ABSTRACT
OBJECTIVE: To evaluate the efficacy of limited margins intensity-modulated radiotherapy (IMRT) with temozolomide chemotherapy in patients with malignant glioma, and explore the prognostic factors of malignant glioma. METHODS: A total of 33 whole-resected patients, 14 partial-resected patients and 3 biopsied patients were randomly divided into limited margins group and routine margins group. The patients were treated with IMRT and temozolomide concurrent chemotherapy, subsequently adjuvant chemotherapy. Then all the patients were evaluated 2 months later after concurrent chemoradiotherapy. Progression-free survival in 1 year (PFS-1), progress free survival rate in 1 year (PFSR-1) and 1 year survival rate (SR-1) were recorded.All the possible prognostic factors were analyzed. RESULTS: Routine margins group: complete response (CR) 19, partial response (PR) 2, stable disease (SD) 2, progressive disease (PD) 2; Limited margins group: CR 16, PR 6, SD 1, PD 2. Mean PFS-1 of the two groups were 11.64 and 11.36 months, respectively. PFSR-1 were 84% in routine margins group and 80% in limited margins group. SR-1 of two groups were both 100%. Surgery results and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status were correlated with immediate-term prognosis by either univariate or multivariate analysis. Both surgery results and immediate-term prognosis were relevant factors to PFS-1. Progression sites in two groups had no statistical difference by analysis. CONCLUSIONS: Both groups gained favorable results, and limited margins doesn't increase local failures. Surgery results are important prognostic factors to immediate-term prognosis and PFS-1.
Subject(s)
Brain Neoplasms , Glioblastoma , Glioma , Radiotherapy, Intensity-Modulated , Antineoplastic Agents, Alkylating , Chemoradiotherapy , Chemotherapy, Adjuvant , DNA Modification Methylases , DNA Repair Enzymes , Dacarbazine/analogs & derivatives , Disease Progression , Disease-Free Survival , Humans , Prognosis , Promoter Regions, Genetic , Remission Induction , Survival Rate , Temozolomide , Tumor Suppressor ProteinsABSTRACT
PURPOSE: MicroRNAs (miRNAs) are noncoding RNAs inhibiting expression of numerous target genes by posttranscriptional regulation. miRNA-221 and miRNA-222 (miRNA-221/-222) expression is elevated in radioresistant tumor cell lines; however, it is not known whether and how miRNAs control cellular responses to ionizing irradiation. METHODS AND MATERIALS: We used bioinformatic analyses, luciferase reporter assay, and genetic knockdown and biochemical assays to characterize the regulation pathways of miRNA-221/-222 in response to radiation treatment. RESULTS: We identified the PTEN gene as a target of miRNA-221/-222. Furthermore, we found that knocking down miRNA-221/-222 by antisense oligonucleotides upregulated PTEN expression. Upregulated PTEN expression suppressed AKT activity and increased radiation-induced apoptosis, resulting in enhancement of radiosensitivity in tumor cells. CONCLUSIONS: miRNA-221/-222 control radiation sensitivity by regulating the PTEN/AKT pathway and can be explored as novel targets for radiosensitization.
