Plasticity of language pathways in patients with low-grade glioma A diffusion tensor imaging study

Knowledge of the plasticity of language pathways neurosurgeons to achieve maximum resection wh n patients with low-grade glioma is important for e preserving neurological function. The current study sought to investigate changes in the ventral language pathways in patients with low-grade glioma located in regions likely to affect the dorsal language pathways. The results revealed no significant difference in fractional anisotropy values in the arcuate fasciculus between groups or between hemispheres. However, fractional anisotropy and lateralization index values in the left inferior longitudinal fasciculus and lateralization index values in the left inferior fronto-occpital fasciculus were higher in patients than in healthy subjects. These results indicate plasticity of language pathways in patients with low-grade glioma. The ventral language pathways may perform more functions in patients than in healthy subjects. As such, it is important to protect the ventral language pathways intraoperatively.

Adaptability of language-related brain network in a low-grade glioma patient

Because functional magnetic resonance imaging can be used for dynamic observation of functional cortical changes after brain injuries, we followed up functional magnetic resonance imaging manifestations of a language-related brain network in a low-grade glioma patient. Disease progression and therapy during a 3-year period were followed up at different time points： before and after reoperation, after radiation therapy, and 1 year after irradiation. During the whole 3-year follow-up period, the patient exhibited no neurological deficits while functional magnetic resonance imaging revealed different topologies of the language-related brain network. During disease progression and after irradiation, the language-related brain network was extended or completely transferred to the nondominant （right） hemisphere. In addition, after reoperation and 1 year after irradiation, language areas were primarily found in the language dominant （left） hemisphere. Our results suggest a high level of adaptability of the language-related cortical network of the bilateral hemispheres in this low-grade glioma patient.

The surgical treatment of low-grade glioma with secondary epilepsy

Objective To explore the methods of surgical treatment of low-grade glioma with secondary epilepsy. Methods Video-EEG, magnetoencephalography (MEG) were performed to localizate the epileptogenic zone and domain in 13 patients,and stereotactic technology ,ultrasoumd,electrocorticogram (EcoG) were combined

MRI investigation for low-grade glioma after gamma knife radiosurgery

Objective： To evaluate the therapeutic efficacy of low-grade glioma （WHO grades Ⅰ-Ⅱ） patients treated with gamma knife radiosurgery and study on the efficacy evaluation method and radiobiological effect. Methods： 140 MRI data of 52 patients after gamma knife radiosurgery were analyzed in tumor size, necrosis or cyst formation, radiation-induced edema and MRI contrast enhancement and circumsciption change for therapeutic efficacy was evaluated. Results： The efficiency rate was 84.3%. The salient efficiency rates were 54.3% for total and 30%, 36.4%, 50%, 68%, 69.2%, and 73.1% for segmenting, respectively. Aggrandizement of tumor related to MRI contrast enhancement and necrosis or cyst formation. Radiation-induced oedema occurred for 32.7%. The MRI contrast enhancement occurred for 57.7% and showed special lace-like ring while some piece-like. Conclusion： Evaluation by MRI has showed gamma knife radiosurgery is efficient for low-grade glioma. The segmenting salient efficiency rate that increase with time is better for evaluation than the efficiency rate especially for long-term MRI follow-up. Radiobiological effect affect the efficacy evaluation. MRI contrast enhancement appears after therapy and shows special as lace-like ring and partly minificates or vanishes subsequently.

Risk factors for early progression of diffuse low-grade glioma in adults

Background:To explore the risk factors for early progression of diffuse low-grade glioma in adults.Methods:A retrospective analysis of pathologic and clinical data of patients diagnosed with diffuse low-grade gliomas at Southwest Hospital between January 2010 and December 2014.The progression-free survival(PFS)less than 60 months was classified as the early progress group,and the PFS greater than 60 months was the control group for comparative analysis.Results:A total of 138 patients were included in this study,including 94 cases of astrocytoma and 44 cases of oligodendroglioma.There were 63 cases with 100%resection,56 cases with 90-100%resection degree,and 19 cases with resection degree<90%.The average follow-up time was 60 months,of which 80 patients progressed and 58 patients did not progress.The average progression-free survival was 61 months.The median progression-free survival was 60 months.There were 68 patients with PFS≤60 months and 70 patients with PFS>60 months.The two groups were compared for statistical analysis.In univariate analysis,there were significant differences in tumor subtype(p=0.005),range(p=0.011),volume(p=0.005),location(p=0.000),and extent of resection(p=0.000).Multifactor analysis shows tumor location(HR=4.549,95%CI:1.324-15.634,p=0.016)and tumor subtype(HR=3.347,95%CI=1.373-8.157,p=0.008),and imcomplete resection is factors influencing early progression of low-grade glioma.Conclusions:Low-grade gliomas involving deep location such as basal ganglia,inner capsule,and corpus callosum are more likely to progress early,while incomplete resection is a risk factor in early progression of astrocytoma.

Asymptomatic low-grade appendiceal mucinous neoplasm:A case report

BACKGROUND Low-grade appendiceal neoplasms(LAMN)are characterized by low incidence and atypical clinical presentations,often leading to misdiagnosis as acute or chronic appendicitis before surgery.The primary diagnostic tool for LAMN is abdominal computed tomography(CT)imaging.Surgical resection remains the cornerstone of LAMN management,necessitating en bloc tumor excision to minimize the risk of iatrogenic rupture.Laparoscopy,known for its minimal invasiveness,reduced postoperative discomfort,and expedited recovery,is a safe and reliable approach for LAMN treatment.Despite the possibility of pseudomyxoma peritonei development,appendectomy and partial appendectomy generally result in negative tumor margins and favorable outcomes,which can be attributed to the disease’s slow growth and lower malignancy.CASE SUMMARY A 71-year-old male patient was admitted to our hospital with a pelvic spaceoccupying lesion detected 1 mo prior.Physical examination showed a soft abdomen without tenderness or rebound and no palpable masses.No shifting dullness was noted,and digital rectal examination revealed no palpable mass.Enteroscopy revealed a raised,smooth-surfaced mass measuring 3.0 cm in the cecum.Abdominal contrast-enhanced CT showed a markedly thickened and dilated appendix with visible cystic shadows.Laparoscopic surgery was performed and revealed a significantly dilated appendix,leading to laparoscopic resection of the appendix and part of the cecum.Post-surgical pathologic analysis confirmed LAMN.The patient received symptomatic and supportive post-operative care and was discharged on postoperative day 4 without complications such as abdominal bleeding,intestinal obstruction,or incision infection.No tumor recurrence was observed during a 7-mo follow-up period.CONCLUSION LAMN is a rare disease that lacks specific clinical manifestations.Abdominal CT plays a crucial role in diagnosing LAMN,and laparoscopic surgery is a safe and effective diagnostic and therapeutic approach.

Low-grade myofibrosarcoma of the maxillary sinus:Two case reports

BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is an extremely rare tumor characterized by the malignant proliferation of myofibroblasts.LGMS most commonly develops in adults,predominantly in males,in the head and neck region,oral cavity,especially on the tongue,mandible,and larynx.This article presents 2 cases of LGMS localized to the maxillary sinus and provides an overview of the available literature.CASE SUMMARY Two patients with LGMS located in the maxillary sinus underwent surgery at the Department of Head and Neck Surgery.Case 1:A 46-year-old patient was admitted to the clinic with suspected LGMS recurrence in the right maxillary sinus(rT4aN0M0),with symptoms of pain in the suborbital area,watering of the right eye,thick discharge from the right nostril,and augmented facial asymmetry.After open biopsy-confirmed LGMS,the patient underwent expanded maxillectomy of the right side with immediate palate reconstruction using a microvascular skin flap harvested surgically from the middle arm.The patient qualified for adjuvant radiotherapy for the postoperative bed,with an additional margin.Currently,the patient is under 1.5 years of observation with no evidence of disease.Case 2:A 45-year-old man was admitted to our clinic with facial asymmetry,strabismus,exophthalmos,and visual impairment in the right eye.Six months earlier,the patient had undergone partial jaw resection at another hospital for fibromatosis.A contrast-enhanced computed tomography scan revealed a tumor mass in the postoperative log after an earlier procedure.An open biopsy confirmed lowgrade fibrosarcoma(rT4aN0M0).The patient qualified for an extended total right maxillectomy with orbital excision and right hemimandibulectomy with immediate microvascular reconstruction using an anterolateral thigh flap.The patient subsequently underwent adjuvant radiotherapy to the postoperative area.After 9 months,recurrence occurred in the right mandibular arch below the irradiated area.The lesion infiltrated the base of the skull,which warranted the withdrawal of radiotherapy and salvage surgery.The patient qualified for palliative chemotherapy with a regimen of doxorubicin+dacarbazine+cyclophosphamide and palliative radiotherapy for bone metastases.The patient died 26 months after surgical treatment.The cases have been assessed and compared with cases in the literature.CONCLUSION No specific diagnostic criteria or treatment strategies have been developed for LGMS.The treatment used for LGMS is the same as that used for sinonasal cancer radical tumor excision;adjuvant radiotherapy or chemoradiotherapy should also be considered.They have low malignant potential but are highly invasive,tend to recur,and metastasize to distant sites.Patients should undergo regular follow-up examinations to detect recurrence or metastasis at an early stage.Patients should be treated and observed at the highest referral centers.

Application of NSR-AISC Method in Reserve Estimation and Technical Economic Evaluation of Low-Grade Polymetallic Deposits: Taking a Low-Grade Copper-Molybdenum Mine in Guangdong Province as an Example

The development and utilization of low-grade polymetallic deposits with strategic mineral resources is one of the important measures to alleviate the current high dependence on strategic mineral resources in China. However, domestic mining enterprises and most mining consulting and design institutes usually use general industrial indicators to carry out reserve estimation and technical and economic feasibility studies on low-grade polymetallic deposits, which cannot truly reflect the economic value of such deposits. The article expounds on the definitions of net return value (NSR) and on-site total maintenance cost (AISC) of common ore smelters in the evaluation of overseas mineral resources. Taking a low-grade polymetallic copper-molybdenum mine in Guangdong Province as an example, comparing the research results showed the NSR-AISC method and the general industrial index method in low-grade polymetallic deposit. There are huge differences in the results of reserve estimation;through the further introduction of Taylor’s formula and the research results on the relationship between investment intensity and production scale, a more reasonable mine life and investment scale are recommended, and a more in-depth comparative study has been carried out in the dimension of technical and economic indicators. Based on the comparative study of the above two methods in reserve estimation and the evaluation results of technical and economic indicators, the author believes that the NSR-AISC method can better reflect the true value of low-grade polymetallic ore projects, and should be popularized and applied in resource evaluation and development practice. This article further describes the application status of the NSR-AISC method for reserve estimation and the evaluation of technical economic indicators, and suggests the main points that should be paid attention to in the use of the NSR-AISC method.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

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.

Focus on current and emerging treatment options for glioma:A comprehensive review

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.

New biomarker:the gene HLA-DRA associated with low-grade glioma prognosis

Background:Low-grade gliomas(LGG)are WHO grade II tumors presenting as the most common primary malignant brain tumors in adults.Currently,LGG treatment involves either or a combination of surgery,radiation therapy,and chemotherapy.Despite the knowledge of constitutive genetic risk factors contributing to gliomas,the role of single genes as diagnostic and prognostic biomarkers is limited.The aim of the current study is to discover the predictive and prognostic genetic markers for LGG.Methods:Transcriptome data and clinical data were obtained from The Cancer Genome Atlas(TCGA)database.We first performed the tumor microenvironment(TME)survival analysis using the Kaplan-Meier method.An analysis was undertaken to screen for differentially expressed genes.The function of these genes was studied by Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Following which a protein-protein interaction network(PPI)was constructed and visualized.Univariate and multivariate COX analyses were performed to obtain the probable prognostic genes.The key genes were selected by an intersection of core and prognostic genes.A clinical correlation analysis of single-gene expression was undertaken.GSEA enrichment analysis was performed to identify the function of key genes.Finally,a single gene-related correlation analysis was performed to identify the core immune cells involved in the development of LGG.Results:A total of 529 transcriptome data and 515 clinical samples were obtained from the TCGA.Immune cells and stromal cells were found to be significantly increased in the LGG microenvironment.The top five core genes intersected with the top 38 prognostically relevant genes and two key genes were identified.Our analysis revealed that a high expression of HLA-DRA was associated with a poor prognosis of LGG.Correlation analysis of immune cells showed that HLA-DRA expression level was related to immune infiltration,positively related to macrophage M1 phenotype,and negatively related to activation of NK cells.Conclusions:HLA-DRA may be an independent prognostic indicator and an important biomarker for diagnosing and predicting survival in LGG patients.It may also be associated with the immune infiltration phenotype in LGG.

Thermally Chargeable Proton Capacitor Based on Redox-Active Effect for Energy Storage and Low-Grade Heat Conversion

Thermal energy is abundantly available in our daily life and industrial production,and especially,low-grade heat is often regarded as a byproduct.Collecting and utilizing this ignored energy by low-cost and simple technologies may become a smart countermeasure to relieve the energy crisis.Here,a unique device has been demonstrated to achieve high value-added conversion of low-grade heat by introducing redox-active organic alizarin(AZ)onto N-doped hollow carbon nanofibers(N–HCNF)surface.As-prepared N–HCNF/AZ can deliver a high specific capacitance of 514.3 F g^(-1)(at 1 A g^(-1))and an outstanding rate capability of 60.3%even at 50 A g^(-1).Meanwhile,the assembled symmetric proton capacitor can deliver a high energy density of 28.0 Wh kg^(-1) at 350.0 W kg^(-1) and a maximum power density of 35.0 kW kg^(-1) at 17.0 Wh kg^(-1).Significantly,the thermally chargeable proton capacitors can attain a surprisingly high Seebeck coefficient of 15.3 mV K^(-1) and a power factor of 6.02µW g^(-1).Taking advantage of such high performance,a satisfying open-circuit voltage of 481.0 mV with a temperature difference of 54 K is achieved.This research provides new insights into construction of high value-added energy systems requiring high electrochemical performances.

Updates on management of gliomas in the molecular age

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.

Anlotinib in combination with pembrolizumab for low-grade myofibroblastic sarcoma of the pancreas: A case report

BACKGROUND Low-grade myofibroblastic sarcoma(LGMS)is a rare spindle cell sarcoma espe-cially in the pancreas,with myofibroblastic differentiation.Hitherto,only a few cases have been reported.CASE SUMMARY Herein,we report a case involving the discovery of a pancreatic mass detected during a routine physical examination.Subsequent imaging and pathological tests of the patient led to the diagnosis of LGMS of the pancreas.Following surgical intervention,the patient experienced recurrence and metastasis.Conventional treatment is not effective for postoperative recurrent pancreatic LGMS with multiple metastases.After communicating with the patients and their families,informed consent was obtained for the treatment of anlotinib combined with pembrolizumab.Evaluation of imaging and clinical symptoms post-treatment revealed a relatively favorable response to the combination of anlotinib and pembrolizumab.CONCLUSION Based on the comprehensive literature review,our report aimed to provide evidence for a better understanding of the disease characteristics,diagnostic criteria,imaging findings,and identification of LGMS.And explore novel treatment strategies for this disease.

Scinderin promotes glioma cell migration and invasion via remodeling actin cytoskeleton

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.

Multimodal cardiac imaging assisted tumor characterization and surgical planning of a patient with rare primary cardiac paraganglioma

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.

Revealing the role of honokiol in human glioma cells by RNA-seq analysis

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.

IQGAP3 promotes the progression of glioma as an immune and prognostic marker

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.

ATM Activation is Key in Vasculogenic Mimicry Formation by Glioma Stem-like Cells

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.

Multi-cohort comprehensive analysis unveiling the clinical value and therapeutic effect of GNAL in glioma

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.