Day 1 :
Keynote Forum
Chieko Kai
IMS University of Tokyo, Japan
Keynote: An oncolytic measles virus as a novel promising tool for cancer therapy
Biography:
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 pathogenicity 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.
Abstract:
Oncolytic viruses are promising tools for novel therapy for various tumor types. Wild type measles virus (MV) has high oncolytic activity. Since wild type MV infects immune cells using signaling lymphocyte activation molecule (SLAM) as a receptor and the infection causes its pathogenicity in host animals, we generated a recombinant MV selectively unable to use SLAM (rMV-SLAMblind). The rMV-SLAMblind lost infectivity to lymphoid cells and lost pathogenicity in monkey models, but maintained its infectivity to breast cancer cells using another receptor of MV, PVRL4 (poliovirus receptor related-4)/ Nectin-4. Recent studies reported that Nectin-4 expression is up-regulated in various types of tumor cells, including breast and non-small-cell lung cancer, which is the leading cause of cancer-related death, whereas it is hardly expressed in other tissues except placenta in healthy adults. 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. In addition, systemic inoculation induced remarkable suppression of tumor growth in a xenograft model. Thus, rMV-SLAMblind is a promising candidate of a novel therapeutic agent for cancer treatment by even systemic treatment.
Keynote Forum
Leung KN,
The Chinese University of Hong Kong, China
Keynote: Mechanistic studies on the anti-tumor activities of omega-3 polyunsaturated fatty acids on the human neuroblastoma LA-N-1 cells
Biography:
Leung K N has received his BSc Degree (with First Class Honors) in Biochemistry from The Chinese University of Hong Kong (CUHK) and obtained PhD Degree in Microbiology and Immunology from The Australian National University. After two years of Post-doctoral work at the Pathology Department of the University of Cambridge, he returned to the CUHK as a Lecturer in the Department of Biochemistry in 1983. He was the former Dean of General Education in Chung Chi College, the Associate Dean of Science (Education) of CUHK and the Chairman of the Hong Kong Society for Immunology. He is now an Adjunct Professor in the School of Life Sciences, CUHK and the School of Science and Engineering, CUHK (Shenzhen). His main research interests include immunopharmacological studies of natural products and Chinese medicinal herbs; cancer immunotherapy; nutrition, immunity and cancer.
Abstract:
Neuroblastoma is the most common extracranial solid cancer among infants and children. The prognosis of patients with advanced stages of neuroblastoma with N-myc amplification remains poor despite intense multimodality therapy, and there is a pressing need for alternative therapeutic strategies. Omega-3 polyunsaturated fatty acids (n-3 PUFAs) are naturallyoccurring long-chain fatty acids containing a carbon-carbon double bond at the omega C-3 position. Although previous studies have demonstrated the anti-proliferative effect of n-3 PUFAs on different cancer cell lines in vitro, the anti-tumor effects and underlying molecular action mechanisms of n-3 PUFAs, including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on human neuroblastoma cells remained poorly understood. In this study, both DHA and EPA were shown to suppress the proliferation of two human neuroblastoma LA-N-1 and SH-SY5Y cell lines in a concentration- and timedependent manner. Mechanistic studies using the LA-N-1 cells with N-myc amplification indicated that DHA and EPA could suppress N-myc expression and caused cell cycle arrest at the G0/G1 phase, which was accompanied by a decrease in CDK 2 and cyclin E protein expression. Remarkably, DHA and EPA could also trigger apoptosis in LA-N-1 cells by inducing DNA fragmentation and phosphatidylserine externalization. Increased in mitochondrial membrane depolarization and Cyt.C release, up-regulation of Bax, caspase-3 and caspase-9 proteins, and down-regulation of Bcl-XL protein suggested the possible involvement of the intrinsic apoptotic pathway. Interestingly, both DHA and EPA failed to induce neuronal differentiation in LA-N-1 cells, as judged by both morphological and functional criteria. Taken together, our results suggest that DHA and EPA might exhibit their anti-tumor effects on the human neuroblastoma LA-N-1 cells by triggering cell cycle arrest and by inducing apoptosis of the cancer cells. Therefore, n-3 PUFAs such as DHA and EPA are potential anti-cancer agents which can be used for the treatment of some forms of human neuroblastoma.