International Cancer Study & Therapy Conference
April 4-6, 2016   Baltimore, USA
Day 2 : 04:05:2016

Keynote Forum

Vikas Kundra

M.D. Anderson Cancer Center, USA
Keynote:
Multimodal magnetic resonance and near-infrared-fluorescent imaging of intraperitoneal ovarian cancer using a dual-mode-dual-gadolinium liposomal contrast agent

Biography :

Vikas Kundra, M.D., Ph.D. is Professor and Director of Molecular Imaging in the Department of Radiology, U.T.-M.D. Anderson Cancer Center with joint appointment in the Department of Cancer Systems Imaging. He received his M.D. and Ph.D. from Harvard University and completed his radiology training at Brigham and Women’s Hospital. He is a Fellow of the Society of Body Computed Tomography-Magnetic Resonance Imaging and a Distinguished Investigator of the Academy of Radiology Research. Clinical work focuses on Body Imaging particularly in cancer and research focuses on molecular imaging, including imaging of gene expression and nanotechnology.

Abstract :

The degree of cytoreduction at surgery is a major prognostic factor for ovarian cancer.A multimodality agent that can be used with magnetic resonance (MR) for staging and pre-surgical planning, and with optical imaging to aid surgical removal of tumors, would present a new paradigm for ovarian cancer. We assessed whether a dual-mode, dual-Gadolinium (DM-Dual Gd-ICG) contrast agent can be used to visualize intraperitoneal ovarian tumors by multimodal MR and near infra-red imaging (NIR).  Intraperitoneal ovarian tumors (Hey-A8 or OVCAR3) in mice enhanced on MR two days after intravenous DM-Dual Gd-ICG injection compared to controls (SNR, p<0.05, n=6). As seen on laparotomy and excised tumors views and confirmed by radiant efficiency measurement, Hey-A8 or OVCAR3 tumors from animals injected with DM-Dual Gd-ICG had increased fluorescence (p<0.05, n=6). This suggests clinical potential to localize ovarian tumors by MR for staging and surgical planning, and, by NIR at surgery for resection.

Keynote Forum

Yoshiaki Omura

New York Medical College, USA
Keynote:
New method of detecting various cancers & their biochemical information from ECGs was found. Using ECGs, we can screen cancers of the same patient & Lyme disease infections of various parts of the heart as one of major cause of atrial fibrillation

Biography :

Yoshiaki Omura received Oncological Residency training at Cancer Institute of Columbia University & Doctor of Science Degree through research on Pharmaco-Electro-Physiology of Single Cardiac Cells in-vivo and in-vitro from Columbia Uni.. He studied & researched on EMF Resonance phenomenon between 2 identical molecules at graduate experimental physics dept. ,Columbia Uni.. He published over 270 original research articles, many chapters, & 9 books. He is currently Adjunct Prof. of Family &Community Medicine, NY Medical College; Director of Medical Research, Heart Disease Research Foundation of NY; President & Prof. of Int’l College of Acupuncture & Electro-Therapeutics, NY; Editor in Chief, Acupuncture & Electro-Therapeutics Research, Int’l Journal of Integrative Medicine, (indexed by 17 major int’l Indexing Periodicals); Editor of Integrative Oncology. Formerly, he was also Adjunct Prof. or Visiting Prof. in Universities in USA, France, Germany, Italy, Ukraine, Brazil, Portugal, Turkey, Serbia, Japan, Korea, Taiwan, & China.

Abstract :

Introduction: During the past 10 years, the author successfully detected biochemical changes, bacterial and viral infections, and identifying the exact location of the infections of different parts of the heart by ECGs. Recently the author found that using ECGs, not only can information on the different parts of the heart be obtained, but various cancers existing in the body can also be detected.

Method: Various cancers existing at any part of the body were detected from rapidly changing QRS complex as well as rising part of T-wave of every ECG by detecting maximum Electromagnetic Field (EMF) Resonance Phenomenon between 2 identical molecules with the same amount using a simple method which received a U.S patent in 1993. From recorded ECGs, EMF Resonance Phenomenon between specific cancer microscope tissue slides and ECG were only detected from rapidly changing part of QRS complexes of ECGs & a part of rising part of T-waves, which corresponds to vulnerable period for Ventricular Fibrillation.

Results: Strong EMF resonance was found between not only rapidly changing dV/dt at QRS complex of ECGs, but also the author found even at rising part of the T-wave where change of dV/dt is insignificantly small. The author was able to detect caner of various organs including lung, esophagus, breast, stomach, colon, uterus, ovary, prostate gland, common bone marrow related malignancies such as Hodgkin’s Lymphoma, Non-Hodgkin’s Lymphoma, Multiple Myeloma as well as Leukemia. In addition, the author was also able to find when the patient had more than one different cancer at different parts of the body. Most of the medicine taken within 8-10 hours before taking ECG can be detected from part of QRS complex & rising part of T-waves. At Borrelia Burgdorferi (B.B.) infected part of ECGs we found significant decrease of Taurine & marked increase of ANP & cardiac Troponin I. At every cancer tissue, Taurine was markedly reduced.Thus, by comparing the same lead of ECGs before and after any treatment, the therapeutic effect of specific cancers or Lyme disease infection of B.B. spirochete infections of AF can be evaluated.

Discussion: If electrocardiogram is taken periodically we can find approximately when cancer information starts appearing in the electrocardiogram. Maximum information from cancer can be found in QRS complex where dV/dt is relatively large. This new concept and method can be applied to any recorded ECGs for detection and Screening of the cancer & infection including Lyme disease. Thus, ECGs can provide not only the information on the heart, but also can provide any single cancer or multiple cancers, which exist in any part of the body of the same individual.

Session 3 : Cancer Care and Psychological Support & Structural Biology and Biomarkers

Session Introduction

Shulamith Kreitler

Tel-Aviv University, Israel
Title: Psychological risk factors in cancer diseases

Biography :

Shulamith Kreitler is a professor of psychology at Tel Aviv University, has established the Unit for Psychooncology at the Ichilov Hospital in Tel Aviv and since 2007 is the head of the psychooncology research center at Sheba Medical Center, Tel Hashomer. She is a certified clinical and health psychologist and has taught at Harvard, Princeton and Yale, as well as in Argentina and Vienna, Austria..Her research is in personality and cognition, with an emphasis on psychological factors involve in the occurrence of oncological diseases and coping with them. Her books include Handbook of Chronic Pain (2007), Pediatric Psycho-Oncology: Psychosocial Aspects and Clinical Interventions (2004, 2012).

Abstract :

The talk will deal with the issue of the psychological correlates for cancer. Psychological correlates of a disease are personality tendencies or responses that can be shown to be risk factors for the disease and possibly contribute also to remission and recovery from the disease. Previous attempts to identify such correlates in oncology have failed, mainly because the psychological variables that have been assessed were likely to be affected by the disease itself (e.g., depression) and not enough consideration has been paid to medical variables.  A set of studies launched at the PsychooncologyResearchCenter approached the issue from the point of view of the innovative theory and methodology of the cognitive orientation theory. The major thesis of this theory is that physiological processes that may be precursors of diseases are affected by psychological factors that are beliefs of four types (about oneself, about reality, about rules and norms and about goals)   referring to themes that have been identified as relevant for a particular disease. Questionnaires assessing different kinds of cancer diseases have been prepared on the basis of the cognitive orientation theory. Studies showed that the questionnaires have enabled identifying correctly cancer patients, such as breast cancer, colon cancer, thyroid cancer and prostate cancer. For example, themes that constitute the personality correlates of colorectal cancer were found to include tendencies for compulsiveness, perfectionism, and self control. The talk will present studies concerning mainly breast cancer and colon cancer. Our claim is that the identified tendencies constitute potentially sources of tension and may be considered as psychological risk factors in oncology. The effects of psychological interventions based on the identified variables will be presented.

Guang Zhu

The Hong Kong University of Science and Technology, Hong Kong
Title: Mechanistic study of human DNA replication proteins that regulate cell proliferation and differentiation

Biography :

Dr. Guang Zhu is a Professor of Division of Life Science, The Hong Kong University of Science and Technology. He obtained his B. Sc and M. Sc in physics. He studied for his Ph.D degree at University of Maryland and National Institutes of Health, USA, specialized in biomolecular NMR spectroscopy. Currently Dr. Guang Zhu’s research focuses on structure-functional study of human proteins in DNA replication. Studies on the molecular mechanisms of proteins involved in DNA replication provide basis for structure-based drug design against cancer. He has published more than 81 peer-reviewed reports. He has served on the editorial boards of International Journal of Spectroscopy and Chinese Journal of Magnetic Resonance.

Abstract :

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

Ancha Baranova

George Mason University, USA
Title: Circulating DNA as a source of novel types of cancer biomarkers

Biography :

Dr. Ancha Baranova, a specialist in the area of functional genomics of complex human diseases, is an Associate Professor in the School of Systems Biology, College of Science, George Mason University in Fairfax, Virginia, USA, and Principal Investigator at Russian Centre for Medical Genetics, Moscow. Dr. Baranova's major academic contributions are in the field of personalized medicine. A significant part of Dr. Baranova’s efforts is dedicated to in silico analysis of the publicly available datasets. Dr. Baranova employs a multidisciplinary approach in order to broaden research perspective in the genetics of complex human diseases.

Abstract :

An assesement of cell-free circulating DNA (cfDNA) fragments, or Liquid biopsy, is indeispensable for early diagnosi and non-invasing monitoring of cancer. However, the majority of the cfDNA studies aim at relatively simple search for cancer-driving mutations or particular variants associated with susceptibility and resistance to targeted therapy. Important, inderstudied properties of cfDNA may become either a treasure trove for mining of novel cancer biomarkers or even indicate that cfDNA, by itself, could be a therapeutical target. The fragmentation patterns of cfDNA are non-random. They reflect fragmentation of DNA during apoptosis, that in turn, may associate with epigenetic landscapes. Circulating nucleotide fragments copy number depends on the nucleosomal positioning in given DNA locus. PCR primer systems may be tuned to the regions that would produce higher DNA amplification outcomes. Sensitivity of detection can be increased by simultanious isolation of “free” DNA molecules and these adsorbed to cells’ surface.The prevalence of certain DNA fragments may directly reflect nucleosome positioning within certain loci and serve as a proxy for gene expression levels. This opens a novel field in biomarker research, tentatively called “fragmentomics”. Moreover, cfDNA fragments are biologically active as they are enriched in 8-oxo-dG. The oxidized DNA is a stress signal released in response to oxidative stress. It might contribute to systemic abscopal effects of localized irradiation treatments. The mass release of oxidized DNA that accompanies apoptotic and necrotic processes in radio- and chemotherapy treated tumors may aid survival of residual cancer cells and even instigate their resistance to further treatment. The selective removal of oxidized DNA from the bloodstream or the block of respective oxidized DNA-dependent signaling may be developed as an adjuvant treatment.Current research is funded by Russian Ministry of Science and Education under the project ID# RFMEFI60714X0098

Abdelhamid Ghazal

Alexandria University, Egypt
Title: Clinical significance of MicroRNA21 expression in colon cancer

Biography :

Dr. Abdelhamid Ghazal is a Professor of General Surgery at the faculty of medicine-Alexandria University in Alexandria-Egypt. He obtained his masters in general surgery in 1998 and his MD in general surgery from the University of Alexandriain 2004. Dr. Abdelhamid Ghazal is experienced in laparoscopic surgeries, Diagnostic and therapeutic endoscopy. His academic professional experience dates since 1998 in teaching and supervision of medical students and general surgery residents in Alexandria Main University Hospital. He supervised surgery master and MD students since 2004. Dr. Abdelhamid Ghazal has many publications in international, peer reviewed journals concerning hepatic resection, pancreatic tumors, laparoscopic and endoscopic biliary surgery, elective and emergency colonic surgeries.

Abstract :

Background: Colorectal cancer (CRC) is a major health problem with high mortality rates. New clinical biomarkers and therapeutic targets are needed for early diagnosis and adequate tumor staging. MicroRNAs are a family of small noncoding RNAs that are involved in regulation of gene expression. They are aberrantly expressed in many types of carcinomas.  MicroRNA-21 (miR-21) was found to be up-regulated in several cancers and is therefore very promising as a clinical biomarker and therapeutic target.

The aim of the study was to assess the microRNA 21 expression in colon cancer tissues and adjacent nontumor tissues to evaluate its potential role in tumor diagnosis and its relation to clinicopathological features of colon cancer.

Methods: Total RNA was extracted with small RNA enrichment from the tissues samples of colon cancer as well as their adjacent non-tumor tissues taken from 60 patients. After reverse transcription, the expression of microRNA-21 was measured using quantitative real-time PCR.

Results: Expression levels of microRNA-21 in colon cancer was significantly higher than that their adjacent non-tumor tissues (p<0.001). Furthermore, high expression of microRNA-21 was associated with lymphovascular invasion, advanced tumor invasion, presence of lymph node, distant metastasis, advanced tumor Stage and high tumor grade of differentiation.  On the other hand, micoRNA 21 expression was not significantly associated with age, sex, tumor size or tumor location.

Conclusion: MicroRNA 21 can differentiate tumor from adjacent non-tumor tissue with high diagnostic accuracy. It can also predict the presence of advanced tumor invasion, lymph node and distant metastasis in patients with colon cancer, which could help in tumor staging, and customized clinical management of colon cancer.

Zhaolin Xu

Dalhousie University, Canada
Title: Lung cancer molecular profiling in clinical practice

Biography :

Dr. Zhaolin Xu, MD, FRCPC, FCAP, is a professor in the Department of Pathology, Dalhousie University, and a pulmonary pathologist and cytopathologist in the Queen Elizabeth II Health Sciences Centre in Halifax, Canada. He obtained Fellowship Certifications from both the Royal College of Physicians and Surgeons of Canada and the American Board of Pathology. In addition Dr. Xu is a cancer researcher and holds the position of Senior Scientist in the Beatrice Hunter Cancer Research Institute, Canada. He is the Expert Panel Member in the Lung National Cancer Pathology and Staging Multidisciplinary Expert Panel, Canadian Partnership against Cancer (CPAC). He is also the Chair of Pathology Working Group and Network Member, Pan-Canadian Lung Cancer Screening Network, CPAC, and Medical Advisory Committee Member, Lung Cancer Canada.

Abstract :

Lung cancer is the leading cause of death from cancer for both men and women worldwide. Majority of lung cancer patients are in the advanced stage at the time of diagnosis and palliative management with chemotherapy and/or radiation being the treatment of choice. The overall response rate is low with a five year survival for a late stage disease being only about 4-5%. These conventional methods also cause significant cytotoxicity /adverse effects to the patients. Recent advances in lung cancer molecular genotyping provide the basis for personalized targeted therapy. It targets the individual’s genetic makeup with encouraging clinical outcomes for highly selected lung cancer patients. Current treatment options are available against lung cancer cells exhibiting mutations of the genes encoding the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) by inhibiting tyrosine-kinases associated with the mutant genes. There are a variety of mutant genes in lung cancer cells which cause cancer cell proliferation, and many of these genes are mutually exclusive. Over 600 cases of surgically resected non-small cell lung cancer including adenocarcinoma, squamous cell carcinoma, large cell carcinoma and a miscellaneous group were selected for the study and all of them were investigated by molecular analysis for six possible gene mutations including KRAS, EGFR, ALK, BRAF, PIK3CA, and HER2 in a multiplexed fashion. The results of the molecular tests were crossed against the clinical data and pathological findings for each case to determine any correlations among them. The analysis yielded positive correlations between presence of a mutation with gender, survival rate, cancer type, vascular invasion and smoking history. The study provides valuable information of lung cancer molecular profiling in the clinical setting with significant impact in the clinical practice.

Chang-Ho Jeon

Daegu Catholic University Medical Center, South Korea
Title: Detection of circulating colorectal cancer cells using MAGE A1-6 and hTERT RT-PCR

Biography :

Professor Chang-Ho Jeon received his M.D. at the University of KeiMyung (South Korea). He obtained specialist degrees in Laboratory Medicine at YeungNam University (South Korea). From 1989 to 1995, He worked as Associate Professor at Medical School of DongGuk University, in Pohang, Korea. In 1995, He moved to Medical School of Daegu Catholic University, then have worked for this University as a Professor of Laboratory Medicine. From 2008 to 2012, He had worked as a Director of adult stem cell research center in Daegu Catholic University Medical Center. In 2008, 2012, and 2013, Heobtained a distinguished scholarship award from Korean Association of Quality Assurance, Korean Society of Laboratory Medicine and Korean Cancer Association respectively. From 2015heis working as a vice president of Korean society of genetic and molecular diagnosis. Main fields of his interest are Molecular diagnosis of Cancer, Circulating tumor cells and anti-cancer drug susceptibility. Hehas authored and co-authored about 100 scientific articles.

Abstract :

Background: To detect circulating colorectal cancer cells, we had developed melanoma associated gene (MAGE) A1-6 and human telomerase reverse transcriptase (hTERT) RT-PCR system. We applied the system for the patients of colorectal cancer patients to detect circulating tumor cells

Methods: We have used 59 bloods of colorectal cancer patients and 50 bloods from the patients of benign diseases. The patients had been evaluated and diagnosed at the Daegu Catholic University Medical Center. After removal of red blood cells, cancer cells were enriched by magnetic separation with anti-CD45 microbeads (Miltenyi Biotec, Auburn, CA). The CD45 negative cells were extracted with RN easy Mini Kit (Qiagen, Duesseldorf, Germany).To amplify the MAGE A1-6 and the hTERT gene, gene specific RT-nested PCR and oligo-dT RT PCR were used using Light Cycler Fast Start DNA Master SYBR Green I (Roche, Mannheim, Germany).GAPDH gene was used as a control gene.
Results: In the blood of benign diseases, MAGE A1-6, hTERT and the MAGE + hTERT gene RT PCR showed the specificities of 92.0%, 88.0% and 80.0%. In the blood of colorectal cancer patients, MAGE A1-6, hTERT and the MAGE + hTERT gene RT PCR showed the sensitivities of 25.0%, 33.9%and 47.5%.Compared with the positive rates of T1 and T2 stage (N=15), those of T3 and T4 state (N=44) were significantly higher: hTERT 13.3% vs. 29.5%, MAGE A1-6 26.7% vs. 36.4% and MAGE + hTERT 26.7% vs. 54.5%.
Conclusion: MAGE A1-6 and hTERT gene RT PCRshowed good result for CTCs detection in the patients of colorectal cancer patients. MAGE A1-6 and hTERT gene RT PCR results correlated with their T stage of colorectal cancer.

Abraham Haim

The Israeli Center for Interdisciplinary Research in Chronobiology, University of Haifa, Israel
Title:

Artificial light at night as a source of environmental pollution - Melatonin suppression and breast cancer

Biography :

Abraham Haim is a full (Emeritus) professor from the University of Haifa. After many years of studying the response mainly of rodents to changes in photoperiod as an initial signal for seasonal acclimatization, he became interested in the reproductive and metabolic responses to light interference what is known today as light pollution. So this became his main topic of research where among others we developed an animal model to test the relations between breast cancer development and exposure to different illuminations. He is the Head of Israeli Center for Interdisciplinary Research in Chronobiology and the Vice president of the Israeli Lighting Society, vice chair of LONNE one of EU, COST programs. Together with collogues and students he has published over 180 scientific papers in pre-reviewed journals. Together with Prof. Portnov, he has published a book entitled: Light Pollution as a New Risk factor for Human Breast and Prostate Cancer, published by Springer, 2013.

Abstract :

Background: The most dramatic environmental change that took place on our planet during the twenty century and is still going these days is the disappearance of dark nights by artificial light at night (ALAN). Throughout evolution humans as other organisms developed under light/dark cycles of 24h an important signal for the entrainment of our biological clockand expresses the rotation of our plant on its axis. If in the first decays of electrical illumination incandescent bulbs were used and as those are considered inefficient in regards to energy saving, in the last five decaysan increase in energetically efficient bulbs which emit short wavelength (SWL) illumination is noted. Under natural conditions SWL-lighting appears at day time and is efficient in suppressing pineal melatonin production. The objectives of our study were: 1) to test the following nexus – ALAN, melatonin suppression, epigenetic modifications and breast cancer (BC) cells proliferation in an animal model. 2) To assess melatonin suppression in response to different illumination types in regards to wavelength.

Materials and Methods: Female BALB/c mice acclimated to short day (8L:16D) were inoculated with 4T1mice BC-cells subcutaneously so tumor size could be calculated with time. Mice were interfered at the middle of the dark period with white LED or Carbon lighting at the same intensity and for the same duration. At the end of the experiments about four weeks, urine was collected for measuring the amount of the melatonin metabolite 6-sulfatoxymelatonin (6-SMT). The tumor was removed and DNA was extracted for measuring global DNA methylation (GDM) levels.

Results: The nexus was revealed and we can further show that SWL-illumination and in particularly LED suppresses melatonin production. This suppression results in hypo-methylation which presumably increases BC-cell proliferation.

Conclusions: The aggressive penetration of the LED-technology into our indoor and outdoor illumination by the name of energy saving should be reconsidered and very carefully calculated. No doubt as SWL-illumination suppresses melatonin production such illumination sources cannot be used for ALAN. As incubation period of BC in humans is between 10-15 years and our results show the involvement of epigenetic modifications which are reversible, efforts should be made to discover what is the threshold from which the direction is nor reversible? We assume that this can be a breakthrough in BC-prevention.

Xiaofeng Dai

JiangNan University, China
Title: Molecular portraits revealing the heterogeneity of breast tumor subtypes defined using immunohistochemistry markers

Biography :

Dr. Xiaofeng Dai, Ph.D., now is an Associate Professor at the National Engineering Laboratory for Cereal Fermentation Technology, School of Biotechnology, JiangNan University, China. She has master degrees both in Molecular Biology and Bioinformatics, and two doctoral degrees, one in Computational System Biology, and one in Quantitative Methods in Economics. Currently Dr. Dai’ researches focus on breast cancer subtyping and heterogeneity, cancer stem cell signaling network and its association with immune response in basal breast cancer. She has published 15 SCI papers as the first author in reputed journals.

Abstract :

Breast cancer is highly heterogeneous. The subtypes defined using immunohistochemistry markers and gene expression profilings (GEP) are related but not equivalent, with inter-connections under investigated. We revealed a set of diff-genes, containing 1015 mRNAs and 69 miRNAs, which characterize the immunohistochemistry-defined breast tumor subtypes at the GEP level. We further reduced the dimension of this gene set to remove redundancy or noisy information. Using hierarchical clustering and nearest-to-center principle, we identified 119 mRNAs and 20 miRNAs best explaining breast tumor heterogeneity with the most succinct number of genes. The final signature panelcontains the 119 mRNAs, whose superiority over diff-genes was replicated in two independent public datasets. The comparison of our signature with two pioneering signatures, the Sorlie’ssignature and PAM50, suggests a novel marker, FOXA1, in breast cancer classification. Subtype-specific feature genes are reported to characterize each immunohistochemistry-defined subgroup. Pathway and network analysis reveal the critical roles of Notch signalings in [ER+|PR+]HER2- and cell cycle in [ER+|PR+]HER2+ tumors. Our study reveals the primary differences among the four immunohistochemistry-defined breast tumors at the mRNA and miRNA expression levels, and proposes a novel signature for breast tumor subtyping given gene expression data.

Session 4 : Cancer Genetics Risk Assessment; Diagnostic Methods for Cancer Treatment & Cancer Survivorship: Opportunities of Cancer Healthcare Providers

Session Introduction

Peter Brust

Helmholtz-Zentrum Dresden - Rossendorf Institute of Radiopharmaceutical Cancer Research, Germany
Title: Design of new18F-labelled radiopharmaceuticals for brain tumor imaging

Biography :

Peter Brust received his M.S. in Immunology in 1981 and his Ph.D. in Neuroscience from Leipzig University in 1986. He worked as a postdoctoral fellow at Montreal Neurological Institute and Johns Hopkins University Baltimore from 1990-1991. He joined the Research Center Rossendorf (now known as Helmholtz-Zentrum Dresden-Rossendorf, HZDR) in 1992 and headed the Department of Biochemistry. Since 2002 he works in Leipzig first at the Institute of Interdisciplinary Isotope Research and since 2010, after operational transfer, again at HZDR where he leads the Department of Radiopharmaceutical Cancer Research. Since 2010 he is Professor of Radiopharmacy at Leipzig University.

Abstract :

Glioblastoma multiforme is the most aggressive type of primary brain tumor with a median overall survival (OS) ofabout 12 months.Brain metastases are the most common form of brain tumors and significantly outnumber primarybrain tumors, with the majority originating from lung cancer, especially non–small cell lung cancer (NSCLC). Despite aggressive treatment, their prognosis is also poor with a median OS of approximately 7 months after diagnosis. Treatment of those tumors remains one of the most challenging tasks in clinical oncology. Although new molecular pathways in tumor biology are being constantly discovered, translation of basic science achievements into clinical practice is rather slow. Major obstacles in resistance to therapy are heterogeneityof brain tumors, multiple genetic alterations, and their diffuse, infiltrative behavior. Hence identifying and investigating pathways related to tumor etiology and growth is highly important. Positron emission tomography (PET) offers the potential to identifykey signaling pathways in brain tumors involving neurotransmitters and -modulators and to discover drugs which may be used for their therapy.

One of the most important prerequisites for PET is the development and evaluation of radio labelled ligands in order to investigate brain functions in living human subjects. Fluorine-18 is currently the most favorable radionuclide that is routinely used for radiolabeling because of its half-life of 109.8 min. The use of PET radio ligands provides brain images of transport, metabolic and neurotransmission processes on the molecular level. PET is currently the most sensitive and specific method for this type of studies. Through integration of chemical/radiochemical, pharmaceutical/radiopharmaceutical, biochemical and radiopharmacological basic research, computational chemistry and with the aid of nuclear medicine diagnostic new approaches in brain tumor treatment will be made available. The presentation will focus on the strategy of radiotracer development bridging from basic science to biomedical application focusing on targets of major importance for the mentioned tumors such as cannabinoid, sigma and nicotinic alpha7 receptors.

Niki Zacharias Millward

The University of Texas MD Anderson Cancer Center, USA
Title: Using metabolism to differentiate aggressive versus indolent prostate cancer for diagnosis and treatment

Biography :

Dr. Niki Zacharias is an Assistant Professor in the Department of Cancer Systems Imaging at the University of Texas MD Anderson Cancer Center.  She received her PhD in chemistry from California Institute of Technology in 2003.  Prior to her faculty appointment, she was the James G. Boswell Fellow between Huntington Medical Research Institute and California Institute of Technology.  As a chemical biologist, she is focused on utilizing chemical methods (imaging, magnetic resonance, hyperpolarization, fluorescence) to probe biological systems.  

Abstract :

Many prostate cancers (PCa) detected by screening are indolent (will not leave the prostate) however, 90% of patients will receive immediate treatment.  What is needed is a diagnostic tool that allows the whole prostate to be examined and is directly correlated to the metastatic behavior of the tumor.  We are using a multi-prong approach to discover the metabolic changes in PCa. (1) We are metabolic profiling tumor and normal prostate tissue. (2) We are metabolic profiling both the intracellular and extracellular metabolites of four human prostate cancer cell lines with different degrees of metastatic behavior. (3) We are exploring the reduction of cell proliferation with metabolic inhibitors for therapeutic treatment. (4) We are following the progression of PCa with hyperpolarized magnetic resonance (MR) agents in PCa animal models.  Hyperpolarization allows for over >10,000 fold sensitivity enhancement using MR.  Polarization (signal enhancement) can be retained on the metabolites of the hyperpolarized molecule allowing for in vivo real time metabolic profiling.  Results:  We observe significant differences in uptake of glutamine and the amount of intracellular glutamine, differences in phosphocholine and glycerophosphocholine, and differences in intracellular succinate levels between aggressive versus non-aggressive cell lines and in PCa tissue versus normal prostate tissue.   In addition, in our hands we see no significant difference in the glycolytic rate (production of lactate) between the indolent and aggressive PCa cell lines in culture.  Using dynamic nuclear polarization, we are designing new in vivo methods for interrogating metabolic pathways such as hyperpolarized choline and glutamine derivatives. 

Conclusions:  Metabolic profiling has revealed significant differences in metabolism between indolent and aggressive PCa.  By using metabolic profiling, we can determine which specific metabolic inhibitors could be utilized to reduce tumor burden and with hyperpolarization this metabolic profiling can be performed in vivo

Lorena Martin

University of California San Diego, USA
Title: Review of the relationships between lifestyle behaviors, telomere length, stem cells, and cancer

Biography :

Lorena Martin, Ph.D. is an applied behavioral scientist, quantitative methodologist, and exercise physiologist at the University of California San Diego. She is also a graduate faculty member at Northwestern University and Visiting Scientist at the Salk Institute for Biological Studies. Her research focuses on the relationships among lifestyle behaviors, telomere length, stem cells, and Cancer. Her training and expertise is transdisciplinary; such that she has been able to integrate the above mentioned topics to produce a more inclusive hypothesis for future transdisciplinary research.

Abstract :

Until recently, telomeres were thought to be inherited, and therefore genetically determined. More recent evidence demonstrates telomere length may also be associated with and potentially modified by lifestyle. Telomeres are DNA structures that have been implicated in the process of aging. The strong correlation of shorter telomeres with aging, and chronic diseases such as cancer, is well documented. However, although it may seem counterintuitive, cancer stem cells display longer telomere length, although individuals at risk for cancer show shorter telomere length. This conundrum merits additional prospective research.
During this presentation, we describe the current cross-sectional associations between certain behaviors, such as physical activity and nutrition, as well as demographic variables and their association with telomere length, vitality of stem cells, and cancer. In addition, we will provide a clearer understanding of the p16 and p21/p53 pathways.  Activation of the p16 pathway is known to contribute to aging.  However, the inactivation of p16 is associated with the development of several cancers, while p21 and p53 appear to extend longevity.  We will discuss their dynamics related to telomere length, telomerase activity, lifestyle behaviors, and cancer.  We will also present information about how stem cells compared to cancer stem cells proliferate, and the cancer-aging hypothesis. In summary, this presentation will include current research on the relationships among lifestyle, telomere length, stem cells, and cancer.

Connie Darmanin

La Trobe University, Australia
Title: In meso crystallization characterization of butyrate receptors, GPR41 and GPR43and new developments in X-ray Free Electron Laser sources to further structure-based drug design

Biography :

Dr. Darmanin completed her PhD at Monash University, Melbourne in 2006 where she focused on protein crystallography solving ultra high resolution structure of Aldose Reductase. After completion of her PhD she moved to CSIRO, Melbourne in 2007 and during her post doctorate she setup a G protein coupled receptor laboratory and gained expertise in Synchrotron Science and Electron Crystallography specializing in developing new methods for solving structures of GPCRs and in meso crystallization. She continued on at CSIRO after her Post Doc as project leader and continued to grow the area of in meso crystallization of GPCRs in Australia developing protocols and trying to understand the process of in meso crystallization to help solve GPCR structures. Recently, 2015 she has moved to La Trobe University, Melbourne to continue her work in in meso crystallization and led the X-ray Free Electron Laser group providing expertise in this new exciting field for structure determination of difficult proteins.

Abstract :

G protein-coupled receptors (GPCRs) are key pharmaceutical targets in a number of biological diseases and until the recent introduction of Lipidic Cubic Phase (LCP) crystallization, otherwise known as in meso crystallization, these protein structure have been extremely difficult to solve. LCP crystallization has been successful in solving the structures of a number of GPCRs. However, understanding the process of LCP crystallization is limited. The butyrate G-protein coupled receptors (GPCRs), GPR41 and GPR43, have been implicated in colorectal cancer.  To date their function has not been elucidated as low levels of protein expression and difficulties in producing diffraction quality crystals have hindered their structural determination.  In meso crystallization, which uses an artificial lipid membrane matrix to facilitate crystal growth, is becoming an increasingly successful crystallization technique, particularly for GPCRs. We report herein the lipid membrane matrix structural characterization for GPR41 and GPR43 within two lipid self-assembly systems (monoolein and phytantriol) commonly used for in meso crystallization and comment on their suitability for crystallizing these GPCRs. Synchrotron small angle X-ray scattering (SAXS) studies were used to determine the initial phase and uptake of these receptors within the lipid matrix and investigate the role of cholesterol in this process. The self-assembled lipid nanostructure was retained in the presence of GPR43 for both lipids but was destabilized for GPR41 in the phytantriol lipid system. The structural changes to the lipid matrix upon protein incorporation were greater for cholesterol-doped systems, potentially indicative of increased receptor uptake.
Elucidating GPCRs structures using conventional crystallography can be challenging due to the size of the crystals grown during in meso crystallization. An alternative and new method of development is serial femtosecond crystallography at an X-ray Free Electron Laser (XFEL) source. These sources are able to generate data from nano-crystals enabling structure determination to be carried out on such finite crystal sizes. This has led the way for new nano-crystallography developments.

Hanwei Yin

Peking University Health Science Center, China
Title: Plasma thioredoxin reductase (TrxR) is a novel clinical biomarker of the early-stage diagnosis and treatment of cancer

Biography :

Dr. Hanwei Yin received his Ph.D from Northwestern University in Cellular and Cancer Biology. He joined Keaise Medicine in 2015, and is currently the director of R&D department. He has published many papers studying the mechanism of benign and malignant tumor development, including the characterization of TrxR as a novel clinical biomarker in hyperplasia and carcinoma, and study of TrxR inhibitors in clinical trials. He is currently leading a group to develop a combinational approach using TrxR with other biomarkers in the early-stage diagnosis and treatment of cancer.

Abstract :

Developing a novel and efficient biomarker for detecting malignant tumors is essentialfor the early-stage diagnosis of cancer.Thioredoxin reductase is a critical catalytic enzyme involved in the biosynthesis of deoxyribonucleotidesandregulation of cellular redox state, and found to be overexpressed in multiple types of cancer.Mechanistically, TrxR has been known to mediate multiple biological processes in cancer cells, including cell cycle progression, cell apoptosis, and ROS accumulation; while several TrxR inhibitors were also designed as anticancer drugs and are currently under clinical trials. By using our patent-protected and China FDA-approved TrxR detection assay, plasma TrxR activities of > 10,000 clinical subjects (malignant tumor patient vs. healthy subject) were measured and data were collected for statistical analyses.As a result, plasma TrxR activity level was observed to be significantly higher in malignant patients (TrxR> 12.0 U/mL) compared with normal group (TrxR< 4.0 U/mL) or non-malignant patients. Interestingly, TrxR activation in tumor samples was dramatically reduced after various anti-cancer treatment including surgery and radio-/chemo-therapy. All these evidences suggest that TrxR activity is an effective clinical biomarker of hyperplasia and carcinoma, and can be applied to detect tumor at early-stage and monitor the therapeutic outcome. Therefore, this study willsignificantly impact our current view on the clinical biomarker in hyperplasia and carcinoma.

Padmanabhan Nair

NonInvasive Tehnologies LLC, Johns Hopkins University Bloomberg School of Public Health, USA
Title: GipsitumabTM : A novel chimeric heterodimeric antibody derived from lineage-directed exfoliated human colonic epithelial GIP-CTM (gastrointestinal progenitor) cells arrest tumor growth in xenotransplants

Biography :

Padmanabhan Nair, Ph.D. (1956) Royal Institute of Science, Bombay (Mumbai), India; Research Officer, (1958-1960) All-India Institute of Medical Sciences, New Delhi, India; Fulbright Scholar and McCollum-Pratt Fellow,(1960-19963) The Johns Hopkins University, Baltimore, Maryland; Head of Medical Research,(1963- 1983) Sinai Hospital of Baltimore, Inc; Research Scientist (1983-1998) Beltsville Human Nutrition Research Center, ARS, USDA, Beltsville, Maryland; Founding President and CEO, (2000) NonInvasive Technologies LLC, Elkridge, Maryland; Adjunct Professor of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland.

Abstract :

Human colonic mucosa is known to be renewed every five days. We pioneered the discovery that these exfoliated cells are viable and that they can be isolated in their pristine state from a small sample of stool (0.5 gm) yielding a heterogenous population of about 20 million cells. These cells exhibit a strong oncolytic activity across a broad spectrum of human cancers mediated via the existence of a novel heterodimeric IgA/IgG chimeric immunoglobulin that can be generated in vitro against human cancers via a lineage-directed differentiation of these GIP-C cells. This antibody has been shown to arrest human colon cancer xenotransplants in nude mice. This technology has opened a new approach to rapid production of therapeutic antibodies to cancer as well as infectious agents such as HIV, Ebola and Marburg without generating a hybridoma.

Yoshiaki Omura

New York Medical College, USA
Title:

Optimal dose of Vitamin D3 400 I.U. has a significant anti-cancer effect, while widely used 2000 I.U. or higher promotes cancer: Since marked reduction of Taurine was found in various cancer tissues, oral intake of optimal dose of Taurine with ω3 fish oil & cilantro was found to be new safe and effective method of cancer treatment

Biography :

Yoshiaki Omura received Oncological Residency training at Cancer Institute of Columbia University & Doctor of Science Degree through research on Pharmaco-Electro-Physiology of Single Cardiac Cells in-vivo and in-vitro from Columbia Uni.. He studied & researched on EMF Resonance phenomenon between 2 identical molecules at graduate experimental physics dept. ,Columbia Uni.. He published over 270 original research articles, many chapters, & 9 books. He is currently Adjunct Prof. of Family &Community Medicine, NY Medical College; Director of Medical Research, Heart Disease Research Foundation of NY; President & Prof. of Int’l College of Acupuncture & Electro-Therapeutics, NY; Editor in Chief, Acupuncture & Electro-Therapeutics Research, Int’l Journal of Integrative Medicine, (indexed by 17 major int’l Indexing Periodicals); Editor of Integrative Oncology. Formerly, he was also Adjunct Prof. or Visiting Prof. in Universities in USA, France, Germany, Italy, Ukraine, Brazil, Portugal, Turkey, Serbia, Japan, Korea, Taiwan, & China.

Abstract :

Introduction: The author had found that the optimal dose of Vitamin D3 400 I.U. has safe &veryeffective anticancer effects, while commonly used 2000~5000 I.U. of Vit. D3 gives a 2~3 times increase in cancer markers. We found Taurine has a similar effect.

Method:Using very strong Electromagnetic Field (EMF) Resonance phenomenon between 2 identical molecules with identical weight for which U.S. patent was given in 1993, non-invasive measurement became possible without expensive bulky measuring instrument. Effects of optimal dose of Vitamin D3& Taurine were compared.

Results:We examined the concentration of Taurine in normal internal organs and in cancer & other malignancies’ tissue. We found that Taurine levels in normal tissue are 4~6ng. But in the cases with malignancies, the amount of Taurine was strikingly reduced to less than 0.25ng in adenocarcinoma of the esophagus, stomach, colon, prostate, breast, and lung. Therefore we determined first what the optimal dose of Taurine would be for the average healthy adult, which we found to be 175mg of Taurine instead of commonly used 500mg. Since in cancer patients Taurine is markedly reduced at least 1/16~1/24th of its normal value, we examined the effect of the optimal dose of Taurine on cancer patients. In a patient with normal tissue, the effects of one optimal dose of Taurine usually lasted one day. However in a cancer patient, the effect did not last as long, and required Taurine 3 times/day. This dosage for cancer patients produced a very significant change in cancer associated parameters, such as Oncogene C-fosAb2 &Integrin α5β1, being reduced to less than 1/1,000th. The optimal dose of Taurine 175mg with omega 3 fish oil (EPA 180mg & DHA 120mg) & cilantro 3 times/day, significantly increases urinary excretion of these cancer parameters, toxic metals, & microorganisms. Thus, optimal dose of Taurine can be used as new safe, effective, economical & non-invasive treatment for various cancer patients together with optimal dose of ω3 fish oil & cilantro.

Discussion: Use of optimal dose of Taurine of about 175mg is very important. Since most of Taurine is available as 500mg tablet or capsule of 500mg powder, people often use 500mg(which is about 3 times over dose), without evaluating optimal dose. In cancer patients, instead of using toxic overdose, it is important to use more frequently optimal dose. Anti-cancer effect as well as urinary excretion effect of bacteria, virus, fungus, and toxic metals& substances are superior with optimal dose of Taurine compared with optimal dose of Vitamin D3.

Paula B Caffrey

California University of Pennsylvania, USA
Title:

The rapid development of cisplatin resistance in A2780 human ovarian tumor cells can be prevented by the folate enzyme inhibitor, berberine

Biography :

Paula B. Caffrey received her Ph.D. from Rutgers University in 1989.  Her graduate research, performed with K. Irwin Keating, explored the interdependence of Se- and Zn- requirements in aquatic systems. As a post doc in Gerald D. Frenkel’s labat Rutgers Newark, she studied selenium’s effect on drug resistant tumor cells. Following postdoctoral projects at UCSD Cancer Center and GeorgetownMedical School, she resumed her collaboration with Dr. Frenkelas a Research Associateat Rutgers from 1995-2007. They developed models of drug resistant ovarian cancer to identify agents that can prevent this resistance. Their findings resulted in a Phase 1 clinical trial at the New Jersey Cancer Institute.  Since 2007, Dr.Caffrey has held the position of Assistant Professor at the California University of Pennsylvania, where she mentors research students and continues collaboration with Dr. Frenkelonthe prevention of drug resistance inSCLC lung cancer and ovarian cancer.

Abstract :

Resistance to the chemotherapy drug cisplatin is a common cause of treatment failure in ovarian cancer. Many studies have focused on agents that might reverse resistance once it has developed. For example, berberine, an isoquinoline alkaloid that interferes with folate cycle enzymes, has been found to induce apoptosis in cisplatin resistant cells. We have pursued an alternative to the resistance reversal strategy: the prevention of the development of resistance. This strategy requires that cells predictably develop resistance to a high dose of cisplatin that effectively inhibits non-resistant tumor cells. For this study, A2780 (Addex) human ovarian tumor cells were cultured in nutrient medium (F12/DMEM plus 7% FBS) alone or with a low, pretreatment dose of 7.5 µM cisplatin (Sigma Aldrich). After 24 hours in pre-treatment conditions, cells were counted and replicate cultures exposed to the high dose of 15 µM cisplatin.  After 24 hours in this high dose, cells were counted again. In non-pretreated cells, high dose cisplatin decreasedcell survival to 51.8 (6.5) % of control cultures. In contrast, cisplatin pretreatment resulted in 90.6 (9.7) % survival following the high dose. Thus, this pretreatment resulted in the rapid induction of resistance. We then employed this protocol to test whether berberinecan prevent the development of this resistance. Replicate cultures were pretreated with either 21 µM or 53 µM berberinehydrochloride (Sigma Aldrich) alone or with 7.5 µM cisplatin pretreatment. Pretreatment with berberine alone had no effect on cell sensitivity to high dose cisplatin: 50.3 (6.1) % survived the subsequent high-dose cisplatin, virtually the same response as cultures with no pretreatment. The addition of berberineon the same day as the cisplatin pretreatment prevented resistance and maintained sensitivity similar to that of controls: 45.3 (5.9) % of cells survived following high dose cisplatin.  The results suggest that berberine pretreatment prevents the development of cisplatin resistance in this protocol, perhaps by preventing the overexpression of folate cycle enzyme genes. Further studies are underway to investigate whether this is the case.

Funded by a grant from Commonwealth of PA University Biologists.

Adriaan Visser

PRO-health, The Netherlands
Title: Can communication training for health care providers at a cancer ward improve the communication climate at the ward and the satisfaction of the cancer patients?

Biography :

Adriaan Visser PhD, social psychologist, thesis (1984) on the methodology of the measurement of patient satisfaction. He worked the rest of his life as health psychologist, engaged in education of students at Dutch universities and colleges on psychology, nursing, research in health care, implementation of health care changes, writing, and editor of several journals. Grants and publications about health promotion, patient education, patient satisfaction, organization of health care, methodology, dental care, diabetes, suicide, contraception, aging, chronically diseases, cancer, palliative care, PNI, depression, mindfulness, creative art, and spirituality. He is the Director of PRO-Health.org, a company for Publications, Research, and Organizational development in Healthcare Organizations.

Abstract :

Objective: In an experimental study we were aiming to show the effects of communication training for health care providers at a cancer ward in order to improve the quality and quantity of the patient education, and satisfaction with the care by the cancer patients.

Methods: A three years in-service communication training was held at a cancer ward of a general hospital. Pre- and post data were collected in an experimental study about (1) the quality and quantity of the communication of nurses, physicians and other HCPs towards patients and colleagues (n=22) as well as the satisfaction of the cancer patients with the quality of the care (n= 90).

Results: The communication training raised significantly the quality and quantity of the communication towards patients and with colleagues. Also the satisfaction of the patients about the quality of care did increase. However, the long-term implementation of these benefits was not-successful.  

Conclusion: In-service communication training is an important mean to raise on the long term the quality of patient education at cancer departments in hospitals. Lasting implementation of the benefits requires although attention to organizational obstacles, budgetary conditions, leadership factors at the ward, and the application of an organizational oriented theoretical frame work.

Practice implications: Improvement of patient education at cancer wards does not only require educational means, organizational facilities and professional training, but may be improved too by in-service communication training This may increases the quality of the patient centered care and oncology wards, but attention is needed to a theoretical implementation framework to guide a lasting effects.   

Xuemei Wang

State Key Laboratory of Bioelectronics, Southeast University, China
Title: Real-time tracking and bio-imaging of cancer cells based on novel nanoscaled probes

Biography :

Dr. Xuemei Wang is currently a full professor in Southeast University, Nanjing, China. She got her PhD degree in Chemistry from Nanjing University in 1995; From February of 1995 to June of 1996 she a lecturer in Department of Chemistry in Nanjing University. In 1996 she got the Alexander von Humboldt fellowship in Germany and engaged in the research of supramolecular chemistry and bio-recognition. After returning to China in February of 1998, she joined school of Biological Science and Medical Engineering, Southeast University. In 2000, she was awarded Hong Kong Croucher Research Fund and Chinese Chemical Society Youth Award in Chemistry. She was elected in New Century Talent Supporting Project in China in 2005 and won Chinese Young Woman Scientist Award in 2007. In 2013, she won The National Science Fund for Distinguished Young Scholar in China. Her current research interests include nanomedicine, bio-imaging and biomedical sensors, especially focusing on the design of multifunctional nanostructures for nanomedicine, in vivo self-bio-labelling and multimode bio-imaging of tumors through in-situ biosynthesized biocompatible metal nano-clusters, and biosensors based on functionalized nanoscaled probes.

Abstract :

The early efficient diagnosis and therapy of some important disease like cancers is still a hot topic in the relative areas involving in patient care and treatments. The multidrug resistance (MDR) is often one of the major obstacles in relevant therapies due to disease-causing organisms to withstand a wide variety of structurally and functionally distinct drugs or chemicals. Diagnosis and therapy in combination with nanotechnology may offer an alternative promising and overcome the difficulty. And the early diagnosis based on some smart supramolecules and nano-biotechnology could be crucial for a successful treatment of cancers.
This study has established some ultrasensitive and intelligently supramolecules and multi-functional nanoprobes as well as multi-mode imaging techniques for real-time dynamic analysis of biomolecules/ cells/tissues. Meanwhile, we have developed a new strategy for the fast and high sensitive recognition of the target biomolecules and cancer cells by combining the supramolecular probes and functionalized nano-interface with the spectra-electrochemical study. Especially, the ultrasensitive in vivo bio-imaging of cancer cells and diseased tissues has been realized through in situ biosynthesized near-infrared fluorescence nanoclusters, establishing creative methods for non-invasive molecular diagnosis and treatment of some difficult diseases like cancers, thus paving the novel path for cancer diagnosis and treatment.

Acknowledgment

This work is supported by the National Natural Science Foundation of China (81325011, 21327902, and 21175020) and National High Technology Research & Development Program of China (2015AA020502).