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Biography
Biography

Editor-in-Chief of OBM Hepatology and Gastroenterology

Osamu Yokosuka is an Emeritus Professor of Chiba University, Japan. He graduated from Chiba University School of Medicine in 1975 then worked as a trainee under Professor K. Okuda in Chiba University Hospital till 1978. Dr. Yokosuka was a research fellow worked under Professor S. Scherlock and Professor B. H. Billing in Royal Free Hospital, London, UK from 1978 to 1980; under Professor M. Omata in Chiba University from 1980 to 1985; and under Dr. J Summers in Fox Chase Cancer Center, PA, USA in 1984. In 1985, he received a Degree of Doctor of Medical Science, and served as an Assistant Professor in Chiba University till 1994, then as Lecturer in Medicine till 2006 when he was appointed as Director and Professor of Medicine. From 2013 to 2015, he served as the Dean of Chiba University School of Medicine.

Dr. Yokosuka was the Secretary General of APASL (2008-2014). In 2016, he was elected as the President of APASL Tokyo, the President of 52nd Annual Meeting of Japan Society of Hepatology, and the President of Funabashi Central Hospital. Dr. Yokosuka’s research mainly focuses on Hepatitis and Hepatocellular Carcinoma. So far, he has published more than 700 original papers.

Biography

The Associate Editor of OBM Hepatology and Gastroenterology

Tatsuo Kanda received a medical degree in 1991 at Niigata University School of Medicine, Japan, and his PhD in 1999 at Chiba University Graduate School of Medicine, Japan. He had post-doctor training for 3 years under Prof. Ratna Ray and Prof. Ranjit Ray at Saint Louis University, St. Louis, MO, USA. In Dec. 2008, Tatsuo Kanda became a Tenure-track Associate Professor at Department of Medicine and Clinical Oncology, Chiba University, Graduate School of Medicine, Japan. In Feb. 2013, Tatsuo Kanda was nominated a permanent Associate Professor at Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Japan. In 2017, Tatsuo Kanda became an Associate Professor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nihon University School of Medicine. For ~25 years, he has focused his scientific interests on the topics related to liver diseases including acute liver failure, viral hepatitis and autoimmune liver diseases, and worked with Prof. Osamu Yokosuka. Tatsuo Kanda is also an expert for hepatitis A virus (HAV), HBV and HCV, and translation and replication of these viruses, and hepatocarcinogenesis. With his expertise in antiviral therapies and hepatitis virus research, Tatsuo Kanda also sees a lot of patients in clinical daily practice. Tatsuo Kanda has published more than 200 articles in peer-reviewed Journal.

Special Issue

Genetic Heterogeneity in Cancer

Submission Deadline: November 30, 2018 (Open)               Submit Now

Guest Editor

Kakoli Das, PhD
Program in Cancer and Stem Cell Biology, Duke-NUS Medical School, 8 College Road, Singapore 169857
E-Mails: [email protected]; [email protected]
Website: https://www.duke-nus.edu.sg/cscb/content/kakoli-das
Research Interests: cancer genomics, molecular genetics, genetic heterogeneity, precision medicine

About This Topic

Genetic heterogeneity in cancer is defined as the occurrence of genetic variation between tumors (inter tumor) and/or within individual tumors (intra tumor) partly due to genomic instability. The genomic instability may arise due to increased mutation rates, chromosomal instability, and microsatellite instability, exposure to mutagens such as smoking, UV rays and radiation. Each of these causes may have a significant impact on cancer genomes resulting in diversity within a tumor that may lead to different clinical outcomes and response to therapies. Recent cancer genomic studies, based on approaches such as multi-region profiling or ultra-deep sequencing have revealed varying degrees of genetic heterogeneity in different tumor types.Understanding tumor heterogeneity has been highlighted as a critical area for translational cancer research.

In this special issue of OBM Genetics, we have chosen topics that highlight the causes and implications of genetic heterogeneity in cancer of different types, methods to identify genetic heterogeneity in cancer, tackling genetic heterogeneity and suggest treatment strategies. Overall, this issue provides a complete understanding of the genetic heterogeneity driven by genomic instability, ways to limit genetic heterogeneity and tackle drug resistance in cancer.

Planned Papers

Title: Active (Patient Specific) Immunotherapy of Adenocarcinomas can Prevent progression of Occult Disease In spite of Genomic Heterogeneity and May Provide a Natural Approach to Selection of Relevant, conserved Neoepitopes
Author: Michael G. Hanna Jr.
Affiliation: Founder and Chairman Emeritus, Vaccinogen Inc.
Abstract:
We present the conceptual and practical basis for Active (Patient specific) Immunotherapy vaccination success in preventing progression of occult disease. This personal treatment, involves the interaction of two known immune functions, antigen competition and immune editing. The result is a sculpting of the tumor from a diverse array of antigenic phenotypes, ranging from weak to strong antigens, to a restricted set of poorly immunogenic clones that can survive and kill an immunocompetent host due to immune tolerance. The personal immunization is administered by an intradermal vaccination with live tumor cells, resected surgery. The autologous tumor cells are admixed with a strong adjuvant capable of recruiting and trafficking large numbers of immunocompetent progenitor cells to the vaccination sites. This reaction cannot be achieved with tumor cells alone. This compounded immunization remarkably breaks immune tolerance and provides a robust immune reaction that consists of cytotoxic T cells and strong immunologic memory that lasts for years. The clinical result in the unmet medical need of stage II (T3 &T4 a&b) colon cancer, is a highly significant and durable recurrence free-survival. Also, the tumor specific immune response in these patients may provide biological resources (Human Monoclonal Antibodies) for naturally identifying mutation associated neoantigens and thus neoepitopes. These will foster research and development of other therapeutic and prophylactic adenocarcinoma vaccines.

Title: RNA editors and DNA mutators: cancer heterogeneity through sequence diversification
Authors: Rafael Tasakis 1, Nina Papavasiliou 1, Rita Shaknovich 2
Affiliations:
1. Helmholtz Professor and Head, Division of Immune Diversity, Deutsches Krebsforschungszentrum, German Cancer Research Center, Foundation under Public Law, Heidelberg, Germany
2. Cancer Genetics Inc, Rutherford, NJ

Title: Clonal heterogeneity in non-small cell lung cancer and the possible role in predicting response to treatment with immune checkpoint inhibitors
Authors: Annapaola Mariniello, Silvia Novello
Affiliation: Oncology Department of Oncology, AOU San Luigi, University of Turin, Italy
Abstract: Immune oncology treatment with immune checkpoint inhibitors (ICIs) is revolutionizing management of advanced non-small cell lung cancer (NSCLC) patients, in terms of longer survival and improved quality of life. To date, the only available biomarker of response is programmed death ligand 1 (PD-L1) expression on tumor cells, however it is considered not accurate and it is more likely that many factors, related to both cancer and host, may better predict response to ICI. Among those factors, great attention is being dedicated to tumor mutation burden, defined as the number of somatic non-synonymous mutations in cancer cells assessed with next-generation sequencing technologies. Moreover, recent evidences have shown that not only the quantity of tumor mutations but also their quality may influence response to treatment with ICI. In fact, it seems that clonal heterogeneity of cancer cells and of predicted neo-antigens may affect anticancer response in patients receiving ICI. Our aim would be to report and discuss the available evidences on this topic along with the techniques used to assess clonal heterogeneity as a biomarker that in future might help physicians to improve NSCLC patients’ selection for immune-oncology treatments.