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Purpose: Atezolizumab-bevacizumab (AB) is the established first-line systemic therapy for patients with unresectable hepatocellular carcinoma (uHCC). However, the optimal second-line treatment for patients unresponsive to AB remains undefined.

Patients And Methods: This multicenter, retrospective study included patients with uHCC who underwent second-line treatment with lenvatinib (LEN) or sorafenib (SOR) after AB failure at two academic centers between June 2018 and November 2023.

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The role of rodent behavioral models of schizophrenia in the ongoing search for novel antipsychotics.

Expert Opin Drug Discov

January 2025

Centro de Investigación en Reproducción Animal, Universidad Autónoma de Tlaxcala - CINVESTAV Tlaxcala, Tlaxcala, México.

Introduction: Existing pharmacotherapies for schizophrenia have not progressed beyond targeting dopamine and serotonin neurotransmission. Rodent models of schizophrenia are a necessary tool for elucidating neuropathological processes and testing potential pharmacotherapies, but positive preclinical results in rodent models often do not translate to positive results in the clinic.

Areas Covered: The authors reviewed PubMed for studies that applied rodent behavioral models of schizophrenia to assess the antipsychotic potential of several novel pharmacotherapies currently under investigation.

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Nicotinic acetylcholine receptors (nAChRs) are a family of ligand-gated ion channels expressed in nervous and non-nervous system tissue important for memory, movement, and sensory processes. The pharmacological targeting of nAChRs, using small molecules or peptides, is a promising approach for the development of compounds for the treatment of various human diseases including inflammatory and neurogenerative disorders such as Alzheimer's disease. Using the acetylcholine binding protein (Ac-AChBP) as an established structural surrogate for human homopentameric α7 nAChRs, we describe an innovative protein painting mass spectrometry (MS) method that can be used to identify interaction sites for various ligands at the extracellular nAChR site.

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The high mortality rate from hepatocellular carcinoma (HCC) is due primarily to challenges in early diagnosis and the development of drug resistance in advanced stages. Many first-line chemotherapeutic drugs induce ferroptosis, a form of programmed cell death dependent on ferrous iron-mediated oxidative stress, suggesting that drug resistance and ensuing tumor progression may in part stem from reduced ferroptosis. Since circular RNAs (circRNAs) have been shown to influence tumor development, we examined whether specific circRNAs may regulate drug-induced ferroptosis in HCC.

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Targeting p38γ synergistically enhances sorafenib-induced cytotoxicity in hepatocellular carcinoma.

Cell Biol Toxicol

January 2025

Division of Abdominal Tumor Multimodality Treatment, Cancer Center and Laboratory of Molecular Targeted Therapy in Oncology, West China Hospital, Sichuan University, 610041, Chengdu, Sichuan Province, China.

Sorafenib (Sora) is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC). It can significantly improve the survival rate of patients with advanced HCC, but it is prone to drug resistance during treatment, so the therapeutic effect is extremely limited. Here, we demonstrate that an elevated expression of protein kinase p38γ in hepatocellular carcinoma cells diminishes the tumor cells' sensitivity to Sora.

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