Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,techno...Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM.Immunotherapies like immune checkpoint inhibitors,CAR-T targeting,oncolytic virus-based therapy,bispecific antibody treatment,and vaccination approaches,etc.,are emerging as promising avenues offering new hope in refining patient’s survival benefits.However,selective trafficking across the blood-brain barrier(BBB),immunosuppressive tumor microenvironment(TME),metabolic alteration,and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM.Furthermore,to address this concern,the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years.With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes,erythrocytes,platelets,glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition.These biomimetic nanotherapy offers advantages over conventional nanoparticles,focusing on greater target specificity,increased circulation stability,higher active loading capacity,BBB permeability(inherent inflammatory chemotaxis of neutrophils),decreased immunogenicity,efficient metabolism-based combinatorial effects,and prevention of tumor recurrence by induction of immunological memory,etc.provide new age of improved immunotherapies outcomes against HGGs and BM.In this review,we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat andmost lethal HGGs and BM.Moreover,the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.展开更多
Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cell...Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.展开更多
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
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
BACKGROUND Despite the increasing number of publications on glioma radiomics,challenges persist in clinical translation.AIM To assess the development and reporting quality of radiomics in brain gliomas since 2019.METH...BACKGROUND Despite the increasing number of publications on glioma radiomics,challenges persist in clinical translation.AIM To assess the development and reporting quality of radiomics in brain gliomas since 2019.METHODS A bibliometric analysis was conducted to reveal trends in brain glioma radiomics research.The Radiomics Quality Score(RQS),a metric for evaluating the quality of radiomics studies,was applied to assess the quality of adult-type diffuse glioma studies published since 2019.The total RQS score and the basic adherence rate for each item were calculated.Subgroup analysis by journal type and research objective was performed,correlating the total RQS score with journal impact factors.RESULTS The radiomics research in glioma was initiated in 2011 and has witnessed a surge since 2019.Among the 260 original studies,the median RQS score was 11,correlating with a basic compliance rate of 46.8%.Subgroup analysis revealed significant differences in domain 1 and its subitems(multiple segmentations)across journal types(P=0.039 and P=0.03,respectively).The Spearman correlation coefficients indicated that the total RQS score had a negative correlation with the Journal Citation Report category(-0.69)and a positive correlation with the five-year impact factors(0.318)of journals.CONCLUSION Glioma radiomics research quality has improved since 2019 but necessitates further advancement with higher publication standards.展开更多
Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have ...Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have lately been described as having roles in a variety of biological functions, such as cell homeostasis and the cellular processes involved in the oncogenesis of many types of tumors. Carrying several key molecules that contribute to tumor development and progression, similar to mRNAs, microRNAs and other non-coding RNAs, DNA and even small proteins, MVs can be considered as a ubiquitous form of novel cell communication that is present in most somatic cells. Although tumor-derived MVs have been demonstrated in different types of cancers, the literature data on MVs in primary central nervous system (CNS) tumors are relatively scarce. In this review, we address the involvement of MVs in diffuse astrocytomas, particularly glioblastomas, as well as oligodendrogliomas and medulloblastomas. We placed particular focus on the cellular crosstalk between tumor and “normal” cells, the putative mechanisms how the tumor microenvironment is modulated and the spread of aggressive phenotypes. Additionally, a better understanding of the participation of tumor-derived MVs in the regulation of key cancer pathways will offer new insights into tumor pathogenesis and the mechanisms of multidrug resistance, and may help to develop new strategies for novel therapies against these infiltrative CNS tumors.展开更多
Objective: To explore the expression of Th1/Th2 cytokines gene in human gliomas and its role in the genesis and development of human gliomas.Methods: Using IL-2 and IFNγ as Th1 type cytokines, IL-4, IL-6 and IL-10 as...Objective: To explore the expression of Th1/Th2 cytokines gene in human gliomas and its role in the genesis and development of human gliomas.Methods: Using IL-2 and IFNγ as Th1 type cytokines, IL-4, IL-6 and IL-10 as Th2 type cytokines, the biological activity of cytokines in the supernatant of glioma cell lines was assayed by ELISA method, and the gene expression of Th1/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes and glioma cell lines were detected by RT-PCR.Results: There was predominant expression of Th2 type cytokines in human glioma cells, glioma infiltrating lymphocytes and glioma cell lines, but there was no such expression in normal brain tissues.Conclusion: It suggested that there is a relationship between the Th2 type cytokines expression in human gliomas and the immunosupressive status of human glioma patients. The predominant expression of Th2 type cytokines may play an important role in the genesis and development of human gliomas. Key words glioma - Th1/Th2 - gene expression - RT-PCR This project was supported by a grant from National Natural Sciences foundation of China (No. 30271335).展开更多
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
Objective： To evaluate correlation between chemosensitivity of tumor cells in vitro and their clinical responsiveness in vivo by comparing the difference of curative effect between chemotherapy of cerebral gliomas di...Objective： To evaluate correlation between chemosensitivity of tumor cells in vitro and their clinical responsiveness in vivo by comparing the difference of curative effect between chemotherapy of cerebral gliomas directed by chemosensitivity test in vitro and its routine chemotherapy. Methods： Sixty-two patients with cerebral gliomas were recruited as the experiment group, who had received total resection or subtotal resection of the tumor. The resected tumor cells were cultured in vitro, followed by chemosensitivity test using colorimetric MTT assay. Finally, chemotherapeutic protocol was made based on the results of the chemosensitivity test. Fifty patients with cerebral gliomas subjected to the routine chemotherapeutic protocol were simultaneously recruited as the control group, whose age, gender, survival functional status and operational fashion were matched with the experiment group. The two groups were equally followed up for the survival functional status, recurrence and death. All data were analyzed using SPSS 10.0 software. Results： At the time of evaluation, KPS values of 64.52 ± 35.84 were seen in the experiment group, and 33.60 ± 36.24 in the control group, showing statistical difference between the two groups （t = 4.5163, P = 0.000）. During 2-4 years of follow up, a recurrence rate of 32.26% was seen in the experimental group, and 60.00% in the control group, showing a statistical difference between the two groups （X^2 = 8.620, P = 0.003）. The fatality was 22.58% in the experiment group, and 48.00% in the control group, showing a statistical difference between the two groups （X^2 = 7.978, P = 0.005）. The survival rate of the experimental group was higher than that of the control group, showing a statistical differences between the two groups （X^2= 7.29, P = 0.0069）. Conclusion： Chemotherapy of glio- mas under the guidance of chemosensitivity test in vitro contributes to obvious improvement on the current survival functional status, a clear decline of the recurrence rates and fatality rate, and raised survival rates of the patients. A close correlation between the chemosensitivity in vitro and clinical responsiveness in vivo is observed.展开更多
Multicentric gliomas are considered to be well recognized but uncommon; often scatter widely in different lobes or hemispheres; and cannot be attributed to a definite pathwayEll. A patient diagnosed as multicentric gl...Multicentric gliomas are considered to be well recognized but uncommon; often scatter widely in different lobes or hemispheres; and cannot be attributed to a definite pathwayEll. A patient diagnosed as multicentric gliomas is presented in this paper. He was firstly misdiagnosed as cerebral metastatic tumors, but later the histopathological examination revealed them to be glioblastoma （WHO grade IV）. Additionally, the aim of the paper was to describe the case history of the patient and the problems encountered in the pathogenesis, pathophysiology, diagnosis and treatment.展开更多
BACKGROUND Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria.The risk assessment of tumor transmission via organ transplant in primary brain tumors is primarily...BACKGROUND Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria.The risk assessment of tumor transmission via organ transplant in primary brain tumors is primarily based on the assessment of tumor histotype and grade.Previous surgeries,chemo-/radiotherapy,and ventriculoperitoneal shunt placement can lead to a disruption of the blood-brain barrier,concurring to an increase in the transmission risk.AIM To investigate the role of tumor transmission risk factors in donors with oligodendrogliomas and astrocytomas.METHODS We searched PubMed and EMBASE databases for studies reporting extraneural spreading of oligoden-drogliomas and astrocytomas and extracted clinical-pathological data on the primary tumor histotype and grade,the elapsed time from the diagnosis to the onset of metastases,sites and number of metastases,prior surgeries,prior radiotherapy and/or chemotherapy,ventriculoatrial or ventriculo-peritoneal shunt placement,and the presence of isocitrate dehydrogenase 1/2 mutation and 1p/19q codeletion.Statistical analysis was performed using R software.Statistical correlation between chemotherapy or radiotherapy and the presence of multiple extra-central nervous system metastases was analyzed usingχ2 and Fischer exact test.The Kaplan-Meier method was used to evaluate the presence of a correlation between the metastasis-free time and:(1)Localization of metastases;(2)The occurrence of intracranial recurrences;and(3)The occurrence of multiple metastases.RESULTS Data on a total of 157 patients were retrieved.The time from the initial diagnosis to metastatic spread ranged from 0 to 325 mo in patients with oligodendrogliomas and 0 to 267 mo in those with astrocytomas.Respectively,19%and 39%of patients with oligodendroglioma and astrocytoma did not receive any adjuvant therapy.The most frequent metastatic sites were bone,bone marrow,and lymph nodes.The lungs and the liver were the most commonly involved visceral sites.There was no significant correlation between the occurrence of multiple metastases and the administration of adjuvant chemo-/radiotherapy.Patients who developed intracranial recurrences/metastases had a significantly longer extraneural metastasis-free time compared to those who developed extraneural metastases in the absence of any intra-central nervous system spread.CONCLUSION A long follow-up time does not exclude the presence of extraneural metastases.Therefore,targeted imaging of bones and cervical lymph nodes may improve safety in the management of these donors.展开更多
OBJECTIVE To explore the relation of cystatin C and cathepsin B expression to the pathological grade and invasion of human gliomas. METHODS A immunohistochemical method was used to detect the expression of cystatin C ...OBJECTIVE To explore the relation of cystatin C and cathepsin B expression to the pathological grade and invasion of human gliomas. METHODS A immunohistochemical method was used to detect the expression of cystatin C and cathepsin B in 57 glioma samples. RESULTS The expression of cystatin C in high-grade （Grade Ⅲ-Ⅳ ）gliomas was significantly weaker than that in low-grade（Grade Ⅰ-Ⅱ, P=0.0001）. On the other hand, the expression of cathepsin B in high-grade gliomas was significantly stronger than that in low-grade （P=0.0001）. Cystatin C expression correlated inversely with cathepsin B expression in gliomas （P=0.01）. CONCLUSION Cystatin C and cathepsin B expression is related to the pathological grade and invasion of gliomas. Combining detection of cystatin C and cathepsin B expressions might provide significant information for clinical assessment of maglignant phenotypes and invasion of gliomas.展开更多
OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confi...OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.展开更多
Objective： To study p27/Kipl expression in gliomas and its application value. Methods： Imo munohistochemical technique was used to detect the exprssion of p27/Kipl gene in 48 different malignant grade human brain gl...Objective： To study p27/Kipl expression in gliomas and its application value. Methods： Imo munohistochemical technique was used to detect the exprssion of p27/Kipl gene in 48 different malignant grade human brain glioma tissues categorized according to WHO classification and 12 normal human brain tissues,which were analyzed quantitatively by using the image system and compared retrospectively with the patients＇ clinical characteristics. Results： In this series, the immunohistochemical reaction for p27/Kipl was confined to the nuclei. The abnormal positive expression rate of p27/Kipl in gliomas was found to be higher than that in normal tissues （P〈0.05）. The positive nuclei expression of p27/Kipl decreased in number and staining intensity with the increasing degree of histological malignancy （P〈0.05）. Lower expression of p27/Kipl was associated with poor prognosis （P〈0.05）. P27/Kipl expression could be regarded as an independent prognostic factor. Conclusion： The abnormal expression of p27/Kipl may be closely related to the occurrence and development of gliomas, and also can be used to evaluate the prognosis independently.展开更多
<strong>Introduction:</strong><span style="font-family:""><span style="font-family:Verdana;"> Malignant gliomas refer to grade III or IV brain tumors de</span><...<strong>Introduction:</strong><span style="font-family:""><span style="font-family:Verdana;"> Malignant gliomas refer to grade III or IV brain tumors de</span><span style="font-family:Verdana;">fined according to the World Health Organization (WHO) classification.</span><span style="font-family:Verdana;"> They </span><span style="font-family:Verdana;">are a heterogeneous group of pathologies and represent a serious health</span><span style="font-family:Verdana;"> problem by their frequency, severity and treatment difficulties. The prognosis of malignant gliomas remains poor despite all the medical advances. </span><b><span style="font-family:Verdana;">Materials</span></b> <b><span style="font-family:Verdana;">and</span></b> <b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> It is a retrospective study included 20 cases of malignant glial </span><span style="font-family:Verdana;">tumors treated at the medical oncology department, Fattouma Bourguiba</span><span style="font-family:Verdana;"> hospital in Monastir between 2012 and 2016, according to the STUPP protocol. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> These were 12 men and 8 women with a median age of 43. Clinical signs were not very specific, dominated by intracranial hypertension and </span><span style="font-family:Verdana;">deficit signs. Imagery referred to the diagnosis of malignant gliomas in 1s</span><span style="font-family:Verdana;">t intention. Surgery consisted of a macroscopically complete exeresis in (15%) cases, a partial exeresis in (50%), the rest of the patients had a stereotactic biopsy. Histology found GBM in 16 patients (80%), 2 cases of Grade III anaplastic astrocytoma (10%), 1 case of anaplastic oligodendroglioma (5%), and 1 case of Grade III anaplastic eppendymoma (5%). Most of our patients received concurrent radio-chemotherapy and adjuvant TMZ chemotherapy was administered in 15 patients, 7 of whom received the full 6 scheduled cures. A relapse treatment was decided in only one of the 12 patients who relapsed. 6 patients are still alive. The median survival is 11.27 months. In our series, overall survival was related to histological type (p = 0.006) and neurological status assessed at the end of RT-CT (p = 0.001). While age, general condition score, type of surgery, and post-therapeutic development did not</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">show </span><span style="font-family:Verdana;">a</span><span style="font-family:""> </span><a name="OLE_LINK16"></a><a name="OLE_LINK15"></a><span style="font-family:Verdana;"><span style="font-family:Verdana;">stat</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">istically</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">significant relationship, although survival rates were consistent with</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">the criteria assessed. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Malignant gliomas are rare tumors, bad</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> prognosis, aggravated in Tunisia by a diagnostic delay. The creation of a multidisciplinary neuro-oncology group can help to improve management.</span></span></span>展开更多
Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is know...Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is known about the mechanisms underlying the glioma-induced tropism of stem cells.Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas.Here we review the possible mechanisms of stem cells tropism for malignant gliomas.展开更多
Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the mali...Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.展开更多
Malignant behaviors of brain gliomas include proliferation and infiltration.It remains unclear which behavior influences the status of adjacent corticospinal tracts.Diffusion tensor imaging can show the status of brai...Malignant behaviors of brain gliomas include proliferation and infiltration.It remains unclear which behavior influences the status of adjacent corticospinal tracts.Diffusion tensor imaging can show the status of brain white matter fiber tracts.Ki-67 and CD44/matrix metalloproteinase 9 are sensitive markers for reflecting the proliferation and infiltration of tumor cells.The present study analyzed pre-operative diffusion tensor images of 24 patients with pathologically confirmed World Health Organization glioma（Ⅰ-Ⅳ）.We observed lapse,infiltration and destruction of the peri-tumor corticospinal tract following reconstruction,and simultaneously detected the expression of Ki-67,CD44/matrix metalloproteinase 9 in samples.Expression of CD44 and matrix metalloproteinase 9was not significantly correlated to the status of the peri-tumor corticospinal tract（r = 1.597,4.859;P = 0.450,0.088）,while Ki-67 expression significantly correlated to its status（r= 6.590,P = 0.037）.These findings demonstrate that highly proliferative gliomas result in damage to the peripheral corticospinal tract.展开更多
Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignan...Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;P<0.0001)in patients with IDH-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDHmutant gliomas.展开更多
文摘Although with aggressive standards of care like surgical resection,chemotherapy,and radiation,high-grade gliomas(HGGs)and brain metastases(BM)treatment has remained challenging for more than two decades.However,technological advances in this field and immunotherapeutic strategies have revolutionized the treatment of HGGs and BM.Immunotherapies like immune checkpoint inhibitors,CAR-T targeting,oncolytic virus-based therapy,bispecific antibody treatment,and vaccination approaches,etc.,are emerging as promising avenues offering new hope in refining patient’s survival benefits.However,selective trafficking across the blood-brain barrier(BBB),immunosuppressive tumor microenvironment(TME),metabolic alteration,and tumor heterogeneity limit the therapeutic efficacy of immunotherapy for HGGs and BM.Furthermore,to address this concern,the NanoBioTechnology-based bioinspired delivery system has been gaining tremendous attention in recent years.With technological advances such as Trojan horse targeting and infusing/camouflaging nanoparticles surface with biological molecules/cells like immunocytes,erythrocytes,platelets,glioma cell lysate and/or integrating these strategies to get hybrid membrane for homotypic recognition.These biomimetic nanotherapy offers advantages over conventional nanoparticles,focusing on greater target specificity,increased circulation stability,higher active loading capacity,BBB permeability(inherent inflammatory chemotaxis of neutrophils),decreased immunogenicity,efficient metabolism-based combinatorial effects,and prevention of tumor recurrence by induction of immunological memory,etc.provide new age of improved immunotherapies outcomes against HGGs and BM.In this review,we emphasize on neuro-immunotherapy and the versatility of these biomimetic nano-delivery strategies for precise targeting of hard-to-treat andmost lethal HGGs and BM.Moreover,the challenges impeding the clinical translatability of these approaches were addressed to unmet medical needs of brain cancers.
基金supported by grants from the Natural Science Foundation of Guangxi Province(Grant No:2022GXNSFAA035639 and 2023GXNSFBA026092)the National Natural Science Foundation of China(Grant No:81860445 and 82260554)the Innovation Project of Guangxi Graduate Education(Grant No:YCBZ2024118)。
文摘Objective Glioma is a highly heterogeneous and malignant intracranial tumor that presents challenges for clinical treatment.ELMO domain containing 2(ELMOD2)is a GTPase-activating protein that regulates a range of cellular biological processes.However,its specific role and prognostic value in tumorigenesis are still unknown.This study aimed to assess the prognostic relevance and signaling function of ELMOD2 in gliomas.Methods The Chinese Glioma Genome Atlas(CGGA)and The Cancer Genome Atlas(TCGA)databases were utilized to conduct a comprehensive analysis of the expression profile of ELMOD2 in gliomas,elucidating its associations with clinicopathological parameters and patient prognosis.Single-cell analysis was performed to characterize ELMOD2 expression across distinct glioma cell subpopulations.Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,and Gene Set Variation Analysis(GSVA)were employed to evaluate the potential biological functions of ELMOD2 in gliomagenesis.Specific small interfering RNAs(siRNAs)were used to knock down ELMOD2 in the glioma cell lines U251 and A172 to assess their cellular behaviors and examine the levels of multiple key signaling molecules associated with the occurrence of gliomas.Results ELMOD2 was overexpressed in gliomas,and this upregulation was correlated with tumor grade,isocitrate dehydrogenase mutation,and 1p/19q codeletion status.Notably,ELMOD2 expression was elevated in classical and mesenchymal subtypes,and single-cell resolution analysis revealed predominant enrichment within malignant cells.Functionally,ELMOD2 regulated cell cycle progression,and its overexpression was related to independent adverse outcomes.In vitro experiments revealed that ELMOD2 was located in the cytoplasm and nucleoplasm.Furthermore,ELMOD2 knockdown reduced proliferation,migration,and invasion and increased apoptosis in U251 and A172 cell lines.Finally,ELMOD2 knockdown significantly decreased p-Erk1/2.Conclusions ELMOD2 expression in glioma is positively correlated with tumorigenesis and is a crucial independent prognostic marker.Thus,ELMOD2 is a promising biomarker and therapeutic target for glioma treatment.
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.
基金Supported by Sichuan Science and Technology Program,No.2023YFQ0002Deyang Science and Technology Program,No.2023SZZ093.
文摘BACKGROUND Despite the increasing number of publications on glioma radiomics,challenges persist in clinical translation.AIM To assess the development and reporting quality of radiomics in brain gliomas since 2019.METHODS A bibliometric analysis was conducted to reveal trends in brain glioma radiomics research.The Radiomics Quality Score(RQS),a metric for evaluating the quality of radiomics studies,was applied to assess the quality of adult-type diffuse glioma studies published since 2019.The total RQS score and the basic adherence rate for each item were calculated.Subgroup analysis by journal type and research objective was performed,correlating the total RQS score with journal impact factors.RESULTS The radiomics research in glioma was initiated in 2011 and has witnessed a surge since 2019.Among the 260 original studies,the median RQS score was 11,correlating with a basic compliance rate of 46.8%.Subgroup analysis revealed significant differences in domain 1 and its subitems(multiple segmentations)across journal types(P=0.039 and P=0.03,respectively).The Spearman correlation coefficients indicated that the total RQS score had a negative correlation with the Journal Citation Report category(-0.69)and a positive correlation with the five-year impact factors(0.318)of journals.CONCLUSION Glioma radiomics research quality has improved since 2019 but necessitates further advancement with higher publication standards.
文摘Microvesicles (MVs) or shedding membrane vesicles have recently been described as a novel model of intercellular communication. Previously, MVs were considered as unnecessary or secreted cellular debris, but MVs have lately been described as having roles in a variety of biological functions, such as cell homeostasis and the cellular processes involved in the oncogenesis of many types of tumors. Carrying several key molecules that contribute to tumor development and progression, similar to mRNAs, microRNAs and other non-coding RNAs, DNA and even small proteins, MVs can be considered as a ubiquitous form of novel cell communication that is present in most somatic cells. Although tumor-derived MVs have been demonstrated in different types of cancers, the literature data on MVs in primary central nervous system (CNS) tumors are relatively scarce. In this review, we address the involvement of MVs in diffuse astrocytomas, particularly glioblastomas, as well as oligodendrogliomas and medulloblastomas. We placed particular focus on the cellular crosstalk between tumor and “normal” cells, the putative mechanisms how the tumor microenvironment is modulated and the spread of aggressive phenotypes. Additionally, a better understanding of the participation of tumor-derived MVs in the regulation of key cancer pathways will offer new insights into tumor pathogenesis and the mechanisms of multidrug resistance, and may help to develop new strategies for novel therapies against these infiltrative CNS tumors.
基金This project was supported by a grant from National Natural Sciences foundation of China(No.30271335).
文摘Objective: To explore the expression of Th1/Th2 cytokines gene in human gliomas and its role in the genesis and development of human gliomas.Methods: Using IL-2 and IFNγ as Th1 type cytokines, IL-4, IL-6 and IL-10 as Th2 type cytokines, the biological activity of cytokines in the supernatant of glioma cell lines was assayed by ELISA method, and the gene expression of Th1/Th2 cytokines in human glioma cells, glioma infiltrating lymphocytes and glioma cell lines were detected by RT-PCR.Results: There was predominant expression of Th2 type cytokines in human glioma cells, glioma infiltrating lymphocytes and glioma cell lines, but there was no such expression in normal brain tissues.Conclusion: It suggested that there is a relationship between the Th2 type cytokines expression in human gliomas and the immunosupressive status of human glioma patients. The predominant expression of Th2 type cytokines may play an important role in the genesis and development of human gliomas. Key words glioma - Th1/Th2 - gene expression - RT-PCR This project was supported by a grant from National Natural Sciences foundation of China (No. 30271335).
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Objective： To evaluate correlation between chemosensitivity of tumor cells in vitro and their clinical responsiveness in vivo by comparing the difference of curative effect between chemotherapy of cerebral gliomas directed by chemosensitivity test in vitro and its routine chemotherapy. Methods： Sixty-two patients with cerebral gliomas were recruited as the experiment group, who had received total resection or subtotal resection of the tumor. The resected tumor cells were cultured in vitro, followed by chemosensitivity test using colorimetric MTT assay. Finally, chemotherapeutic protocol was made based on the results of the chemosensitivity test. Fifty patients with cerebral gliomas subjected to the routine chemotherapeutic protocol were simultaneously recruited as the control group, whose age, gender, survival functional status and operational fashion were matched with the experiment group. The two groups were equally followed up for the survival functional status, recurrence and death. All data were analyzed using SPSS 10.0 software. Results： At the time of evaluation, KPS values of 64.52 ± 35.84 were seen in the experiment group, and 33.60 ± 36.24 in the control group, showing statistical difference between the two groups （t = 4.5163, P = 0.000）. During 2-4 years of follow up, a recurrence rate of 32.26% was seen in the experimental group, and 60.00% in the control group, showing a statistical difference between the two groups （X^2 = 8.620, P = 0.003）. The fatality was 22.58% in the experiment group, and 48.00% in the control group, showing a statistical difference between the two groups （X^2 = 7.978, P = 0.005）. The survival rate of the experimental group was higher than that of the control group, showing a statistical differences between the two groups （X^2= 7.29, P = 0.0069）. Conclusion： Chemotherapy of glio- mas under the guidance of chemosensitivity test in vitro contributes to obvious improvement on the current survival functional status, a clear decline of the recurrence rates and fatality rate, and raised survival rates of the patients. A close correlation between the chemosensitivity in vitro and clinical responsiveness in vivo is observed.
文摘Multicentric gliomas are considered to be well recognized but uncommon; often scatter widely in different lobes or hemispheres; and cannot be attributed to a definite pathwayEll. A patient diagnosed as multicentric gliomas is presented in this paper. He was firstly misdiagnosed as cerebral metastatic tumors, but later the histopathological examination revealed them to be glioblastoma （WHO grade IV）. Additionally, the aim of the paper was to describe the case history of the patient and the problems encountered in the pathogenesis, pathophysiology, diagnosis and treatment.
文摘BACKGROUND Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria.The risk assessment of tumor transmission via organ transplant in primary brain tumors is primarily based on the assessment of tumor histotype and grade.Previous surgeries,chemo-/radiotherapy,and ventriculoperitoneal shunt placement can lead to a disruption of the blood-brain barrier,concurring to an increase in the transmission risk.AIM To investigate the role of tumor transmission risk factors in donors with oligodendrogliomas and astrocytomas.METHODS We searched PubMed and EMBASE databases for studies reporting extraneural spreading of oligoden-drogliomas and astrocytomas and extracted clinical-pathological data on the primary tumor histotype and grade,the elapsed time from the diagnosis to the onset of metastases,sites and number of metastases,prior surgeries,prior radiotherapy and/or chemotherapy,ventriculoatrial or ventriculo-peritoneal shunt placement,and the presence of isocitrate dehydrogenase 1/2 mutation and 1p/19q codeletion.Statistical analysis was performed using R software.Statistical correlation between chemotherapy or radiotherapy and the presence of multiple extra-central nervous system metastases was analyzed usingχ2 and Fischer exact test.The Kaplan-Meier method was used to evaluate the presence of a correlation between the metastasis-free time and:(1)Localization of metastases;(2)The occurrence of intracranial recurrences;and(3)The occurrence of multiple metastases.RESULTS Data on a total of 157 patients were retrieved.The time from the initial diagnosis to metastatic spread ranged from 0 to 325 mo in patients with oligodendrogliomas and 0 to 267 mo in those with astrocytomas.Respectively,19%and 39%of patients with oligodendroglioma and astrocytoma did not receive any adjuvant therapy.The most frequent metastatic sites were bone,bone marrow,and lymph nodes.The lungs and the liver were the most commonly involved visceral sites.There was no significant correlation between the occurrence of multiple metastases and the administration of adjuvant chemo-/radiotherapy.Patients who developed intracranial recurrences/metastases had a significantly longer extraneural metastasis-free time compared to those who developed extraneural metastases in the absence of any intra-central nervous system spread.CONCLUSION A long follow-up time does not exclude the presence of extraneural metastases.Therefore,targeted imaging of bones and cervical lymph nodes may improve safety in the management of these donors.
基金a grant from Lia-oning Science and Technology Fund of China (No.20051071).
文摘OBJECTIVE To explore the relation of cystatin C and cathepsin B expression to the pathological grade and invasion of human gliomas. METHODS A immunohistochemical method was used to detect the expression of cystatin C and cathepsin B in 57 glioma samples. RESULTS The expression of cystatin C in high-grade （Grade Ⅲ-Ⅳ ）gliomas was significantly weaker than that in low-grade（Grade Ⅰ-Ⅱ, P=0.0001）. On the other hand, the expression of cathepsin B in high-grade gliomas was significantly stronger than that in low-grade （P=0.0001）. Cystatin C expression correlated inversely with cathepsin B expression in gliomas （P=0.01）. CONCLUSION Cystatin C and cathepsin B expression is related to the pathological grade and invasion of gliomas. Combining detection of cystatin C and cathepsin B expressions might provide significant information for clinical assessment of maglignant phenotypes and invasion of gliomas.
文摘OBJECT:Progression of infiltrative low-grade gliomas(LGGs)has been reported previously.The limitations ofsuch studies include diverse histological grading systems,intervening therapy,and the lack of histological confir-mation of malignant tumor progression.The aim of this study was to determine tumor progression in adult patientswith an initial diagnosis of infiltrative LGG who subsequently underwent a repeated operation,but no other inter-vening therapy.The authors examined factors that may be associated with tumor progression.
文摘Objective： To study p27/Kipl expression in gliomas and its application value. Methods： Imo munohistochemical technique was used to detect the exprssion of p27/Kipl gene in 48 different malignant grade human brain glioma tissues categorized according to WHO classification and 12 normal human brain tissues,which were analyzed quantitatively by using the image system and compared retrospectively with the patients＇ clinical characteristics. Results： In this series, the immunohistochemical reaction for p27/Kipl was confined to the nuclei. The abnormal positive expression rate of p27/Kipl in gliomas was found to be higher than that in normal tissues （P〈0.05）. The positive nuclei expression of p27/Kipl decreased in number and staining intensity with the increasing degree of histological malignancy （P〈0.05）. Lower expression of p27/Kipl was associated with poor prognosis （P〈0.05）. P27/Kipl expression could be regarded as an independent prognostic factor. Conclusion： The abnormal expression of p27/Kipl may be closely related to the occurrence and development of gliomas, and also can be used to evaluate the prognosis independently.
文摘<strong>Introduction:</strong><span style="font-family:""><span style="font-family:Verdana;"> Malignant gliomas refer to grade III or IV brain tumors de</span><span style="font-family:Verdana;">fined according to the World Health Organization (WHO) classification.</span><span style="font-family:Verdana;"> They </span><span style="font-family:Verdana;">are a heterogeneous group of pathologies and represent a serious health</span><span style="font-family:Verdana;"> problem by their frequency, severity and treatment difficulties. The prognosis of malignant gliomas remains poor despite all the medical advances. </span><b><span style="font-family:Verdana;">Materials</span></b> <b><span style="font-family:Verdana;">and</span></b> <b><span style="font-family:Verdana;">Methods:</span></b><span style="font-family:Verdana;"> It is a retrospective study included 20 cases of malignant glial </span><span style="font-family:Verdana;">tumors treated at the medical oncology department, Fattouma Bourguiba</span><span style="font-family:Verdana;"> hospital in Monastir between 2012 and 2016, according to the STUPP protocol. </span><b><span style="font-family:Verdana;">Results:</span></b><span style="font-family:Verdana;"> These were 12 men and 8 women with a median age of 43. Clinical signs were not very specific, dominated by intracranial hypertension and </span><span style="font-family:Verdana;">deficit signs. Imagery referred to the diagnosis of malignant gliomas in 1s</span><span style="font-family:Verdana;">t intention. Surgery consisted of a macroscopically complete exeresis in (15%) cases, a partial exeresis in (50%), the rest of the patients had a stereotactic biopsy. Histology found GBM in 16 patients (80%), 2 cases of Grade III anaplastic astrocytoma (10%), 1 case of anaplastic oligodendroglioma (5%), and 1 case of Grade III anaplastic eppendymoma (5%). Most of our patients received concurrent radio-chemotherapy and adjuvant TMZ chemotherapy was administered in 15 patients, 7 of whom received the full 6 scheduled cures. A relapse treatment was decided in only one of the 12 patients who relapsed. 6 patients are still alive. The median survival is 11.27 months. In our series, overall survival was related to histological type (p = 0.006) and neurological status assessed at the end of RT-CT (p = 0.001). While age, general condition score, type of surgery, and post-therapeutic development did not</span></span><span style="font-family:""> </span><span style="font-family:Verdana;">show </span><span style="font-family:Verdana;">a</span><span style="font-family:""> </span><a name="OLE_LINK16"></a><a name="OLE_LINK15"></a><span style="font-family:Verdana;"><span style="font-family:Verdana;">stat</span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">istically</span></span></span><span><span><span style="font-family:""> </span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;">significant relationship, although survival rates were consistent with</span></span></span><span><span><span style="font-family:""> </span></span></span><span><span><span style="font-family:""><span style="font-family:Verdana;">the criteria assessed. </span><b><span style="font-family:Verdana;">Conclusion:</span></b><span style="font-family:Verdana;"> Malignant gliomas are rare tumors, bad</span></span></span></span><span style="font-family:Verdana;"><span style="font-family:Verdana;"><span style="font-family:Verdana;"> prognosis, aggravated in Tunisia by a diagnostic delay. The creation of a multidisciplinary neuro-oncology group can help to improve management.</span></span></span>
文摘Various studies have demonstrated the tremendous tropism of stem cells for malignant gliomas,making these cells a potential vehicle for delivery of therapeutic genes to disseminated glioma cells.However,little is known about the mechanisms underlying the glioma-induced tropism of stem cells.Soluble factors including chemokines or growth factors released and expressed by glioma cells at least mediate the tropism of stem cells for gliomas.Here we review the possible mechanisms of stem cells tropism for malignant gliomas.
基金supported by grants from High-level students returning to China (team) project in Hangzhou (2017)Zhejiang Provincial Natural Science Foundation of China (LY19C090002, LQ18C090005)Hangzhou Agriculture and Social Development Project (20191203B20)。
文摘Glioma is the most common type of tumor in the central nervous system, accounting for around 80% of all malignant brain tumors. Previous studies showed a significant association between nuclear morphology and the malignant progress of gliomas. By virtue of integrated proteomics and genomics analyses as well as experimental validations, we identify three nuclear lamin genes(LMNA, LMNB1, and LMNB2) that are significantly upregulated in glioma tissues compared with normal brain tissues. We show that elevated expressions of LMNB1, LMNB2, and LMNA in glioma cells are highly associated with the rapid progression of the disease and the knockdown of LMNB1, LMNB2, and LMNA dramatically suppresses glioma progression in both in vitro and in vivo mouse models. Moreover, the repression of glioma cell growth by lamin knockdown is mediated by the p Rb-mediated G1-S inhibition. On the contrary, overexpression of lamins in normal human astrocytes dramatically induced nuclear morphological aberrations and accelerated cell growth. Together, our multi-omics-based analysis has revealed a previously unrecognized role of lamin genes in gliomagenesis, providing a strong support for the key link between aberrant tumor nuclear shape and the survival of glioma patients. Based on these findings, lamins are proposed to be potential oncogene targets for therapeutic treatments of brain tumors.
基金Anhui Prov-ince Grant of Tackle Key Problems in Science and Technology, No. 07010302202
文摘Malignant behaviors of brain gliomas include proliferation and infiltration.It remains unclear which behavior influences the status of adjacent corticospinal tracts.Diffusion tensor imaging can show the status of brain white matter fiber tracts.Ki-67 and CD44/matrix metalloproteinase 9 are sensitive markers for reflecting the proliferation and infiltration of tumor cells.The present study analyzed pre-operative diffusion tensor images of 24 patients with pathologically confirmed World Health Organization glioma（Ⅰ-Ⅳ）.We observed lapse,infiltration and destruction of the peri-tumor corticospinal tract following reconstruction,and simultaneously detected the expression of Ki-67,CD44/matrix metalloproteinase 9 in samples.Expression of CD44 and matrix metalloproteinase 9was not significantly correlated to the status of the peri-tumor corticospinal tract（r = 1.597,4.859;P = 0.450,0.088）,while Ki-67 expression significantly correlated to its status（r= 6.590,P = 0.037）.These findings demonstrate that highly proliferative gliomas result in damage to the peripheral corticospinal tract.
基金supported bygrants from the Beijing Hospitals Authority Youth Programme(Grant No.QML20190506)the Capital Health Development Research Project(Grant No.2020-2-1072).
文摘Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;P<0.0001)in patients with IDH-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDHmutant gliomas.
