ABSTRACT
Glutathione (GSH) is the most important small-molecule, active oligopeptide in the maintenance of redox balance. GSH contributes to antioxidant and thiol equilibrium, as well as modulates the activities of many signaling molecules and redox-sensi-tive transcription factors by S-glutathionylation. Several studies have shown that the GSH level increased in various tumors. Additional-ly, increased GSH significantly contributes to drug resistance by eliminating ROS, detoxifying drugs, or participating in DNA repair. GSH-related metabolic enzymes are overexpressed in resistant cells, thereby regulating cellular response to chemotherapy drugs. Deple-tion of GSH or downregulation of GSH-related metabolic enzymes may effectively reverse drug resistance and promote resistant cells to restore sensitivity. This potential indicates that the GSH antioxidant system plays an important role in drug resistance. The GSH anti-oxidant system, as a potential target for antitumor therapy and reversal of drug resistance, has recently become an attractive focus in cancer research. This paper presents a review of the role of the GSH antioxidant system in drug resistance and discusses the therapeutic strategies targeting the GSH antioxidant system.
ABSTRACT
Cancer cells frequently share biological characteristics and energy metabolic processes distinct from normal cells. The specific metabolic phenotype was originally known as the Warburg effect. Researchers later discovered that cancer cells prefer to synthesize fatty acid de novo . Moreover, key enzymes involved in fatty acid synthesis and β-oxidation are overexpressed in tumor tissues, with low or without expression in normal tissues. Abnormal fatty acid metabolism is related to the survival and invasiveness of cancer cells, indicating that abnormal fatty acid metabolism provides the crucial components and energy sources of cancer cells. In recent years, the specific phenotype of abnormal fatty acid metabolism and the exploration of the role of this metabolic alteration in cancer biology and therapeutic strategies targeting the fatty acid metabolic pathways have become attractive focuses in cancer research. The role of active fatty acid metabolism in tumorigenesis and development, as well as the research progress in the development of the specific inhibitors, is reviewed in this paper.
ABSTRACT
Objective: To evaluate the pharmacokinetics of palonosetron hydrochloride in healthy volunteers. Methods: Thir-ty-one healthy volunteers were grouped into three palonosetron hydrochloride dosage regimens of 0.125, 0.25, and 0.5 mg. The plasma concentrations of palonosetron were determined by ultra high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). DAS 2.1 software was applied to assess the plasma concentration-time data. Results:After intravenous injection of 0.125, 0.25, and 0.5 mg palonosetron to the subjects, the AUC0-168h values of palonosetron were (7.5±2.5), (15.2±4.0), and (34.8±9.7) μg· h·mL-1. The t1/2 values were (27.2±9.5), ( 27.2±6.5), and (31.4±5.6) h. Palonosetron exposure increased proportionally with the dose range of 0.125 mg to 0.5 mg. The correlation coefficient was 0.998. No grade 3 or grade 4 toxicity was observed during the study. Con-clusion:A rapid, sensitive, and selective UPLC-MS/MS method for palonosetron quantification in human plasma was developed and validated. All the participants indicated high tolerance throughout the study. Our data showed that palonosetron exhibits linear pharma-cokinetics over the the dose range of 0.125 mg to 0.5 mg.