7^th International Conference and Expo on Molecular & Cancer Biomarkers September 15-16, 2016 Berlin, Germany

Biography:

Guoxiong Xu is a Professor of Oncology, Scientist and Director of Center Laboratory in Jinshan Hospital, Fudan University, China. He obtained a MD from the Faculty of Medicine, Shanghai Second Medical University in China, a Master’s degree in Medical and Pharmaceutical Research from the Free University of Brussels in Belgium and a PhD degree from York University in Canada. He has worked as a Clinician and Research Scientist at various universities and institutes. He has published more than 50 papers in peer-reviewed journals and has been serving as a Member of the Editorial Board in many scientific journals.

Abstract:

Human epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy in women. It is highly lethal because of being an advanced stage upon diagnosis. Despite the improvement of treatment during last two decades, overall survival of patient with ovarian cancer at the advanced stage has not been enhanced significantly. Therefore gaining biomarkers of early detection at an early curable stage and understanding how the EOC develops, are most important. Using proteomics, tissue microarray, immunohistochemistry and ELISA, several potential epithelial-type ovarian tumor progression markers were identified. The association of these tumor progression markers with clinicopathological features was further analyzed. We found that several proteins were differentially expressed between normal ovarian tissue and ovarian surface epithelial benign, borderline and malignant tumors, including serous, mucinous and clear cell tumors. Using loss-of-function approach, we found that these molecules were involved in EOC cell proliferation, migration and invation. We also demonstrated that these molecules were regulated by the TGF-β signaling pathway. Furthermore, some of these biomarkers affected tumor formation in nude mice. Thus, the identification of tumor markers as novel EOC-related proteins may implicate for understanding tumorigenesis and provide a diagnostic tool and better therapeutic strategy.

Biography:

Irina Velikyan is an Associate Professor in Biomedical Radiation Sciences, Uppsala University, and a Senior Scientist at PET Centre, Uppsala University Hospital, Sweden. Born in Yerevan, Armenia, she graduated from Yerevan State University (MSc, 1988). She received her PhD from Uppsala University (2005). The focus of her scientific activity is development and clinical implementation of positron emission tomography radiopharmaceuticals for molecular diagnostic imaging and quantification as well as bridging molecular imaging and therapy for personalized patient treatment.
 

Abstract:

The development of a personalized approach in healthcare is motivated by the call for improved efficiency, safety, and quality of treatment. Early diagnosis plays an important role and is one of the major factors that reduces the mortality and cancer management costs. The remarkable achievements in genomics, proteomics, and biotechnology have contributed drastically to the emergence of individualized diagnosis and therapy on molecular level. High-resolution molecular imaging is one of the fastest growing imaging procedures worldwide and is considered as a major breakthrough that strongly contributes to the realization of personalized medicine. Nuclear medicine includes such technology as positron emission tomography (PET) that utilizes positron emitting radionuclides and ligands towards various biomarkers for the generation of a signal that results in a whole-body scan in a single examination. PET provides fast and noninvasive real-time evaluation of physiology and pathology, and together with external and internal radiotherapy merge into theranostics of personalized medicine. Theranostics in its broader meaning embraces diagnostic methods conducted for the prediction of the efficacy of specific therapeutic interventions on an individual basis as well as for monitoring the response to the treatment. The clinical value of molecular imaging diagnostics is greatly elevated by its improved accuracy and safety as compared to biopsy with regard to discrimination of the heterogeneity of a primary tumor and between a primary tumor and metastases. The selection of the molecular biomarkers and development of the respective positron emitting imaging agents is the core of PET diagnostic method. Imaging agents targeted to biomarkers specifically expressed in particular diseases are of strong interest. Clinical imaging and quantification of neuroendocrine tumors and breast cancer lesions as well as the impact on the therapeutic patient management will be presented in this talk.   

Biography:

Wancai Yang is a Professor of Pathology and Dean of the School of Basic Medical Sciences and Institue of Precision Medicine, Jining Medical University, China; and an Adjunct Professor of University of Illinois at Chicago, Chicago, Illinois, USA. He was trained as a Pathologist in China and received Post-doctoral training in Rockefeller University and Albert Einstein Cancer Center, New York, USA. He has published more than 80 papers in high-impact journals about his research on colorectal and esophageal cancers. He has also been serving as Grant Reviewer, Article Reviewer and Editorial Board Members of reputed journals.

Abstract:

Besides the canonical and non-canonical Wnt pathway to colorectal cancer, chronic colitis is strongly associated with colorectal cancer formation. However, the mechanisms of colitis develops and how chronic colitis progress to malignance is not clear.  To determine the mechanisms of the malignant transformation, we conducted miRNA array on the colonic epithelial cells from the 3-month Muc2-/- and +/+ mice. MicroRNA profiling showed differential expression of miRNAs (i.e. lower or higher expression enrichments) in Muc2-/- mice. Based on relevance to cytokines and cancer, some miRNAs were validate and were found significantly downregulated in human colitis and colorectal cancer tissues. Using a unique mouse model, we have demonstrated that the mice with targeted disruption of the intestinal mucin gene Muc2 spontaneously develop chronic inflammation at colon and rectum at early age, whose histopathology was similar to ulcerative colitis in human. After 3 months of age, the Muc2-/- mice develop colonic and rectal adenocarcinoma accompanying severe inflammation. We further characterized one of the most changed miRNA – miR-27a. We found that miR-27a was significantly reduced in colorectal cancer tissues and colorectal cancer cell lines, and that the reduced miR-27a was associated with distant metastasis and colorectal cancer clinical pathological stages. Functional studies showed that increasing miR-27a inhibited colon cancer cell proliferation, promoted apoptosis and attenuated cell migration, which were also linked to downregulation of p-STAT3 and upregulation of cleaved caspase 3. In vivo, miR-27a inhibited colon cancer cell growth in tumor-bearing mice. Bioinformatic and systemic biological analysis predicted several targets of miR-27a, among them SGPP1 and Smad2 were significantly affected, and interestedly, miRNA-associated cytokines were also significantly increased in Muc2-/-mice. SGPP1 and Smad2 were negatively correlated with miR-27a in human colorectal cancer tissues and cancer cell lines. More studies from the Muc2-/- mice showed disorder of gut microbiota. The disorder of gut microbiota could result in genetic mutations, epigenetic alterations, and activation of oncogenic signaling, in colorectal epithelial cells, leading to colitis development, promoting malignant transformation and mediating colorectal cancer metastasis. 

Biography:

Feng Yan is the Vice Director of Department of Clinical Laboratory in Nanjing Medical University Cancer Hospital & Jiangsu Cancer Hospital. The research works focus on the bioanalytical chemistry in laboratory medical diagnostics. She has published more than 42 papers in reputed journals.

Abstract:

The UHRF1 protein is pivotal for DNA methylation and heterochromatin formation, leading to decreased expressions of tumor suppressor genes and contributing to tumorigenesis. However, the factors that modulate UHRF1 expression in colorectal cancer (CRC) remain unclear. Here we showed that, compared with corresponding normal tissues, UHRF1 was upregulated and microRNA-9 (miR-9) was downregulated in CRC tissues. The expression of UHRF1 was inversely correlated with overall survival rates of patients with CRC. Overexpression of miR-9 in CRC cell lines significantly attenuated CRC cell proliferation and promoted cell apoptosis. The expression of UHRF1 was markedly reduced in pre-miR-9 transfected CRC cells.  Using  luciferase  reporter  assay,  we  confirmed  that  miR-9  was  a  direct upstream  regulator  of  UHRF1.  Finally,  analysis  of  miR-9  and  UHRF1  levels  in human  CRC  tissues  revealed  that  expression  of  miR-9  was  inversely  correlated with UHRF1 expression. Collectively, our results offer in vitro validation of the concept  that  miR-9  could  repress  the  expression  of  UHRF1,  and  function  as  a tumor-suppressive microRNA in CRC. It may serve as a prognostic and therapeutic marker for CRC for diagnosis and a gene target for therapy. 

Biography:

Husham Y M Ali Bayazed has completed his PhD from University of Mosul, College of Medicine. He is now Consultant at the Scientific Research Center, University of Zakho / Kurdistan Region, Iraq. He is specialist in immunology and has published more than 25 papers in reputed journals and has been serving as Scientific Reviewer of many local and international medical journals. He has membership of World Stroke Organization, Membership of Metabolomics (USA) and Membership of American Association of Science & Technology.

Abstract:

Objective: The present study was performed to assess the immune response in women with HPV DNA positive and negative cervical lesions.

Methods & Patients: Eighty women with cervical lesions (age range of 25-70 years) were studied. The lesions were cytologically classified into 4 groups: ASC-US (20), CINI (30), CINII-III (16), and cervical carcinoma (14), prior to HPV DNA detection. Estimation of IL-10 and TNF-α cytokines was performed via enzyme linked immunosorrbent assay (ELISA) technique in cervical secretions and serum and PCR screening kits were utilized to detect HPV DNA on cervical smears.

Results: The detected levels of IL-10 (mean±SE) concentration in cervical secretions of patients with HPV DNA positive and negative states and control group were 88.73±16.90 pg/ml, 24.00±2.84 pg/ml and 8.27±0.59 pg/ml respectively with significant differences (p<0.05), while levels of TNF-α in cervical secretion of the studied groups were 12.18±3.49 pg/ml, 9.90±0.73 pg/ml and 7.90±0.87 pg/ml respectively with non significant differences. The detected levels of IL-10 in cervical secretions of HPV DNA positive cases (88.73±16.90 pg/ml) were significantly higher than in the sera (13.69±2.41 pg/ml) (p<0.05), while the levels of TNF-α in their cervical secretions (12.18±3.49 pg/ml) was slightly raised than in their sera (11.5 9±3.14 pg/ml) with non significance differences.

Conclusions: A raised levels of both IL-10 and TNF-α in secretions of HPV DNA positive women with different cervical lesions were detected. However, the observed higher levels of IL-10 than TNF-α indicate down-modulation of tumor-specific immune response to HPV infected lesions via significant raised concentrations of the first cytokine than the second one. Therefore, this phenomenon seems to provide a tumor progressive microenvironment by the immunosuppressant properties of IL-10 with minimal antitumor activity of TNF-α. 

Biography:

N Y Gbandjaba has completed his PhD in Biochemistry from Hassan II­University­ Casablanca Morocco in 2013. As a student, he develops a good collaboration with Sherbrooke University, Research Centre on Ageing, Sherbrooke (QC), Canada and the International Pasteur Institute of Morocco. In 2009, he won a grant from the IRSC to accomplish his Doctoral thesis in the Research Centre on Ageing. He is also called the Whistle Blower. His research focuses on the development of oxidative stress biomarkers involved in cardiovascular diseases related to successful ageing. He has more than 5 articles in reputed journals, 16 lectures, 32 posters and having won PASRES Prize in 2016. 

Abstract:

Paraoxonase1 (PON1) expressed in the Islets of Langerhans is an antioxidant high density lipoprotein bound enzyme. We investigate the Paraoxonase 1 phenotype distribution and we measure oxidative stress biomarkers (Vitamin E/CT, MDA) in healthy, diabetic and hemodialysis patients. Three hundred subjects (healthy, diabetic and chronic renal failure patients) aged between 40 and 80 years were recruited for the study (divided in three groups of 100 subjects each). Total MDA content in plasma was measured by HPLC with thiobarbituric acid (TBA) and with fluorescence detection. Vitamin E (α-tocopherol) as the principal plasma antioxidant was also measured by HPLC with electrochemical detection. We observe that, Vitamin E-Tot. Chol ratio increases significantly with age in diabetic patients (r= 0.30; p <0.01). The plasma Vitamin E - Total Cholesterol ratio decreases significantly with age in hemodialysis patients (r = -0.17; p<0.05) and in healthy subjects (r = -0.15; p=0.44). Plasma MDA concentration increases with age in diabetic patients (r = 0.09; p=0.15). The distribution of PON 1 phenotype in healthy, diabetic and hemodialysis patients was as follows: AA 79.31%, 75.00% and 69.31%; AB 14.94%, 19.04% and 20.45%; BB 5.74%, 5.95% and 10.22%. Adjusted odds ratio comparing the AA variant with the BB variant were 1.97 [95% confidence interval (CI): 0.63-6.21] in hemodialysis patients. In diabetic patients, the adjusted odds ratio comparing the AA variant with the AB variant of PON1 were 1.37 [95% CI: 0.62-3.04]. Our studies show that PON1 phenotype distribution and oxidative stress markers are associated with cardiovascular diseases risk in healthy, diabetic and hemodialysis patients.

Biography:

Hing Leung Eric Lee has completed his PhD in 2013 from Clemson University. He is currently a Post-doctoral Associate in Fox Chase Cancer Center. His research focuses on different regulatory partners in the sonic hedgehog pathway. Currently he is working on the regulatory and functional role of Nestin and different factors in the stem cell niche. 

Abstract:

The transcriptional activation by sonic hedgehog signaling (SHH) depends on the Gli family of transcription factors. Among the Gli proteins, Gli3 regulates shh signaling by either serving as transcriptional activators or being phosphorylated and process into truncated transcriptional repressors. In this study, we show that nestin, a type VI intermediate filament protein, plays a regulatory role in Gli3 processing in medulloblastoma tumorigenesis. We found that overexpression of nestin resulted in minimal Gli3 processing, conversely, Gli3 processing is dramatically increased with the loss of nestin. Our results demonstrate that binding of nestin to Gli3 blocks Gli3 phosphorylation and its subsequent proteolytic processing. Furthermore, deletion of nestin in medulloblastoma cells inhibited cell proliferation. These data suggest that nestin serves as a regulator by overcoming negative regulation of shh pathway, a pathway that plays important roles in both development and cancer. 

Biography:

Devika Agarwal  is a final year Postdoctorate student at the John van Geest Cancer Research, Notitngham Trent Univeristy, UK. Her thesis title is “Systems biology approaches for the identification of molecular characteristics of proliferation in breast cancer”.  She has co-authoured 17 papers with collaborating institutes in reputable journals.

Abstract:

Despite immense success in the diagnosis and treatment of  breast cancer (BC), effective delivery of personalised medicine is needed. This requires the discovery of novel therapeutic targets in subgroups of BC and improvements in treatment efficiency by identifying biomarkers that can predict an individuals response to therapy.  Although chemotherapy is offered in combination with other targeted therapies to 60% of BC patients, it reduces recurrence and mortality rates by only 30%. Given that all the prognostic power of majority of  commercial gene assays for guiding therapy comes from genes related to cell proliferation, a St Gallens Expert consensus have recommended the use of proliferation markers/gene assays when choosing an optimal systemic treatment. However, the decision for the the best molecular test/marker to be used continues to be debated. The use of novel non-linear computational approaches with sufficient power are urgently needed to identify biomarkers with high specificity and sensitivity. An aritificial neural network based integrative data mining approach was  applied to multiple BC gene expressions studies (n=2000), using factors (e.g. Grade) that are associated with proliferation as clinical class questions and individual genes as predictors.  This analysis identified the marker SPAG5 , among the 30 most common genes for the top 100 ranked genes for the proliferation factors across the datasets. Further clinical validation in excess of 10,000 patients revealed amplication of SPAG5 in 10-20% of BC , SPAG5 gene CNAs , mRNA and protein expression are associated with poor clinical outcome and predictors of response to chemotherapy. 

Biography:

Christian Tiede received his Doctorate in Antibody Engineering and Phage Display from the Charite Berlin. He joined Aptuscan (now Avacta) and set up the phage display technology based on the antibody alternative scaffold Stefin A. In 2011 he moved to the University of Leeds to establish the BioScreening Technology Group under Prof. Mike McPherson and Dr. Darren Tomlinson. He is now the Manager of the group.

Abstract:

Molecular recognition is key to understanding the basics of biological processes and is used globally by scientists to study protein expression and localisation. Antibodies are the tools of choice for molecular recognition, yet their performance, validation and batch-to-batch variation often hinders research and diagnostics. Antibody-mimetic reagents provide alternative tools that address these issues. Antibody-mimetics are protein scaffolds that constrain variable peptide regions that serve as molecular recognition motifs. Here, we will discuss the development of an antibody-mimetic named Affimer and the bioscreening of target proteins, peptides, chemical compounds as well as more complex samples such as cells or biofluids. We have generated a large phage display library up to 2.3x10E10 based on Affimers, proved to be capable in selecting highly specific Affimers against a number of known biomarkers such as toxin A and toxin B of Clostridium difficile. Furthermore, we have recently shown the selection of highly specific Affimers to breast cancer cells. We hypothesize that our phage display library can also be used to identify novel biomarkers in biofluids or tissue samples. In my presentation I will give examples of how Affimers can be used in biomarker applications.

Biography:

Amr Al-Haidari is a senior PhD student at Lund University. His research interest is focused on cancer and translational cancer research, molecular medicine, and cancer metastasis research. He has published 2 peer-reviwed papers in reputed journals and has 2 on the way of submission. He is an active scientific cancer research blogger on web. Beside his PhD work, he is also the head of PhDlive group aimed at supporting newly arrived PhD students at faculty of medicine Lund University.  
 

Abstract:

Colorectal cancer is one of the most commonly diagnosed cancers worldwide and most of death-related cases are due to metastasis. It is becoming interestingly obvious that mciroRNAs play a pivotal role in the tumorgenesis of different tumors including colon cancer. MiR-155 has been shown to regulate key proteins involved in the metastasis process. In our present study, we shed the light on the regulation mechanism of chemokine-induced colon cancer cell migration by miR-155 in serum starved HT-29 colon cancer cells. MiR-155-5p knockdown experiments using antagomiR-155-5p decreased HT-29 CCL17-induced colon cancer cells migration. Using GLISA assays, knocking down miR-155-5p demonstrated significant inhibition of CCL17-induced activation of RhoA suggesting that RhoA could be a potential target for miR-155-5p in HT-29 colon cancer cells. Bioinformatics analysis predicted a putative binding AU-rich elements regulatory site in 3´-UTR of RhoA. MiR-155-5p:RhoA binding was verified using target site blockers and functionally validated using RIP assays indicating that RhoA-positive regulation is mediated by the AU-rich elements present 3´-UTR of RhoA mRNA. These results showed that miR-155-5p positively regulates RhoA in starved HT-29 colon cancer cells and inhibiting miR-155-5p could be a useful strategy to antagonize colon cancer metastasis.

Biography:

Bobbie Jo M Webb Robertson has a MS in Statistics and Operations Research and PhD in Decision Sciences and Engineering Systems from Rensselaer Polytechnic Institute. She leads a research portfolio in statistical and software development for high-throughput proteomic analyses with over 75 peer-reviewed publications in the field. In addition, she is currently the Technical Group Manager of the Applied Statistics and Computational Modeling Group at Pacific Northwest National Laboratory.

Abstract:

For the field of clinical proteomics to successfully identify new prognostics or diagnostics of disease or response to therapies requires not only requires high quality data with respect to the instrument, but also high quality statistical analysis of the data. However, one of the major challenges to the discovery of robust cancer biomarker candidates from global shotgun mass spectrometry (MS)-based proteomic experiments is processing these large and complex datasets in a manner that accounts for the underlying statistical hypothesis of interest. P-Mart is a new interactive web-based software environment that enables biomedical and biological scientists to perform in-depth analyses of global proteomics data without requiring knowledge of processing raw mass spectra or complex matrices of peptide abundances. P- Mart offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification and exploratory data analyses. Currently, P-Mart offers access to multiple cancer proteomic datasets generated through the clinical proteomics tumor analysis consortium (CPTAC) at the peptide, gene and protein levels. Analyses are performed in P-Mart via customized workflows and interactive visualizations. P-Mart is funded through the National Cancer Institute’s Informatics Technology for Cancer Research (ITCR) program under grant U01-CA184738-01. 

Biography:

Andreas Scherer has been working in biomarker R&D in various roles in academia and industry for the past 17 years. Currently, he is Finland’s National Coordinator for EATRIS, the European Research Infrastructrue for Translational Medicine, and serves as Co-Chair of the EATRIS Biomarker Platform. He also has a role as Biomarker and Molecular Diagnostics Project Coordinator at the Institute for Molecular Medicine Finland (FIMM), University of Helsinki. Since 2007, he has been Consultant for omics-based biomarker development in his own company, Spheromics.

Abstract:

Valid biomarkers are in high demand for drug development, playing an increasingly important role in clinical applications to support and enable e.g. patient stratification, drug selectivity and prediction of toxicity. Individual investigators are not always aware of the complexity of the steps from translating fundamental research findings to clinical applicability, thus facing an immense failure rate due to mostly irreproducible data, e.g. in the area of biomarker research. Efforts by individual groups to publish confirmatory datasets exist but are rare, maybe exemplified by some of our own research on biomarkers in clear cell renal cell carcinoma. However, clinical relevance of such data can only be tested by using large sample numbers and efforts by large teams of investigators. The European Research Infrastructure for Translational Medicine EATRIS is a distributed consortium with currently 80 academic centers in 11 European countries which supports translational medical research towards clinical applications. According to EATRIS’ vision to increase awareness of the challenges of translation from fundamental research to clinical application among investigators, we believe that international and global research scale can provide validatable insights into clinical biomarkers and other technologies, impacting clinical care worldwide. EATRIS currently establishes collaborations of global scale to develop strategic plans to reveal sources of irreproducibility in the pre-clinical space including the biomarker field, thus reducing the high attrition rate of drug development pipelines and identifying opportunities for data quality improvement, ultimately for the benefit of human healthcare. 

Biography:

Martin Kleinschmidt has received his PhD in 2004 from the Martin-Luther-University Halle-Wittenberg. At the Probiodrug AG, he was responsible for biophysical characterization of interactions by SPR, ITC and X-ray structure analysis. Later he was the Project Manager for assay development. In 2013 he changed over to Fraunhofer IZI-MWT and is now Head of lab clinical and biophysical analytics. He has published 17 papers in well-known journals and is currently Associated Editor for the Journal of Alzheimer’s Disease.

Abstract:

Current treatment of Alzheimer’s disease (AD) is initiated at stages where the brain has irrevocably lost numerous neurons. Simple biochemical tests to differentiate normal aging from prodromal or demented stages are needed. Current standards identifying preclinical AD are neuroimaging and cerebrospinal fluid (CSF) analysis, but these methods are more cost-effective and more invasive than blood-based biomarker assays. However; in contrast to the approved methods quantifying the AD biomarker amyloid β (Aβ), Tau and P-Tau in CSF, detection of these biomarkers in blood is much more difficult due to at least 10-fold lower concentrations, but the 100-fold higher overall protein content leading to massive interference in currently used assay systems. Therefore, an assay was developed isolating Aβ by a multivalent capture system which exploits avidity effects by interactions of several anti-Aβ antibodies to multiple epitopes of the Aβ molecule. In our study, all participants were classified by a comprehensive neuropsychological assessment into controls, mild cognitive impairment (MCI), and AD. Blood samples were analyzed for several Aβ species, pro-inflammatory markers, anti-Aβ autoantibodies, and ApoE allele status, respectively. Plasma Aβ(1-42) was significantly decreased in MCI and AD compared to controls and strongly correlates with carrying ApoE ε4 allele. Furthermore, the Aβ(1-42)/Aβ(1-40) ratio is stepwise decreased in controls, MCI and AD, differentiating these groups significantly. Autoantibodies against pyroglutamate-modified Aβ (pGlu-Aβ), but not unmodified Aβ, were significantly decreased in AD compared to MCI and controls. Interestingly, the autoantibodies don’t correlate with ApoE ε4, supporting the associated plasma Aβ analysis with additional and independent information.

Biography:

Josephine Worseck is the Head of Business Development at Metabolomic Discoveries and has a scientific background in the field of systems biology. Her research at the Max Planck Institute for Molecular Genetics has been focused on the integrative analysis of data derived from high-throughput ‘omics technologies. After six years of applied science, she is now responsible for the consulting of scientists that want to resolve complex biological questions by metabolomics.
 

Abstract:

The Kenkodo Kit -offered by the German biotech company Metabolomic Discoveries- reveals exciting insights into the relationship between lifestyle and biochemical blood composition. Kenkodo is the first personalized metabolism analysis that combines personal lifestyle data with cutting-edge blood analytics. Users benefit from an easy and convenient blood sampling at home and insights that help to optimize well-being and to avoid diseases. The Kenkodo companion app integrates, tracks and visualizes the impact of human lifestyle in relationship to their metabolism with the aim to improve personal health outcomes. Metabolomic Discoveries GmbH is a leading company in the field of diagnostic biomarker research. Using high-throughput GC/MS and LC/MS combined with bioinformatic methods, Metabolomic Discoveries identifies and quantifies endogenous metabolites in body fluid or tissue samples and develops them into powerful biomarkers. 

Biography:

Joon Kim has completed his BS and MS from Seoul National University, PhD in Biochemistry from the University of California at Berkeley and Postdoctoral study from Harvard Medical School. He is a Professor in the Division of Life Sciences, and the Director of Radiation Safety and Management Center, Korea University, Seoul, Korea. He has published more than 150 papers in reputed journals

Abstract:

Ribosomal protein S3 (rpS3) has been known as a genuine component of the 40S ribosomal small subunit. However, it has been recently discovered that it has multiple other extra-ribosomal functions in apoptosis, cell cycle control, DNA repair etc. It has a DNA repair endonuclease activity which is related with various cancers. Recently, we have discovered that this protein is secreted as a dimer after glycosylation in the ER. It is secreted only from various cancer cell lines but not in normal cells. We also confirmed that rpS3 is secreted more into media from the more invasive cancer cell lines. The secretion pathway turned out to be an ER-Golgi dependent pathway. We propose that secreted rpS3 could be used as a useful marker for cancer or cell invasiveness.

Biography:

Weimin Miao has obtained the Medical degree from Shanghai Second Military Medical Univeristy and has completed his PhD from Fudan University in China. He did his Post-doctoral studies from Harvard Medical School in US and McGill Univeristy in Canada. He used to work as an Assistant Professor in Univeristy of Tennessee. Currently he is Professor of Chinese Academy of Medical Sciences and Peking Union Medical College, a top medical research organization. He has published more than 50 papers in reputed journals. He also served as a Chief Scientist in VCANBIO company, developing advanced molecular diagnostic products for clinical use. 

Abstract:

Extensive studies conducted over the last two decades have identified recurrent genomic abnormalities as potential driving factors underlying a variety of cancers. With respect to biomarker detection, a series of innovative high-throughput molecular tests, such as array-based comparative genome hybridization (aCGH), single nucleotide polymorphism (SNP) arrays and next generation sequencing, have recently been developed and incorporated into routine clinical practice. However, although it is a classical low-throughput cytogenetic test, fluorescence in situ hybridization (FISH) does not show signs of fading; on the contrary, it plays an increasingly important role in detecting specific biomarkers in solid and hematologic neoplasms and has therefore become an indispensable part of the rapidly developing field of personalized medicine. For example, FISH has become gold standards for detecting cancer biomarkers, such as BCR-ABL1, PML-Rara, Her-2, EML4-ALK, BRAF, ROS1 and FGFR. Many of these FISH assays are actually the companion diagnostic tests directly involved in the targeted therapies and personalized medicine. Furthermore, FISH, especially quntitative multi-gene FISH has been increasingly used for molecular pathology subtyping, disease stratification, therapeutic guidance and prognosis evaluation. In this talk, I will summariz recent advances in FISH application for both de novo discovery and routine diagnosis for chromosomal rearrangements and amplification or deletion of genomic components that are associated with the pathogenesis of various hematopoietic and non-hematopoietic malignancies. I will also briefly review the recent developments in FISH methodology. Finally, I will introduce a new methodology-sequential FISH that we have developed recently for multi-gene analysis at the single-cell level. 

Biography:

Shashwati Basak serves as the Head and Sr. Lead Investigator of Clinical Genomics Group in Exploratory Clinical and Translational Research (ECTR), Biocon Bristol-Myers Squibb Research and Development Center (BBRC), Bangalore. She started the ECTR department in 2010 and played an instrumental role in setting up the Clinical Biomarkers laboratories at BBRC. Her current research interests involve assay development and qualification of Clinical Biomarkers, especially in Oncology and Immuno-oncology and its use in clinical trials, while collaborating with multiple internal teams and global stakeholders. Her other interests are to pursue exploratory and translational research to understand the underlying mechanisms of cancer. In her additional roles, she also provides leadership in Managing the regulatory paperwork and clinical sample logistics to handle global clinical trial sample shipments for BMS to support the clinical biomarker work. She obtained a PhD in Molecular and Cellular Biology from the Indian Institute of Science, Bangalore and studied DNA-protein interactions to decipher novel transcription activation mechanisms in prokaryotic model systems. She carried out Post-doctoral research from The Salk Institute for Biological Sciences, San Diego and Stanford School of Medicine, Palo Alto. Her research in these two places was focused on understanding the intriguing complexities of cancer signaling pathways. She worked as a Research Scientist in the Veterans Affairs Medical Center (VAMC), San Francisco on multiple projects involving translational research in Cancer. She has published her research work in numerous top peer-reviewed international journals such as Cell, Molecular Cell etc. She has also served as a Reviewer for many American Association of Cancer Research (AACR) Journals like Cancer Research and Clinical Cancer Research and written and obtained international grants.

Abstract:

Biomarkers have many significant applications in oncology, including diagnosis, prognosis, risk assessment, prediction of response to treatment and screening and monitoring progression of the disease. Further, cancer biomarkers play an important role during all phases of drug discovery and development and in guiding early decision in clinical trials. Real-time quantitative polymerase chain reaction (RT-qPCR) technology has become the method of choice for clinical biomarker detection and quantification since it is accurate, sensitive, fast and relatively cheaper than other available gene expression-based technologies. Although a thorough analytical and clinical biomarker assay validation is not required for discovery-phase work, as a drug progresses into preclinical and early-phase clinical studies, it becomes important to have more rigorously qualified biomarkers. A “fit-for purpose” assay development and validation to meet the clinical requirements plays a significant role in cancer biomarker quantification. Development and use of RT-qPCR technology for robust, accurate and reliable method is required for the “fit-for-purpose” biomarker assay qualification. Few important factors influencing assay performance such as sample matrix, sample preparation, experimental precision, reproducibility, sensitivity, specificity, dilution linearity and dynamic range and their impact on the assay outcome will be discussed. Based on these, we will put forth recommendations for consideration and optimization of qPCR-based clinical cancer biomarker assays by demonstrating a few examples. Lastly, a few representative case studies of safety/efficacy and pharmacodynamic cancer biomarkers will be discussed that exemplify enabling of early decision making in Oncology and Immuno-oncology clinical trials.

Biography:

Mohammad O Hoque is an Associate Professor of Otolaryngology-Head & Neck Surgery, Urology and Oncology at Johns Hopkins University School of Medicine. His major research interests includes: a) To understand molecular biologic basis of head and neck, lung and genitourinary cancer b) To develop and validate genetic and epigenetic approach for early cancer diagnosis, cancer risk assessment and cancer prognosis and c) To identify molecular alterations due to environmental exposures such as active smoking, passive smoking and arsenic. He has published over 95 papers in reputed journals and has been serving as an Editor and/or Editorial Board Member of several bio-medical journals.

Abstract:

Over 90% of bladder cancer in the western world present as urothelial carcinoma (UC), from which non-muscle invasive urothelial cancers (NMIBC) is the most common histology at presentation (around 75%). NMIBC is usually treated by trans-urethral resection of bladder tumor (TURBT) where 20% of patients will be cured, 70% will recur at least once every 5 years, and the remaining will progress to muscle-invasive disease with poor prognosis. Currently there are no well validated markers that can discern the tumors at the time of diagnosis that will recur/progress from those that will not. Moreover, conventional approaches are not ideal to predict risk of recurrence/progression. Hence, it is crucial to develop molecular markers that can predict recurrence/progression at the time of diagnosis and such markers will allow a more individualized therapy based on a patient’s risk. Furthermore, it would also be important to develop a test that could provide cost-effective, non-invasive monitoring for low-risk patients, while using a more active approach to identify high-risk cancers before they progress. By a candidate gene approach, we analyzed the promoter methylation (PM) of 8 genes genes (ARF, TIMP3, RAR-β2, NID2, CCNA1, AIM1, CALCA and CCND2) by quantitative methylation specific PCR (QMSP) in DNA of 17 non-recurrent and 19 recurrent noninvasive low grade papillary urothelial carcinoma (LGPUC) archival tissues. Among the genes tested, by establishing an empiric cutoff value, CCND2, CCNA1, NID2, and CALCA showed higher frequency of methylation in recurrent than in non-recurrent LGPUCC: CCND2 10/19 (53%) vs. 2/17 (12%) (p=0.014); CCNA1 11/19 (58%) vs. 4/17 (23.5%) (p=0.048); NID2 13/19 (68%) vs. 3/17 (18%) (p=0.003) and CALCA 10/19 (53%) vs. 4/17 (23.5%) (p=0.097), respectively. We further analyzed PM of CCND2, CCNA1, and CALCA in urine DNA from UC patients including LGPUC and controls. The frequency of CCND2, CCNA1 and CALCA was significantly higher (p<0.0001) in urine of UC cases [38/148 (26%), 50/73 (68%) and 94/148 (63.5%) respectively] than controls [0/56 (0%), 10/60 (17%) and 16/56 (28.5%), respectively)]. Most importantly we found any one of the 3 markers methylation positive in 25 out of 30 (83%) cytology negative LGPUC cases. We also explored the biological function of CCNA1 in UC. Prospective confirmatory studies are needed to develop a reliable tool for prediction of recurrence using primary LGUC tissues and/or urine.

Biography:

Masamichi Hayashi has completed his MD and PhD from Nagoya University, and Post-doctoral studies from Johns Hopkins University School of Medicine. Now he is an Assistant Professor of the Department of Gastroenterological Surgery 2, Nagoya University Hospital. He has published more than 20 papers in reputed journals, and he is also a General Surgeon of the hospital.

Abstract:

Oncologic evaluation of surgical margins has long depended on visible histologic diagnosis. Although intraoperative cytology or frozen section diagnosis directs surgery to be performed in a more adequate way, some histologic negative surgical margins still have genetic or epigenetic alterations associated with disease recurrence. This phenomenon may be partly explained by "field cancerization," which is characterized as the presence of clonally related cells with malignant potential containing one or more cancer-associated genetic or epigenetic alterations in the tumor-surrounding mucosal areas. Another issue linked to recurrence is undetected fully developed residual tumor cells especially at the deep surgical margins. Histologically undetected residual cancer cells may be left behind due to the "tumor budding" phenomenon, defined as a single cancer cell or a cluster of <5 cancer cells protruding into the stroma beyond the invasive front. These are hard to detect in intraoperative frozen samples by light microscopy, which depends on the identification of visible clusters of cells having the malignant phenotype. To overcome the problem, we developed the molecular surgical margin analysis using nitrocellulose sheet which can collect unvisible tiny cancerous cells on the surface of the surgical specimen. We also utilized rapid quantitative methylation specific PCR (QMSP) and digital QMSP. All included surgical samples were histopathologically margin-negative. Our data indicated the association of molecularly positive margin with postoperative locoregional recurrences. We applied the assay to Head and neck squamous cell carcinoma cases, and try to apply it to other gastroenterological cancers.

Biography:

Inmaculada Ibanez de Caceres has completed her PhD from Complutense University of Madrid, Spain; 6 years of Post-doctoral studies from Fox Chase cancer Center at Philadelphia, and IIB/CSIC, from the National Research Council, Spain. She coordinates the experimental therapies and biomarkers group at The Sanitary Research Institution IdiPAZ, and is the Director of the Cancer Epigenetics Group at University Hospital La Paz, Madrid. She has published more than 30 papers in reputed journals, is the main author of two patents based on biomarkers of clinical use, one of them already licensed and under exploitation, and has been serving as a Full Member representing her institution at the biomarkers platform form the European Infrastructure for Translational Medicine (EATRIS).

Abstract:

One of the major problems associated with the identification of biomarkers for clinical use, is the lack of validation in different cohorts of patients after publication in scientific journals. More than 50,000 manuscripts/year are currently estimated in this field, and only 18 candidates in recent decades have been studied further in clinical trials with cancer patients. Within the cancer markers, the predictive ones are most needed in order to help in the treatment election, as nowadays, the vast majority of tumors are still treated with the same conventional therapy of the last 20 years, characterized by its low specificity, high toxicity and lack of ability to discriminate between patients with different sensitivity. Platinum compounds, are the standard treatment of tumors with high incidence such as lung, ovary and colorectal, so finding markers able to discriminate differential response to its use would allow patient selection and optimizing the use of chemotherapy and associated health spending. My laboratory is focussed in the study of the epigenetic biomarkers that we have identified and published from previous research projects, expanding their use to other validation cohorts of patients with solid tumors treated with platinum, that could eventually benefit from its use. We are also working in the identification of novel biomarkers for therapy response election, first through exosomal content characterization, coming both, from resistant cells and circulating in the serum of cancer patients; and secondly, through the development of platinum-predictive artificial intelligence systems generated by the omics data "in vitro", "in silico" and from the health system patients. We validate our findings through different high sensitivity epigenetic methodologies of routine in the laboratory and establish functional assays to validate in all cases the association with the response to therapy.