Day 2 :
Institute of Hematology and Blood Transfusion, Czech Republic
Keynote: Hematopoietic stem cell-based therapy for HIV disease: Prostaglandinmodulated transplantation
Time : 10:00-10:30
Josef Bodor received his Ph.D. (1990) with honors from Institute of Molecular Genetics in Prague, Czech Republic. As of 2013, he is a Senior Investigator working at the Instituternof Experimental Medicine in Prague, Czech Republic. Dr. Bodor is a senior scientist with faculty experience from Ivy League Institutions in US hosting on sabbatical leaves aroundrnthe world (Harvard University Boston, MA, Columbia University; New York, NY, Kyoto University, Kyoto, Japan, Würzburg University, Würzburg, Germany, and Johannes GutenbergrnUniversity in Mainz, Germany). Dr. Bodor as an Associate Member of Transregio 52 published series of original reports summarized in authoritative reviews. Currently, Dr. Bodor isrnfaculty member at the Institute of Hematology and Blood Transfusion in Prague, Czech Republic.
At present, the general consensus is that ‘true’ self-renewing human hematopoietic stem cells (HSCs) are found within the CD34+ populationrnand that engraft ment of a suitably conditioned host with a suffi cient number of such cells will result in long-term multilineage hematopoiesis.rnUmbilical Cord Blood (UCB) cells are a valuable source of HSCs for use in allogeneic transplantation. Key advantages are easy availability andrnless stringent requirements for HLA matching. However, UCB cells contain an inherently limited HSC count associated with delayed time ofrnengraft ment, high graft failure rates and early mortality. PGE2 derivative (16, 16 dimethylprostaglandin E2; dmPGE2) was recently identifi edrnto be a critical regulator of HSC homeostasis (1). Recent data have shown that brief ex vivo modulation with dmPGE2 could improve patientrnoutcomes by increasing the ‘eff ective dose’ of HSCs with preferential long-term engraft ment of the dmPGE2 treated HSCs in allogeneicrntransplantation. Moreover, it was demonstrated that conventional CD4+ T cells (Tcons) could be developed in vitro into CD4+CD25+Foxp3+rninducible regulatory T cells (iTregs) with an equivalent suppressive potential as naturally occuring regulatory T cells (nTregs) by continuousrnpolyclonal activation with anti-CD3/CD28 mAbs (2). During the diff erentiation process, the iTregs express cyclooxygenase 2 (COX-2) andrnproduce PGE2. Interestingly, neither resting nor activated nTregs express COX-2. Th e PGE2 production from iTregs can be fully suppressed byrnthe COX inhibitor indomethacin. Th ese data indicate that PGE2 plays an important role in diff erentiation of HSCs thus releasing stringencyrnrequired for HLAmatching donors with potential recipients as well as with potential role in dominant suppressive eff ects of iTregs expressingrnCOX-2 with acquired ability to produce copious amounts of PGE2 responsible for delivery of suppressive function through elevated levels ofrncAMP (3). Prostaglandin E2 (PGE2)-mediated mechanisms, which have potential to downregulate CCR5 expression in umbilical cord bloodrn(UCB) cells heterozygous for CCR5Δ32 mutation (CCR5wt/Δ32), could reduce or eliminate surface expression of CCR5 (CCR5 null cells)rnand thus facilitate allogeneic transplantation, UCB cell-engraft ment, and preferential cord chimerism in parallel with CCR5 downregulation.rnKey advantages of this process are higher frequency of heterozygous CCR5wt/Δ32 donors, less stringent requirements for HLA matching,rnand better engraft ment of the cells resistant to HIV. To eliminate the need for indefi nite treatment, our ultimate goal is to create a functionalrnHIVresistant immune system through the use of modifi ed HSCs with emphasis on post-transplant amelioration of GvHD enabled viarnpotentiation of regulatory T cell (Treg) cell-mediated suppression.
Naxospharma srl Cesate, Italy
Time : 10:30-11:00
Paolo Lombardi graduated from Milan University and completed his PhD from Southampton University. He has over 35 yr experience in the pharmaceutical industrial setting. He has backgrounds in organic synthetic chemistry, process research chemistry and therapeutic chemistry. As Vice-president for Chemistry in Menarini Ricerche, he fostered the discovery of Sabarubicin, a 3rd generation antitumor anthracycline presently in advanced clinical studies. He acted as a consultant for the pharma company IBI G. Lorenzini and the French start up biotech Chrysalon. He founded his own small biotech company, Naxospharma, which has been the recipient of research grants from several national and European funding agencies, and co-founded Aesis Therapeutics, a start-up shell company aimed at developing Naxospharma\'s findings. He is the inventor of over 70 patents in Medicinal and Process Chemistry, author and co-author of over 150 research papers, reviews, abstracts, invited lectures and seminars. He has teaching appointments at Universities, Master courses & Specialist Schools. He is the member of several scientific societies.
Berberine is an isoquinoline quaternary plant alkaloid which has been used in the Ayurvedic and Chinese medicines since hundreds of years. The diverse pharmacological properties exhibited by berberine not only indicate that the alkaloid has a definite potential in a wide spectrum of clinical applications, but also that it represents an attractive natural lead compound by providing a biologically interesting skeleton for the introduction of chemical modifications in search for more selective and specific medical indications. Anticancer properties of berberine have also been reported and our studies identified berberine as a novel, non specific inhibitor of the nascent synthesis of some proteins, supposedly acting as a RNA silencing agent. In normal cells, signaling transduction pathways converge into several components of translational machinery. However, these components are often deregulated in cancer cells making the translated proteins becoming oncogenic. Accordingly, the appreciation of the differences in mRNA translational control between normal cells and cancerous cells makes it a possible therapeutic opportunity against cancer. In this respect we discovered novel 1, 3-diarylalkylberberine derivatives with improved anticancer properties. Several of the new berberine derivatives show remarkable anti-proliferative effects on a variety of human cancer cell lines which either acquired resistance or are normally refractory to chemotherapy. Although the precise molecular basis of the biological activities of berberine is still debated, at least for the anticancer activity we present new information and data regarding down regulation of cancer related protein expression as the putative major biological effect of this class of compounds which is exploitable for clinical applications. These new derivatives are believed to have the property to bind to oligonucleotides and to function as selecting suppressors of protein synthesis.
Margalit Doron has completed his MA in expressive art therapy at Lesley University in Boston in 1995 and currently living in Israel. Since then he has been working with children and adults mainly focusing on trauma and P.T.S.D. In the last ten years he is practicing therapy with families and an individual going through cancer treatment and provides near death support to the family. In his work he uses expressive therapy to support the treatment and encourages his patients to strengthen their vitality. In his work shop he will let us experience the potential that expressive therapy has for cancer therapy.
In this workshop I would like to go through the process of \"awakening\" using the imaginary thought by our doctors that we have very few months to live. We will use this short time to experience threw art and drama the curing ability that is enfold in this process. We will also borrow parts of the existential approach to intense the understanding of why it actually worked for Sara. I will use the term \"wake-up call\" and investigate the meaning. We will dive into an essential question introduced by Irvin Yalom in his book about existential therapy “are we living our lives?” Or as Nietzsche presents it to us in his question “If you live your life over again how would you do it?”