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.
- Cancer Cell Biology l Cancer Biomarkers l Cancer Vaccines
Session Introduction
Tzu Ching Chang
China Medical University, Taiwan
Title: Mesenchymal stem cells in inflammatory microenvironment promotes cancer cell migration and epithelial-mesenchymal transition through osteopontin
Biography:
Tzu-Ching Chang has completed her PhD from Graduate Institute of Life Science, National Defense Medical Center, Taiwan. She did her Master’s degree from Institute of Physiology, National Taiwan University, College of Medicine, Taiwan. Her areas of research include Molecular Cell Biology, Stem Cell Biology and Cancer Cell Biology.
Abstract:
Backgrounds: Mesenchymal stem cells (MSCs) provide potential regenerative effects on chronic kidney disease (CKD) due to their paracrine signaling with cell tropic and anti-inflammation properties. However, in CKD patients combined with renal cell carcinoma (RCC), the roles of MSCs in inflammatory or tumors’ microenvironment are still controversial. Methods & Results: To evaluate the real characteristics of MSCs in inflammatory microenvironment, we first detected the human MSC secretome by cytokine array after MSCs were incubated with or without inflammatory cytokines (IL-1β or TNF-α). The array data showed that, compared to control MSCs, osteopontin (OPN) were significantly increased after MSCs were incubated with inflammatory cytokines. Furthermore, OPN mRNA level and protein secretion were confirmed by quantitative real-time PCR and ELISA respectively. We further collected MSC condition medium (MSC-CM) after inflammatory cytokine treatments to test the effects of MSC-CM as well as OPN alone on RCC migration. MSC-CM and OPN alone facilitated RCC migration by Boydon chamber assay. The epithelial-mesenchymal transition (EMT) of RCC was significantly promoted by MSC-CM and OPN alone since the reduction of E-cadherin and increase of Snail and vimentin. Using OPN-specific antibody to neutralize OPN in MSC-CM would attenuate the RCC migration and EMT that were stimulated by whole MSC-CM. Moreover, the activities of cancer-associated fibroblasts (CAF) were enhanced by treating CAF with MSC-CM and OPN alone. Conclusion & Significance: In this study, we demonstrated that OPN secreted by MSCs would promote cancer cell migration, EMT progression and CAF activation while MSCs were incubated in an inflammatory microenvironment. We hope that this study will provide another consideration of MSC application in kidney regeneration while CKD patients combined with RCC.
Surangkana Sanmai
Khon Kaen University, Thailand
Title: High expression of Pyruvate Dehydrogenase Kinase in Cholangiocarcinoma patients
Biography:
Surangkana Sanmai is currently pursuing a Master’s degree in Medical Sciences at the Faculty of Associated Medical Sciences, Khon Kaen University, Thailand. She is interested in cancer biomarkers and chemotherapeutic target.
Abstract:
In our previous demonstration, we found the differential mitochondrial proteom between CCA and adjacent non-canerous tissues assessed by mass spectrometry. Cancer cells are well-know for their altered metabolic state and the main cause under this phenomenon is mitochondrial metabolic enzyme permutation. So in this study, the glucose metabolism-involved proteins were selected from data and fold-change analysis was performed. The data showed the overexpression of pyruvate dehydrogenase kinase (PDK) isoform 2 and 3 in CCA compared to its adjacent non-cancerous tissues. Especially, PDK3 showed the highest fold-change at 13. PDK is a Ser/Thr kinase that inactivates mitochondrial pyruvate dehydrogenase and plays a keystone of Warburg effect that lead cancer cells survive in hypoxia condition. PDK isoforms consist of PDK1, PDK2, PDK3 and PDK4. All PDK isoforms notably express on specific tissues and there is no report of PDK pattern in CCA yet. In this work, all PDK isoforms immunohistochemistry was performed in CCA and adjacent non-cancerous tissues to confirm mass spectrometric data. The results showed the pattern of PDK isoform expression where PDK1, PDK2 and PDK3 exhibited high expression on CCA tissues at H-score 240±69, 210±30 and 262±28 respectively (maximum H-score=300), while the weak staining was observed in adjacent tissues. In contrast, PDK4 showed no staining in CCA tissues. Taken together, the specification of PDKs pattern in CCA may provide a good tumor marker for CCA. Futhermore, PDK1 and PDK3 may be considered as potential prognostic markers for CCA patients due to their tumor progression involvement.
Doungdean Tummanatsakun
Khon Kaen University, Thailand
Title: Serum apurinic/apyrimidinic endodeoxyribonuclease 1 in cholangiocarcinoma patients
Biography:
Doungdean Tummanatsakun is currently pursuing a Doctor of Philosophy Program in Medical Technology at the Faculty of Associated Medical Sciences, Khon Kaen University, Thailand. She is interested in cancer biomarkers.
Abstract:
Cholangiocarcinoma (CCA) is a cancer from intra- and extra-hepatic biliary epithelial cells. The incidence of CCA in the northeastern part of Thailand is very high, especially Khon Kaen province. Metastasis of tumor provides important prognostic information and can help guide therapy. This study is to discover CCA prognosis marker to distinguish between non-metastatic and metastatic patients from our database in CCA cell lines secretome. Using bioinformatics include SignalP, SecretomeP, TMHMM, Plasma Proteome Database and EMBOSS for selected candidate proteins from three CCA secretome but not in control immortalized cholangiocyte by GeLC-MS/MS. Secretory protein was selected for further validation studies according to criteria including proteins predicted to have signal peptide or non-classical proteins that have no transmembrane helix, identified in serum and selected proteins with maximum of signal peptide cleavage sites. Apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1) was selected for further validation analysis. APEX1 has been reported to play a role in metastatic function. Thus, to validate APEX1 protein was differentially expressed in CCA and western blot (WB) for APEX1 was performed for metastatic and non-metastatic group in serum CCA. This revealed that APEX1 intensity ratio was highly expressed in metastatic compared to non-metastatic group (4.73±2.02 for metastatic vs. 1.14±0.81 for non-metastatic group). In conclusion, serum APEX1 might be useful as a prognosis biomarker for treatment in CCA patients.
Daraporn Chua-on
Khon Kaen University, Thailand
Title: High expression of apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) in human cholangiocarcinoma
Biography:
Daraporn Chua-on is currently pursuing a Doctoral degree in Medical Sciences at the Faculty of Associated Medical Sciences, Khon Kaen University, Thailand. She is interested in cancer biomarkers and chemotherapeutic target.
Abstract:
Diagnostic biomarker of cholangiocarcinoma (CCA) patients is absolutely poor in spite of extensive efforts for the improvment of diagnosis. Mitochondial proteins play key roles in carcinogenesis of various cancer. Therefore, mitochondria are considered as the target organelles for discovering biomarkers of several cancers including CCA. The purpose of this study is to identify potential candidate proteins for diagnosis using mitochondrial proteome analysis for CCA tissues. A shotgun proteomic approch using SDSPAGE coupled with LC-MS/MS was applied to compare the expression of mitochondrial proteins in CCA and the adjacent noncancerous tissues. Using the proteomic analysis for the pooled mitochondrial proteins purified from three each of papillary and nonpapillary types of CCA and their adjacent tissues, 281 proteins were identified as mitochondrial proteins, and 105 of them showed significantly different expression compared with the corresponding counterparts. Among 105 proteins, apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3) was a unique protein commonly over-expressed in both papillary and non-papillary types ot CCA tissues but not in the adjacent non-cancerous tissues. Immunohistochemistry showed expression of AIFM3 staining was significantly higher in CCA than in the corresponding adjacent non-cancerous tissues. Furthermore, high expression of AIFM3 was also significantly expressed in human serum CCA. In conclusion, AIFM3 was aberrantly expressed in both CCA tissues and serum. This finding suggeests that AIFM3 could be a potential biomarker for CCA diagnosis.