Scientific Program

Conference Series Ltd invites all the participants across the globe to attend 9th World Biomarkers Congress Madrid, Spain.

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Scientific Program Day 1
Scientific Program Day 2

Day 2 :

Keynote Forum

Jianhua Luo

University of Pittsburgh School of Medicine, USA

Keynote: Cancer genomics and its role in human cancers

Time : 10:00-10:30

Conference Series World Biomarkers 2017 International Conference Keynote Speaker Jianhua Luo photo
Biography:

Jianhua Luo has been studying molecular mechanism related to human malignancies in the last 24 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 16 years, he has been largely focusing on genetic and molecular mechanism of human prostate cancer and hepatocellular carcinomas. He has characterized several signaling pathways that play critical role in prostate cancer development. He proposed prostate cancer field effect in 2002 and he is one of the pioneers in utilizing high throughput gene expression and genome analyses to analyze fi eld effects in prostate cancer and liver cancer. He is also the fi rst in using methylation array and whole genome methylation sequencing to analyze prostate cancer. Recently, his 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 signifi cant new insight into the fi eld of prostate cancer research. Overall, these findings advance our understanding on how cancer develops and behaves and lay down the foundation for better future diagnosis and treatment of human malignancies

Abstract:

Cancer remains one of the most lethal diseases for human. In recent studies, we performed whole genome analysis on prostate and liver cancers. Our result showed that combination of genome copy number variance, genome methylation pattern and novel fusion transcripts specifi c for cancer achieved high accuracy in predicting clinical outcomes of these cancers. Interestingly, some of these fusion genes are also present in a variety of human malignancies. Some of these fusion gene products trigger new pathways that are essential for carcinogenesis in multiple human cancers, and create novel functions that are not present in wild type gene counterparts. Some of these novel fusion genes are highly targetable and treatment of cancers with drugs specifi c for these genes and their signaling pathways produced dramatic improvement of metastasis and survival rate of animals xenograft ed with cancers positive for these fusion genes.Our analyses suggest that targeting therapy for fusion genes holds promise as an eff ective treatment for human cancers.

Keynote Forum

Isabel Desgagné-Penix,

Université du Québec à Trois-Rivières, Canada

Keynote: Systems biology and metabolic engineering of microalgae for the production of pharmaceutical Amaryllidaceae alkaloids

Time : 10:30-11:00

Conference Series World Biomarkers 2017 International Conference Keynote Speaker Isabel Desgagné-Penix, photo
Biography:

Isabel Desgagné-Penix has her expertise in Plant Biochemistry and specialized metabolism. Her research program is aimed at understanding the Molecular Biology and Biochemistry of isoquinoline alkaloid metabolism in Amaryllidaceae plants. Narcisses and snowdrops remains the only commercial source for the anti-cholinesterase galantamine and several potential alkaloid pharmaceuticals. The recent availability of some Amaryllidaceae alkaloid biosynthetic genes creates metabolic engineering opportunities in plants and microorganisms. Her innovative and creative new ways to attempt production of valuable plant metabolites are of interest.

Abstract:

Several Amarylllidaceae plant alkaloids (AAs) possess powerful pharmaceutical and biotechnological properties. Thus, AA metabolism and its fascinating molecules, including anti acetylcholinesterase galantamine, anti-microbial lycorine and anti-cancer narciclasine, have attracted the attention of both the industry and researchers involved in plant science, chemical bioengineering and medicine. Currently, access and availability of high-value AAs [commercialized (e.g. galantamine) or not (e.g. narciclasine)] is limited by low concentration in nature, seasonal production and time-consuming low-yield extraction methods. Nevertheless, commercial AA galantamine is still extracted from plant sources. Eff orts to improve the production of AA have largely been impaired by the lack of knowledge on AA metabolism. Th e purpose of this study was to use recent development and integration of next-generation sequencing technologies and metabolomics analyses to unravel metabolic pathways allowing the use of metabolic engineering and synthetic biology approaches to increase production of valuable AAs. Novel genes encoding AA biosynthetic enzymes were identifi ed from our transcriptome databases using bioinformatics tools. The genes were characterized, and their activities were studied through classical biochemistry experiment such as cloning into expression vectors, heterologous expression, recombinant protein purifi cation and specifi c enzyme assays. In addition, AA precursor pathway was introduced into microalgae cells to validate the function of the biosynthetic genes and to produce AA metabolites (precursors and intermediates). Next, the final steps of the AA biosynthetic pathway will be added to reach galantamine or other AA synthesis in microalgae. Metabolic engineering provides opportunity to overcome issues related to restricted availability, diversifi cation and productivity of plant alkaloids. Engineered cells can act as iofactories by off ering their metabolic machinery for the purpose of optimizing the conditions and increasing the productivity of a specific alkaloid.

  • Biomarkers | Cancer Biomarkers | Pathology Diagnosis
Location: Burgos
Speaker

Chair

Wancai Yang

University of Illinois at Chicago, USA

Session Introduction

Wancai Yang

University of Illinois at Chicago, USA

Title: Genetic and epigenetic alterations in chronic colitis malignant transformation
Speaker
Biography:

Wancai Yang is the Dean of the Institute of Precision Medicine and School of Basic Medical Sciences, Jining Medical University, China, and a Professor of Pathology, University of Illinois at Chicago, USA. He is also an Adjunct Professor of Biological Sciences, University of Texas, El Paso, USA. He obtained his MD degree and was trained as a Pathologist from China and received Post-doctoral training on Cancer Biology from Rockefeller University and Albert Einstein Cancer Center, US, and was promoted as Assistant Professor. In 2006, he moved to the Department of Pathology, UIC and serving as a Grant Reviewer for the National Institutes of Health (USA) and the National Nature Science Foundation of China. His research focuses on: (1) the determination of mechanisms of gastrointestinal carcinogenesis, (2) identifi cation of biomarkers for cancer detection and patient selection for chemotherapy, (3) implication of precision medicine in cancers. He has published more than 80 peer-reviewed articles and has brought important impact in clinical signifi cance.
 

Abstract:

Chronic colitis malignant transformation is one of major causes to colorectal cancer, but the mechanisms of colitis develops and how the chronic colitis progress to malignance is largely unknown. Using a unique mouse model, we have demonstrated that the mice with targeted disruption of the intestinal mucin gene Muc2 spontaneously develop chronic infl ammation at colon and rectum at early age, whose histopathology was similar to ulcerative colitis in human. In the aged mice, Muc2-/- mice develop colonic and rectal adenocarcinoma accompanying severe infl ammation. To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from Muc2-/- and +/+ mice. MicroRNA profi ling showed diff erential expression of miRNAs (i.e. lower or higher expression enrichments) in Muc2-/- mice. Based on relevance to cytokines and cancer, the miRNAs were validate and were found signifi cantly downregulated or upregulated in human colitis and colorectal cancer tissues, respectively. Th e targets of the miRNAs were further characterized and their functions were investigated. More studies from the Muc2-/- mice showed disorder of gut microbiota. Moreover, a novel tumor suppressor PRSS8 also plays a critical role in colorectal carcinogenesis and progression, for instance, tissue-specific deletion of the PRSS8 gene resulted in intestinal infl ammation and tumor formation in mice. Gene set enrichment analysis showed that the colitis and tumorigenesis were linked to the activation of Wnt/beta-catenin, PI3K/AKT and EMT (epithelial-mesenchymal transition) signaling pathways. Taken above, the disorder of gut microbiota could result in genetic mutations, epigenetic alterations, leading to the activation of oncogenic signaling, in colorectal epithelial cells, and fi nally, to colitis development, promoting malignant transformation and mediating colorectal cancer metastasis.
 

Yonghua Bao

Jining Medical University, China

Title: Genetic deficiency of PRSS8 causes mouse intestinal inflammation and tumors
Speaker
Biography:

Yonghua Bao graduated from Jiamusi Medical University (China) with a Clinical Medicine background, received PhD on Biochemistry and Molecular Biology from Jilin University and Post-doctoral training on Biochemistry and Molecular Biology in the State Key Laboratory of China Agricultural University. She was promoted as Associate Professor and worked in cancer and cell signal transduction lab since 2012. She was recruited by Jining Medical University as a Professor of Pathology in 2015, and was appointed as Vice Dean of Institute of Precision Medicine. Her study focuses on cancer biology and cell signaling pathways in gastrointestinal carcinogenesis, progression and metastasis. As PI, she was funded by the National Natural Science Foundation of China. She has published 22 papers and was awarded 3 patents.
 

Abstract:

PRSS8 is a glycosylphosphatidylinositol anchored serine protease, has physiological and pathophysiological functions and shows important roles in the epidermal barrier function and in the regulation of glucose homeostasis. However, the biological functions of PRSS8 in cancer initiation and progression is unknown. We have found that PRSS8 was signifi cantly reduced in esophageal and colorectal cancers and acted as a tumor suppressor in colitis-associated colorectal cancer through targeting Sphk1/Stat3/Akt signaling pathway. To determine the roles of PRSS8 in colorectal cancer in vivo, we developed a conditional knockout mouse model - intestine-specifi c deletion of Prss8 in mice (Prss8 fl /fl -Cre+, Prss8 CKO), and found that PRSS8 deletion caused spontaneous formation of intestinal infl ammation and tumors. At the age of 3 months, about 20% of the Prss8 CKO mice exhibited infl amed rectum and then exerted rectal prolapse. Histopathologic analysis showed that 65% Prss8 CKO mice had developed chronic infl ammation in large intestine at 3 months. Interestingly, 45% Prss8 CKO mice had developed hyperplasia in small intestine at 3 months. At the age of 6 months, 53 % of the Prss8 CKO mice developed adenomas, and at the age of 9 months, 75% of the Prss8 CKO mice developed adenomas. Further studies showed that gastrointestinal tumorigenesis was linked to the disruption of intestinal epithelial cell maturation: more proliferative cells and moved faster in the Prss 8 CKO mouse, assayed by BrdU staining and migration assay. Moreover, Prss 8 CKO mouse intestine exhibited less mature mucin drops and goblet cells at the crypts of small and large intestine in comparison with the WT mice. Gene profi le using mouse intestinal epithelial cells and gene set enrichment analysis showed that the tumorigenesis was associated with oncogenic signaling pathways, including Wnt/beta-catenin and infl ammatory signaling. Th e underlying mechanisms are under further investigation.

M Davenport

Salford Royal NHS Foundation Trust, UK

Title: Gastric Endoscopic Submucosal Dissection (ESD) as a treatment for early neoplasia and for accurate staging of early cancers in UK Caucasian population
Speaker
Biography:

M Davenport is a Foundation Year 2 Doctor at Salford Royal Hospital, Manchester, UK. He is presenting on behalf of a team headed by Dr. Yeng S Ang, MD, FRCP, Consultant Gastroenterologist, Salford Royal University Hospital, UK. Honorary Reader, University of Manchester, Manchester, UK. 

Abstract:

Aim: To investigate the effi cacy of Endoscopic Submucosal Dissection (ESD) at diagnosing and treating superfi cial neoplastic lesions of the stomach in a Caucasian population.

Methods: Data of Caucasian patients treated with or considered for ESD at a tertiary referral center were retrieved for a 3-year period. Primary outcomes were curative resection (CR), which was defi ned as ESD resections with clear margins and an absence of lymphovascular invasion, poor diff erentiation and submucosal involvement on histology. Secondary outcomes were reversal of dysplasia at 12 months follow-up and/or at the latest follow up. Change in histological diagnosis pre and post ESD was recorded.

Results: Twenty four patients were identifi ed with intention to treat. Nineteen patients were considered eligible, and ESD was attempted on 25 lesions, 4 of which failed and were aborted. Out of 21 ESD performed, en-bloc resection was achieved in 71.4% of cases. Resection was considered complete on endoscopy in 90.5% of cases compared to only 38.1% on histology. Six resections were considered curative (28%), 5 non-curative (48%) and 10 indefi nite (24%). ESD changed the histological diagnosis in 66.6% of cases post ESD. Endoscopic follow-up in the indefi nite group and CR group showed that 50% and 80% of patients were clear of dysplasia at the latest follow-up respectively; 2 cases of recurrence were observed in the indefi nite group and survival rate for the entire cohort was 91.7%.

Conclusion: This study provides evidence for the effi  cacy of ESD as a therapeutic and diagnostic intervention in Caucasian populations and supports its application in the UK.

Yeng S Ang

Salford Royal University Hospital, UK

Title: The ERK MAP kinase-PEA3/ETV4-MMP-1 axis is operative in oesophageal adenocarcinoma
Speaker
Biography:

Yeng S Ang has an international professional standing and research expertise to enhance clinical interventions in Barrett's oesophagus and oesophageal cancer. He is a Member of the BSG/National Clinical Research Institute Upper GI early cancer prevention research subgroup. He is 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 his contribution for the management of GORD, Barrett’s oesophagus and oesophageal cancer. He has published over 45 articles and he is 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 tumorigenesis. Their activation by Ras-ERK pathway signaling is particularly relevant to the tumorigenic properties of many ETS-domain transcription factors. The PEA3 subfamily of ETS-domain transcription factors have been implicated in tumor metastasis in several solid tumors. 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 and a key target gene is MMP-1. Th e 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.
 

  • Biopharmaceuticals | Computer Aided Drug Design (CADD) | Medicinal Chemistry in Modern Drug Discovery | Drug Metabolism and Drug Designing
Location: Burgos
Speaker

Chair

Vladimir A Baulin

Universitat Rovira I Virgili, Spain

Session Introduction

Wolfgang B Fischer

National Yang-Ming University, Taiwan

Title: Targeting viral membrane proteins in silico
Speaker
Biography:

Wolfgang B Fischer is Professor at the Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei, Taiwan. He has obtained his PhD in Chemistry at Heidelberg University, Germany, working in the fi eld of vibrational spectroscopy in 1991. After years in the US, he has completed his Postdoctoral, working on bacteriorhodopsin using vibrational spectroscopy in Boston University, Germany. Then he has worked in Analytical Chemistry, working on ion channels as potential biosensors, UK (Oxford University as EU Marie Curie Research Fellow and later as Lecturer, working on viral ion channels using bilayer recordings and molecular dynamics simulations. He has moved to Taiwan. The field of research is on biophysical aspects describing dynamics and energetic of protein-protein interactions (PPIs) of membrane proteins. The focus is on the development of computational platform technologies to support drug discovery and design as well as materials sciences.

Abstract:

Many viral membrane proteins interact with membrane proteins of the host to steer the cell for a successful mass production of novel virions. The viral proteins rely on selective interactions of their transmembrane domains (TMDs) with those of the host protein. An understanding of the modalities of recognizing the proper host target, on the revers, can be turned against the virus. Getting insights into the specifi city of binding, the interaction of oncoprotein E5 of Human papillomavirus-16 (HPV16), an 83-amino acid membrane protein containing 3 TMDS, with a peptide corresponding to the fourth TMD (TMD4) of the 16 kDa subunit of the ATP6V0C is investigated as an example. HPV-16 is the major cause of cervical cancer diagnosed today. E5 is a membrane protein which is expressed at an early (hence the letter E) stage of the infectivity cycle when the virus turns the cell malignant. Th e protein interacts with a series of host factors, but has also been identified experimentally to allow channel activity when most likely in a hexameric assembled form. Computational modeling suggests a weak selectivity of the channel. Docking approaches as well as coarse grained molecular dynamics (CGMD) simulations of the peptides within a hydrated lipid membrane specify the mode of binding of TMD4 with either E5 protein or its individual TMDs. From potential of mean force calculations (PMF) and statistical analysis enthalpy and entropy contributions are attributed of TMD4 binding to TMD3 and TMD2 of E5, respectively.

Sepehr Soleymani

Pasteur Institute of Iran, Iran

Title: Crocin, a carotenoid pigment of saffron inhibits the replication of HSV and HIV in vitro
Speaker
Biography:

Sepehr Soleymani has graduated from Tehran University of Medical Science in Clinical Laboratory Science. Currently, he is a Master student of Medical Biotechnology in Blood Transfusion Organization and also as a Research Assistant in Pasteur Institute of Iran for 3 years. His activity focuses on natural and synthetic antiviral agents, drug delivery system and vaccine research.
 

Abstract:

Human immunodeficiency virus type 1 (HIV-1) belonging to the retrovirus family is the major agent of acquired immunodefi ciency syndrome as a public health problem in the world. There are more than 253 types of approved antiHIV drugs, but further development of novel anti-HIV agents would be needed especially in low-income countries without anti-retroviral treatment. Some limitations of the recent viral therapies include high risk of resistant viruses, and adverse side eff ects in long-term therapy. Th erefore, it is necessary for improvement of novel potent and safe anti-HIV drugs with decreased side effects especially tolerability and toxicity. Furthermore, other problem in treatment of HIV-infected patients is their susceptibility to Herpes simplex virus (HSV) infection; thus, both anti-HSV and anti-HIV drugs with novel modes of action are required. Recently, saff ron components have been proposed to treat various pathological conditions. In this study, crocin, a major carotenoid of saff ron, was extracted from the ethanolic saffron extract by adsorption chromatography using neutral aluminum oxide 90 active. Then, the anti-HSV-1 and anti-HIV-1 activities of crocin were assessed as well as its cytotoxicity in vitro. Th e data indicated that crocin was active against HIV-1 and HSV-1 virions at certain doses. Crocin inhibited the HSV replication at before and aft er entry of virions into Vero cells. Indeed, crocin carotenoid suppressed HSV penetration in the target cells as well as disturbed virus replication aft er entry to the cells. Th is sugar-containing compound extracted from saff ron showed to be an eff ective anti-herpetic drug candidate. In general, crocin would be a promising anti-HSV and anti-HIV agent for herbal therapy against viral infections. 

Şükrü Tüzmen

Eastern Mediterranean University, Turkey

Title: RNAi-based tailored therapeutic strategies: Are we there yet?
Speaker
Biography:

Åžükrü Tüzmen is a Molecular Biologist and Geneticist. He has more than 28 years of multi-disciplinary research experience integrating studies of the molecular basis of human diseases, including cancer genetics. He has a passion for advancing the molecular genetics of diseases by studying the associations between drugs, genes, pathways, and diseases. His mission is to discover and validate links between gene states and disease phenotypes, and further use these links to identify druggable targets to be utilized as biomarkers in the early diagnostic stages of genetic diseases. He has focused his career on developing and applying cutting edge methods and technologies to ensure excellence in translation of his basic scientifi c research including cancer genetics, from bench to bedside. He has been invited to deliver talks in many national and international settings, and he has served on many expert panels including The Research Grant Council, Hong Kong, China.

Abstract:

A classical technique to determine the function of a gene is to experimentally inhibit its gene expression in order to examine the resulting phenotype or eff ect on molecular endpoints and signaling pathways. RNA interference (RNAi) is one of the recent discoveries of a naturally occurring mechanism of gene regulation facilitated by the induction of double stranded RNA into a cell. Th is event can be utilized to silence the expression of specifi c genes by transfecting mammalian cells with synthetic short interfering RNAs (siRNAs). siRNAs can be designed to silence the expression of specifi c genes bearing a particular target sequence and may potentially be presented as a therapeutic strategy for inhibiting transcriptional regulation of genes, which in such instances constitute a more attractive strategy than small molecule drugs. Low dose drug and siRNA combination studies are promising strategies for the purpose of identifying synergistic targets that facilitate reduction of undesired gene expression and/or cell growth depending on the research of interest. Commercially available RNAi libraries have made high-throughput genome-scale screening a feasible methodology for studying complex mammalian cell systems. However, it is crucial that any observed phenotypic change be confi rmed at either the mRNA and/or protein level to determine the validity of the targeted genes. Currently, qPCR is widely utilized for accurate evaluation and validation of gene expression profi ling. In this study, we describe a high-throughput screening of RNAi based gene knock-down approach and qPCR validation of specifi c transcript levels. Considering such advantageous applications, siRNA technology has become an ideal research tool for studying gene function in research fi elds including Pharmaceutical Biotechnology, and holds the promise that the utilization of siRNA-based therapeutic agents will accelerate drug discovery in clinical trials. 

Saad M Alshahrani

Prince Sattam Bin Abdulaziz University, Saudi Arabia

Title: Anticancer effi cacy of self-nanoemulsifying drug delivery system of sunitinib malate
Speaker
Biography:

Abstract:

Sunitinib malate (SM) is reported as a weakly soluble drug in water due to its poor dissolution rate and oral bioavailability. Hence, in the current study, various “self-nanoemulsifying drug delivery systems (SNEDDS)” of SM were prepared, characterized and evaluated for the enhancement of its in vitro dissolution rate and anticancer effi  cacy. On the basis of solubilization potential of SM in various excipients, “Lauroglycol-90 (oil), Triton-X100 (surfactant) and Transcutol-P (cosurfactant)” were selected for the preparation of SM SNEDDS. SM-loaded SNEDDS were developed by spontaneous emulsifi cation method, characterized and evaluated for “thermodynamic stability, self-nanoemulsifi cation effi  ciency, droplet size, polydispersity index (PDI), zeta potential (ZP), surface morphology, refractive index (RI), the percent of transmittance (% T) and drug release profi le.” In vitro dissolution rate of SM was signifi cantly enhanced from an optimized SNEDDS in comparison with SM suspension. Th e optimized SNEDDS of SM with droplet size of 42.3 nm, PDI value of 0.174, ZP value of −36.4 mV, RI value of 1.339% T value of 97.3%, and drug release profi le of 95.4% (aft er 24 h via dialysis membrane) was selected for in vitro anticancer effi  cacy in human colon cancer cells (HT-29) by MTT assay. MTT assay indicated signifi cant anticancer effi  cacy of optimized SM SNEDDS against HT-29 cells in comparison with free SM. Th e results of this study showed the great potential of SNEDDS in the enhancement of in vitro dissolution rate and anticancer effi  cacy of poorly soluble drug such as SM. 

Nima Sanadgol

University of Zabol, Iran

Title: Cucurbitacin B mitigates experimental autoimmune encephalomyelitis by inhibition of IL-17/IL-23 immune axis
Speaker
Biography:

Nima Sanadgol is expert in field of Cell and Molecular Neurobiology. His recent research emphasis is in treatment of neurodegenerative disease with use of new natural compounds. He has particular interest in evaluation of mechanisms of neuron-glia interactions, in order to fascinating myelin repair and control of neuroinfl ammatory and neuro-degenerative diseases (Multiple sclerosis, Alzheimer, Parkinson, etc.). He has already gained so much experience in neuro-immune and circuit-specifi c signaling in glial-neuron networks (T cell biology, NF-κB, Nrf2, MAP kinase, AMP kinase, apoptosis and autophagy).
 

Abstract:

Pharmacological approaches to inhibit brain acute infl ammation may represent important strategies for the control of autoimmune diseases. Multiple sclerosis (MS) is a chronic, infl ammatory, demyelinating and autoimmune disease of the central nervous system (CNS). Cucurbitacin B (CuB), an oxygenated tetracyclic triterpenoid compound extracted from Cucurbitaceae plant species, is a bioactive agent by disruption of microtubule polymerization and inhibition of JAK/STAT signaling. However, there has been little information about impact of CuB on MS treatment. In this research, for the fi rst time we examine eff ects of CuB (specifi c STAT3 blocker), in experimental autoimmune encephalomyelitis (EAE) mouse model of MS. EAE was induced by subcutaneous immunization of MOG35-55 in 8-week-old C57BL/6 mice. CuB was administered at diff erent doses (0.25, 0.5 and 1 mg/kg body weight/day/i.p) from the fi rst day of the experiment. Infl ammatory responses were examined using qRT-PCR, western blot and immunohistochemistry (IHC) analysis of specifi c markers such as p-STAT3, IL17A, IL-23A, CD11b and CD45. CuB reduced STAT3 activation, leukocyte traffi  cking, and also IL-17/IL-23 immune axis in this model. Treated mice with lower doses of CuB exhibited a considerable depletion in the EAE clinical score which correlated with decreased expression of IL-17, IL-23 and infi ltration of CD11b+ and CD45+ cells into the CNS. Our in vivo results suggest that STAT3 inhibition by CuB will be an eff ective and new approach for the treatment of neuro-infl ammatory disease such as MS.
 

Vladimir A Baulin

Universitat Rovira I Virgili, Spain

Title: Design strategies for nanoparticles translocating through lipid bilayers
Speaker
Biography:

Design of nanomaterials able to cross lipid bilayers is a challenging task in nanotechnology. Large variety of shapes, sizes and surface coatings are used for the design of nanomaterials to overcome this barrier. However, the potential barrier is quite high for carbon nanotubes and nanoparticles to cross the lipid bilayer to translocate by thermal motion. It is generally accepted that small hydrophobic nanoparticles are blocked by lipid bilayers and accumulate in the bilayer core, while nanoparticles with sizes larger than 5 nm can only penetrate cells through a slow energy-dependent processes such as endocytosis, lasting minutes. In one example, we show how variation of hydrophobicity of the nanoparticles can lead to passive translocation of nanoparticles through lipid bilayer. Th is adsorption transition through reversible destabilization of the structure of the bilayer induces enhanced permeability for water and small solutes. In another example, we demonstrate that lipid-covered hydrophobic nanoparticles may translocate through lipid membranes by direct penetration within milliseconds. We identifi ed the threshold size for translocation: nanoparticles with diameters smaller than 5 nm stay trapped in the bilayer, while nanoparticles larger than 5 nm insert into bilayer, open transient pore in the bilayer. Using the Single Chain Mean Field (SCMF) theory a mechanism of passive translocation through lipid bilayers is proposed. Observing individual translocation events of gold nanoparticles with 1-dodecanethiol chains through DMPC bilayers, we confi rm the particle translocation and characterize the kinetic pathway in agreement with our numerical predictions. Mechanism relies on spontaneous pore formation in the lipid bilayer. Th e observed universal interaction behavior of neutral and chemically inert nanoparticles with bilayer can be classifi ed according to size and surface properties.
 

Abstract:

Vladimir A Baulin has completed his graduation with honors from the Physics Department at Moscow State University in 2000. He spent three years in the Commissariat à l’Energie Atomique, Grenoble, France, pursuing his PhD in theory of polymer physics and received a PhD in Physics in 2003. In 2004-2006 he was a Postdoctoral Researcher at the Institut Charles Sadron, Strasbourg, France. Since 2008, he leads a group of Soft mater theory at the University Rovira i Virgili, Tarragona, Spain. He is a Coordinator of EU funded initial training network SNAL: smart nano-objects for alteration of lipid bilayers.
 

  • Advance in Biomarkers Discovery | Biomarkers and Non Cancerous Diseases | Cell Free Biomarkers
Location: Burgos
Speaker

Chair

Bodour Salhia

University of Southern California, USA

Session Introduction

Bodour Salhia

University of Southern California, USA

Title: Clinical utility of cell-free DNA methylation in managing breast cancer recurrence
Speaker
Biography:

Bodour Salhia is an Assistant Professor at the University of Southern California and is a Translational Genomics Scientist with extensive knowledge and expertise in mechanisms that underlie tumorigenesis and tumor biology. She received her Honors Bachelor of Science Degree (1998), Master of Health Science (2001) and PhD (2006) degrees in Human Molecular and Cellular Biology from the University of Toronto. She completed a Post-doctoral fellowship (2006-2011) at the Translational Genomics Research Institute (Phoenix, Arizona) in cancer genetics and epigenetics. She has published more than 30 papers in peer-reviewed and reputed journals.
 

Abstract:

A number of clinico-pathological criteria and molecular profi les have been used to stratify breast cancer (BC) patients into high and low risk groups. Currently, there are still no eff ective methods to determine which patients harbor micrometastatic disease aft er standard BC therapy and who will eventually develop local or distant recurrence.  Cell-free (cf) DNA has attracted attention for clinical use in the context of risk prediction, prognostication and prediction of response to chemotherapy in human cancer. Several groups including ours have reported the detection of tumor-associated methylation changes in cfDNA extracted from plasma or serum. We are specifi cally interested in the use of cfDNA methylation biomarkers for the prediction of cancer metastasis in the early stage setting. Accordingly, we are validating a DNA methylation signature, referred to as CpG4C, which discriminates metastatic BC from healthy individuals or disease free survivors using a targeted bisulfi te amplicon sequencing approach. In addition, we have been investigating whether a surge of cfDNA levels aft er cytotoxic chemotherapy aff ects the sensitivity and specifi city of the CpG4C assay. Lastly, we are also working on determining the technical and biological limits of detection of CpG4C in plasma. CpG4C is a potential blood-based biomarker that could be advantageous at the time of surgery and/or aft er the completion of chemotherapy to indicate patients with micrometastatic disease who are at high-risk of recurrence, and who could benefi t from additional therapy. 

Elena V Pikuta

Athens State University, USA

Title: Antiae a novel biomarker for cytodiagnostics
Speaker
Biography:

Elena V Pikuta received her MS in 1995 at Perm State University in Russia, on Biology faculty. She was a practicing nurse in Surgery Department of the Regional Hospital in Perm for one year.She received her BS degree received in 1984 from Perm Medical College. In University she also defended Diploma in Biophysics “The Dielectric Parameters of Tissues at Hypoxia”. She was employed by the Institute of Ecology and Genetics of Microorganisms, The Ural Branch of Russian Academy of Sciences, as a research assistant. She had fi nished her PhD in 1997 at the Institute of icrobiology of RAS in Moscow, the thesis was “Alkaliphilic Sulfate-Reducing Bacteria.
 

Abstract:

Antiae is a recently discovered novel external organelle responsible for the gliding motility in bacteria. Th e antiae composed of plural thin fibers entangled in plexa that may be 10-20 folds of the cellular size, and spin in a coherent, unison rotation around the cell cylinder causing a high-sequence trembling that results a smooth slow gliding.  DAPI stain of strain A7P-90mT demonstrated the absorbance of the stain by the antiae that indicates on possible RNA or DNA molecules involvement in cellular constitution. UV absorbency pick of the living culture was at 300 nm as well as a filtrated through 0.2 μm fi lter liquid containing antiae. Here we discuss the results of the proton, sodium pumps and ATPase inhibition effects on the cellular motion. We also present the results of RNase and DNase treatment along with the thiamine bromide stain with UV imaging.  We also discuss the chemical composition of the antiae with increased amounts of fluorine and silicon according to X-ray spectrophotometry. Presence of the antiae was shown in other bacterial species and Archaea, as well as in viruses. Histopathology of sarcoma and other malignant cancers demonstrated presence of antiae in cell-free areas aff ected by cancer tissues that makes them an important biomarker in cytodiagnostics.
Keywords: bacterial gliding, external organelle antiae, cytodiagnostics, pathohistology, X-ray spectroscopy.

Ana Cristina Calvo

University of Zaragoza, Spain

Title: Prognostic biomarkers of Amyotrophic Lateral Sclerosis (ALS): A step forward in the understanding of the disease
Speaker
Biography:

Ana Cristina Calvo has completed her PhD in 2003 from the Anatomy and Human Histology Department in the University of Zaragoza in Spain and Post-doctoral studies from the ALS Unit in the Hospital 12 October in Madrid (Spain) and from Faculty of Medicine in the Universidad Autónoma in Barcelona (Spain). She is an Associate Professor in Genetics and member of the Laboratory of Genetics and Biochemistry (LAGENBIO, IA2-IIS) in the Faculty of Veterinary Sciences in the University of Zaragoza (Spain). She has published 30 papers in reputed journals and participated as a coauthor in three licensed patents.
 

Abstract:

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of unknown origin that causes progressive muscle paralysis and motor neuron death. The need of reliable biomarkers of ALS that can be accurately monitoring along disease progression is an increasing fi eld of research. In this sense, our main objective is to identify molecular biomarkers as key elements of the induced neurodegeneration in ALS. Previous studies in our research workgroup analysed the transcriptional expression of a group of genes, whose expression was found up and down-regulated signifi cantly in a preliminary microarray study and in muscle biopsy samples from transgenic SOD1G93A mice, the best characterized murine model for the disease. In this study we identifi ed fi ve genes, Mef2c, Gsr, Col19a1, Calm1 and Snx10 as potential genetic biomarkers of longevity in this animal model. Next, we translated this study to ALS patient’s samples to validate the potential nature of these biomarkers. Skeletal muscle biopsies and blood samples from sporadic and familial ALS patients were analyzed by real time PCR and Western blot to test the expression levels of fi ft een genes and fourteen proteins. ROC curves, multinomial regression and timedependent Cox regression analysis were performed. COL19A1 gene and protein levels were identifi ed as potential prognostic candidates in skeletal muscle samples from ALS patients. In addition, the same gene improved prognosis in blood samples from sporadic ALS patients. Th ese fi ndings provide an important fi rst step towards the accurate prediction of potential biomarkers in ALS be the initial springboard to new clinical trials and promising therapeutic strategies.
 

Amanda Costa

Federal University of Sergipe, Brazil

Title: Advances on fl ow cytometry and new immunophenotypic markers on AML diagnosis, prognosis determination and overall survival
Speaker
Biography:

Amanda Costa is a Pharmacist, graduated from the Pharmacy School of Federal University of Rio Grande do Norte, Brazil. She has completed her Master’s degree in Pharmaceutical Sciences from Federal University of Sergipe, Brazil, and is currently pursuing PhD from the same University, in which she teaches Hematology in the Pharmacy School. She has been serving as an Editorial Board Member of the Journal of Hematology and Serology.

Abstract:

Even though there has been improvements in the understanding and treatment of acute myeloid leukemia (AML), not much advances are noted when it comes to outcome and survival. It is still substantial the association of AML to a poor prognosis followed by low remission and survival rates, where 60‒70% of adult patients reach complete remission, but only about 25% survive with chances of being cured. Although younger patients show a 5-year survival rate of 62.8%, there is a decrease for people older than 65 years that hits 4%. AML diagnosis remains challenging, being cytogenetics and molecular biology primary tools for risk stratifi cation and prognostic determination. Moreover, flow cytometry has recently stood out as a useful tool in AML diagnosis, classification and treatment evaluation, for being able to characterize heterogeneous populations of blast cells and analyze multiple parameters simultaneously. Important improvements in fl ow cytometry instrumentation and new analytical strategies were obtained, nevertheless, there are still limitations regarding new immunophenotypic markers for AML diagnosis, highlighting the need of new markers in clinical routines, what would increase its diagnosis and prognosis value, and also be useful for monitoring minimal residual disease (MRD) and improvement of new targeted therapy. Some research has been developed around the world to evaluate the effi ciency of incorporation of new markers on AML immunophenotypic panels, which has demonstrated a relevant association with the development of the disease, either for its association to a decreased survival and poor prognosis, for being a possible therapeutic target or because its eff ectiveness as marker for MRD.

 

  • Cancer Biomarkers | Biomarkers & Immuno-Oncology | Biomarkers Detection & Discovery | Clinical Biomarkers | Advances in Biomarkers Discovery
Location: Burgos
Speaker

Chair

Topolcan Ondrej

Charles University, Czech Republic

Session Introduction

P G Lokhov

Institute of Biomedical Chemistry, Russia

Title: Usage of metabolomics profile as biomarkers itself for diagnostic diseases
Speaker
Biography:

P G Lokhov is the Head of Laboratory for Mass Spectrometry-based Medical Metabolomics in the Department of Proteomic Research and Mass Spectrometry of IBMC, a position he has held since 2012. He is mainly interested in mass spectrometry-based metabolomics and proteomics, and their application for diagnostics. He graduated from the 2nd Moscow Medical Institute, took the post-graduate course and thereafter received a PhD degree in Biochemistry in 2002. During his career Dr. Lokhov has received several awards, including the State Prize of the Government of Russia.

Abstract:

Recently, the researches to fi nd proteins as biomarkers of various diseases have become widespread. Especially these studies are popular in оncology. However, until now proteins specifi c for cancer cells are not detected. In spite of it, to diagnose cancer diseases biomarkers which are specifi c for a neoplastic process generally are widely used (such as CA-125, CA 19-9, CA 15-3, PSA, α-fetoprotein etc.). However, they can’t discharge the main task: to diagnose the initial stages of disease, because their opportunity is limited by low sensitivity of existing laboratory technologies. Th e situation is much better in the case of using RNA’s as biomarkers, because PCR takes off such restrictions. In the case of metabolomic diagnostics there are the same concentration limits as in proteomics. Th erefore, it was decided not to use separate low molecular weight compounds as biomarkers but the whole metabolomic profile of the sick person as a biomarker itself of a disease. With this purpose, at the fi rst stage that profi le was clusterized using the method of principle component analysis to detect clusters of metabolites which are diff erent from the clusters of healthy person. At the second stage, the specifi city and sensitivity of the proposed technology was evaluated using the SVM and ROC analyses, for diagnostics of lung, prostate and other cancers.

Mercedes Piedad de León-Bautista

Central adn, Mexico

Title: RhoGDI3, is this small molecular regulator key orchestring the movement and tumor mass in PDAC?
Speaker
Biography:

Mercedes Piedad de León Bautista has completed her Bachelor’s Degree from UPAEP University School of Medicine, and an MSc and PhD from CINVESTAV-IPN in the Dept. of Molecular Biomedicine. She is the Medical Director and Laboratory Chief of Central ADN, a molecular laboratory focusing on human health and translational medicine. She has been working with PDAC and, nowadays, her biomedical efforts are based on molecular platforms to fi nd new markers in cancer and hereditary diseases.

Abstract:

Pancreatic ductal adenocarcinoma (PDAC) is a complex pathology with poor prognosis. Eff orts have been focused on understanding the role of RhoGDI's in PDAC, in particular, RhoGDI1 and RhoGDI2. However, the role of RhoGDI3 has neither been studied in relation to cancer nor to PDAC. Our group have characterized the expression and functionality of RhoGDI3 and its target GTPases, RhoG and RhoB, in pancreatic cell lines and compared it to human tissue. Th rough immunofl uorescences, pull down assays, subcellular fractionation and immunohistochemistry, we found a reduction in RhoGDI3 expression in PDAC late stages, and this reduction correlates with tumor progression and aggressiveness. Despite the reduction in the expression of RhoGDI3 in PDAC, we found that RhoB was under expressed while RhoG was over expressed, suggesting that cancerous cells keep their capacity to
activate this pathway, thus these cells may be eager to the stimuli needed to proliferate and become invasive. Surprisingly, we found nuclear localization of RhoGDI3 in non-cancerous pancreatic cell line and normal pancreatic tissue biopsies, which could open the possibility of novel nuclear functions for this protein, impacting gene expression regulation and cellular homeostasis. To elucidate the possible functions of RhoGDI3 in cancer maintenance, the overexpression assays have demonstrated that increased RhoGDI3 protein increases proliferation rate; besides, the xenograft tumor was smaller compared to the mock, suggesting and predicting that overexpression of RhoGDI3 is an important molecule to constrain the tumoral volume. In conclusion, RhoGDI3 protein decreases the malignant behavior in PDAC.

Topolcan Ondrej

Charles University, Czech Republic

Title: PHI and prostate cancer - optimal management
Speaker
Biography:

Topolcan Ondrej has graduated from the Medical Faculty, Charles University in Pilsen. He is working in the Dep. of Nuclear Medicine Faculty Hospital in Pilsen
and he was the Head of Imunoanalytic Laboratory in 2000. He is a Member of Scientific Committee Endocrinology Institute Prague and he was awarded the Carl
R Jolliff award for lifetime achievement in Clinical and Diagnostic Immunology by the American Association for Clinical Chemistry (AACC) in 2011.

Abstract:

Background: Prostate cancer is the fi ft h leading cause of cancer death among men. More than one million cases are worldwide diagnosed every year, and the mortality is over 300,000 deaths per year. Prostatic specifi c antigen (PSA) is a serine protease composed of 240 amino acids in a single polypeptide chain. In serum, PSA is primarily bound to alpha1-anti-chymotrypsin (95% of total PSA), to a lesser extent to alpha2-macroglobulin. 10-30% serum PSA occurs in the free form (fPSA). Since the 80s of the last century, total level of prostatic specifi c antigen (tPSA) is used as a tumor marker in the prostate cancer diagnostics. Most of the prostate tumors are diagnosed using biopsy based on the elevated levels of PSA. It is also useful to determine the part of PSA called proPSA. This part of PSA is more produced by tumor cells. Based on the levels of PSA, proPSA, and free PSA, the prostate health index PHI can be calculated.
Aim: Demonstration of the usefulness of PHI in the management of prostate cancer patients.
Materials & Methods: Cohort of 1865 patients was evaluated. Th e total of 5800 biopsies, 1448 MRI and 150 PET/MRI were performed in this cohort of patients. 4900 samples with the results of PSA, fPSA, -2proPSA, fPSA/tPSA calculated results and PHI during the follow-up period. Gleason score was established in all patients.
Results: By comparison of AUC sensitivity for each laboratory parameter, PHI achieved the highest value (0.8118). PHI achieved also the best correlation with the Gleason score (G6-G9) which allows PHI to be a reliable marker of aggressiveness of the prostate cancer. An optimal PHI cut-off value was 31 with specifi city 20.4%, sensitivity 97.6%, PV+ 18%, PV- 97%, RR 8.7.
Conclusions: Determining PHI allows proposing the optimal diagnostic algorithm for prostate cancer, improvement of diff erential diagnosis of carcinoma vs. prostate hypertrophy, reducing biopsies and imaging techniques, more accurate prognosis estimation, optimizing the type of surgery, optimizing of the postoperative treatment and optimizing of follow-up.

Yeng S Ang

Salford Royal University Hospital, UK

Title: PEA3/ETV4-related transcription factors coupled with active ERK signalling are associated with poor prognosis in gastric adenocarcinoma
Speaker
Biography:

Yeng S Ang has an international professional standing and research expertise to enhance clinical interventions in Barrett's oesophagus and oesophageal cancer. He is a Member of the BSG/National Clinical Research Institute Upper GI early cancer prevention research subgroup. He is 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 his contribution for the management of GORD, Barrett’s oesophagus and oesophageal cancer. He has published over 45 articles and he is a Supervisor for PhD and MD students in the molecular cancer group of the University of Manchester.

Abstract:

Background: Transcription factors often play important roles in tumorigenesis. Members of the PEA3 subfamily of ETS-domain transcription factors fulfill such a role and have been associated with tumor metastasis in several diff erent cancers. Moreover, the activity of the PEA3 subfamily transcription factors is potentiated by Ras-ERK pathway signalling, which is itself often deregulated in tumor cells.
Methods: Immunohistochemical patterns of PEA3 expression and active ERK signalling were analyzed and mRNA expression levels
of PEA3, ER81, MMP-1 and MMP-7 were determined in gastric adenocarcinoma samples.
Results: Here, we have studied the expression of the PEA3 subfamily members PEA3/ETV4 and ER81/ETV1 in gastricadenocarcinomas. PEA3 is upregulated at the protein level in gastric adenocarcinomas and both PEA3/ETV4 and ER81/ETV1 are upregulated at the mRNA level in gastric adenocarcinoma tissues. This increased expression correlates with the expression of a target gene associated with metastasis, MMP-1. Enhanced ERK signalling is also more prevalent in late-stage gastric adenocarcinomas and the co-association of ERK signalling and PEA3 expression also occurs in late-stage gastric adenocarcinomas. Furthermore, the coassociation of ERK signalling and PEA3 expression correlates with decreased survival rates.
Conclusions: This study shows that members of the PEA3 subfamily of transcription factors are upregulated in gastric adenocarcinomas and that the simultaneous upregulation of PEA3 expression and ERK pathway signalling is indicative of late-stage disease and a poor survival prognosis.

Varda Shoshan-Barmatz

Ben-Gurion University of the Negev, Israel

Title: Novel biomarker proteins for cancer: Impact on diagnosis, prognosis and treatment
Speaker
Biography:

Varda Shoshan Barmatz is the Hyman-Kreitman Chair in Bioenergetics at Ben-Gurion University (BGU). Her PhD is from the Weizmann Institute; Post-doctoral training was from the University of Wisconsin-Madison and the University of Toronto. In 1982, she joined the Department of Life Sciences, BGU, and served as Chair (2000-2004). Her awards include the Hestrin Prize of the Israel Biochemistry Society, Teva Award for Young Scientists (1993) and Teva Founders Award (2016). Lady Globes magazine selected her as one of the 50 most infl uential women in Israel (2009) and one of five who made breakthroughs in science (2016). She was the Founder and Director (2006-2015) of the National Institute for Biotechnology in the Negev.

Abstract:

Cancer cells undergo re-programing of metabolism, cell survival and anti-apoptotic defenses, with the proteins mediating these re-programing representing potential biomarkers. Here, using specific antibodies, mass spectrometry and bioinformatics tools; we searched for novel biomarker proteins in chronic lymphocytic leukemia (CLL) and in non-small cell lung cancer (NSCLC) patient samples that can impact diagnosis, treatment and prognosis. By comparing protein expression profi les of CLL- and healthy donorderived lymphocytes, we identified 1,360 diff erentially expressed proteins, some shown for the first time to be associated CLL. Downregulated expression of two proteins resulted in cell growth inhibition, pointing to their essential functions. Based on changes in the levels of several proteins in CLL patients, we could distinguish between patients in a stable disease state and those who would be later subjected to anti-cancer treatments, 2-3 years before the physician’s decision. In NSCLC, the adenocarcinoma (AC) and squamous cell carcinoma (SCC), sub-types present unique genomes, transcriptomes, and proteomes, and share clinical and histopathological characteristics, yet diff er in treatment. We identifi ed novel biomarker proteins in NSCLC, with 378 proteins showing a ≥|100|-fold change in level. Several, identifi ed for the fi rst time, allow for distinguishing between AC and SCC. These, together with markers previously proposed and confi rmed here, lead us to propose a list of proteins for discriminating SCC and AC, with four being secreted. Precise diagnosis of AC and SCC is essential for selecting appropriate treatment. Finally, some of these biomarkers can serve as new targets and lead to new treatments for lung and CLL cancers.

M Al Hassan

Beirut Arab University, Lebanon

Title: Soarfenib effect on human colon cancer cells HCT116 and HCT116 p53-/-
Speaker
Biography:

M Al Hassan is a current PhD candidate at the Beirut Arab University, working in collaboration with the American University of Beirut on Sorafenib and its in-vitro
and in-vivo effects on colorectal cancer. She has graduated from the Lebanese American University with a Master’s degree in Cells and Molecular Biology. Her MS thesis was about the effect of metformin on the metastasis and the 3D motility of glioblastoma cancer cells.

Abstract:

Sorafenib, a kinase inhibitor, has been approved among the drugs for the treatment of radioactive iodine resistant thyroid carcinoma, primary kidney and liver cancer. Reported targets of sorafenib include VEGFR, af family, and PDGFR belonging to the general class of tyrosine kinases. Blocking growth signals in kidney and breast cancers underlie one of the mechanisms of sorafenib antitumor effects’ leading to cell death. We hereby examine the effect of sorafenib on human colon carcinoma cell-line HCT116. We also investigate the possible role of p53 in mediating this eff ect using mutant HCT116 p53-/- cells. Cultured wild and mutant cells are treated with sorafenib (0-75μM) for 24 hr. Th is is followed by assessing the viability of cells using MTT and trypan blue exclusion assays. We also examined if sorafenib mode of action is mediated by ROS. Levels of ROS were determined in the presence and absence of antioxidants using the colorimetric NBT assay. Our preliminary results show a concentration dependent decrease in viability (trypan blue) with an estimated EC50 of 10 and 25 μM for HCT116 and HCT116 p53-/- respectively. Compared to trypan blue, MTT results were similar in case of HCT116 p53-/- but were signifi cantly diff erent with HCT116. Furthermore we obtained a significant increase in level of ROS of: 37.11% and 31.30% for HCT116 and HCT116p53-/- respectively. However, 2 hr. pre-incubation of cells with antioxidants, Trolox, N-acetylcysteine (NAC), and catalase, prior to sorafenib treatment, exerted no diff erent eff ect. No restoration of viability or decrease in generated ROS level was noted. Our preliminary fi ndings show that sorafenib action is independent of ROS level and p53 expression and further investigations on the mechanism(s) of sorafenib action are ongoing.

Sayda Omer Ebnaof

University of Khartoum, Sudan

Title: Diagnostic and prognostic microRNAs in the serum of breast cancer patients measured by droplet digital PCR
Speaker
Biography:

Sayda Omer Ebnaof has completed her PhD in Molecular Biology from University of Ferrara, Italy in 2016 and MSc in Molecular Medicine from Institute of Endemic Diseases, University of Khartoum-Sudan. She is a Lecturer of Histopathology and Cytology at University of Khartoum. She has published four papers in reputed
journals.

 

Abstract:

Background: Breast cancer circulating biomarkers include carcinoembryonic antigen and carbohydrate antigen 15–3, which are used for patient follow-up.Since sensitivity and specifi city are low, novel and more useful biomarkers are needed. The presence of stable circulating microRNAs (miRNAs) in serum or plasma suggested a promising role for these tiny RNAs as cancer biomarkers. To acquire an absolute concentration of circulating miRNAs and reduce the impact of preanalytical and analytical variables, we used the droplet digital PCR (ddPCR) technique.
Results: We investigated a panel of fi ve miRNAs in the sera of two independent cohorts of breast cancer patients and disease-free
controls. The study showed that miR-148b-3p and miR-652-3p levels were significantly lower in the serum of breast cancer patients than that in controls in both cohorts. For these two miRNAs, the stratifi cation of breast cancer patients versus controls was confirmed by receiver operating characteristic curve analyses. In addition, we showed that higher levels of serum miR-10b-5p were associated with clinicobiological markers of poor prognosis.
Conclusions: Th e study revealed the usefulness of the ddPCR approach for the quantification of circulating miRNAas.The use of the ddPCR quantitative approach revealed very good agreement between two independent cohorts in terms of comparable absolute miRNA concentrations and consistent trends of dysregulation in breast cancer patients versus controls. Overall, this study supports the use of the quantitative ddPCR approach for monitoring the absolute levels of diagnostic and prognostic tumor-specific circulating miRNAs.

 

Maimoona Sabir

University of Haripur, Pakistan

Title: Association of human papilloma virus with head and neck cancer patients from Khyber Pakhtunkhwa, Pakistan
Speaker
Biography:

Maimoona Sabir has completed her PhD from the Department of Biosciences, COMSATS, Institute of Information Technolgy, Islamabad, Pakistan. She is currently working as Assistant Professor in the Department of Microbiology, University of Haripur, KP, Pakistan. She has published more than 15 reserach papers in reputed journals. She has won grant from Higher Education Commssion of Pakistan for research work, “role of HPV in head and neck cancer in Pakistani population”.

Abstract:

Head and neck cancer (HNC) is the sixth most common cancer causing a high mortality rate worldwide. There are number of risk factors involved in head and neck cancer such as tobacco, alcohol, radiations, inhaling asbestos, wood dust, paint fumes and viruses. Most common virus involved in the subset of head and neck cancer is human Papilloma virus (HPV). Human papilloma virus is double stranded DNA virus which is about 8Kb surrounded by protein coat consisting of two proteins L1 and L2. Out of 100 diff erent types of HPV 15 are considered as highly pathogenic. HPV is divided into two major types; High risk HPV and Low risk HPV. In current study 150 HNC patients were screened for HPV genotyping and risk factors possibly associated with HNC. DNA was extrracted by standard phenol chloroform extraction method followed by HPV genotyping by polymerase chain reaction and agarose gel electrophoresis. In study, among the HNC aff ected individuals 81(54%) were HPV+ive and 69 (46%) HPV–ive. Statistically, no significant diff erence was observed between HPV+ive and HPV-ive. HNC cases in terms of gender. In terms of age group, statistically no significant diff erence was observed between two groups (age group >40, <40). With respect to anatomic site of head and neck cancer patients, highest number of HPV+iv was observed in oral cavity 51(63%) followed by pharynx 20(25%), larynx 7(8%) and hypopharynx 3(4%). Disease was more common among illiterate individuals with low socioeconomic status and trend of HPV+ive HNC cases have increaed from year 2011 to 2016. It can be concluded from the data that HPV infection can be the main risk factor for HNC cases in Pakistan. Further research is needed to elucidate the mechanism involved in HPV infection with head and neck carcinogenesis.

Maimoona Sabir

University of Haripur, Pakistan

Title: Association of human papilloma virus with head and neck cancer patients from Khyber Pakhtunkhwa, Pakistan
Biography:

Maimoona Sabir has completed her PhD from the Department of Biosciences, COMSATS, Institute of Information Technolgy, Islamabad, Pakistan. She is currently working as Assistant Professor in the Department of Microbiology, University of Haripur, KP, Pakistan. She has published more than 15 reserach papers in reputed journals. She has won grant from Higher Education Commssion of Pakistan for research work, “role of HPV in head and neck cancer in Pakistani population”.

Abstract:

Head and neck cancer (HNC) is the sixth most common cancer causing a high mortality rate worldwide. There are number of risk factors involved in head and neck cancer such as tobacco, alcohol, radiations, inhaling asbestos, wood dust, paint fumes and viruses. Most common virus involved in the subset of head and neck cancer is human Papilloma virus (HPV). Human papilloma virus is double stranded DNA virus which is about 8Kb surrounded by protein coat consisting of two proteins L1 and L2. Out of 100 diff erent types of HPV 15 are considered as highly pathogenic. HPV is divided into two major types; High risk HPV and Low risk HPV. In current study 150 HNC patients were screened for HPV genotyping and risk factors possibly associated with HNC. DNA was extrracted by standard phenol chloroform extraction method followed by HPV genotyping by polymerase chain reaction and agarose gel electrophoresis. In study, among the HNC aff ected individuals 81(54%) were HPV+ive and 69 (46%) HPV–ive. Statistically, no significant diff erence was observed between HPV+ive and HPV-ive. HNC cases in terms of gender. In terms of age group, statistically no significant diff erence was observed between two groups (age group >40, <40). With respect to anatomic site of head and neck cancer patients, highest number of HPV+iv was observed in oral cavity 51(63%) followed by pharynx 20(25%), larynx 7(8%) and hypopharynx 3(4%). Disease was more common among illiterate individuals with low socioeconomic status and trend of HPV+ive HNC cases have increaed from year 2011 to 2016. It can be concluded from the data that HPV infection can be the main risk factor for HNC cases in Pakistan. Further research is needed to elucidate the mechanism involved in HPV infection with head and neck carcinogenesis.