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.

Correlations of MUC15 Overexpression with Clinicopathological Features and Prognosis of Glioma

The abnormal expression of MUC15, a novel cell membrane-associated mucin, has been reported to predict poor survival in several cancers. The aim of the present study was to examine the expression of MUC15 in glioma and its correlation with clinicopathological features, including the sur- vival of patients with glioma. The mRNA expression level of MUC15 was determined by RT-PCR, quantitative RT-PCR （RT-qPCR） and Western blotting in seven normal brain tissues and seven glioma tissues, respectively. The protein expression level of MUC15 was immunohistochemically detected in paraffin-embedded samples of 317 glioma tissues and 115 noncancerous brain tissues. The association of MUC 15 expression levels with the clinicopathologic features and the prognosis was analyzed. The results showed that both mRNA and protein levels of MUC 15 were significantly increased in glioma as com- pared with those in noncancerous brain tissue. Moreover, MUC15 overexpression was positively corre- lated with the advanced clinical stages of glioam patients （P〈0.01）. Furthermore, MUC15 expression levels were significantly correlated with the progression of glioma （P〈0.001）. Survival analysis indicated that glioma patients with higher MUC 15 expression had a significantly shorter overall and 5-year survival time than those with low MUC15 expression. Multivariate analysis suggested that MUC15 overexpres- sion was an independent factor for prognosis （hazard risk： 3.216; P=-0.009）. It was concluded that MUC 15 is overexpressed in glioma tissues. Its overexpression correlates with tumor progression and it is a po- tentially unfavorable prognostic factor for patients with glioma.

Relation of Cystatin C and Cathepsin B Expression to the Pathological Grade and Invasion of Human Gliomas

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.

Clinicopathological features and treatment outcomes of brain stem gliomas in Saudi population

AIM: To analyze experiences to identify treatment outcomes and prognostic factors in a Saudi population.METHODS: Medical records of patients with brainstem gliomas treated from July 2001 to December 2012 were reviewed to identify treatment outcomes of surgery, radiation therapy and chemotherapy and associated prognostic factors in a Saudi population.RESULTS: We analyzed 49 brain stem glioma(BSG) patients from July 2001 to December 2012; 31 of them were males(63.3%) with a median age of 12.6 years(range: 8-64 mo). Twenty-two patients(44.9%) had diffuse intrinsic pontine gliomas(DIPG) and 15(30.6%) presented with focal/tectal BSG. Histopathology was available in 30 patients(61.2%). Median survival time for the whole cohort was 1.5 years. One and two year OS rates were 51.1% and 41.9% respectively. Two year OS rates for focal/tectal, dorsally exophytic, cervicomedullary and DIPG tumors were 60%, 33.3%, 33.3% and 13.6% respectively(P < 0.0001). Significant prognostic factors related to OS were age at diagnosis(worse for > 18 years) P = 0.01, KPS < 70 P = 0.02, duration of symptoms(< 60 d) P = 0.002, histology(better for favorable) P = 0.002, surgery(maximal resection) P = 0.002, and concurrent chemotherapy with radiation therapy in DIPG(better if given) P = 0.01.CONCLUSION: BSG, especially the DIPG subgroup, had a dismal prognosis, needing more aggressive neurosurgical, radiation and chemotherapy techniques, while focal and tectal tumors were found to have a better prognosis.

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.

Clinical and Pathological Studies of Meningioma-Glioma Mixed Tumor

Meningioma-glioma mixed tumor is rare central nervous system tumor. It is necessary to study its clinical and pathological characteristics as well as its possible genesis. This case was a 54-year-old man who was readmitted for recurrent glioma. Magnetic resonance imaging showed a big mass in right temporal lobe which was confirmed as meningioma-glioma by immunohistochemical analysis. Specific immunohistochemical staining is significant in tumor differential diagnosis, and helps to confirm tumor histic origin. By pathological studies, we found that glioma could stimulate adjacent normal meninges into neoplastic proliferation.

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.

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.

Relationship between methylation of promoter region of miR-147 and clinicopathological characteristics of glioman

Objective:To investigate the methylation of the promoter region of microRNA-147 in glioma and its relationship with clinicopathological characteristics.Methods:Totally forty-five patients with glioma underwent surgical resection from November 2016 to September 2018 in the First Hospital of Shanxi Medical University,Affiliated Hospital of Shanxi Medical University.Methylation was detected by methylation-specific PCR(MSP).Results:Methylation was found in the promoter region of microRNA-147 in 30(66.7%)of 45 glioma patients,and methylation was not related to gender and age(P>0.05),but related to WHO classification(P<0.05).As a result,abnormal methylation of the promoter region of microRNA-147 may be one of the factors that affect the occurrence and development of glioma,and the higher the grade of glioma,the more prone the promoter region of microRNA-147 to methylation.

Expression of CyclinD1／Bcl-1 and p27／Kip1 in Gliomas： Their Correlation with Pathological Grade and Prognosis

Objective: To study cyclinD1/bcl-1 and p27/kip1 expression in gliomas and their correlation with pathological grade and prognosis. Methods: Immunohistochemical technique was used to detect the cyclinD1/bcl-1 and p27/kip1 expression in 48 human brain glioma tissues of different malignant grades, and 12 normal non-neoplastic tissues collected from internal decompression. The data were analyzed quantitatively by the image system and also correlated retrospectively with the patients' clinical characteristics. Results: The immunohistochemical reaction for cyclinD1/bcl-1 and p27/kip1 was confined to the nuclei. The abnormal positive expression rates of both cyclinD1/bcl-1 and p27/kip1 in gliomas were found higher than that in non-neoplastic tissues(P<0.05). The number and staining intensity of cyclinD1/bcl-1 positive nuclei increased with malignant grades (P<0.05). On the contrary, the positive nuclei of p27/kip1 expression decreased in number and staining intensity with malignant grades(P<0.05). Higher expression of cyclinD1/bcl-1 or/and lower expression of p27/kip1 were associated with poor prognosis(P<0.05). Conclusion: The abnormal expression of both cyclinD1/bcl-1 and p27/kip1 might be closely related to the occurrence and development of gliomas and they might have synergistic effect. These data suggest that both cyclinD1/bcl-1 expression and p27/kip1 expression can act as an independent prognostic factor.

MEOX2 promotes glioma growth and temozolomide chemoresistance

Glioblastoma(GBM)is a primary and fatal subtype of adult brain tumors.Despite standard treatments,including surgical resection and temozolomide(TMZ)chemotherapy,overall survival is only 16 months[1].Profound genomic heterogeneity and altered transcriptional profiles drive chemoresistance,leading to tumor recurrence and a poor prognosis.Gain of chromosome 7 is a pivotal event in initiation and recurrence[2].

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.

Using multi-omics analysis to explore diagnostic tool and optimize drug therapy selection for patients with glioma based on cross-talk gene signature

Background:The heterogeneity of prognosis and treatment benefits among patients with gliomas is due to tumor microenvironment characteristics.However,biomarkers that reflect microenvironmental characteristics and predict the prognosis of gliomas are limited.Therefore,we aimed to develop a model that can effectively predict prognosis,differentiate microenvironment signatures,and optimize drug selection for patients with glioma.Materials and Methods:The CIBERSORT algorithm,bulk sequencing analysis,and single-cell RNA(scRNA)analysis were employed to identify significant cross-talk genes between M2 macrophages and cancer cells in glioma tissues.A predictive model was constructed based on cross-talk gene expression,and its effect on prognosis,recurrence prediction,and microenvironment characteristics was validated in multiple cohorts.The effect of the predictive model on drug selection was evaluated using the OncoPredict algorithm and relevant cellular biology experiments.Results:A high abundance of M2 macrophages in glioma tissues indicates poor prognosis,and cross-talk between macrophages and cancer cells plays a crucial role in shaping the tumor microenvironment.Eight genes involved in the cross-talk between macrophages and cancer cells were identified.Among them,periostin(POSTN),chitinase 3 like 1(CHI3L1),serum amyloid A1(SAA1),and matrix metallopeptidase 9(MMP9)were selected to construct a predictive model.The developed model demonstrated significant efficacy in distinguishing patient prognosis,recurrent cases,and characteristics of high inflammation,hypoxia,and immunosuppression.Furthermore,this model can serve as a valuable tool for guiding the use of trametinib.Conclusions:In summary,this study provides a comprehensive understanding of the interplay between M2 macrophages and cancer cells in glioma;utilizes a cross-talk gene signature to develop a predictive model that can predict the differentiation of patient prognosis,recurrence instances,and microenvironment characteristics;and aids in optimizing the application of trametinib in glioma patients.

A comprehensive and systematic analysis of Dihydrolipoamide S-acetyltransferase (DLAT) as a novel prognostic biomarker in pan-cancer and glioma

Background:Dihydrolipoamide S-acetyltransferase(DLAT)is a subunit of the pyruvate dehydrogenase complex(PDC),a rate-limiting enzyme complex,that can participate in either glycolysis or the tricarboxylic acid cycle(TCA).However,the pathogenesis is not fully understood.We aimed to perform a more systematic and comprehensive analysis of DLAT in the occurrence and progression of tumors,and to investigate its function in patients’prognosis and immunotherapy.Methods:The differential expression,diagnosis,prognosis,genetic and epigenetic alterations,tumor microenvironment,stemness,immune infiltration cells,function enrichment,single-cell analysis,and drug response across cancers were conducted based on multiple computational tools.Additionally,we validated its carcinogenic effect and possible mechanism in glioma cells.Results:We exhibited that DLAT expression was increased in most tumors,especially in glioma,and affected the survival of tumor patients.DLAT was related to RNA modification genes,DNA methylation,immune infiltration,and immune infiltration cells,including CD4+T cells,CD8+T cells,Tregs,and cancer-associatedfibroblasts.Single-cell analysis displayed that DLAT might regulate cancer by mediating angiogenesis,inflammation,and stemness.Enrichment analysis revealed that DLAT might take part in the cell cycle pathway.Increased expression of DLAT leads tumor cells to be more resistant to many kinds of compounds,including PI3Kβinhibitors,PKC inhibitors,HSP90 inhibitors,and MEK inhibitors.In addition,glioma cells with DLAT silence inhibited proliferation,migration,and invasion ability,and promoted cell apoptosis.Conclusion:We conducted a comprehensive analysis of DLAT in the occurrence and progression of tumors,and its possible functions and mechanisms.DLAT is a potential diagnostic,prognostic,and immunotherapeutic biomarker for cancer patients.

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.

ResMHA-Net:Enhancing Glioma Segmentation and Survival Prediction Using a Novel Deep Learning Framework

Gliomas are aggressive brain tumors known for their heterogeneity,unclear borders,and diverse locations on Magnetic Resonance Imaging(MRI)scans.These factors present significant challenges for MRI-based segmentation,a crucial step for effective treatment planning and monitoring of glioma progression.This study proposes a novel deep learning framework,ResNet Multi-Head Attention U-Net(ResMHA-Net),to address these challenges and enhance glioma segmentation accuracy.ResMHA-Net leverages the strengths of both residual blocks from the ResNet architecture and multi-head attention mechanisms.This powerful combination empowers the network to prioritize informative regions within the 3D MRI data and capture long-range dependencies.By doing so,ResMHANet effectively segments intricate glioma sub-regions and reduces the impact of uncertain tumor boundaries.We rigorously trained and validated ResMHA-Net on the BraTS 2018,2019,2020 and 2021 datasets.Notably,ResMHA-Net achieved superior segmentation accuracy on the BraTS 2021 dataset compared to the previous years,demonstrating its remarkable adaptability and robustness across diverse datasets.Furthermore,we collected the predicted masks obtained from three datasets to enhance survival prediction,effectively augmenting the dataset size.Radiomic features were then extracted from these predicted masks and,along with clinical data,were used to train a novel ensemble learning-based machine learning model for survival prediction.This model employs a voting mechanism aggregating predictions from multiple models,leading to significant improvements over existing methods.This ensemble approach capitalizes on the strengths of various models,resulting in more accurate and reliable predictions for patient survival.Importantly,we achieved an impressive accuracy of 73%for overall survival(OS)prediction.

Gene Expression Profile Identifies LncRNA AL355974.3 As a Potential Glioma Biomarker

Objective Glioma is a central nervous system tumor arising from glial cells.Despite significant advances in diagnosis and treatment,most patients with high-grade gliomas have a poor prognosis.Many studies have shown that long noncoding RNAs(lncRNAs)may play important roles in the development,progression and treatment of many tumors,including gliomas.Molecularly targeted therapy may be a new direction for the adjuvant treatment of glioma.Therefore,we hope that by studying differentially expressed lncRNAs(DElncRNAs)in glioma,we can discover lncRNAs that can serve as biomarkers for glioma and provide better therapeutic modalities for glioma patients.Methods First,the expression of lncRNAs in 5 normal brain(NB)tissues and 10 glioma tissues was examined by RNA sequencing(RNA-seq).Next,we performed Kaplan-Meier analysis of data from The Cancer Genome Atlas(TCGA)database to assess the prognostic value of these variables.Finally,functional analysis of the DElncRNAs was performed by means of Gene Ontology(GO)enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis.Results RNA sequencing analysis revealed 85 upregulated miRNAs and 71 downregulated lncRNAs in low-grade glioma(LGG)and 50 upregulated lncRNAs and 70 downregulated lncRNAs in glioblastoma(GBM).Among them,AL355974.3 was the most upregulated lncRNA.LINC00632 was the most downregulated lncRNA.Second,LGG patients with higher AL355974.3 expression had worse overall survival according to Kaplan-Meier analysis of the TCGA database.Finally,bioinformatics analysis revealed that the target genes of these DElncRNAs were enriched in various biological processes and signaling pathways,such as cell metabolic and developmental processes.Conclusion Our findings provide evidence that AL355974.3 may be a new biomarker for glioma.

Survival Analysis of Patients Undergoing Intraoperative Contrast-enhanced Ultrasound in the Surgical Treatment of Malignant Glioma

Objective:Complete resection of malignant gliomas is often challenging.Our previous study indicated that intraoperative contrast-enhanced ultrasound(ICEUS)could aid in the detection of residual tumor remnants and the total removal of brain lesions.This study aimed to investigate the survival rates of patients undergoing resection with or without the use of ICEUS and to assess the impact of ICEUS on the prognosis of patients with malignant glioma.Methods:A total of 64 patients diagnosed with malignant glioma(WHO grade HI and IV)who underwent surgery between 2012 and 2018 were included.Among them,29 patients received ICEUS.The effects of ICEUS on overall survival(OS)and progression-free survival(PFS)of patients were evaluated.A quantitative analysis was performed to compare ICEUS parameters between gliomas and the surrounding tissues.Results:The ICEUS group showed better survival rates both in OS and PFS than the control group.The univariate analysis revealed that age,pathology and ICEUS were significant prognostic factors for PFS,with only age being a significant prognostic factor for OS.In multivariate analysis,age and ICEUS were significant prognostic factors for both OS and PFS.The quantitative analysis showed that the intensity and transit time of microbubbles reaching the tumors were significantly different from those of microbubbles reaching the surrounding tissue.Conclusion:ICEUS facilitates the identification of residual tumors.Age and ICEUS are prognostic factors for malignant glioma surgery,and use of ICEUS offers a better prognosis for patients with malignant glioma.

Recent advances in spatio-temporally controllable systems for management of glioma

Malignant glioma remains one of the most aggressive intracranial tumors with devastating clinical outcomes despite the great advances in conventional treatment approaches,including surgery and chemotherapy.Spatio-temporally controllable approaches to glioma are now being actively investigated due to the preponderance,including spatio-temporal adjustability,minimally invasive,repetitive properties,etc.External stimuli can be readily controlled by adjusting the site and density of stimuli to exert the cytotoxic on glioma tissue and avoid undesired injury to normal tissues.It is worth noting that the removability of external stimuli allows for on-demand treatment,which effectively reduces the occurrence of side effects.In this review,we highlight recent advancements in drug delivery systems for spatio-temporally controllable treatments of glioma,focusing on the mechanisms and design principles of sensitizers utilized in these controllable therapies.Moreover,the potential challenges regarding spatio-temporally controllable therapy for glioma are also described,aiming to provide insights into future advancements in this field and their potential clinical applications.