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Biography


Prof. Yangchao Chen
The Chinese University of Hong Kong, Hong Kong (China)
Title:
Anti -liver cancer efficacy of a small molecule modulator of microRNA 34a
Abstract:
MicroRNA-34a functions as a tumor suppressor and is frequently downregulated or silenced in various cancers including hepatocellular carcinoma (HCC) (Gastroenterology 2013). We identified a small molecule modulator of miR-34a named Compound 3 which could selectively restore the expression of miR-34a in cancer cells. We demonstrated the in vitro and in vivo anti-cancer activities of Compound 3 in HCC cell and animal models. Compound 3 has shown better anticancer efficacy than Sorafenib in HCC animal models (Cancer Research 2014).  
In this presentation, I will firstly present the anti-cancer activities of Coumpound 3 in vitro in cell line models and in vivo in HCC xenografted mice models. I will next present our most updated data on the metabolism study of Compound 3. The metabolites of compound 3 in human and mouse liver microsomes were identified by LC-MSn. Ten metabolites of compound 3 were detected in human and CD-1 mouse liver microsomes. They were assigned as below: M1, M2, M4 and M6: Mono-oxygenation and demethylation. M3, M7 and M8: Mono-oxygenation. M9 and M10: Demethylation.  M5: Dehydrogenation and demethylation. Based on the UV chromatogram, M7, M8 and M10 were considered to be the major metabolites in human liver microsomes, accounting for 3.51%, 3.84% and 5.05%; M3, M9 and M10 were considered to be the major metabolites in CD-1 mouse liver microsomes, accounting for 3.21%, 7.65% and 7.50%. Metabolic profiling of Compound 3 was further conducted in mouse plasma following oral administration and intravenous administration to mice. A total of one metabolite of Compound 3 in mouse plasma was searched and identified by LC-MSn. The metabolite of Compound 3 was detected and further characterized by using LC-MS/MS. The structure of the putative metabolite was elucidated by comparative analysis of fragments between the parent and individual metabolite.  
I will also present the updated data from pharmacokinetic and toxicology study of Compound 3 in mice. Overall, our data showed that Compound 3 is a promising potential anti-cancer agent which warrants further development.  
Reference: 
1. Gastroenterology, 2013, 144:1086-1097. 
2. Cancer Res. 2014;74:6236-47.  
3. Int J Biochem Cell Biol, 2013, 45:1895-1910. 
4. Tumor Biology, 2014, 35:205-12. 
5. Curr Protein Pept Sci. 2015, 16:559-70. 
6. Current Genomics, 2015, 16: 319-326. 
7. International Journal of Cancer, 2016.  
Biography:
DR. Yangchao Chen is currently Associate Professor at School of Biomedical Sciences, Faculty of Medicine, CUHK. He is also Principal Investigator at Shenzhen Research Institute of CUHK. He obtained his PhD from Zhongshan University in 2003 and later on obtained his postdoctoral training at University of Washington, Seattle. His research interests include epigenetics in cancer, histone modification particularly methylation, long and short non-coding RNAs, development of novel therapeutics for cancer. The ultimate goal of his lab is aimed at the identification of novel diagnostic markers and therapeutic targets for pancreatic and liver cancer.
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