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.