Gliomas are primary brain tumors derived from glial cells of the central nervous system,afflicting both adults and children with distinct characteristics and therapeutic challenges.Recent developments have ushered in ...Gliomas are primary brain tumors derived from glial cells of the central nervous system,afflicting both adults and children with distinct characteristics and therapeutic challenges.Recent developments have ushered in novel clinical and molecular prognostic factors,reshaping treatment paradigms based on classi-fication and grading,determined by histological attributes and cellular lineage.This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023.For adults,the therapeutic triad typically consists of surgical resection,chemotherapy,and radiotherapy.In contrast,pediatric gliomas,due to their diversity,require a more tailored approach.Although complete tumor excision can be curative based on the location and grade of the glioma,certain non-resectable cases demand a chemotherapy approach usually involving,vincristine and carboplatin.Addi-tionally,if surgery or chemotherapy strategies are unsuccessful,Vinblastine can be used.Despite recent advancements in treatment methodologies,there remains a need of exploration in the literature,particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts.This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.展开更多
Gliomas originate from glial cells in the central nervous system.Approximately 80%-85%of malignant brain tumors in adults are gliomas.The most common central nervous system tumor in children is low-grade pediatric gli...Gliomas originate from glial cells in the central nervous system.Approximately 80%-85%of malignant brain tumors in adults are gliomas.The most common central nervous system tumor in children is low-grade pediatric glioma.Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral diagnosis.Molecular characterization has led to better diagnostic and prognostic staging,which in turn has increased the precision of treatment.Current efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with glioma.However,improvements in survival have been modest.Currently,clinical guidelines,as well as the article by Mohamed et al accompanying this editorial piece,are adapting treatment recommendations(surgery,chemotherapy,and radiotherapy)according to diagnosis and prognosis guided by molecular biomarkers.Furthermore,this paves the way for the design of clinical trials with new therapies,which is especially important in pediatric gliomas.展开更多
BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-rel...BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several cancers.AIM To investigate the role and mechanism of SCIN in glioma.METHODS The expression and clinical significance of SCIN in glioma were analyzed based on public databases.SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting.Gene silencing was performed using short hairpin RNA transfection.Cell viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin staining.RESULTS SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase.Furthermore,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 cells.Moreover,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 cells.CONCLUSION SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma cells.This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.展开更多
Gliomas are aggressive brain tumors known for their heterogeneity,unclear borders,and diverse locations on Magnetic Resonance Imaging(MRI)scans.These factors present significant challenges for MRI-based segmentation,a...Gliomas are aggressive brain tumors known for their heterogeneity,unclear borders,and diverse locations on Magnetic Resonance Imaging(MRI)scans.These factors present significant challenges for MRI-based segmentation,a crucial step for effective treatment planning and monitoring of glioma progression.This study proposes a novel deep learning framework,ResNet Multi-Head Attention U-Net(ResMHA-Net),to address these challenges and enhance glioma segmentation accuracy.ResMHA-Net leverages the strengths of both residual blocks from the ResNet architecture and multi-head attention mechanisms.This powerful combination empowers the network to prioritize informative regions within the 3D MRI data and capture long-range dependencies.By doing so,ResMHANet effectively segments intricate glioma sub-regions and reduces the impact of uncertain tumor boundaries.We rigorously trained and validated ResMHA-Net on the BraTS 2018,2019,2020 and 2021 datasets.Notably,ResMHA-Net achieved superior segmentation accuracy on the BraTS 2021 dataset compared to the previous years,demonstrating its remarkable adaptability and robustness across diverse datasets.Furthermore,we collected the predicted masks obtained from three datasets to enhance survival prediction,effectively augmenting the dataset size.Radiomic features were then extracted from these predicted masks and,along with clinical data,were used to train a novel ensemble learning-based machine learning model for survival prediction.This model employs a voting mechanism aggregating predictions from multiple models,leading to significant improvements over existing methods.This ensemble approach capitalizes on the strengths of various models,resulting in more accurate and reliable predictions for patient survival.Importantly,we achieved an impressive accuracy of 73%for overall survival(OS)prediction.展开更多
Paragangliomas,also known as pheochromocytomas(1–9 cases per million),arise in the paraganglia.[1]Pheochromocytomas occur in the adrenal glands,while paragangliomas occur elsewhere.[2]Paragangliomas originate from pa...Paragangliomas,also known as pheochromocytomas(1–9 cases per million),arise in the paraganglia.[1]Pheochromocytomas occur in the adrenal glands,while paragangliomas occur elsewhere.[2]Paragangliomas originate from paraganglion cells,which are derived from the neural ectoderm of the nerves and migrate along both sides of the median axis from the base of the skull to the pelvis during embryonic development.展开更多
Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark ...Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae plants.It also has anti-infection,antitumor,and immunomodulatory effects.In this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and U251-MG.However,the mechanism through which honokiol regulates glioma cell apoptosis is still unknown.Methods:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control cells.Protein-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative PCR.Furthermore,MAPK signaling and ferroptosis were detected via western blotting.Results:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased genes.Analysis of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were verified.Conclusion:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling pathways.These data could lead to new ideas for future research and therapy for patients with glioma.展开更多
Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kina...Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains unclear.Methods We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM specimens.Glioma stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional culture.For the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were studied.Results VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall survival.Patients with VM-positive GBMs exhibited higher pATM levels(r_(s)=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in vitro.ATM inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin B2.Conclusion VM may predict a poor GBM prognosis and is associated with pATM expression.We propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.展开更多
Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predic...Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.展开更多
Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well und...Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.展开更多
Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the ...Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.展开更多
Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA...Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA).However,the pathogenesis is not fully understood.We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors,and to investigate its function in patients’prognosis and immunotherapy.Methods:The differential expression,diagnosis,prognosis,genetic and epigenetic alterations,tumor microenvironment,stemness,immune infiltration cells,function enrichment,single-cell analysis,and drug response across cancers were conducted based on multiple computational tools.Additionally,we validated its carcinogenic effect and possible mechanism in glioma cells.Results:We exhibited that DLAT expression was increased in most tumors,especially in glioma,and affected the survival of tumor patients.DLAT was related to RNA modification genes,DNA methylation,immune infiltration,and immune infiltration cells,including CD4+T cells,CD8+T cells,Tregs,and cancer-associatedfibroblasts.Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis,inflammation,and stemness.Enrichment analysis revealed that DLAT might take part in the cell cycle pathway.Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds,including PI3Kβinhibitors,PKC inhibitors,HSP90 inhibitors,and MEK inhibitors.In addition,glioma cells with DLAT silence inhibited proliferation,migration,and invasion ability,and promoted cell apoptosis.Conclusion:We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors,and its possible functions and mechanisms.DLAT is a potential diagnostic,prognostic,and immunotherapeutic biomarker for cancer patients.展开更多
Objective Glioma is a central nervous system tumor arising from glial cells.Despite significant advances in diagnosis and treatment,most patients with high-grade gliomas have a poor prognosis.Many studies have shown t...Objective Glioma is a central nervous system tumor arising from glial cells.Despite significant advances in diagnosis and treatment,most patients with high-grade gliomas have a poor prognosis.Many studies have shown that long noncoding RNAs(lncRNAs)may play important roles in the development,progression and treatment of many tumors,including gliomas.Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma.Therefore,we hope that by studying differentially expressed lncRNAs(DElncRNAs)in glioma,we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients.Methods First,the expression of lncRNAs in 5 normal brain(NB)tissues and 10 glioma tissues was examined by RNA sequencing(RNA-seq).Next,we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas(TCGA)database to assess the prognostic value of these variables.Finally,functional analysis of the DElncRNAs was performed by means of Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Results RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma(LGG)and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma(GBM).Among them,AL355974.3 was the most upregulated lncRNA.LINC00632 was the most downregulated lncRNA.Second,LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database.Finally,bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways,such as cell metabolic and developmental processes.Conclusion Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.展开更多
Clinical data indicates that glioma patients have poor treatment outcomes and clinical prognosis.The role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully elucidated.In this study,we ai...Clinical data indicates that glioma patients have poor treatment outcomes and clinical prognosis.The role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully elucidated.In this study,we aimed to investigate the role and relationship between OSPRGs and glioma.Univariate and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha L,GNAL)was screened.The association of GNAL expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was performed.Immunohistochemistry was used to evaluate GNAL level in glioma.Further analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of GNAL.GNAL was an independent prognostic factor,and patients with low GNAL expression have a poor prognosis.Expression of GNAL was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related pathways.Immune infiltration analysis indicated that GNAL levels were negatively correlated with immune scores.GNAL low-expression group showed efficacy with anti-PD-1 therapy.Ten compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAL high and low-expression groups were identified.Furthermore,its expression was associated with several immune cells,immune-related genes,and NOCGs.The expression of GNAL is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.展开更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiqu...Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.展开更多
BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,...BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.展开更多
BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify ...BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.展开更多
Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram.Methods Data from elderly individuals(age≥65 years)histologicall...Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram.Methods Data from elderly individuals(age≥65 years)histologically diagnosed with brain glioma were sourced from the Surveillance,Epidemiology,and End Results(SEER)database.The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio.Additionally,data obtained from Tangdu Hospital constituted an external validation cohort for the study.The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator(LASSO)and multivariate Cox regression analysis,enabling the construction of a nomogram.Model performance was evaluated using C-index,ROC curves,calibration plot and decision curve analysis(DCA).Results A cohort of 20483 elderly glioma patients was selected from the SEER database.Five prognostic factors(age,marital status,histological type,stage,and treatment)were found to significantly impact overall survival(OS)and cancer-specific survival(CSS),with tumor location emerging as a sixth variable independently linked to CSS.Subsequently,nomogram models were developed to predict the probabilities of survival at 6,12,and 24 months.The assessment findings from the validation queue indicate a that the model exhibited strong performance.Conclusion Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients.They can potentially assist in risk stratification and clinical decision-making.展开更多
This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas(LGG),the predominant primary tumors in the central nervous system.With a general incidence r...This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas(LGG),the predominant primary tumors in the central nervous system.With a general incidence rate of 5.81 per 100000,gliomas pose a significant global concern,necessitating advancements in treatment techniques to reduce mortality and morbidity.This review places a particular focus on immunotherapies,discussing promising agents such as Zotiraciclib and Lerapolturev.Zotiraciclib,a CDK9 inhibitor,has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies,showing its potential as a therapeutic breakthrough.Lerapolturev,a viral immunotherapy,induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients.Exploration of immunotherapy extends to Pembrolizumab,Nivolumab,and Entrectinib,revealing the challenges and variabilities in patient responses.Despite promising preclinical data,the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment,emphasizing the critical need to understand resistance mechanisms.The review also covers the success of radiation therapy in pediatric LGG,with evolving techniques,such as proton therapy,showing potential improvements in patient quality of life.Surgical treatment is discussed in the context of achieving a balance between preserving the patient’s quality of life and attaining gross total resection,with the extent of surgical resection significantly influencing the survival outcomes.In addition to advancements in cancer vaccine development,this review highlights the evolving landscape of LGG treatment,emphasizing a shift toward personalized and targeted therapies.Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.展开更多
Glioma is one of the most common primary intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event in tumor cell migration.Scinderin(SCIN),an actin ...Glioma is one of the most common primary intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event in tumor cell migration.Scinderin(SCIN),an actin severing and capping protein that regulates the actin cytoskeleton,is involved in the prolif-eration and migration of certain cancer cells.However,its biological role and molecular mechanism in glioma remain unclear.Lin et al explored the role and mechanism of SCIN in gliomas.The results showed that SCIN mechanically affected cytoskeleton remodeling and inhibited the formation of lamellipodia via RhoA/FAK signaling pathway.This study identifies the cancer-promoting role of SCIN and provides a potential therapeutic target for SCIN in glioma treatment.展开更多
Brainstem gliomas comprise both slow-growing and highly aggressive tumors,the latter carrying a dismal prognosis of approximately 10 months in children.Given their common locations along the brainstem,they are often n...Brainstem gliomas comprise both slow-growing and highly aggressive tumors,the latter carrying a dismal prognosis of approximately 10 months in children.Given their common locations along the brainstem,they are often not amenable to surgical resection.There are currently a host of exploratory therapies under investigation ranging from immunotherapy,small molecular inhibitors,epigenetic-modifying agents,and radiation protocols to combat these difficult-to-treat tumors.Recent discoveries highlighting the role of H3 histone mutations in diffuse midline glioma oncogenesis have yielded a variety of new targetable antigens and aberrant signaling pathways.Although many of these studies have shown promise in terms of inhibiting tumor growth and disease progression,results to date have been modest in their ability to translate into meaningful clinical benefit.This review will serve as an updated report on the current state of literature concerning pre-clinical and clinical therapies being investigated for brainstem glioma.In addition,this review will serve as a guide for clinicians as we review the evolving nomenclature of brainstem gliomas,commonly presenting symptoms,diagnostic tools,and standard therapies.展开更多
文摘Gliomas are primary brain tumors derived from glial cells of the central nervous system,afflicting both adults and children with distinct characteristics and therapeutic challenges.Recent developments have ushered in novel clinical and molecular prognostic factors,reshaping treatment paradigms based on classi-fication and grading,determined by histological attributes and cellular lineage.This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023.For adults,the therapeutic triad typically consists of surgical resection,chemotherapy,and radiotherapy.In contrast,pediatric gliomas,due to their diversity,require a more tailored approach.Although complete tumor excision can be curative based on the location and grade of the glioma,certain non-resectable cases demand a chemotherapy approach usually involving,vincristine and carboplatin.Addi-tionally,if surgery or chemotherapy strategies are unsuccessful,Vinblastine can be used.Despite recent advancements in treatment methodologies,there remains a need of exploration in the literature,particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts.This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.
文摘Gliomas originate from glial cells in the central nervous system.Approximately 80%-85%of malignant brain tumors in adults are gliomas.The most common central nervous system tumor in children is low-grade pediatric glioma.Diagnosis was determined by histological features until 2016 when the World Health Organization classification integrated molecular data with anatomopathological information to achieve a more integral diagnosis.Molecular characterization has led to better diagnostic and prognostic staging,which in turn has increased the precision of treatment.Current efforts are focused on more effective therapies to prolong survival and improve the quality of life of adult and pediatric patients with glioma.However,improvements in survival have been modest.Currently,clinical guidelines,as well as the article by Mohamed et al accompanying this editorial piece,are adapting treatment recommendations(surgery,chemotherapy,and radiotherapy)according to diagnosis and prognosis guided by molecular biomarkers.Furthermore,this paves the way for the design of clinical trials with new therapies,which is especially important in pediatric gliomas.
文摘BACKGROUND Glioma is one of the most common intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event of tumor cell migration.The actin dynamics-related protein scinderin(SCIN)has been reported to be closely related to tumor cell migration and invasion in several cancers.AIM To investigate the role and mechanism of SCIN in glioma.METHODS The expression and clinical significance of SCIN in glioma were analyzed based on public databases.SCIN expression was examined using real-time quantitative polymerase chain reaction and Western blotting.Gene silencing was performed using short hairpin RNA transfection.Cell viability,migration,and invasion were assessed using cell counting kit 8 assay,wound healing,and Matrigel invasion assays,respectively.F-actin cytoskeleton organization was assessed using F-actin staining.RESULTS SCIN expression was significantly elevated in glioma,and high levels of SCIN were associated with advanced tumor grade and wild-type isocitrate dehydrogenase.Furthermore,SCIN-deficient cells exhibited decreased proliferation,migration,and invasion in U87 and U251 cells.Moreover,knockdown of SCIN inhibited the RhoA/focal adhesion kinase(FAK)signaling to promote F-actin depolymerization in U87 and U251 cells.CONCLUSION SCIN modulates the actin cytoskeleton via activating RhoA/FAK signaling,thereby promoting the migration and invasion of glioma cells.This study identified the cancer-promoting effect of SCIN and provided a potential therapeutic target for the treatment of glioma.
基金the Deanship of Research and Graduate Studies at King Khalid University for funding this work through a Large Research Project under grant number RGP2/254/45.
文摘Gliomas are aggressive brain tumors known for their heterogeneity,unclear borders,and diverse locations on Magnetic Resonance Imaging(MRI)scans.These factors present significant challenges for MRI-based segmentation,a crucial step for effective treatment planning and monitoring of glioma progression.This study proposes a novel deep learning framework,ResNet Multi-Head Attention U-Net(ResMHA-Net),to address these challenges and enhance glioma segmentation accuracy.ResMHA-Net leverages the strengths of both residual blocks from the ResNet architecture and multi-head attention mechanisms.This powerful combination empowers the network to prioritize informative regions within the 3D MRI data and capture long-range dependencies.By doing so,ResMHANet effectively segments intricate glioma sub-regions and reduces the impact of uncertain tumor boundaries.We rigorously trained and validated ResMHA-Net on the BraTS 2018,2019,2020 and 2021 datasets.Notably,ResMHA-Net achieved superior segmentation accuracy on the BraTS 2021 dataset compared to the previous years,demonstrating its remarkable adaptability and robustness across diverse datasets.Furthermore,we collected the predicted masks obtained from three datasets to enhance survival prediction,effectively augmenting the dataset size.Radiomic features were then extracted from these predicted masks and,along with clinical data,were used to train a novel ensemble learning-based machine learning model for survival prediction.This model employs a voting mechanism aggregating predictions from multiple models,leading to significant improvements over existing methods.This ensemble approach capitalizes on the strengths of various models,resulting in more accurate and reliable predictions for patient survival.Importantly,we achieved an impressive accuracy of 73%for overall survival(OS)prediction.
文摘Paragangliomas,also known as pheochromocytomas(1–9 cases per million),arise in the paraganglia.[1]Pheochromocytomas occur in the adrenal glands,while paragangliomas occur elsewhere.[2]Paragangliomas originate from paraganglion cells,which are derived from the neural ectoderm of the nerves and migrate along both sides of the median axis from the base of the skull to the pelvis during embryonic development.
基金The study was supported by the Natural Science Foundation of Jilin Province(Grant No.20200201444JC).
文摘Background:Glioma is a kind of tumor that easily deteriorates and originates from glial cells in nerve tissue.Honokiol is a bisphenol compound that is an essential monomeric compound extracted from the roots and bark of Magnoliaceae plants.It also has anti-infection,antitumor,and immunomodulatory effects.In this study,we found that honokiol induces cell apoptosis in the human glioma cell lines U87-MG and U251-MG.However,the mechanism through which honokiol regulates glioma cell apoptosis is still unknown.Methods:We performed RNA-seq analysis of U251-MG cells treated with honokiol and control cells.Protein-protein interaction(PPI)network analysis was performed,and the 10 top hub unigenes were examined via real-time quantitative PCR.Furthermore,MAPK signaling and ferroptosis were detected via western blotting.Results:332 differentially expressed genes(DEGs)were found,comprising 163 increased and 169 decreased genes.Analysis of the DEGs revealed that various biological processes were enriched,including‘response to hypoxia’,‘cerebellum development cellular response to hypoxia,’‘iron ion binding,’‘oxygen transporter activity,’‘oxygen binding,’‘ferric iron binding,’and‘structural constituent of cytoskeleton.’Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis revealed that the DEGs were enriched in the following pathways:‘mitogen-activated protein kinases(MAPK)’,‘Hypoxia-inducible factor 1(HIF-1)’,‘ferroptosis,’‘Peroxisome proliferator-activated receptor(PPAR),’‘Phosphatidylinositol-4,5-bisphosphate 3-kinase(PI3K)-protein kinase B(Akt),’and‘phagosome.’Among these pathways,the MAPK signaling pathway and ferroptosis were verified.Conclusion:This study revealed the potential mechanism by which honokiol induces apoptosis and provided a comprehensive analysis of DEGs in honokiol-treated U251-MG cells and the associated signaling pathways.These data could lead to new ideas for future research and therapy for patients with glioma.
基金supported by the Natural Science Foundation of Anhui Province(2208085MH250,2308085MH272)National Key Research and Development Program of China(2021YFF1201000)+2 种基金Natural Science Research Project of the Anhui Educational Committee(2023AH040404,2023AH053402)Anhui Provincial Health and Medical Research Project(AHWJ2023A10143)Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM(2023IHM01043)。
文摘Objective Vasculogenic mimicry(VM)is a novel vasculogenic process integral to glioma stem cells(GSCs)in glioblastoma(GBM).However,the relationship between VM and ataxia-telangiectasia mutated(ATM)serine/threonine kinase activation,which confers chemoradiotherapy resistance,remains unclear.Methods We investigated VM formation and phosphorylated ATM(pATM)levels by CD31/GFAPperiodic acid-Schiff dual staining and immunohistochemical staining in 145 GBM specimens.Glioma stem-like cells(GSLCs)derived from the formatted spheres of U87 and U251 cell lines and their pATM level and VM formation ability were examined using western blot and three-dimensional culture.For the examination of the function of pATM in VM formation by GSLCs,ATM knockdown by shRNAs and deactivated via ATM phosphorylation inhibitor KU55933 were studied.Results VM and high pATM expression occurred in 38.5% and 41.8% of tumors,respectively,and were significantly associated with reduced progression-free and overall survival.Patients with VM-positive GBMs exhibited higher pATM levels(r_(s)=0.425,P=0.01).The multivariate analysis established VM as an independent negative prognostic factor(P=0.002).Furthermore,GSLCs expressed high levels of pATM and formed vascular-like networks in vitro.ATM inactivation or knockdown hindered VM-like network formation concomitant with the downregulation of pVEGFR-2,VE-cadherin,and laminin B2.Conclusion VM may predict a poor GBM prognosis and is associated with pATM expression.We propose that pATM promotes VM through extracellular matrix modulation and VE-Cadherin/pVEGFR-2 activation,thereby highlighting ATM activation as a potential target for enhancing anti-angiogenesis therapies for GBM.
基金funded by the Scientific Research Project of the Higher Education Department of Guizhou Province[Qianjiaoji 2022(187)]Department of Education of Guizhou Province[Guizhou Teaching and Technology(2023)015]+1 种基金Guizhou Medical University National Natural Science Foundation Cultivation Project(22NSFCP45)China Postdoctoral Science Foundation Project(General Program No.2022M720929).
文摘Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.
基金supported by the Doctoral Foundation of HuBei University of Science and Technology(Grant Numbers BK202007 and BK202028 to L.W.and Z.Z.)Special Research Fund Project of School of Stomatology and Optometry,Xianning Medical College,Hubei University of Science and Technology(Grant Number 2020XZ37 to L.W.)+3 种基金Hubei Provincial Department of Education“Hundred Schools and Hundred Counties”(Grant Number BXLBX0806 to Z.Z.)the Foundation of Hubei University of Science and Technology“Double Hundred Project”(Grant Number 2022HKSB01 to Z.Z.)the Foundation of Innovation Team of Hubei University of Science and Technology(Grant Number 2023T13 to S.Y.)Natural Science Foundation of Hubei Province(Grant Number 2023AFB1027 to Z.Z.).
文摘Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.
基金funded by grants from the Natural Science Foundation of Hubei Province,China(No.2022CFB307)and the Foundation of Tongji Hospital(No.2020JZKT292).
文摘Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.
基金supported by Achievement Transformation Project(No.CGZH21001)1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(No.ZYJC21007)+4 种基金Translational Research Grant of NCRCH(No.2021WWB03)Chengdu Science and Technology Program(No.2022-YF05-01444-SN)Key Research and Development Program of Sichuan Province(No.2023YFS0031)National Key Research and Development Program of China(Nos.2022YFC2502600,2022YFC2502603)National Natural Science Foundation of China(No.82370192).
文摘Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA).However,the pathogenesis is not fully understood.We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors,and to investigate its function in patients’prognosis and immunotherapy.Methods:The differential expression,diagnosis,prognosis,genetic and epigenetic alterations,tumor microenvironment,stemness,immune infiltration cells,function enrichment,single-cell analysis,and drug response across cancers were conducted based on multiple computational tools.Additionally,we validated its carcinogenic effect and possible mechanism in glioma cells.Results:We exhibited that DLAT expression was increased in most tumors,especially in glioma,and affected the survival of tumor patients.DLAT was related to RNA modification genes,DNA methylation,immune infiltration,and immune infiltration cells,including CD4+T cells,CD8+T cells,Tregs,and cancer-associatedfibroblasts.Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis,inflammation,and stemness.Enrichment analysis revealed that DLAT might take part in the cell cycle pathway.Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds,including PI3Kβinhibitors,PKC inhibitors,HSP90 inhibitors,and MEK inhibitors.In addition,glioma cells with DLAT silence inhibited proliferation,migration,and invasion ability,and promoted cell apoptosis.Conclusion:We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors,and its possible functions and mechanisms.DLAT is a potential diagnostic,prognostic,and immunotherapeutic biomarker for cancer patients.
基金supported by grants from the National Natural Science Foundation of China(No.82260554)Natural Science Foundation of Guangxi Province(No.2023GXNSFBA026092 and No.2024GXNSFAA010100)Key Research and development Program of Guangxi Province(No.2023AB22116).
文摘Objective Glioma is a central nervous system tumor arising from glial cells.Despite significant advances in diagnosis and treatment,most patients with high-grade gliomas have a poor prognosis.Many studies have shown that long noncoding RNAs(lncRNAs)may play important roles in the development,progression and treatment of many tumors,including gliomas.Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma.Therefore,we hope that by studying differentially expressed lncRNAs(DElncRNAs)in glioma,we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients.Methods First,the expression of lncRNAs in 5 normal brain(NB)tissues and 10 glioma tissues was examined by RNA sequencing(RNA-seq).Next,we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas(TCGA)database to assess the prognostic value of these variables.Finally,functional analysis of the DElncRNAs was performed by means of Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Results RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma(LGG)and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma(GBM).Among them,AL355974.3 was the most upregulated lncRNA.LINC00632 was the most downregulated lncRNA.Second,LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database.Finally,bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways,such as cell metabolic and developmental processes.Conclusion Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.
基金supported by the Hainan Provincial Natural Science Foundation of China(Grant No.821MS137)the Innovative Research Project of Hainan Graduate Students(Grant No.Qhyb2021-58).
文摘Clinical data indicates that glioma patients have poor treatment outcomes and clinical prognosis.The role of olfactory signaling pathway-related genes(OSPRGs)in glioma has not been fully elucidated.In this study,we aimed to investigate the role and relationship between OSPRGs and glioma.Univariate and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts,and the target gene(G Protein Subunit Alpha L,GNAL)was screened.The association of GNAL expression with clinicopathological characteristics,gene mutation landscape,tumor immune microenvironment(TIME),deoxyribonucleic acid(DNA)methylation,and naris-occlusion controlled genes(NOCGs)was performed.Immunohistochemistry was used to evaluate GNAL level in glioma.Further analysis was conducted to evaluate the drug sensitivity,immunotherapy response,and functional enrichment of GNAL.GNAL was an independent prognostic factor,and patients with low GNAL expression have a poor prognosis.Expression of GNAL was closely associated with clinicopathological characteristics,DNA methylation,and several immune-related pathways.Immune infiltration analysis indicated that GNAL levels were negatively correlated with immune scores.GNAL low-expression group showed efficacy with anti-PD-1 therapy.Ten compounds with significantly different half-maximal inhibitory concentration(IC50)values between the GNAL high and low-expression groups were identified.Furthermore,its expression was associated with several immune cells,immune-related genes,and NOCGs.The expression of GNAL is closely associated with clinicopathological characteristics,TIME,and the response to therapeutic interventions,highlighting its potential as a prognostic biomarker for glioma.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.
文摘BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.
文摘BACKGROUND Gliomas are the most common primary central nervous system neoplasm.Despite recent advances in the diagnosis and treatment of gliomas,patient prognosis remains dismal.Therefore,it is imperative to identify novel diagnostic biomarkers and therapeutic targets of glioma to effectively improve treatment outcomes.AIM To investigate the association between oligodendrocyte transcription factor 2(Olig2)expression and the outcomes of glioma patients.METHODS The PubMed,Embase,Cochrane Library,and China National Knowledge Infrastructure databases were searched for studies(published up to October 2023)that investigated the relationship between Olig2 expression and prognosis of glioma patients.The quality of the studies was assessed using the Newcastle Ottawa Scale.Data analyses were performed using Stata Version 12.0 software.RESULTS A total of 1205 glioma patients from six studies were included in the metaanalysis.High Olig2 expression was associated with better outcomes in glioma patients[hazard ratio(HR):0.81;95%(confidence interval)CI:0.51-1.27;P=0.000].Furthermore,the results of subgroup meta-analysis showed that high expression of Olig2 was associated with poor overall survival in European patients(HR:1.34;95%CI:0.79-2.27)and better prognosis in Asian patients(HR:0.43;95%CI:0.22-0.84).The sensitivity analysis showed that no single study had a significant effect on pooled HR,and there was also no indication of publication bias according to the Egger’s and Begger’s P value test or funnel plot test.CONCLUSION High Olig2 expression may have a positive impact on the prognosis of glioma patients,and should be investigated further as a prognostic biomarker and therapeutic target for glioma.
基金supported by the Fund for Distinguished Young Scientists of the Department of Science and Technology of Shaanxi Province(No.2023-JC-JQ-68).
文摘Objective To determine the factors that contribute to the survival of elderly individuals diagnosed with brain glioma and develop a prognostic nomogram.Methods Data from elderly individuals(age≥65 years)histologically diagnosed with brain glioma were sourced from the Surveillance,Epidemiology,and End Results(SEER)database.The dataset was randomly divided into a training cohort and an internal validation cohort at a 6:4 ratio.Additionally,data obtained from Tangdu Hospital constituted an external validation cohort for the study.The identification of independent prognostic factors was achieved through the least absolute shrinkage and selection operator(LASSO)and multivariate Cox regression analysis,enabling the construction of a nomogram.Model performance was evaluated using C-index,ROC curves,calibration plot and decision curve analysis(DCA).Results A cohort of 20483 elderly glioma patients was selected from the SEER database.Five prognostic factors(age,marital status,histological type,stage,and treatment)were found to significantly impact overall survival(OS)and cancer-specific survival(CSS),with tumor location emerging as a sixth variable independently linked to CSS.Subsequently,nomogram models were developed to predict the probabilities of survival at 6,12,and 24 months.The assessment findings from the validation queue indicate a that the model exhibited strong performance.Conclusion Our nomograms serve as valuable prognostic tools for assessing the survival probability of elderly glioma patients.They can potentially assist in risk stratification and clinical decision-making.
文摘This comprehensive review delves into the current updates and challenges associated with the management of low-grade gliomas(LGG),the predominant primary tumors in the central nervous system.With a general incidence rate of 5.81 per 100000,gliomas pose a significant global concern,necessitating advancements in treatment techniques to reduce mortality and morbidity.This review places a particular focus on immunotherapies,discussing promising agents such as Zotiraciclib and Lerapolturev.Zotiraciclib,a CDK9 inhibitor,has demonstrated efficacy in glioblastoma treatment in preclinical and clinical studies,showing its potential as a therapeutic breakthrough.Lerapolturev,a viral immunotherapy,induces inflammation in glioblastoma and displays positive outcomes in both adult and pediatric patients.Exploration of immunotherapy extends to Pembrolizumab,Nivolumab,and Entrectinib,revealing the challenges and variabilities in patient responses.Despite promising preclinical data,the monoclonal antibody Depatuxizumab has proven ineffective in glioblastoma treatment,emphasizing the critical need to understand resistance mechanisms.The review also covers the success of radiation therapy in pediatric LGG,with evolving techniques,such as proton therapy,showing potential improvements in patient quality of life.Surgical treatment is discussed in the context of achieving a balance between preserving the patient’s quality of life and attaining gross total resection,with the extent of surgical resection significantly influencing the survival outcomes.In addition to advancements in cancer vaccine development,this review highlights the evolving landscape of LGG treatment,emphasizing a shift toward personalized and targeted therapies.Ongoing research is essential for refining strategies and enhancing outcomes in the management of LGG.
文摘Glioma is one of the most common primary intracranial tumors,characterized by invasive growth and poor prognosis.Actin cytoskeletal rearrangement is an essential event in tumor cell migration.Scinderin(SCIN),an actin severing and capping protein that regulates the actin cytoskeleton,is involved in the prolif-eration and migration of certain cancer cells.However,its biological role and molecular mechanism in glioma remain unclear.Lin et al explored the role and mechanism of SCIN in gliomas.The results showed that SCIN mechanically affected cytoskeleton remodeling and inhibited the formation of lamellipodia via RhoA/FAK signaling pathway.This study identifies the cancer-promoting role of SCIN and provides a potential therapeutic target for SCIN in glioma treatment.
文摘Brainstem gliomas comprise both slow-growing and highly aggressive tumors,the latter carrying a dismal prognosis of approximately 10 months in children.Given their common locations along the brainstem,they are often not amenable to surgical resection.There are currently a host of exploratory therapies under investigation ranging from immunotherapy,small molecular inhibitors,epigenetic-modifying agents,and radiation protocols to combat these difficult-to-treat tumors.Recent discoveries highlighting the role of H3 histone mutations in diffuse midline glioma oncogenesis have yielded a variety of new targetable antigens and aberrant signaling pathways.Although many of these studies have shown promise in terms of inhibiting tumor growth and disease progression,results to date have been modest in their ability to translate into meaningful clinical benefit.This review will serve as an updated report on the current state of literature concerning pre-clinical and clinical therapies being investigated for brainstem glioma.In addition,this review will serve as a guide for clinicians as we review the evolving nomenclature of brainstem gliomas,commonly presenting symptoms,diagnostic tools,and standard therapies.
