Ionizing radiation is a popular and effective treatment option for glioblastoma(GBM).However,resistance to radiation therapy inevitably occurs during treatment.It is urgent to investigate the mechanisms of radioresist...Ionizing radiation is a popular and effective treatment option for glioblastoma(GBM).However,resistance to radiation therapy inevitably occurs during treatment.It is urgent to investigate the mechanisms of radioresistance in GBM and to find ways to improve radiosensitivity.Here,we found that heat shock protein 90 beta family member 1(HSP90B1)was significantly upregulated in radioresistant GBM cell lines.More importantly,HSP90B1 promoted the localization of glucose transporter type 1,a key rate-limiting factor of glycolysis,on the plasma membrane,which in turn enhanced glycolytic activity and subsequently tumor growth and radioresistance of GBM cells.These findings imply that targeting HSP90B1 may effectively improve the efficacy of radiotherapy for GBM patients,a potential new approach to the treatment of glioblastoma.展开更多
Objective: Glioblastoma(GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy.Therefore, a robust, multi-gene signature-d...Objective: Glioblastoma(GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy.Therefore, a robust, multi-gene signature-derived model is required to predict the prognosis and treatment response in GBM.Methods: Gene expression data of GBM from TCGA and GEO datasets were used to identify differentially expressed genes(DEGs)through DESeq2 or LIMMA methods.The DEGs were then overlapped and used for survival analysis by univariate and multivariate COX regression.Based on the gene signature of multiple survival-associated DEGs, a risk score model was established,and its prognostic and predictive role was estimated through Kaplan–Meier analysis and log-rank test.Gene set enrichment analysis(GSEA) was conducted to explore high-risk score-associated pathways.Western blot was used for protein detection.Results: Four survival-associated DEGs of GBM were identified: OSMR, HOXC10, SCARA3, and SLC39A10.The four-gene signature-derived risk score was higher in GBM than in normal brain tissues.GBM patients with a high-risk score had poor survival outcomes.The high-risk group treated with temozolomide chemotherapy or radiotherapy survived for a shorter duration than the low-risk group.GSEA showed that the high-risk score was enriched with pathways such as vasculature development and cell adhesion.Western blot confirmed that the proteins of these four genes were differentially expressed in GBM cells.Conclusions: The four-gene signature-derived risk score functions well in predicting the prognosis and treatment response in GBM and will be useful for guiding therapeutic strategies for GBM patients.展开更多
Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5^(th) and 6^(th) d...Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5^(th) and 6^(th) decades of life and extremely rare in children. It is highly aggressive tumour and managed like glioblastoma multiforme. A 12-year-old female child presented with complaints of headache and vomiting from 15d and blurring of vision from 3d. Magnetic resonance imaging of brain shows heterogeneous mass in right parieto-occipital cortex. A right parieto-occipito-temporal craniotomy with complete excision of mass revealed a primary glioblastoma on histopathological investigation. Treatment consists of maximum surgical excision followed by adjuvant radiotherapy. The etiopathogenesis, treatment modalities and prognosis is discussed. The available literature is also reviewed.展开更多
Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide(TMZ) in addition to radiotherapy. High-...Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide(TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. In spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy(hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.展开更多
Backgrond: To compare the survival of glioblastoma multiforme (GBM) patients operated on at public hospital with that of patients operated on at the private hospital. Method: We carried out a retrospective analysis of...Backgrond: To compare the survival of glioblastoma multiforme (GBM) patients operated on at public hospital with that of patients operated on at the private hospital. Method: We carried out a retrospective analysis of the patients’ medical records, the surgical reports, and the pre and post-operative images of patients with a histopathological confirmed adult supratentorial glioblastoma multiform (GBM). Sixty-three patients were treated at public hospital and 21 at private hospitals. Results: The present study revealed that the survival of patients treated in private hospitals was statistically superior to that of patients treated in public hospitals (11.9 vs 7.7). Conclusions: Our study advances towards the confirmation of the hypothesis that socioeconomic and educational factors influence the KPS and the performance of RT treatment, with negative effects over the GBM patients’ survival.展开更多
Glioblastoma(GBM,WHO grade Ⅳ) is the most common and the most malignant primary brain tumor occurring during adulthood,with an annual incidence of 5 cases per 100 000.Treatment involves surgical resection,followed by...Glioblastoma(GBM,WHO grade Ⅳ) is the most common and the most malignant primary brain tumor occurring during adulthood,with an annual incidence of 5 cases per 100 000.Treatment involves surgical resection,followed by radiotherapy and concomitant and adjuvant temozolomide.Despite multimodality treatment,the median survival time is 15 months.Herewith we discuss the value of neuroimaging in differentiating GBM from other types of brain tumors,in guiding tumor biopsy,in making non-invasive assessment of tumor's aggressiveness,in estimating overall prognosis,in differentiating treatment-induced brain necrosis from tumor recurrence and in assessing response to treatment.展开更多
基金supported by the National Natural Science Foundation of China(Grant Nos.82072765 to X.Q.and 82172667 to X.W.).
文摘Ionizing radiation is a popular and effective treatment option for glioblastoma(GBM).However,resistance to radiation therapy inevitably occurs during treatment.It is urgent to investigate the mechanisms of radioresistance in GBM and to find ways to improve radiosensitivity.Here,we found that heat shock protein 90 beta family member 1(HSP90B1)was significantly upregulated in radioresistant GBM cell lines.More importantly,HSP90B1 promoted the localization of glucose transporter type 1,a key rate-limiting factor of glycolysis,on the plasma membrane,which in turn enhanced glycolytic activity and subsequently tumor growth and radioresistance of GBM cells.These findings imply that targeting HSP90B1 may effectively improve the efficacy of radiotherapy for GBM patients,a potential new approach to the treatment of glioblastoma.
基金supported by the National Key R&D Program of China (Grant No.2016YFA0101203 to XB and 2016YFC1201801 to XZ)the National Natural Science Foundation of China (Grant No.81372273 and 81773145 to XZ)+1 种基金the funding from Key Laboratory of Tumor Immunology and Pathology (Army Medical University), Ministry of Education of China (Grant No.2017jszl09 to MC)the Basic and Applied Fund of First Affiliated Hospital of Army Military Medical University (Grant No.SWH2016BZGFSBJ-04 and SWH2016JCZD-04 to XZ)
文摘Objective: Glioblastoma(GBM) is the most common primary malignant brain tumor regulated by numerous genes, with poor survival outcomes and unsatisfactory response to therapy.Therefore, a robust, multi-gene signature-derived model is required to predict the prognosis and treatment response in GBM.Methods: Gene expression data of GBM from TCGA and GEO datasets were used to identify differentially expressed genes(DEGs)through DESeq2 or LIMMA methods.The DEGs were then overlapped and used for survival analysis by univariate and multivariate COX regression.Based on the gene signature of multiple survival-associated DEGs, a risk score model was established,and its prognostic and predictive role was estimated through Kaplan–Meier analysis and log-rank test.Gene set enrichment analysis(GSEA) was conducted to explore high-risk score-associated pathways.Western blot was used for protein detection.Results: Four survival-associated DEGs of GBM were identified: OSMR, HOXC10, SCARA3, and SLC39A10.The four-gene signature-derived risk score was higher in GBM than in normal brain tissues.GBM patients with a high-risk score had poor survival outcomes.The high-risk group treated with temozolomide chemotherapy or radiotherapy survived for a shorter duration than the low-risk group.GSEA showed that the high-risk score was enriched with pathways such as vasculature development and cell adhesion.Western blot confirmed that the proteins of these four genes were differentially expressed in GBM cells.Conclusions: The four-gene signature-derived risk score functions well in predicting the prognosis and treatment response in GBM and will be useful for guiding therapeutic strategies for GBM patients.
文摘Gliosarcoma is rare central nervous system tumour and a variant of glioblastoma multiforme with bimorphic histological pattern of glial and sarcomatous differentiation. It occurs in elderly between 5^(th) and 6^(th) decades of life and extremely rare in children. It is highly aggressive tumour and managed like glioblastoma multiforme. A 12-year-old female child presented with complaints of headache and vomiting from 15d and blurring of vision from 3d. Magnetic resonance imaging of brain shows heterogeneous mass in right parieto-occipital cortex. A right parieto-occipito-temporal craniotomy with complete excision of mass revealed a primary glioblastoma on histopathological investigation. Treatment consists of maximum surgical excision followed by adjuvant radiotherapy. The etiopathogenesis, treatment modalities and prognosis is discussed. The available literature is also reviewed.
文摘Postoperative external beam radiotherapy was considered the standard adjuvant treatment for patients with glioblastoma multiforme until the advent of using the drug temozolomide(TMZ) in addition to radiotherapy. High-dose volume should be focal, minimizing whole brain irradiation. Modern imaging, using several magnetic resonance sequences, has improved the planning target volume definition. The total dose delivered should be in the range of 60 Gy in fraction sizes of 1.8-2.0 Gy. Currently, TMZ concomitant and adjuvant to radiotherapy has become the standard of care for glioblastoma multiforme patients. Radiotherapy dose-intensification and radiosensitizer approaches have not improved the outcome. In spite of the lack of high quality evidence, stereotactic radiotherapy can be considered for a selected group of patients. For elderly patients, data suggest that the same survival benefit can be achieved with similar morbidity using a shorter course of radiotherapy(hypofractionation). Elderly patients with tumors that exhibit methylation of the O-6-methylguanine-DNA methyltransferase promoter can benefit from TMZ alone.
文摘Backgrond: To compare the survival of glioblastoma multiforme (GBM) patients operated on at public hospital with that of patients operated on at the private hospital. Method: We carried out a retrospective analysis of the patients’ medical records, the surgical reports, and the pre and post-operative images of patients with a histopathological confirmed adult supratentorial glioblastoma multiform (GBM). Sixty-three patients were treated at public hospital and 21 at private hospitals. Results: The present study revealed that the survival of patients treated in private hospitals was statistically superior to that of patients treated in public hospitals (11.9 vs 7.7). Conclusions: Our study advances towards the confirmation of the hypothesis that socioeconomic and educational factors influence the KPS and the performance of RT treatment, with negative effects over the GBM patients’ survival.
文摘Glioblastoma(GBM,WHO grade Ⅳ) is the most common and the most malignant primary brain tumor occurring during adulthood,with an annual incidence of 5 cases per 100 000.Treatment involves surgical resection,followed by radiotherapy and concomitant and adjuvant temozolomide.Despite multimodality treatment,the median survival time is 15 months.Herewith we discuss the value of neuroimaging in differentiating GBM from other types of brain tumors,in guiding tumor biopsy,in making non-invasive assessment of tumor's aggressiveness,in estimating overall prognosis,in differentiating treatment-induced brain necrosis from tumor recurrence and in assessing response to treatment.
