Day 1 :
University of Tokyo, Japan
Time : 09:30-10:00
Chieko Kai is a full Professor and Director of Animal Research Center, Institute of Medical Science, the University of Tokyo since 1999, and is also a Professor of International Research Center for Infectious Diseases, in the same institute. She is a member of Science Council of Japan. Her major interests are mechanisms of pathogenisity of RNA viruses, and to control viral diseases. Her current research focus is on developing a novel cancer therapy using oncolytic viruses by genetic engineering.
Oncolytic virus therapy is a promising therapy for various tumor types. We previously reported that a wild-type measles virus (MV) efficiently infects and shows high oncolytic activity to breast cancer cells. Since wild type MV infects immune cells using signaling lymphocyte activation molecule (SLAM) as a receptor, and causes its pathogenicity in host animals, we generated a recombinant MV selectively unable to use SLAM (rMV-SLAMblind). The rMV-SLAM blind lost infectivity to lymphoid cells, but maintained its infectivity to breast cancer cells using another receptor of MV, PVRL4 (poliovirus receptor related-4)/Nectin-4. Nectin-4 is hardly expressed in other tissues except placenta in healthy adults. Recent studies reported that Nectin-4 expression is up-regulated in various types of tumor cells, including breast cancer and non-small-cell lung cancer, which is the leading cause of cancer-related death. We examined the efficacy of rMV-SLAMblind on various cell lines derived from refractory cancers, in which Nectin-4/PVRL4 was expressed. The virus showed high oncolytic activity against them and also effectively suppressed tumor mass growth in xenotransplanted immunodeficient mice. Thus, rMV-SLAMblind should be a promising candidate of a novel therapeutic agent for caner treatment.
Wayne State University, USA
Time : 10:00
Dr. Sarkar has completed his Ph.D at the age of 26 years from Banaras Hindu University andcontinued postdoctoral studies at Memorial Sloan-Kettering Cancer Institute in New York. He has published 555 peer-reviewed research articles and review articles, and also published 50 book chapters. He edited four books and he is an Academic Editor for PLoS One, and alsoserves in the editorial board of 10 cancer journals. His basic science research led to drugdiscovery and he is an expert in conducting translational research including clinical trials.
Prostate cancer (PCa) is treated with androgen deprivation therapy (ADT) but it becomes refractory and leads to metastasis (mCRPC) which is incurable, suggesting that innovative treatment options are urgently needed. We found deregulated expression of microRNAs (miRNAs) such as miR-34a, miR-124, miR-27b, miR-320 and the let-7 family, and it appears to play important roles in regulating androgen receptor (AR) splice variant expression. The miR-320 and let-7 family inhibit the expression of stem cell markers such as Lin28B, EZH2, Nanog, Oct4 and CD44, which are associated with enzalutamide resistance, and thus could be responsible for the development of mCRPC. These dysregulations can be attenuated by treatment of PCa cells with 3,3’-Diindolylmethane (BR-DIM), which led to conduct a clinical trial. In the phase II clinical trial with localized PCa pateints were treated with BR-DIM at a dose of 225 mg orally twice daily for a minimum of 14 days. DIM levels and AR activity were measured at the time of prostatectomy. Moreover, we also assessed the level of expression of miRNAs and the expression of AR and its splice variants in the radical prostatectomy specimens and compared it with diagnostic biopsy specimens. We found that BR-DIM treatment caused down regulation in the expression of AR, AR splice variants, Lin28B and EZH2, which appears to be mediated through the re-expression of let-7, miR-27b and miR-320 and miR-34a in human PCa specimens after BR-DIM treatment. In summary, our results provides the scientific basis for a “proof-of-concept” for therapeutic clinical trial for achieving better treatment outcome which will have a significant impact on the management of PCa patients.