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Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation.

ABSTRACT: Radiofrequency ablation (RFA) is an important strategy for treatment of advanced hepatocellular carcinoma (HCC). However, the prognostic indicators of RFA therapy are not known, and there are few strategies for RFA sensitization. The transcription factor sterol regulatory element binding protein 1 (SREBP)-1 regulates fatty-acid synthesis but also promotes the proliferation or metastasis of HCC cells. Here, the clinical importance of SREBP-1 and potential application of knockdown of SREBP-1 expression in RFA of advanced HCC was elucidated. In patients with advanced HCC receiving RFA, a high level of endogenous SREBP-1 expression correlated to poor survival. Inhibition of SREBP-1 activation using a novel small-molecule inhibitor, SI-1, not only inhibited the aerobic glycolysis of HCC cells, it also enhanced the antitumor effects of RFA on xenograft tumors. Overall, our results: (i) revealed the correlation between SREBP-1 and HCC severity; (ii) indicated that inhibition of SREBP-1 activation could be a promising approach for treatment of advanced HCC.

SUBMITTER: Zou XZ

PROVIDER: S-EPMC8660695 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation.

Zou Xiao-Zheng XZ Hao Jun-Feng JF Zhou Xiu-Hua XH

Frontiers in oncology 20211126

Radiofrequency ablation (RFA) is an important strategy for treatment of advanced hepatocellular carcinoma (HCC). However, the prognostic indicators of RFA therapy are not known, and there are few strategies for RFA sensitization. The transcription factor sterol regulatory element binding protein 1 (SREBP)-1 regulates fatty-acid synthesis but also promotes the proliferation or metastasis of HCC cells. Here, the clinical importance of SREBP-1 and potential application of knockdown of SREBP-1 expre ...[more]

PMID: 34900747

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Project description:ObjectivesAt present, there are no established clinical guidelines for radiofrequency ablation (RFA) of peribiliary hepatocellular carcinoma (HCC). Therefore, the aim of this study was to compare the long-term outcomes of RFA for peribiliary vs. non-peribiliary HCC.MethodsThis retrospective study included 282 patients with peribiliary HCC (n = 109) or non-peribiliary HCC (n = 173) who received RFA between February 2013 and May 2021. Local tumor progression (LTP), overall survival (OS), disease-free survival (DFS), and complications were compared before and after propensity score matching (PSM).ResultsBefore PSM, there were no significant differences in 5-year LTP rates (26.3% vs. 23.6%, p = 0.602), OS rates (56.6% vs. 68.0%, p = 0.586), or DFS rates (22.9% vs. 25.7%, p = 0.239) between the peribiliary and non-peribiliary groups. After PSM, there were no significant differences in the 1-, 3-, and 5-year LTP rates (13.0%, 23.1%, and 26.3% vs. 12.1%, 25.1%, and 28.2%, respectively, p = 0.857), OS rates (97.2%, 73.5%, and 56.6% vs. 95.3%, 79.5%, and 70.6%, p = 0.727), or DFS rates (59.4%, 29.4%, and 22.9% vs. 64.2%, 33.1%, and 23.8%, p = 0.568) between the peribiliary non-peribiliary groups. Peribiliary location was not a significant prognostic factor for LTP (p = 0.622) or OS (p = 0.587). In addition, mild intrahepatic bile duct dilatation was more frequent in the peribiliary group (9.2% vs. 2.8%, p = 0.045).ConclusionLong-term outcomes of RFA were similar for peribiliary and non-peribiliary HCC. RFA is a viable alternative for treatment of peribiliary HCC.Critical relevance statementThe local tumor progression (LTP), overall survival (OS), and disease-free survival (DFS) rates after radiofrequency ablation (RFA) were similar for peribiliary and non-peribiliary hepatocellular carcinoma (HCC).Key pointsThere are currently no clinical guidelines for radiofrequency ablation (RFA) of peribiliary hepatocellular carcinoma (HCC). Local tumor progression, overall survival, and disease-free survival after RFA were similar for peribiliary and non-peribiliary HCC. RFA is a viable alternative for the treatment of peribiliary HCC.

Dataset Information

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation.

Publications

Inhibition of SREBP-1 Activation by a Novel Small-Molecule Inhibitor Enhances the Sensitivity of Hepatocellular Carcinoma Tissue to Radiofrequency Ablation.

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