Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams.Improved radiation therapy techniques,new imaging methods,...Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams.Improved radiation therapy techniques,new imaging methods,published experience,and a better radiobiological knowledge of brain tissue have positioned re-irradiation(re-RT)as an option for many of these patients.Decisions must be individualized,taking into account the pattern of relapse,previous treatment,and functional status,as well as the patient’s preferences and expected quality of life.Many questions remain unanswered with respect to re-RT:Who is the most appropriate candidate,which dose and fractionation are most effective,how to define the target volume,which imaging technique is best for planning,and what is the optimal timing?This review will focus on describing the most relevant studies that include re-RT as salvage therapy,with the aim of simplifying decision-making and designing the best available therapeutic strategy.展开更多
PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relat...PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,展开更多
Objective:gliomas are the most common intracranial tumors.Fibroblast growth factor-12(FGF12),which belongs to the fibroblast growth factor(FGFs)family,plays an important role in cell mitosis,as well as in other life f...Objective:gliomas are the most common intracranial tumors.Fibroblast growth factor-12(FGF12),which belongs to the fibroblast growth factor(FGFs)family,plays an important role in cell mitosis,as well as in other life functions,such as embryo development,tissue repair,cell proliferation,and tumor growth and invasion.The purpose of this study was to explore the potential value of FGF12 in high-grade gliomas and to predict its drug sensitivity.To provide a possible therapeutic target for glioma.Methods:high-grade glioma gene expression data and clinical information were downloaded from the gene expression omnibus(GEO)database,using the R language“impute”and“survival”survival analysis package.The FGF12 genes closely related to survival were screened,a survival curve was drawn,and clinical correlation analysis was conducted.The differentially expressed genes(DEGs)were defined as |logFC|>1,adj.PVal<0.05 as the standard.We used the David for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,and constructed the protein-protein interactions(PPI)network.Then we used the Connectivity Map(CMAP)database for drug location,and the validation group was verified by the Chinese Glioma Genome Atlas(CGGA)database in the same way.Results:we found that high FGF12 expression was associated with a higher survival rate.The same validation was performed in the validation group through the CGGA database,and the survival curve showed the same trend.The expression level of FGF12 is an independent factor that affects the life time and status of the samples,and it is a low risk factor.GO enrichment analysis showed that differential genes were enriched in matrix transmembrane transporter activity,ion channels and calcium ion active channels.KEGG showed that DEGs were enriched in the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)signaling pathway,dopaminergic synapse and cyclic adenosine monophosphate(cAMP)signaling pathway.Four seed genes,GRIA2,COLLA2,GRIA4 and HES6,were obtained by PPI network analysis.The cAMP was used to analyze and obtained 7 small molecule drugs,such as merbromin,naloxone,AH-2384&ticarcillin,vincamine,amoxicillin,azacyclonol,which may be helpful in the prognosis of high-grade gliomas.Conclusion:FGF12 and its pathway may serve as a biomarker or therapeutic target for high-grade gliomas.展开更多
Objective:To investigate the expression level of long chain non coding RNAH19 in advanced gliomas and its relationship with glioma cell temozolomide (TMZ) resistance, and make a preliminary study on their related mech...Objective:To investigate the expression level of long chain non coding RNAH19 in advanced gliomas and its relationship with glioma cell temozolomide (TMZ) resistance, and make a preliminary study on their related mechanism.Methods:Tissue samples of normal brain tissue, early onset and recurrence of high grade gliomas were collected, and the expression of LNC H19 was detected by reverse transcription polymerase chain reaction (RT-PCR). The construction of Resistant U251 TMZ Resistant (U251-TR) Cell Lines were completed by intermittent concentration gradient increments and verified by MTT method. The changes in the expression of LncRNA H19 was detected by RT-PCR, lovirus transfection was used to construct U251-TR cell line with stable interference with LNC H19 (U251-TRsiLNC H19), and MTT assay was used to observe the changes of TMZ half-maximal inhibitory concentration (IC50). Western Blot and RT-PCR were used to detect the changes of O6-methylguanine DNA methyltransferase (MGMT) in U251, U251-TR and U251-TRsiLNC H19.Results: The results of RT-PCR showed that the expression of LNC H19 in high-grade glioma was significantly higher than that in primary glioma tissue and normal brain tissue. The IC50 value and drug resistance index of U251-TR cell line were significantly increased, the expression of LncRNA H19 in U251-TR cell line was significantly higher than that in U251 cells and the expression of MGMT were also increased. We succeeded in interfering with the expression of LNC H19 in the U251-TR cell line, and found that the IC50 value and drug resistance index of U251-TR cell line were decreased significantly and the expression of MGMT were also decreased.Conclusion:LNC H19 is highly expressed in recurrent high-grade gliomas, which may increase the level of MGMT, leading to the occurrence of glioma cell TMZ resistance. LNC H19 is a key factor in the occurrence of TMZ resistance in glioma cells.展开更多
Background Multimodal techniques-assisted resection of glioma under general anesthesia(GA)has been shown to achieve similar clinical outcomes as awake craniotomy(AC)in some studies.In this study,we aim to validate the...Background Multimodal techniques-assisted resection of glioma under general anesthesia(GA)has been shown to achieve similar clinical outcomes as awake craniotomy(AC)in some studies.In this study,we aim to validate the use of multimodal techniques can achieve the maximal safe resection of high-grade glioma involving language areas(HGILAs)under GA.Methods HGILAs cases were reviewed and collected between January 2009 and December 2020 in our center.Patients were separated into multimodal group(using neuronavigation,intraoperative MRI combined with direct electrical stimulation[DES]and neuromonitoring[IONM])and conventional group(neuronavigation alone)and clinical outcomes were compared between groups.Studies of HGILAs were reviewed systematically and the meta-analysis results of previous(GA or AC)studies were compared with our results.Results Finally,there were 263 patients in multimodal group and 137 patients in conventional group.Compared to the conventional group,the multimodal group achieved the higher median EOR(100%versus 94.32%,P<0.001)and rate of gross total resection(GTR)(73.8%versus 36.5%,P<0.001)and the lower incidence of permanent language deficit(PLD)(9.5%versus 19.7%,P=0.004).The multimodal group achieved the longer median PFS(16.8 versus 10.3 months,P<0.001)and OS(23.7 versus 15.7 months,P<0.001)than the conventional group.The multimodal group achieved a higher rate of GTR than the cohorts in previous multimodal studies under GA and AC(73.8%versus 55.7%[95%CI 32.0-79.3%]versus 53.4%[35.5-71.2%]).The multimodal group had a lower incidence of PLD than the cohorts in previous multimodal studies under GA(9.5%versus 14.0%[5.8-22.1%])and our incidence of PLD was a little higher than that of previous multimodal studies under AC(9.5%versus 7.5%[3.7-11.2%]).Our multimodal group also achieved a relative longer survival than previous studies.Conclusions Surgery assisted by multimodal techniques can achieve maximal safe resection for HGILAs under GA.Further prospective studies are needed to compare GA with AC for HGILAs.展开更多
[Objectives] The paper was to comprehensively assess the available evidence on the diagnostic value of high-field intraoperative MRI (iMRI) for residual tumor in high-grade glioma (HGG) and its prognostic impact on HG...[Objectives] The paper was to comprehensively assess the available evidence on the diagnostic value of high-field intraoperative MRI (iMRI) for residual tumor in high-grade glioma (HGG) and its prognostic impact on HGG. [Methods] We conducted a systematic literature search of electronic databases including PubMed, Embase and Cochrane Library to identify eligible studies. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The primary outcome was the gross total resection rate, with secondary outcomes including overall survival and 6-month progression-free survival. [Results] From a review of 132 candidate articles, we identified six articles with a total of 573 patients. The pooled risk ratio (RR) was 1.583 (95% CI : 1.235-2.029), indicating that high-field intraoperative MRI guided resection was associated with a reduced risk of 6-month progression-free survival, with a HR of 0.53 (95% CI : 0.348-0.806 ). The pooled HR of overall survival was 0.796 (95% CI : 0.581-1.089) between the two groups. [Conclusions] High-field iMRI appears to enable achievement of an ideal resection, although no strong evidence indicates that its application is associated with patient survival. Our study innovatively considered the effect of magnetic field intensity on tumor resection, and we found that 3 Tesla did not show a more favorable impact on improving the tumor resection rate compared with 1.5 Tesla.展开更多
Background:Adjuvant temozolomide(TMZ)chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma(HGG).However,the influence of long-term TMZ chemotherapy on serum ions concentrat...Background:Adjuvant temozolomide(TMZ)chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma(HGG).However,the influence of long-term TMZ chemotherapy on serum ions concentration is unclear.Methods:One hundred and thirty-eight patients with HGG were included.Their blood samples were collected for blood biochemistry and routine test.The alteration in serum ions concentration,total protein,albumin,globin,and blood cells counts were used to identify the impact of long-term TMZ chemotherapy.Results:Through the comparation of quantitative value of diverse parameters among different chemotherapy cycles,we identified that serum potassium concentration had a downward trend after TMZ administration(1st vs.6th,p<0.001;1st vs.12th,p<0.001).Additionally,the correlation analysis showed that platelets was negatively correlated with chemotherapy cycles(r=−0.649,p=0.023).The hematological adverse events mainly centered on grade 1 to 2.Conclusion:Long-term administration of TMZ may lead to serum ions disturbance.Besides the myelosuppression,we should pay attention to the alteration in serum ions concentration,and give patients proper symptomatic treatment when necessary.展开更多
文摘Optimal management after recurrence or progression of high-grade gliomas is still undefined and remains a challenge for neuro-oncology multidisciplinary teams.Improved radiation therapy techniques,new imaging methods,published experience,and a better radiobiological knowledge of brain tissue have positioned re-irradiation(re-RT)as an option for many of these patients.Decisions must be individualized,taking into account the pattern of relapse,previous treatment,and functional status,as well as the patient’s preferences and expected quality of life.Many questions remain unanswered with respect to re-RT:Who is the most appropriate candidate,which dose and fractionation are most effective,how to define the target volume,which imaging technique is best for planning,and what is the optimal timing?This review will focus on describing the most relevant studies that include re-RT as salvage therapy,with the aim of simplifying decision-making and designing the best available therapeutic strategy.
文摘PURPOSE:This study was conducted to investigate the incidence of ERBB1 amplification and overexpression in samples of diffusely infiltrative (WHO grades Ⅱ-Ⅳ) pediatric brain stem glioma (BSG) and determine the relationship of these abnormalities to expression and mutation of TP53 and tumor grade. Experimental Design: After central pathology review, the incidence of ERBB1 amplification and overexpression was determined in 28 samples (18 surgical biopsy and 10 postmortem specimens) of BSG using quantitative PCR and immunohistochemistry,
文摘Objective:gliomas are the most common intracranial tumors.Fibroblast growth factor-12(FGF12),which belongs to the fibroblast growth factor(FGFs)family,plays an important role in cell mitosis,as well as in other life functions,such as embryo development,tissue repair,cell proliferation,and tumor growth and invasion.The purpose of this study was to explore the potential value of FGF12 in high-grade gliomas and to predict its drug sensitivity.To provide a possible therapeutic target for glioma.Methods:high-grade glioma gene expression data and clinical information were downloaded from the gene expression omnibus(GEO)database,using the R language“impute”and“survival”survival analysis package.The FGF12 genes closely related to survival were screened,a survival curve was drawn,and clinical correlation analysis was conducted.The differentially expressed genes(DEGs)were defined as |logFC|>1,adj.PVal<0.05 as the standard.We used the David for Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis,and constructed the protein-protein interactions(PPI)network.Then we used the Connectivity Map(CMAP)database for drug location,and the validation group was verified by the Chinese Glioma Genome Atlas(CGGA)database in the same way.Results:we found that high FGF12 expression was associated with a higher survival rate.The same validation was performed in the validation group through the CGGA database,and the survival curve showed the same trend.The expression level of FGF12 is an independent factor that affects the life time and status of the samples,and it is a low risk factor.GO enrichment analysis showed that differential genes were enriched in matrix transmembrane transporter activity,ion channels and calcium ion active channels.KEGG showed that DEGs were enriched in the phosphatidylinositol 3-kinase(PI3K)-protein kinase B(Akt)signaling pathway,dopaminergic synapse and cyclic adenosine monophosphate(cAMP)signaling pathway.Four seed genes,GRIA2,COLLA2,GRIA4 and HES6,were obtained by PPI network analysis.The cAMP was used to analyze and obtained 7 small molecule drugs,such as merbromin,naloxone,AH-2384&ticarcillin,vincamine,amoxicillin,azacyclonol,which may be helpful in the prognosis of high-grade gliomas.Conclusion:FGF12 and its pathway may serve as a biomarker or therapeutic target for high-grade gliomas.
文摘Objective:To investigate the expression level of long chain non coding RNAH19 in advanced gliomas and its relationship with glioma cell temozolomide (TMZ) resistance, and make a preliminary study on their related mechanism.Methods:Tissue samples of normal brain tissue, early onset and recurrence of high grade gliomas were collected, and the expression of LNC H19 was detected by reverse transcription polymerase chain reaction (RT-PCR). The construction of Resistant U251 TMZ Resistant (U251-TR) Cell Lines were completed by intermittent concentration gradient increments and verified by MTT method. The changes in the expression of LncRNA H19 was detected by RT-PCR, lovirus transfection was used to construct U251-TR cell line with stable interference with LNC H19 (U251-TRsiLNC H19), and MTT assay was used to observe the changes of TMZ half-maximal inhibitory concentration (IC50). Western Blot and RT-PCR were used to detect the changes of O6-methylguanine DNA methyltransferase (MGMT) in U251, U251-TR and U251-TRsiLNC H19.Results: The results of RT-PCR showed that the expression of LNC H19 in high-grade glioma was significantly higher than that in primary glioma tissue and normal brain tissue. The IC50 value and drug resistance index of U251-TR cell line were significantly increased, the expression of LncRNA H19 in U251-TR cell line was significantly higher than that in U251 cells and the expression of MGMT were also increased. We succeeded in interfering with the expression of LNC H19 in the U251-TR cell line, and found that the IC50 value and drug resistance index of U251-TR cell line were decreased significantly and the expression of MGMT were also decreased.Conclusion:LNC H19 is highly expressed in recurrent high-grade gliomas, which may increase the level of MGMT, leading to the occurrence of glioma cell TMZ resistance. LNC H19 is a key factor in the occurrence of TMZ resistance in glioma cells.
文摘Background Multimodal techniques-assisted resection of glioma under general anesthesia(GA)has been shown to achieve similar clinical outcomes as awake craniotomy(AC)in some studies.In this study,we aim to validate the use of multimodal techniques can achieve the maximal safe resection of high-grade glioma involving language areas(HGILAs)under GA.Methods HGILAs cases were reviewed and collected between January 2009 and December 2020 in our center.Patients were separated into multimodal group(using neuronavigation,intraoperative MRI combined with direct electrical stimulation[DES]and neuromonitoring[IONM])and conventional group(neuronavigation alone)and clinical outcomes were compared between groups.Studies of HGILAs were reviewed systematically and the meta-analysis results of previous(GA or AC)studies were compared with our results.Results Finally,there were 263 patients in multimodal group and 137 patients in conventional group.Compared to the conventional group,the multimodal group achieved the higher median EOR(100%versus 94.32%,P<0.001)and rate of gross total resection(GTR)(73.8%versus 36.5%,P<0.001)and the lower incidence of permanent language deficit(PLD)(9.5%versus 19.7%,P=0.004).The multimodal group achieved the longer median PFS(16.8 versus 10.3 months,P<0.001)and OS(23.7 versus 15.7 months,P<0.001)than the conventional group.The multimodal group achieved a higher rate of GTR than the cohorts in previous multimodal studies under GA and AC(73.8%versus 55.7%[95%CI 32.0-79.3%]versus 53.4%[35.5-71.2%]).The multimodal group had a lower incidence of PLD than the cohorts in previous multimodal studies under GA(9.5%versus 14.0%[5.8-22.1%])and our incidence of PLD was a little higher than that of previous multimodal studies under AC(9.5%versus 7.5%[3.7-11.2%]).Our multimodal group also achieved a relative longer survival than previous studies.Conclusions Surgery assisted by multimodal techniques can achieve maximal safe resection for HGILAs under GA.Further prospective studies are needed to compare GA with AC for HGILAs.
文摘[Objectives] The paper was to comprehensively assess the available evidence on the diagnostic value of high-field intraoperative MRI (iMRI) for residual tumor in high-grade glioma (HGG) and its prognostic impact on HGG. [Methods] We conducted a systematic literature search of electronic databases including PubMed, Embase and Cochrane Library to identify eligible studies. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). The primary outcome was the gross total resection rate, with secondary outcomes including overall survival and 6-month progression-free survival. [Results] From a review of 132 candidate articles, we identified six articles with a total of 573 patients. The pooled risk ratio (RR) was 1.583 (95% CI : 1.235-2.029), indicating that high-field intraoperative MRI guided resection was associated with a reduced risk of 6-month progression-free survival, with a HR of 0.53 (95% CI : 0.348-0.806 ). The pooled HR of overall survival was 0.796 (95% CI : 0.581-1.089) between the two groups. [Conclusions] High-field iMRI appears to enable achievement of an ideal resection, although no strong evidence indicates that its application is associated with patient survival. Our study innovatively considered the effect of magnetic field intensity on tumor resection, and we found that 3 Tesla did not show a more favorable impact on improving the tumor resection rate compared with 1.5 Tesla.
基金This work was supported by funding from the National Key Research and Development Plan(No. 2016YFC0902500)the National Natural Science Foundation of China(No. 81903060)the Cultivation Plan of Beijing Hospital Management Center(PX2021025)
文摘Background:Adjuvant temozolomide(TMZ)chemotherapy with standard regimen remarkably improves survival in patients with high-grade glioma(HGG).However,the influence of long-term TMZ chemotherapy on serum ions concentration is unclear.Methods:One hundred and thirty-eight patients with HGG were included.Their blood samples were collected for blood biochemistry and routine test.The alteration in serum ions concentration,total protein,albumin,globin,and blood cells counts were used to identify the impact of long-term TMZ chemotherapy.Results:Through the comparation of quantitative value of diverse parameters among different chemotherapy cycles,we identified that serum potassium concentration had a downward trend after TMZ administration(1st vs.6th,p<0.001;1st vs.12th,p<0.001).Additionally,the correlation analysis showed that platelets was negatively correlated with chemotherapy cycles(r=−0.649,p=0.023).The hematological adverse events mainly centered on grade 1 to 2.Conclusion:Long-term administration of TMZ may lead to serum ions disturbance.Besides the myelosuppression,we should pay attention to the alteration in serum ions concentration,and give patients proper symptomatic treatment when necessary.
