miR-93-5p suppresses ovarian cancer malignancy and negatively regulate CCND2 by binding to its 3'UTR region.

Ovarian cancer is the most fatal gynecological cancer worldwide, yet the fundamental mechanism of malignancy acquisition in ovarian cancer remains unknown. miRNA has been implicated to a variety of diseases, including cancer initiation and progression. Cyclin-D2 (CCND2) is ubiquitously implicated in cancer uncontrol cell proliferation. Bioinformatic research revealed that CCND2 is a candidate gene for miR-93-5p with a binding site in its 3'UTR region in the current study. Using our ovarian cancer sample, we verified that miR-93-5p is negatively correlated with CCND2 mRNA and protein levels. Luciferase report assay revealed miR-93-5p inhibits CCND2 production through binding to the 3'UTR region. The expression of miR-93-5p in ovarian cancer patient samples was then determined, and a survival analysis was performed. Our findings showed that miR-93-5p is downregulated in ovarian cancer and is a favorable predictive factor in ovarian cancer patient. CCK8 assay, wound healing assay and flow cytometry-based cell cycle and apoptotic cell analyses were employed here. We found that miR-93-5p suppresses ovarian cancer cell proliferation and migration while enhances cell death. Our research certified that miR-93-5p reduces ovarian cancer malignancy by targeting CCND2.

Immune-checkpoint inhibitors versus other systemic therapies in advanced head and neck cancer: a network meta-analysis.

Aim: We assessed the efficiency of immune checkpoint inhibitors relative to other systemic therapies in previously treated recurrent/metastatic head and neck cancer. Materials & methods: Relative treatment effects were assessed from eligible randomized controlled trials using Bayesian network meta-analyses. Results: Among 15 trials evaluating 14 treatments, nivolumab achieved the best overall survival (OS) benefit; zalutumumab and buparlisib + paclitaxel provided the best progression-free survival benefit and objective response rate. Buparlisib + paclitaxel and zalutumumab were associated with the best OS rate at 6 and 12 months, respectively; nivolumab yielded the best OS rate at 18-24 months. Conclusion: Nivolumab was the most favorable treatment. Zalutumumab and buparlisib + paclitaxel had better efficiency, and might be a better selection for patients with programmed death-ligand 1-low/negative tumors than other treatments.

hMOF reduction enhances radiosensitivity through the homologous recombination pathway in non-small-cell lung cancer.

PURPOSE: Human males absent on the first (hMOF) is a histone acetyltransferase (HAT) and is responsible for acetylating histone H4 at lysine 16 (H4K16). Recent studies have indicated that hMOF is overexpressed in non-small-cell lung cancer (NSCLC) as an oncogene. The aim of this study is to profile the prognostic roles of hMOF in patients with unresectable stage III NSCLC undergoing definitive radiotherapy (RT) and in the radiosensitivity of human NSCLC cells. MATERIALS AND METHODS: The expression of hMOF was detected in 24 normal and tumor-paired fresh-frozen NSCLC tissue samples. The immunohistochemistry was conducted, and the correlation of hMOF with clinicopathological parameters was studied in tissues from 90 patients with unresectable stage III NSCLC who underwent definitive RT. Radiation sensitivity was monitored using clonogenic assays in NCI-H1299 and A549 NSCLC cell lines with hMOF knockdown. RESULTS: hMOF was overexpressed in NSCLC tissues compared with non-cancerous tissues. Compared to patients with downregulated hMOF, upregulated hMOF was observed in 51.1% (46/90) of the patients, who showed a significantly worse 5-year survival rate (5.4% vs 22.9%, P=0.025). hMOF expression was an independent prognostic factor of unresectable stage III NSCLC patients who underwent definitive RT. Silencing hMOF increased in vitro the sensitive enhancing ratio (SER) of NSCLC cell lines and downregulated the expression of phospho-ataxia telangiectasia mutated (p-ATM) and RAD51 after irradiation (IR). CONCLUSION: Overexpression of hMOF predicts poor prognosis in patients with unresectable stage III NSCLC undergoing definitive RT. Downregulating hMOF might be a promising intervention to improve the outcome after RT.

Programmed death ligand 1 expression in esophageal cancer following definitive chemoradiotherapy: Prognostic significance and association with inflammatory biomarkers.

Immunotherapy with anti-programmed cell death protein 1 or programmed death ligand 1 (PD-L1) agents has demonstrated promising efficacy for the treatment of various types of malignancies. However, the role of PD-L1 as a tumor prognostic marker remains poorly understood. In the present study, the prognostic value of PD-L1 expression in esophageal carcinoma (EC) following definitive chemoradiotherapy (CRT) was investigated, and its associations with three systemic inflammation biomarkers, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and lymphocyte-to-monocyte ratio (LMR) were further explored. A total of 104 patients with non-metastatic EC, who underwent definitive CRT between January 2009 and December 2012, were retrospectively analyzed. The expression of PD-L1 was examined by immunohistochemistry and the impact of PD-L1 expression level on overall survival (OS) was assessed. Furthermore, pretreatment neutrophil, lymphocyte, platelet and monocyte counts were obtained from routine blood tests to calculate the NLR, PLR and LMR. PD-L1 was overexpressed in EC compared with normal esophageal epithelium, with a positive expression rate of 37.5%. Additionally, patients with positive PD-L1 expression had a lower NLR than those with negative PD-L1 expression (P=0.001). On multivariate analysis, the positive staining of PD-L1 was significantly associated with improved OS (HR, 0.6; 95% CI, 0.372-0.965; P=0.035). Kaplan-Meier survival analysis showed a similar result (P=0.009). Additionally, sex (HR, 0.449; 95% CI, 0.229-0.880; P=0.020), clinical stage III (HR, 2.471; 95% CI, 1.171-5.212; P=0.018), and receipt of concurrent chemoradiation (HR, 0.590; 95% CI, 0.368-0.945; P=0.028) were all independent prognostic factors in EC treated with definitive CRT. The correlation of NLR with PD-L1 expression validated the relevance of immunity and inflammation. In summary, the present study demonstrated that positive PD-L1 expression is associated with improved survival in patients with EC treated with radical CRT, indicating that PD-L1 is a promising prognostic marker.

Primary atrial fibromyxosarcoma with multiple-system metastases: A case report.

RATIONALE: Fibromyxosarcoma is common in head and neck, vessel, omentum, and reproductive system, with low-grade malignant behavior. However, primary atrial fibromyxosarcoma with highly malignant behavior is extremely rare. PATIENT CONCERNS: A 34-year-old female presented with oppression in the chest, short breath, and onset of headache as initial symptoms. The preoperative echocardiogram showed a medium-size echogenic mass close to the posterior leaflet of the mitral valve in the left atrium. DIAGNOSIS: Primary atrial fibromyxosarcoma with multiple-system metastases. INTERVENTIONS: The patient underwent surgery, and the tumor was removed completely. The diagnosis of left atrium fibromyxosarcoma was confirmed through postoperative histopathological examination. Positron emission tomography/computed tomography scan was performed, which revealed multiple metastases to left adnexa, bilateral adrenal glands, left iliacus, right lateral ventricle, and skeletal system. OUTCOMES: The patient died of cerebral hernia caused by hemorrhage from the metastatic brain tumor, 30 days after the surgery, without receiving chemotherapy or radiotherapy. LESSONS: Cardiac fibromyxosarcoma is a rare primary malignant cardiac neoplasm, probably with systemic metastases. The possibility of malignancy should be considered as differential diagnosis for cardiac mass.

SIX1 overexpression predicts poor prognosis and induces radioresistance through AKT signaling in esophageal squamous cell carcinoma.

The Sineoculis homeobox homolog 1 (SIX1) protein has been found to be overexpressed in several human cancers. However, its expression pattern and biological roles in esophageal squamous cell carcinoma (ESCC) remain unexplored. This study examined the clinical significance of SIX1 in 119 ESCC tissues. It was found that SIX1 protein was upregulated in 36.9% (44/119) cases. SIX1 overexpression was an independent predictor for short survival of ESCC patients. siRNA knockdown and plasmid transfection were carried out in ESCC cell lines. SIX1 depletion inhibited cell growth, invasion, and colony formation, whereas its overexpression facilitated in vivo and in vitro cell growth, invasion, and colony formation. The apoptosis rate induced by X-ray irradiation was substantially increased by SIX1 knockdown in Eca-109 cells. Ectopic overexpression of SIX1 in TE-1 cells dramatically enhanced resistance to irradiation. Western blot analysis showed that SIX1 depletion downregulated cyclin E, matrix metalloproteinase-2 (MMP-2), Bcl-2 expression and upregulated Bim expression. SIX1 overexpression exhibited the opposite effect on these proteins. In addition, it was found that SIX1 could positively regulate extracellular signal-regulated kinase (ERK) and AKT signaling pathway. ERK inhibitor abolished the effect of SIX1 on MMP-2 expression. AKT inhibitor treatment blocked the role of SIX1 on anti-apoptotic protein Bcl-2. In conclusion, this study demonstrates that SIX1 overexpression predicts poor survival in ESCC patients and confers radioresistance through activation of AKT signaling pathways.