Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism betwee...Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.展开更多
Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occu...Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.展开更多
Introduction: Despite recent advances in neuroimaging and microsurgical techniques, surgical resection of spinal cord tumours remains a challenge. However, the evolution with advances and refinement of neurophysiologi...Introduction: Despite recent advances in neuroimaging and microsurgical techniques, surgical resection of spinal cord tumours remains a challenge. However, the evolution with advances and refinement of neurophysiological equipment and methodologies, intra-operative neurophysiolo- gical monitoring (IONM) is now regarded as an essential adjunct to the surgical management of intramedullary spinal cord tumours. This study aims to report our preliminary experience with IONM and emphasise its effective role of achieving maximum tumour resection and minimising neurological injury. Methods: This is a retrospective study performed at our institution between July 2012 and August 2013. It included a cohort of 6 consecutive patients presented with intramedullary spinal cord tumours. Their mean age was 26 years (range, 4 months - 37 years), all were males, and the mean follow up was 11.6 months. Results: We combined the use of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in spinal cord surgery. SSEPs are monitored during the incision of the dorsal midline of the spinal cord and this was used in two of our patients and MEPs were used as an essential monitoring during the tumour resection. In addition, we used free-running electromyography (EMG) and muscle MEPs (mMEPs) during tumour resection. Four of our patients (two with ependymoma, one with ganglioglioma, and one with pilocytic astrocytoma) had complete tumour resection and two patients (pilocytic and diffuse astrocytoma) had IONM changes during surgery and had partial tumour resection. At 6-month follow up all our patients had made a good recovery with no new neurological sequelae. Conclusion: This small series and literature review is presented to add and improve the understanding of IONM in intramedullary spinal cord procedures and to reinforce the importance of IONM in optimising tumour resection and neurological outcome. Our series confirm that without D-wave monitoring, free-running EMG and MEP monitoring during tumour resection remain an important adjunct. We also draw attention to the fact that changes in the free-running EMG occur before any changes in the MEPs are noted.展开更多
Background:Glioblastoma(GBM)remains themost aggressive primary brain tumour in adults,marked by pronounced cellular heterogeneity,diffuse infiltration,and resistance to conventional treatment.In recent years,transcrip...Background:Glioblastoma(GBM)remains themost aggressive primary brain tumour in adults,marked by pronounced cellular heterogeneity,diffuse infiltration,and resistance to conventional treatment.In recent years,transcriptomic profiling has provided valuable insights into the molecular mechanisms that govern the progression of glioblastoma.This systematic review aims to synthesise the current literature on dysregulated gene expression in GBM,focusing on gene signatures associatedwith stemness,immunemodulation,extracellularmatrix remodelling,metabolic adaptation,and therapeutic resistance.Methods:We conducted a systematic search of PubMed,The Cancer Genome Atlas(TCGA),Chinese Glioma Genome Atlas(CGGA),and the GlioVis portal for studies published between January 2005 and April 2025,limited to English-language reports.Studies were eligible if they included adult glioblastoma tissue or patient-derived datasets and reported gene-level expression or clinical associations.Reviews,commentaries,and studies on non-GBM gliomas were excluded.Screening followed the PRISMA 2020 checklist,with 410 records initially identified,90 duplicates removed,and 125 studies retained after full-text review.Data were synthesised descriptively,and findings were validated against TCGA/CGGA expression datasets to ensure consistency across cohorts.Results:We categorised recurrently dysregulated genes by their biological function,including transcription factors(SOX2,ZEB2),growth factor receptors(EGFR,PDGFRA),immune-related markers(PD-L1,TAP1,B2M),extracellular matrix regulators(MMP2,LAMC1,HAS2),and metabolic genes(SLC7A11,PRMT5,NRF2).For each group,we examine the functional consequences of transcriptional alterations and their role in driving key glioblastoma phenotypes,including angiogenesis,immunosuppression,invasiveness,and recurrence.Conclusion:We further discuss the prognostic implications of these gene signatures and evaluate their potential utility in precisionmedicine,including current clinical trials that target molecular pathways identified through transcriptomic data.This review highlights the power of gene expression profiling to stratify glioblastoma subtypes and improve personalised therapeutic strategies.展开更多
文摘Background:The dysregulation of Isocitrate dehydrogenase(IDH)and the subsequent production of 2-Hydroxyglutrate(2HG)may alter the expression of epigenetic proteins in Grade 4 astrocytoma.The interplay mechanism between IDH,O-6-methylguanine-DNA methyltransferase(MGMT)-promoter methylation,and protein methyltransferase proteins-5(PRMT5)activity,with tumor progression has never been described.Methods:A retrospective cohort of 34 patients with G4 astrocytoma is classified into IDH-mutant and IDH-wildtype tumors.Both groups were tested for MGMT-promoter methylation and PRMT5 through methylation-specific and gene expression PCR analysis.Inter-cohort statistical significance was evaluated.Results:Both IDH-mutant WHO grade 4 astrocytomas(n=22,64.7%)and IDH-wildtype glioblastomas(n=12,35.3%)had upregulated PRMT5 gene expression except in one case.Out of the 22 IDH-mutant tumors,10(45.5%)tumors showed MGMT-promoter methylation and 12(54.5%)tumors had unmethylated MGMT.All IDH-wildtype tumors had unmethylated MGMT.There was a statistically significant relationship between MGMT-promoter methylation and IDH in G4 astrocytoma(p-value=0.006).Statistically significant differences in progression-free survival(PFS)were also observed among all G4 astrocytomas that expressed PRMT5 and received either temozolomide(TMZ)or TMZ plus other chemotherapies,regardless of their IDH or MGMT-methylation status(p-value=0.0014).Specifically,IDH-mutant tumors that had upregulated PRMT5 activity and MGMT-promoter methylation,who received only TMZ,have exhibited longer PFS.Conclusions:The relationship between PRMT5,MGMT-promoter,and IDH is not tridirectional.However,accumulation of D2-hydroxyglutarate(2-HG),which partially activates 2-OG-dependent deoxygenase,may not affect their activities.In IDH-wildtype glioblastomas,the 2HG-2OG pathway is typically inactive,leading to PRMT5 upregulation.TMZ alone,compared to TMZ-plus,can increase PFS in upregulated PRMT5 tumors.Thus,using a PRMT5 inhibitor in G4 astrocytomas may help in tumor regression.
文摘Medulloblastoma(MB)is considered the commonest malignant brain tumor in children.Multimodal treatments consisting of surgery,radiation,and chemotherapy have improved patients’survival.Nevertheless,the recurrence occurs in 30%of cases.The persistent mortality rates,the failure of current therapies to extend life expectancy,and the serious complications of non-targeted cytotoxic treatment indicate the need for more refined therapeutic approaches.Most MBs originating from the neurons of external granular layer line the outer surface of neocerebellum and responsible for the afferent and efferent connections.Recently,MBs have been segregated into four molecular subgroups:Wingless-activated(WNT-MB)(Group 1);Sonichedgehog-activated(SHH-MB)(Group 2);Group 3 and 4 MBs.These molecular alterations follow specific gene mutations and disease-risk stratifications.The current treatment protocols and ongoing clinical trials against these molecular subgroups are still using common chemotherapeutic agents by which their efficacy have improved the progression-free survival but did not change the overall survival.However,the need to explore new therapies targeting specific receptors in MB microenvironment became essential.The immune microenvironment of MBs consists of distinctive cellular heterogeneities including immune cells and none-immune cells.Tumour associate macrophage and tumour infiltrating lymphocyte are considered the main principal cells in tumour microenvironment,and their role are still under investigation.In this review,we discuss the mechanism of interaction between MB cells and immune cells in the microenvironment,with an overview of the recent investigations and clinical trials.
文摘Introduction: Despite recent advances in neuroimaging and microsurgical techniques, surgical resection of spinal cord tumours remains a challenge. However, the evolution with advances and refinement of neurophysiological equipment and methodologies, intra-operative neurophysiolo- gical monitoring (IONM) is now regarded as an essential adjunct to the surgical management of intramedullary spinal cord tumours. This study aims to report our preliminary experience with IONM and emphasise its effective role of achieving maximum tumour resection and minimising neurological injury. Methods: This is a retrospective study performed at our institution between July 2012 and August 2013. It included a cohort of 6 consecutive patients presented with intramedullary spinal cord tumours. Their mean age was 26 years (range, 4 months - 37 years), all were males, and the mean follow up was 11.6 months. Results: We combined the use of somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) in spinal cord surgery. SSEPs are monitored during the incision of the dorsal midline of the spinal cord and this was used in two of our patients and MEPs were used as an essential monitoring during the tumour resection. In addition, we used free-running electromyography (EMG) and muscle MEPs (mMEPs) during tumour resection. Four of our patients (two with ependymoma, one with ganglioglioma, and one with pilocytic astrocytoma) had complete tumour resection and two patients (pilocytic and diffuse astrocytoma) had IONM changes during surgery and had partial tumour resection. At 6-month follow up all our patients had made a good recovery with no new neurological sequelae. Conclusion: This small series and literature review is presented to add and improve the understanding of IONM in intramedullary spinal cord procedures and to reinforce the importance of IONM in optimising tumour resection and neurological outcome. Our series confirm that without D-wave monitoring, free-running EMG and MEP monitoring during tumour resection remain an important adjunct. We also draw attention to the fact that changes in the free-running EMG occur before any changes in the MEPs are noted.
文摘Background:Glioblastoma(GBM)remains themost aggressive primary brain tumour in adults,marked by pronounced cellular heterogeneity,diffuse infiltration,and resistance to conventional treatment.In recent years,transcriptomic profiling has provided valuable insights into the molecular mechanisms that govern the progression of glioblastoma.This systematic review aims to synthesise the current literature on dysregulated gene expression in GBM,focusing on gene signatures associatedwith stemness,immunemodulation,extracellularmatrix remodelling,metabolic adaptation,and therapeutic resistance.Methods:We conducted a systematic search of PubMed,The Cancer Genome Atlas(TCGA),Chinese Glioma Genome Atlas(CGGA),and the GlioVis portal for studies published between January 2005 and April 2025,limited to English-language reports.Studies were eligible if they included adult glioblastoma tissue or patient-derived datasets and reported gene-level expression or clinical associations.Reviews,commentaries,and studies on non-GBM gliomas were excluded.Screening followed the PRISMA 2020 checklist,with 410 records initially identified,90 duplicates removed,and 125 studies retained after full-text review.Data were synthesised descriptively,and findings were validated against TCGA/CGGA expression datasets to ensure consistency across cohorts.Results:We categorised recurrently dysregulated genes by their biological function,including transcription factors(SOX2,ZEB2),growth factor receptors(EGFR,PDGFRA),immune-related markers(PD-L1,TAP1,B2M),extracellular matrix regulators(MMP2,LAMC1,HAS2),and metabolic genes(SLC7A11,PRMT5,NRF2).For each group,we examine the functional consequences of transcriptional alterations and their role in driving key glioblastoma phenotypes,including angiogenesis,immunosuppression,invasiveness,and recurrence.Conclusion:We further discuss the prognostic implications of these gene signatures and evaluate their potential utility in precisionmedicine,including current clinical trials that target molecular pathways identified through transcriptomic data.This review highlights the power of gene expression profiling to stratify glioblastoma subtypes and improve personalised therapeutic strategies.
