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PURPOSE: A prognostic nomogram was applied to predict survival in osteosarcoma patients. PATIENTS AND METHODS: Data collected from 2,195 osteosarcoma patients in the Surveillance, Epidemiology, and End Results (SEER) database between 1983 and 2014 were analyzed. Independent prognostic factors were identified via univariate and multivariate Cox analyses. These were incorporated into a nomogram to predict 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates. Internal and external data were used for validation. Concordance indices (C-indices) were used to estimate nomogram accuracy. RESULTS: Patients were randomly assigned into a training cohort (n=1,098) or validation cohort (n=1,097). Age at diagnosis, tumor site, histology, tumor size, tumor stage, use of surgery, and tumor grade were identified as independent prognostic factors via univariate and multivariate Cox analyses (all P<0.05) and then included in the prognostic nomogram. C-indices for OS and CSS prediction in the training cohort were 0.763 (95% CI 0.761-0.764) and 0.764 (95% CI 0.762-0.765), respectively. C-indices for OS and CSS prediction in the external validation cohort were 0.739 (95% CI 0.737-0.740) and 0.740 (95% CI, 0.738-0.741), respectively. Calibration plots revealed excellent consistency between actual survival and nomogram prediction. CONCLUSION: Nomograms were constructed to predict OS and CSS for osteosarcoma patients in the SEER database. They provide accurate and individualized survival prediction.
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Previous studies have shown that BMS-345541 (BMS, a specific IκB kinase ß inhibitor) sensitized various tumor cells including MCF-7 breast cancer cells to ionizing radiation (IR). However, the mechanisms of BMS action are unknown. Since the expression of E1A-like inhibitor of differentiation 3 (EID3) was highly upregulated in MCF-7 cells after BMS treatment, we investigated the role of EID3 in the response of MCF-7 cells to IR. We found that BMS induced EID3 expression in MCF-7 cells in a time- and dose-dependent manner. Knockdown of EID3 by specific shRNA attenuated BMS-induced radiosensitization in MCF-7 cells. In contrast, induction of EID3 expression in an inducible EID3 expressing MCF-7 cell line with doxycycline sensitized the cells to IR. EID3-mediated sensitization of MCF-7 cells to IR was not attributed to an increase in apoptosis. Instead, EID3-expressing MCF-7 cells exhibited significantly higher levels of senescence associated ß-galactosidase (SA-ß-gal) activity and higher levels of p21 and p57 than EID3-MCF-7 cells without induction of EID3 after exposure to IR. Similar findings were observed when EID3-expressing MCF-7 cells were treated with etoposide, a topoisomerase II inhibitor. Taken together, our findings reveal a novel function of EID3 and suggest that the induction of EID3 by BMS may be exploited as a new strategy to sensitize breast cancer cells to IR and chemotherapy by inducing cancer cell senescence.