التفاصيل البيبلوغرافية
| العنوان: |
A highly selective and potent CXCR4 antagonist for hepatocellular carcinoma treatment. |
| المؤلفون: |
Jen-Shin Song, Chih-Chun Chang, Chien-Huang Wu, Trinh Kieu Dinh, Jiing-Jyh Jan, Kuan-Wei Huang, Ming-Chen Chou, Ting-Yun Shiue, Kai-Chia Yeh, Yi-Yu Ke, Teng-Kuang Yeh, Yen-Nhi Ngoc Ta, Chia-Jui Lee, Jing-Kai Huang, Yun-Chieh Sung, Kak-Shan Shia, Yunching Chen |
| المصدر: |
Proceedings of the National Academy of Sciences of the United States of America; 3/30/2021, Vol. 118 Issue 13, p1-11, 11p |
| مصطلحات موضوعية: |
HEPATOCELLULAR carcinoma, CXCR4 receptors, CYTOTOXIC T cells, CHEMOKINE receptors, CELL migration, CURCUMIN, COMMERCIAL products |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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