OBJECT:Glioblastoma multiforme(GBM)is the most common and lethal primary brain tumor in adults.It isnearly uniformly fatal,with a median survival time of approximately l year,despite modem treatment modalities.Neverth...OBJECT:Glioblastoma multiforme(GBM)is the most common and lethal primary brain tumor in adults.It isnearly uniformly fatal,with a median survival time of approximately l year,despite modem treatment modalities.Nevertheless,a range of survival times exists around this median.Efforts to understand why some patients livelonger or shorter than the average may provide insight into the biology of these neoplasms.The annexin VII(ANX7)gene is located on the human chromosome 10q21,a site long hypothesized to harbor tumor展开更多
Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the...Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.展开更多
Ionizing radiation is a popular and effective treatment option for glioblastoma(GBM).However,resistance to radiation therapy inevitably occurs during treatment.It is urgent to investigate the mechanisms of radioresist...Ionizing radiation is a popular and effective treatment option for glioblastoma(GBM).However,resistance to radiation therapy inevitably occurs during treatment.It is urgent to investigate the mechanisms of radioresistance in GBM and to find ways to improve radiosensitivity.Here,we found that heat shock protein 90 beta family member 1(HSP90B1)was significantly upregulated in radioresistant GBM cell lines.More importantly,HSP90B1 promoted the localization of glucose transporter type 1,a key rate-limiting factor of glycolysis,on the plasma membrane,which in turn enhanced glycolytic activity and subsequently tumor growth and radioresistance of GBM cells.These findings imply that targeting HSP90B1 may effectively improve the efficacy of radiotherapy for GBM patients,a potential new approach to the treatment of glioblastoma.展开更多
Objectives Glioblastoma multiforme(GBM)is highly resistant to apoptosis.This study investigates the role of Selenoprotein M(SELENOM),a redox-regulating protein,in the response of human glioblastoma A-172 cells to stau...Objectives Glioblastoma multiforme(GBM)is highly resistant to apoptosis.This study investigates the role of Selenoprotein M(SELENOM),a redox-regulating protein,in the response of human glioblastoma A-172 cells to staurosporine(STS)and hyperthermia.Methods A stable SELENOM-knockdown(SELENOM-KD)cell line was created.We measured reactive oxygen species(ROS),mitochondrial membrane potential(ΔΨm),cell death,and apoptotic gene expression.Results SELENOM-KD increased basal ROS levels and induced mitochondrial dysfunction.It sensitized cells to STS-induced apoptosis,enhancing the upregulation of pro-apoptotic genes.Conversely,under hyperthermia(42°C),SELENOM-KD cells exhibited significant thermoresistance,with 52%survival vs.99%death in controls,associated with suppressed pro-apoptotic signaling.Conclusions SELENOM is a critical redox and mitochondrial regulator in GBM.Its loss produces a context-dependent effect on cell fate:sensitizing to chemical apoptosis while conferring resistance to hyperthermia.SELENOM expression is a promising predictive biomarker for stratifying GBM patients for hyperthermia-based therapies.展开更多
Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving resear...Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.展开更多
Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),wh...Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.展开更多
Background Recent studies have suggested that cancer stem cells are one of the major causes for tumor recurrence due to their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of gliobla...Background Recent studies have suggested that cancer stem cells are one of the major causes for tumor recurrence due to their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma （GBM） cells is also implicated in the failure of current therapies, it is not clear how glioma stem cells （GSCs） are involved in invasiveness. Racl activity is necessary for inducing reorganization of actin cytoskeleton and cell movement. In this study, we aimed to investigate the distribution characteristics of CD133＋ cells and Racl＋ cells in GBM as well as Racl activity in CD133＋ GBM cells, and analyze the migration and invasion potential of these cells. Methods A series of 21 patients with GBM were admitted consecutively and received tumor resection in Tianjin Medical University General Hospital during the first half of the year 2011. Tissue specimens were collected both from the peripheral and the central parts for each tumor under magnetic resonance imaging （MRI） navigation guidance. Immunohistochemical staining was used to detect the CD133＋ cells and Racl＋ cells distribution in GBM specimens. Double-labeling immunofluorescence was further used to analyze CD133 and Racl co-expression and the relationship between CD133＋ cells distribution and Racl expression. Serum-free medium culture and magnetic sorting were used to isolate CD133＋ cells from U87 cell line. Racl activation assay was conducted to assess the activation of Racl in CD133＋ and CD133- U87 cells. The migration and invasive ability of CD133＋ and CD133- U87 cells were determined by cell migration and invasion assays in vitro. Student＇s t-test and one-way analysis of variance （ANOVA） test were used to determine statistical significance in this study. Results In the central parts of GBMs, CD133＋ cells were found to cluster around necrosis and occasionally cluster around the vessels under the microscope by immunohistological staining. In the peripheral parts of the tumors, CD133＋ cells were lined up along the basement membrane of the vessels and myelinated nerve fibers. Racl expression was high and diffused in the central parts of the GBMs, and the Racl＋ cells were distributed basically in accordance with CD133＋ cells both in the central and peripheral parts of GBMs. In double-labeling immunofluorescence, Racl was expressed in （83.14＋4.23）% of CD133＋ cells, and CD133 and Racl co-expressed cells were located around the vessels in GBMs. Significantly higher amounts of Racl-GTP were expressed in the CD133＋ cells （0.378±0.007）, compared to CD133- cells （0.195±0.004） （t=-27.81; P 〈0.05）. CD133＋ cells had stronger ability to migrate （74.34±2.40 vs. 38.72±2.60, t=42.71, P 〈0.005） and invade （52.00±2.28 vs. 31.26±1.82, t=30.76, P 〈0.005）, compared to their counterpart CD133- cells in transwell cell migration/invasion assay. Conclusions These data suggest that CD133＋ GBM cells highly express Racl and have greater potential to migrate and invade through activated Racl-GTP. The accordance of distribution between Racl＋ cells and CD133＋ cells in GBMs implies that Racl might be an inhibited target to prevent invasion and migration and to avoid malignant glioma recurrence展开更多
Glioblastoma multiforme （GBM） is the most common adult primary tumor of the cen- tral nervous system. The current standard of care for glioblastoma patients involves a combination of surgery, radiotherapy and chemot...Glioblastoma multiforme （GBM） is the most common adult primary tumor of the cen- tral nervous system. The current standard of care for glioblastoma patients involves a combination of surgery, radiotherapy and chemotherapy with the alkylating agent temozolomide. Several mech- anisms underlying the inherent and acquired temozolomide resistance have been identified and con- tribute to treatment failure. Early identification of temozolomide-resistant GBM patients and improvement of the therapeutic strategies available to treat this malignancy are of uttermost impor- tance. This review initially looks at the molecular pathways underlying GBM formation and devel- opment with a particular emphasis placed on recent therapeutic advances made in the field. Our focus will next be directed toward the molecular mechanisms modulating temozolomide resistance in GBM patients and the strategies envisioned to circumvent this resistance. Finallyl we highlight the diagnostic and prognostic value of metabolomics in cancers and assess its potential usefulness in improving the current standard of care for GBM patients.展开更多
Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific ...Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy and money being directed towards understanding and utilizing this connection for eventual therapeutic purposes. Nevertheless, the association between GBM and HCMV remains controversial. Several studies have reported conflicting results, further undermining the potential clinical value of this association. In this review, the authors will discuss the latest developments on this evolving issue. Specifically, the results of the latest studies, both positive and negative, will be discussed. Furthermore, potential theories to explain discrepancies reported in the literature will be proposed. Clinical implications including potential targets for anti-HCMV therapy and the latest developments in anti-HCMV therapy will be presented. Finally, solutions to remedy this controversial issue in neuro-oncology will be offered.展开更多
The poor prognosis of glioblastoma multiforme(GBM)patients is in part due to resistance to current standard-of-care treatments including chemotherapy[predominantly temozolomide(TMZ;Temodar)],radiation therapy and an a...The poor prognosis of glioblastoma multiforme(GBM)patients is in part due to resistance to current standard-of-care treatments including chemotherapy[predominantly temozolomide(TMZ;Temodar)],radiation therapy and an anti-angiogenic therapy[an antibody against the vascular endothelial growth factor(bevacizumab;Avastin)],resulting in recurrent tumors.Several recurrent GBM tumors are commonly resistant to either TMZ,radiation or bevacizumab,which contributes to the low survival rate for GBM patients.This review will focus on novel targets and therapeutic approaches that are currently being considered to combat GBM chemoresistance.One of these therapeutic options is a small molecule called OKlahoma Nitrone 007(OKN-007),which was discovered to inhibit the transforming growth factor β1 pathway,reduce TMZ-resistance and enhance TMZ-sensitivity.OKN-007 is currently an investigational new drug in clinical trials for both newly-diagnosed and recurrent GBM patients.Another novel target is ELTD1(epidermal growth factor,latrophilin and seven transmembrane domain-containing protein 1;alternatively known as ADGRL4,Adhesion G protein-coupled receptor L4),which we used a monoclonal antibody against,where a therapy against it was found to inhibit Notch 1 in a pre-clinical GBM xenograft model.Notch 1 is known to be associated with chemoresistance in GBM.Other potential therapeutic targets to combat GBM chemoresistance include the phosphoinositide 3-kinase pathway,nuclear factor-κB,the hepatocyte/scatter factor(c-MET),the epidermal growth factor receptor,and the tumor microenvironment.展开更多
Glioblastoma multiforme(GBM),a highly malignant and heterogeneous brain tumor,contains various types of tumor and non-tumor cells.Whether GBM cells can trans-differentiate into non-neural cell types,including mural ce...Glioblastoma multiforme(GBM),a highly malignant and heterogeneous brain tumor,contains various types of tumor and non-tumor cells.Whether GBM cells can trans-differentiate into non-neural cell types,including mural cells or endothelial cells(ECs),to support tumor growth and invasion remains controversial.Here we generated two genetic GBM models de novo in immunocompetent mouse brains,mimicking essential pathological and molecular features of human GBMs.Lineage-tracing and transplantation studies demonstrated that,although blood vessels in GBM brains underwent drastic remodeling,evidence of trans-differentiation of GBM cells into vascular cells was barely detected.Intriguingly,GBM cells could promiscuously express markers for mural cells during gliomagenesis.Furthermore,single-cell RNA sequencing showed that patterns of copy number variations(CNVs)of mural cells and ECs were distinct from those of GBM cells,indicating discrete origins of GBM cells and vascular components.Importantly,single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages.Rather than expansion owing to trans-differentiation,vascular cell expanded by proliferation during tumorigenesis.Therefore,cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis.Our findings advance understanding of cell lineage dynamics during gliomagenesis,and have implications for targeted treatment of GBMs.展开更多
Glioblastoma(GBM)is the most aggressive primary brain tumor with a median survival of 15 months despite standard care therapy consisting of maximal surgical debulking,followed by radiation therapy with concurrent and ...Glioblastoma(GBM)is the most aggressive primary brain tumor with a median survival of 15 months despite standard care therapy consisting of maximal surgical debulking,followed by radiation therapy with concurrent and adjuvant temozolomide treatment.The natural history of GBM is characterized by inevitable recurrence with patients dying from increasingly resistant tumor regrowth after therapy.Several mechanisms including inter-and intratumoral heterogeneity,the evolution of therapy-resistant clonal subpopulations,reacquisition of stemness in glioblastoma stem cells,multiple drug efflux mechanisms,the tumor-promoting microenvironment,metabolic adaptations,and enhanced repair of drug-induced DNA damage have been implicated in therapy failure.Extracellular vesicles(EVs)have emerged as crucial mediators in the maintenance and establishment of GBM.Multiple seminal studies have uncovered the multi-dynamic role of EVs in the acquisition of drug resistance.Mechanisms include EV-mediated cargo transfer and EVs functioning as drug efflux channels and decoys for antibody-based therapies.In this review,we discuss the various mechanisms of therapy resistance in GBM,highlighting the emerging role of EV-orchestrated drug resistance.Understanding the landscape of GBM resistance is critical in devising novel therapeutic approaches to fight this deadly disease.展开更多
Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiqu...Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.展开更多
Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers....Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers.This study aims to investigate the role of AFAP1L1 in glioma and to explore changes in AFAP1L1 expression during glioma progression.Methods:Clinical and transcriptomic data of glioma patients were downloaded from The Cancer Genome Atlas(TCGA),the Chinese Glioma Genome Atlas(CGGA),and the Gene Expression Omnibus(GEO)databases to analyze the associations between AFAP1L1 expression and glioma prognosis,somatic mutations,immune cell infiltration,and enriched signaling pathways.Western blotting and real-time polymerase chain reaction(PCR)were used to detect AFAP1L1 messenger RNA(mRNA)and protein expression in glioma patients.Results:Patients with high AFAP1L1 expression had poorer prognosis,and AFAP1L1 was identified as an independent risk factor for glioma.In addition,glioma patients with high AFAP1L1 expression exhibited lower levels of somatic mutations,including amplification of oncogenes such as epidermal growth factor receptor and deletion of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A(CDKN2A).Estimation of STromal and Immune cells in Malignant Tumours using Expression(ESTIMATE)algorithm analysis showed that AFAP1L1 expression was positively correlated with the immune microenvironment.Tumor immune dysfunction and exclusion(TIDE)analysis indicated that glioma patients with high AFAP1L1 expression responded poorly to immunotherapy.Single cell analysis showed that AFAP1L1 expression was mainly concentrated in glioma cells.Enrichment analysis suggested that AFAP1L1 was potentially associated with small guanosine triphosphatases(GTPases),hypoxia-inducible factor-1(HIF-1),focal adhesion,and mitogen-activated protein kinase(MAPK)signaling pathways.Conclusion:AFAP1L1 is a novel biomarker indicating glioma progression and a potential therapeutic target for glioma.展开更多
BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involvin...BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involving mouse brain xenografts,are often time-consuming and limited in efficiency.In this context,stem cell-derived neural organoids(NOs)have emerged as advanced,threedimensional,human-relevant platforms that mimic the cellular architecture and microenvironment of the human brain.These models provide novel opportunities to investigate glioblastoma stem cell invasion,a critical driver of tumor progression and therapeutic resistance.AIM To evaluate studies using stem cell-derived NOs to model glioblastoma migration/invasion,focusing on methodologies,applications and therapeutic implications.METHODS We conducted a systematic review following PRISMA guidelines,searching PubMed and Scopus for studies published between March 2019 and March 2025 that investigated NOs in the context of glioblastoma invasion/migration.After screening 377 articles based on predefined inclusion and exclusion criteria,10 original research articles were selected for analysis.Extracted data were categorized into four analytical domains:(1)Tumor model formation;(2)NO characteristics;(3)NO differentiation protocols;and(4)Invasion/migration assessment methodologies.RESULTS The included studies exhibit significant methodological heterogeneity GBM model development,particularly regarding model type,cell source and culture conditions.Most studies(70%)used suspension cell models,while 30%employed spheroids,with most research focusing on patient-derived glioblastoma stem cells.NOs were predominantly generated from human induced pluripotent stem cells using both guided and unguided differentiation protocols.Confocal fluorescence microscopy was the primary method used for assessing invasion,revealing invasion depths of up to 300μm.Organoid maturity and co-culture duration influenced results,while key factors for model optimization included tumor cell density,organoid age and extracellular matrix composition.Some studies also tested therapeutic strategies such as Zika virus and microRNA modulation.Collectively,findings support the utility of NOs as effective tools for studying GBM behavior and therapeutic responses in a humanized three-dimensional context.CONCLUSION Human NOs represent promising platforms for modeling glioblastoma invasion in a humanized three-dimensional environment.However,a limited number of studies and methodological heterogeneity hinder reproducibility.Protocol standardization is essential to enhance the translational application of these models.展开更多
D-D’-A type aza-borondipyrromethenes(aza-BODIPYs)were prepared by Suzuki cross-coupling reaction.Photothermal conversion efficiency of self-assemble aza-BODIPY-based nanoparticles(DA-azaBDP-NPs)with NIR-Ⅱ emission(...D-D’-A type aza-borondipyrromethenes(aza-BODIPYs)were prepared by Suzuki cross-coupling reaction.Photothermal conversion efficiency of self-assemble aza-BODIPY-based nanoparticles(DA-azaBDP-NPs)with NIR-Ⅱ emission(λ_(em)=1065 nm)was 37.2%under near infrared(NIR)irradiation,and the outstanding cytotoxicity was triggered by coexistence of DA-azaBDP-NPs and the NIR irradiation,with the decrease of glioblastoma migration and the inhibition of glioblastoma proliferation.DA-azaBDP-NPs could promote glioblastoma autophagy and accelerate the process of cell death.The photothermal therapy(PTT)of DAazaBDP-NPs can effectively induce glioblastoma death by apoptosis under the NIR irradiation,which is highly promising to be applied in vivo experiments of brain.展开更多
Objectives:Cisplatin(CDDP)therapy for glioblastoma(GBM)is linked with several limitations,which include poor penetration of the blood-brain barrier(BBB),systemic toxicity,and the development of drug resistance mechani...Objectives:Cisplatin(CDDP)therapy for glioblastoma(GBM)is linked with several limitations,which include poor penetration of the blood-brain barrier(BBB),systemic toxicity,and the development of drug resistance mechanisms implicating oxidative stress dysregulation and compromised apoptotic pathways.This study evaluates C-Phycocyanin(C-PC)as a potential adjuvant to enhance CDDP efficacy by modulating redox balance and apoptosis.Methods:GBM cells(U87 and U87-EGFRvIII)were treated with CDDP,C-PC,or their combination.Cell viability was assessed by MTT assay;apoptosis was evaluated by DAPI staining andWestern blot analysis of cleaved Caspase-3 and poly(ADP-ribose)polymerase(PARP).Both intracellular and extracellular reactive oxygen species(ROS)were measured using 2′,7′-dichlorodihydrofluorescein diacetate(DCF-DA)fluorescence and lucigenin chemiluminescence,respectively.Catalase activity was quantified via hydrogen peroxide(H2O2)decomposition assay,and manganese superoxide dismutase(MnSOD)expression byWestern blot.Results:C-PCselectively decreased U87GBMcell viability while sparing normal cells.C-PC enhanced CDDP cytotoxicity,reducing viability to 26.5%vs.53.2%for CDDP alone.This effect correlated with increased apoptosis,evidenced by DNA fragmentation and higher cleaved caspase-3 and PARP levels.Combined treatment lowered ROS below survival thresholds while upregulating MnSOD and catalase activity.In U87-EGFRvIII cells,CDDP reduced viability modestly(85.2%),C-PC alone decreased viability significantly(51.5%)and induced cell death,but the combination did not further increase apoptosis.Here,C-PC’s pro-apoptotic effects,alone or with CDDP,were also associated with reduced oxidative stress in cells.Conclusion:We demonstrate that C-PC enhances CDDP cytotoxicity in sensitive U87 cells by promoting apoptosis and modulating ROS,suggesting potential for improved therapeutic efficacy with reduced systemic toxicity.Compared to the combination,C-PC monotherapy achieves superior cytotoxicity in CDDP-resistant U87-EGFRvIII cells,underscoring its potential as a standalone therapeutic approach for chemotherapy-resistant glioblastoma subtypes.展开更多
1.HOU J,DU Y,SHAO Y,et al.Identification,Albanol B inhibits glioblastoma progression by inducing senescence and apoptosis via the RNF6/p27 signaling axis.Phytomedicine.DOI:10.1016/j.phymed.2025.157056.(2025)[题目]Alba...1.HOU J,DU Y,SHAO Y,et al.Identification,Albanol B inhibits glioblastoma progression by inducing senescence and apoptosis via the RNF6/p27 signaling axis.Phytomedicine.DOI:10.1016/j.phymed.2025.157056.(2025)[题目]Albanol B通过RNF6/p27信号轴诱导细胞衰老与凋亡,从而抑制胶质母细胞瘤进展。展开更多
文摘OBJECT:Glioblastoma multiforme(GBM)is the most common and lethal primary brain tumor in adults.It isnearly uniformly fatal,with a median survival time of approximately l year,despite modem treatment modalities.Nevertheless,a range of survival times exists around this median.Efforts to understand why some patients livelonger or shorter than the average may provide insight into the biology of these neoplasms.The annexin VII(ANX7)gene is located on the human chromosome 10q21,a site long hypothesized to harbor tumor
基金supported by the National Key Research and Development Programs of China(Grant No.2018YFA0209700)National Natural Science Foundation of China(Grant No.22077073)+1 种基金Frontiers Science Center for New Organic Matter,Nankai University(Grant No.63181206)the Fundamental Research Funds for the Central Universities,Nankai University(Grant No.63206015)。
文摘Glioblastoma(GBM)is the most common malignant brain tumor.Although current treatment strategies,including surgery,chemotherapy,and radiotherapy,have achieved clinical effects and prolonged the survival of patients,the gradual development of resistance against current therapies has led to a high recurrence rate and treatment failure.Mechanisms underlying the development of resistance involve multiple factors,including drug efflux,DNA damage repair,glioma stem cells,and a hypoxic tumor environment,which are usually correlative and promote each other.As many potential therapeutic targets have been discovered,combination therapy that regulates multiple resistance-related molecule pathways is considered an attractive strategy.In recent years,nanomedicine has revolutionized cancer therapies with optimized accumulation,penetration,internalization,and controlled release.Blood-brain barrier(BBB)penetration efficiency is also significantly improved through modifying ligands on nanomedicine and interacting with the receptors or transporters on the BBB.Moreover,different drugs for combination therapy usually process different pharmacokinetics and biodistribution,which can be further optimized with drug delivery systems to maximize the therapeutic efficiency of combination therapies.Herein the current achievements in nanomedicine-based combination therapy for GBM are discussed.This review aimed to provide a broader understanding of resistance mechanisms and nanomedicine-based combination therapies for future research on GBM treatment.
基金supported by the National Natural Science Foundation of China(Grant Nos.82072765 to X.Q.and 82172667 to X.W.).
文摘Ionizing radiation is a popular and effective treatment option for glioblastoma(GBM).However,resistance to radiation therapy inevitably occurs during treatment.It is urgent to investigate the mechanisms of radioresistance in GBM and to find ways to improve radiosensitivity.Here,we found that heat shock protein 90 beta family member 1(HSP90B1)was significantly upregulated in radioresistant GBM cell lines.More importantly,HSP90B1 promoted the localization of glucose transporter type 1,a key rate-limiting factor of glycolysis,on the plasma membrane,which in turn enhanced glycolytic activity and subsequently tumor growth and radioresistance of GBM cells.These findings imply that targeting HSP90B1 may effectively improve the efficacy of radiotherapy for GBM patients,a potential new approach to the treatment of glioblastoma.
基金the framework of the State assignment No.075-00607-25-00.
文摘Objectives Glioblastoma multiforme(GBM)is highly resistant to apoptosis.This study investigates the role of Selenoprotein M(SELENOM),a redox-regulating protein,in the response of human glioblastoma A-172 cells to staurosporine(STS)and hyperthermia.Methods A stable SELENOM-knockdown(SELENOM-KD)cell line was created.We measured reactive oxygen species(ROS),mitochondrial membrane potential(ΔΨm),cell death,and apoptotic gene expression.Results SELENOM-KD increased basal ROS levels and induced mitochondrial dysfunction.It sensitized cells to STS-induced apoptosis,enhancing the upregulation of pro-apoptotic genes.Conversely,under hyperthermia(42°C),SELENOM-KD cells exhibited significant thermoresistance,with 52%survival vs.99%death in controls,associated with suppressed pro-apoptotic signaling.Conclusions SELENOM is a critical redox and mitochondrial regulator in GBM.Its loss produces a context-dependent effect on cell fate:sensitizing to chemical apoptosis while conferring resistance to hyperthermia.SELENOM expression is a promising predictive biomarker for stratifying GBM patients for hyperthermia-based therapies.
基金supported by Key Research and Development Plan of Hunan Province(2024DK2006)the Fundamental Research Funds for the Central Universities of Central South University(1053320221769)+2 种基金Hunan Provincial Respiratory Disease Rehabilitation and Nursing Engineering Research Center Innovation Capacity Building Project(No.202012)the Zhangjiajie Science and Technology Development Key Special Project(No.202304)the National Key Clinical Specialty Major Scientific Research Project(No.20230382).
文摘Background:Glioblastoma(GBM)prognosis has seen little improvement over the past two decades.While immunotherapy has revolutionized cancer treatment,its impact on GBM remains limited.To characterize the evolving research landscape and identify future directions in GBM immunotherapy,we conducted a comprehensive bibliometric review.Methods:All literature related to immunotherapy in GBM from 1999 to 2024 was collected from the Web of Science Core Collection.CtieSpace and VOSviewer were used to conduct bibliometric analysis and visualize the data.Results:Bibliometric analysis identified 5038 publications authored by 23,335 researchers from 4699 institutions across 96 countries/regions,published in 945 journals.The United States produced the highest number of publications,while Switzerland achieved the highest average citation rate.Duke University led in institutional output and citations.John H Sampson was the most productive author,and Roger Stupp was the most cited.Frontiers in Immunology published the most papers,while Clinical Cancer Research was the most cited journal.Research focus centered on adoptive T cell therapy,particularly chimeric antigen receptor(CAR)-T cells with 572 dedicated publications.Within CAR-T research for GBM,the University of Pennsylvania was the leading institution,Frontiers in Immunology the predominant journal,and Christine E Brown(City of Hope National Medical Center)was the most prolific and cited author.Conclusions:There has been a growing interest in GBM immunotherapy over past decades.The United States is the dominant contributor.CAR-T therapy represents the primary research focus.Emerging strategies like chimeric antigen receptor-modified natural killer(CAR-NK)cells,chimeric antigen receptor-engineered macrophages(CAR-M),and cytomegalovirus-specific T cell receptor(CMV-TCR)T cells are gaining prominence,aiming to address limitations in antigen recognition inherent to CAR-T therapy for GBM.
基金supported by research grants from the Ministry of Science and Technology(MOST 108-2314-B-400-026 and 109-2013-B-400-036)National Science and Technology Council(NSTC 112-2320-B-214-010 and 113-2320-B-214-002)+1 种基金I-Shou University(ISU-112-01-12A,ISU112-S-02 and ISU114-S-04)National Health Research Institutes,Taiwan(CA-111-PP-19).
文摘Objectives:Glioblastoma(GBM)is a prevalent malignant brain tumor prone to drug resistance.We previously found a strong correlation between SH3 domain GRB2-like endophilin B1(SH3GLB1)and superoxide dismutase 2(SOD2),which converts O_(2) to hydrogen peroxide(H_(2)O_(2)).Prior studies show that H_(2)O_(2) redox signaling is vital for physiological processes and can drive tumor progression.Therefore,we aim to define how H_(2)O_(2) signaling regulates SH3GLB1 and AKT(protein kinase B)pathways in GBM and to assess whether modulating H_(2)O_(2) reverses temozolomide(TMZ)resistance.Methods:We used cultured cells and pharmacological inhibitors and activators to confirm the significance of H_(2)O_(2) signaling.GBM cells were used to verify the role of H_(2)O_(2) signaling in cell state transitions and animal experiments identified optimal treatment strategies.Results:We found that SOD2 acts as an upstream regulator of SH3GLB1.When SOD inhibitors and TMZ were combined,cells showed reduced SH3GLB1 and autophagy levels.SH3GLB1 was found to be regulated by H_(2)O_(2) via AKT signaling using redox homeostasis-regulating experiments.Although treatment-induced changes in mitochondrial H_(2)O_(2) levels mirrored those in the cytosol,parental and resistant cells exhibited divergent fates,highlighting cell-fate plasticity.TMZ combined with a redox modulator reduced resistant tumor cell growth(about 2/3 reduction of tumor size;p<0.05)and suppressed SH3GLB1 and autophagy levels in animal models.The TMZ-induced increase in SH3GLB1 expression was reversed by HgCl2,which inhibited the aquaporin-9/AKT signaling.Conclusion:Overall,these findings underscore the importance of H_(2)O_(2)-SH3GLB1 signaling in GBM and may inform future therapeutic strategies for overcoming TMZ resistance.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 81272782）.
文摘Background Recent studies have suggested that cancer stem cells are one of the major causes for tumor recurrence due to their resistance to radiotherapy and chemotherapy. Although the highly invasive nature of glioblastoma （GBM） cells is also implicated in the failure of current therapies, it is not clear how glioma stem cells （GSCs） are involved in invasiveness. Racl activity is necessary for inducing reorganization of actin cytoskeleton and cell movement. In this study, we aimed to investigate the distribution characteristics of CD133＋ cells and Racl＋ cells in GBM as well as Racl activity in CD133＋ GBM cells, and analyze the migration and invasion potential of these cells. Methods A series of 21 patients with GBM were admitted consecutively and received tumor resection in Tianjin Medical University General Hospital during the first half of the year 2011. Tissue specimens were collected both from the peripheral and the central parts for each tumor under magnetic resonance imaging （MRI） navigation guidance. Immunohistochemical staining was used to detect the CD133＋ cells and Racl＋ cells distribution in GBM specimens. Double-labeling immunofluorescence was further used to analyze CD133 and Racl co-expression and the relationship between CD133＋ cells distribution and Racl expression. Serum-free medium culture and magnetic sorting were used to isolate CD133＋ cells from U87 cell line. Racl activation assay was conducted to assess the activation of Racl in CD133＋ and CD133- U87 cells. The migration and invasive ability of CD133＋ and CD133- U87 cells were determined by cell migration and invasion assays in vitro. Student＇s t-test and one-way analysis of variance （ANOVA） test were used to determine statistical significance in this study. Results In the central parts of GBMs, CD133＋ cells were found to cluster around necrosis and occasionally cluster around the vessels under the microscope by immunohistological staining. In the peripheral parts of the tumors, CD133＋ cells were lined up along the basement membrane of the vessels and myelinated nerve fibers. Racl expression was high and diffused in the central parts of the GBMs, and the Racl＋ cells were distributed basically in accordance with CD133＋ cells both in the central and peripheral parts of GBMs. In double-labeling immunofluorescence, Racl was expressed in （83.14＋4.23）% of CD133＋ cells, and CD133 and Racl co-expressed cells were located around the vessels in GBMs. Significantly higher amounts of Racl-GTP were expressed in the CD133＋ cells （0.378±0.007）, compared to CD133- cells （0.195±0.004） （t=-27.81; P 〈0.05）. CD133＋ cells had stronger ability to migrate （74.34±2.40 vs. 38.72±2.60, t=42.71, P 〈0.005） and invade （52.00±2.28 vs. 31.26±1.82, t=30.76, P 〈0.005）, compared to their counterpart CD133- cells in transwell cell migration/invasion assay. Conclusions These data suggest that CD133＋ GBM cells highly express Racl and have greater potential to migrate and invade through activated Racl-GTP. The accordance of distribution between Racl＋ cells and CD133＋ cells in GBMs implies that Racl might be an inhibited target to prevent invasion and migration and to avoid malignant glioma recurrence
基金the Beatrice Hunter Cancer Research Institutethe Brain Tumour Foundation of Canada
文摘Glioblastoma multiforme （GBM） is the most common adult primary tumor of the cen- tral nervous system. The current standard of care for glioblastoma patients involves a combination of surgery, radiotherapy and chemotherapy with the alkylating agent temozolomide. Several mech- anisms underlying the inherent and acquired temozolomide resistance have been identified and con- tribute to treatment failure. Early identification of temozolomide-resistant GBM patients and improvement of the therapeutic strategies available to treat this malignancy are of uttermost impor- tance. This review initially looks at the molecular pathways underlying GBM formation and devel- opment with a particular emphasis placed on recent therapeutic advances made in the field. Our focus will next be directed toward the molecular mechanisms modulating temozolomide resistance in GBM patients and the strategies envisioned to circumvent this resistance. Finallyl we highlight the diagnostic and prognostic value of metabolomics in cancers and assess its potential usefulness in improving the current standard of care for GBM patients.
文摘Human cytomegalovirus (HCMV) was reported in glioblastoma multiforme (GBM) over a decade ago and this finding has the potential to increase our understanding of the disease and it offers an alternative tumor-specific therapeutic target. Due of this promise, there is a fair amount of time, energy and money being directed towards understanding and utilizing this connection for eventual therapeutic purposes. Nevertheless, the association between GBM and HCMV remains controversial. Several studies have reported conflicting results, further undermining the potential clinical value of this association. In this review, the authors will discuss the latest developments on this evolving issue. Specifically, the results of the latest studies, both positive and negative, will be discussed. Furthermore, potential theories to explain discrepancies reported in the literature will be proposed. Clinical implications including potential targets for anti-HCMV therapy and the latest developments in anti-HCMV therapy will be presented. Finally, solutions to remedy this controversial issue in neuro-oncology will be offered.
基金This work was supported by the Oklahoma Medical Research Foundation,and Oblato,Inc.,as reported in published manuscripts.
文摘The poor prognosis of glioblastoma multiforme(GBM)patients is in part due to resistance to current standard-of-care treatments including chemotherapy[predominantly temozolomide(TMZ;Temodar)],radiation therapy and an anti-angiogenic therapy[an antibody against the vascular endothelial growth factor(bevacizumab;Avastin)],resulting in recurrent tumors.Several recurrent GBM tumors are commonly resistant to either TMZ,radiation or bevacizumab,which contributes to the low survival rate for GBM patients.This review will focus on novel targets and therapeutic approaches that are currently being considered to combat GBM chemoresistance.One of these therapeutic options is a small molecule called OKlahoma Nitrone 007(OKN-007),which was discovered to inhibit the transforming growth factor β1 pathway,reduce TMZ-resistance and enhance TMZ-sensitivity.OKN-007 is currently an investigational new drug in clinical trials for both newly-diagnosed and recurrent GBM patients.Another novel target is ELTD1(epidermal growth factor,latrophilin and seven transmembrane domain-containing protein 1;alternatively known as ADGRL4,Adhesion G protein-coupled receptor L4),which we used a monoclonal antibody against,where a therapy against it was found to inhibit Notch 1 in a pre-clinical GBM xenograft model.Notch 1 is known to be associated with chemoresistance in GBM.Other potential therapeutic targets to combat GBM chemoresistance include the phosphoinositide 3-kinase pathway,nuclear factor-κB,the hepatocyte/scatter factor(c-MET),the epidermal growth factor receptor,and the tumor microenvironment.
基金supported by grants from the National Natural Science Foundation of China(Nos.31970676,31970770,32270876)the National Key R&D Program of China(No.2018 YFA0800700,2022YFA0806600),and the Fundamental Research Funds for the Central Universities.
文摘Glioblastoma multiforme(GBM),a highly malignant and heterogeneous brain tumor,contains various types of tumor and non-tumor cells.Whether GBM cells can trans-differentiate into non-neural cell types,including mural cells or endothelial cells(ECs),to support tumor growth and invasion remains controversial.Here we generated two genetic GBM models de novo in immunocompetent mouse brains,mimicking essential pathological and molecular features of human GBMs.Lineage-tracing and transplantation studies demonstrated that,although blood vessels in GBM brains underwent drastic remodeling,evidence of trans-differentiation of GBM cells into vascular cells was barely detected.Intriguingly,GBM cells could promiscuously express markers for mural cells during gliomagenesis.Furthermore,single-cell RNA sequencing showed that patterns of copy number variations(CNVs)of mural cells and ECs were distinct from those of GBM cells,indicating discrete origins of GBM cells and vascular components.Importantly,single-cell CNV analysis of human GBM specimens also suggested that GBM cells and vascular cells are likely separate lineages.Rather than expansion owing to trans-differentiation,vascular cell expanded by proliferation during tumorigenesis.Therefore,cross-lineage trans-differentiation of GBM cells is very unlikely to occur during gliomagenesis.Our findings advance understanding of cell lineage dynamics during gliomagenesis,and have implications for targeted treatment of GBMs.
文摘Glioblastoma(GBM)is the most aggressive primary brain tumor with a median survival of 15 months despite standard care therapy consisting of maximal surgical debulking,followed by radiation therapy with concurrent and adjuvant temozolomide treatment.The natural history of GBM is characterized by inevitable recurrence with patients dying from increasingly resistant tumor regrowth after therapy.Several mechanisms including inter-and intratumoral heterogeneity,the evolution of therapy-resistant clonal subpopulations,reacquisition of stemness in glioblastoma stem cells,multiple drug efflux mechanisms,the tumor-promoting microenvironment,metabolic adaptations,and enhanced repair of drug-induced DNA damage have been implicated in therapy failure.Extracellular vesicles(EVs)have emerged as crucial mediators in the maintenance and establishment of GBM.Multiple seminal studies have uncovered the multi-dynamic role of EVs in the acquisition of drug resistance.Mechanisms include EV-mediated cargo transfer and EVs functioning as drug efflux channels and decoys for antibody-based therapies.In this review,we discuss the various mechanisms of therapy resistance in GBM,highlighting the emerging role of EV-orchestrated drug resistance.Understanding the landscape of GBM resistance is critical in devising novel therapeutic approaches to fight this deadly disease.
基金supported by Project of the Health Shanghai Initiative Special Fund(Medical-Sports Integration,Creating a New Model of Exercise for Health),No.JKSHZX-2022-02(to SC).
文摘Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.
基金supported by the National Natural Science Foundation(82073850)the Hunan Provincial Youth Science Foundation Project(2019JJ50964),China.
文摘Objective:Actin filament-associated protein 1 like 1(AFAP1L1)is an adaptor protein lacking enzymatic and transcriptional activity,but the AFAP1L1 gene functions as an oncogene in colorectal cancer and gastric cancers.This study aims to investigate the role of AFAP1L1 in glioma and to explore changes in AFAP1L1 expression during glioma progression.Methods:Clinical and transcriptomic data of glioma patients were downloaded from The Cancer Genome Atlas(TCGA),the Chinese Glioma Genome Atlas(CGGA),and the Gene Expression Omnibus(GEO)databases to analyze the associations between AFAP1L1 expression and glioma prognosis,somatic mutations,immune cell infiltration,and enriched signaling pathways.Western blotting and real-time polymerase chain reaction(PCR)were used to detect AFAP1L1 messenger RNA(mRNA)and protein expression in glioma patients.Results:Patients with high AFAP1L1 expression had poorer prognosis,and AFAP1L1 was identified as an independent risk factor for glioma.In addition,glioma patients with high AFAP1L1 expression exhibited lower levels of somatic mutations,including amplification of oncogenes such as epidermal growth factor receptor and deletion of tumor suppressor genes such as cyclin-dependent kinase inhibitor 2A(CDKN2A).Estimation of STromal and Immune cells in Malignant Tumours using Expression(ESTIMATE)algorithm analysis showed that AFAP1L1 expression was positively correlated with the immune microenvironment.Tumor immune dysfunction and exclusion(TIDE)analysis indicated that glioma patients with high AFAP1L1 expression responded poorly to immunotherapy.Single cell analysis showed that AFAP1L1 expression was mainly concentrated in glioma cells.Enrichment analysis suggested that AFAP1L1 was potentially associated with small guanosine triphosphatases(GTPases),hypoxia-inducible factor-1(HIF-1),focal adhesion,and mitogen-activated protein kinase(MAPK)signaling pathways.Conclusion:AFAP1L1 is a novel biomarker indicating glioma progression and a potential therapeutic target for glioma.
基金Supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico,No.307318/2023-0 and No.102035/2024-5Fundação de AmparoàPesquisa do Estado de São Paulo,No.2023/10843-7 and No 2019/21070-3Nanotechnology National Laboratory System 2.0,Ministry of Science,Technology,Innovation and Communication,No.442539/2019-3.
文摘BACKGROUND Glioblastoma multiforme(GBM)is the most aggressive and prevalent primary malignant brain tumor in adults,marked by poor prognosis and high invasiveness.Traditional GBM invasion assays,such as those involving mouse brain xenografts,are often time-consuming and limited in efficiency.In this context,stem cell-derived neural organoids(NOs)have emerged as advanced,threedimensional,human-relevant platforms that mimic the cellular architecture and microenvironment of the human brain.These models provide novel opportunities to investigate glioblastoma stem cell invasion,a critical driver of tumor progression and therapeutic resistance.AIM To evaluate studies using stem cell-derived NOs to model glioblastoma migration/invasion,focusing on methodologies,applications and therapeutic implications.METHODS We conducted a systematic review following PRISMA guidelines,searching PubMed and Scopus for studies published between March 2019 and March 2025 that investigated NOs in the context of glioblastoma invasion/migration.After screening 377 articles based on predefined inclusion and exclusion criteria,10 original research articles were selected for analysis.Extracted data were categorized into four analytical domains:(1)Tumor model formation;(2)NO characteristics;(3)NO differentiation protocols;and(4)Invasion/migration assessment methodologies.RESULTS The included studies exhibit significant methodological heterogeneity GBM model development,particularly regarding model type,cell source and culture conditions.Most studies(70%)used suspension cell models,while 30%employed spheroids,with most research focusing on patient-derived glioblastoma stem cells.NOs were predominantly generated from human induced pluripotent stem cells using both guided and unguided differentiation protocols.Confocal fluorescence microscopy was the primary method used for assessing invasion,revealing invasion depths of up to 300μm.Organoid maturity and co-culture duration influenced results,while key factors for model optimization included tumor cell density,organoid age and extracellular matrix composition.Some studies also tested therapeutic strategies such as Zika virus and microRNA modulation.Collectively,findings support the utility of NOs as effective tools for studying GBM behavior and therapeutic responses in a humanized three-dimensional context.CONCLUSION Human NOs represent promising platforms for modeling glioblastoma invasion in a humanized three-dimensional environment.However,a limited number of studies and methodological heterogeneity hinder reproducibility.Protocol standardization is essential to enhance the translational application of these models.
基金supported by the National Natural Science Foundation of China(Nos.22078201,U1908202)Liaoning&Shenyang Key Laboratory of Functional Dye and Pigment(Nos.2021JH13/10200018,21-104-0-23).
文摘D-D’-A type aza-borondipyrromethenes(aza-BODIPYs)were prepared by Suzuki cross-coupling reaction.Photothermal conversion efficiency of self-assemble aza-BODIPY-based nanoparticles(DA-azaBDP-NPs)with NIR-Ⅱ emission(λ_(em)=1065 nm)was 37.2%under near infrared(NIR)irradiation,and the outstanding cytotoxicity was triggered by coexistence of DA-azaBDP-NPs and the NIR irradiation,with the decrease of glioblastoma migration and the inhibition of glioblastoma proliferation.DA-azaBDP-NPs could promote glioblastoma autophagy and accelerate the process of cell death.The photothermal therapy(PTT)of DAazaBDP-NPs can effectively induce glioblastoma death by apoptosis under the NIR irradiation,which is highly promising to be applied in vivo experiments of brain.
文摘Objectives:Cisplatin(CDDP)therapy for glioblastoma(GBM)is linked with several limitations,which include poor penetration of the blood-brain barrier(BBB),systemic toxicity,and the development of drug resistance mechanisms implicating oxidative stress dysregulation and compromised apoptotic pathways.This study evaluates C-Phycocyanin(C-PC)as a potential adjuvant to enhance CDDP efficacy by modulating redox balance and apoptosis.Methods:GBM cells(U87 and U87-EGFRvIII)were treated with CDDP,C-PC,or their combination.Cell viability was assessed by MTT assay;apoptosis was evaluated by DAPI staining andWestern blot analysis of cleaved Caspase-3 and poly(ADP-ribose)polymerase(PARP).Both intracellular and extracellular reactive oxygen species(ROS)were measured using 2′,7′-dichlorodihydrofluorescein diacetate(DCF-DA)fluorescence and lucigenin chemiluminescence,respectively.Catalase activity was quantified via hydrogen peroxide(H2O2)decomposition assay,and manganese superoxide dismutase(MnSOD)expression byWestern blot.Results:C-PCselectively decreased U87GBMcell viability while sparing normal cells.C-PC enhanced CDDP cytotoxicity,reducing viability to 26.5%vs.53.2%for CDDP alone.This effect correlated with increased apoptosis,evidenced by DNA fragmentation and higher cleaved caspase-3 and PARP levels.Combined treatment lowered ROS below survival thresholds while upregulating MnSOD and catalase activity.In U87-EGFRvIII cells,CDDP reduced viability modestly(85.2%),C-PC alone decreased viability significantly(51.5%)and induced cell death,but the combination did not further increase apoptosis.Here,C-PC’s pro-apoptotic effects,alone or with CDDP,were also associated with reduced oxidative stress in cells.Conclusion:We demonstrate that C-PC enhances CDDP cytotoxicity in sensitive U87 cells by promoting apoptosis and modulating ROS,suggesting potential for improved therapeutic efficacy with reduced systemic toxicity.Compared to the combination,C-PC monotherapy achieves superior cytotoxicity in CDDP-resistant U87-EGFRvIII cells,underscoring its potential as a standalone therapeutic approach for chemotherapy-resistant glioblastoma subtypes.
文摘1.HOU J,DU Y,SHAO Y,et al.Identification,Albanol B inhibits glioblastoma progression by inducing senescence and apoptosis via the RNF6/p27 signaling axis.Phytomedicine.DOI:10.1016/j.phymed.2025.157056.(2025)[题目]Albanol B通过RNF6/p27信号轴诱导细胞衰老与凋亡,从而抑制胶质母细胞瘤进展。
