The aim of the present study was to investigate the effects of microRNA (miR-)146a on the cisplatin sensitivity of the non-small cell lung cancer (NSCLC) A549 cell line and study the underlying molecular mechanism. The differences in expression of miRNAs between A549 and A549/cisplatin (A549/DDP) cells were determined, and miR-146a was selected to study its effect on cisplatin sensitivity of A549/DDP cells. miR-146a mimic and inhibitor transient transfection systems were constructed using vectors, and A549/DDP cells were infected with miR-146a mimic and inhibitor to investigate growth, apoptosis and migration. The directed target of miR-146a was determined and the underlying molecular mechanism was validated in the present study. The results of the present study demonstrated that miR-146a was downregulated in NSCLC A549/DDP cells, compared with A549 cells. The overexpression of miR-146a induced apoptosis and inhibited the growth and invasion of A549/DDP cells, which resulted in increased cisplatin sensitivity in NSCLC cells. The JNK2 gene was determined as the direct target of miR-146a, and may be activated by the overexpression of miR-146a. Additionally, JNK2 activated the expression of p53 and inhibited B cell lymphoma 2. The upregulation of miR-146a increased cisplatin sensitivity of the A549 cell line by targeting JNK2, which may provide a novel method for treating NSCLC cisplatin resistance.
Background: Immune checkpoint inhibitors (ICIs) have shown clinical benefit in many advanced tumors, however, pseudo-progression is a noted phenomenon of ICIs characterized by radiologic enlargement of the tumor burden, followed by regression. How to differentiate pseudo-progression from progression remains a critical clinical issue. Recent studies have demonstrated the association between immune-related adverse events (irAEs) and efficacy of ICIs. Here we demonstrated an ovarian cancer patient treated with nivolumab in whom the early-onset irAE was identified to differentiate pseudo-progression from progression. Case presentation: Here we present the case of a 47-years-old woman with histopathologically confirmed diagnosis of metastatic ovarian cystadenocarcinoma. Immunohistochemical examination showed 10% of tumor cells to express the programmed cell death receptor ligand 1 (PD-L1) and a 381-gene panel sequencing in a College of American Pathologists (CAP) certificated lab revealed a moderate mutational tumor burden with 5.7 Mutants/Mb. The patient received nivolumab 100 mg every 2 weeks as a fourth line treatment. Within the first 2 months, the tumor volume increased by 23.6%. However, the patient experienced an elevation of Alanine aminotransferase (ALT) and Aspartate aminotransmerase (AST), which was diagnosed as the immune-related hepatitis. Thus, the treatment continued and afterwards, the patient reached a partial response (PR) to nivolumab and the progression-free survival was 9 months. Conclusion: To our knowledge, this is the first case describing early-onset immune-related adverse events to identify pseudo-progression in a patient with ovarian cancer treated with nivolumab, and PD-L1 expression level may be a predictive biomarker in the immunotherapy of ovarian cancer.
Background: The aim of this study was to investigate the relationship between positive lymph node ratio (PLNR) and postoperative distant metastasis and prognosis in esophageal squamous cell carcinoma (ESCC). Patients and Methods: 167 ESCC patients with regional lymph node metastasis, who underwent radical esophagectomy and lymphadenectomy at the Ningbo Yinzhou People's Hospital between October 2005 and December 2010, were enrolled in this study. The prognostic value of PLNR was calculated by univariate Kaplan-Meier survival analysis and multivariate Cox proportional hazard model analysis. Results: After a median follow-up time of 34 months, 88 (52.7%) of the 167 patients had distant metastasis and 76 (45.5%) had died. Patients with a PLNR of less than 0.15 had a 5-year distant metastasis-free survival (DMFS) rate of 33.3% while those with a PLNR greater than 0.15 had a 5-year DMFS rate of 25.5% (log-rank test, p = 0.002). Multivariate analysis indicated that a PLNR > 0.15 was an independent poor prognostic factor for DMFS (hazard ratio (HR) 1.92, 95% confidence interval (CI) 1.21-3.05) and overall survival (OS) (HR 2.08, 95% CI 1.26-3.43). This analysis was adjusted for patient age, sex, smoking behavior, and pT stage. Conclusion: The PLNR is an independent prognostic factor for predicting postoperative distant metastasis and prognosis in ESCC, and patients with a PLNR ≤ 0.15 have better OS.
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