研究內容

研究主題 I

訊息傳導途徑與肝癌及癌幹細胞之相關性研究與臨床研究 肝細胞癌仍然是世界上造成癌症死亡的首要疾病之一。化學治療用於病患無法進行手術或者在肝臟移植前需要降階治療或肝臟手術後復發之病患。化學治療可使用於靜脈途徑或者肝動脈栓塞治療，其中doxorubicin目前為肝動脈栓塞治療常用的化療藥物。然而病患對化學治療藥物反應差或者無反應甚至是具抗藥性，仍是一大問題。此外，如何減少藥物劑量使降低藥引致的副作用，是一大挑戰。我們研究發現Shh訊息傳導途徑對肝癌之生成、侵襲性、復發及癌幹細胞，扮演重要角色。抑制Shh訊息傳導途徑能夠抑制小鼠肝癌細胞及其幹細胞，有研究者指出Shh之抑制可以加強肝細胞癌之放射敏感性。本研究團隊探討抑制Shh訊息傳導途徑是否能有助於增加肝細胞癌對化學治療藥物doxorubicin之敏感性，並研究治療效果及其分子機轉。

 

研究主題II

訊息傳導途徑與乳癌再復發之相關性 乳癌是世界上女性首要癌症致死之一，侵襲性造成遠端轉移及復發是主要致死原因。乳癌幹細胞及初始細胞(CD44+CD24-)，具有侵襲性且並能不受治療影響。超音速刺蝟狀訊息傳導途徑(Sonic Hedgehog signaling pathway)於乳癌癌化過程扮演重要角色，並且此途徑高度活化於癌細胞相對於癌細胞鄰近組織。此訊息傳導途徑扮演維持癌幹細胞的必須角色。乳癌較高表現刺蝟狀訊息蛋白(Shh, Smo, Ptch, Gli)與較差預後及疾病進展狀態可能具相關性。本團隊分析超音速刺蝟狀訊息調控侵襲性的機制及微環境之免疫反應，預期能有助於開發臨床診斷及治療上之應用。

團隊成員

團隊主持人 鄭國祥 醫師 (Dr. Kuo-Shyang Jeng)

主治醫師 黃俊傑 醫師 (Dr. Chun-Chieh Huang)

主治醫師 林政寬 醫師 (Dr. Chen-Kuan Lin)

主治醫師 林建助 醫師 (Dr. Chien-Chu Lin)

合作單位

國立陽明大學

私立元智大學

論文發表

1. Glemarie C. Hermosa, Chien-Shiun Liao, Ho-Shing Wu, Sea-Fue Wang, Ting-Yu Liu, Kuo-Shyang Jeng, Shu-Sheng Lin, Chiung-Fang Chang*, An-Cheng Aidan Sun*. Green Synthesis of Magnetic Ferrites (Fe3O4, CoFe2O4, and NiFe2O4) Stabilized by Aloe Vera Extract for Cancer Hyperthermia Activities. IEEE Transactions on Magnetics. 2022, Aug 58(8): 1-7. doi: 10.1109/TMAG.2022.3158835 (IF:1.848)
2. Kuo-Shyang Jeng*, Chiung-Fang Chang, I-Shyan Sheen, Chi-Juei Jeng, Chih-Hsuan Wang. Upper Gastrointestinal Cancer and Liver Cirrhosis. Cancers (Basel). 2022 May 2;14(9):2269. doi: 10.3390/cancers14092269. (IF: 6.575)
3. Yi-Wen Tsai+, Kuo-Shyang Jeng+, Mu-Kuang He, Yang-Wen Hsieh, Hsin-Hung Lai, Chi-Yu Lai, Chun-Chieh Huang, Chiung-Fang Chang, Chung-Tsui Huang, Guor Mour Her. MXD3 Promotes Obesity and the Androgen Receptor Signaling Pathway in Gender-Disparity Hepatocarcinogenesis. Cells. 2021 Dec 6;10(12):3434. doi: 10.3390/cells10123434. PMID: 34943942; PMCID: PMC8700344. (IF: 7.666)
4. Kuo-Shyang Jeng, I-Shyan Sheen, Shu-Sheng Lin, Chuen-Miin Leu, Chiung-Fang Chang*. The Role of Endoglin in Hepatocellular Carcinoma. Int J Mol Sci. 2021 Mar 22;22(6):3208. doi: 10.3390/ijms22063208. PMID: 33809908; PMCID: PMC8004096. (IF: 6.208)
5. Ke-Hsun Hsu, Chin-Wen Wei, Yi-Ru Su, Tung Chou, Yueh-Ling Lin, Fu-Chen Yang, Ann-Ping Tsou, Chia-Lin Hsu, Ping-Hui Tseng, Nien-Jung Chen, Kuo-Shyang Jeng, Chuen-Miin Leu*. Upregulation of RelB in the miR-122 knockout mice contributes to increased levels of proinflammatory chemokines/cytokines in the liver and macrophages. Immunol Lett. 2020 Oct;226:22-30. doi: 10.1016/j.imlet.2020.06.015. (IF: 4.230)
6. Kuo-Shyang Jeng, I-Shyan Sheen, Chuen-Miin Leu, Ping-Hui Tseng, Chiung-Fang Chang*. The Role of Smoothened in Cancer. Int J Mol Sci. 2020 Sep 18;21(18):6863. doi: 10.3390/ijms21186863. PMID: 32962123; PMCID: PMC7555769. (IF: 6.208)
7. Kuo-Shyang Jeng, Ssu-Jung Lu, Chih-Hsuan Wang, Chiung-Fang Chang*. Liver Fibrosis and Inflammation under the Control of ERK2. Int J Mol Sci. 2020 May 27;21(11):3796. doi: 10.3390/ijms21113796. PMID: 32471201; PMCID: PMC7312875. (IF: 6.208)
8. Kuo-Shyang Jeng*, Chiung-Fang Chang, Shu-Sheng Lin. Sonic Hedgehog Signaling in Organogenesis, Tumors, and Tumor Microenvironments. Int J Mol Sci. 2020 Jan 23;21(3):758. doi: 10.3390/ijms21030758. PMID: 31979397; PMCID: PMC7037908. (IF: 6.208)
9. Kuo-Shyang Jeng, Chi-Juei Jeng, Wen-Juei Jeng, I-Shyan Sheen, Shih-Yun Li, Chuen-Miin Leu*, Yeou-Guang Tsay, Chiung-Fang Chang*. Sonic Hedgehog signaling pathway as a potential target to inhibit the progression of hepatocellular carcinoma. Oncol Lett. 2019 Nov;18(5):4377-4384. doi: 10.3892/ol.2019.10826. Epub 2019 Sep 9. PMID: 31611946; PMCID: PMC6781692. (IF: 3.111)
10. Kuo-Shyang Jeng*, Chun-Chieh Huang, Chien-Chu Lin, Cheng-Kuan Lin, Chung-Jen Teng, Kuo-Hsin Chen. Liver Transplantation After Downstagings of Ruptured Advanced Hepatocellular Carcinoma in Cirrhotic Liver: Is It Advisable? A Case Report. Transplant Proc. 2019 Jun;51(5):1468-1471. doi:10.1016/j.transproceed.2019.01.125. (IF: 0.799)
11. Kuo-Shyang Jeng*, Chun-Chieh Huang, Cheng-Kuan Lin, Chien-Chu Lin, Chung-Tsui Huang, Chen-Shuan Chung, Meng-Tzu Weng, Kuo-Hsin Chen. Reappraisal of Failures in Downstaging Treatment of Hepatocellular Carcinoma Prior to Liver Transplant-Preliminary Report on the Impact of Underestimations of Tumor Numbers and Tumor Sizes as Measured From Imaging Before Transplant. Transplant Proc. 2019 Jun;51(5):1428-1434. doi: 10.1016/j.transproceed.2019.03.020. (IF: 0.799)
12. Kuo-Shyang Jeng, Chi-Juei Jeng, I-Shyan Sheen, Szu-Hua Wu, Ssu-Jung Lu, Chih-Hsuan Wang, Chiung-Fang Chang*. Glioma-Associated Oncogene Homolog Inhibitors Have the Potential of Suppressing Cancer Stem Cells of Breast Cancer. Int J Mol Sci. 2018 May 5;19(5):1375. doi: 10.3390/ijms19051375. PMID: 29734730; PMCID: PMC5983844. (IF: 6.208)
13. Kuo-Shyang Jeng, Chi-Juei Jeng, Wen-Juei Jeng, I-Shyan Sheen, Shih-Yun Li, Ssu-Jung Lu, Chiung-Fang Chang*. Tropism of liver epithelial cells toward hepatocellular carcinoma in vitro and in vivo with altering gene expression of cancer stem cells. Am J Surg. 2018 Apr;215(4):735-743. doi: 10.1016/j.amjsurg.2017.11.041. Epub 2017 Dec 6. PMID: 29246405. (IF: 3.125)
14. Kuo-Shyang Jeng*, Chi-Juei Jeng, Wen-Juei Jeng, Chiung-Fang Chang, I-Shyan Sheen. Role of C-X-C chemokine ligand 12/C-X-C chemokine receptor 4 in the progression of hepatocellular carcinoma. Oncol Lett. 2017 Aug;14(2):1905-1910. doi: 10.3892/ol.2017.6396. Epub 2017 Jun 16. PMID: 28789425; PMCID: PMC5529928. (IF: 3.111)
15. Yunching Chen, Ya-Chi Liu, Yun-Chieh Sung, Rakesh R. Ramjiawan, Ts-Ting Lin, Chih-Chun Chang, Kuo-Shyang Jeng, Chiung-Fang Chang, Chun-Hung Liu, Dong-Yu Gao, Fu-Fei Hsu, Annique M. Duyverman, Shuji Kitahara, Peigen Huang, Simona Dima, Irinel Popescu, Keith T. Flaherty, Andrew X. Zhu, Nabeel Bardeesy, Rakesh K. Jain, Cyril H. Benes, Dan G. Duda*. Overcoming sorafenib evasion in hepatocellular carcinoma using CXCR4-targeted nanoparticles to co-deliver MEK-inhibitors. Sci Rep. 2017 Mar 9;7:44123. doi: 10.1038/srep44123. PMID: 28276530; PMCID: PMC5343435. (IF: 4.996)
16. Kuo-Shyang Jeng*, Chun-Chieh Huang, Cheng-Kuan Lin, Chien-Chu Lin, Kuo-Hsin Chen. Graft calcification caused by a torsion of the hepatic vein after a living-related donor liver transplantation. Ann Hepatol. 2017;16(1):164-168. doi: 10.5604/16652681.1226954. (IF:3.388)
17. Kuo-Shyang Jeng ,Chi-Juei Jeng, Wen-Juei Jeng, I-Shyan Sheen, Shih-Yun Li, Zih-Hang Hung, Hsin-I Hsiau, Ming-Che Yu, Chiung-Fang Chang*. Liver epithelial cells inhibit proliferation and invasiveness of hepatoma cells. Oncol Rep. 2016 Mar;35(3):1622-8. doi: 10.3892/or.2015.4478. Epub 2015 Dec 8. PMID: 26647726. (IF: 4.136)
18. Kuo-Shyang Jeng*, Chi-Juei Jeng, Wen-Juei Jeng, I-Shyan Sheen, Chiung-Fang Chang, Hsin-I Hsiau, Zih-Hang Hung, Ming-Che Yu, Fang-Yu Chang. Sonic hedgehog pathway inhibitor mitigates mouse hepatocellular carcinoma. Am J Surg. 2015 Sep;210(3):554-60. doi: 10.1016/j.amjsurg.2015.03.001. Epub 2015 May 8. PMID: 26073903. (IF: 3.125)
19. Kuo-Shyang Jeng*, Chiung-Fang Chang, Wen-Juei Jeng, I-Shyan Sheen, Chi-Juei Jeng. Heterogeneity of hepatocellular carcinoma contributes to cancer progression. Crit Rev Oncol Hematol. 2015 Jun;94(3):337-47. doi: 10.1016/j.critrevonc.2015.01.009. Epub 2015 Jan 29. PMID: 25680939. (IF: 6.625)
20. Kuo-Shyang Jeng*. Education and imaging. Hepatology: Chilaiditi sign after right hepatectomy for hepatocellular carcinoma. J Gastroenterol Hepatol. 2015 Mar;30(3):439. doi: 10.1111/jgh.12850. (IF: 4.369)
21. Pi-Jung Hsiao, Jo-Chi Jao, Jin-Lian Tsai, Wen-Tsan Chang, Kuo-Shyang Jeng, Kung-Kai Kuo*. Inorganic arsenic trioxide induces gap junction loss in association with the downregulation of connexin43 and E-cadherin in rat hepatic "stem-like" cells. Kaohsiung J Med Sci. 2014 Feb;30(2):57-67. doi: 10.1016/j.kjms.2013.10.002. (IF: 2.996)
22. Kuo-Hsin Chen, Shian-Dian Chen, Ying-Da Chen, Yin-Jen Chang, Tzu-Chao Lin, Tiing-Foong Siow, U-Chon Chio, Shu-Yi Huang, Jiann-Ming Wu, Kuo-Shyang Jeng. Robotic left hepatectomy with revision of hepaticojejunostomy. Asian J Surg. 2014 Apr;37(2):106-9. doi: 10.1016/j.asjsur.2014.01.005. (IF:2.808)
23. Kuo-Shyang Jeng*, I-Shyan Sheen, Wen-Juei Jeng, Ming-Che Yu, Hsin-I Hsiau, Fang-Yu Chang. High expression of Sonic Hedgehog signaling pathway genes indicates a risk of recurrence of breast carcinoma. Onco Targets Ther. 2013 Dec 27;7:79-86. doi: 10.2147/OTT.S54702. eCollection 2013. (IF: 4.345)
24. Kuo-Shyang Jeng*, I-Shyan Sheen, Wen-Juei Jeng, Chien-Chu Lin, Chien-Kuan Lin, Jui-Chih Su, Ming-Che Yu, Hsin-Yi Fang. High expression of patched homolog-1 messenger RNA and glioma-associated oncogene-1 messenger RNA of sonic hedgehog signaling pathway indicates a risk of postresection recurrence of hepatocellular carcinoma. Ann Surg Oncol. 2013 Feb;20(2):464-73. doi: 10.1245/s10434-012-2593-y. (IF: 4.339)