This is the report of a histological and clinical investigation of 4 cases of glioblastoma, a rare tumor, in whom poor contrast enhancement of the tumor was visualized on magnetic resonance imaging (MRI). Among the 94...This is the report of a histological and clinical investigation of 4 cases of glioblastoma, a rare tumor, in whom poor contrast enhancement of the tumor was visualized on magnetic resonance imaging (MRI). Among the 94 patients with first-occurrence glioblastoma treated between January 2000 and August 2011, 4 were enrolled in this retrospective study. There were 2 men and 2 women, ranging in age from 41 to 70 years (mean, 57 years). All the patients underwent tumor resection, postoperative irradiation, and chemotherapy. One died of local tumor recurrence after 36 months;the remaining three remain alive as of 25 to 72 months after the initial treatment. The histopathology was glioblastoma with nuclear pleomorphism and pseudopalisading necrosis in all cases. However, the typical vascular endothelial proliferation was not found in 3 cases. All glioblastomas were immunopositive for p53 and immunonegative for epidermal growth factor receptor (EGFR) and isocitrate dehydrogenase 1 (IDH1). These glioblastomas showing unclear contrast enhancement on MRI had similar clinical and pathological characteristics, but differed in characteristics from glioblastoma patients showing marked contrast enhancement of the tumor on MRI.展开更多
Reprogrammed metabolism is a hallmark of cancer. Glioblastoma（GBM） tumor cells predominantly utilize aerobic glycolysis for the biogenesis of energy and intermediate nutrients. However, in GBM, the clinical signific...Reprogrammed metabolism is a hallmark of cancer. Glioblastoma（GBM） tumor cells predominantly utilize aerobic glycolysis for the biogenesis of energy and intermediate nutrients. However, in GBM, the clinical significance of glycolysis and its underlying relations with the molecular features such as IDH1 mutation and subtype have not been elucidated yet. Herein, based on glioma datasets including TCGA（The Cancer Genome Atlas）, REMBRANDT（Repository for Molecular Brain Neoplasia Data） and GSE16011 we established a glycolytic gene expression signature score（GGESS） by incorporating ten glycolytic genes. Then we performed survival analyses and investigated the correlations between GGESS and IDH1 mutation as well as the molecular subtypes in GBMs. The results showed that GGESS independently predicted unfavorable prognosis and poor response to chemotherapy of GBM patients. Notably, GGESS was high in GBMs of mesenchymal subtype but low in IDH1-mutant GBMs. Furthermore, we found that the promoter regions of tumor-promoting glycolytic genes were hypermethylated in IDH1-mutant GBMs.Finally, we found that high GGESS also predicted poor prognosis and poor response to chemotherapy when investigating IDH1-wild type GBM patients only. Collectively, glycolysis represented by GGESS predicts unfavorable clinical outcome of GBM patients and is closely associated with mesenchymal subtype and IDH1 mutation in GBMs.展开更多
Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy o...Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy of vebreltinib among more glioma patients.This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/IDH mutant glioblastoma patients with the ZM fusion gene.Methods This multicentric,randomized,open-label,controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene.This trial enrolls sGBM or IDH mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria.It was registered with chinadrugtrials.org.cn(CTR20181664).The primary efficacy endpoint is overall survival(OS).The secondary endpoints are progression-free survival(PFS)and objective response rate(ORR).Discussion If proven effective,this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors.Trial registration It was registered with chinadrugtrials.org.cn(CTR20181664).展开更多
文摘This is the report of a histological and clinical investigation of 4 cases of glioblastoma, a rare tumor, in whom poor contrast enhancement of the tumor was visualized on magnetic resonance imaging (MRI). Among the 94 patients with first-occurrence glioblastoma treated between January 2000 and August 2011, 4 were enrolled in this retrospective study. There were 2 men and 2 women, ranging in age from 41 to 70 years (mean, 57 years). All the patients underwent tumor resection, postoperative irradiation, and chemotherapy. One died of local tumor recurrence after 36 months;the remaining three remain alive as of 25 to 72 months after the initial treatment. The histopathology was glioblastoma with nuclear pleomorphism and pseudopalisading necrosis in all cases. However, the typical vascular endothelial proliferation was not found in 3 cases. All glioblastomas were immunopositive for p53 and immunonegative for epidermal growth factor receptor (EGFR) and isocitrate dehydrogenase 1 (IDH1). These glioblastomas showing unclear contrast enhancement on MRI had similar clinical and pathological characteristics, but differed in characteristics from glioblastoma patients showing marked contrast enhancement of the tumor on MRI.
基金supported by grants from the China National Science and Technology Major Project (2016YFA0101203)
文摘Reprogrammed metabolism is a hallmark of cancer. Glioblastoma（GBM） tumor cells predominantly utilize aerobic glycolysis for the biogenesis of energy and intermediate nutrients. However, in GBM, the clinical significance of glycolysis and its underlying relations with the molecular features such as IDH1 mutation and subtype have not been elucidated yet. Herein, based on glioma datasets including TCGA（The Cancer Genome Atlas）, REMBRANDT（Repository for Molecular Brain Neoplasia Data） and GSE16011 we established a glycolytic gene expression signature score（GGESS） by incorporating ten glycolytic genes. Then we performed survival analyses and investigated the correlations between GGESS and IDH1 mutation as well as the molecular subtypes in GBMs. The results showed that GGESS independently predicted unfavorable prognosis and poor response to chemotherapy of GBM patients. Notably, GGESS was high in GBMs of mesenchymal subtype but low in IDH1-mutant GBMs. Furthermore, we found that the promoter regions of tumor-promoting glycolytic genes were hypermethylated in IDH1-mutant GBMs.Finally, we found that high GGESS also predicted poor prognosis and poor response to chemotherapy when investigating IDH1-wild type GBM patients only. Collectively, glycolysis represented by GGESS predicts unfavorable clinical outcome of GBM patients and is closely associated with mesenchymal subtype and IDH1 mutation in GBMs.
基金funded by The National Key Research and Development Program of China(2019YFE0109400)National Natural Science Foundation of China(No.81972337 and No.81802994)+1 种基金Beijing Natural Science Foundation(No.JQ20030)Outstanding Young Talents of the Capital Medical University(No.B2101)
文摘Background PTPRZ1-MET fusion was reported to associate with glioma progression from low-grade to high-grade glioma,which was a target by a MET inhibitor vebreltinib.However,little is known about the further efficacy of vebreltinib among more glioma patients.This trial aims to evaluate the safety and efficacy of vebreltinib enteric-coated capsules in the treatment of sGBM/IDH mutant glioblastoma patients with the ZM fusion gene.Methods This multicentric,randomized,open-label,controlled trial plans to include 19 neurosurgical centers and recruit 84 sGBM or IDH mutant glioblastoma patients with the ZM fusion gene.This trial enrolls sGBM or IDH mutant glioblastoma patients with the inclusion criteria and without the exclusion criteria.It was registered with chinadrugtrials.org.cn(CTR20181664).The primary efficacy endpoint is overall survival(OS).The secondary endpoints are progression-free survival(PFS)and objective response rate(ORR).Discussion If proven effective,this targeted multifaceted intervention protocol will be extended for more glioma patients as a protocol to evaluate the safety and efficacy of MET inhibitors.Trial registration It was registered with chinadrugtrials.org.cn(CTR20181664).
