RESUMO
Pyroptosis is a newly recognized type of programmed cell death mediated by the gasdermin family and caspase. It is characterized by the formation of inflammasomes and the following inflammatory responses. Recent studies have elucidated the value of pyroptosis induction in cancer treatment. The inflammatory cytokines produced during pyroptosis can trigger immune responses to suppress malignancy. Physical approaches for cancer treatment, including radiotherapy, light-based techniques (photodynamic and photothermal therapy), ultrasound-based techniques (sonodynamic therapy and focused ultrasound), and electricity-based techniques (irreversible electroporation and radiofrequency ablation), are effective in clinical application. Recent studies have reported that pyroptosis is involved in the treatment process of physical approaches. Manipulating pyroptosis using physical approaches can be utilized in combating cancer, according to recent studies. Pyroptosis-triggered immunotherapy can be combined with the original anti-tumor methods to achieve a synergistic therapy and improve the therapeutic effect. Studies have also revealed that enhancing pyroptosis may increase the sensitivity of cancer cells to some physical approaches. Herein, we present a comprehensive review of the literature focusing on the associations between pyroptosis and various physical approaches for cancer and its underlying mechanisms. We also discussed the role of pyroptosis-triggered immunotherapy in the treatment process of physical manipulation.
RESUMO
Alpelisib, an oral selective and small-molecule phosphoinositide 3-kinase inhibitor, was lately approved in the United States to treat breast cancer. A sensitive method to quantify alpelisib levels in rat plasma on the basis of ultra-performance liquid chromatography-tandem mass spectrometry technique was established and validated, which was successfully employed to explore the effects of CYP3A4 inhibitors on alpelisib pharmacokinetics in rats. A C18 column named Acquity UPLC BEH C18 was applied to achieve the separation of alpelisib and internal standard duvelisib after protein precipitation with acetonitrile. The mobile phase in this study had two components, namely, acetonitrile and water having 0.1% formic acid, and a program with gradient elution method was used at a flow rate of 0.40 ml/min. Mass spectrometry in a positive multiple reaction monitoring mode was operated. In the scope of 1-5,000 ng/ml, this assay had excellent linearity. Our newly developed assay was verified in all aspects of bioanalytical method validation, involving lower limit of quantification, selectivity, accuracy and precision, calibration curve, extraction recovery, matrix effect, and stability. Then, this assay was used to detect the plasma levels of alpelisib from a drug-drug interaction investigation, where ketoconazole remarkably increased the plasma concentration of alpelisib and changed alpelisib pharmacokinetics more than itraconazole. This study will help better understand the pharmacokinetic properties of alpelisib, and further clinical studies should be done to confirm this result in patients.
RESUMO
De novo designed lipidated methotrexate was synthesized and self-assembled into microbubbles for targeted rheumatoid arthritis theranostic treatment. Controlled lipidatedmethotrexate delivery was achieved by ultrasound-targetedmicrobubble destruction technique. Methotrexate was dissociated inflammatory microenvironment of synovial cavity, owing to representive low pH and enriched leucocyte esterase. We first manipulated methotrexate controlled release with RAW 264.7 cell line in vitro and further verified with rheumatoid arthritis rabbits in vivo. Results showed that lipidated methotrexate microbubbles precisely affected infection focus and significantly enhanced rheumatoid arthritis curative effect comparing with dissociative methotrexate. This study indicates that lipidated methotrexate microbubbles might be considered as a promising rheumatoid arthritis theranostics medicine.