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ABSTRACT:The main treatment for chondrosarcoma is surgical resection with a wide margin. However, there are certain chondrosarcomas, such as those found in the pelvis and the spine, which cannot be resected adequately with surgery alone. Unfortunately, most chondrosarcomas are resistant to radiation and chemotherapy. Radiation and chemotherapy are thought to kill chondrosarcoma cells by inducing apoptosis, or programmed cell death. In this article, we hypothesize that antiapoptotic gene silencing enhances radiosensitivity in chondrosarcoma cells by facilitating apoptotic pathways. We knocked down antiapoptotic genes in chondrosarcoma cells using small interfering RNAs (siRNAs). Two well-established Grade II human chondrosarcoma cell lines were pretreated with siRNAs that specifically target mRNAs for Bcl-2, Bcl-xL, or XIAP. The cells were then treated with radiation. Cell death was assessed by flow cytometry. Cell survival and proliferation were measured by clonogenic survival assays. Chondrosarcoma cells exhibited radioresistance and increased the expression of Bcl-2, Bcl-xL, and XIAP in response to radiation. When one of the Bcl-2, Bcl-xL, or XIAP genes was silenced with the corresponding siRNA, radiosensitivity increased up to 9.2-fold (p < 0.05). When two out of the three antiapoptotic mRNAs were knocked down simultaneously, there was an 11.3-fold increase in cell death after radiation (p < 0.05). Our findings support a novel therapeutic concept that gene silencing may be used as a molecular adjuvant therapy for radioresistant sarcomas. ß

ObjectiveKidneys are organs having a biological clock, and it is well known that the disruption of the circadian rhythm increases the risk of chronic kidney disease (CKD), including the decline of renal and proteinuria. Because shift work causes circadian disruption, it can directly or indirectly affect the incidence of chronic kidney disease. Therefore, the purpose of this study was to investigate the association between shift work and chronic kidney disease using a Korean representative survey dataset.MethodsThis study was comprised of 3504 manual labor workers over 20 years of age from data from the fifth and sixth Korea National Health and Nutrition Examination Survey (2011–2014). The work schedules were classified into two types: day work and shift work. The estimated glomerular filtration rate, which is the ideal marker of renal function, was estimated according to the Chronic Kidney Disease Epidemiology Collaboration creatinine equation, and chronic kidney disease was defined as urinary albumin to a creatinine ratio equal to or high than 30 mg/g and/or estimated glomerular filtration rate lower than 60 mL/min/1.73 m2. The cross-tabulation analysis and multivariate logistic regression analysis were performed to confirm the association between shift work and chronic kidney disease stratified by gender.ResultsThe risk of CKD showed a significant increase (odds ratio = 2.04, 95% confidence interval = 1.22, 3.41) in the female worker group. The same results were obtained after all confounding variables were adjusted (odds ratio = 2.34, 95% confidence interval = 1.35, 4.07). However, the results of the male worker group were not significant.ConclusionsIn this study using nationally representative surveys, we found that the risk of CKD was higher female workers and shift work. Future prospective cohort studies will be needed to clarify the causal relationship between shift work and CKD.