International Conference and Exhibition on Molecular Medicine and Diagnostics August 24-26, 2015 West Drayton, London, UK

Biography:

Luo been studying molecular pathology related to human malignancies in the last 23 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 13 years, Dr. Luo has been largely focusing on genetic and molecular mechanism of human prostate and hepatocellular carcinomas. In this period, his group has identified and characterized several genes that are related to prostate cancer and hepatocellular carcinoma, including SAPC, myopodin, CSR1, GPx3, ITGA7, MCM7, MT1h and GPC3. He has characterized several signaling pathways that play critical role in prostate cancer development, including Myopodin-ILK-MCM7 inhibitory signaling, myopodin-zyxin motility inhibition pathway, CSR1-CPSF3 and CSR1-XIAP apoptotic pathways, MT1h-EHMT1 egigenomic signaling, ITGA7-HtrA2 tumor suppression pathway, GPx3-PIG3 cell death pathway, and AR-MCM7 oncogenic pathway. He proposed prostate cancer field effect in 2002. He is one of the pioneers in utilizing high throughput gene expression and genome analyses to analyze field effects in prostate cancer and liver cancer. He is also the first in using methylation array and whole genome methylation sequencing to analyze prostate cancer. Recently, Dr. Luo’s group found that patterns of copy number variants of certain specific genome loci are predictive of prostate cancer clinical outcomes, regardless tissue origin. His discovery of several novel fusion transcripts and their association with aggressive prostate cancer has brought significant new insight into the field of prostate cancer research. Overall, these findings advance our understanding on how cancer develops and behave, and lay down the foundation for better future diagnosis and treatment of human malignancies.

Abstract:

Despite a high incidence, only a fraction of men diagnosed with prostate cancer (PCa) develop metastases and even fewer die from the disease. The majority of prostate cancers remain asymptomatic and clinically indolent. The precise mechanisms for the development of progressive, clinically relevant PCa remain elusive. Recently, we found large numbers of copy number variations in the blood, benign prostate tissues and prostate cancer samples from prostate cancer patients. Interestingly, the sizes of CNVs in the blood samples of prostate cancer patients are highly correlated with the clinical outcomes in terms of prostate cancer recurrence and prostate cancer related death. Using least square regression model, we achieved 75% accuracy in predicting prostate cancer recurrence after radical prostatectomy using CNV information from the blood samples of prostate cancer patients, significantly higher than the prediction rates generated by Gleason scores or Nomogram. When blood CNV combined with the status of Nomogram and fusion gene, the accurate prediction rate is 87.6%. The blood CNV prediction model is of particular interest, since it offers an alternative in predicting prostate cancer clinical courses when radical prostatectomy is not performed, and nomogram information cannot be obtained. As a result, we conclude that the formation of large size germline CNVs predisposed patients to aggressive prostate cancer clinical courses.

Biography:

Sughrue is the current director of the comprehensive brain tumor center at the University of Oklahoma. He attended medical school at Columbia University before completing his neurosurgery residency at UCSF. He performs over 400 operations for brain tumors annually in addition to numerous active research efforts in brain tumor treatment. He has authored over 140 peer reviewed publications in addition to editing several text books.

Abstract:

Objective:While the ascribed role of complement has generally been limited to inflammation and the immune response to pathogens, recent data suggest that the system has far broader functions, including that of a proliferation signal. We sought to determine the effect of necrosis-induced activation of the complement protein C3 in medulloblastoma.
Materials/Methods:Twelve medulloblastoma surgical specimens were evaluated for complement activation using immunohistochemistry, with H&E stains performed on adjacent tissue sections to determine the relationship of complement activation to necrotic tissue. Flow cytometry and Western blot were performed on 3 established medulloblastoma lines and 1 surgically procured cell culture to determine expression of C3a receptor (C3aR) in medulloblastoma. In vitro proliferation of siRNA C3aR knockdown cells was compared to that of control siRNA cells with cell line Daoy.
Results:Three surgical specimens were found to have necrosis on H&E sections. In each case, iC3b staining was identified on adjacent sections, limited to the necrotic region. In no case did necrosis occur without iC3b staining on adjacent sections. C3aR protein was demonstrated on both the 3 established cell lines and on the surgical culture. Proliferation assays of Daoy cells with siRNA knockdown vs. control siRNA revealed significantly reduced proliferation at 72 hours (p = 0.001).
Conclusions: Necrosis is associated with complement activation in medulloblastoma. Medulloblastoma cells express C3aR, and siRNA-mediated knockdown of C3aR inhibits proliferation of these cells in vitro.

Biography:

Chhabra is working as an assistant professor in the Department of Medicine, University of Connecticut Health Center, Farmington, Connecticut. His research is aimed at developing an effective immune based cancer therapy. He has published more than 15 research manuscripts in prominent journals, and has also received several awards at international cancer immunotherapy meetings. Besides his work on human melanoma antigen specific T cells, Dr. Chhabra is also working towards utilizing the human pluripotent stem cells [hPS, i.e. human embryonic stem cells (hES) and induced pluripotent stem cells (iPS)] for developing patient specific cancer immunotherapy approaches through TCR engineering approach.

Abstract:

TCR engineered anti-tumor T cells have produced remarkable responses in cancer patients, however, generation of customized anti-tumor T cells with predefined functional characteristics remains a challenge. We are working on characterizing the biology of tumor antigen specific TCR engineered T cells, to develop methodologies for generating T cells with predefined functional profiles. We have recently shown that TCR engineering approach can also be utilized to program human CD4 T cells to function as MHC class I restricted anti-tumor effectors that can simultaneously exhibit a helper response as well as cytolytic effector response (Chhabra et al., JI, 2008 and Ray et al., J. Clin. Immunol., 2010). Interestingly, we have found that these MHC class I restricted multifunctional CD4 T cells can also mitigate regulatory T cell (Treg) mediated immune suppression. Furthermore, we have found that these engineered CD4 T cells are also susceptible to epitope specific activation induced cell death (AICD), that has distinct differences from AICD in TCR engineered CD8 T cells (Chhabra et al., JI, 2013). We will share our recent findings on biology of MHC class I restricted CD4 T cells, such as their effector function profile, ability to mitigate Treg-mediated immune suppression, and their susceptibility to undergo AICD. We will also discuss molecular pathways involved in development of multifunctional effector profile of MHC class I restricted CD4 T cells, and strategies for generating customized anti-tumor T cells with predefined functional profiles.

Biography:

Dana L Abramovitz received her Ph.D. in Biochemistry and Molecular Biophysics from Columbia University and did her post‐doctoral fellowship at The Scripps Research Institute. She then moved to Ingenuity Systems, a software development company for life sciences researchers. Dana went to business school at the Stanford Graduate School of Business and focused on healthcare new ventures, earning a Master’s in Management. Following Stanford, Dana worked for Strand Life Sciences, primarily a software company, to help them transition from life sciences research to healthcare. Dana recently moved to Austin and is currently working with SXSW, focusing on Health and Med Tech.

Abstract:

Humans are creatures of habit, we like what is familiar to us. As scientists we explore and push the boundaries of knowledge, but we are still human and tend to read the same journals and attend conferences in our field. But biology is not limited, nor does it adhere, to our specified boundaries. Limiting our scope to our defined fields prevents us from observing problems from all possible angles. It also limits our access to new technologies and techniques and from creating new uses from existing standards. Are there successful, real--‐world models for a more inter--‐disciplinary approach? SXSW Interactive was introduced over 20 years ago as a way to broaden the conversation around the uses of technology and promote collaboration. The outcomes from enabling the collaboration of people with different disciplines and areas of interest have led to new insights and new innovations, and the ability to take on and solve much larger and more complex problems. The same approach can be applied to molecular medicine and diagnostics and could perhaps help us expand the research and techniques, leading to new solutions and opportunities.

Biography:

Louise Mackenzie completed her PhD at the age of 29 at Imperial College, London, and continued in postdoctoral study at Imperial College and the William Harvey Research Institute. Currently a Senior lecturer in Pharmacology at the University of Hertfordshire, Louise has published 22 Full Papers and 5 Review Articles in reputed journals.

Abstract:

Pancreatic adenocarcinoma (PDAC) is one of the most lethal human cancers with a 5-year survival of less than 5% due mostly to the lack of effective therapy and difficulty of detection at an early stage of development. Recent studies have shown a high prevalence of S100 proteins in PDAC, in particular the calcium-binding protein S100P. It has been proposed that the metastasis-promoting calcium-binding protein S100P which possesses both intracellular and extracellular functions activates key cell signaling pathways, including MAP kinase and nuclear factor NFκB pathways through its extracellular interaction with the receptor for advanced glycation end products (RAGE). The interaction between RAGE-S100P stimulates pancreatic tumor proliferation, survival, invasion and metastasis progression in vitro and tumor metastasis in vivo. Using computational chemistry methods, our laboratory have identified 87 novel compounds that prevent S100P binding to RAGE. Here in this talk we will outline the key challenges and methodology used to validate an ELISA to measure S100P and RAGE interaction. Our initial results highlight 22 new lead compounds that inhibit S100P-RAGE interaction, some of which have shown an ability to decrease pancreatic cell line growth. This work is supported by the Association for International cancer research and the University of Hertfordshire.

Biography:

I have completed my Bachelor of Science & Master degree from Vinoba Bhave University, Hazaribag, India. Currently I am doing my Ph.D in Cardiovascular disease at CSIR-Indian Institute of Chemical Biology, Kolkata, India. My primary objective of research is to understand the extracellular matrix remodelling in Rheumatic Heart Disease. Part of the work is already published in a peer–reviewed journal and presented at various national and international meetings. I have publications in namely International journal of cardiology, Plos One, Clinical Proteomics etc and have also two patents in my name.

Abstract:

Background:Rheumatic Heart Disease (RHD) results from Acute Rheumatic Fever. It is a major public health concern in Low and Middle Income Countries (LMICs). In general, mitral valve is affected and show thickening and fibrosis with or without calcification. It is predicted that RHD would continue to cause high mortality and morbidity in LMICs and hence requires improved diagnosis and treatment strategies.
Objective:The present study was conducted to investigate whether extracellular matrix remodelling in rheumatic valve leads to altered levels of collagen metabolism markers and if such markers can be clinically used to diagnose or monitor disease progression.
Methods:The study included the subjects with rheumatic heart disease before and after valve replacement surgery and age and sex matched controls in Indian subpopulation. Periodic clinical monitoring was performed with echocardiography. Circulating levels of markers of collagen turnover were monitored by immunoassay. Histopathology studies were performed on excised mitral valve leaflets. A p value <0.05 was considered statistically significant.
Results: Plasma PICP and PIIINP concentrations increased significantly (p<0.01) in MS and MR subjects compared to controls but decreased gradually over a one year period post mitral valve replacement (p<0.05). In MS, PICP level and MMP-1/TIMP-1 ratio strongly correlated with mitral valve area (r = -0.40; r = 0.49 respectively) and pulmonary artery systolic pressure (r = 0.49; r = -0.49 respectively); while in MR they correlated with left ventricular internal diastolic (r = 0.68; r = -0.48 respectively) and systolic diameters (r = 0.65; r = -0.55 respectively). Receiver operating characteristic curve analysis established PICP as a better marker (AUC = 0.95; 95% CI = 0.91 - 0.99; p<0.0001). A cut-off > 459 ng /mL for PICP provided 91% sensitivity, 90% specificity and a likelihood ratio of 9 in diagnosing RHD. Histopathological studies were done on excised mitral valve leaflets to examine tissue architecture, altered abundance of fibrillar collagens, inflammation, scarring, neovascularisation and extensive leaflet fibrosis in diseased mitral valve. It has been found that circulating levels of interleukin (IL-6) is increased whereas IL-10 act as an anti-inflammatory marker in RHD.
Conclusions: Levels of collagen metabolism markers correlated with echocardiographic parameters for RHD diagnosis. Therefore, progressive fibrosis in rheumatic valve could be monitored by a robust increase in collagen metabolism markers particularly PICP. They also determined disease prognosis.

Biography:

Masahide Takahashi received his M.D. and Ph.D. from Nagoya University in 1979 and 1983, respectively. He carried out postdoctoral research at Dana-Farber Cancer Institute in Boston. He joined Aichi Cancer Center Research Institute (Nagoya) as a research scientist in 1985 and moved to Nagoya University as an assistant professor in 1990. He was promoted to full professor of Department of Pathology at Nagoya University in 1996. He was a director of Center for Neurological Disease and Cancer at Nagoya University (2003-2012). His research interests include oncogene function, cancer invasion and metastasis, and development of the nervous system.

Abstract:

Girdin is an actin-binding Akt substrate that plays an important role in actin organization and Akt-dependent cell motility in fibroblasts and cancer cells. Girdin is expressed in a variety of cancer cells including breast cancer cells and glioblastoma cells, and is phosphorylated by the stimulation of growth factors. Girdin knockdown markedly inhibited migration and invasion of cancer cells in vitro and in vivo. Recently, we found that Girdin is also expressed and activated by Akt phosphorylation in cancer-associated fibroblast (CAF) and blood vessels within the tumor microenvironment. We established a knock-in mouse line (designated SA mice) engineered to express a Girdin mutant that lacks the Akt phosphorylation site at serine 1416 (S1416A). The growth of allogeneic tumors (Lewis lung tumors) was decreased in SA mice compare with wild-type (WT) counterparts. Notably, the co-transplantation of tumor cells with either skin fibroblasts or CAF derived from　SA mice also attenuated tumor growth compared to co-transplantation with WT fibroblasts or CAF, indicating the in vivo relevance of Girdin phosphorylation in formation of the tumor microenvironment. Our results revealed a role for Akt-mediated Girdin phosphorylation in CAF during tumor progression, highlighting the need to inhibit Akt function in both tumor cells a CAF.

Biography:

Rajaa Fakhoury has completed her PhD in Medical Biochemistry at the age of 29 from Manchester University. She worked as a dean of the Faculty of Science at Beirut Arab University. Her research interest is to find association between molecular biomarkers and chronic diseases such as diabetes, hypercholesterolemia and Alzheimer. She has more than 30 publications in this field.

Abstract:

Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most common cause of dementia. AD is characterized by impairment in memory and other cognitive functions. The two pathological hallmarks of AD are the large extracellular plaques deposits of the β-amyloid peptides (Aβ) and the intra-neuronal fibrillary tangles of the microtubule binding protein tau. Aβ peptides are proteolytically derived from a type 1 integral protein termed amyloid precursor protein (APP) and are constantly anabolized and catabolized in the brain. The accumulation and aggregation of Aβ which is the primary cause of AD, induce an inflammatory response followed by neuritic injury, hyperphosphorylation of tau protein and formation of fibrillary tangles, leading ultimately to neuronal dysfunction and cell death. Angiotensin converting enzyme (ACE) is a membrane-bound ectoenzyme that has been demonstrated to inhibit Aβ peptides aggregation and plaque formation in vitro. ACE gene has been extensively studied as a candidate gene for Alzheimer’s disease (AD) since ACE was found to be significantly increased in AD patients in several previous studies. ACE is a dipeptidyl carboxypeptidase widely distributed in the body. ACE gene is located on chromosome 17q23, and has an insertion and deletion polymorphism (I/D) of a 287 bp Alu repetitive sequence in intron 16. The association of ACE polymorphism with AD is still controversial. Some meta-analyses addressing the relationship between ACE I/D polymorphism and AD have shown that the D/ D genotype is associated with a reduced risk for AD and that both ID and II genotypes were associated with an increased AD risk, thus making ACE I allele a risk factor for AD. However, few studies found no evidence to support linkage between ACE I/D polymorphism and AD. This apparent discrepancy may be due to ethic differences. This study was performed to examine for the first time the association between ACE I/D polymorphism and the risk of Alzheimer’s disease in Lebanese patients. Forty-five patients diagnosed as having Alzheimer’s disease and forty-eight age-matched controls from Dar Al-Ajaza Al-Islamia Hospital in Beirut were recruited, relevant clinical data were confidentially collected such as age, medical history, smoking habits, blood chemistry tests (such as glucose, lipid profile). A confidentiality letter was signed to safeguard the collected information. Patients and controls were tested for ACE I/D genotype by PCR. Results showed that the distribution of genotypes between Alzheimer’s patients was: 28.9% DD, 53.3% ID and 17.8% II while the controls showed 35.4% DD, 64.6% ID and 0% II. According to our findings, the II genotype was significantly higher in Alzheimer’s patients than in controls. Therefore, our study demonstrated the I/I genotype to be associated with an increased risk of AD in Lebanese population.

Biography:

Working as Consultant, Department of Lab Medicine in The Calcutta Medical Research Institute (CMRI) and B. M. Birla Heart Research Center since June, 2005. Passed MD (Biochemistry) in June, 2005 from Burdwan Medical College, University of Burdwan, Burdwan , West Bengal, India. Passed DNB (Biochemistry) in November, 2005 from National Board of Examination, Department of Health & Family Welfare, Govt. of India. Passed P.G. Dip Diabetology passed in September, 2007 from Annamalai University, Chennai, Tamil Nadu. President , Association of Clinical Chemistry & Lab Medicine Practiioners ( ACCLMP) NABL (National Accreditation Board for Testing & Calibration of Laboratories) Assessor since 2010 & CAP(College of American Pathologist) International inspector since 2011

Abstract:

Lipemia is known to interfere in the measurement of electrolytes using indirect potentiometry, whereas effect of lipemia using direct potentiometry is yet to be fully understood. The objective of this experiment is to observe whether lipemia affects the measurement of electrolytes using direct potentiometry by increasing concentration of triglyceride on the serum samples in vitro and if it does so, then at what specific concentration the effect occurs. Methods: Two instruments, VITROS250 and HDC LYTE were used for a comparative study to measure electrolytes by direct potentiometric method (where direct serum sample is used for the measurement of electrolytes). For the characterization of this experiment, we collected one hundred& five serum samples and divided each of them into five aliquots, of which no intralipid was added to the first aliquot and to the rest four , 0.83% , 1.96% , 5% and 15% concentration of intravenous fat emulsion was added respectively to induce lipemia. This is followed by measurement of the electrolyte concentration of these prepared serum samples, resulting in five data set for each serum sample. In the VITROS250 machine, three parameters are measured, i.e., sodium , potassium and triglyceride content of the samples. In the HDC LYTE machine two parameters are measured, i.e., sodium and potassium concentration of the samples. The results are thus recorded and the results as measured in the two separate machines i.e VITROS 250 and HDC LYTE are used to compare accordingly to ascertain the influence of increasing lipid concentration on the electrolytes are significant or not by statistical analysis. Result: It was revealed that the electrolytic measurement of both sodium and potassium were significantly affected when the triglyceride concentration was gradually increased in serum samples. A considerable change in sodium concentration has been observed. Sample with 167mmol/L in normal condition underwent an abrupt change to 145mmol/L , when the triglyceride concentration was 1550mg/dl or beyond . Beyond 650 mg/ml triglyceride concentration , the electrolyte values were significantly lower than the baseline values in both the analysers. So it is evident that, lipemia even if it is about 650 mg/ml may bias the electrolyte concentration measured by ISE methods. Conclusion: A correction method is required for the amendment of this interference property of lipemic serum samples for the major electrolyte (i.e sodium and potassium) measurements to deliver quality and safe patient care.

Biography:

Adhip P N Majumdar from Wayne State University School of Medicine, USA made his valuable remarks at 2nd International Conference on Gastroenterology & Urology held during June 10-12, 2013 at Hilton Chicago/Northbrook, USA

Abstract:

A primary conceptual challenge in the study of mammalian aging is the occurrence of disease and the intricate relationship of disease processes to aging. One of the most consistent pathological conditions in the gastrointestinal tract (GI) tract with advancing age is malignancy, specifically colorectal cancer, the incidence of which increases sharply with aging. Although the underlying cellular and molecular events for the age-related rise in colorectal cancer is not fully understood, we have suggested a role for self-renewing, pluripotent cancer stem/stem-like cells (CSCs) in regulating these processes. In support of this, we have demonstrated that the age-related increase in adenomatous polyps in the colon of humans is associated with a concomitant rise in the expression of several CSC markers such as CD44, CD166 and ESA in macroscopically normal appearing colon. A similar increase in CSCs was also observed in the colonic mucosa of aged Fischer-344 Fischer-344 rats. Since CSCs are thought to be the mutated counterpart of normal stem cells, which in the colon are primarily located at the bottom of the crypt, we hypothesize that an age-related increase in mutated CSC gradually replicating and eventually occupying the entire crypt-villous axis will lead to the formation of colon tumor. To test this hypothesis, we isolated mucosal cells from the upper-1/3, middle and lower regions of the colon of young (4-month) and aged (24-months) Fischer-344 rats. The cells isolated from all three regions were subjected to spheroid formation and gene mutation analysis. We observed that mucosal cells from the middle and lower, but not the upper region of the colon from aged rats formed a large number of sphere/spheroid-like structures. These spheroids could be extended to 2nd generation. Mucosal cells from the lower region of the colon of young animals were also able to form a small number of spheroids, but they were much smaller and this formation was not very consistent. No spheroids were formed by cells from the middle and upper regions of young animals. This increased spheroid forming ability of mucosal cells from aged rats was associated with increased expression of CD44 and catenin. In contrast, CK-20, a marker of differentiation, was greatly augmented in the middle and upper part of the colon of aged rats, compared to cells from the lower region. Frequency of gene mutation was also higher in colonic mucosal cells from the lower region of the colon of aged than young animals. We conclude that with aging there is a gradual increase in CSCs in the colonic crypt which may partly be response for the age-related rise in colorectal cancer

Biography:

Carlos Fernando Prada Quiroga is Biologist, MSc in genetics and evolution of Universidade Federal de Sao Carlos in Brazil. He has completed his PhD in genetics at the age of 32 years from Universidad Autónoma de Barcelona, Spain. He has had teaching experience in countries like 2 Brazil, Spain and Colombia. He is Associate Professor and director of Bacteriology and Clinical Laboratory research group. He has published more than 10 papers in reputed journals. His research focuses on the evolutionary origin of genomic rearrangements and its relationship to different human pathologies, using mainly bioinformatics tools.

Abstract:

Mitochondrial genome plays a variety of important roles, including the generation of ATP through respiration and oxidative phosphorylation (OXPHOS), production of reactive oxygen species (ROS), and initiation and execution of apoptosis. Therefore, variation in these genes can directly influence metabolic performance. The mitochondrial genome presents a gene structure relatively stable through the evolution of species with a relatively low rate of gene rearrangements compared to the nuclear genome. The recent increase in the number of sequenced mitochondrial genomes of hundreds of species, it has become clear that some groups of species the gene order is more conserved than in other groups. For example, mammals and birds have relatively stable gene orders, while in amphibians, reptiles and fish rearrangements are more common. Recent studies have found that the mammalian mitochondrial genome has a higher rate of rearrangements than expected. 244 mitochondrial events were identified: Inversions, deletions and non-homologous regions (non-HR: less than 10% nucleotide identity). Inversions were found at a frequency of 84.0 % (205/244). These inversions, classified as microinversions (<1Kb) are recurrent in tRNAs genes; deletion are detected on D-loop region and tRNAs; and non-HR located on control region. Based on the breakpoints (BP) of mitochondrial inversions, there were postulated fourteen fragile regions in the human mitochondrial genome. Over 250 pathogenic human mtDNA mutations have been characterized to show the cause a wide variety of diseases with heterogeneity of phenotypes and a variable age of onset. Most of deletions and duplications BP reported in the human mitochondrial genome match with the fragile regions previously postulated. These findings could indicate the important role of tRNA in the origin of rearrangements in the human mitochondrial genome and in mammals in general.

Biography:

Deputy Director Cancer Therapeutics at University of Bradford. Professor of Molecular Pathology and Cancer Therapeutics at University of Bradford. Over 20 years’ experience in clinical biochemistry and molecular oncology undertaking the molecular mechanism of malignant transformation, biomarker discovery and small molecule drug discovery and its mechanisms of action. Employed at king Khalid hospital (Saudi Arabia) and Alexandria University hospital as a consultant of Clinical Biochemistry and then moved to full research posts in University of Liverpool and then moved to Queen’s University Belfast as lecturer and senior lecturer. Responsible for the discovery of Ran biomarker, a tumour biomarker gene which Gold test for early detection of cancer metastasis and patient stratify for personalised medicine. Member of different company advisory board including UniDiagnostics Ltd (UK) and European Screening port (Germany). Act as Editor and senior editor for several international high profile journal

Abstract:

Ran is a Ras-related GTPase that is critical for mitosis, apoptosis and nucleo-cytoplasmic transport. Ran is overexpressed in cancer cell lines and tumour tissues at both the mRNA and protein levels compared with their normal counterpart. It has been shown that cancer cells are more susceptible to Ran silencing than normal cells. mRNA and protein levels of Ran are shown to be a prognostic marker for poor prognosis in both breast and lung cancers. Ran prognostic significance is dramatically enhanced in cancers with increased c-Met, c-myc or OPN expression or with oncogenic mutation of KRas or PI3KCA, that correlate with activation of the PI3K/Akt/mTORC1 and Ras/MEK/ERK pathways. These results suggest that overexpression of Ran in clinical specimens is significantly associated with poor patient outcome in both breast and lung cancers.

Biography:

Jenny Ruedlinger is a PhD student at the Center of Molecular Biology & Pharmacogenetics in the University of La Frontera. The main focus of her research project is to evaluate genetic and epigenetic determinants involved in coronary artery restenosis after angioplasty.

Abstract:

Coronary artery angioplasty with stent is a common procedure to restore myocardial blood flow. However, 20-30% of those who receive bare metal stents and 5 to 10% with drug eluted stents develop in-stent restenosis (ISR), which involves clinical and genetic factors. NOS3 and TNF genes participate in ISR pathophysiology, as nitric oxide has vasodilatory, antithrombotic, antiinflammatory and antiproliferative properties, and TNF is a key regulator of inflammation. This study is aimed to assess whether allelic distribution of NOS3 and TNF polymorphisms differ among patients who develop and those who not develop ISR. A number of 155 patients were included. Patients with stenosis > 50% in the angioplasty site were defined as cases, and those with <50%. as controls. Clinical and demographic variables were registered. Four SNPs were genotyped rs2070744 and rs1799983 in NOS3, and rs361525 and rs1799964 in TNF. This was performed by real-time PCR using allele-specific TaqMan® probes. For statistical analysis a p value of <0.05 was considered significant. Genotypic distribution and allelic frequencies did not differ between cases and controls. OR values for the mutated alleles were 1.07 (95% CI: 0.66 to 1.7) for rs2070744, 0.95 (95% CI: 0.56 to 1.61) for rs1799983, 0.83 (95% CI: 0.34 to 2) for rs361525, and 1 (95% CI: 0.56to 1.79) for rs1799964. We find association for Diabetes but not for the SNPs between cases and controls, however it is still not possible to discard its influence on ISR in Chilean population, a higher number of patients must be assessed. Fondecyt Nº1141292.

Biography:

In 2008 has completed her PhD at the age of 27 years from Siberian State Medical University and postdoctoral studies from Siberian State Medical University. Evgeniya Kaigorodova - PhD, MD physician of clinical laboratory diagnostics of the highest category, Leading researcher, Department of Pathological Anatomy and Cytology, Tomsk Cancer Research Institute (2012-present); Leading researcher Laboratory of Translational Cell and Molecular Biomedicine, Tomsk State University (2014-present); Professor of the Department of Biochemistry and molecular biology of the Siberian State Medical University (2014-present).She has published more than 50 papers in reputed journals.

Abstract:

Heat shock protein 27 kDa (Hsp27) is a chaperone of the sHsp (small heat shock protein). The common functions of sHsps are chaperone activity, inhibition of apoptosis, regulation of cell development, and cell differentiation, take part in signal transduction. Objective: To study the intracellular localization of phosphorylated features and non-phosphorylated forms of Hsp27in primary breast cancer cells and to evaluate their relationship with regional lymphatic metastasis. Material and Methods: Tumor biopsies of breast tissue were collected from 100 patients with a confirmed diagnosis of invasive carcinoma, nonspecific type, between the ages of 31-80 years. Immunohistochemistry was used to determine the intracellular localization of phosphorylated and non-phosphorylated forms of Hsp27. Results: The result of this study showed that biopsies from patients with lymph node metastasis exhibited significantly higher levels of phosphorylated forms of Hsp27 in the nucleus and cytoplasm compared with the group without lymph node metastasis. Analysis showed that the expression of phosphorylated forms of the chaperone Hsp27 correlates with the amount and percentage of lymph node metastases affected. Conclusion: The nuclear expression of phosphorylated and non-phosphorylated forms of the chaperone Hsp27 is a marker of tumor cells associated with lymphatic metastasis of breast cancer.

Biography:

Ashraf A Khalil holds a position of professor at City of Scientific Research (SRTA-City), Egypt. He got postdoctoral trainings at Dept of Biotechnology, Dept of Developmental Biology, Dept of Protein Chemistry and Dept of Neurosurgery. All were at Lund University, Sweden. In 2007, he came back Egypt and built his own team and supervising many biotechnological-oriented studies, including disease biomarkers, natural products, bioactive proteins and proteomics. Along his career he published more than 35 articles in peer-reviewed journals. He is a member of the editorial board of many peer-reviewed journals and is a fellow of European Organization for Molecular Biology (EMBO) and American Association for Cancer Research (AACR). Prof Khalil is the founder of Euro-Mediterranean Association of Life Sciences (EMALS). EMALS initiated a series of conferences called Euro-Mediterranean Conferences of Natural Products (BioNat) which were held four times successfully, in which Prof Khalil was the key leader.

Abstract:

PPARγ, a ligand-stimulated transcription factor with differentiation promoting activity is overexpressed in a variety of cancers. Perturbation of PPAR-γ signaling is now believed to be a strategy for treatment of several cancers, including breast cancer. A set of genes regulated by PPAR-γ ligands is expected to mediate the antiproliferative and prodifferentiation effects in cancer cells. Because 14-3-3 family of proteins shows a debatable activity and varying expression levels in different tumors, in the studies presented here we explored the transcriptional regulatory role of Pioglitazone on the seven 14-3-3 isoforms presenting in MCF-7 breast cancer cells. This study demonstrated that the potent PPAR-γ agonist, Pioglitazone exerted a regulatory role on expression of 14-3-3 genes where it upregulated 14-3-3 gamma, epsilon, zeta and tau by 3.8, 5.2, 2.7 and 739 folds, respectively. However, it had a negative regulatory effect on 14-3-3 beta, sigma and Eta by 16.94, 4.58 and 2.12 folds, respectively compared with control cells. These results correlated with growth arrest and a great increase in BRCA1 gene expression by 1076 folds. In summary, these findings are the first time showing that PPAR-γ regulates 14-3-3 genes and raises question whether PPAR-γ ligands mediate their anticancer effects via regulation of 14-3-3 proteins.

Biography:

Zhen Wang has completed her MM at the Capital Institute of Pediatrics in 2012, and became a young researcher at Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics. The main work of her research is about the interaction of genetics and epigenetics in the mechanism of birth defects. Since 2012, she has published about 4 articles on genetic and epigenetic alternations in birth defects as the first author or joint first author.

Abstract:

SHH signaling pathway played an important role in the formation of dorsal ventral neural plate, Neural tube defects (NTDs) were caused through the overactive of SHH signaling pathway. It has been shown in mice that genes of SHH signaling pathway mutations increased the incidence of NTDs, such as spina bifida and brain anomalies. However, the relationship between the single nucleotide polymorphisms (SNPs) of SHH signaling pathway and neural tube defects NTDs remains unclear. A case-control study was designed; NTDs and control samples were obtained from the Lvliang area of Shanxi Province in northern China. Polymorphisms were genotyped for 187 NTD and 212 control samples and genotyping was conducted with a MassArray high-throughput DNA analyzer. The G allele of rs357564 in PTCH1 increased the risk of NTDs especially spina bifida. The A allele of rs12132032 in PKA signifcantly increased the incidence of NTDs especially anencephaly. The AG allele of rs10786691 in SUFU was related with NTDs and encephalocele. The C allele of rs3824 in SMO increased the risk of spina bifda. High methylation levels around rs357564 were detected in the control group with the G phenotype of the site in PTCH1. Data shown here implying that the gene polymorphisms of SHH signaling pathway maybe a potential risk factor for NTDs in our study population, and the SNP may have an impact on surrounding methylation status.

Biography:

Cuilan Li has completed her M.D. from Wuhan University, MPH and PhD from the University of Hong Kong. Through The Recruitment Program of Global Experts, She is recruited to work as the associate Head of Key Laboratory for Major Obstetric Diseases of Guangdong Province, Guangzhou Institute of Obstetrics and Gynecology, the Third Affiliated Hospital of Guangzhou Medical University. She has published more than 50 peer-reviewed papers in top national and international journals, is presiding more than 10 national and international projects, and has been serving as an editorial board member of 12 high impact national and international journals.

Abstract:

Nowadays, two members were found at Golph3 family, Golph3 and its paralogue Golph3L. Golph3 has recently been reported to involve in the clinical progression in several human cancers including ovarian cancer. However, the expression status and function of Golph3L were rarely reported. We explored the expressions of Golph3 and Golph3L in ovarian cancer and their relationship with the disease. Methods: The expressions level of Golph3 and Golph3L were detected by ELISA, quantitative PCR (Q-PCR), western blot (WB) and immunohistochemical staining (IHC). Their expression levels in ovarian tumors were compared with normal, borderline tissues and also correlated with clinicopathological parameters. Results: No detectable Golph3 and Golph3L expression in serum. A continuous up regulation of Golph3 and Golph3L in the order of normal, borderline and malignant tissues was observed by Q-PCR, western-blot and IHC detection. Statistical analysis based on IHC detection showed significant difference (P<0.001 & P<0.05). Univariate and multivariate analysis indicate that overexpression of Golph3 and Golph3L are associated with clinical stage (P=0.006, P=0.03), T classification (P=0.07, P=0.04), N classification (P=0.02, P=0.03), chemo-sensitivity (P=0.045, P=0.045), tumor-free survival (P=0.014, P=0.034) and overall survival time (P=0.023, P=0.037). Univariate and multivariate analysis showed that Golph3 and Golph3L overexpression were, respectively, independent prognostic factor in ovarian cancer. Kaplan-Meier analysis revealed that patients with Golph3 and/or Golph3L over-expression experienced significantly disease-free and much shorter overall survival time (log-rank P<0.001 & P<0.05). Conclusions: Both Golph3 and Golph3L were over-expression in ovarian cancer. Correlations with clinical parameters suggested that Golph3 and Golph3L are both independent prognostic factors for ovarian cancer.

Biography:

Rasime Kalkan has completed her PhD at the age of 27 years from EskiÅŸehir Osmangazi University, Turkey and starts her postdoctoral studies from Near East University Faculty of Medicine, Department of Medical Genetics. Her research was focused on the genetic background of the glioblastomas and investigations for personalized medicine.

Abstract:

Background: To establish the frequency of MGMT and RARβ methylation in primary glioblastomas. We screened primary glioblastoma multiforme (GBM) in a population-based study for MGMT and RARβ methylation and correlated them with clinical data and treatment. Results: MGMT methylation was detected in 13 of the 40 patients (32,5%). MGMT-promoter methylation did not correlate with overall survival (OS; p >0.05). RARB methylation was detected in 24 of the 40 patients (60%). The overall survival time of the patients with methylated RARβ was 19 months, and nonmethylated RARB was 15 months. There was statically (OS;p<0,05) significance between the patients who were treated with chemotherapy and radiotherapy.
Conclusion: In summary, this study is suggested to the RARβ gene is also a new prognostic and predictive candidate marker for the primary GBM patients for choosing therapy strategy. Furthermore MGMT promoter methylation had no prognostic value and lower frequency in primary glioblastomas.

Biography:

Abstract:

Esophageal Cancer (EC) represents the third most common G.I malignancy and ranks among the ten most common cancers worldwide. The highest incidence of this cancer in India has been reported from Assam in the North-east region where it is the second leading cancer in men and third leading cancer in women. A familial aggregation of esophagial cancer has been reported in Assam region of North East India along with high consumption of beetle quid, tobacco and alcohal suggesting that environmental carcinogens in addition to geographic and genetic factors may play major etiological role. Integrated genomic approaches have been under taken to understand molecular carcinogenesis and to identify biomarker. Analysis of gene expression profile of tumour tissue from 16 non familial betel quid/tobacco chewing patients of esophageal cancer from Dr. B. Borooah cancer Hospital, Guwahati, Assam showed up regulation of MAPK pathway, G-protein coupled receptor family, ion transport activity, and serine or threonine kinase activity and down regulation of structural constituent of ribosome, endopeptidase inhibitor activity, structural constituent of cytoskeleton, antioxidant activity, acyl group transferase activity, eukaryotic translation elongation factor activit Gene expression profile of patients having family history of esophageal cancer showed downregulation of genes involved in humoral immune response (PF4), extracellular matrix organization (COL4A4), metabolism of xenobiotics (EPHX1), TGF-β signaling (SMAD1) and calcium signaling pathways (VDAC1) and up regulation of genes involved in regulation of actin cytoskeleton (WASL), neuroactive ligand receptor interaction (GRM3), Toll-like receptor (CD14), B-cell receptor (IFITM1) and insulin signaling pathways (FOXO1A). Study of high-resolution chromosomal instability profile showed amplifications on chromosomes arms 1p36.13, 1q21.1, 2p14, 3q28, 3q27, 3q26.1, 5p15.2, 5q11.2, 6p25.3, 7q11.21, 9q31.3, and17p13.1 and frequent deletions on chromosome arms 3p, 4p, 5q, 8p, 9p, 11q, 13q, 17p, and 18q. In this study we identified five genes COL11A1, FGF12, PAK1, DLC1 and NPHP4 by using different bioinformatics tools. In which gene enrichment analysis showed FGF12 was more suitable candidate marker for esophageal cancer among the all other cancer. On the basis of the insilico analysis, validations of candidate biomarker FGF12 gene by siRNA knockdown was done in esophageal cancer cell lines KYSE410 followed by Proliferation assay, colony formation assay, and wound healing assay. Since DNA methylation, histone modification and miRNA-mediated epigenetic processes alter the gene expression, we investigated genome wide differential methylation profiling and differential expression profiling of chromatin modification enzymes in tumor and normal tissue collected ESCC patients. Genome wide differential methylation profiling of esophageal squamous cell carcinoma (ESCC) patients from Northeast India had been done along with integeration of data with gene expression data studied earlier. To prepare a network of genes displaying enriched pathways together with list of genes for each case i.e. hypermethylation with downregulation and hypomethylation with upregulation an Integrome analysis was also done. The study resulted in 23 Integrome network enriched genes having relevance to tumor progression as they are associated with the processes involved in metastasis like cell adhesion, integrin signaling, cytoskeleton organization and extracellular matrix organizations. To further scale down the most relevant genes to ESCC Methylation Efficiency Index (MEI) was calculated for all 23 genes found in Integrome analysis. Further higher expression of enzymes regulating methylation (DOT1L and PRMT1) and acetylation (KAT7, KAT8, KAT2A and KAT6A) of histone was found associated with ESCC risk. Tissue microarray done in independent cohort of 75 patients revealed higher nuclear protein expression of KAT8 and PRMT1 in tumor similar to mRNA expression. Expression status of PRMT1 and KAT8 was found declined with progression of tumor from low grade to high grade suggesting their association with esophageal cancer risk and progression. The study exposes the differential status of chromatin modification enzymes between tumor and normal tissue and point outs that relaxed state of chromatin facilitates more transcriptionally active genome in esophageal carcinogenesis.

Biography:

Md Maidul Islam has completed his MSc in chemistry and M.Tech in biotechnology from Jadavapur University. He has completed PhD at the age of 30 years from Indian Institute of Chemical Biology (CSIR) and postdoctoral studies from same institute. He is the Assistant Professor of department of chemistry, Aliah University. He has published more than 15 papers in reputed journals and has been serving as a reviewer of repute journals.

Abstract:

Food additives are substances added to food to preserve flavor or enhance its taste and appearance. Food coloring, or color additive, is any synthetic or natural dye, pigment or substance that imparts color when it is added to food or drink. Besides coloring food, food-dyes also show a several bioactivities. A lot of natural and synthetic dyes show antioxidant, antimicrobial and anticancer activity. We studied Rhodamine B (a common food dye in India) and its derivative with double stranded DNA structure using various biophysical techniques. All the derivatives bound with DNA showing the binding affinities in the order 105-106 M-1. Circular dichroic results suggested that the conformation of DNA was perturbed by all the derivatives. Fluorescence quenching studies gave evidence for groove binding mode. Isothermal titration calorimetry revealed that the binding was characterized by negative enthalpy and positive entropy changes. The overall binding affinity of the derivatives to the DNA revealed that other derivatives of Rhodamine bind strongly in comparison to Rhodamine B. The temperature dependence of the enthalpy changes afforded large negative values of heat capacity changes for the binding to ds DNA suggesting substantial hydrophobic contribution in the binding process. These results further advance our understanding on the binding of food dyes to DNA sequences.

Biography:

Arkady Mustaev graduated from Novosibirsk State University (Russia). Received his PhD degree from Novosibirsk Institute of Bioorganic Chemistry. Postdoctoral training was at Irkutsk Limnological Institute, Moscow Institute of Molecular Genetics, Columbia University, and Public Health Research Institute of New York City. Presently he is Assistant Professor at PHRI Center, NJMS at Rutgers, the State University of New Jersey. He has published over 90 papers in reputed journals. The main research areas are: catalytic mechanisms of transcription, bacterial and cancer drug development, in vivo detection of human microbial pathogens, bioorganic chemistry and chemistry of natural compounds.

Abstract:

Invasive fungal infections (IFI) are a major threat to human health. In particular, medical advances in the management of cancer patients and hematopoietic stem cell and organ transplantation, in addition to immunocompromising diseases such as AIDS, have increased the population at risk for IFI. Successful treatment of fungal infections relies on unequivocal diagnosis and rapid response. In the case of mould infections due to Aspergillus species, diagnosis represents a significant challenge resulting in a mortality rate of around 85% for patients in Europe and the USA. For IFI detection we suggest the approach based on using high-affinity and high specificity labeled antifungal drugs as diagnostic molecules. As a result the fungal cells become labeled and therefore can be detected. The exceptional diagnostic ability of our compounds relies of their high binding constants to targets that are only present on fungi and are not present in the host. In our preliminary studies we successfully validated this approach by imaging fungal infections in vitro and in vivo in a murine model of candidiasis using fluorescently labeled drugs emitting in near-infrared spectral range, in which body tissues are transparent for excitation and emission light. The power of this approach is not limited to fungal infections, but in fact represents a broader platform useful for detection of other classes of human microbial pathogens.

Biography:

Peter L. Nagy received his MD degree from the University of Pecs, Hungary in 1989. He obtained his PHD at Purdue University in Biochemistry under the mentorship of Dr. Howard Zalkin and his Anatomic and Molecular Genetic Pathology training at Stanford University working on the MLL gene with Michael Cleary and Roger Kornberg. His research is on neurodegenerative disorders like ALS and young adult onset ataxias (AOA2). He built and oversees the clinical next-generation sequencing facility in the Laboratory of Personalized Genomic Medicine at Columbia University Medical Center.

Abstract:

Our Laboratory of Personalized Genomic Medicine (LPGM) at Columbia University Medical Center started to offer clinical whole exome sequencing (WES) in January 2013 and cancer whole exome/transcriptome (CWES) testing a year later. We processed and issued reports on over 500 constitutional cases and about 70 cancer cases. Next-generation sequencing in the clinical practice allows for a critical review of the literature describing the pathogenicity of specific mutations or the disease relatedness of specific genes and also provides an important discovery tool for new disease genes and disease causing mutations. Because of the large volume and complex nature of the data obtained from large panels and whole exome sequencing testing, the management of the data in a transparent, yet powerful analytical framework is key to a successful clinical operation. We have provided diagnosis for constitutional patients and information affecting clinical management for cancer patients in about one third of the cases we analyzed. The full potential for discovery of new disease associated genes and disease causing mutations can only be realized if there is a tight collaborative effort between the clinicians performing the interpretation and structural biologists and analytical chemists and cell biologists who can help predict and verify the effects of variants identified.

Biography:

Marisa Martin-Fernandez is Head of the Functional Biosystems Imaging Group, Central Laser Facility, Science & Technology Facilities Council, Dr Martin-Fernandez received a degree in Physics from the Autonomous University of Madrid, and her PhD in biophysics at the University of Keele. After several postdoctoral research appointments she was appointed Principal Scientist at the Science and Technology Research Council in 2002. She has run a research group since 2003 with a focus on developing novel instrumentation and methods to improve our understanding of cancer at the molecular level and to exploit these instruments to derive models of anti-cancer drug-induced behaviour.

Abstract:

Many new targeted therapies are currently in use, undergoing trials, or being developed as alternatives to conventional chemotherapy. The majority of these treatments are aimed at modifying the action of receptors located in the plasma membrane and involved in cell signalling, as mutations or overexpression of these receptors is linked with the development of a significant number of human cancers. However, only 30-70% of the patients respond positively to any particular type of drug. Moreover, the majority of patients undergoing targeted cancer therapy develop drug resistance, resulting in a relapse. Stratified medicine is an emerging field where the cancer patients are classified based on the presence or absence of underlying mutations to prescribe personalised treatment. We have developed a novel super-resolution microscopy based technology, and used this to show that mutations result in changes in the structure of clinically relevant protein complexes in cells, and that these structural changes can be altered or reversed through the application of targeted drugs. This should allow stratification of the patients based on variations in protein complex structure rather than the underlying mutations. This approach would provide targeted treatment of cancer patients as well as continuing assessment to monitor any development of drug resistance. Also, by providing a direct measurement of the effect of drugs on the structure of receptor complexes, this technique has the potential to rapidly identify effective new therapeutics.

Biography:

Born in 1940, graduated from the State Medical Institute in Lvov (Ukraina), took postgraduate course and thereafter received a PhD degree in Embryology in 1976. From 1966 till 1987 he was working at the Institute of Experimental Medicine RAMN (Saint-Petersburg) as a scientific collaborator at the Department of embryology and from 1980 in the Laboratory of biochemical genetics. From 1987 till the present time is the Chief of laboratory for prenatal diagnosis of inherited and inborn diseases at the Ott’s Institute of Obstetrics, Gynecology & Reproduction. Mainly interested in genetic and cytogenetic aspects of early human development, gene testing of inherited predisposition to common diseases, personalized predictive medicine, gene therapy. During the period of 1995-2009 he was awarded by A.A.Bayev Prize, Honorary Prizes from Russian Academy of Medical Sciences, I.P.Pavlov Prize, S.N.Davidenkov Prize. V.S.Baranov – is a chief City Expert in Medical Genetics, Chief of Federal Center for prenatal diagnosis of cystic fibrosis, Chief of Federal Medical Genetic Center, WHO expert on human genetics, Member of HUGO and Human Variome Project Consortium. Member of editorial boards of scientific journals “Medical Genetics”, “Prenatal Diagnosis”, “Ecological Genetics”, “Balkan J.Medical Genetics” The author of 29 books (1 in English “Cytogenetics of Mammalian Embryonic Development” Oxford University Press 1987,356pp) and over 400 scientific papers.

Abstract:

Endometriosis (E) is a common multigenetic disorder affecting almost 10% of women of reproductive age. Complex molecular, genetic, immunological analysis and endocrinology tests were applied in the studies of 257 women with E and in 117 women in the control Participation of the genes responsible for steroid hormone activity, their receptors, inflammation, proliferation, cell migration, apoptosis, intercellular adhesion, angiogenesis as well as the genes regulating their activity have been suggested as plausible candidates. A handful of very interesting new candidate genes involved in oncogenesis , metaplasia of endometrium cells and embryonic development of female reproductive system were identified by GWAS technology and also by conventional genetic testing. Genetic polymorphisms and differential expression of the candidate genes regulated by different epigenetic factors were thoroughly studied and substantiated complex epigenetic landscape of E . According to recent hypothesis ( Baranov et al,2015) E could be induced by different combinations of relevant genetic and epigenetic factors with subsequent canalization of pathological process , which soon becomes irreversible and inevitably proceeds to clinical manifestations following “ direct or reverse epigenetic landscapes” routs. Two hypothetical stages of E include: the origin of primary incipient endometrioitic cells (PIEC) resulting as transition products of emdometrial epithelia to mesenchymal cells ( metaplasia), as well as from vestigial embryonic or dormant stem cells (St 1) ; progression of PIEC into E. lesions augmented by numerous genetic and epigenetic factors ( St.2) . Identification PIEC cells and complex molecular genetic analysis of their origin and progression may be fruitful in diagnostic biomarker search and may substantiate further advancement of prediction, prevention and treatment of E .

Biography:

Martin Flück is the Professor for Muscle Plasticity located at the Balgrist Hospital of the University of Zurich. His research centers on the adaptive pathways governing skeletal muscle function with specific focus on an integrative omics approach. He has published over 70 articles in peer reviews journal (H-index>24) and has served as an editorial board member of repute.

Abstract:

Hypoperfusion of skeletal muscle due to resistance to insulin-mediated vasodilation is an early hallmark of a cluster of metabolic diseases that represent a major economic substrate for the medical industry. Absence of an insertion sequence (the I-allele) in the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is associated with reduced aerobic fitness and the development of type 2 diabetes. Our investigations identify out of norm elevations in serum glucose concentration after the metabolic challenge of exhaustive endurance exercise in ACE-DD genotypes that do not carry the ACE I-allele. Explorative assessment of the muscle metabolome and transcriptome exposed that the defect involves a reduced oxidation of glucose and compensatory adjustments in mitochondria-associated pyruvate and amino acid metabolism; all of which corresponded to a reduced muscle capillarisation and elevated serum levels of the ACE product, angiotensin 2. Compared to ACE-II genotypes, ACE-DD genotypes had a lower capacity for oxygen extraction during exhaustive exercise and the subsequent response in mitochondrial biogenesis was blunted. Anti-hypertensive treatment with ACE inhibitor pronouncedly modulated mitochondrial and angiogenic gene expression in exercised muscle. Our observations imply that the monitoring of glucose import and combustion in working muscle exposes the genetic risk of developing metabolic disease.

Biography:

I have an international professional standing and research expertise to enhance clinical interventions in Barrett\'s oesophagus and oesophageal cancer. I am a member of the BSG/National Clinical Research Institute Upper GI early cancer prevention research subgroup. I am a peer reviewer for the NIHR RFPB programme and a member of the Research Steering Board of Manchester Cancer Research Centre (Cancer Research UK Manchester Institute). These research initiatives have shaped my contribution for the management of GORD, Barrett’s oesophagus and oesophageal cancer. I have published over 45 articles and I am a supervisor for PhD and MD students in the molecular cancer group of the University of Manchester.

Abstract:

Many members of the ETS-domain transcription factor family are important drivers of tumourigenesis. Their activation by Ras-ERK pathway signaling is particularly relevant to the tumourigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumour metastasis in several solid tumours. We have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in oesophageal adenocarcinomas and determined their role in oesophageal adenocarcinoma cell function. PEA3 plays an important role in controlling both the proliferation and invasive properties of OE33 oesophageal adenocarcinoma cells. A key target gene is MMP-1. The ERK MAP kinase pathway activates PEA3 subfamily members and also plays a role in these PEA3 controlled events, establishing the ERK-PEA3-MMP-1 axis as important in OE33 cells. PEA3 subfamily members are upregulated in human adenocarcinomas and expression correlates with MMP-1 expression and late stage metastatic disease. Enhanced ERK signaling is also more prevalent in late stage oesophageal adenocarcinomas. This study shows that the ERK-PEA3-MMP-1 axis is upregulated in oesophageal adenocarcinoma cells and is a potentially important driver of the metastatic progression of oesophageal adenocarcinomas.

Biography:

Abstract:

We analyzed the glycine-rich secreted peptides (GRSPs) of 10 species genomes: Homo sapiens, Dani rerio, Drosophila melanogaster, Caenorhabditis elegans, Caenorhabditis briggsae, Arabidopsis thaliana, Monosiga brevicollis, Saccharomyces cerevisiae, Dictyostelium discoideum, and Guillardia theta. The number of Grsps in each genome was 4, 6, 53, 93, 78, 52, 0, 0, 5 and 0, respectively. Interestingly, there were fewer Grsps in human genome than in D. discoideum genome, despite the greater complexity of humans. The two nematode species C. elegans and C. briggsae possessed the highest abundance of Grsps, of which 98.7% were orthologous. Mapping these Grsps strengthened clustering and illustrated the clear co-linearity between the chromosomes of the two nematodes. In particular, most of Grsps were found on chromosome V: 44 of 93 C. elegans and 41 of 78 C. briggsae. A comparative analysis of orthologous Grsps from other species resulted in the successful annotation of 17 C. elegans Grsps with DAVID and 21 C. elegans and 3 C. briggsae Grsps with Blast2Go. This observation highlighted the nematode-specific expansion of Grsps originating from tandem duplications during ecological adaptation of the two nematodes. The phenomenon goes against the general rule that gene families also experience evolutionary expansion in abundance in increasingly complex species.

Biography:

Jurgen Dittmer has completed his PhD from University Bremen (Germany) and postdoctoral studies from the University of Zürich (Switzerland), the National Institutes of Health (USA) and the University of Tübingen (Germany). He is head of the research laboratory in the Clinic for Gynecology at the University of Halle (Germany) and is currently secretary of the EORTC Pathobiology Group. He has published more than 50 papers in reputed journals and has been serving as an editorial board member of BMC Molecular Biology and BMC Research Notes.

Abstract:

Cancer lesions are complex organ-like tissues that are not only composed of a heterogenous population of cancer cells but also of different types of stromal cells. The tumor stroma is not a bystander, but heavily involved in tumor progression and therapy resistance. Stroma-mediated drug resistance is a new challenge and needs to be considered in therapy decisions. However, we have just begun to understand the mechanisms underlying stroma-mediated drug resistance. The acquisition of such resistance requires the interaction between the tumor cells and the stroma which is supposedly quite complex given the different types of stroma cells and the heterogeneity within the cancer cell population. Hence, the outcome of such interactions in terms of drug resistance may vary depending on the particular cells involved. To address this issue, we are analyzing the effects of different stromal cells on a variety of subtypes of breast cancers and on different subclones residing in a heterogenous breast cancer cell population.

Biography:

Professor Janak Kishore, graduated in medicine in 1978, did M.D. in 1985 and is now Chief of Molecular Virology and Serology Divisions. He was Associate Editor Indian Journal of Virology, member National Academy Medical Sciences, American Society for Virology, Fellow of JICA, Japan. Dr Kishore taught for over 30 yrs and published over 50 papers. His pioneer work on B19 bagged many award owing to publication of three novel clinical associations and possible Oncolytic property of B19. Dr Kishore, served as reviewer for reputed journals, organized conferences, Chaired sessions and frequently invited to speak at international conferences.

Abstract:

Parvovirus B19 (B19), (discovered 1975) listed as newly emerging virus (1981-1987) but could not gain importance due to asymptomatic/self-limiting infections, myriads of clinical afflictions not known to many clinicians, limited diagnostic facilities, unknown disease burden and sinister complications. Hence in-house diagnostic methods of DNA extraction from serum, PCR, nested-PCR, IgM and IgG ELISA were standardised. Seroprevalence of B19 was found to be 39.9% among 1000 blood donors i.e. 60% of Indian population (1.2 billion) at risk of B19. We published fatal cases of B19 induced pure red cell aplasia, thrombocytopenia with hepatitis and hemophagocytic syndrome. B19 infections were unveiled by us in 27.5% arthropathy (n=69), 19.8% recurrent aborters (n=116), 60% high-risk pregnant women (n=60), 17.1% paediatric haematological malignancies (n=35) and 41% beta-thalassemia major (n=90). Novel clinical associations like amegakaryocytic thrombocytopenia ,myositis as a complication of erythema infectiosum and recently non-occlusive ischemic gangrene of stomach and bowel were reported. Our limited work denotes high/alarming situation of B19 infections, hence B19 be looked/recognised and prevented by a licensed B19 vaccine.

Biography:

Laura Hill is a Senior Scientist in the Design and Development department at QIAGEN Manchester, UK. She has significant experience of companion diagnostic development, specialising in primer and multiplex assay design, feasibility studies and novel technologies. She previously worked at Life Technologies on the development and manufacture of primer mixes for DNA testing kits. She has a degree in Genetics from the University of Liverpool

Abstract:

The ModaplexTM system is a fully automated platform that combines a real time PCR module with a capillary electrophoresis detection module. The combination of these two modules allows for a large number of targets to be detected in a single reaction. Multiplexing systems that allow such a broad range of targets to be detected are desirable in companion diagnostic assays; to reduce intrusive procedures to patients, by requiring less sample material, and to reduce laboratory processing time. To investigate how the ModaplexTM system can make use of these benefits, we have undertaken a feasibility study to combine the detection of 42 mutation targets and 2 control targets in a single reaction. Gene panels comprising of 13 KRAS mutation targets and 29 EGFR mutation targets are the focus of this multiplexing challenge. EGFR and KRAS are key molecules in the MAPK cellular signaling pathway. Since mutations in these genes alter cellular functions, determining the mutation status is a key requirement for personalised cancer therapies. The primer designs for the 44-plex assay have initially been tested using synthetic oligonucleotides and will be further challenged with the use of FFPE extracted clinical samples. This feasibility study will demonstrate the multiplexing capabilities of the ModaplexTM system to meet the growing market need for quicker, less intrusive mutation detection.

Biography:

After a degree in Chemistry from Oxford University, UK, Margaret Wheatley completed her PhD in Chemical Engineering at the University of Toronto and postdoctoral studies at MIT, Cambridge MA, USA. She holds the John M. Reid chair of Biomedical Engineering at Drexel University in the School of Biomedical Engineering, Science and Health Systems. She has published more than 100 papers in areas of imaging, drug delivery and spinal cord repair.

Abstract:

Hypoxia in tumors inhibits sensitivity to radiation therapy. We studied the delivery of oxygen to tumors using an ultrasound-sensitive microbubble platform developed at Drexel consisting of a mixed surfactant shell surrounding either oxygen (SE61O2) or nitrogen (SE61N2). Oxygen release kinetics were measured using an Oxy Lite 2000 bare fiber pO2 probe. In vitro ultrasound used a Sonix RP scanner with a PA4-2 probe in power Doppler mode. Samples in 100 ml degassed saline were triggered over 20 minutes (readings obtained every 30s). In vivo proof of concept (two mice with MDA-MB-231 breast tumor xenografts) introduced the probe into the tumor via 21G catheter. Flash-replenishment imaging at the fiber tip was performed using a Vevo 2100 scanner in nonlinear imaging mode at 18 MHz during IV injection of 0.05 ml of agent. Partial oxygen pressures were recorded every 5s until returned to baseline. Release profiles were compared to untriggered SE61O2, and triggered SE61N2. Two ml of SE61O2 triggered with ultrasound elevated oxygen partial pressures of 100 ml of degassed saline 13.8 mmHg more than untriggered bubbles and 20.6 mmHg more than triggered nitrogen-filled bubbles. In vivo controls produced no discernible increase in oxygen partial pressure except for a brief (25s) 5.6 mmHg increase in one animal. Ultrasound triggered SE61O2 resulted in a 30.4 mmHg increase in one tumor, with elevated tumor oxygen levels lasting over 4 minutes, and an increase of 27.4 mmHg, with elevated tumor oxygen levels lasting 1.7 minutes in the second. We conclude that in vivo elevation of tumor oxygenation levels using SE61O2 appears feasible but highly tumor dependent.

Biography:

Katrin Beyer has completed her PhD in molecular biology at the Autonomous University of Barcelona and has worked for 20 years in dementia research. Recently, she focused on the molecular characterization and biomarker search for the early and differential diagnosis of dementia with Lewy bodies. She has requested four patents during the past five years, has published more than 35 papers in reputed journals, and has been serving as an editorial board member of repute and peer reviewer for more than 20 biomedical journals.

Abstract:

Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are synucleinopathies and DLB is the most frequent cause of dementia after Alzheimer’s diseases (AD). All three show an important neuropathological overlap and especially DLB is difficult to diagnose. DLB results from complex interactions among different susceptibility genes and environmental risk factors with particular impact for each individual. Although all patients fulfill diagnostic criteria fitting within certain spectrum of symptoms and disease course, the primary cause of DLB may not be the same in all cases. So far, alpha-synuclein pathology caused by alpha-synuclein oligomerization and further aggregation, and cholinergic deficit that is even more pronounced in DLB than in AD brains, have been unequivocally involved in DLB pathogenesis. But even these main pathologic processes reach different degrees of severity in each patient and are accompanied by other pathological events. Similar severity degrees of the various processes define molecular subgroups of DLB, and these are detectable independently each one by its own biomarkers. We have recently described two molecular subgroups of DLB. One of them comprises about 30% of all patients and is characterized by the absence of beta-synuclein in cortical regions. The other constitutes around 10% with cortical butyrylcholinesterase diminution. For both molecular defects we have identified the associated genetic biomarkers useful for the early detection of these patients. Our results also indicate that DLB can develop as primary or secondary synucleinopathy. In the latter, alpha-synuclein pathology would develop after action of primary alterations such as lysosomal dysfunction or transcriptional deregulation.

Biography:

Jeng-Long Hsieh had completed her Master degree from Rutgers University in United States and PhD degree from National Cheng Kung University Medical College in Taiwan. She is a former Dean of College of Medicine and Life Science, Chung Hwa University of Medical Technology, and now a professor in the Department of Nursing. Her research focus on two fields, cancer gene therapy and molecular factors in bone related diseases. She has published 20 papers in reputed journals and has been serving as a reviewer of repute.

Abstract:

De Quervain’s disease, or stenosing tenosynovitis of the first dorsal compartment of the wrist, is a common ailment. How estrogen is involved in this disease is not clear. We previously showed that inflammation was involved in the pathogenesis of de Quervain’s disease. In this study, the expression of estrogen receptor (ER)- is further examined to delineate the possible roles of estrogen in this disease. Postoperative retinaculum samples were collected from 16 patients with de Quervain’s disease. The specimens were histologically graded by collagen structure. They were immunohistochemically evaluated by quantifying the expression of ER-, interleukin (IL)-1, IL-6, cyclooxygenase (COX)-2, vascular endothelial growth factor (VEGF), and Von Willebrand’s factor (vWF). De Quervain’s disease occurs primarily in women. The female:male ratio in our study was 7:1. ER- was detected in the retinaculum and its expression increased with the grade of the disease and the age of the patient. Moreover, disease severity was related to the inflammatory cytokines IL-1 and IL-6, the inflammatory enzyme COX-2, and the angiogenic factors VEGF and vWF in the tenosynovial tissue. The severity of de Quervain’s disease is associated with increased ER- expression, tissue inflammation, and angiogenesis. ER- might be a useful target for treating de Quervain’s disease.

Biography:

After getting the PhD degree of Pathology and Pathophysiology in Shantou University Medical College (SUMC), China, Dr. Ting Long serves as an associate professor in Department of Physiology at SUMC. He dedicates in diabetes associated male sexual dysfunction studies investigating the mechanism of diabetic erectile dysfunction and sexual behavior disorder. There were several TNF-α related publication recently which suggests that TNF-α is both a significant molecular biomarker and highly potential target in diabetes associated male sexual disorder.

Abstract:

Background: Sexual dysfunction, including decreased libido, sexual behavior disorder and erectile dysfunction (ED), is common in male patients with diabetes mellitus (DM). We previously demonstrated that increased peripheral tumor necrosis factor alpha (TNF-α) expression, associated with inflammation in DM, contributes to ED in the rat corpus cavernosum. However, the role of TNF-α in the central pathophysiology of DM-associated male sexual dysfunction is unknown. In this study, we examined the effects of TNF-α inhibition, i.e. etanercept (ETN) via chronic intra-cerebroventricular (ICV) infusion on nNOS expression in the hypothalamic paraventricular nucleus (PVN) and sexual behavior disorder in male diabetic rats.
Results: Male diabetic rats with ICV aCSF treatment displayed significantly severe sexual disorder accompanied with blunted nNOS expression and activity in the PVN in addition to local upregulated TNF-α and TNFR-1 expression, and increased ROS generation compared with non-diabetic controls. The sexual behavioral parameters were significantly improved in the treated group with ETN. ICV ETN significantly inhibited TNF-α and TNFR-1 expression and reduced ROS generation in the PVN in diabetic rats. In addition, ICV ETN appeared to induce marked increased in nNOS expression in the PVN of diabetic animals compared with ICV aCSF-treated diabetic rats.
Conclusion: Increased TNF-α and TNFR1 expression in the hypothalamic PVN associated with DM contributes to male sexual disorder by centrally inhibiting nNOS expression and activity in the PVN via promoting local ROS generation. Central TNF-α blockade may have beneficial effects on the male sexual disorder in diabetes through improvement of NO pathway within the PVN.

Biography:

Jinwei Du has completed his PhD at the age of 27 years from Peking University and postdoctoral studies from Case Western Reserve University School of Medicine. He is the Vice President of R&D at Shanghai Tissuebank Biotech. He has published more than 20 papers in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Alleles at the D7S820 STR locus have 6–14 different numbers of a four-nucleotide (GATA) repeat motif arranged in tandem. The D7S820 tri-allelic pattern is rare and has not been reported in the Chinese population. In this study we report a three-banded pattern at the D7S820 locus observed in a Chinese family, in which four family members in two generations had tri-allelic D7S820 genotype 10-11-12 and one family member had an abnormal bi-allele genotype 10– 11. All of the four tri-allelic cases had the genotype 10-11-12, probably due to three copies of the D7S820 STR sequence in all cells (Type 2 tri-allelic pattern), and deduced alleles 10–11 were a linked inheritance in this family.

Biography:

Xiaolin Lu has completed her MM at the Capital Institute of Pediatrics in 2007, and became a young researcher at Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics.The main work of her research is about the interaction of genetics and epigenetics in the mechanism of birth defects. Since 2013, she has published about 2 articles on genetic and epigenetic alternations in birth defects as the first author and joint first author.

Abstract:

SHH signaling pathway played an important role in the formation of dorsal ventral neural plate. It has been shown in mice that genes of SHH signaling pathway mutations increased the incidence of NTDs, such as spina bifida and brain anomalies. Moreover, the single nucleotide polymorphisms (SNPs) of several key genes belonging to SHH pathway have been verified to increase the risk of NTDs in our previous studies. GLI2 is a key mediator of the Sonic hedgehog (Shh) signaling pathway and plays an important role in neural tube development during vertebrate embryogenesis; however, the role of gli2 in human folate-related neural tube defects remains unclear. In this study, we compared the methylation status and polymorphisms of gli2 between spina bifida patients and a control group to explore the underlying mechanisms related to folate deficiency in spina bifida. No single nucleotide polymorphism was distributed significantly differently between the two groups, although gli2 methylation levels were significantly increased in spina bifida samples, accompanied by aberrant GLI2 expression. Moreover, a significant negative correlation was found between the folate level of brain tissue and the gli2 methylation status (r=−0.41, P=0.014), while gli2 hypermethylation increased the risk of spina bifida with an odds ratio of 12.45 (95% confidence interval: 2.71–57.22, P=0.001). We also used a cell model to illustrate the effect of gli2 expression and the accessibility of chromatin affected by methylation. High gli2 and gli1 mRNA expression was detected in 5-Aza-treated cells, while gli2 hypermethylation resulted in chromatin inaccessibility and a reduced association with nuclear proteins containing transcriptional factors. More meaningful to the pathway, the effect gene of the Shh pathway, gli1, was found to have less expression along with decreased expression of gli2 in the cell model. Aberrant high methylation resulted in the low expression of gli2 in spina bifida, which was affected by the change in chromatin status and the capacity of transcription factor binding.

Biography:

Lei Shang has completed his PhD at the age of 28 years from Central South University. He is the research worker of Hunan Cancer Hospital in the department of Translational Medicine Research, a premier Cancer Research Institute in Central South Region of China. He has published more than 10 papers in reputed journals.

Abstract:

Necroptosis is an important neuronal death mode in retinal ischemia, but the mechanism still needs clarify. RIP3 is characterized as an N-terminal Serine/Threonine kinase, which participates in cell death signaling. Previous studies indicated RIP3 may participate in neuronal necroptosis, and the activation of caspase-8 could cleave RIP3 to inactive form. In the present study, we explored the effects of RIP3 in retinal necroptosis following elevated hydrostatic pressure (EHP) and discussed the possible role of caspase-8 on regulation of RIP3 activity. Necrosis levels detection were repeated with pretreatment of Nec-1 of 24h to confirm the existence of necroptosis. The expression of RIP3, downstream molecules in the pathway of RIP3-induced necroptosis and necrosis levels of RGC-5 cells were detected by immunoblotting, immunofluorescence and flow cytometry at 6h, 12h or 24h after EHP. Then, RNAi to rip3 was used for further confirming RIP3’s effects on retinal necroptosis. Finally, caspase-8 inhibitor and activity peptide were applied to try to unveil the regulated mechanism of RIP3 activity. The results showed that, RIP3 expression was up-regulated and RIP3 enhance-labeled cells were coexisted with PI-positive cells after injury. PI-positive cells were reduced and ratios of necrosis were decreased after injury when treating with Nec-1and rip3 RNAi. The ROS and PYGL levels in pathway of RIP3-induced necroptosis had been found to be decreased after rip3 knockdown. Caspase-8 inhibitor and activity peptide usage affected ratio of necrosis and levels of ROS or PYGL. Our results indicated RIP3 participated in RGC-5 necroptosis following EHP and caspase-8 may interference RIP3-induced necroptosis. This work was supported by the National Natural Science Foundation of China (No.81070729), and National Key Technologies Research and Development Program of China(No. 2012BAK14B03) .

Biography:

F. Bandarian has completed his MD degree at the age of 27 years from Tehran University of Medical Sciences and completed PhD at Shahid Beheshti University Medicine Sciences in 2013. She is the Research Assistant of Diabetes Research Center at Tehran University of Medical Sciences. She has published more than 30 papers in reputed journals and has been serving as section editor of Journal of Dibetes and Metabolic Disorders.

Abstract:

Metabolic Syndrome (MetS) increases the risk for cardiovascular disease and diabetes. This study aim was to investigate the association between APOA1 polymorphisms and MetS in an Iranian population. Thirty-seven patients with MetS and 94 healthy controls were selected randomly from the population of Tehran Lipid and Glucose Study. Variant was identified by direct sequencing. The mean age of participants in MetS and control groups was 44.76±14.25 and 38.74±15.37, respectively. Frequency of mutant allele in MetS group was 1.35% while its frequency in control group was 13.8%. There was a significant association between rs201148448 and MetS. Also, there was a significant association between rs201148448 and serum triglyceride and HDL concentration as well as BMI and waist circumference (p=0.001). APOA1 variants rs201148448 contribute in MetS phenotype and protect against it in Iranian population. In relation to MetS, variants in other variants of APOA1 gene should be studied in future.

Biography:

Ievgeniia Burlaka is is a Professor in the Department of Pediatrics in National O O Bogomolets Medical University, Ukraine.

Abstract:

Proteinuria not only is a sign of kidney damage, but also is involved in the progression of renal diseases as an independent pathologic factor. Clinically, glomerular proteinuria is the most commonly observed, which relates to structural and functional anomalies in the glomerular filtration barrier. The objective of this project was to study the markers of apoptosis in kidney tissue in children with chronic glomerular diseases. 32 patients aged 5-18 years with an active stage of nephrotic syndrome were included to the study. Immunohistochemical examination of proapoptotic factor Bax, antiapoptotic factor Bcl-xL levels, apoptosis evaluation in kidney biopsy specimens was done. Analysis of the level of proapoptotic factor Bax in kidney slices obtained from children with morphological form focal segmental glomerulosclerosis (FSGS) showed the presence of high levels of Bax in both glomerular and tubular-interstitial segments. However, higher imunosignal was recorded in glomeruli with FSGS I-II st. compared to tubular segment. When complete glomerular sclerosis observed high levels of Bax were observed in the surrounding tubuli and interstitial segment. In kidney tissue from nephrotic patients the presence of a certain level Bcl-xL in both glomeruli, tubuli and interstitium was found. Higher imunosignal was recorded in tubuli, interstitial segment compared to glomeruli with FSGS I-II st. When complete glomerular sclerosis occures relatively high imunosignal of Bcl-xL is localized in the surrounding tubuli, interstitial segment with the almost complete absence in glomeruli. Quantitative analysis of apoptosis levels in kidney sections of patients with nephrotic syndrome and FSGS I-II st. revealed apoptotic index (AI) in glomeruli at level 21,5 ± 0,9%, in the tubuli and interstitial component - 9,12 ± 0,34% (p˂0,01). With FSGS III-IV st. high AI was found in tubuli, interstitial component - 31,22 ± 1,14%, in the glomeruli - 4,15 ± 0,6% (p˂0,001). Thus, progression of glomerulosclerosis as an irreversible kidney damage induced by chronic albuminuria is associated with increased activity of proapoptotic factor Bax and simultaneous reduction of anti-apoptotic factor Bcl-xL. The manner of Bax and Bcl-xL distribution in relation to the stages of FSGS is an indicator of step-dependent manner of glomerular and interstitial injuries development under the influence of proteinuria.

Biography:

N’Guessan Kouassi Raymond, is working in Institut Pasteur in Côte d'Ivoire, National Laboratory of Tuberculosis Reference. He also worked as Pneumology Service CHU de Cocody and National Programme against Tuberculosis.

Abstract:

Tuberculosis is explicitly recognized as a major global public health problem. In Côte d'Ivoire, relapse cases represent 66.5% of patients eligible for retreatment according to the National Tuberclosis Control Program. This study objective was to detect multidrug-resistance tuberculosis among relapse cases. Patients were recruited in tuberculosis centres in routine. A standardized questioning was administrated. Two sputum samples were collected and transported at Institut Pasteur. Sputum samples were decontaminated by NALC method. The DNA extraction was realized with 500µl of decontaminated sputum sample with smear-positive. MTBDRplus assay version 2.0 was performed according to the manufacturer’s instruction. An internal quality control program with positive and negative controls was implemented for interpretation of results. In total 146 relapse cases with smear positive were studied. Out of selected patients,130 had received the 2RHZE/4RH regimen and 16, the 2RHZES/1RHZE/5HRE. In group of relapse cases previously treated with 2RHZE/4RH regimen,40 (31.3%, IC95% : [0.23 ; 0.39]) had punctual mutations at codon 526 in rpoB gene. Although, in patients under treated with 2RHZES/1RHZE/5HRE, a mutation in rpoB gene was identified in 12 of 16 sputum samples. Thirteen mutations conferring a resistance to Isoniazid were observed of which 9 in katG gene and 4 in katG and promoter region of inhA gene. The comparison (Chi-square with Yates correction) of resistance rates to Rifampin estimated showed a statistically significant difference.

Biography:

Abstract:

The advancement in hepatitis C virus therapeutics has profoundly enhanced by an improved understanding of viral life cycle in host cells, development of novel direct-acting antivirals and exploring the other emerging treatment paradigms on the horizon. The approvals of first and second-generation direct-acting antivirals highlight the swift pace of progress in the successful development of an expending variety of therapeutic strategies for use in patients with chronic hepatitis C virus infection. Triple and quadruple therapies based on the combination of different direct-acting antivirals with or without pegylated interferon and ribavirin have raised the hopes to improve the current treatment strategies for other difficult-to-treat individuals. All-oral interferon free therapeutic regimens directed against hepatitis C virus infection are shown to be highly effective in the entire spectrum of patient populations, including the previously difficult-to-treat “special” situations. These revolutionary drug strategies now incorporate a cocktail of agents blended to take advantage of synergistic mechanism of action. The development of more efficacious, well tolerated, and cost effective interferons with low frequency of adverse events and short treatment durations are also in the pipeline. An experimental protective vaccine against hepatitis C virus demonstrated promise in preliminary human safety trials, and a larger phase II clinical trials are under consideration to further determine the efficacy of the vaccine. This review article describes the current state of knowledge in hepatitis C virus therapeutics, insights the potential pitfalls of current therapies, and provides a conceptual framework of emerging and investigational treatment strategies directed against hepatitis C virus.

Biography:

David Meridor has completed his Master degree and PhD degree in Chemistry from Bar-Ilan University in Israel, after publishing 4 papers. In the current position as a postocdorate researcher at Ben-Gurion University, he was involved in a project that entails synthesis of humanin derivatives, cell culture as well as in vivo studies in a model of traumatic brain injury.

Abstract:

Humanin is a 24-amino acid peptide known for its anti-apoptotic activity, especially against neuronal cell death caused by Alzheimer insults. Herein, we show a novel function of humanin and its derivatives, namely protection against necrosis, demonstrated both in vitro and in vivo. The synthesis of humanin is difficult due to hydrophobic amino acids that impose aggregation on the resin. Solid-phase peptide synthesis of humanin and its three derivatives, AGA-HNG, HNG and HN17 gave low yields.
In order to avoid aggregation and overcome difficult sequences couplings, we developed efficient synthetic procedures that are based on fragment condensation in solution. Furthermore, native chemical ligation was applied to overcome resin aggregation for synthesis of peptides that contain cysteine.
We found that humanin and its derivatives conferred protection in PC-12 and NSC34 cell lines in which necrosis was induced in glucose free medium by either chemohypoxia or upon staurosporine/oligomycin-A treatment. Moreover, in-vivo protective effect was shown in traumatic brain injury model in mice, where necrosis is the main mode of the neuronal cell death. We show that humanin derivatives antagonize the decrease in ATP levels associated with necrosis and also directly enhance the activity of isolated ATP synthase complex, indicating that humanin derivatives target the mitochondria, regulating ATP levels. The present findings could provide new therapeutic protocols for treatment of brain ischemic states, such as stroke, and traumatic brain injury, conditions for which no efficient drug-based treatment is currently available.

Biography:

After getting the PhD degree of Biomedical Sciences in Chang Gung University, Taiwan, Ya-Ching Lu is a postdoctoral fellow of Department of Medical Biotechnology and Laboratory Science from 2012. She dedicates in head-neck cancer associated studies including investigation of the mechanism of head-neck carcinogenesis, and identification of significant biomarkers for head-neck cancer disease management. There were several microRNA related publications in 2012-2014 and it was found miR-196 molecules are highly potential as circulating biomarker for head-neck cancer detection.

Abstract:

Molecular targets for cancer diagnosis and therapeutic usage are important for disease management. Here, we characterized the function of miR-196, elucidated its molecular mechanism and clinical significance in head-neck cancer. Both miR-196a and miR-196b were highly over-expressed in the cancer tissue and correlated with lymph node metastasis (P<0.01). Functionally, miR-196s actively promoted cell migration and invasion without affecting cell growth. Next, the miR-196 target gene and downstream molecular mechanisms was confirmed. Mechanistically, miR-196s perform their functions by directly inhibiting NME4 expression and further activating p-JNK, suppressing TIMP1, and augmenting MMP1/9. Comparing to normal subjects, both circulating miR-196a and miR-196b were substantially up-regulated in patients with pre-cancer lesions (5.9- and 14.8-fold, respectively; P < 0.01), as well as in head-neck cancer patients (9.3- and 17.0-fold, respectively; P < 0.01). The combined determination of miR-196a and miR-196b levels produces excellent sensitivity and specificity in the diagnosis of patients with pre-cancer (AUC = 0.845) or head-neck cancer (AUC = 0.963), as well as in the prediction of potential malignancy (AUC = 0.950, sensitivity = 91%, specificity = 85%). In conclusion, miR-196 contributes to head-neck cancer by promoting cell migration and invasion. MiR-196 exerts these functions by targeting to the NME4 and regulating the downstream JNK-TIMP1-MMP signaling pathway. In addition, miR-196a/b was significantly over-expressed in the cancer tissues and up-regulated in the plasma from head-neck cancer/pre-cancer patients. Our study provides knowledge foundation for the applications of miR-196 as a molecular therapeutic target or circulating early detection biomarker for head-neck cancer management.

Biography:

Ryou-u Takahashi is a staff scientist of Division of Molecular and Cellular Medicine at the National Cancer Center Research Institute, Tokyo. After he got a Ph.D. in 2008 in Tokyo Institute of technology and then went to do a post-doc at the National Cancer Center Research Institute. Dr. Takahashi focuses the development of novel animal models, methods, and strategies to study the molecular mechanisms for the acquisition of CSC properties. Especially, the current focus is siRNA- and miRNA-based therapy against CSCs.

Abstract:

Accumulating lines of evidence suggest that the key property that distinguishes cancer stem cells (CSCs) from non-CSCs is the ability to create their abnormal niche that remains in a dormant and tolerant state under stressful exposures such as conventional chemotherapy and radiotherapy. However, the molecular mechanisms for the generation of CSC niche remain elusive. In this study, we show that microRNA-27b (miR-27b) plays important roles in the generation of breast CSCs (BCSCs). The down-regulation of miR-27b was essential for the generation of BCSCs that show the self-renewal, drug tolerant and high tumorigenic activities. Further analysis revealed that miR-27b overexpression inhibited the drug-resistance and tumor seeding ability of breast cancer cells via suppressing the non-CSC to CSC transition under stressful exposures. Therefore, these findings elucidate a new molecular mechanism for the generation of BCSCs and suggest that modulating miR-27b with conventional anticancer treatments might be a promising approach to overcome BCSCs.

Biography:

Vimal Karani is a Lecturer in Nutrigenetics at the University of Reading, UK. He did his post-doctoral training at the MRC Epidemiology unit (Cambridge, UK) and University College London (UK). He has an interdisciplinary academic background, with qualifications from Medical Genetics, Bioinformatics, Molecular Biology and Genetic Epidemiology. His primary research interests focus on the investigation of gene-nutrient interactions on metabolic- and CVD-related outcomes using combined approaches from genetic epidemiology, statistical genetics and molecular biology. His long term goal is to use the findings from observational studies to carry out human intervention studies with a view towards developing industrial collaborations to facilitate ‘Personalized Nutrition’.

Abstract:

The ability of Nutrigenetics to determine what nutrients will produce the desired impact on metabolic balance (as influenced by individual genetic make-up) is at the core of Personalized Nutrition. Metabolic diseases such as obesity and diabetes are heritable traits that arise from the interactions between multiple genes and lifestyle factors such as diet and physical inactivity. Dietary factors play an important role in the development of metabolic diseases because of the variation in the food that is being consumed in different parts of the world. Although several studies have examined the gene-nutrient interactions, the findings have been quite inconsistent and hence, unable to develop an optimum diet for each ancestral population. Some of the challenges in performing nutrigenetics research are 1) genetic heterogeneity, 2) lack of understanding of the metabolic pathways and 3) insufficient sample size. With genome-wide association study (GWAS) data now available on numerous large cohorts, it has become possible to embed candidate gene studies within GWASs, testing for association on a much larger number of candidate genes than previously possible. The talk will highlight three main aspects: 1). Why do we do gene-diet interaction analysis? – Findings from DiOGenes study, 2). Why large samples are required to conduct genetic epidemiological studies? – Findings from D-CarDia Collaboration and 3). Nutrigenetics in developing countries – Findings from GeNuIne Collaboration

Biography:

Li Wang has completed her PhD at the China Agriculture of University in 2007, and became a junior faculty member at Beijing Municipal Key Laboratory of Child Development and Nutriomics, Capital Institute of Pediatrics, and since 2014, she became the director of Medical Genetic Department of CIP. The primary interest of her lab is in the interaction of genetics and environment, in particular early nutrition and developmental programming. She has published over 10 articles on a variety of epigenetic alternations that range from diseases to cell and animal models with experiences.

Abstract:

Periconceptional maternal folate deficiency is a risk factor for neural tube defects (NTDs), the mechanism underlied remains unclear. Intracellular folic acid is thought to be key player in providing an adequate source of methyl groups for methylation of DNA and proteins, and methylation modifications of repeat elements and imprinting genes is suggested to be sensitive to epigenetic regulation of folate acid nutrition in developmental programming. However, the mechanism of how folate deficiency altered methylations modification of repeat elements and imprinting genes in earlier development is still unclear. Our present studying analyzed methylation modification alternations of LINE-1 and imprinting genes using NTD cases, mESCs with folate deficiency, and also in mouse models with periconceptional folate-deficiency. The results implying that hypomethylation of LINE-1 was associated with an increased risk of NTDs. Folate insufficiency induced LINE-1 hypomethylation at the lowest levels in folate-free ESCs, compared with that in the folate-normal group. Moreover, LINE-1 methylation level was positively correlated with folate content, and negatively correlated with homocysteine content. Similar, kinds of imprinting genes also altered imprinting modifications in NTDs with folate deficiency, including Gnas imprinting cluster, DLK-MEG3 imprinting cluster, MEST imprinting and H19/IGF2 imprinting. Mouse embryos exhibited a significantly increased ratio of IUGR and developmental dysplasia of the brain in response to folate deficiency. Data shown here implying that periconceptional maternal folate deficiency altered the imprinting established and gene expression in fetal brains, which may be associated with the higher ratio of developmental dysplasia.

Biography:

Evguenia Alechine is a biochemist from Argentina. She got her Master degree in Biomedical Sciences at the age of 27, and completed her PhD at the age of 30, both from the University of Buenos Aires. She has been working in the field of Forensic Genetics, and specialized on the research of the genetics of male infertility. She has published 9 papers in top peer reviewed journals in the field, and presented her work at more than 20 national and international scientific meetings.

Abstract:

The bases of the diagnosis of genetics causes of male infertility have been established more than 10 years ago. Nevertheless, its accuracy and predictive value are still controversial. While the update of the international recommendations still point to the study of a specific set makers located in the AZF region of the Y chromosome, many research groups worldwide question their utility in populations with different ethnic origin. The Argentinean male population is characterized by AZF microdeletions that do not correlate with testicular sperm recovery, together with the majority of the azoospermic patients without classical microdeletions belonging to the Native American Y-chromosome haplogroup Q-M3. Our research is focused on the analysis of complete and partial AZF microdeletions, haplogroup characterization for ethnicity association, and correlation with sperm count and sperm recovery from testicular biopsies. Taken together our results show that AZFb and AZFc microdeletions do not correlate with absence of sperm in the testis, and that partial gr/gr microdeletions are not associated with male infertility in the Argentinean population. This scenario underscores the importance to reconsider the international guidelines regarding the predictive value and application of the suggested markers in populations with different ethnic backgrounds. Therefore, we developed a method for spermatogenesis candidate genes screening in infertile patients that could improve the diagnostic and prognostic value of the genetic testing.

Biography:

Ashwani Kumar has completed his PhD in Information and Communication Engineering in 2014. He is Assistant professor in electrical and instrumentaion engineering depaertemnt at Sant Longowal Institute of Engineering and Technology, SLIET, Longowal, Sangrur, Punjab, INDIA. He published more than 10 papers in reputed journals and conferences.

Abstract:

Use of light for imaging the biological tissue and to quantify its optical properties is a good choice over other invasive methods. Optical tomography involves two steps. One is the forward problem and the other is the reconstruction problem. The forward problem consists of finding the measurements of transmitted light through the tissue from source to detector, given the spatial distribution of absorption and scattering properties. The second step is the reconstruction problem. In X-ray tomography, there is standard method for reconstruction called filtered back projection method or the algebraic reconstruction methods. But this method cannot be applied as such, in optical tomography due to highly scattering nature of biological tissue. A hybrid algorithm for reconstruction has been implemented in this work which takes into account the highly scattered path taken by photons while back projecting the forward data obtained during Monte Carlo simulation. The reconstructed image suffers from blurring due to point spread function.

Biography:

Raj Kumar did his master dgree in Instrumentation engineering from SLIET Longowal and currently pursuing PhD from IIT Delhi, India. His areas of interest are signal processing and power quality. He has published more than 10 papers in journals and conferences of repute.

Abstract:

EMG (Electromyogram) signal contains wealth information about muscle function which is widely used in clinical and engineering application to investigate muscle activity. EMG signals are acquired by surface electrodes which are placed on the targeted muscle set. In order to use the EMG signal as a diagnosis signal or a control signal, a feature is often extracted before performing analysis or classification stage. This study would provide a method for myoelectric control of the movement of forearm prosthetic limbs and human-machine interface for applications in different tasks as hand close, hand open, supination, pronation, flextion, extension. EMG signals has been recorded from BIOPAC MP 100 c System, the forearm muscles of subjects for six movement set mentioned above. The healthy subject aged between 23-30 years have been used for this purpose. The recording was done for six different motions using two active surface electrodes were placed on the skin surface covering the ‘Flexor Carpi Ulnaris’ and ‘Brachioradialis’ muscle in the forearm in differential mode placed with 20 millimeter apart. The single surface electrode was placed on the unconcerned muscle for the reference purpose. Time-Frequency domain features were calculated to extract the information from the signals. ANN has been used to classify between these different movements of forearm which gives accuracy of 85.56% and 86.26% for channel 1and channel 2 (left and right hand) at IMF-1 level with 10 number of hidden layers which are trained by scaled conjugate gradient method for supervised learning in MATLAB.

Biography:

Kondo brings a high level of additional expertise to our group of editors. In 2012 he was appointed as a full professor at the Institute for Genetic Medicine, Hokkaido University in Sapporo, Japan. His laboratory studies how neural stem/precursor cells are involved in the development of CNS diseases, such as brain tumor and Alzheimer’s disease. He is particularly interested in identifying new molecules associated with these disorders, characterizing them and developing new therapeutic methods. He has also a keen interest in the molecular mechanism of oligodendrocyte precursor cell differentiation. He hopes one day the knowledge gained from his work will contribute to the development of therapeutic applications.

Abstract:

Recent findings suggest that tissue-specific stem/precursor cells, including neural stem cells (NSCs) and oligodendrocyte precursor cells (OPCs), acquire mutations during life time and eventually either become senescent or transform into cancer cells. Cell senescence is described as an irreversible growth arrest and acts as a potent barrier to tumorigenesis. Such senescent cells are often found in the surrounding area of malignant tumors, although it still uncertain what is the exact role of cell senescence in tumorigenesis. We recently identified a novel senescence-messaging secretome factor, the esophageal cancer related gene 4 (Ecrg4), which is induced in the senescent NSCs and OPCs as well as in the passaged mouse embryonic fibroblasts in culture and in vivo. Overexpression of Ecrg4 induces NSCs and OPCs to become senescent, while its knockdown prevent them to do so. Using mouse glioblastoma-initiating cell (GIC) models and human glioblastoma tissues, we found a novel tumor suppressor function of Ecrg4. I would like to discuss about Ecrg4 as a new tumor suppressor and a potential therapeutic target.

Biography:

Abstract:

Cure liver cancer by because apoptosis in liver cancer cell by Active liver receptor inhibit hydrogen peroxide and B12 to induced apoptosis Liver cancer is one of most dangerous disease it controls in liver function and other organs in the body. Cancer cells spread and control in every organ and liquid in the body except brain. The present study aimed to investigate the role of activated receptors on human liver cancer cell apoptosis and its interrelation with the mitochondria .this study aim to make cancer have cancer and die .H2o2 will do apoptosis in liver cancer cell and damage mitochondrial of cancer cell which make unbalance in tumor control but there more cancer cells in the body which will repeat cancer again to liver if we damage it so B12 active immune and make it able to identify on cancer cell and damage it because cancer cell use human cell to be his carrier so it shown to immune as normal cell so B12 isolate it from normal cell and make it appear alone in the blood this the only method to damage all cancer cell and this thing was problem in past because all pervious study was cure liver cancer and leave other cancer cell in the body which collect again by signaling between each other . all this happen through liver cancer receptor which active to accept H2o2 and b12 because cancer cell have the ability to close his receptor but it will active by enzymes .liver cells will not attack by H2o2 because it will induce apoptosis through receptor of cancer cell and liver receptor is different than cancer receptor so all the body is protected from that because difference of receptor.

Biography:

Alexandra completed her PhD in Molecular Biology in 2005 (University of Manchester), followed by a postdoctoral post at Imperial College London. Since 2009 she has worked in the Molecular and Cell Biology Team at LGC with a focus on nucleic acid metrology. Her area of expertise is trace detection of nucleic acids using digital PCR. She has published the use of digital PCR in a wide range of applications including quantification of microorganisms, detection of copy number variation and rare sequences in cancer. Her research also includs the use of digital PCR to investigate sampling bias in low concentration samples.

Abstract:

Rare mutation detection is offering increasingly important potential in cancer management, the detection of antimicroibal resistance and in monitoring organ transplant rejection. The main challenge is detecting the rare mutant due to background signal from cross reactvity with the predominant wild type sequences. Digital PCR (dPCR) is the latest incarnation of PCR that subdivides the reaction across a large number of smaller reactions (termed ‘partitions’) so that some contains no template molecules. PCR is then performed with fluorescent probes to generate partitions with either an amplification signal or no amplification signal, hence the name ‘digital’. While this subdivision increases the precision of dPCR over qPCR, it also improves the detection of rare mutant variants, which in a normal qPCR would be lost within the high wild type background. Using a range of different models, we are investigating the ability of dPCR to detect rare mutations in DNA and RNA templates. This presentation will demonstrate the ability of dPCR to detect a mutation in less than 1% of the population and to highlight the many factors that can confound this method such as reduced template concentration and competitive PCR.

Biography:

Alessandra Rejane Ericsson de Oliveira Xavier has completed her PhD at age of 32 years at University of Brasilia and she has being attempted post-doctoral studies at Federal University of Minas Gerais. She worked in the QC Microbiology at Novo Nordisk, where she had experience in industrial microbiology acting on: Validation of microbiological analytical methods, writing standard operating procedures, training in microbiological methods, qualification of equipment and Rapid Microorganisms Identification methods. She also has experience in teaching in higher education, mainly teaching and researching in the Microbiology and Molecular Biology’s areas, focusing on diagnostics methods. She has been member of the validation committee at Novo Nordisk, as well as Director of Research and Ethics Committee’s member at University. She is expert in rapid methods for microorganism’s identification and molecular diagnostic of diseases. Current, she is professor in the medicine graduation and Biotechnology post-graduation courses at State University of Montes Claros.

Abstract:

Visceral leishmaniasis (VL) is an endemic and high mortality rate disease detected in around 65 countries, including Brazil. Three hundred and fifty million people are in the risk area and arise five hundred thousand new cases each year. Among the Brazilian area, the north of Minas Gerais state is considered high risk area. Mortality and severity of VL can be prevented with correct diagnosis, resulting in appropriate treatment. The definitive VL diagnosis is the demonstration of amastigotes parasite cells (Giemsa-stained slides) in splenic smears (sensitivity from 95% to 98%) or bone marrow aspirates (sensitivity from 53% to 95%). The Serology-based tests, such as rK39 ELISA and dipstick have high sensitivities and specificities but are not able to discriminate between past and current infections. The molecular diagnosis of VL by PCR on blood samples is an alternative method that presents high sensitivity and specificity. Therefore, efforts have been made to develop PCR methods using peripheral blood instead of bone narrow aspirates or splenic smear. We have being designing and testing specific primers to rRNA 18S and kDNA to be used as tool for VL diagnosis. Our results are very optimistic (sensitivity of 92%). The detection of DNA from parasite after VL treatment could be of great importance in the diagnosis, since it can be regarded as an important marker for healing. The molecular diagnosis of VL is a project performed by State University of Montes Claros and supported by University of Brasilia. The Ethical clearance for this project was obtained.

Biography:

Lei Shang has completed his PhD at the age of 28 years from Central South University. He is the research worker of Hunan Cancer Hospital in the department of Translational Medicine Research, a premier Cancer Research Institute in Central South Region of China. He has published more than 10 papers in reputed journals.

Abstract:

Necroptosis is an important neuronal death mode in retinal ischemia, but the mechanism still needs clarify. RIP3 is characterized as an N-terminal Serine/Threonine kinase, which participates in cell death signaling. Previous studies indicated RIP3 may participate in neuronal necroptosis, and the activation of caspase-8 could cleave RIP3 to inactive form. In the present study, we explored the effects of RIP3 in retinal necroptosis following elevated hydrostatic pressure (EHP) and discussed the possible role of caspase-8 on regulation of RIP3 activity. Necrosis levels detection were repeated with pretreatment of Nec-1 of 24h to confirm the existence of necroptosis. The expression of RIP3, downstream molecules in the pathway of RIP3-induced necroptosis and necrosis levels of RGC-5 cells were detected by immunoblotting, immunofluorescence and flow cytometry at 6h, 12h or 24h after EHP. Then, RNAi to rip3 was used for further confirming RIP3’s effects on retinal necroptosis. Finally, caspase-8 inhibitor and activity peptide were applied to try to unveil the regulated mechanism of RIP3 activity. The results showed that, RIP3 expression was up-regulated and RIP3 enhance-labeled cells were coexisted with PI-positive cells after injury. PI-positive cells were reduced and ratios of necrosis were decreased after injury when treating with Nec-1and rip3 RNAi. The ROS and PYGL levels in pathway of RIP3-induced necroptosis had been found to be decreased after rip3 knockdown. Caspase-8 inhibitor and activity peptide usage affected ratio of necrosis and levels of ROS or PYGL. Our results indicated RIP3 participated in RGC-5 necroptosis following EHP and caspase-8 may interference RIP3-induced necroptosis. This work was supported by the National Natural Science Foundation of China (No.81070729), and National Key Technologies Research and Development Program of China(No. 2012BAK14B03) .

Biography:

Alexander N Parkhomenko is a Professor and Chair in the Emergency Cardiology Department in Institute of Cardiology, Ukraine.

Abstract:

In 492 patits with acute coronary syndromes (ACS) we studied polymorphisms of different genes - NOS3 (eNOS), LMP2, LMP7, HIF1α, ACE, PPARG, PSMA6, AGT, MGP, AGTR1, BMP, A2M, MMP2, MMP9 и XRCC1. Polymorphisms of NOS3 and MGP were found as markers of the disease and may be used for individual pathophysiological profile characteristics and prediction of pharmacological agents effects. Frequency of eNOS Т-786С promoter polymorphism and influence of this polymorphism on reactive hyperemia and arterial stiffness were determined. Higher degree of brachial arteries diameter increase in response to ischemia in patients with Т/Т genotype: 8,03  0,71% compared to 5,55  0,92 % in Т/С (Р<0.05) and 5,30  1,21 % in С/С genotypes (P<0.05). Speed of pulse wave spreading on carotid-radial and carotid-femoral arteries segments was also depended on patients genotype: in Т/Т genotype was 9,10  0,15 and 8,68  0,26 correspondingly, in Т/С - 9,38  0,18 and 8,74  0,21, and in С/С carriers - 9,71  0,22 and 10,02  0,71 (P<0.05). Obtained data indicate on significant influence of Т-786С polymorphism on integral parameters of functional status of arterial vessels in ACS patients. Matrix g-carboxyglutamic acid protein (MGP) is known be a potent inhibitor of calcification in blood vessels and is highly expressed on calcified atherosclerotic plaques in humans; we defined a significant association between the G–7→A promoter polymorphism of the MGP gene and ACS. From clinical point of view it is important to understand transformation of genetic data into prediction of disease complication and possibility to improve effectiveness of medication. We found that efficacy of early statin therapy in patients with ACS is determined by polymorphism of eNOS gene promoter : -786TT genotype of eNOS gene promoter was associated with decreased risk of recurrent ischemic events (myocardial infarction -MI and post-MI angina) and acute heart failure in statin treated patients. While there were no benefits of early statin treatment in patients with TC, CC and both (TC+CC) genotypes. A new class of small noncoding RNAs known as microRNAs (miRNAs) has recently been proposed to play a critical role in genetic regulation of physiological and pathological processes. Changes in levels of microRNA-1, -155, -210, -208a, -208b, and -499 in blood plasma, platelets and monocytes of patients with acute MI have been tested. The results of research allows us to make the assumption that higher level of microRNA-155 in monocytes can be a marker of MI development. The indicators of favorable MI follow-up correlated with the microRNA-155 level - higher level was associated with better kidney fuction (higher GFR, lower level of creatinine) and less frequency of heart failure. In conclusion, our studies confirm the possibility of individualized clinical assessment of patients with ACS, implementation of a new standards for tradional management and development of novel treatment by using modern genetic and epigenetic approaches.

Biography:

Liubov Tashireva has completed her PhD at the age of 28 years from Siberian State Medical University. She is the Research Fellow of pathological anatomy department of Tomsk Cancer Research Institute. She has published more than 9 papers in reputed journals.

Abstract:

Invasive carcinoma of non-specific type (IC NST) is characterized by different morphological structures presence. These structure is divided into two subtypes. The first group includes tubular, trabecular structure and discrete tumor cells and is characterized association of tumor cells not only with other tumor cells, but with the stroma. The second group, which includes solid and alveolar structure characterized connections between tumor cells without any connection with the stroma excepting external layer of cells. Significance of morphological intratumoral heterogeneity of IC NST described for tumor progression dependent on the menstrual status of patients. Furthermore, our research team demonstrated that the presence of alveolar structures increases the risk of nodal metastasis of IC NST. However, until now the role of the microenvironment of various structures in tumor progression is unknown. Gene expression analyze shows heterogeneity of microenvironment of morphological structures of IC NST. The microenvironment of alveolar structures presented Th2-type immune response. Since the properties of the tumor microenvironment is closely interact with tumor progression. It can be concluded that the development of Th2 immune response in microenvironment of alveolar structures contributes to the manifestation its invasive properties.

Biography:

K S Jain a Ph.D. in Medicinal Chemistry, holds rich academic and industrial research experience of over 31 years. His areas of interest are New Drug Discovery Research, Chemical Process Development for API, Green Chemistry, Custom Synthesis and Library Synthesis. He has good h-Index, I-20 Index and CIF index scores, over 95 research publications, 170 presentations, 06 text books and 5 patents to credit. He is currently guest editor for Curr. Topics Med. Chem. (Bentham Sci.Publ.), Co-Editor for Indian J. Pharm. Edu.Res, Member Editorial Board : Austin J.Anal. Pharm.Chem. A regular reviewer for many quality scientific research journals and funded for research projects of Univ. of Pune, Indian Council of Med.Res. and National Science Board, Poland, he is a recognized PG and doctoral guide for 07 Indian Universities and recipient of several research awards and grants.

Abstract:

High levels of cholesterol and other lipid constituents are major risk factors in the development of atherosclerosis as well as diseases and disorders associated with it. Though, drugs of various categories acting through different mechanisms are available for antihyperlipidemic therapy, there are limitations associated with each of them, keeping the interest in discovery of newer and better antihyperlipidemic drugs alive. Identification and exploitation of novel molecular targets for discovery of new antihyperlipidemic drugs is an important area of research. Twenty such drug targets shall be discussed for their biochemical roles, structures, estimations, as well as, exploitation for new drug discovery research. Few recently discovered drugs based on such molecular targets shall also be cited. Also discussed will be an investigation into the mechanism of antihyperlipidemic action of a few potential NCE’s from our lab. carried out through docking experiments with few of the above molecular targets; e.g., Niemann Pick C1 Like1 protein (NPC1L1), ATP citrate lyase (ACL), C-reactive protein (CRP), lanosterol 14α-demethylase(LDM), squalene synthase (SqS) and farnesiod X-receptor (FXR) etc. The interactions of these NCE’s with these molecular targets (receptors) were compared with the interactions of the respective co-crystallized native ligands at the active sites of these receptors. These comparisons are based on the docking parameters, as well as, types of interactions and vicinity with various amino acids in the active site pockets. On the basis of favorable interactions with molecular targets assessment of pharmacodynamics has been made in this study.

Biography:

Raj Kumar did his master dgree in Instrumentation engineering from SLIET Longowal and currently pursuing PhD from IIT Delhi, India. His areas of interest are signal processing and power quality. He has published more than 10 papers in journals and conferences of repute.

Abstract:

EMG (Electromyogram) signal contains wealth information about muscle function which is widely used in clinical and engineering application to investigate muscle activity. EMG signals are acquired by surface electrodes which are placed on the targeted muscle set. In order to use the EMG signal as a diagnosis signal or a control signal, a feature is often extracted before performing analysis or classification stage. This study would provide a method for myoelectric control of the movement of forearm prosthetic limbs and human-machine interface for applications in different tasks as hand close, hand open, supination, pronation, flextion, extension. EMG signals has been recorded from BIOPAC MP 100 c System, the forearm muscles of subjects for six movement set mentioned above. The healthy subject aged between 23-30 years have been used for this purpose. The recording was done for six different motions using two active surface electrodes were placed on the skin surface covering the ‘Flexor Carpi Ulnaris’ and ‘Brachioradialis’ muscle in the forearm in differential mode placed with 20 millimeter apart. The single surface electrode was placed on the unconcerned muscle for the reference purpose. Time-Frequency domain features were calculated to extract the information from the signals. ANN has been used to classify between these different movements of forearm which gives accuracy of 85.56% and 86.26% for channel 1and channel 2 (left and right hand) at IMF-1 level with 10 number of hidden layers which are trained by scaled conjugate gradient method for supervised learning in MATLAB.