.Case series with non-metastatic breast cancer or non-small-cell lung cancer (NSCLC) showed similar favorable results. Very remarkable is the maintenance of life quality in the patients.

Speaker
Biography:

Sarah Crawford is a Professor in Southern Connecticut State University, USA. Her research interest includes genetics and cancer biology.

Abstract:

A novel pre-clinical approach developed in this laboratory for the fi rst time demonstrates the successful growth of human solid tumors of the brain, breast, colon and pancreas in unfertilized chick eggs. Th e research suggests that the avian system is a suitable and in many ways more advantageous culture system for the growth of human tumors than current in vitro and mouse model systems. Growth advantages off ered by the avian system include: • High success transfer rate (at least 80%) from in vitro spheroid culture to avian culture. • Rapid establishment within days of solid tumor growth. • Broad spectrum application to tumors of diverse tumor type grown successfully in this system, including tumor spheroids of the brain (glioblastoma), pancreas (ductal adenocarcinoma), colon, and breast (primary and metastatic origins). • Capacity for long-term cultivation not possible in fertilized chick eggs by serial transfer. • Avian embryonic environment aff ords biochemical, biophysical parameters and determinants of growth properties diffi cult to achieve in adult animal models or in vitro systems. • Ease of culture manipulation and tumor growth assessment. • Tumor growth in avian eggs displays heterogeneous growth parameters more similar to in vivo growth than spheroid cultures, including clear distinctions between necrotic tumor centers and active growth zones, increased invasiveness compared to traditional spheroid growth models and histological heterogeneity similar to that observed in human tumor specimens observed surgically and histologically. In summary, research demonstrating the simplicity, effi cacy and greater similarity in tumor growth properties in the avian system as compared to in vitro spheroid culture methods will be presented, including data showing the use of this model system to assess the potential effi cacy of novel therapeutic approaches and as a comparative tool for assessing pre-clinical versus patient treatment responses.

Guang Zhu

The Hong Kong University of Science and Technology, China

Title: Mechanistic study of human proteins that regulate cell proliferation and differentiation

Time : 17:00-17:20

Biography:

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 PhD degree at University of Maryland and National Institutes of Health, USA, specialized in biomolecular NMR spectroscopy. Currently his 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 75 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 diff erentiation). 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 diff erentiation. 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 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 cellcycle regulator and plays an important role in the developmental program of metazoans.

Speaker
Biography:

Marie-Josee Boucher completed her PhD in Cell Biology at the University of Sherbrooke, Canada and then pursued Post-doctoral training at the Umea Center for Molecular Medicine, Sweden. She is now an Associate Professor at the University of Sherbrooke, and devotes her career to the identifi cation of key signaling pathways involved in the maintenance of the transformed phenotype of pancreatic cancer cells. She is the Deputy Director of research of the Medicine Department, University of Sherbrooke. She is currently serving as an academic editor for PLoS ONE and on the editorial board of Advances in Medicine: Gastroenterology

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is the 4th leading cause of cancer-related death worldwide and the only malignancy with a 5-year survival rate still in the single-digit i.e., 6%. Th ese statistics have not improved over the last 40 years and, although the identifi cation of the most frequently mutated genes in PDAC (KRAS, p53, p16, SMAD4) provided important insights into PDAC pathogenesis, they have not lead to improvement of diagnostic or treatment. Consequently, PDAC is still lately diagnosed and highly resistant to current chemotherapeutic agents. Finding the Achilles heel of pancreatic cancer cells and/or new therapeutic options to sensitize pancreatic cancer cells to chemotherapeutic agents will defi nitively help in our quest to improve PDAC patients fate. We and others have previously demonstrated that inhibition of glycogen synthase kinase-3 (GSK3) impairs pancreatic cancer cell growth providing a rationale for evaluating the potential clinical utility of GSK3 inhibitors in the setting of PDAC patients. Notably, we have shown that GSK3 inhibition triggers JNK-dependent apoptosis of pancreatic cancer cells. Recently, we found out that exposure to a GSK3 inhibitor concomitantly elicits an autophagic response independently of the JNK-cJUN pathway. Preventing this autophagic response sensitizes pancreatic cancer cells to apoptosis suggesting a pro-survival role for autophagy upon GSK3 inhibition. Interestingly, we found that treatment with GSK3 inhibitors impacts on the transcription factor EB (TFEB) recently identifi ed as a master regulator of autophagy and lysosomal biogenesis. Our results underline the need to better defi ne the downstream GSK3’s eff ectors in order to propose better combination therapy for PDAC patients.

Biography:

Peter Herrlich has studied tumor molecular biology for 30+ years, during which time he has authored more than 300 peer-reviewed reports. He has served on the editorial boards for the International Journal of Cancer and Molecular Carcinogenesis for which he also served as editor. He was Scientific Director of the Leibniz Institute for Age Research and is currently an Emeritus at the same location. Aspasia Ploubidou is a Group Leader at the Leibniz Institute for Age Research. She specialized in the role of the cytoskeleton in disease and in oncogenesis by human papilloma virus.

Abstract:

Stem cells are recruited to refill cells and tissues that are worn out, or to repair injuries. The homeostasis of an organism depends on reliable maintenance of the stem cell pool. Stem cells undergo symmetric cell divisions for stem cell maintenance, and asymmetric division to obtain one differentiating daughter cell and one daughter with stem cell property. Misregulation of this delicate decision between symmetric vs asymmetric division causes severe consequences: elevated asymmetric divisions cause in case of neural stem cells microcephaly, in case of spermatogonia infertility. We report here on a regulatory molecule, RHAMM, that functions in the proper assembly of centrosomes and in the regulation of spindle orientation which determines the type of stem cell division. Mouse mutants in the RHAMM gene suffer from reduced fertility and development of seminoma (testicular germ cell tumor). All of 40 human seminomas showed reduced RHAMM expression. We found that the RHAMM gene represents one of the germ cell tumor susceptibility loci that had been identified previously. RHAMM appears to be a master gene downstream of other genes determining germ cell tumors. The talk will try to derive a general scheme how spindle orientation regulation affects normal and cancer initiating stem cells.

Jayeeta Bhaumik

National Institute of Pharmaceutical Education and Research (NIPER), India

Title: Combining Nanotheranostics and Photomedicine: Design and Synthesis of Nanophotomedicine for Cancer Treatment

Time : 18:00-18:20

Biography:

Jayeeta Bhaumik obtained Ph.D. in Organic Chemistry from North Carolina State University, Raleigh, USA in 2007. She carried out NIH postdoctoral fellowship at the Center for Systems Biology and later at the Dept. of Radiation Oncology, Massachusetts General Hospital and Harvard Medical School (2007-2011). Since 2012 she is a Scientist (sponsored by Dept. of Science & Technology, Govt. of India) at the Dept. of Pharmaceutical Technology (Biotechnology), NIPER, Mohali, India and pursuing research in the fields of nanobiotechnology and photomedicine for the cure of cancer and microbial infection.

Abstract:

Porphyrinic photosensitizers play essential role in photodynamic therapy (PDT), which is commonly used to treat diseases including cancer, cardiovascular disease and microbial infection. Tetrapyrrolic macrocycles are important members of porphyrin family, which largely contributes to PDT-mediated disease treatment. Though important as photomedicine, their hydrophobic nature prevents them to act efficiently in biological systems. Biocompatible nanomaterials are gaining high popularity in diverse biological applications. Nanoparticles are nowadays largely being applied as multifunctional probes, which can simultaneously be used for imaging and drug delivery. Combining photosensitizers with nanoparticles can large compensate limitations of their hydrophobicity. Various compact, hydrophilic and bio-conjugatable porphyrins were synthesized through rational routes. Taking advantage of the biocompatibility of NPs along with their large surface area for drug incorporation, porphyrins were successfully conjugated on NP surface via EDC mediated coupling. All those novel photosensitizers nanoconjugates were fully characterized by various techniques (e.g. spectrophotometric methods, HPLC). These newly developed nanophotosensitizer scaffolds are highly valuable for possible photomedical and biomedical applications of PDT due to their biocompatibility.

Hakan Ozturk

Faculty

Title: Prognostic features of renal sarcomas

Time : 18:20-18:40

Speaker
Biography:

Hakan Ozturk is a faculty in Department of Urology, School of Medicine, Sifa University, Turkey

Abstract:

Objective:
The aim of the present study was to evaluate the prognostic features of primary sarcomas of the kidney.

Material and Methods:
A literature review was conducted in various databases, including Medline (PubMed) and Scorpus for articles published between January 1992 and December 2013. Among the articles published in English, those describing prognostic features in primary sarcomas of the kidney were recorded. The electronic search was limited to the following keywords: sarcoma, renal sarcoma, prognosis, diagnosis, immunohistochemistry, genetic, and survey. There were no review articles and/or meta-analyses related to the prognosis of primary sarcoma of the kidney. A total of 31 articles related to case reports, case series, and overall prognosis of urological soft tissue sarcomas were reviewed.

Results: Primary sarcoma of the kidney has a poor prognosis compared to other sarcomas of the urogenital system. Other than surgical excision of the renal sarcomas, pathological, molecular, and genetic prognostic factors are also considered to exist. There are no studies randomizing the prognostic features due to the small number of cases. The elucidation of the so-called "chaotic" genetic and molecular basis of the tumor will help to predict the prognosis. Conclusion: Surgical excision is the most significant parameter determining the prognosis in the sarcomas of the kidney. However, sarcomas have prognostic features based on their pathological, genetic, and molecular basis. The current study suggests that other factors could also be important in predicting the prognosis, and clinicians should plan treatment and follow-up according to these factors.

  • Track 1: Cancer Cell Biology, Diagnostic and Prognostic Cancer Biomarkers Track 2: Organ-Specific Cancers, Cancer Genetics, Drug Development & Diagnostics Track 4: Tumor Science
Speaker

Chair

Raoudha Soufi -Mahjoubi

Novartis Pharmaceuticals Corporation, USA

Session Introduction

Rafael Silva Torres

Instituto Politecnico Nacional, Mexico

Title: Prunus serotina Erth rich in fl avonoids and coumarins, is cytotoxic to the tumor cell line Hela

Time : 12:00-12:20

Speaker
Biography:

Rafael Silva Torres has completed his PhD. at the age of 57 years from EscuelaNacional de CienciasBiológica of National Polytechnic Institute and abroad studies M. Phil. from Loughborough University of Technology Great Britain and sabbatical year from Museum National D`HistoireNaturelle Paris France. He has published more than 14 papers in reputed journals and 1 book chapters and hasbeen serving as an editorial board member of repute journals. He was director of 45 Bsc. Thesis and he was participated in more than 150 national and international congress. He is membership of National Association of Pharmaceutical Sciences and American Chemical Society. He is investigating the properties antitumor of medicinal plants such as: Sedum praealtum DC., PrunuaserotinaErth and Hylocereuspolyhizus.

Abstract:

There is great diversity in Mexico and many fl ora and faunaspeciesthat remain to be studied. One example is Prunusserotina Erth. Anethanolic extract from the fruit was prepared, in its chemical composition showed a lot of secondary metabolites. Besides, since cancer is adisease with high incidence rate and mortality, there is much interest in developing new treatments for chemotherapy or chemoprotection, based in Mexican plants. In Mexico, breast and cervical cancer stand out with high fi gures of impact and mortality. Cancer is defi ned as the alteration of cell cycle, resulting of uncontrolled proliferation and inhibition of apoptosis. Certainly, secondary metabolites from plants may perform as inhibitors of proliferation or directly as cytotoxic molecules, inducing apoptosis or necrosis in tumor cells.A probable antitumor eff ect of the fruit from Prunusserotina Erth (locally named capulín), is currently being conductedin our labs, using the HeLa cells in vitro model. Th e ethanolic extract from the fruit was further chromatographed on a dry silica gel column. Th e fractions were chemically and biological tested for their content. Th e extract and fractions were used for treatments to the HeLa cells in vitro and the cytotoxic eff ect was initially observed by inverted optic microscopy and death was estimated by fl ow cytometry techniques. Th e fractions were obtained using 80-20 % methanol-acetone and numbers 3 and 4 tested positive for alkaloids, fl avonoids and cumarins. Both showed cytotoxic eff ectand the fractions had better cytotoxicity than the ethanolic extract.

Speaker
Biography:

Yasmin Husaini has completed her PhD from Banaras Hindu University, India in 1994. She has done her Postdoctoral studies in Molecular Biology and Cancer from University of New South Wales, University of Sydney and University of Technology Sydney, Australia. She has been working on prostate cancer since 2005. At present she is leading a research team investigating the role of MIC-1/GDF15 in the biology of cancer at St Vincent’s Centre for Applied Medical Research, St Vincent’s Hospital, Sydney, Australia. She has published more than 20 papers in reputed journals.

Abstract:

MIC-1/GDF15 is a member of the TGF-β superfamily that plays role in the pathogenesis of a number of disease processes including cancer. MIC-1/GDF15 is overexpressed in prostate cancer (PCa) and other common malignancies and its expression is linked to cancer outcome. We have evaluated the eff ect of MIC-1/GDF15 overexpression and deletion on the evolution of PCa in transgenic TRAMP prostate cancer prone mice. We generated two syngeneic TRAMP mouse lines, one that overexpresses MIC-1/GDF15 (TRAMPfmsmic-1) and the other that lacks MIC-1/GDF15 expression (TRAMPMIC-/-). We then compared their survival, prostate tumor size, histopathological grade and extent of metastases with that of TRAMP mice. TRAMPMIC-/- had 4-5 weeks shorter survival but had larger prostate tumors at necropsy than TRAMP mice. However, TRAMPfmsmic-1 mice had 7 weeks longer survival, smaller genitourinary tumors and lower PCa grades but had higher incidence of metastasis than TRAMP mice. To confi rm this, we compared metastasis of TC1-T5, an androgen independent TRAMP cell line that lacks MIC-1/GDF15 expression, by injecting intravenously into MIC-1/GDF15 overexpressing (MIC-1fms) and syngeneic WT C57BL/6 mice. We observed a signifi cantly higher number of TC1-T5 lung tumor colonies in MIC-1fms mice than WT C57BL/6 mice. Our studies suggest that MIC-1/GDF15 plays a diff erent role in early compared to advanced cancer: Early in disease it may protect from and slows the growth of PCa. However, with advancing disease, MIC-1/GDF15 overexpression may promote metastases. As all cancer treatments induce MIC-1/GDF15 expression and metastasis is the major cause of cancer treatment failure, these results may have a direct impact on patient care.

Nisar Ahmad chowdri

Sher-i-kashmir institute of Medical sciences, India

Title: Low rectal cancer: Still a challenge for surgeons

Time : 12:40-13:00

Speaker
Biography:

Nisar Ahmad Chowdri is Professor & Head ,Colorectal Division; Department of General and Min Access Surgery at Sheri Kashmir Institute of Medical Sciences, Srinagar. India. He is the Founder Chairman of J&K State Chapter of Association of Surgeons of India, Governing Council member, Association of Surgeons of India, Jt Academic Convenor: Association of Colon & Rectal Surgeons of India (ACRSI),Vice President: Association of Colon & Rectal Surgeons of India (ACRSI), 2010-11,Vice President: International College of Surgeons (Indian Section), 2012-13. After getting his Postgraduation he has been working as a Faculty in Sheri- Kashmir Institute of Medical Sciences, Srinagar, Kashmir, India on different posts since 1991. He has been honoured with fellowships from Asso. of Indian Surgeons, International College of Surgeons (IS), Asso. of Colon & Rectal Surgeons of India, Association of Min Access Surgeons of India and American College of Surgeons and some prestigious travelling Fellowships/Professorship in colorectal surgery. He has published about 80 research articles in various national and international journals, authored/co-authored books/chapters and presented about 60 guest lectures/orations in various national and international forums.

Abstract:

The lecture will discuss the various options for management of low rectal cancers and highlight the advantages and drawbacks with these procedures in accordance with the evidence available in the world literature. Inspite of advances made in various surgical fi elds, low rectal cancers continue to pose challenge for a surgeon. No doubt now the rate of permanent stoma has come down and more and more patients with low rectal cancers are treated with sphincter conserving procedures. Apart from psychological set back, stoma itself is associated with various complications. Low and ultra low anterior resections are not without problems. Anterior resection syndrome is a complex of symtoms which has been reported with various degree of severity upto 50% of patients undergoing sphincter preserving operations. Infact sometimes these can be so distressing that both surgeon and patient repent on their decision and in certain circumstances one is compelled to convert to permanent stoma. Th erefor the author will try to explain the delegates the importance of proper decision making and discussion with the patient in detail about prones and cons of both these procedures before selecting the type of operation keeping in view the various risk factors for tumor recurrence and anterior resection syndrome.

Nathalie Rivard

Université de Sherbrooke, Canada

Title: Dual functions of SHP-2 tyrosine phosphatase in colorectal cancer

Time : 13:00-13:20

Speaker
Biography:

Nathalie Rivard received her PhD from Université de Sherbrooke in 1994 and completed a 3.5-year Postdoctorate at the Centre de Biochimie-CNRS, Université de Nice, in France with Dr. J.Pouysségur in 1997. Then, she accepted a Faculty position in the Department of Anatomy and Cell Biology at the Université de Sherbrooke. Her research focuses on the analysis of signalling pathways that control proliferation, differentiation, tumorigenesis and infl ammatory response of intestinal epithelial cells. She has published more than 80 papers in reputed journals. She is the recipient of 2013 Canadian Association of Gastroenterology Research Excellence Award andholds a Canada Research Chair.

Abstract:

Colorectal cancer (CRC) is the third most common cancer in the world. A major risk factor to develop CRC is the presence of chronic infl ammation in the colon. But how chronic infl ammation contributes to the development of CRC is not so clear. In seeking to answer this question, we have focused on the signalling molecule SHP-2, a tyrosine phosphatase modulating cellular signals induced by both growth factors and pro-infl ammatory cytokines. Polymorphisms in the PTPN11 locus encoding SHP-2 have been reported to be markers of colitis susceptibility. Conversely, gain-of-function mutations in PTPN11 have recently been associated with sporadic CRC. To investigate the role of SHP-2 in intestinal homeostasis, we have generated mice with an intestinal epithelial cell (IEC)-specifi c deletion of its expression. We demonstrated that IEC disruption of SHP-2 causes severe chronic infl ammation in the colon. Th is infl ammatory phenotype is associated with a dramatic increase in proliferation and activation of Wnt/-catenin, NFkB and STAT3 signallings in colonic epithelium. With age, these mice develop malignant lesions in the colon suggesting that SHP-2 can act as a tumor suppressor in this tissue. Furthermore, SHP-2 epithelial defi ciency severely increased colon tumor load in apcmin/+mice. Aside from these observations, we found increased expression and activating mutations of SHP-2 in sporadic human colorectal tumors and SHP-2 silencing markedly attenuated KRAS-induced transformation of IECs in culture. Hence, this suggests that SHP-2 can act as an oncogene in the colonic epithelium. Opposing roles for SHP-2in promoting and suppressing tumorigenesis in the large intestine are therefore proposed.

Thomas Brefort

Comprehensive Biomarker Center GmbH, Germany

Title: MicroRNA biomarkers for non-invasive diagnosis in oncology

Time : 13:20-13:40

Biography:

Thomas Brefort, Vice President Biomarker Development & Services is heading his multi-disciplinary team. He is responsible for the discovery, development and validation of novel non-invasive biomarkers includes scouting, validation and implementation of relevant innovative technologies. He established standardized SOP based processing and ensures comprehensive bioinformatic analyses of the different projects. Furthermore, he provides his scientifi c expertise in consultations on study design and results to CBC´s global Pharmaceutical Industry and Academic Customers and Partners. He joined the company in 2009 as Director Application Development (R&D), heading a cross-functional team on the Integration of Key Molecular Profi ling Applications on the proprietary Geniom® platform. Adding the wealth of scientifi c expertises from his career at the Max Planck Institute for Terrestrial Microbiology and his work at the Institute for Transplantation Diagnostics and Cell Therapeutics in Düsseldorf he steadily gained responsibilities culminating in his current position as CBC´s Vice President Biomarker Development and Services. A molecular biologist by training, he received his Diploma from the Department of Microbiology at the University of Marburg and his PhD in Cell Signaling and Functional Phytopathology and Secretomics at the Max Planck Institute for Terrestrial Microbiology. His broad and profound scientifi c expertise and hands-on experience and enthusiasm for (molecular) biology is refl ected in numerous scientifi c publications in Science, Nature and others.

Abstract:

MicroRNAs represent a group of short, non-coding RNAs that were shown to govern numerous physiological processes by post transcriptional interference with cellular mRNA transcripts. Originally discovered on tissue and cell culture samples, changes in the expression level of microRNAs were pinned to numerous pathological mechanism in an ever growing number of diseases including diff erent cancers. More recently, it became evident that microRNA levels detected from a broad range of body fl uids, blood, plasma/serum, CSF, urine also refl ect patho-physiological conditions of patients. We exploit microRNAs from body fl uids as novel non-invasive biomarkers to enable molecular diagnostic testing. Focussing on blood as our primary source, we teamed up with leading clinicians in the fi elds of cancer, and other diseases, and performed discovery projects on whole blood derived microRNA profi les. We successfully identifi ed high performance diagnostic and monitoring microRNA biomarker signatures. Currently, we validate these fi ndings and in parallel complement them by profi ling cell-free nucleic acids from serum/plasma samples as liquid biopsies. Case studies will be presented to demonstrate the potential of microRNA biomarkers for use in non-invasive diagnosis of Lung Cancer and Prostate Cancer.

Break: Lunch Break 13:40-14:25 @ Athens

Otavio Alberto Curioni

Hospital Heliopolis, Brazil

Title: The change of paradigm in initial therapy of head neck cancer

Time : 14:25-14:45

Speaker
Biography:

Otavio Alberto Curioni works in Hospital Heliopolis, Brazil.

Abstract:

Introduction: Due to advances in surgical techniques, radiotherapy and chemotherapy, there has been constant changes in the initial management of early and advanced head and neck cancer. Objective: To evaluate paradigm changes along the time. Data Synthesis: Surgery evolved rapidly from the improvement in anesthetic techniques, antibiotics, blood replacement, new reconstruction procedures, management strategies of neck metastasis and laryngeal cancer. Recognized as an eff ective staging and therapeutic procedure, elective neck dissection diminished functional and aesthetic sequelae. Partial laryngectomies and endoscopic transoral laser resection could keep the function of speech and swallowing without defi nitive tracheostomy. Advances in creating algorithms calculation and distribution of more accurate dose enabled the development of dosimetry and quality control in radiotherapy,providing a more conservative approach. Th e radiotherapy with intensity modulation has high precision with better protection of organs at risk. Altered fractionation schemes can reduce the late toxicity with survival benefi t. Tomotherapy, volumetric modulated archoterapy, stereotactic radiotherapy and FDG-PET CT are recent approaches. Induction and sequential chemotherapy is a key component in the treatment of locally advanced head and neck cancer. Th e receiver of Epidermal Growth Factor IgG1 monoclonal antibody (EGFR) showed signifi cant clinical benefi ts in the treatment of locally advanced, recurrent and/or metastatic cancer. Conclusion: Th us, the treatment of head and neck cancer patients should be multidisciplinary and advances in strategies have improved the outcome.

Maher Salamoon

Bairouni university hospital, Syria

Title: Metastatic breast cancer: Getting the facts from peripheral blood

Time : 14:45-15:05

Biography:

Maher Salamoon obtained his MD from the Faculty of Medicine from Damascus University School of Medicine (Syria) in 1998 then a Master degree in Medical Oncology and Hemato-Oncology from the Nuclear Medicine Centre, Damascus University in 2003, then a Post-doctoral study in Medical Oncology and Molecular Biology from Curie Institution in Paris (France). He did subspecialty in Non-Hodgkin Lymphoma and bone marrow transplant from Lyon-Sud University Hospital in Lyon (France) in 2006. He is the Head of Breast Cancer Department at Al Bairouni University Hospital 2008-2011, Damascus (Syria) and Head of Department of Soft Tissue Sarcoma at the same hospital (2011-2013). At present, he is the Team Leader of translational research at al Bairouni University Hospital and the institute of bio-technology. He contributed more than 10 papers on translational research in several international oncology and hematology conference and 7 of them are in peer review, with more than 50 national and international publications. He was a speaker in several international and national meetings and reviewed more than 200 papers for international reputable journals.

Abstract:

Background: Breast cancer is still a major challenge for oncologists worldwide, though giant steps made on orienting treatment, however, understanding tumor biology and cancer cell behavior is still at the beginning especially when we deal with an immortal, pluripotent cell. Objective: Th e study is aiming at isolating both circulating breast cancer cells and breast cancer stem cells, expanding them by cell culture and transforming them to paraffi n embedded tissue like biopsy with a good yield upon immunohistochemistry. Patients and methods: Th e study was performed at al Bairouni University Hospital and Kenj Cytogenetic Lab in Damascus (SYRIA). Blood samples were obtained from 100 chemonaive metastatic breast cancer patients. Samples were cultured in (DMEM) media, and aft er certain passages we obtained breast cancer stem cells CD44 high/CD24 low confi rmed through passage in fl owcytometer and PCR of protein product of CD44 surface protein. Th en, obtained cells were subjected to immunohistochemistry for ER/PR/Her-2 aft er they were embedded in paraffi n by means of Liquid based cytology. Results and discussion: We obtained good population of cells through expanding the circulating cancer cells and results of immunophenotyping were the same with the results obtained from the primary tumors (P 0.0001) except in 4 cases where Her-2 was positive on circulating cancer cells while it was negative on the primary. Conclusion: Isolating tumor cells from circulation seems to be an effi cient method in evaluating tumor characteristics and behavior. Our method is simple, cheap and informative; however, much work should be done to validate our results.

Speaker
Biography:

Daniela Barsotti Santos is a psychologist and obtained PhD in Health Sciences, is a Postdoctoral Fellow in the Department of Social Medicine, Ribeirão Preto Medical School, University of São Paulo.

Abstract:

Introduction: Sexuality can be aff ected aft er the impairment by an illness such as breast cancer which the treatment causes several body modifi cations impacting sexual function. Objective: To understand the psychosocial aspects of the sexuality aft er breast cancer by the comparison of sexual function evaluation with the types of treatments, sexual frequency, satisfaction with the loving relationship and gender roles. Method: Th is mixed methods study of convergent design included data of a survey with 139 women analyzed by clusters and the data of qualitative interviews conducted with 24 participants using semi-structured guideline. Th ese interviews were analyzed based on the theory of Sexual Scripts. Results: In the quantitative component, 67 women answered the Female Sexual Function Index (FSFI) among the total of 139 participants. By the FSFI score it was obtained 6 clusters in which half of them presented sexual dysfunction or suggestion of some sexual problems. Th ree sexual scripts were identifi ed: the script of sexuality based on traditional gender roles, the script of sexuality related to aging, and the script of sexuality based on wellbeing. Th e alteration of sexual function was not decisive for some women consider worsening of their sexual life aft er cancer. Th ere were some reports of improvement of sexual life and some women reported that sex life remained the same as before. Final considerations: It is important to health professionals deconstruct stereotypes related to sexuality issues in the breast cancer to assist women in the refl exivity process and development of positive ways to deal with the sexuality.

Biography:

Elke Wagler works in Pleissental-Clinic Werdau/Saxony, Germany.

Abstract:

Introduction: In case of primary peritoneal carcinomatosis of unexplained origin deferred hyperthermic intraperitoneal chemotherapy (HIPEC) is given in our oncological focused clinic. With primary confi rmed histology one-stage HIPEC will be carried out following resection. Several studies have discussed the ideal time of HIPEC in relation to intraoperatively complications. Objectives: Analysis of the results of the two-stage proceeding in terms of morbidity and mortality, Hospitalization. Methods: Peritoneal carcinomatosis patients with resection of diff erent locations were used in this for our observations. According to the histological fi ndings, the patients were treated with one- or two-stage HIPEC. Th e analysis occurred retrospectively in terms of morbidity and mortality. Results: Th e morbidity in our series was very low. One patient died due to cardiac complications. Prolonged intensive care was needed in patients with two-stage HIPEC. However, the total average length of stay in hospital was not signifi cantly higher. Th e apportionment of the individual complications will be discussed at the congress. Conclusion: Comparing the published data with the one-stage approach, a signifi cant diff erence of the total hospitalization time as well as time needed in intensive care has been shown. Th e documented morbidity and mortality is comparable to the documented results of other studies. In terms of long-term survival rates, no diff erence can be detected in our relatively small group of patients compared to the published data on one-stage procedures.

Biography:

S N Morozkina is working in steroid research at the Department of Natural Chemistry Department at Saint-Petersburg State University start from 2004 after Postdoctoralship in Organic Chemistry. She has 15 patents and more than 45 articles.

Abstract:

Atherosclerosis, hardening of arteries, is the primary cause of cardiovascular disease. Oxidative damage plays an important role in atherogenesis, the key events of which are modifi cation of low density lipoprotein (LDL) and its retention in arterial wall. In addition to atherosclerosis, oxidative stress and lipid peroxidation have been implicated in neurodegenerative diseases and aging. Estrogens are known antioxidants. Th e antioxidant eff ects of estrogens are mainly due to direct free-radical scavenging, independent of binding to estrogen receptors. Other possible mechanisms include reduction or chelation of redoxactive metal ions. Based on previous studies on human endogenous estrogens, the structural determinants for the in vitro antioxidant activity include a phenolic A-ring, 1 or 2 adjacent methoxy groups to the phenolic OH, and incorporation of an aromatic B-ring. In the present study, we describe the synthesis of novel steroidal estrogen analogues with various substitutions in the steroidal skeleton. In addition to develop synthetic methodology, the aim was to study structural determinants of estrogen antioxidant eff ects.We set out to explore the in vitro antioxidant activity of the new estrogen analogues in aqueous LDL solution, in comparison with the principal endogenous estrogen, 17β-estradiol. We tested a wide series of steroidal estrogen analogues (n=45) with unnatural ring junction and having various substituents on the steroidal skeleton, most of these compounds (n=22) were new and thus, their antioxidant or other biological eff ects unknown. Th e synthetic strategy was based on the method of Torgov and Ananchenko, which enables to synthesize steroidal compounds of diverse structures. In summary, our results demonstrate the way of increasing of antioxidant capacity through structural changes. For example in the group of 6-oxa analogues, the extension of D-ring led to increment of activity up to level of 17β-E2. Analogues with fl uorine atom at C-2 exhibited antioxidant eff ects similar or more potent to 17β-E2. Th us, in addition to their metabolic stability, these compounds are of interest as antioxidative agents. Antioxidant activity of estrogen analogues without a free phenolic hydroxyl group was observed for the fi rst time and it is worth further investigations. More studies are also needed to determine the role of steric factors in the interaction between antioxidants and LDL particles, using synthetic estrogen analogues with substitutions in D-ring and diff erent orientation of ring junction.

Break: Coffee Break 16:05-16:20 @ Versailles Foyer
Speaker
Biography:

Guoqiang Shao completed his PhD in Nanjing Medical University from 2009 to 2012. He further studied in Shuang Liu`s Lab in Purdue University as visiting Scholar from May 2011 to March 2012. He took part in several research project in targeted brachytherpy with biodegradable seeds encapsulating 32P-Chromic phophate. His interest focused on integrin αvβ3, folate and prostate specifi c membrane antigen receptor targeted tumor imaging and therapy. Two of his grants were funded by the Natural Science Foundation of China (NSFC) and of Jiangsu Province.

Abstract:

Backgroud and Aim: Ovarian cancer is the leading cause of death among women with gynecologic malignancies. Th e survival rate has remained low largely because of diffi culties of an early diagnosis. Th e high-affi nity folate receptor (FR) has proven a valuable target for nuclear imaging using folic acid radioconjugates because of its frequent over expression in ovarian cancer but limited expression in normal human tissues and organs. Folate monomer, commonly used for folate receptor targeted imaging, demonstrate relatively low tumor uptake and high kidney accumulatioin. We prepared 68Ga-DOTA-FA2 with the aim to optimize its biodistribution and increase tumor uptake. Methods: 68Ga-DOTA-FA2 was synthesised straightforward and its stability experiments were conducted in plasma. Cell uptake studies were performed on FR-positive SKOV3 Ovarian cancer cells. Biodistribution studies were performed in nude mice bearing SKOV3 ovarian tumors 1, 2, 4h aft er administration of 68Ga-DOTA-FA2 or 68Ga-DOTA-FA monomer. MicroPET-CT imaging were carried out in nude mice bearing SKOV3 ovarian tumors or FR-negative A549 lung cancer 2h aft er tail vein injection of 68Ga-DOTA-FA2. All animals accepted folate-free diet for 2 weeks. Results: 68Ga-DOTA-FA2 was synthesised at a specifi c activity of 25MBq/nmol, a radiochemical yield of more than 95%. It was stable with radioactive purity of (96.3±1.5) over 4h in plasma. SKOV3 cells uptake and internalization of 68Ga-DOTA-FA2 was FR specifi c. Th is is confi rmed by the biodistribution data. In biodistribution studies tumor uptake of 68Ga-DOTA-FA2 in SKOV3 group was (11.07±1.83)%ID/g at 2h and (12.19±1.72)%ID/g at 4h. Th ey were higher than that of 68Ga-DOTAFA (7.36±1.28)%ID/g at 2h and (9.72±2.04)%ID/g at 4h. Retention of 68Ga-DOTA-FA2 in kidneys at 4h aft er injection (49.3±11.02%)ID/g was lower than that of 68Ga-DOTA-FA (78.5±18.33)%ID/g. MicroPET-CT imaging demonstrated signifi cantly higher tumor accumulation of 68Ga-DOTA-FA2 in SKOV3 ovarian tumors (10.18±1.52)%ID/g than that in A549 lung cancer (2.25±0.92)%ID/g. Conclusions: 68Ga-DOTA-FA2, with higher tumor uptake and less undesired accumulation in kidneys than FA monomer, was potential for targeted imaging of FR-positive ovarian tumors.

Biography:

Michailidou Evangelia is a PhD student in the Aristotle University of Greece. She completed her Master’s degree in Oral Medicine and Maxillofacial Pathology, awarded with a scholarship from the State Scholarships Foundation. During the Master her research was focused on angiogenesis in oral cancer and the role of VEGF (vascular endothelial growth factor) and mast cells in this procedure. Her PhD research won the annual sponsorship “Koulouridis” sponsored by Procter & Gamble Company and is focused on biomarkers in the early diagnosis of oral cancer. Her work has been published in reputed journals and she has also served as a reviewer.

Abstract:

Early detection of oral squamous cell carcinoma is the key to its management and successful early therapeutic approach. Th e aim of the present study was to evaluate the possibility that saliva could serve as a tool in the early detection of oral squamous cell carcinoma. Th e presence of extracellular mRNAs of IL-1B, IL-8, OAZ and SAT, which were previously reported as signifi cantly elevated in patients suff ering from the disease, was evaluated in RNA isolated from saliva samples. Patients and Methods: 37 patients with oral squamous cell carcinoma stage T1N0M0 or T2N0M0 , 23 patients suff ering from oral leukoplakia with various degrees of dysplasia and 31 healthy-control subjects matched were included in the study. Th is is the fi rst study of these markers were tested as potential biomarkers in the early detection of oral squamous cell carcinoma in both patients with oral leukoplakia a potentially malignant disorder and patients with oral squamous cell carcinoma. Th e expression of the 4 mRNAs was detected using sequence-specifi c primers by the real-time RT-PCR based detection methodology. Th e ROC curve analysis was used to estimate the ability of the markers to detect oral cancer. Results: Th e four biomarkers only combined gave us a good predictive ability in oral cancer, a predictive ability of 80%. Conclusion: Th e results shed some light on the role of saliva and salivary mRNAs in the early detection of oral squamous cell carcinomas, much work has yet to be done down the road.

Biography:

Yanming Wang is an Associate Professor in Pennsylvania State University, University Park with expertise in Cancer Research, Cell Biology is on ResearchGate. He has 64 publications and 5, 501 citations.

Abstract:

We previously reported that a pan-PAD inhibitor YW3-56 activates p53 target genes to inhibit cancer growth. However, the broad anticancer effi cacy and drug mechanisms of YW3-56 remained largely elusive. Here, gene expression analyses found that ATF4 target genes involved in ER stress response and oxidative stress response were activated by YW3- 56. Depletion of ATF4 greatly attenuated YW3-56 mediated activation of the mTORC1 regulatory genes, SESN2 and DDIT4. Using the ChIP-exo method, high-resolution genomic binding sites of ATF4 and CEBPB were generated prior to and aft er YW3-56 treatment. Moreover, YW3-56 increases cellular ROS levels to facilitate ATF4 target gene activation and cancer cell killing. YW3-56 mediated cell death features mitochondria depletion and autophagy perturbation. At last, YW3-56 treatment eff ectively inhibits the growth of triple negative breast cancer xenograft tumors in nude mice. Taken together, we unveiled the anticancer mechanisms and therapeutic potentials of the pan-PAD inhibitor YW3-56.

Speaker
Biography:

Raoudha Soufi -Mahjoubi MD is Senior Medical Director of US Oncology at Novartis Pharmaceutical Corporation. She obtained her medical degree from Faculté de Médecine, Tunis and specialized in Medical Oncology at Université René Descartes, Paris. She has academic experience in medical oncology, and has 18 years of experience in the pharmaceutical industry with a strong expertise in clinical research and drug development in oncology.

Abstract:

Activation of the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway in cancer is associated with tumor growth, progression, and the development of resistance to anticancer therapy. PI3K is therefore a promising target for drug development. Various PI3K inhibitors are currently under evaluation in clinical trials, including the pan-PI3K inhibitor buparlisib (BKM120) and the PI3Kα-specifi c inhibitor alpelisib (BYL719). Early clinical studies with these compounds indicated the safety profi les were manageable, with mostly on-target adverse events, such as hyperglycemia. Early signs of clinical activity were also observed. However, consistent with preclinical models suggesting PI3K inhibition can overcome resistance to other anticancer drugs, the greatest opportunities for these compounds appear to be in combination, particularly with endocrine and other targeted therapies. Buparlisib is currently being evaluated in various combinations in Phase III studies in breast cancer, including BELLE-2 and BELLE-3, and Phase II studies in other indications. Alpelisib isbeing evaluated in combination in Phase II studies in breast cancer and head and neck cancer, among other indications. As these compounds advance through clinical development,several questions remain. In particular, which PI3K inhibitor is likely to be most eff ective in which tumor type, and what biomarker will predict the patient population most likely to benefi t from PI3K inhibitor therapy? Novartis is employing a fl exible approach to biomarker-driven study design to address these questions and maximise the benefi ts of clinical studies with buparlisib and alpelisib. An overview of the Novartis PI3Kinhibitor program utilising these approachesin diff erent cancers will be described.

Luciano Neder Serafini

University of São Paulo, Brazil

Title: Revealing micro RNAs in malignant progression of oligodendrogliomas

Time : 17:40-18:00

Speaker
Biography:

Luciano Neder Serafini is a faculty in University of São Paulo, Brazil.

Abstract:

MicroRNAs (miRNAs, miRs) are short non-coding regulatory RNA molecules found ubiquitously in living beings. Recently, miRNAs have also been implicated in oncogenesis, acting as tumor suppressors or oncogenes. Hitherto, the role of miRNAs in CNS tumors has been intensively investigated in glioblastomas and medulloblastomas, but there are few data regarding the role of miRNAs in oligo dendrogliomas. We performed a systematic evaluation of miRNAs and mRNAs expressions in a series of oligo dendrogliomas of diff erent grades of malignancy to determine miRNAs and putative target genes that are diff erentially expressed in grade III oligo dendrogliomas. Total RNA was extract from 14 cases of bona fi de grade II and III oligo dendrogliomas naïve of treatment (7 cases per grade) aft er tumor micro dissection. For each case, the expression of miRNAs (100 ng) and mRNAs (200 ng) was evaluated using microarray-based expression profi ling platforms (723 transcripts and 41,000 genes, respectively). Samples of temporal white matter from patients operated for epilepsy were used as controls (n=15). Th e study was approved by Ethical Committee. Fift een and 20 miRNAs were signifi cantly overand under expressed in anaplastic oligodendrogliomas, respectively. However, aft er matching with the expressions of putative target-mRNAs disclosed by microarray, we were able to validate 8 out of 10 miRNAs by RT-qPCR (assays in duplicate). Among the hypo-expressed miRNAs, we found some miRs that were previously described in cell diff erentiation of embryonic stem cells (miR27a, miR-30a/PDGFA and miR24/HDAC2) as well as miR193a-3p and miR30c/RARB. Conversely, among the hyper-expressed miRNAs, we validated the microarray data of miR301/BCL-2 and miR378/FGF2, and PPP4R4 and CD44. Nonetheless, we were able to identify and validate some oncogenic miRNAs and putative target-mRNAs that can be operating in malignant progression of oligodendrogliomas. Th e biological roles of these miRNAs are being addressed through functional assays in primary cell lines of gliomas.

Speaker
Biography:

Taketoshi Suehiro has completed his MD (1989) and PhD (2000) from Kyushu University. He did the clinical training and research of the liver transplantation in Mount Sinai Hospital, New York from 1993 to 1996. He is Assistant Director of Onga-Nakama Medical Association Onga Hospital. His specialty is wide with digestive organ surgery, endoscope, infectious disease, nutrition and so on. He has published more than 70 papers insurgical journals and has been serving as an Editorial Board Member of Hepato-Gastroenterology Journal.

Abstract:

We have developed the fi rst of its kind- automatic pharmaceutical and operating room product recognition system. Th is is a new and very novel technology and clearly the fi rst of its kind in the world: “CUMLUS”. Our intent is to examine the eff ectiveness and usefulness in the operating room of the hospital. We collected the data of G.I. surgery cases and we’re able to calculate procedure cost, improved billing accuracy by capturing missed charges and improved the effi ciency of the circulating nurse. Nurses were able to return to patient care versus focusing on logistic data entry. By using the CUMLUS system we observed a signifi cant savings and profi t realization. Th e overtime for the OR nurse was also reduced in half due to the reduction of ineffi cient nursing duties. Furthermore, as a result of cost analysis by data from the CUMLUS system, we were able to capture of 1,600 dollars per laparoscopic cholecystectomy procedure. Th is alone was a $80,000.00 annual savings. We concluded that the use of the CUMLUS system facilitated effi cient and accurate management of the Operating Room’s inventory. Th is system improved accuracy of patient billing, replenishment and timely purchasing allowing for real time inventory recognition and control plus provided immediate Profi t and Loss reports for each procedure. As a result, this improved quality of patient care versus logistical time spent on data entry.

Break: 18:30-19:30:
Cocktails sponsored by Journal of Cancer Science & Therapy @ Athens