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 1 :

Keynote Forum

Elena Gómez-Sanz

ETHZ, Switzerland

Keynote: Mobilome and resistome analysis of canine multidrug resistant methicillin-Resistant Staphylococcus sciuri strain C2865 and comparative genomics of S. sciuri species group

Time : 09:15-09:45

Conference Series World Biomarkers 2017 International Conference Keynote Speaker Elena Gómez-Sanz photo
Biography:

Elena Gómez-Sanz is an expert on staphylococcal antimicrobial resistance and currently focusses her research is on animal and environmental antimicrobial resistancefrom a one health perspective following next-generation approaches. She has participated in six national and international projects, and is currently Principal Investigator for the Swiss National Science Foundation NFP72 (“Antimicrobial Resistance”). She has developed her research career in Spain, UK, Germany, Australia and Switzerland, and has been awarded a number of grants and fellowships in competitive, merit-based calls from national and international organizations. She has participated in more than 40 scientifi c publications and contributed with 75 presentations in international and national conferences. She participates as reviewer for several scientifi c editorials and is Member of several scientifi c societies. Since December 2016, she is a Postdoctoral Fellow at the Swiss Federal Institute of Technology Zurich (ETHZ).

Abstract:

Statement of the Problem: Antibiotic resistance is one of the biggest threats to global health, food security, and development today. Staphylococci are common member of our skin and mucosa, but they are also a common cause of severe infections and resistance to fi rst line antimicrobial to treat their infections is widespread. Here, a multidrug- and methicillin-resistant Staphylococcus sciuri strain C2865 (canine nasal sample, Nigeria) showed trimethoprim resistance for which all staphylococcal dfr genes were negative. Th is strain was subjected to whole-genome-sequencing (WGS) for resistome and mobilome profi ling and to comparative genomics with all NCBI-deposited S. sciuri species group genomes for diversity analysis.
Methodology & Th eoretical Orientation: Illumina Miseq was used for C2865 WGS and in-house pipelines (SPAdes, Prodigal, tRNAscan-SE, RNAmmer, NCBI NR, COG, TIGRfam, RAST, ISsaga2) were followed for data processing and analysis. Plasmid contigs identifi cation and plasmids reconstruction were achieved by contig coverage, sequence similarity and composition. PCR plus sequencing was done for scaff olding regions of interest. Average Nucleotide Identity (ANI) between all 22 available S. sciuri group strains and comparative and pangenome analysis of S. sciuri group strains was calculated using J Species progressive mauve, clonal frame and roary, respectively.
Findings: S. sciuri C2865 revealed 2,937,715 bp in size, a GC content of 32.7%, and 3316 CDSs, with 1887 genes categorized into COG functional groups. Two small resistance plasmids and two novel mobilizable plasmids were reconstructed. p2865-3, a multidrug resistance plasmid, revealed a trimethoprim resistance gene described for the fi rst time in marine Exiguobacterium (order Bacillales). p2865-4 carried the intercellular adhesion gene cluster involved in biofi lm formation. A novel staphylococcal cassette chromosome (SCCmec) was identifi ed. Additional chromosomal resistance genes (antibiotic, metal, biocide) and mobile genetic elements (MGEs) were detected. C2865 shared highest ID with S. sciuri Z8 and SNUDS-18 (99-98%), comprising a diff erent branch within the species. WG alignment among all S. sciuri genomes revealed a core genome of 1.7 Mb (60.7%). Synteny was preserved among these genomes while there were several genomic islands with distinct gene content.
Conclusion & Significance: Several novel MGEs are detected revealing, among others, a novel dfr gene conferring thrimethoprim
resistance not only in S. sciuri but also in an environmental species. 2) WGS reveals a trustful tool to identify and characterize novel and already known resistance & virulence determinants and MGEs. 3) Comparative genomics shows high S. sciuri intraspecies diversity and high genome plasticity. 4) Commensal staphylococci represent a reservoir for mobilizable AMR & virulence determinants.

Keynote Forum

Topolcan Ondrej

Charles University, Czech Republic

Keynote: Biomarkers and liver cancer process

Time : 09:45-10:15

Conference Series World Biomarkers 2017 International Conference Keynote Speaker Topolcan Ondrej photo
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 was Head of Imunoanalytic Laboratory in 2000. He is a Member of Scientific Committee Endocrinology Institute Prague and 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:

The use of biomarkers in primary liver cancer and metastatic cancer will be presented. Both diagnoses have improved in prognosis and overall survival. The early diagnostics and the aggressiveness estimation have been essential for the successful surgical therapy. But both processes may require the individual and diff erent approaches and regarding to the primary liver cancer it seems to be important to identify the risk group of patients to involve in screening programs. Metastatic liver process will require the optimal follow-up proposal particularly in colorectal and breast cancer in order to make a good decision to perform the surgery resection instead of palliative therapy (Radiofrequency ablation RFA) or chemotherapy. It was confirmed that biomarkers combination of AFP and CA19-9 is appropriate for primary hepatocellular carcinoma diagnosis, in some cases using also cytokeratins, but CEA assessment provided no more benefits. PIVKA and some new procollagens seem to be challenging for this diagnostic process and no biomarkers for routine practice in metastatic liver carcinoma have been performed so far. Based on our long term systematic monitoring we can conclude that using biomarkers seems to be beneficial both for diagnostics and prognosis estimation. Th e highest sensitivity was achieved for cytokeratins (up to 88%), CEA (around 70%) and very low sensitivity was found for CA 19-9. AFP was not commonly elevated and it seems to be useless to assess it. Biomarkers assessment means for the patient: early diagnostics of cancer project; imaging techniques reduction; prognosis estimation and optimal proposal for therapy procedure and optimal follow-up an optimal complex of biomarkers monitored.

  • 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.