Day 2 :
- Immunotherapy | Genetic Medicine
Location: Austria
Session Introduction
Walter Birchmeirm
Max Delbrueck Center for Molecular Medicine (MDC) in the Helmholtz Association, Germany
Title: Epigenetic mechanisms downstream of Wnt in carcinomas and cancer stem cells
Time : 9:00-9:40
Biography:
Walter Birchmeier is a graduate in biology of Zürich University in 1973. After postdoctoral years at Cornell University Ithaca, the Biocenter Basel, and the University of California at San Diego, he became laboratory head at the Max-Planck-Institute Tübingen in 1982 and full Professor at the University of Essen Medical School in 1988. He joined the Max-Delbrück-Center for Molecular Medicine in Berlin in 1993. He was Director of the Max-Delbrück-Center from 04/2004 to 12/2008 and is Professor at the Charité/Humboldt University Berlin. His major research interests have been the role of cell adhesion and signal transduction in development and tumor progression.
Abstract:
Head and neck squamous cell carcinomas (HNSCCs) of the upper airways, which also include salivary gland cancers, are the fifth frequent human malignancy. The most important risk factors for HNSCCs are smoking, excess alcohol consumption and infection by high-risk human papillomaviruses. Patients with advanced tumors exhibit high mortality due to lack of effective molecular therapies. We found in a mouse model of salivary glands squamous cell carcinoma with conditional beta-catenin gain-of-function mutation that a histone modifier, which induces H3K4me3, acts downstream of Wnt/beta-catenin signaling. Conditional ablation of the histone modifier gene prevented tumor formation, reduced proliferation and induced apoptosis. ChIP-seq revealed a genome-wide increase in the active histone mark H3K4me3 and chromatin opening in cancer stem cells (CSCs). Mutations by CRISPR/Cas9 of the histone modifier at the β-catenin-, Menin-, Brd4-, and Wdr5-binding and Set-H3K4me3 enzymatic sites in mice strongly reduced CSC self-renewal. Pharmacological interference that disrupted these interactions also strongly reduced the self-renewal of mouse and human CSCs. We thus identified an essential downstream layer downstream of Wnt/beta-catenin, which are H3K4me3 and opening of chromatin that are essential in HNSCC formation. Targeting the histone modifier and its interactions with small interfering molecules allow promising new therapies for head and neck squamous cell carcinomas.
Zhengping Liu
Maternal & Child Health Hospital of Foshan - Southern Medical University, China
Title: Mesenchymal stem cells in the treatment for caesarean section skin scars
Time : 9:40-10:20
Biography:
Zhengping Liu is an Obstetrician. He completed his MD from the Second Military Medical University in 1993. Currently, he is a Professor and Director of the Department of Obstetrics, Southern Medical University affiliated Maternal & Child Health Hospital of Foshan, and the Deputy Director of the Foshan Institute of Fetal Medicine. His research interests include placenta previa and abnormally invasive placenta, fetal in utero treatment, and regenerative medicine and stem cell clinical therapy. More than 30 articles reflect his research in reputed journals and has been serving as an Editorial Board Member of repute. He is the pioneer of fetal surgery therapy in utero in China, and has extensive collaborations with The Children’s Hospital of Philadelphia. So far, he already performed dozens of clinical participants with stem cells during the past year.
Abstract:
Ceasarean delivery has already become a very common way of delivery around the world, especially in low-income countries. Hypertrophic scars and wound infections have affected younger mothers and frustrated obstetricians for a long time. Previous studies have demonstrated that MSCs are involved in enhancing diabetic wound healing. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the caesarean section skin scars. This trial is a prospective, randomized, double-blind, placebo-controlled, single-center trial with three parallel groups. Eligible participants are randomly allocated to placebo, low-dose (3×106 cells transdermal hydrogel MSCs) or high-dose group (6×106 cells transdermal hydrogel MSCs), once a day for consecutive six days. Study duration is 6 months. The primary outcome of this trial is to evaluate the change of Vancouver scar scale during the 6 months. Adverse events, including severe and slight signs and symptoms, are documented in case report form. The study is conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan. The first participant was recruited on September 14th, 2016. We hope to complete enrolment for the trial by September 2017 with all 6-month follow-up data expected by March 2018. This trial is the first investigation of the potential for therapeutic use of MSCs for the management of women’s skin scar after cesarean delivery. The results will give us an effective therapeutic strategy to combat caesarean section skin scars, even in the uterine scar.
Ganapathi Bhat Mugulthimole
Jaslok Hospital and Research Centre, India
Title: Frontier of hope and despair-immunobiology of Allogenic Hematopoietic Stem Cell Transplant
Time : 10:50-11:30
Biography:
Ganapathi Bhat Mugulthimoole is Senior Consultant Medical Oncologist & Stem cell transplant Physician at Jaslok Hospital & Research Centre Since 2006. He gained specialized training in stem cell transplantation as part of the ESH-EBMT (2007), 2011(Labaule, France) and ICAS training program (2009) from ULM University, Germany. He is also a member of academic organizations namely ESMO, IELSHG, EHA, Asia Pacific Bone Marrow Transplant and an Affiliate of American Association for Cancer Research and BITs Congress Tank. He served on the board of teaching faculty (Kuwait) for MRCP (Pathology & Haematology). He is also editorial member of various international scientific Journals.
Abstract:
Allogeneic hematopoietic stem cell transplantation (HSCT) is cellular immunotherapy in the true sense for the treatment of a number of benign and malignant disorders with a curative intent. Delays in immune reconstitution following HSCT considerably limit the positive outcomes and increase the risk for infection and disease relapse in the transplant recipient. Ways to measure and manipulate immune recovery following HSCT are emerging and their success depends directly upon an enhanced understanding for the underlying mechanisms responsible for reconstituted immunity and haematopoiesis. Research in transplant immunology has made considerable efforts in understanding the role of immune effector cells in HSCT. Understanding the transplant immunobiology is fundamental to elucidate the immunological process involved in engraftment, immunotolerance, immune reconstitution, and donor and host reactions such as graft-versus-host disease (GVHD), graft-versus-leukaemia (GVL) effect, graft rejections and reinstatement of hematopoietic and immunological function to prevent transplant-related opportunistic infections. Although much of our understanding of immunobiology in allogeneic HSCT is from research in preclinical models, the findings can however be correlated with clinical observations in transplant recipients. Meanwhile, several pharmacological and cellular therapeutic interventions have been shown impact on immunobiology and influence the outcome. As our knowledge continues to evolve in understanding immunobiology, so will our ability to decrease disease- and transplant-related morbidity and mortality in the setting of HSCT.
Asuman Sunguroglu
Ankara University, Turkey
Title: Expression profile of cancer Stem Cell markers in Glioblastoma derived CD133 + and CD133- cells
Time : 11:30-12:10
Biography:
Asuman SunguroÄŸlu is Professor at Medical Faculty of Ankara University. She graduated from Hacettepe University, Faculty of Science, Department of Biology, Ankara, Turkey. She got the Master’s Degree in “Tumour Immunology” in 1987 from Medical Faculty of Hacettepe University. She received her PhD degree in “Medical Biology” from Ankara University, Medical Faculty in 1992. Her research focuses on cancer and leukaemia cytogenetics in humans. In order to specialise and gain knowledge and practice, she was assigned in the University of Welsh, Medical Faculty in Cardiff for 6 months in 1996. She was named Associate Professor in 1997 and Professor in 2003. She has been Chair of Medical Biology Department since 2003. She is the member of Advisory Committee of the Scientific and Technological Research Council of Turkey (TUBÄ°TAK). She received several grants, awards and fellowships from organizations such as Turkish Heart Association, Ankara University and TUBÄ°TAK for her research projects. Her current research interests in molecular mechanisms of cancer stem cells, understanding the molecular basis of Infertility, Monoclonal Antibody production and immunotherapies for cancer.
Abstract:
Background/Aim: Glioblastoma, known as Glioblastoma Multiforme (GBM), is the most common and aggressive type of brain tumours in adults and contains self-renewing, tumorigenic cancer stem cells (CSCs) that can account for tumour initiation and acquisition of resistance to the given anti-GBM therapies. The neural stem cell marker CD133, known as prominin-1, has been widely used as a CSCs marker in GBM. Although, there is some controversy regarding tumour-initiating properties of CD133+ and CD133- GBM cells, a growing number of studies have revealed GBM initiating stem cell capability of CD133+ cells. Elucidation of the molecular characterization of GBM CSCs is essential for the development of novel targeted therapeutics for GBM. Therefore, we aimed to determine the expression levels of other potential CSC markers in CD133+ GBM CSCs.
Dilara Akcora-Yildiz
Mehmet Akif Ersoy University, Turkey
Title: Increased expression of CD24 in Glioblastoma Cell Lines after treatment with Temozolomide and Bortezomib
Time : 12:10-12:50
Biography:
Dilara Akcora Yildiz is an Assistant Professor at Biology Department, Mehmet Akif Ersoy University. She has been the Vice Director at the Institute of Science and Technology since 2016. She graduated from the Biology Department, Faculty of Science, Ege University, Turkey in 2004. She received her master’s degree from the Medical Biology Department, Faculty of Medicine, Ankara University, Turkey in 2007 and studied the effect of T315I, E255K and M351T mutations in imatinib resistance in chronic myeloid leukaemia patients. In the same year she was awarded with a Postgraduate Education Scholarship in Australia by the Ministry of National Education of Turkey (MEB) (2008-2012). She then earned her Ph.D. degree in intestinal stem cell biology at Department of Pathology at The University of Melbourne in 2012 under the supervision of Prof. Dr. Robert G. RAMSAY. During her doctoral studies, she characterized the role of colony stimulating factor 1 receptor-ligand pair (Cfms/CSF1) and granulocyte macrophage colony-stimulating factor (GM-CSF) in intestinal biology. She was the principal investigator of a research project titled as ‘The effect of WRN and MGMT proteins which play a role in DNA repair on drug resistance occured in Multiple Myeloma disease’ and supported by The Scientific And Technological Research Council Of Turkey (TUBITAK - 3501 National Young Investigator Career Development Program). She is currently working as an investigator in other projects focused on brain tumors, cancer stem cells and antibody production. Dr. Akcora Yildiz was a participant at 9th HOPE Meeting with Nobel Laureates in 2017. Her research interests include stem cell biomarkers, DNA repair mechanisms, apoptosis and autophagy signaling in cancer biology.
Abstract:
Glioblastoma Multiforme (GBM), is the most prevalent and aggressive type of primary brain tumour with a median survival of only 15 months due to recurrence of tumour after surgical resection and acquisition of resistance to radiotherapy or chemotherapy. Temozolomide (TMZ) an oral alkylating agent leading to the occurrence of DNA damage has been still used for GBM treatment. Other than TMZ, Bortezomib (BZ), currently in clinical use for the treatment of myeloma by achieving proteasome inhibition, has been revealed to induce apoptosis and growth inhibition in GBM cells. Our purpose was to examine the role of potential cancer stem cell markers including CD133, CD38, CD24, CD70 and DR6 in cell survival after either TMZ or bortezomib treatment. U118 GBM cell line and other GBM cell lines including U87, U138 and T98 were incubated with TMZ and BZ for 48 hr, respectively. Real Time Cancer Stem Cell, Integrin, Apoptosis and Cell Adhesion PCR Arrays (Bio-Rad) were performed in U118 cells treated with TMZ for 48 hr. Flow cytometry assay was used to determine the protein amounts of the genes of interest after BZ treatment. Treatment with TMZ led to an increase in mRNA expression of CD38 and CD24 but not in CD70 and DR6. BZ decreased the expression of CD133 and CD38, whereas CD24 expression was found to be increased in a dose-dependent manner in all GBM cell lines. Furthermore, CD70 protein expression was elevated, while DR6 protein expression was reduced with the increase of the dose of BZ. Our results suggest that CD24 seems to be involved in GBM cell survival after either TMZ or BZ treatment, indicating inhibition of its expression might benefit to overcome chemo resistance. This research has been supported by The Scientific and Technological Research Council of Turkey (No: 114S189).
Biography:
Sergey Suchkov was born in the City of Astrakhan, Russia, in a family of dynasty medical doctors. In 1980, graduated from Astrakhan State Medical University and was awarded with MD. In 1985, Suchkov maintained his PhD as a PhD student of the I.M. Sechenov Moscow Medical Academy and Institute of Medical Enzymology. In 2001, Suchkov maintained his Doctor Degree at the National Institute of Immunology, Russia. From 1989 through 1995, Dr Suchkov was being a Head of the Lab of Clinical Immunology, Helmholtz Eye Research Institute in Moscow. From 1995 through 2004 - a Chair of the Dept for Clinical Immunology, Moscow Clinical Research Institute (MONIKI). In 1993-1996, Dr Suchkov was a Secretary-in-Chief of the Editorial Board, Biomedical Science, an international journal published jointly by the USSR Academy of Sciences and the Royal Society of Chemistry, UK.
Abstract:
A new systems approach to diseased states and wellness result in a new branch in the healthcare services, namely, personalized and precision medicine (PPM). To achieve the implementation of PPM concept, it is necessary to create a fundamentally new strategy based upon the subclinical recognition of biomarkers of hidden abnormalities long before the disease clinically manifests itself. Each decision-maker values the impact of their decision to use PPM on their own budget and well-being, which may not necessarily be optimal for society as a whole. It would be extremely useful to integrate data harvesting from different databanks for applications such as prediction and personalization of further treatment to thus provide more tailored measures for the patients resulting in improved patient outcomes, reduced adverse events, and more cost effective use of the latest health care resources including diagnostic (companion ones), preventive and therapeutic (targeted molecular and cellular) etc. A lack of medical guidelines has been identified by responders as the predominant barrier for adoption, indicating a need for the development of best practices and guidelines to support the implementation of PPM! Implementation of PPM requires a lot before the current model “physician-patient†could be gradually displaced by a new model “medical advisor-healthy person-at-riskâ€. This is the reason for developing global scientific, clinical, social, and educational projects in the area of PPM to elicit the content of the new branch.