Oncotarget
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Numerous clinical trials show crizotinib has promising efficacy for anaplastic lymphoma kinase (ALK) positive non-small cell lung cancer (NSCLC) patients which trigger the substitution of traditional chemotherapy to be the current standard first-line treatment for these patients. Conversely, few reports systematically analyze toxicity of crizotinib. Hence, we performed a first meta-analysis to determine the risk of crizotinib-related severe adverse events (SAEs) and fatal adverse events (FAEs) in ALK positive NSCLC patients. ⋯ Crizotinib may not increase the risk of SAEs and FAEs in patients with ALK positive NSCLC compared with chemotherapy.
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Pulmonary arterial hypertension (PAH) is a lethal disease that often affects the young. Although Bone Morphogenetic Protein Receptor Type 2 gene (BMPR2) mutations are related with idiopathic and heritable PAH, the low penetrance and variable expressivity in PAH suggest the existence of other genetic and/or environmental factors. In this study, we aimed to identify novel genetic factors associated with PAH, irrespective of BMPR2 mutation. ⋯ Seven loci identified in the genome-wide study were submitted to the validation study, and a novel susceptibility locus, PDE1A|DNAJC10, was identified that maps to 2q32.1 (rs71427857, P = 7.9 × 10-9, odds ratio in the validation study = 5.18; 95% CI 1.86 - 14.42). We also found the augmentation of PDE1A protein in distal remodeled pulmonary artery walls in idiopathic PAH patients. Given that phosphodiesterase 5 inhibitors are effective for the treatment of idiopathic and heritable PAH, our findings suggest that PDE1A could be a novel therapeutic target of PAH.
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Breast carcinoma is a major health issue for millions of women. Current therapies have serious side effects, and are only partially effective in patients with metastatic tumors. Thus, the need for novel and less toxic therapies is urgent. ⋯ Here, we evaluated SP17 expression levels in breast cancer cell lines, invasive ductal breast carcinoma, including patients with TNBC, and adjacent non-neoplastic breast tissue, and determined whether SP17 was capable of generating SP17-specific cytotoxic T lymphocytes in vitro. We showed that SP17 is expressed in breast cancer cell lines and primary breast tumors and importantly in TNBC subtype, but not in adjacent non-tumoral breast tissue or unaffected tissues, except in male germinal cells. Furthermore, we detected specific anti-SP17 antibodies in patients' sera and we generated SP17-specific, HLA class I-restricted, cytotoxic T lymphocytes capable of efficiently killing breast cancer cells.
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Diallyl trisulfide (DATS), the major active ingredient in garlic, has been reported to confer cardioprotective effects. However, its effect on myocardial ischemia-reperfusion (MI/R) injury in diabetic state and the underlying mechanism are still unknown. We hypothesize that DATS reduces MI/R injury in diabetic state via AMPK-mediated AKT/GSK-3β/HIF-1α activation. ⋯ While 2-methoxyestradiol (a HIF-1α inhibitor) reduced HIF-1α expression without affecting AKT/GSK-3β signaling. Taken together, these data showed that DATS protected against MI/R injury in diabetic state by attenuating cellular apoptosis via AMPK-mediated AKT/GSK-3β/HIF-1α signaling. Its cardioprotective effect deserves further study.
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Epidural use can provide a better short-term outcome and protect patients from the postoperative development of tumour recurrence and metastases. In this study, we sought to assess the effects of intra- and postoperative anaesthesia and analgesia choice on outcome after gastric cancer resection, searched for evidence of interaction between intra-and postoperative epidural use and outcomes of gastric cancer patients. ⋯ These results indicated that epidural anaesthesia combined with general anaesthesia and patient-controlled epidural analgesia may be associated with the improved overall survival in gastric cancer patients who underwent resection.