Establishment of a detection platform for glioblastoma-dendritic cell (DC) vaccine preparation and to determine the efficacy of the vaccine in a clinical trial. Autologous glioblastoma-DC vaccine was prepared from a glioblast specimen procured from surgical resection. The specimen was used to enrich the vaccine with peripherally blood-derived DCs after heat-shock induced, glioblastoma apoptosis. The control group received conventional treatment of surgery and radio-chemotherapy post-operation. The therapeutic group received a combination of glioblastoma-DC vaccine and conventional therapy. A comparison of the functional immune parameters, including tumor control, rate live time, Karnofsky scores, and complications occurring in each group were observed and recorded. The proportions of peripheral CD3(+), CD3(+)CD4(+), CD4(+)/CD8(+), and NK cells were significantly higher after DC vaccination than the control group (P < 0.05). Serum levels of IL-2, IL-12, and IFN-γ were significantly higher after DC vaccination than in the control group (P < 0.05). Nine months after vaccination, tumor control rate is significantly improved in the DC group compared with the control group (P < 0.05); survival rate was significantly higher in DC group than in control group (P < 0.05) and the time to relapse was significantly longer in DC group than that in control group (P < 0.05). Karnofsky scores were better in DC vaccination group 6 and 9 months post-treatment compared with the control group (P < 0.05). The combination of glioma DC vaccine and radiotherapy/chemotherapy post-operatively enhances the immune function of patients, increases the tumor control rate, prolongs the survival time and relapse duration, improves the quality of life, and therefore provides a more effective intervention of treating glioblastoma.
Study Design.A retrospective study.Objective.This study aims to develop a new scoring system that can guild surgeons to select the best candidates for decompressive surgery in patients with metastatic spinal cord compression (MSCC).Summary of Background Data.Predicting survival and functional outcome is essential when selecting the individual treatment for patients with MSCC. The criteria for identifying MSCC patients who are most likely to benefit from decompressive surgery remain unclear.Methods.We retrospectively analyzed 12 preoperative characteristics for postoperative survival in a series of 206 patients with MSCC who were operated with decompressive surgery and spine stabilization. Characteristics significantly associated with survival in the multivariate analysis were included in the scoring system. Postoperative function outcome was also analyzed on the basis of the scoring system.Results.According to the multivariate analysis, primary site (P < 0.01), preoperative ambulatory status (P < 0.01), visceral metastases (P < 0.01), preoperative chemotherapy (P = 0.02), and bone metastasis at cancer diagnosis (P = 0.03) had a significant impact on postoperative survival and were included in the scoring system. According to the prognostic scores, which ranged from 0 to 10 points, three risk groups were designed: 0 to 2, 3 to 5, and 6 to 10 points. The corresponding 6 months survival rates were 8.2%, 56.5%, and 91.5%, respectively (P < 0.01), and postoperative ambulatory rates were 35.7%, 73.3%, and 95.9%, respectively (P < 0.01).Conclusion.We present a new scoring system for predicting survival and function outcome of MSCC patients after surgical decompression and spine stabilization. This new scoring system can help surgeons select the best candidates for surgical treatment.Level of Evidence: 4
Radiation resistance is a major problem preventing successful treatment. Therefore, identifying sensitizers is vitally important for radiotherapy success. Epigenetic events such as DNA methylation have been proposed to mediate the sensitivity of tumor therapy. In this study, we investigated the influence of demethylating agent 5-Aza-2'-deoxycytidine (5-Aza-CdR) on the radiosensitivity of human osteosarcoma cell lines. 5-Aza-CdR was capable of sensitizing three osteosarcoma cells to irradiation in a time-dependent manner, with the maximum effect attained by 48 h. Pretreatment with 5-Aza-CdR synchronized cells in G2/M phase of the cell cycle and enhanced irradiation-induced apoptosis compared with irradiation alone in SaOS2, HOS, and U2OS cells. Moreover, 5-Aza-CdR restored mRNA expressions of 14-3-3σ, CHK2, and DAPK-1 in the three cells, accompanied with demethylation of their promoters. These findings demonstrate that demethylation with 5-Aza-CdR increases radiosensitivity in some osteosarcoma cells through arresting cells at G2/M phase and increasing apoptosis, which is partly mediated by upregulation of 14-3-3σ, CHK2, and DAPK-1 genes, suggesting that 5-Aza-CdR may be a potential radiosensitizer to improve the therapy effect in osteosarcoma.
To investigate the relativity of MGMT(O-6-methylguanine-DNA methyltransferase) gene methylation from patients with protein expression and osteosarcoma necrosis rate after chemotherapy. Fifty-one oteosarcoma tissues were collected, Methylation of MGMT gene promoter was detected by methylation-specific PCR method, and protein expression of MGMT was examined by immunohistochemistry procedure, the relationship between methylated MGMT gene expression and patients response to chemotherapy was analyzed. The positive ratio of methylation MGMT gene promoter in 51 patients was 23.5% (12 in 51). Negative percentage of protein expression of MGMT was 27.5% (14 in 51). It seemed that methylation of MGMT gene in osteosarcoma tissues had no evident relationship with the patient's age, sexuality, and the size and type of neoplasms, etc. The necrosis rates of methylated MGMT of osteosarcoma (tumor grade from I to IV) were 0 (0/51), 3.9% (2/51), 5.9% (3/51), 13.7% (7/51), respectively. In contrast, the necrosis rates of unmethylated MGMT of osteosarcoma (tumor grade from I to IV) were 45.1% (23/51), 25.5% (13/51), 3.9% (2/51), 2.0% (1/51), respectively. It suggest that methylated and unmethylated MGMT gene of osteosarcoma have significant difference in protein expression. The unmethylated MGMT gene has higher positive protein expression (u = -4.92, P < 0.001). Methylation of MGMT gene has higher tumor necrosis rate in osteosarcoma patients. Methylation in MGMT promoter may be important for judging the effect of chemotherapy in Osteosarcoma patients.
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