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- W4247160908 abstract "Abstract Background: Currently, most clinicians prescribe angiotensin-converting enzyme inhibitors (ACEIs) to alleviate proteinuria caused by anti-angiogenic drugs (AADs) according to diabetic nephropathy guidelines or expert recommendations. However, the efficacy ACEIs and potential cancer promoting effect are controversial. This study aimed at confirming whether ACEIs are beneficial in anti-angiogenesis therapy for hepatocellular carcinoma. Methods: In clinic, we observed the impact of ACEIs on AADs during the treatment of hepatocellular carcinoma. Next, we established different tumor-bearing mouse models to confirm that whether ACEIs have any effect on the anti-cancer efficacy and proteinuria side effects of AADs. Further, we confirmed the relevant mechanism in vivo. Results: Our clinical data have shown that some hepatocellular carcinoma (HCC) patients experienced tumor progression by ACEIs administration for the treatment of hypertension or proteinuria caused by AADs. We have confirmed that in different tumor-bearing mouse models, ACEIs did not delay the appearance of proteinuria or alleviate proteinuria caused by AADs but compromised the anticancer efficacy of AADs. This effect is unrelated to a change in the VEGF signaling pathway. Our data showed that the combination of ACEIs and AADs flared the production of kidney-derived erythropoietin (EPO). In turn, EPO compromises the anti-angiogenic effects of AADs and decreases antitumor activity. Conclusions: For the treatment of proteinuria caused by AADs, ACEIs have no efficacy but promote drug resistance. Kidney-derived EPO is mainly responsible for ACEIs induced anti-angiogenesis resistance." @default.
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- W4247160908 date "2020-09-10" @default.
- W4247160908 modified "2023-10-16" @default.
- W4247160908 title "Angiotensin-converting Enzyme Inhibitors Have Adverse Effects in Anti-angiogenesis Therapy for Hepatocellular Carcinoma" @default.
- W4247160908 doi "https://doi.org/10.21203/rs.3.rs-72739/v1" @default.
- W4247160908 hasPublicationYear "2020" @default.
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