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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/13316
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| Title: | A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment |
| Authors: | Song, JS;Chang, CC;Wu, CH;Dinh, TK;Jan, JJ;Huang, KW;Chou, MC;Shiue, TY;Yeh, KC;Ke, YY;Yeh, TK;Ta, YNN;Lee, CJ;Huang, JK;Sung, YC;Shia, KS;Chen, Y |
| Contributors: | Institute of Biotechnology and Pharmaceutical Research |
| Abstract: | The CXC chemokine receptor type 4 (CXCR4) receptor and its ligand, CXCL12, are overexpressed in various cancers and mediate tumor progression and hypoxia-mediated resistance to cancer therapy. While CXCR4 antagonists have potential anticancer effects when combined with conventional anticancer drugs, their poor potency against CXCL12/CXCR4 downstream signaling pathways and systemic toxicity had precluded clinical application. Herein, BPRCX807, known as a safe, selective, and potent CXCR4 antagonist, has been designed and experimentally realized. In in vitro and in vivo hepatocellular carcinoma mouse models it can significantly suppress primary tumor growth, prevent distant metastasis/cell migration, reduce angiogenesis, and normalize the immunosuppressive tumor microenvironment by reducing tumor-associated macrophages (TAMs) infiltration, reprogramming TAMs toward an immunostimulatory phenotype and promoting cytotoxic T cell infiltration into tumor. Although BPRCX807 treatment alone prolongs overall survival as effectively as both marketed sorafenib and anti–PD-1, it could synergize with either of them in combination therapy to further extend life expectancy and suppress distant metastasis more significantly. |
| Date: | 2021-03-30 |
| Relation: | Proceedings of the National Academy of Sciences of the United States of America. 2021 Mar 30;118(13):Article number e2015433118. |
| Link to: | http://dx.doi.org/10.1073/pnas.2015433118 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0027-8424&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000637394200021 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85103063097 |
| Appears in Collections: | [夏克山] 期刊論文
[葉燈光] 期刊論文
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| SCP85103063097.pdf | | 2630Kb | Adobe PDF | 390 | View/Open |
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