Age-Related Sex Disparities in Esophageal Cancer Survival: A Population-Based Study in the United States.

Background: The association between sex and the survival of patients with esophageal cancer (EC) remains controversial. We sought to systematically investigate sex-based disparities in EC survival using the Surveillance, Epidemiology, and End Results (SEER) registry data from the United States. Methods: Patients with EC diagnosed from 2004 to 2015 registered in the SEER database were selected. The association between sex and cancer-specific survival (CSS) was evaluated using survival analysis. The Inverse Probability Weighting (IPW) approach was applied to reduce the observed bias between males and females. Subgroup analyses were used to investigate the robustness of the sex-based disparity and to explore potential interaction effects with other variables. Results: Overall, 29,312 eligible EC patients were analyzed, of whom 5,781 were females, and 23,531 were males. Females had higher crude CSS compared to males (10-year CSS: 24.5 vs. 21.3%; P < 0.001). Similar results were obtained after adjusting for selection bias using the IPW approach and multivariate regression. Subgroup analyses confirmed the relative robustness of sex as a prognostic factor. However, significant interactions were observed between sex and other variables, such as age, race, tumor grade, histology, and treatment modality. In particular, there was no survival advantage for premenopausal females compared to their male counterparts, but the association between sex and EC survival was prominent in 46-55-year-old patients. Conclusions: Female EC patients had better long-term survival than males. The association between sex and EC survival vary according to age, race, tumor grade, histology, and treatment modality. Sex-based disparity in EC-specific survival was age-related in the United States population.

Benefit of chemotherapy in stage III nasopharyngeal carcinoma: Analysis of the surveillance, epidemiology, and end results database.

OBJECTIVES: Chemoradiotherapy is the standard treatment for locoregionally advanced nasopharyngeal carcinoma (NPC). We aimed to reveal factors associated with chemotherapy use and evaluate chemotherapy's benefit in patients with stage III NPC stratified by lymph node status. PATIENTS AND METHODS: Overall, 1452 patients with stage III NPC who underwent radiotherapy with (n = 1361) or without (n = 91) chemotherapy were identified in the SEER database. We examined predictors for chemotherapy use using logistic regression analysis. We compared all-cause mortality (ACM) and cancer-specific mortality (CSM) using the Kaplan-Meier method. Cox regression and competing risk analyses were used to evaluate the benefit of chemotherapy. The inverse probability of treatment weighting (IPTW) approach was applied to reduce selection bias and adjust for competing risks. Subgroup analyses and interaction effects were explored. RESULTS: Factors including age, sex, insured status, tumor grade, and N category were associated with chemotherapy use. Chemotherapy was associated with decreased 5-year ACM (31.4% vs. 48.4%, p < 0.001) and CSM (25.5% vs. 35.8%; p = 0.017) in stage III NPC patients. The IPTW-adjusted hazard ratio for 5-year ACM was 0.57 (95% CI: 0.38-0.86, p = 0.008), whereas IPTW-adjusted sub-hazard ratio for 5-year CSM was 0.62 (95% CI: 0.42-0.93, p = 0.003). A significant interaction effect existed between lymph node status and treatment modality. Chemotherapy offered a significant survival benefit in node-positive stage III NPC. However, no chemotherapy benefit for the node-negative disease was observed. CONCLUSION: Chemotherapy adds survival benefit in stage III NPC, especially in patients with node-positive disease. The magnitude of chemotherapy benefit in node-negative stage III NPC warrants further investigation.

Bortezomib could down-regulate the expression of RANKL, inhibit cell proliferation and induce cell apoptosis in the human myeloma cell line RPMI 8226 by activating casepase-3.

OBJECTIVE: In spite of bortezomib being developed and demonstrated as a safe drug therapy for multiple myeloma (MM), the role of bortezomib-induced receptor activator of nuclear factor (NF)-κB ligand (RANKL) in the MM cell lines remains to be understood. Thus the present study aims to explore the impact of bortezomib on RANKL expression, cell growth and apoptosis in human myeloma cell line RPMI 8226. METHODS: Four experiment groups were set according to different concentrations of bortezomib, namely blank group (treated with DMEM solution free of other drugs), low-dose group (treated with 10 nmol/L bortezomib), middle-dose group (treated with 20 nmol/L bortezomib) and high-dose group (treated with 40 nmol/L bortezomib). Western blotting was adopted to detect RANKL protein expression. MTT assay was performed to detect cell proliferation. Flow cytometry was used to analyze cell cycle and apoptosis. Spectrophotometry was applied to determine caspases-3 activity. RESULTS: Compared with the blank group, the RANKL protein expression, cell number at the S stage was reduced while cell inhibition rate, cell apoptosis rate and caspase-3 activity enhanced remarkably in the low-dose, middle-dose and high-dose groups with dose-dependent manner. Compared with those treated with bortezomib (20 nmol/L and 40 nmol/L) for 6 h, the RANKL expression was down-regulated, cell inhibition rate was increased, cells at the S stage were reduced, cell apoptosis rate was enhanced, and caspase-3 activity elevated in the RPMI 8226 cells as treated with bortezomib for 24 h, with a dose- and time-dependent manner. CONCLUSIONS: Bortezomib could reduce the RANKL expression, inhibit cell proliferation and activate caspase-3 activity to induce cell apoptosis in RPMI 8266 cells.

The effects of miR-1207-5p expression in peripheral blood on cisplatin-based chemosensitivity of primary gallbladder carcinoma.

OBJECTIVE: The aim of this study was to investigate the association between miR-1207-5p expression in peripheral blood and the chemosensitivity of primary gallbladder carcinoma (PGBC). METHODS: A total of 85 patients with PGBC undergoing preoperative chemotherapy were divided into effective (n=18) and ineffective (n=67) groups. Another 70 healthy individuals were selected as the control group. An miR-1207-5p mimic (mimic group), an inhibitor (inhibitor group), and a negative control (NC group) sequence were transfected into human gallbladder carcinoma GBC-SD cells. Real-time quantitative polymerase chain reaction was used to determine miR-1207-5p expression. After 48 hours of cisplatin treatment, CCK-8 method was used to detect cell proliferation and flow cytometry were performed to examine cell apoptosis. RESULTS: miR-1207-5p expression in peripheral blood was significantly associated with tumor node metastasis staging of PGBC (P<0.05). Before chemotherapy, miR-1207-5p expression in patients was higher than in healthy individuals (P<0.05). After chemotherapy, the effective group had lower miR-1207-5p expression than the ineffective group (P<0.05). The rates of positive expression of Ki67 protein in the effective group were significantly lower than those in the ineffective group (P<0.05). Receiver operating characteristic curves showed that the area under curve, sensitivity, and specificity of miR-1207-5p used to diagnose PGBC were 0.898, 77.6%, and 97.1% at a cutoff of 1.470, respectively. After 48 hours of cisplatin treatment, compared with the NC group and nontransfected (non-T) group, the mimic group had decreased rates of cell inhibition and apoptosis, but the inhibitor group had increased rates (all P<0.05). The expression levels of caspase3 protein were increased in the mimic group and decreased in the inhibitor group. Cell survival rates in the mimic group at different time points after cisplatin treatment were significantly higher than the corresponding rates in the NC and non-T groups, whereas the cell survival rates in the inhibitor group were significantly lower than the rates in the NC and non-T groups (all P<0.05). The concentration and action time of cisplatin were negatively associated with the cell survival rate in each group (all P<0.05). CONCLUSION: Cisplatin-based chemosensitivity of PGBC increased as expression of miR-1207-5p in peripheral blood declined. Thus, miR-1207-5p appears to be a promising and novel chemosensitizer for the treatment of PGBC.