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Donafenib activates the p53 signaling pathway in hepatocellular carcinoma, induces ferroptosis, and enhances cell apoptosis.
Clin Exp Med
January 2025
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Guangxi Medical University, Nanning, China.
Donafenib is an improved version of sorafenib in which deuterium is substituted into the drug's chemical structure, enhancing its stability and antitumor activity. Donafenib exhibits enhanced antitumor activity and better tolerance than sorafenib in preclinical and clinical studies. However, the specific mechanism of its effect on hepatocellular carcinoma has not been reported.
View Article and Find Full Text PDFTranscription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC.
Front Pharmacol
December 2024
Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Background: Sorafenib is a first-line treatment for hepatocellular carcinoma (HCC); however, acquired resistance often results in a poor prognosis, indicating a need for more effective therapies. Sorafenib induces cell death through an iron-dependent mechanism known as ferroptosis, which is closely associated with the onset and progression of HCC.
Methods: This study investigated the role of ACSL3 in sorafenib resistance and ferroptosis in HCC.
PEROXYNITRITE IS INVOLVED IN THE MITOCHONDRIAL DYSFUNCTION INDUCED BY SORAFENIB IN LIVER CANCER CELLS.
Free Radic Biol Med
December 2024
Institute of Biomedicine of Seville (IBiS), Hospital University "Virgen del Rocío"/CSIC/University of Seville, Seville, Spain; Department of Medical Physiology and Biophysics, University of Seville, Seville, Spain; Biomedical Research Center for Hepatic and Digestive Diseases (CIBERehd), Madrid, Spain. Electronic address:
Background: Sorafenib is a tyrosine kinase inhibitor (TKI) that belongs to the landscape of treatments for advanced stages of hepatocellular carcinoma (HCC). The induction of cell death and cell cycle arrest by Sorafenib has been associated with mitochondrial dysfunction in liver cancer cells. Our research aim was to decipher underlying oxidative and nitrosative stress induced by Sorafenib leading to mitochondrial dysfunction in liver cancer cells.
View Article and Find Full Text PDFSorafenib promotes Treg cell differentiation to compromise its efficacy via VEGFR/AKT/Foxo1 signaling in hepatocellular carcinoma.
Cell Mol Gastroenterol Hepatol
December 2024
Department of Medical Oncology, Cancer Center of Zhejiang University, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, Zhejiang 310020, China.
Unlabelled: Our study revealed that sorafenib (Sora) induced the formation of an immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) by promoting the differentiation of regulatory T (Treg) cells through VEGFR/AKT/Foxo1 signaling, leading to compromised Sora efficacy. Importantly, combination treatment with an anti-CD25 antibody or the Foxo1 inhibitor AS1842856 inhibited Treg cell differentiation and increased the therapeutic efficacy of Sora in HCC.
Background & Aims: Sora is the first-line drug for advanced HCC.
A real-world pharmacovigilance study of Sorafenib based on the FDA Adverse Event Reporting System.
Front Pharmacol
December 2024
Department of Gastroenterology, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
Article Synopsis
- The study aimed to monitor adverse events (AEs) linked to Sorafenib, a drug used for treating liver, kidney, and thyroid cancers, focusing on enhancing patient safety.
- Reports from the FDA Adverse Event Reporting System (FAERS) from 2004 to 2024 were analyzed, revealing a total of 18,624 patients and 82,857 AEs across 26 organ systems.
- The findings included both expected AEs, like diarrhea and fatigue, and unexpected ones, such as gait inability and hyperkeratosis, highlighting the need for ongoing monitoring to identify new reactions and improve patient care.
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