Biography:

Karin Schuetze is a Biologist and expert in non-contact cell handling and label-free cell analysis using innovative photonic technologies. She did her PhD work at the Institute for Applied Physical Chemistry in Heidelberg and her Postdoc Research at the University of California in Berkeley where she assembled her first Optical Trap. In 1993 she and her husband founded the PALM company, which was successfully sold to Zeiss. In 2008, they both founded their second company, the CellTool GmbH, where they develop Raman microscope systems for biomedical applications, providing physicians and biologists with a label-free and non-invasive tool for cell analysis.

Abstract:

In the last years, the field of stem cell medicine has opened unforeseen therapeutic opportunities. In order to ensure functionality and safety of cell based therapies used for patient care, methods allowing reliable quality control during all steps of product development are essential. Raman Spectroscopy (RS) is a highly sensitive technology increasingly used for biomedical applications like cell identification, diffentiation and characterization, as well as quality control of cell based products as it reveals detailed information on the metabolic state of living single cells in a label-free and non-invasive way. Here, we demonstrate that RS is a valuable tool also in stem cell research and medicine. It helps to understand basic cellular processes, to ensure quality of cell based products and to improve current gold standard methods. We provide latest data from Raman analyses of single cells as well as of 3D cell culture and tissues, including investigations on retina tissue, insights on the influence of stem cell freezing and quality control of chondrocytes and blood products, showing that this non-invasive approach provides new insights on the whole metabolome of cells which help to improve and secure approaches in stem cell medicine.

Biography:

­­­Francisco Ruiz-Navarro is a Research Associate and R&D Director of the Austrian Society for Regenerative Medicine in Vienna, Austria where he focuses his research in stem cell therapies for neurological disorders. Before, he was performing research in the Cerebrovascular Department at the National Institute for Neurology and Neurosurgery in Mexico City with special interest in multicentric population studies with Hispanic stroke patients. He was a Research Assistant in the Brain Bank, Center for Research and Physiology, Department of Biology and Neuroscience at the Institute of Advanced Studies at National Polytechnic Institute in Mexico City. He obtained his Medical degree in the Anahuac University in Mexico City, became USMLE board certified in the United States of America and he got his Doctor of Medicine from the Medical University of Vienna.

Abstract:

After reviewing several current clinical guidelines, we found that less than 1% of all the recommendations for neurological diseases in the clinical guidelines are sustained by a level 1A of evidence (Systematic review of RCT with homogeneity, according to the Oxford Centre of Evidence). When reviewing the scientific evidence of stem cells treatment, we found that several stem cell therapies are based on the same or even stronger scientific evidence than the current medical treatment. This means accepted treatments and stem cell treatments nearly have the same level of evidence. Although both are far from level A, it is apparently enough for several clinicians and regulatory agencies to maintain a reluctant posture towards stem cell therapies but not towards other kinds of treatment. We propose that not just level 1A of evidence should be accepted as treatment, especially in cases where there are no options for patients besides experimental treatments. In this debate, the necessity of RCT or blinded trials arises, especially because SCs therapies are a procedure rather than medication and conducting clinical studies with “surgical placebos” is ethically controversial. There are analyses that describe how series of observational studies found results similar to those obtained from RCTs, which means that certain number of cohort or case-control studies would yield enough valuable information to bring treatments to the clinical practice, although we plan to wait for better-design RCT to confirm the results, if possible. We reviewed the most relevant literature concerning the use of stem cells to treat several neurological disorders. This literature review will provide key information on how stem cell’s interventions were performed with the analysis of the level of evidence they are providing. Drawing on the gathered information we then compared the scientific evidence that underlies the current treatment guidelines with the scientific evidence on currently available stem cells publications. As a result of this survey and analysis we conclude with a series of recommendations for the use of stem cells in clinical settings.

Biography:

MichaÅ‚ PikuÅ‚a is an Associate Professor at the Department of Clinical Immunology and Transplantology, Medical University of Gdansk. He has completed his MPharm from Medical University of Gdansk (Pharmacy Practice), MSc from University of Gdansk (Molecular Biology) and his PhD in Medical Biology from Medical University of Gdansk (Faculty in Medicine) in 2007. He is currently responsible for several projects focused on Regenerative Medicine and Experimental Immunology. He is also a Group Leader in a prestigious REGENNOVA consortium grant STRATEGMEDI (“Novel Technologies for Pharmacological Stimulation of Regeneration”).

Abstract:

Human adipose tissue constitutes a rich source of multipotent stem cells. Adipose-derived Stem Cells (ASCs) have been in the center of scientific and clinical attention, due to a wide range of possible implementations in tissue engineering, regenerative medicine and clinical immunology. These cells are characterized by a multipotent activity including high proliferative potential, secretion of trophic factors, direct interactions with immune cells and ability to differentiate into different kind of cells. Despite being extensively studied, phenotypic characterization of specific surface markers and details of differentiation potential need to be elucidated. The data obtained in our studies, based on flow cytometry technique, show that ASCs cultured in vitro express elevated levels of ASCs markers typical for mesenchymal stem cells (CD73, CD90, CD105, CD29). The variable level of expression was observed for CD31 and CD34, what seems to be a donor-to-donor variability. The observed markers expression did not affect the differentiation capacity of ASCs into chondrocytes, adipocytes and osteocytes. Additionally, our results show that the long term in vitro culture of ASCs has no impact on the surface expression markers pattern. According to our observations, no significant differences in the surface markers level and differentiation potential were noted between the cells obtained from oncological patients or from plastic surgery procedures. Summarizing, our studies reveal that ASCs are a promising tool in postoperative tissue reconstruction in oncological patients due to their high regenerative potential. However, further studies are required to provide more insight into the therapeutic potential of ASCs in postoperative management of patients undergoing oncology surgery.

Biography:

Vassilis Katsares is a Biologist with a PhD on Populational Molecular Genetics. He completed three Postdoctoral Fellowships. He also served as a lecturer for undergraduate and postgraduate courses. He had worked as Technical Sales Support for immunology analyzers and afterwards he was the Laboratory Director at a biopharmaceutical company. His main research interests cover many aspects of Molecular Genetics, Cellular Therapy projects, and bioethics. He has authored 21 scientific papers and 36 announcements at national and international conferences. He is a referee in various journals. He is member in many international Scientific Organisation and Societies. His CV is included in “Who is Who in the World”, and in “Who is Who in Science and Engineering”.

Abstract:

Stem cells play a significant role in the novel branch of modern Biology and Medicine, known as Regenerative Medicine. Due to their regenerative ability, stem cells are looked at as a promising tool for improving infertility treatments in women and men. It has been shown that fully mature egg cells, as well as sperm cells can be grown in the lab, raising hope for new infertility treatments. There has been also evidence that eggs could be fertilised, implanted into a surrogate female and go on to produce live offspring. All the obtained offspring grew up normally without evidence of premature death. Artificially created sperm and eggs could spell the end of infertility at the near future. Stem cells can potentially be developed into any tissue in the human body. Reproductive scientists think it is only a matter of time before the technique is used as an alternative IVF treatment. Nowadays, there is also the new trend of ovarian rejuvenation, using stem cells growth factors to improve the ovulation of older ovaries. However, for all these techniques to become a clinical reality, many potential risks and ethical concerns about the use of stem cells must first be addressed. If the treatment works, it could be extended to even older post-menopausal women. Should the law review the ceiling on how old a woman can be to have this treatment since there is no law stopping a man from having a child late in life? All this research may alter our understanding of male and female infertility and provide solutions to IVF treatments. Though a long way off, if ever, it would be an incredible change in how we view and treat infertility.

Biography:

Joseph Choukroun completed MD from University of Montpellier, France 1979 and is a Specialist in General Surgery, Anesthesiology from the same university. He is also a Specialist in Pain Management from University of Strasbourg France. He is the Owner of Private Pain Clinic, Nice France. He is the President of SYFAC, international symposium on growth factors. He is the Inventor of the PRF techniques: L-PRF, A-PRF and i-PRF. He is a Researcher working in Form Lab at University of Frankfurt. He is the author of several scientific publications and is recognized as an International Speaker.

Abstract:

Regenerative therapy with stem cells has gained tremendous momentum over the past decade as a modality geared towards markedly improving wound healing of various tissues by utilizing undifferentiated autologous host cells. While stem cells may be isolated from various locations in the human body, more recently it has been shown that low levels of mesenchymal stem cells also exist circulating within peripheral blood. Platelet rich fibrin (PRF) is a regenerative modality that utilizes peripheral blood + centrifugation protocols without the use of anti-coagulants to create a three-dimensional tissue engineering scaffold containing both growth factors and autologous cells. Very recently, it has been shown that modifications to centrifugation speed and time following recently developed concepts (the low-speed centrifugation concept or LSCC) resulted in a marked increase in host cells and growth factors. Within these scaffold constructs, mesenchymal stems cells were also found following collection with this relatively painless and low-cost modality. The objective of the present talk will be to present recent modifications to centrifugation speed and time to optimize stem cell quantities within PRF. Thereafter, the biological data supporting their numbers, as well as their potential for clinical applications will be presented with data coming from many fields of medicine including for the regeneration of osteoarthritic knees, dental regenerative medicine, orthopedic grafting, and for facial esthetics.

Biography:

Simon Haas is Group Leader at the Heidelberg Institute for Stem Cell Technology and Experimental Medicine and the German Cancer Research Center. He is an expert in hematopoiesis, with a special focus on stem cell biology. His research centers around the question how hematopoietic stem cells make complex lineage decisions to produce the variety of blood and immune cells.

Abstract:

Multipotent hematopoietic stem cells are responsible for the livelong production of all blood and immune cells. In the classical model of hematopoiesis, blood formation is believed to occur through stepwise progression of hematopoietic stem cells following a tree-like hierarchy of oligo-, bi- and unipotent progenitors. However, this model is based on experimental approaches unable to describe how individual HSCs and their progeny enter lineage commitment during steady-state hematopoiesis. To establish a comprehensive model of human hematopoiesis, we have developed single-cell approaches that integrate single-cell RNA-sequencing with flow cytometric and functional lineage potency data. This allows us to reconstruct developmental trajectories and to gain a detailed view on lineage commitment of individual HSCs into all major branches of human haematopoiesis. We found that individual HSCs do not pass through discrete intermediate progenitor cell stages. In contrast, HSC lineage commitment occurs in a gradual manner best described by a continuous Waddington landscape with initially flat but progressively deepening valleys. Our data determine a detailed model of developmental trajectories within this landscape and demonstrates that distinct gene expression modules operate in a combinatorial manner to control stemness, early lineage priming and the subsequent progression into all major branches of hematopoiesis. These results establish the concept of a developmental continuum, which can replace the differentiation tree as a comprehensive model of human steady-state hematopoiesis and provide a basis for the understanding of hematopoietic malignancies.

Biography:

Hany E. S. Marei is the Project Manager of Biomedical Research Center, Qatar University since May 2015. His research interest lies in the field of neural stem cells, induced pluripotent stem cells, genomics, transcriptomics and epigenomics of Neurological diseases/disorders. He is the editorial board member/reviewer for several international journals. He served as a member for promotion committee for Professors at the Supreme Council of Universities Egypt from 2012-2015.

Abstract:

Neural stem cells (NSCs) are multipotent self-renewing cells that could be used in cellular-based therapy for a wide variety of neurodegenerative diseases. Here, to assess the ability of carbon nanotubes (CNTs) to enhance the therapeutic potential of human olfactory bulb neural stem (OBNSCs) for restoring cognitive deficits and neurodegenerative lesions, we co-engrafted CNTs and human OBNSCs in trimethyltin(TMT) -neurodegeneration rat model. The present study revealed that engrafted human OBNSCS-CNTs restored cognitive deficits, and neurodegenerative changes associated with TMT-induced rat neurodegeneration model. Moreover, the CNTs seemed to provide a support for engrafted OBNSCs, with increasing their tendency to differentiate into neurons rather than into glial cells.

Biography:

Tamara Lah Turnšek has completed her graduation (organic chemistry), magisterium (biochemistry) and doctorate (biochemistry), she worked at the Department of Biochemistry and Molecular Biology at the Jožef Stefan Institute and for quite a while likewise at the Clinical Laboratory of the Paediatric Clinic in Ljubljana. Since 1996, she has been Director of the National Institute of Biology, where in the vicinity of 1997 and 2004 she additionally filled in as Head of the Department of Genetic Toxicology and Cancer Biology.

Abstract:

The most aggressive brain tumour glioblastoma multiforme is characterized by aggressive GBM cell infiltration into surrounding brain parenchyma. We hypothesise that this invasion process is supported by mesenchymal stem cells, comprising GBM microenvironment. MSCs are recruited from bone marrow or endogenous brain tissue to the GBM tumour, but their interactions with GBM cells are still poorly understood. To elucidate the direct interaction between bone marrow-derived MSCs and two distinct GBM cell lines, U87 and U373, we tested cells’ invasion in vitro, as well as in vivo, using zebrafish embryo model. Since proteases are crucial for GBM cell invasion, we focused on their role in invasion of cells in MSC/GBM direct co-cultures by analysing their expression at gene and protein levels and by applying selective protease inhibitors in the 3D-invasion model in vitro. We demonstrated that the effect of MSC/GBM cellular cross-talk on GBM cell invasion is GBM cell type specific. Namely, MSCs decreased the invasion of U87 cells, whereas they increased the invasion of U373 cells in vitro and in vivo. In contrast, both GBM cell lines increased the invasiveness of MSCs upon direct interactions. Moreover, we observed that increased U373 cell invasion in co-cultures correlated with increased expression of cathepsin B, calpain1, uPA/uPAR, MMP-9 and -14, all involved in the protease signalling cascade in GBM cells, leading to increased invasion via extracellular matrix degradation. Using selective inhibitors, we confirmed involvement of cathepsin B, MMP-9 and -14 in MSC-enhanced invasion of U373 cells. By contrast, decreased invasion of U87 upon co-culturing seemed to be independent of these proteases, implicating that the MSC regulatory potential in MSC/GBM co-cultures is dependent on GBM phenotype. Finally, we identified the genes, associated with cell response to TGF-ß that were differentially expressed in U87 vs. U373 cells that could explain different response of these cell lines to MSCs. Taken together, our findings are the first to suggest that the response of GBM cells to MSCs depends on the cancer cell’s genetic subtype. This notion may be generalized to other types of stromal cells as well as to other tumours.

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.

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 14^th, 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.

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.

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.

Materials and Methods: Primary GBM cells were isolated from freshly obtained GBM tissue samples derived from ten individual patients. These cells were cultured with DMEM with high glucose including 1% Penicillin-Streptomycin and 10% fetal bovine serum. Then, CD133+ and CD133- cells were separated by MACS (Miltenyi) method from those GBM primary cells. The CD133+ selected and CD133- cell populations were collected in different tubes. Following RNA isolation from CD133+ and CD133- cells, cDNA synthesis was performed. mRNA expression levels of 88 genes were detected by Real Time Cancer Stem Cell PCR Array (Bio-Rad). The Student T test was used to identify statistically significant differences between groups. Differences were accepted to be statistically significant at p<0.05. Confocal microscopy was performed to examine the localization of CD38 and CD24 proteins in CD133+ GBM CSCs.

Results: Based on the results of PCR Array, we found that the mRNA levels of ABCG2, ALCAM, CD24, CD38, CD4, DDR1, EGF, ENG, ETFA, FGFR2, FLOT2, FZD7, GSK3B, ID1, IKBKB, ITGA2, ITGA4, ITGA6, ITGB1, JAG1, MAML1, MUC1, MYCN, NFKB1, NOTCH2, PLAT, PLAUR, POU5F1 and BMP7 were statistically different in CD133+ GBM CSCs when compared to expression of those in CD133- cells. Furthermore, we investigated protein levels of CD38 and CD24 in both CD133+ and CD133- cells and observed that protein expression of both CD38 and CD24 was more prominent in CD133+ GBM CSCs than in CD133- cells.

Conclusion: Our results suggest that in addition to the presence of CD133 expression GBM initiating cells have also the expression of different genes involved in distinct survival pathways, indicating tracing these possible candidates could be useful for characterization of CD133+ GBM stem cells. This research has been supported by The Scientific and Technological Research Council of Turkey (No: 114S189).

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).