Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Combined administration of two or more drugs is emerging as a new strategy in triple-negative breast neoplasms. This is the first study to investigate the combination of the histone deacetylase inhibitor mocetinostat and the antimetabolite drug capecitabine in triple-negative mammary neoplasms in a preclinical mouse model. Thirty-five female mice were grouped into the control group, capecitabine group, mocetinostat group, and combined drugs group. ⋯ Tumor weights were also reduced by 21% in the mocetinostat group, 27.5% in the capecitabine group, and 45% in the combined group. The combination of mocetinostat and capecitabine decreased the formation of tumors and metastases in lung tissue. In summary, the combination of mocetinostat and capecitabine was more effective than either drug alone in reducing the size of triple-negative breast neoplasms in a mouse model.
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Autoimmune thyroid disorders (AITD) are the most common autoimmune human disorders as the thyroid gland is a main target for autoimmunity. The association between rheumatologic and thyroid disorders has long been known, the most common being the association with rheumatoid arthritis. Our study was conducted to screen for the presence of symptoms, signs, and immune markers suggesting the presence of Sjogren's syndrome among patients with autoimmune thyroid disorders. ⋯ Anti-Ro was detected in serum of seven patients of the AITD patients with Sjogren syndrome while anti-La was detected in serum of eight patients. The most independent predictors of Sjogren's syndrome in AITD patients are anti-La, ESR, and salivary gland sonographic change. Sjogren's syndrome has been found in patients with AITD, and also patients with AITD have symptoms that mimic sicca disease despite not fulfilling the criteria for diagnosis.
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Pancreatic cancer is characterized by occult onset, low early diagnosis rate, rapid progress, and poor prognosis. Due to the low response rate and low PD-L1 expression in pancreatic cancer, the therapeutic application of PL-L1 inhibitors in pancreatic cancer is greatly limited. In vitro studies showed that the expression of PD-L1 increased in pancreatic cancer cells stimulated by fluorouracil (5-FU). ⋯ Moreover, the combination with the 5-FU remarkably enhanced the immune cytotoxicity of anti-PD-L1 antibodies in mice. In vitro analysis demonstrates that 5-FU increases the expression of PD-L1 on the surface of pancreatic cancer cell lines via up-regulating NF-κB and AKT pathways. This synergistic effect could be abolished by NF-κB and AKT inhibitors.
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Letter
EXPRESS: Pharmacokinetic advantages of lipophilic statins over rosuvastatin in COVID-19 management.
Not applicable.
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Cisplatin (DDP) resistance represents a pivotal contributing factor to chemotherapy failure and adverse patient outcomes in gastric cancer (GC). The objective of the present study was to investigate the roles and underlying mechanisms of myocyte enhancer factor 2A (MEF2A) in DDP resistance in GC. GC cell line AGS and MKN-45 cells were applied to construct DDP-resistant cells. ⋯ Mechanistically, MEF2A acts as a transcriptional activator of NFKBIA, which led to the reduction of phosphorylation of p65 and cytoplasmic retention. Moreover, MEF2A overexpression promoted the sensitivity of GC cells to DDP and tumor growth, whereas these effects were partially reversed by NFKBIA silence. Collectively, MEF2A mitigated the DDP resistance in GC cells by modulatory actions on the NFKBIA/NF-κB signaling, shedding light on MEF2A/NFKBIA might be a promising intervention target for improving DDP resistance in GC.