Chinese medical journal
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Chinese medical journal · Oct 2022
Inhibition of MYC suppresses programmed cell death ligand-1 expression and enhances immunotherapy in triple-negative breast cancer.
Cancer immunotherapy has emerged as a promising strategy against triple-negative breast cancer (TNBC). One of the immunosuppressive pathways involves programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), but many patients derived little benefit from PD-1/PD-L1 checkpoint blockades treatment. Prior research has shown that MYC, a master transcription amplifier highly expressed in TNBC cells, can regulate the tumor immune microenvironment and constrain the efficacy of immunotherapy. This study aims to investigate the regulatory relationship between MYC and PD-L1, and whether a cyclin-dependent kinase (CDK) inhibitor that inhibits MYC expression in combination with anti-PD-L1 antibodies can enhance the response to immunotherapy. ⋯ The combined therapy of CDK7 inhibitor THZ1 and anti-PD-L1 antibody appeared to have a synergistic effect, which might offer new insight for enhancing immunotherapy in TNBC.
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Chinese medical journal · Oct 2022
Molecular mechanisms and roles of pyroptosis in acute lung injury.
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), which are characterized by excessive inflammation and accompanied by diffuse injury of alveoli, can result in severe respiratory failures. The morbidity and mortality of patients remain high because the major treatments for ALI/ARDS are mainly supportive due to the lack of effective therapies. ⋯ Clinical and experimental evidence corroborates that pyroptosis of various cells in the lung, such as immune cells and structural cells, may play an important role in the pathogenesis of "cytokine storms" in ALI/ARDS, including those induced by COVID-19. Here, with a focus on ALI/ARDS and COVID-19, we summarized the recent advances in this field and proposed the theory of an inflammatory cascade in pyroptosis to identify new targets and pave the way for new approaches to treat these diseases.