ArticleJournal of gastroenterology2014
Combination of sorafenib and angiotensin-II receptor blocker attenuates preneoplastic lesion development in a non-diabetic rat model of steatohepatitis.
Article in Journal of gastroenterology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12 citing papers in PubMed, 24 citations in OpenAlex.
- Evaluation of the effects of Theranekron and Sorafenib treatments on alpha-fetoprotein, heat shock protein 90 alpha and indoleamine 2,3 dioxygenase 1 enzyme levels in experimental hepatocellular carcinoma in rats.Molecular biology reports · 2025Article
- Liver endothelial cells in NAFLD and transition to NASH and HCC.Cellular and molecular life sciences : CMLS · 2023Review
- Antiangiogenic Drugs in NASH: Evidence of a Possible New Therapeutic Approach.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Article
- Combined Treatment with Sodium-Glucose Cotransporter-2 Inhibitor (Canagliflozin) and Dipeptidyl Peptidase-4 Inhibitor (Teneligliptin) Alleviates NASH Progression in A Non-Diabetic Rat Model of Steatohepatitis.International journal of molecular sciences · 2020Article
- The Role of Sinusoidal Endothelial Cells in the Axis of Inflammation and Cancer Within the Liver.Frontiers in physiology · 2020Review
- Renin-angiotensin inhibitors were associated with improving outcomes of hepatocellular carcinoma with primary hypertension after hepatectomy.Annals of translational medicine · 2019Article
- Disease Progression and Pharmacological Intervention in a Nutrient-Deficient Rat Model of Nonalcoholic Steatohepatitis.Digestive diseases and sciences · 2019Article
- von Willebrand factor is a useful biomarker for liver fibrosis and prediction of hepatocellular carcinoma development in patients with hepatitis B and C.United European gastroenterology journal · 2018Article
- Article
- Use of inhibitors of the renin-angiotensin system is associated with longer survival in patients with hepatocellular carcinoma.United European gastroenterology journal · 2017Article
- Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib.Journal of clinical biochemistry and nutrition · 2016Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGiven the well-documented adverse side effects of sorafenib, many sorafenib-treated patients may need the reduced initial dose of the compound, and an alternative sorafenib-based therapy, which exerts similar clinical benefit, is anticipated. An angiostatic therapy with sorafenib is considered one of the promising approaches for chemoprevention of hepatocellular carcinoma. The aim of the current study was to elucidate the combination effect of low dose of sorafenib and angiotensin-II receptor blocker (ARB) on hepatocarcinogenesis, especially in conjunction with angiogenesis.
methodsThe chemopreventive effect on the development of liver preneoplastic lesions, angiogenesis, and several indices was elucidated in rats. We also performed several sets of in vitro experiments to examine the mechanisms involved.
resultsUsing a non-diabetic rat model of steatohepatitis with choline deficient L-amino acid-defined diet, sorafenib demonstrated marked inhibition of preneoplastic lesions in a dose dependent manner. Combined treatment with ARB (losartan) at a clinically comparable dose and half dose of sorafenib resulted in the inhibitory effect equivalent to that of common dose of sorafenib along with suppression of hepatic neovascularization and potent angiogenic factor, vascular endothelial growth factor. Furthermore, similar combined inhibitory outcomes were observed in several sets of in vitro studies.
conclusionSince the combinatorial treatment using low doses of sorafenib and ARB could sufficiently induce inhibitory effect on the development of preneoplastic lesions at the magnitude similar to the conventional dose of sorafenib, this regimen may provide new strategy for patients intolerant of the usual dose of sorafenib in the future.
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