Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 3rd International Conference on Translational Medicine Las Vegas, USA.

Day 1 :

Keynote Forum

Mingzhao Xing

Johns Hopkins University USA

Keynote: Use of BRAF V600E mutation in the prognostication of thyroid cancer

Time : 09:00-09:30

OMICS International Translational Medicine-2014 International Conference Keynote Speaker Mingzhao Xing photo
Biography:

Mingzhao Xing, MD, PhD, is Professor of Medicine, Oncology and Pathology, Co-Director of the Thyroid Tumor Center, and Chief of the Laboratory for Cellular and Molecular Thyroid Research at the Johns Hopkins University School of Medicine. He subsequently completed his medical residency at the Greater Baltimore Medical Center and clinical fellowship in endocrinology and metabolism at the Johns Hopkins Hospital before joining the Johns Hopkins endocrine faculty. Dually certified in Internal Medicine and Endocrinology, he practices clinical endocrinology as a subspecialty consultant and teaching attending at the Johns Hopkins Hospital while leading a research laboratory there focused on thyroid studies as a physician scientist. Supported by the American Cancer Society and NIH R0-1 grants, his laboratory has been studying molecular, genetic, and epigenetic mechanisms of thyroid cancer and their clinical translation. He has published extensively in prestigious journals including Journal of Clinical Endocrinology and Metabolism, Cancer Research, Clinical Cancer Research, Journal of Biological Chemistry, Journal of Clinical Investigation, JNCI, Journal of Clinical Oncology, JAMA, The Lancet, and Nature Reviews Cancer. He is co-holder of the USA patent on the initial discovery and clinical characterization of the BRAF V600E mutation in thyroid cancer. He received various awards, such as the Maryland Innovator Award, American Cancer Society’s RSG Award and many more.

Abstract:

Thyroid cancer is a common endocrine malignancy with a rapidly rising incidence in many countries in recent years. Most cases of thyroid cancer have a good prognosis, but some seem to be bound to poor outcomes with increased disease recurrence, treatment refractoriness, and mortality. Conventional approach to risk stratification of thyroid cancer is solely based on clinic pathological criteria, which has proven to be often ineffective. An area that is revolutionizing the risk stratification and hence management of thyroid cancer is the clinical translational research on prognostic molecular markers in thyroid cancer, as best exemplified by BRAFV600E mutation. Numerous studies have demonstrated a strong association of BRAF V600E mutation with poor clinic pathological characteristics of PTC, such as lymph node metastasis, extra thyroidal invasion, advanced tumor stages, tumor recurrence, and patient mortality, establishing a remarkable prognostic value of this molecular marker. BRAF mutation can be detected on thyroid fine needle aspiration biopsy specimens, so this prognostic marker can be used even preoperatively to assist risk stratification and surgical and medical managements at an early stage of the treatment of thyroid cancer. The use of the recently discovered TERT promoter mutations in combination with BRAF mutation makes even more effective this molecular marker-based risk stratification and hence tailored management of thyroid cancer. Our group has played a leading role in the last 10 years in the discovery and characterization of these prominent molecular markers in thyroid cancer. This presentation will provide a comprehensive discussion on this exciting clinical translational research area of thyroid cancer medicine.

OMICS International Translational Medicine-2014 International Conference Keynote Speaker Afaf El-Ansary photo
Biography:

Afaf El-Ansary has completed her PhD at the age of 37 years from Ain Shams University-Egypt and Postdoctoral studies from National Research Centre. She is a Professor in Biochemistry Department, Science College, King Saud University. She has published more than 85 papers in high impact factor journals and serving as a reviewer and as an Editorial Board Member of repute journals.

Abstract:

Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Progress in understanding and treating autism will require translational research efforts to transfer knowledge through successive fields of research from basic scientific discovery to public health impact. A developmentally abnormal gut microbiota may in turn affect both the gut-brain axis and brain development and contribute to the etiology of autism. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. In a three successive independent experimental design, we tested the neurotoxic effect of PA either orally administered or biologically induced in clindamycin-treated rat pups. The oral administration was used to confirm the role of gut-brain axis in the induction of autistic features probably found in treated rats. Additionally, Clindamycin was used to ascertain the role of overgrowth of Clostridia species as PA producer in inducing autistic features in animals. In both groups, a panel of biomarkers were measured compared to healthy untreated rat pups. These biomarkers were selected to represent DNA damage, oxidative stress, and neurochemistry, and neuroinflammation related signaling. The selection of these markers was based on our clinical data obtained from patients with autism which recorded highspecificity and sensitivity when analyzed usingReceiver Operating Characteristics (ROC) and excellent predictive values using predictiveness curves. Our work was extended to test the therapeutic efficacy of carnosine, and carnitine. The obtained data confirm the role of propionic acid in inducing persistent autistic features in rat pups with oral administration being more neurotoxic than theinduction of propionic acid bacterial producers. Additionally, both supplements were effective in ameliorating the toxic effects of PA. In conclusion, although our investigations show evidences of the efficacy of the tested supplementsin ameliorating most of the impaired biomarkers in PA- rodent model of autism, still there is need for better designed and registered trials for at least six months in order reliably to identify a confirmed proper effect.

Keynote Forum

Kyung-Hyun Cho

Yeungnam University Republic of Korea

Keynote: Change of high-density lipoprotein (HDL) in aging-related disease as reliable biomarker

Time : 10:00-10:30

OMICS International Translational Medicine-2014 International Conference Keynote Speaker Kyung-Hyun Cho photo
Biography:

Kyung-Hyun Cho obtained his PhD from the Kyungpook National University of South Korea in 1998 and gained his Postdoctoral training at the University of Illinois at Urbana-Champaign until 2000. He joined Cleveland Clinic Foundation as a Research Doctor until 2001. Back home, he worked at Korea Research Institute of Bioscience and Biotechnology as senior scientist for 4 years. Then he moved to the Yeungnam University (YU), in 2005, where he is currently the Full Professor (tenured) and Head of the Research Institute of Protein Sensor (RIPS) and BK21 plus Serum Biomedical Research and Education Team in the YU. He published more than 70 papers in well known journals and filed more than 20 patents.

Abstract:

It has been reported that glycation could also occur in high-density lipoproteins (HDL) in blood. High-density lipoproteincholesterol (HDL-C) is inversely associated with incidence of cardiovascular disease and is directly related to longevity. In type 2 diabetes patients, blood infusion of rHDL caused reduction of plasma glucose levels by increasing plasma insulin in pancreatic beta cells, which raised the feasibility of a wider clinical application of rHDL from cardiovascular disease to diabetes. The glycation resulted in severe loss of beneficial functions of HDL regarding anti-senescence and anti-diabetic, and anti-atherosclerosis activity due to functional and structural modification with increased protein degradation. To compare the change in lipoprotein metabolism with aging, we analyzed the lipid and protein compositions of individual lipoprotein fractions. Healthy and non-obese elderly subjects (elderly group, n=26) had a serum lipid profile within the normal range, although slightly higher than in young subjects (control group, n=18). However, the elderly group had a 2-fold higher serum uric acid level and triglyceride (TG)/high-density lipoprotein (HDL)-cholesterol ratio. The elderly group had less antioxidant ability and elevated TG content in HDL with enhanced cholesteryl ester transfer activity. An elevated level of advanced glycated end products in lipoproteins and fragmentation of apoA-I were present in the elderly group, with detected lower apoA-I level and more multimerizedapoA-I in HDL. The protein levels of apoA-I, apoC-III, and serum amyloid A in lipoprotein-deficient serum were increased in the elderly group.

Keynote Forum

Sergey Suchkov

I M Sechenov First Moscow State Medical University Russia

Keynote: Antibodies with functionality as a new generation of translational tools to monitor, to predict and to prevent demyelination

Time : 10:30-11:00

OMICS International Translational Medicine-2014 International Conference Keynote Speaker Sergey Suchkov photo
Biography:

Sergey Suchkov was born in 11.01.1957, a researcher-immunologist, a clinician, graduated from Astrakhan State Medical University, Russia, in 1980. He has been trained at the Institute for Medical Enzymology, The USSR Academy of Medical Sciences,National Center for Immunology (Russia), NIH, Bethesda, USA) and British Society for Immunology to cover 4 British university facilities. Since 2005, he has been working as Faculty Professor of I.M. Sechenov First Moscow State Medical University and Of A.I.Evdokimov Moscow State Medical & Dental University. From 2007, he is the First Vice-President and Dean of the School of PPPM Politics and Management of the University of World Politics and Law.In 1991-1995, He was a Scientific Secretary-in-Chief of the Editorial Board of the International Journal “Biomedical Science” (Russian Academy of Sciences and Royal Society of Chemistry, UK) and The International Publishing Bureau at the Presidium of the Russian Academy of Sciences. In 1995-2005, he was a Director of the Russian-American Program in Immunology of the Eye Diseases. He is a member of EPMA (European Association of Predictive, Preventive and Personalized Medicine, Brussels-Bonn), a member of the NY Academy of Sciences, a member of the Editorial Boards for Open Journal of Immunology and others. He is known as an author of the Concept of post-infectious clinical and immunological syndrome, co-author of a concept of abzymes and their impact into the pathogenesis of auto immunity conditions, and as one of the pioneers in promoting the Concept of PPPM into a practical branch of health services

Abstract:

Biomarkers enable early diagnosis, guide targeted therapy and monitor the activity and therapeutic responses across the diseases. So, identification and validation of biomarkers of newer generationsto create a new strategy based upon subclinical recognition of the latter long before the disease clinically manifests itself is of great value. Among the best-validated predictive biomarkers are autoimmunity-related ones (including antibodies/Abs). Meanwhile, multiple sclerosis (MS)whilst beinga chronic autoimmune disorder would result in a destruction of myelin by different factors, including autoAbs. Along with canonical Abs, we have discovered a new family of Abs proven to be endowed with myelin basic protein (MBP)-targeted proteolytic activity (Ab-proteases). The proteolytic property mentioned is considered to serve a functional property of the biomolecule. Most (72-78%) of anti-MBP autoAbsharvested from MS patients and mice with EAE exhibited MBP-specific proteolytic cleavage of MBP.The activity of Ab-proteases markedly differed: (i)betweenMS patients and healthy controls and (ii) inpatients with different types of MS course. Moreover, the activity demonstrated a significant correlation with demyelination, neurological deficiency and thus with the disability of the patients. Of greater value isa sequencespecificity of Ab-proteasesto attack targeted sequences located in dominant fivesites of MBP. Most of those sites whilst being immuno dominant are concentrated within 43-170 of MBP.Two sites from the set would comprise 81-103and 82-98, which, in turn,whilst being sequence-specific, highly immunogeneic and encephalitogeneic both, proved to be major inducers of very aggressive EAE in SJL mice.In humans, both 81-103 and 82-98 have been proven to be major MBP targets to be attacked by Ab-proteases obtained from patients with secondary-progradient courses of MS, progression phase (SPPP), and with remittent course of MS, exacerbation phase (REP), both are with aggressive inflammation. Two extra sites from the same 43-170set are located within 43-68 and 146-170 that proved to be inducers of moderate EAE and thus targets to be attacked by Ab-proteases in MS patients with secondary-progradient courses, stabilization phase (SPSP), and with remittent course, remission phase (RRP), both are with inflammation quenched. So, the most immunogeneic and encephalitogeneic epitopes responsible for generating aggressive bursts are concentrated in three specific areas of MBP: (i) the strongest one is in the smallest 82-98; (ii) a weaker epitope is formed by a longer 81-103 subsequence; and (iii) an epitope with the lowest immunogeneic and encephalitogeneic properties is rooted in a rather long 143-170 sequence defined. The relatives being seropositive for Ab-proteases were being monitored for 3 years whilst demonstrating stable growth of the Ab-associated proteolytic activity when were being under the study.And when the activity reached its mid-level, we identified primary clinical and MRI manifestations to be coincided with the Ab-associated proteolytic activity. And then the proteolytic activity was being further escalated due to the time of progression, type of the disorder, and disability of the patient.Meanwhile, a substantial proportion (around 34%) of relatives demonstrating low-active Ab-proteases with no trends to grow had hadsubclinical evidence of autoimmunity without developing clinically overt dis-ease. The activity of Ab-proteases was first registered at the pre-early (subclinical) stages of the disorder, whenAb-proteases were still low-active whilst attacking presumably low-immunogeneicsequences, the inflammation is moderate, and the manifestations are thus scarcely visible.As the disorder progresses to transform from subclinical into clinical stages, the activity of Ab-proteases is being escalated to reach the indices to be typical for the clinical stage. And, when bursts of the proteolytic activity were evident, the pre-early stages of REP stage could be predicted, even at no seeing any clinical manifestations.And along with the evolution of the sequence specificity, when we saw an extensive growth of the activity, we could predict transformations in the clinical course, i.e., changing of RRP (moderate one) into SPP (severe one) prior to changing of the clinical manifestations. A spread from one type of epitope to the other one could also be a combinatorial biomarker event to serveas a biopredictor of the interstage transformations and serve prognostically as a dynamic biomarker for monitoring MS patients and persons atrisk at both subclinical and clinicalstages to use specific Ab-proteases (Abs with functionality) defined. In fact, a spread from one sequence to another one could also be used prognostically in the development of chronic autoimmune inflammation and thus neurodegeneration (demyelination and axon loss). So, the activity of Ab-proteases in combination with their sequencespecificity to attack well-defined sets of epitopes to be released from MBP during Epitope Spreading, would confirm a practical value of Ab-proteases to monitor both clinical and subclinical courses of chronic autoimmune inflammation. The primary translational potential of this knowledge is in the rational design of novel diagnostic and therapeutic too to exploit the role of those tools in influencing disease. Ab-proteases can be programmed and re-programmed to suit the needs of the body metabolism or could be designed for the development of principally new catalysts with no natural counterparts. By changing sequence specificity of the Ab-mediated proteolysis one may reach reduction of a density of negative shots made by Ab-proteases against MBP as a target and thus could minimize the overall negative effect on the myelin sheath and, finally, minimizing scales of demyelination. So, further translational studies ofAb-mediated MBP proteolysis may provide a newer generation of posttranslational tools and thus a supplementary biomarker and a targeted tool for assessing the disease progression and predicting disability of the patients.

Break: Coffee Break 11:00-11:20@Atrium
  • Biomarkers in Translational Medicine, Role of Translational Research in blood disorders, Translational cardiology and Vascular medicine, Translation of Animal Models to Clinic
Location: Tropicana-2

Session Introduction

Ilia Fishbein

The Childrens Hospital of Philadelphia USA

Title: Induction of pro-healing macrophages through the reprogramming of invading monocytes: A new antirestenotic strategy

Time : 11:20-11:45

Speaker
Biography:

Ilia Fishbein received an MD degree from the University of Saratov (Russia) in 1987. He completed his PhD studies on polymeric delivery systems for the prevention of restenosis at the Hebrew University of Jerusalem (Israel) in 2000. His Postdoctoral research at the Childrens Hospital of Philadelphia (USA) has been concerned with vascular gene therapy and substrate-mediated delivery systems of viral vectors to diseased vasculature. He is an Assistant Professor at the University of Pennsylvania. His current work is related to gene-eluting stents and pharmacological modulation of vascular gene therapy for the prevention of restenosis.

Abstract:

Introduction: Monocyte-derived macrophages are implicated in inflammatory reactions characteristic of restenosis after angioplasty and/or stent implantation. Since the role of macrophage-mediated chronic inflammation in the progression of restenosis is well-established, multiple approaches have been devised to decrease the number and/or functionality of mononuclear phagocytic cells residing in angioplastied and stented arteries. However, no prior research has exploited the capability of monocytes to target sites of vascular injury in order to introduce pro-healing “therapeutic” genes into diseased vasculature. Here we report preliminary results demonstrating the feasibility of this concept. Methods and Results: Monocytes were isolated from heparinized rat blood by sequential Ficoll gradient centrifugation and negative selection with immunomagnetic techniques. 5x105 cells fluorescently labeled monocytes were administered via tail vein to rats that underwent balloon denudation injury of carotid arteries 4 days prior to cell therapy. The labeled cells were observed both in the nascent neointima and in the adventitia of balloon-injured arteries of rats sacrificed 4 days after cell therapy (8 days after balloon injury). The labeled cells unvaryingly carried CD68 pan-macrophage marker as assessed by immunofluorescence analysis, and comprised 30% of total macrophages in the neointimal tissue of rats treated with ex vivo modified monocytes. To verify functional competence of adoptively transferred monocytes, isolated monocytes were transduced with adenoviral vectors encoding firefly luciferase and were administered to rats that underwent Fogarty balloon injury 4 days prior to the cell delivery. One and 4 daysafter cell delivery, luciferase expression in balloon injured arteries was confirmed by bioluminescence imaging. Furthermore, monocytes exogenously transduced with adenovector driving expression of adiponectin, an M2-macrophage inductive factor, were capable of reducing neointimal hyperplasia in balloon injured carotid arteries upon systemic administration to rats 2 days after balloon injury. Conclusions: These pilot studies demonstrate the feasibility of using ex vivo transfected autologous or syngeneic monocytes as a means to introduce pro-healing factors to angioplastied and/or stented vasculature with the aim of restenosis mitigation

Speaker
Biography:

Prof Alina Borkowska is head of Clinical Neuropsychology Department in Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun and head of Clinical Psychology Department of Medical University in Lodz, Poland. Her research concerns on neurobiology and genetics of cognitive dysfunctions in psychiatric diseases, especially schizophrenia, bipolar disorder, OCD , MCI, dementia and pathological obesity. She is a head of numerous university and national Polish grants in this area and participates in international programs concerning genetics, neurobiology and treatment of cognitive dysfunctions in psychiatric diseases. Prof Borkowska was awarded with national and international scientific awards. She is a member of Polish Psychiatric Association, European Psychiatrist Association and member of scientific board in numerous scientific journals and Polish Committee of Science. She is invited speaker on international conferences and author of numerous publications in international journals.

Abstract:

Background: Obesity is an serious health problem, especially in countries with high economic development associated with neuropsychiatric disturbances. The results of current studies indicate that psychological factors, affective disorders and cognitive dysfunctions may play an important role in etiopathogenesis and in the course of this disease. We explore the relationships between obesity, depression, five dimensions of affective temperament, cognitive functions and polymorphism of genes connected with emotional and cognitive processes. Subjects: 520 obese patients (BMI>35), aged 18-56 (mean 42,3 + 12) years were included to the study. The results of patients with obesity were compared with the results obtained by 200 healthy controls (BMI<25), sex, age and education matched to the investigated group. Methods: The intensity of depressed symptoms were assessed by Beck Depression Inventory and Hamilton Depression Scale. For evaluation of five dimensions of affective temperament (depressive, cyclothymic, hyperthymic, irritable and anxious) the Polish version of TEMPS-A Akiskal scale were used. Cognitive functions connected with activity of prefrontal cortex were evaluated by Wisconsin Card Sorting Test. The polymorphism of genes connected with serotonine and dopamine system and BDNF gene were evaluated using PCR method. All subjects were also checked by Food Addiction Scale. The results: Obese patients presented higher prevalence of depression (up to 50% of the whole group presents severe intensity of depression), worse performance of cognitive tests (especially WCST and TMT B) and higher score in Food Addiction Scale compared to healthy controls. Patients with obesity presents higher prevalence of depressive, cyclothymic and anxious temperament than healthy subjects. Female higher scores on depressive and anxious, while males on the irritable and hyperthymic temperament. The intensity of depression were correlated with depressive temperament especially in females. The higher scores of Food Addition Scale show positive correlation with hyperthymic and cyclothymic temperament. The higher score of depressive temperament in TEMPS-A scale was associated with the s/s allele of 5-HTT polymorphism gene. The val/val allele of Val/Met polymorphism of BDNF gene was associated with higher score of depressive and anxious temperament, while met/met allele of this gene was connected with higher score of hyperthymic temperament in TEMPS-A scale. The results of all parameters of WCST were connected with the polymorphism of COMT gene. The G/G allele of 5-HTT gene was associated with worse results on two dimensions on WCST (non-perseverative errors and numbers of cards needed to complete 1st category). Conclusions: Obese patients presents higher prevalence of depression, difficulties in prefrontal cognitive functions and different pattern of affective temperament compared to healthy control subjects. The polymorphism of serotonine transporter 5-HTT and BDNF genes were associated with depression and affective temperament, while dopaminergic COMT gene to the cognitive abilities. This may indicate different influence of serotonine, dopamine and neurodevelopmental system genes on emotional and cognitive functions in patients with obesity.

Ray Greek

Americans for Medical Advancement USA

Title: Trans-species modeling theory

Time : 12:10-12:35

Speaker
Biography:

Ray Greek received his MD from the University of Alabama at Birmingham in 1985 and completed a residency in anesthesiology in 1989 at the University of Wisconsin. He has taught at the medical schools of the University of Wisconsin and Thomas Jefferson University in Philadelphia. He has performed research with animals and humans. He is the President and Co-founder of the not-for-profit Americans for Medical Advancement (AFMA).

Abstract:

Humans and animals are examples of evolved complex adaptive systems. It is difficult to predict the outcome from perturbations to such systems because of the characteristics of complex systems. Modeling even one complex adaptive system in order to predict outcomes from perturbations is difficult. Predicting outcomes to one evolved complex adaptive system based on outcomes from a second, especially when the perturbation occurs at higher levels of organization, is even more problematic. Using animal models to predict human outcomes to perturbations such as disease and drugs should have a very low predictive value. The author will present empirical evidence confirming this and suggest a theory to explain this phenomenon. Trans-Species Modeling Theory states: “While trans-species extrapolation is possible when perturbations concern lower levels of organization or when studying morphology and function on the gross level, one evolved, complex system will not be of predictive value for another when the perturbation affects higher levels of organization.” TSMT is supported by vast amounts of empirical evidence, is consistent with science outside of the specific areas of biology it addresses, and both explains current scientific facts as well as predicting the answers to future questions. The author will elaborate on TSMT, complex systems, evolutionary biology, and the empirical evidence supporting TSMT

Speaker
Biography:

Richard G Pestell received his MD from the University of Western Australia and his PhD from the University of Melbourne. He serves as the Director of the Sidney Kimmel Cancer Center and Executive Vice President at Thomas Jefferson University. He has authored ~500 peer-reviewed publications with ~38,500 citations and an H-index of 102. His papers have been published in prominent peer reviewed journals including Cell, Science, Nature Medicine, Molecular Cell and EMBO J. Dr. Pestell is funded as the Principal Investigator of three RO1 grants and Principal Investigator of the Kimmel Cancer Center CCSG grant.

Abstract:

Cancer is a leading cause of death worldwide and accounted for 7.6 million deaths (around 13% of all deaths. With an estimated 258 000 deaths in 2008, prostate cancer is the sixth leading cause of death from cancer in men (6.1% of the total). Breast cancer claimed more than 458,000 lives last year. In most cases the death of patients is due to metastasis. The identification of new therapeutic targets and treatments to reduce tumor metastasis requires alternative interrogation approaches and alternative strategies. We have identified a new approach through blocking the tumor metastasis “homing” process, to essentially interfere with the tumor’s “GPS”. Interrogation of microarray analysis of 2,254 human breast cancers demonstrated increased expression of CCL5 and its receptor CCR5, but not CCR3, in the basal and HER-2 genetic subtypes of breast cancer. Genome wide interrogation of pathways activated in patient normal breast vs. tumor identified upregulation of a CCR5 signaling module. Human breast cancer cell lines expressed CCR5 by flow cytometry and displayed a functional response to CCL5 by calcium mobilization assays and invasion assays. Using isogenic oncogene transformed breast and prostate cancer cell lines we show oncogene transformation induces CCR5 expression and that the subpopulation of cells that express functional CCR5 display increased invasiveness. CCR5 promoted metastasis homing in vivo. The CCR5 antagonists Maraviroc or Vicriviroc, developed to block CCR5 HIV co-receptor function, reduced in vitro invasion of basal breast cancer and prostate cancer cell lines without affecting cell proliferation or viability. In a series of preclinical mouse models, Maraviroc decreased breast cancer pulmonary metastasis. The isogenic prostate cancer cell lines metastasized to bones and brain in immune-competent mice representing an ideal model for testing anti-metastasis therapies. Maraviroc or Vicriviroc, reduced prostate cancer metastasis to brain, bones and lungs. Our findings provide evidence for a key role of CCL5/CCR5 in the metastasis of basal breast cancer and prostate cancer cell lines and suggest that CCR5 antagonists may be used as an adjuvant therapy to reduce the risk of metastasis in patients with the basal breast cancer subtype and prostate cancer.

Break: Lunch Break 13:00-14:00@ Atrium

Stefan R Hansson

Dept. of Clinical Sciences Obstetrics and Gynecology Lund University Sweden

Title: Fetal hemoglobin and alpha-1-microglobulin in preeclampsia: A new etiological factor and a potential therapy

Time : 14:00-14:25

Speaker
Biography:

Stefan Hansson works as professor and senior consultant in Obstetrics and Gynecology at Lund University and Skåne University Hospital in southern Sweden. He combines research and clinical work. SH has a basic training in chemistry. He graduated from medical school in 1994. In parallel with his clinical training he pursued a scientific career. Between 1994 and 1997 he held a postdoc position at National Institutes of Health, Bethesda, USA, were he trained in molecular biology and neuroscience. In 2004 he became specialist in Obstetrics and Gynecology and associate professor. In 2010 he became professor in obstetrics and gynecology. Since 1994, seventy papers have been published and three patents have been filed.

Abstract:

Preeclampsia (PE), one of the leading causes of pregnancy complications, affecting 3–7 percent of pregnant women worldwide. We now present knowledge of a new potential etiology of the disease and suggest a method for its prediction/diagnosis and a possible treatment. The findings are both based on recent findings on the involvement of fetal hemoglobin (HbF) and the heme and radical scavenging protein A1M (alpha-1-microglobulin). Gene and protein profiling studies have independently shown that increased amount of free HbF is accumulated in the PE placenta. Perfusion of the placenta with free Hb showed damage similar to what is seen in PE, predominantly oxidative stress effects and damage to the blood-placenta barrier. As a consequence, HbF leaks over to the maternal blood circulation and causes endothelial and kidney damage. Elevated levels can be measured already in the first trimester and therefor a potential valuable biomarker for first trimester screening. Later in pregnancy the levels correlate with the blood pressure in women with PE and therefor an important biomarker for specific diagnosis of PE. Ex vivo data show that the human protein A1M, an endogeneous antioxidation and heme-binding protein, can prevent Hb-induced damage to the placenta, restore the blood-placental barrier and prevent maternal tissue damage. Recently, A1M was evaluated as a treatment for PE in the pregnant ewe PE model, in which starvation induces PE symptoms via hemolysis. The free Hb in the PE model caused structural damages to the placenta and kidneys. The kidney function was affected; an increased glomerular sieving coefficient indicated a defect filtration barrier and increased protein leakage. Treatment with A1M ameliorated these changes without signs of side-effects. In conclusion, Free HbF may provide both a predictive and a diagnostic clinical biomarker from the first trimester. A1M has a potential as a future pharmacological treatment for PE, it displayed positive therapeutic effects ex-vivo and in-vivo using the ewe starvation PE model. Therefore, we suggest HbF as a first trimester biomarker and A1M as a plausible treatment for PE in humans.

Speaker
Biography:

Dr Suchkov is an author of more than 500 publications including 10 patents and more than 10 monographs, handbooks and textbooks published in Russia and USA. Dr Suchkov is a Supervisor for 18 dissertations maintained including 14 Candidates and 4 Doctors of Science. At present, 10 dissertaions are being supervised by Dr Suchkov. Dr Suchkov is a member of the: ● New York Academy of Sciences, USA ● EPMA (European Association for Predictive, Preventive and Personalized Medicine), Brussels, EU; ● ARVO (American Association for Research in Vision and Ophthalmology); ● ISER (International Society for Eye Research); ● All-Union (from 1992 - Russian) Biochemical Society; ● All-Union (from 1992 - Russian) Immunological Society.

Abstract:

Any innovations in healthcare services are an important driver to move medicine and thus biopharma forward. In this sense, a new systems approach to disease would result in a new trend in the healthcare services, namely, predictive, preventive and personalized medicine (PPPM). The latter is defined as: “…the capacity to predict disease development and influence decisions about lifestyle choices or to tailor medical practice to an individual.” All chronic disorders develop gradually over a period of time to take years for a process to reach a level where it could be diagnosed definitively and treatment initiated properly and in time before changes are irreversible! But a majority of medical interventions occur late in the pathological process, when treatment outcome can be less predictable and effective. Moreover, those interventions used led to so-called ‘‘chronification’’ of complex, previously fatal diseases. And despite the benefits of being able to offer such treatments to patients (but not to persons-at-risk), the intervention and maintenance of treatment at this level of disease progression was and still is inefficient and expensive. With healthcare costs amounting to US$2.6 trillion in 2010, and three out of four treatment dollars being spent on the management of chronic conditions (e.g., Parkinson’s costs society $27 billion per year in medical bills and lost wages; worldwide, projected cases of Parkinson’s will more than double by 2030!), the need for new approaches to address these issues has never been more pressing. The above-mentioned would highlight the need for new precise and preventive (PPPM-based) therapeutic development strategies. To achieve the implementation of PPPM concept, it is necessary to create a fundamentally new strategy based upon the subclinical recognition of biomarkers and biopredictors of hidden abnormalities long before the disease clinically manifests itself. This strategy would give a real opportunity to secure preventive measures whose personalization could have a significant influence on demographics! Two key objectives of PPPM are: (i) detection of subclinical abnormalities with a selection of suitable targets for the next step of PPPM protocol, i.e., drug-based prevention; (ii) drug-based correction of the abnormalities detected under the heading of preventive measures. PPPM is thus a medical model being tailored to the individual and dictates a construction of PPPM algorithms to diagnose, to predict, and to prevent in time whilst following a concept of biomarkers impact into the daily practice! The key benefits of PPPM include new abilities: I. to detect disease at a subclinical stage, when it is easier and less expensive to treat effectively; II. to stratify patients into groups that enable the selection of optimal preventive treatment; III. to reduce adverse drug effects by more effective early assessment of individual drug responses; IV. to improve the selection of new molecular targets for drug discovery; V. to shift the emphasis from illness to wellness. Despite an increasing ability to compare and contrast different disease entities at a range of biological levels of organization, an important challenge lies in translating this into clinical decision making tools. And translational armamentarium and thus its tools are appearing to become well-positioned to contribute to the many challenges inherent in bridging this gap between our current reactive methods of healthcare delivery and the intent of PPPM. The first discriminatory step illustrating the PPPM-oriented survey and positive outcome of translational efforts is estimating of the correlation strength between genetic polymorphism and risks of the disease, and subsequent construction of the groups at risks. Those goals can be solved by using of BioChip methodology (each disease has specific genomic biomarkers and thus the individual fingerprints). As a result, a patient becomes a data carrier (i.e., he/she knows about possible risks of a disease), and the physician whilst managing the Biobank services can reasonably select of preventive and/or prophylactic protocol, proceeding from the assays made. Individuals, selected at the first stage, undergo the second phase of the survey, which uses a panel of phenotypic biomarkers and biopredictors to get a stage of subclinical & predictive diagnostics finalized. In many pathologies, subclinical (pre-disease) conditions can now be identified (e.g., pre-hypertension, pre-T1D etc.), states which imply increased for a patient, and in some cases, with an accompanying opportunity to engage in pre-early preventive and/or prophylactic strategies (e.g., exercise prescriptions, dietary changes, medications) which can reduce the risk of progression. Some of pre-disease states which represent significantly increased risk of future adverse health outcomes, identifying reliable biomarkers of these pre-disease states, and developing the key challenges in this paradigm of disease screening are in identifying useful therapeutic strategies to offer individuals should they receive a pre-disease diagnosis. The aforementioned is can enable the identification of the ‘‘key drivers’’ of pathology, which may represent novel therapeutic targets or biomarker candidates that play a more direct role in the etiology of disease. Meanwhile, while some methods (e.g., the use of disease biomarkers to drive treatment choices) already reflect a standard of care within certain areas of medicine, other areas (e.g., the modeling of causal disease networks) which do not yet routinely impact clinical care, are expected to add insight to the identification of high quality drug targets to inform drug development, as well as guiding the interpretation of individual genetic variation in creating tailored therapeutic strategies. The development of safe and effective targeted medicine is obviously needed. The latter would include methods for datadriven disease classification, drug repositioning, identification of disease biomarkers, and the creation of disease network models, each with significant impacts on drug development approaches. However, the current biopharma development pipeline is not presently well poised to meet this need. An important bottleneck in the application of updated technologies in translational research is the lack of educated investigators who are versed in both biomedical domains and informatics. For instance, it would be extremely useful to integrate data harvesting from different data- and biobanks for applications such as prediction and personalization of further treatment. Medical practitioners will be able to thus provide more tailored prevention and treatment programs for their patients resulting in improved patient outcomes, reduced adverse events, and more cost effective use of health care resources. Use of PPPM is categorized into predictive and preventive medicine and personalized treatment optimization. The latter refers to pharmacogenomics which aims to match the best available drug or dose to an individual’s genomic profile. So PPPM whilst utilizing a highly promising concept of biomarkers and biopredictors to be translated into the daily practice, would offer great and real challenge for the future, and next generations will speak about the XXI century as a time, when healthcare services became predictive and preventive whilst utilizing translational armamentarium, and its outcomes – secured and guaranteed!

Speaker
Biography:

Professor Cho obtained his PhD from the Kyungpook National University of South Korea in 1998 and gained his postdoctoral training at the University of Illinois at Urbana-Champaign until 2000. He joined Cleveland Clinic Foundation as a Research Doctor until 2001. After back home, he worked at Korea Research Institute of Bioscience and Biotechnology as senior scientist for 4 years. Then he moved to the Yeungnam University (YU), in 2005, where he is currently the Full Professor (tenured) and Head of the Research Institute of Protein Sensor (RIPS) and BK21plus Serum Biomedical Research and Education Team in the YU. He published more than 70 papers in well known journals and filed more than 20 patents.

Abstract:

Rapamycin and curmin are nonsoluble drug although they have potent pharmaceutical activity. Rapamycin (rapa) is a fungicide, it is now believed to possess the capacity to extend mammalian lifespan. Because rapamycin is insoluble in water, its study in the aqueous phase has been limited. We therefore solubilized rapamycin in isotonic buffer using reconstituted high-density lipoprotein containing V156K-apolipoprotein A-I (V156K-rHDL). Rapamycin (final concentration, 0.1 mg/mL) was solubilized in rHDL containing either wild-type (WT) or V156K apoA-I (1 mg/mL of protein) prepared using the sodium cholate dialysis method. V156K-rHDL containing rapamycin (V156K-rapa-rHDL) had a slightly larger particle size than rapamycin-loaded WT-rHDL (WT-rapa-rHDL). V156K-rapa-rHDL exhibited enhanced antioxidant ability, CETP inhibitory activity, and anti-atherosclerotic activity. Treatment with V156K-rapa-rHDL resulted in attenuation of senescence in human cells with increased cell survival and enhancement of tissue regenerative activities in zebrafish model compared to WT-rapa-rHDL or rHDL alone. Using the rHDL, adenoviral gene delivery and virus stability are also significantly enhanced in mice and zebrafish model.

Ferdinand Sasváry

General Hospital Slovakia

Title: Management of venous thromboembolism at General Hospital Sahy

Time : 15:15-15:40

Speaker
Biography:

Ferdinand Sasváry, graduated as MD in 1992 completed his PhD from the Comenius University, Bratislava, Slovakia. He achieved certification first in Internal Medicine, later in Hematology and Transfusion Medicine at Slovak Health University. Since 2000, he is employed as Primarius of Hematology Dept., simultaneously as Internist at Outpatient Dept. and since 2012 as Deputy-Primarius of Internal Dept. He is elected member of American Society of Hematology and active member of European Hematology Association, member of national (Slovak) medical associations. He is Assistant Professor of Public Health at Slovak Health University. He is contributor of textbook of pathologic physiology, author of more than 20 publications, at least 4 of them indexed in PubMed.

Abstract:

Background: Pulmonary embolism and deep-vein thrombosis are the two components of a single disease called venous thromboembolism (VTE). Approximately 30% of apparently isolated episodes of pulmonary embolism are associated with silent deep-vein thrombosis, and in patients presenting with symptoms of deep-vein thrombosis, the frequency of silent pulmonary embolism ranges from 40 to 50%. Both diagnoses might be life-threatening with serious acute and chronic complications. Anticoagulation treatment is based on classic and novel anticoagulants. The treatment is to be personalized depending on patients´ risk stratification, comorbidities, as well as the thrombotic event characteristic. Adequate treatment of the recent VTE is the basis of preventing complications as well as of secondary prevention of recidive of VTE. Aim: The author provides a review of known and registered anticoagulants, summarizes the accepted guidelines. Data of all patients admitted to the General Hospital Sahy during the last 5 years episode for the suspection of venous thromboembolism are analyzed and the diagnostic and treatment strategy is presented. Method: Data of all admitted patients are characterized – demography, diagnosis, provoking factor of thrombotic event. Patients were admitted to the Internal Department or Intensive Care Unit, depending on the severity of initial findings. The diagnosis was based on clinical finding, laboratory test results, as well as imaging studies. In the earlier period occlusion rheography and ventilation-perfusion scintigraphy the lungs were performed, but in the recent time CT angiography and compressive ultrasound are available 24 hours a day. The adherence to therapy and variation of coagulation parameters in 160 anticoagulated patients during the year 2013 are presented and reasons of inappropriate results are discussed. Results: Results are mainly graphically presented. Warfarin remains the most widely used anticoagulant in patients with VTE. The duration of treatment depends upon the risk factors of the patient as well as on the character of VTE event. In selected patients long term use of low-molecular-weight heparin is the method of choice. Most recently novel oral anticoagulants (NOAC) might be used. The author discusses the necessity of identifying the appropriate patient indicated to treatment with NOACs. Conclusion: Continuing education of both patients and physicians in diagnosis and treatment of VTE is required for assurance of adequate anticoagulation treatment, adherence to treatment and patient safety. The presented study performed at a general hospital presents the progress in diagnostic opportunities, imaging techniques, as well as therapeutic options in patients suffering from VTE.

Break: Coffee Break @ 15:40-16:00@ Atrium
Speaker
Biography:

Rocco de Filippis completed his MD and PhD from Catholic University of the Sacred Heart in Rome. He holds a Master’s degree and he improved respectively in Bipolar Disorders and Addictive behavior in the years 2011/2012. He currently works at the Institute of Psychopathology, Rome as a Psychiatrist and Addictive Medicine, and up to now presented as scientific coordinator of CME and Master of Addictive Behaviors; he is also an official candidate at the Psychoanalytic Italian Society of the First Italian Center of Rome.

Abstract:

Objective: The authors review the mechanisms and establish the risk of torsade de pointes and sudden death with all antidepressant in clinical practice and older and new antipsychotic drugs. Method: The author hasconducted Medline and manual searches of literature to identify articles describing efficacy and safety in the treatment of patients with major mental illness, focusing on the associated risk of QTcprolongation that should be considered in clinical decision-making. A review of original concepts, the distinction between familial and drug-induced cases of torsade de pointes, and the recognition of the role of non-cardiac drugs in torsade de pointes and sudden death have been presented. The author reviews the evidence linking QTc interval prolongation, potassium channels, and torsade de pointes from both the long QT syndrome and drugs. The risk for torsade de pointes from antipsychotic drugs and was examined and the frequency of sudden death on the basis of epidemiological data in mental health populations estimated. Results: All drugs that cause torsade de pointes prolong the QTc interval and bind to the potassium rectifier channel, but the relationships are not precise. Prediction of torsade de pointes and sudden death can be improved by examining dose dependency, the percent of QTc intervals higher than 500 msec, and the risk of drug-drug interactions.

Speaker
Biography:

AW by his profession is biotechnologist and associate professor for molecular biology at the University of Natural Resources and Applied Life Sciences, Vienna. Working from 1995-2004 at the Children’s Cancer Research Institute, Vienna he is experienced in human molecular genetic diagnostics and specialized on diagnostic-testing of syndromal and hereditary neoplastic disease. In 2001 AW obtained the post-doctoral graduation “Specialist in Human Genetics”. Along with diagnostic testing of imprinting disorders he started methylation testing as well as autoantibody testing on protein-microarrays on cancerous disease. Since 2004 at the AIT- Austrian Institute of Technology he specialized on DNA-methylation- and protein-biomarker research. He has filed 6 patents dealing with biomarkers and molecular diagnostics and published more than 50 papers in reputed journals.

Abstract:

An estimated 2.7 million new cancer cases and 7.6 million cancer related deaths were reported worldwide in 2008. It is well accepted that early cancer diagnosis can improve survival, thus there is a great need and anticipation to identify novel biomarkers for cancer diagnosis at the earliest possible stage, which can ideally be integrated in minimal-invasive diagnostic assays. DNA methylation changes are a hallmark of cancer and these epigenetic changes in tumors can be used as markers for detection of circulating tumor DNA in serum/plasma as well in saliva samples. In addition cancer onset and progression produces mutated or aberrantly expressed proteins generally also termed as tumor associated antigens (TAAs) which are able to act as antigens and evoke an immune response which results in the production of autoantibodies. These autoantibodies and the early DNA methylation changes during neoplastic transformation are able to be detected months or years before the clinical diagnosis of cancer and can therefore be used as biomarkers for the early diagnosis of cancer. We have setup genome- and immunome-wide discovery technologies for elucidation of novel biomarkers. From microarray based discovery-studies we have defined cancer-specific multivariate classifiers with very good diagnostic performance, obtaining AUC-values of 0.9- 1 for the big 4 cancer entities. Efficient targeted multiplexed technologies were established for validation of findings. Using methylation sensitive restriction digestion based high throughput qPCR we can detect 0,1-1% of tumor-derived methylated DNA in the very limited amounts (10ng) of cell free DNA in plasma. As an example data we have tested 680 plasma samples, and could obtain AUC values of 0,84-0,91 for the 4 different lung cancer subtypes using a multiplexed methylation test. In addition we have tested these patients using autoantibody-profiles. Current developments of 100-plex Luminex-assays for testing candidate antigenic markers and multimodal analyses combining both autoantibody and DNA-methylation data for improving cancer diagnostics will be presented. In addition recent developments from protein-based to peptide based tools for autoantibody and immunome-analyses will be presented. Based on findings form different cancer-studies, both DNA methylation and autoantibody based strategies outperform the current clinical diagnostic methods and would be of high value for improving cancer diagnostics and patient management.

Speaker
Biography:

Afaf El-Ansary has completed her Ph.D at the age of 37 years from Ain Shams University-Egypt and postdoctoral studies from National Research Centre. She is a professor in Biochemistry Department, Science College, King Saud University. She has published more than 85 papers in high impact factor journals and serving as a reviewer and as an editorial board member

Abstract:

Fatty acids are essential dietary nutrients, and one of their important roles is providing polyunsaturated fatty acids (PUFA) for growth and function of nervous tissue. Short chain fatty acids SCFAs represent a group of compounds derived from the host microbiome that are recently known to induce many effects on gut, brain, and behavior and thus can be linked to neurodevelopmental disorders like autism. Reduced levels of PUFA are associated with impairments in cognitive and behavioral performance, effects which are particularly important during brain development. Recent studies suggest that omega -3 fatty acids as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) functions in neurogenesis, neurotransmission, and protection against oxidative stress. Omega-3 PUFAs mediate some of these effects by antagonizing Omega-6 PUFA (arachidonic acid, ARA) - induced proinflammatory prostaglandin E₂ (PGE₂) formation. In this work, absolute and relative concentrations of propionic (PPA), butyric and acetic acids together with PUFA and their precursors (α-Linolenic and linoleic), were measured in brain tissues of PPA- neurointoxicated rat pups (Recieved 250 mg PPA/Kg body weight for 3 consecutive days) as rodent model with persistent autistic features compared to healthy controls. The obtained data recorded remarkably lower levels of omega6/omega3, α-Linolenic/Linoleic, α-Linolenic/EPA, α-Linolenic/DHA, EPA / DHA, and ARA/Linoleic in PPA-intoxicated rats. Role of these impaired ratios was discussed in relation to the activity of desaturases and elongases as two enzymatic groups involved in the synthesis of PUFA from their corresponding precursors. The relationship between the abnormal relative concentrations of the studied fatty acids and oxidative stress, neurotransmission, and neuroinflammation was also discussed in details. Conclusion: This study proved that fatty acids ratios is useful for the rational understanding of the mechanism of PPA neurotoxicity in rodent model of autism and hence a possibility to use these ratios for predictive implications among patients with this disorder. Additionally, nutritional supplementation of depleted omega-3 fatty acids could be suggested as treatment strategy.

Robert McKee

University of Notre Dame USA

Title: Using zebrafish to model acute kidney injury

Time : 17:15-17:40

Speaker
Biography:

Robert McKee is a Graduate student in his third year at the University of Notre Dame and previously completed his Bachelor of Science at Saint Vincent College as well as a certificate in Biotechnology. His current projects in the Wingert Lab include creating the above mentioned transgenic line as well as interrogating a specific pathway involved in the development of the pronephros and regeneration of the adult mesonephric kidney.

Abstract:

Acute Kidney Injury (AKI) results in a rapid loss of renal function and arises from a wide range of insults including reduced blood flow to the kidney, as well as exposure to toxins or some medications.If AKI progresses unchecked, it can lead to renal failure necessitating kidney dialysis or transplant – treatments which incur great costs to the patient and health care field alike. Zebrafish due to their simplified kidney structure provide a useful animal system in which to study AKI, allowing for interrogation of both the damage response and regenerative pathways. Furthermore, conserved nephron segmentation patterns and function allow for comparison with the mammalian kidney. Traditionally, regenerative studies have focused on the adult kidney to elucidate how a pre-constructed organ re-establishes itself after insult; however, analysis of these regenerative processes first requires injuring the tissue of interest. Currently, the zebrafish field utilizes antibiotic injections to induce AKI. While characterized in detail, this method is susceptible to variability, complicating the ability to compare data between different labs. Toaddress this issue we have begun generating transgenic zebrafish lines which will utilize segment specific promoter regions to drive targeted damage in conjunction with the nitroreductase-metronidazole system. Isolating injury to a specific cell type in this way will allow for more critical investigations of the signaling pathways involved during renal restoration. In the long term, ourmodels will be used for wide scale drug screens to identify molecules with potential clinical value for the treatment of AKI.