2021/12/23
Play for Biomedicine
演講相關內容如下：
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時間：12/24（五）13:10-15:30
地點：社科院北棟2樓心理系階梯教室
講題：Play for Biomedicine
講者：Chia-Hung Chien簡嘉宏 (義守大學醫學系助理教授)
演講內容：
From clinic to bench:
Background
Intratumor subsets with tumor-initiating features in glioblastoma are likely to survive treatment. Our goal is to identify the key factor in the process by which cells develop temozolomide (TMZ) resistance.
Methods
Resistant cell lines derived from U87MG and A172 were established through long-term co-incubation of TMZ. Primary tumors obtained from patients were maintained as patient-derived xenograft for studies of tumor-initiating cell (TIC) features. The cell manifestations were assessed in the gene modulated cells for relevance to drug resistance.
Results
Among the mitochondria-related genes in the gene expression databases, superoxide dismutase 2 (SOD2) was a significant factor in resistance and patient survival. SOD2 in the resistant cells functionally determined the cell fate by limiting TMZ-stimulated superoxide reaction and cleavage of caspase-3. Genetic inhibition of the protein led to retrieval of drug effect in mouse study. SOD2 was also associated with the TIC features, which enriched in the resistant cells. The CD133+ specific subsets in the resistant cells exhibited superior superoxide regulation and the SOD2-related caspase-3 reaction. Experiments applying SOD2 modulation showed a positive correlation between the TIC features and the protein expression. Finally, co-treatment with TMZ and the SOD inhibitor sodium diethyldithiocarbamate trihydrate in xenograft mouse models with the TMZ-resistant primary tumor resulted in lower tumor proliferation, longer survival, and less CD133, Bmi-1, and SOD2 expression.
Conclusion
SOD2 plays crucial roles in the tumor-initiating features that are related to TMZ resistance. Inhibition of the protein is a potential therapeutic strategy that can be used to enhance the effects of chemotherapy.
個人簡介或CV：臺灣大學生命科學系博士
經歷:
國家衛生研究院癌症研究所
臺灣大學醫學院藥物研究中心
研究興趣:
自由基與抗氧化物醫學、癌症細胞生物學、神經分子生物學
近三年著作:
1. Hsueh, W. T., Chen, S. H., Chien, C.H., Chou, S. W., Chi, P. I., Chu, J.M., Chang, K.Y. SOD2 Enhancement by Long-Term Inhibition of the PI3K Pathway Confers Multi-Drug Resistance and Enhanced Tumor-Initiating Features in Head and Neck Cancer. International Journal of Molecular Sciences. 2021 October, 22(20), 11260
2. Chien, C.H., Hsueh, W. T., Chuang, J.Y., Chang, K.Y., Dissecting the mechanism of temozolomide resistance and its association with the role of intracellular reactive oxygen species regulation in glioblastoma. Journal of Biomedical Science. 2020 March, 28:18.
3. Chien, C.H., Chuang, J.Y., Yang, S. T., Yang, W. B., Chen, P. Y., Hsu, T. I., Huang, C. Y., Lo, W. L., Yang, K. Y., Liu, M.S., Chu, J.M., Chung, P.H., Liu, J. J., Chou, S. W., Chen, S. H., Chang, K.Y. Enrichment of superoxide dismutase 2 in glioblastoma confers to acquisition of temozolomide resistance that is associated with tumor-initiating cell subsets. Journal of Biomedical Science. 2019 October, 26:77.
4. Chien, C.H., Hsueh, W. T., Chuang, J.Y., Chang, K.Y., Role of autophagy in therapeutic resistance of glioblastoma. Journal of Cancer Metastasis and Treatment. 2019 September, 5; 66.
個人網站：
https://www.isu.edu.tw/2018/showpage_v01.php?dept_mno=671&dept_id=0&page_id=32800
參考文獻：
https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0565-2
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敬請準時出席，謝謝。