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TAK-994 Mechanistic Investigation into Drug-Induced Liver Injury.
Toxicol Sci
January 2025
Takeda Development Center Americas, Inc, Cambridge, MA, USA.
The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.
View Article and Find Full Text PDFHAIC plus lenvatinib and tislelizumab for advanced hepatocellular carcinoma with Vp4 portal vein invasion.
Hepatol Int
January 2025
Department of Interventional Radiology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510062, China.
Background/objective: The treatment strategy for hepatocellular carcinoma (HCC) with Vp4 (main trunk) portal vein tumor thrombosis (PVTT) remains controversial due to the dismal prognosis. We aimed to investigate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus lenvatinib and tislelizumab in these patients.
Methods: This multicenter retrospective study included treatment-naive HCC patients with Vp4 PVTT from 2017 to 2022.
The tumor distance to the main hepatic vessels is a predictor of recurrence-free survival and overall survival in hepatocellular cancer.
Langenbecks Arch Surg
January 2025
Department of Surgery, Medical Faculty Mannheim, Universitätsmedizin Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
Introduction: The impact of the distance of the tumor from the main hepatic vessels (DTV), such as the Glissonean pedicle or hepatic veins, on oncological outcomes for Hepatocellular carcinoma (HCC) patients is relatively understudied. Therefore, the objective of this study was to explore the correlation between DTV and survival in patients with HCC after curative hepatic resection.
Methods: Consecutive patients who underwent curative-intent liver surgery for HCC between April 2018 and May 2023 were identified from a prospective database.
Hepatobiliary scintigraphy and liver function changes in patients with hepatocellular carcinoma treated with Ho-radioembolization : HBS in HCC treated with holmium-166.
EJNMMI Res
January 2025
Department of Radiology & Nuclear Medicine, University Medical Center Utrecht, Heidelberglaan 100, Utrecht, 3584 CX, the Netherlands.
Background: To study the feasibility of hepatobiliary scintigraphy (HBS) to improve selection and planning of patients with hepatocellular carcinoma (HCC) treated with holmium-166 (Ho)-microspheres radioembolization.
Results: Thirty-one patients with HCC were included and treated with Ho- radioembolization as part of a prospective phase 2 study. Twenty-seven patients were eligible for analysis, 67% had a cirrhotic liver morphology on imaging, 70% had multifocal disease and 51% had bilobar disease.
Percutaneous transhepatic arterial access for coil embolization of hepatic artery infusion pump-associated bleeding.
CVIR Endovasc
January 2025
Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.
Background: Hepatic artery infusion pump (HAIP) chemotherapy is a locoregional treatment for intrahepatic malignancies. HAIPs are surgically implanted, and the catheter tip is typically inserted into a ligated gastroduodenal artery stump. Potential complications at the catheter insertion site include dehiscence, pseudoaneurysm or extravasation, and adjacent hepatic arterial stenosis and thrombosis.
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