Neuro-oncology最新文献

{"title":"Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.","authors":"Jenny Roesler, Daniel Spitzer, Xiaoxiong Jia, Synnøve Nymark Aasen, Kathleen Sommer, Bastian Roller, Niels Olshausen, Nils R Hebach, Nawid Albinger, Evelyn Ullrich, Ling Zhu, Fan Wang, Jadranka Macas, Marie-Therese Forster, Joachim P Steinbach, Lisa Sevenich, Kavi Devraj, Frits Thorsen, Matthia A Karreman, Karl H Plate, Yvonne Reiss, Patrick N Harter","doi":"10.1093/neuonc/noae094","DOIUrl":"10.1093/neuonc/noae094","url":null,"abstract":"<p><strong>Background: </strong>Brain metastases (BM) constitute an increasing challenge in oncology due to their impact on neurological function, limited treatment options, and poor prognosis. BM occurs through extravasation of circulating tumor cells across the blood-brain barrier. However, the extravasation processes are still poorly understood. We here propose a brain colonization process which mimics infarction-like microenvironmental reactions, that are dependent on Angiopoietin-2 (Ang-2) and vascular endothelial growth factor (VEGF).</p><p><strong>Methods: </strong>In this study, intracardiac BM models were used, and cerebral blood microcirculation was monitored by 2-photon microscopy through a cranial window. BM formation was observed using cranial magnetic resonance, bioluminescent imaging, and postmortem autopsy. Ang-2/VEGF targeting strategies and Ang-2 gain-of-function (GOF) mice were employed to interfere with BM formation. In addition, vascular and stromal factors as well as clinical outcomes were analyzed in BM patients.</p><p><strong>Results: </strong>Blood vessel occlusions by cancer cells were detected, accompanied by significant disturbances of cerebral blood microcirculation, and focal stroke-like histological signs. Cerebral endothelial cells showed an elevated Ang-2 expression both in mouse and human BM. Ang-2 GOF resulted in an increased BM burden. Combined anti-Ang-2/anti-VEGF therapy led to a decrease in brain metastasis size and number. Ang-2 expression in tumor vessels of established human BM negatively correlated with survival.</p><p><strong>Conclusions: </strong>Our observations revealed a relationship between disturbance of cerebral blood microcirculation and brain metastasis formation. This suggests that vessel occlusion by tumor cells facilitates brain metastatic extravasation and seeding, while combined inhibition of microenvironmental effects of Ang-2 and VEGF prevents the outgrowth of macrometastases.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2084-2099"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141238350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Medulloblastoma in children with Fanconi anemia: Association with FA-D1/FA-N, SHH type and poor survival independent of treatment strategies.","authors":"Marthe Sönksen, Denise Obrecht-Sturm, Pablo Hernáiz Driever, Axel Sauerbrey, Norbert Graf, Udo Kontny, Christian Reimann, Mina Langhein, Uwe R Kordes, Rudolf Schwarz, Tobias Obser, Felix Boschann, Ulrich Schüller, Lea Altendorf, Tobias Goschzik, Torsten Pietsch, Martin Mynarek, Stefan Rutkowski","doi":"10.1093/neuonc/noae111","DOIUrl":"10.1093/neuonc/noae111","url":null,"abstract":"<p><strong>Background: </strong>The outcome of children with medulloblastoma (MB) and Fanconi Anemia (FA), an inherited DNA repair deficiency, has not been described systematically. Treatment is complicated by high vulnerability to treatment-associated side effects, yet structured data are lacking. This study aims to give a comprehensive overview of clinical and molecular characteristics of pediatric FA MB patients.</p><p><strong>Methods: </strong>Clinical data including detailed information on the treatment and toxicities of 6 previously unreported FA MB patients were supplemented with data of 16 published cases.</p><p><strong>Results: </strong>We identified 22 cases of children with FA and MB with clinical data available. All MBs with subgroup reporting were SHH-activated (n = 9), confirmed by methylation profiling in 5 patients. FA MB patients exclusively belonged to complementation groups FA-D1 (n = 16) or FA-N (n = 3). Patients were treated with postoperative chemotherapy only (50%) or radiotherapy (RT) ± chemotherapy (27%). Of 23% did not receive adjuvant therapy. Excessive treatment-related toxicities were frequent. Severe hematological toxicity occurred in 91% of patients treated with alkylating chemotherapy, while non-alkylating agents and RT were less toxic. Median overall survival (OS) was 1 year (95%CI: 0.3-1.8). 1-year-progression-free-survival (PFS) was 26.3% ± 10.1% and 1-year-OS was 42.1% ± 11.3%. Adjuvant therapy prolonged survival (1y-OS/1y-PFS 0%/0% without adjuvant therapy vs. 53.3% ± 12.9%/33.3 ± 12.2% with adjuvant therapy, P = .006/P = .086).</p><p><strong>Conclusions: </strong>MB in FA patients is strongly associated with SHH activation and FA-D1/FA-N. Despite the dismal prognosis, adjuvant therapy may prolong survival. Non-alkylating chemotherapy and RT are feasible in selected patients with careful monitoring of toxicities and dose adjustments. Curative therapy for FA MB-SHH remains an unmet medical need.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":"2125-2139"},"PeriodicalIF":16.4,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534319/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141451080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phase II Trial of Pathology-based Tripartite Treatment Stratification for Patients with CNS Germ Cell Tumors: A Long-term Follow-up Study.","authors":"Hirokazu Takami, Masao Matsutani, Tomonari Suzuki, Kazuhiko Takabatake, Takamitsu Fujimaki, Michinari Okamoto, Shigeru Yamaguchi, Masayuki Kanamori, Kenichiro Matsuda, Yukihiko Sonoda, Manabu Natsumeda, Toshiya Ichinose, Mitsutoshi Nakada, Ai Muroi, Eiichi Ishikawa, Masamichi Takahashi, Yoshitaka Narita, Shota Tanaka, Nobuhito Saito, Fumi Higuchi, Masahiro Shin, Yohei Mineharu, Yoshiki Arakawa, Naoki Kagawa, Shinji Kawabata, Masahiko Wanibuchi, Takeshi Takayasu, Fumiyuki Yamasaki, Kentaro Fujii, Joji Ishida, Isao Date, Keisuke Miyake, Yutaka Fujioka, Daisuke Kuga, Shinji Yamashita, Hideo Takeshima, Naoki Shinojima, Akitake Mukasa, Akio Asai, Ryo Nishikawa","doi":"10.1093/neuonc/noae229","DOIUrl":"https://doi.org/10.1093/neuonc/noae229","url":null,"abstract":"<p><strong>Background: </strong>A previous Phase II clinical trial, conducted from 1995 to 2003, evaluated CNS germ cell tumors (GCTs) using a three-group treatment stratification based on histopathology. The primary objective of the study was to assess the long-term efficacy of standardized treatment regimens, while the secondary objective focused on identifying associated long-term complications.</p><p><strong>Methods: </strong>Total 228 patients were classified into three groups for treatment: germinoma (n=161), intermediate prognosis (n=38), and poor prognosis (n=28), excluding one mature teratoma case. Treatment involved stratified chemotherapy regimens and varied radiation doses/coverage. Clinical data was retrospectively analyzed at a median follow-up of 18.5 years.</p><p><strong>Results: </strong>The treatment outcomes for germinoma, with or without syncytiotrophoblastic giant cell, were similar. The 10- and 20-year event-free survival rates for the germinoma, intermediate, and poor prognosis groups were 82/76/49% and 73/66/49%, respectively. Overall survival (OS) rates were 97/87/61% at 10 years and 92/70/53% at 20 years. Germinomas in the basal ganglia, treated without whole-brain radiation therapy (WBRT), frequently relapsed but were effectively managed with subsequent WBRT. Deaths in germinoma cases had varied causes, whereas deaths in the poor prognosis group were predominantly disease-related. Nineteen treatment-related complications were identified in 16 patients, with cumulative event rates of 1.9% at 10 years and 11.3% at 20 years. OS rates at 1 and 2 years post-relapse for tumors initially classified as germinoma, intermediate, and poor prognosis were 94/88/18% and 91/50/9%, respectively.</p><p><strong>Conclusions: </strong>Initial treatment intensity is crucial for managing non-germinomatous GCTs, while long-term follow-up for relapse and complications is imperative in germinomas. Irradiation extending beyond the immediate tumor site is essential for basal ganglia germinomas. Addressing relapse in non-germinomatous GCT remains a significant challenge.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy of 3D-TSE Sequence-based Radiosurgery in Prolonging Time to Distant Intracranial Failure: A Session-wise Analysis in a Histology-Diverse Patient Cohort.","authors":"Eyub Y Akdemir, Selin Gurdikyan, Muni Rubens, Kevin J Abrams, Charif Sidani, Margaret C Chaneles, Matthew D Hall, Robert H Press, D Jay Wieczorek, Ranjini Tolakanahalli, Alonso N Gutierrez, Omer Gal, Alonso La Rosa, Tugce Kutuk, Michael W McDermott, Yazmin Odia, Minesh P Mehta, Rupesh Kotecha","doi":"10.1093/neuonc/noae232","DOIUrl":"https://doi.org/10.1093/neuonc/noae232","url":null,"abstract":"<p><strong>Background: </strong>Stereotactic radiosurgery (SRS) for patients with brain metastases (BM) is associated with a risk of distant intracranial failure (DIF). This study evaluates the impact of integrating dedicated 3D-TSE sequences to MPRAGE in BM detection and DIF prolongation in a histology-agnostic patient cohort.</p><p><strong>Methods: </strong>The study population included adults treated with SRS from February 2019 to January 2024 who underwent MPRAGE alone or dual-sequence with the addition of 3D-TSE starting from February 2020. Median times to DIF were estimated using the Kaplan-Meier method.</p><p><strong>Results: </strong>The 216 study patients who underwent 332 SRS courses for 1456 BM imaged with MPRAGE and 3D-TSE (primary cohort) were compared to a control cohort (92 patients, 135 SRS courses, 462 BM). In the session-wise analysis, the median time to DIF between the cohorts was significantly prolonged in the primary vs. control cohorts (11.4 vs. 6.8 months, p=0.029), more pronounced in the subgroups with 1-4 metastases (14.7 vs. 8.1 months, p=0.008) and with solitary BM (36.4 vs. 10.9 months, p=0.001). While patients relapsing on immunotherapy or targeted therapy did not significantly benefit from 3D-FSE (7.2 vs. 5.7 months, p=0.280), those who relapsed on chemotherapy or who were off systemic therapy (including synchronous metastases) exhibited a trend towards longer time to DIF with 3D-TSE integration (14.7 vs. 7.9 months, p=0.057).</p><p><strong>Conclusions: </strong>Implementing 3D-TSE sequences into SRS practice increases BM detection across all patients and translates into clinical relevance by prolonging time to DIF, particularly in those with limited intracranial disease and those not receiving CNS-active agents.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EVA1-Antibody Drug Conjugate is a new therapeutic strategy for eliminating glioblastoma-initiating cells.","authors":"Jiahui Hou, Tamami Uejima, Miho Tanaka, You Lee Son, Kazuharu Hanada, Mutsuko Kukimoto-Niino, Shigeru Yamaguchi, Shigeru Hashimoto, Shigeyuki Yokoyama, Toshitada Takemori, Takashi Saito, Mikako Shirouzu, Toru Kondo","doi":"10.1093/neuonc/noae226","DOIUrl":"10.1093/neuonc/noae226","url":null,"abstract":"<p><strong>Background: </strong>The discovery of glioblastoma (GBM)-initiating cells (GICs) has impacted GBM research. These cells are not only tumorigenic, but also exhibit resistance to radiotherapy and chemotherapy. Therefore, it is crucial to characterize GICs thoroughly and identify new therapeutic targets. In a previous study, we successfully identified Epithelial V-like antigen 1 (EVA1) as a novel functional factor specific to GICs.</p><p><strong>Methods: </strong>Hybridoma cells were generated by immunizing BALB/c mice with EVA1-Fc fusion protein. The reactivity of the supernatant from these hybridoma cells was examined using EVA1-overexpressing cells and GICs. Candidate antibodies were further selected using Biacore surface plasmon resonance analysis and two cytotoxicity assays, antibody-dependent cell cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Among the antibodies, the cytotoxicity of the B2E5-antibody drug conjugate (B2E5-ADC) was evaluated by both adding it to cultured GICs and injecting it into GIC tumor-bearing brains.</p><p><strong>Results: </strong>B2E5 demonstrated a high affinity for human EVA1 and effectively killed both EVA1-expressing cell lines and GICs in culture through ADCC and CDC. B2E5-ADC also exhibited strong cytotoxicity to GICs in culture and prevented their tumorigenesis in the brain when administered intracranially to the tumor-bearing brain.</p><p><strong>Conclusion: </strong>Our data indicate that B2E5-ADC is a new and promising therapeutic strategy for GBM.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imaging PD-L1 in the brain-Journey from the lab to the clinic.","authors":"Dawoud Dar, Magdalena Rodak, Chiara Da Pieve, Izabela Gorczewska, Gitanjali Sharma, Ewa Chmielik, Marcin Niedbala, Pawel Bzowski, Andrea d'Amico, Barbara Bobek-Billewicz, Elzbieta Nowicka, Rafal Tarnawski, Wojciech Kaspera, Gabriela Kramer-Marek","doi":"10.1093/neuonc/noae190","DOIUrl":"10.1093/neuonc/noae190","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICPIs) have proven to restore adaptive anti-tumor immunity in many cancers; however, no noteworthy therapeutic schedule has been established for patients with glioblastoma (GBM). High programmed death-ligand 1 (PD-L1) expression is associated with immunosuppressive and aggressive phenotypes in GBM. Presently, there is no standardized protocol for assessing PD-L1 expression levels to select patients and monitor their response to ICPI therapy. The aim of this study was to investigate the use of 89Zr-DFO-Atezolizumab to image the spatio-temporal distribution of PD-L1 in preclinical mouse models and in patients with newly diagnosed GBM treated with/without neoadjuvant Pembrolizumab.</p><p><strong>Methods: </strong>The immunoreactivity, binding affinity, and specificity of 89Zr-DFO-Atezolizumab were confirmed in vitro. Mice-bearing orthotopic GBM tumors or patients with newly diagnosed GBM treated with/without Pembrolizumab were intravenously injected with 89Zr-DFO-Atezolizumab, and PET/CT images were acquired 24, 48, and 72 hours in mice and at 48 and 72 post-injection in patients. Radioconjugate uptake was quantified in the tumor and healthy tissues. Ex vivo immunohistochemistry (IHC) and immunophenotyping were performed on mouse tumor samples or resected human tumors.</p><p><strong>Results: </strong>89Zr-DFO-Atezolizumab was prepared with high radiochemical purity (RCP > 99%). In vitro cell-associated radioactivity of 89Zr-DFO-Atezolizumab corroborated cell line PD-L1 expression. PD-L1 in mouse GBM tumors was detected with high specificity using 89Zr-DFO-Atezolizumab and radioconjugate uptake correlated with IHC. Patients experienced no 89Zr-DFO-Atezolizumab-related side effects. High 89Zr-DFO-Atezolizumab uptake was observed in patient tumors at 48 hours post-injection, however, the uptake varied between patients treated with/without Pembrolizumab.</p><p><strong>Conclusions: </strong>89Zr-DFO-Atezolizumab can visualize distinct PD-L1 expression levels with high specificity in preclinical mouse models and in patients with GBM, whilst complementing ex vivo analysis.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sleep disorders associated with cranial radiation - a systematic review.","authors":"Maeve Pascoe, Emma Byrne, Amanda King, Diane Cooper, Nancy Foldvary-Schaefer, Reena Mehra, Justin Lathia, Mark R Gilbert, Terri S Armstrong","doi":"10.1093/neuonc/noae174","DOIUrl":"https://doi.org/10.1093/neuonc/noae174","url":null,"abstract":"<p><strong>Background: </strong>Radiation is standard-of-care treatment for primary brain tumors but may have profound effects on sleep that have not yet been fully characterized. This systematic review aims to further our understanding of radiation therapy on risk of development of sleep disorders in patients with primary brain tumors (PBTs), as well as potential opportunities for prevention and treatment.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, and Web of Science was performed (last Jan 2024) with predefined inclusion (PBT patients, radiation therapy, somnolence/circadian disruption) and exclusion (reviews/abstracts/cases/chapters, non-PBT cancer, lack of radiation) criteria, yielding 267 papers initially and 38 studies included. Data extraction and analysis (descriptive statistics, individual study summary) focused on incidence of sleep disturbances, radiation types/doses, and pharmacologic interventions. Risk of bias assessment was conducted with Effective Public Health Practice Project's Quality Assessment Tool for Quantitative Studies.</p><p><strong>Results: </strong>The included 38 studies (n=2948 patients) demonstrated high incidence of sleep disturbances in patients with primary brain tumors throughout radiation therapy, but primarily from the end of radiation to 6 months after. Sleep symptoms were associated with radiation (dose-dependent), and pharmacotherapies were helpful in patients with formal sleep disorder diagnoses. Terminology and incidence reporting of sleep symptoms are inconsistent, and many studies had high risk of bias.</p><p><strong>Conclusions: </strong>This systematic review highlights the ongoing challenges with sleep symptoms/disorders related to cranial irradiation treatment in the primary brain tumor population. Further investigations on the interconnectedness of sleep disturbance constructs and possible pharmacotherapies to alleviate symptoms are warranted.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142522569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prospective Longitudinal Analysis of Physiologic MRI-based Tumor Habitat Predicts Short-term Patient Outcomes in IDH-wildtype Glioblastoma.","authors":"Hye Hyeon Moon, Ji Eun Park, Nak Young Kim, Seo Young Park, Young-Hoon Kim, Sang Woo Song, Chang Ki Hong, Jeong Hoon Kim, Ho Sung Kim","doi":"10.1093/neuonc/noae227","DOIUrl":"https://doi.org/10.1093/neuonc/noae227","url":null,"abstract":"<p><strong>Background: </strong>This study validates MRI-based tumor habitats in predicting time-to-progression (TTP), overall survival (OS), and progression site in isocitrate dehydrogenase (IDH)-wildtype glioblastoma patients.</p><p><strong>Methods: </strong>Seventy-nine patients were prospectively enrolled between January 2020 and June 2022. MRI, including diffusion-weighted and dynamic susceptibility contrast imaging, were obtained immediately post-operation and at three serial timepoints. Voxels from cerebral blood volume and apparent diffusion coefficient maps were grouped into three habitats (hypervascular cellular, hypovascular cellular, and nonviable tissue) using k-means clustering. Pre-defined cutoffs for increases in hypervascular and hypovascular cellular habitat were applied to calculate the habitat risk score. Associations between spatiotemporal habitats, habitat risk score, TTP, and OS were investigated using Cox proportional hazards modeling. Habitat risk score was compared to tumor volume using time-dependent receiver operating characteristics analysis. Progression sites were matched with spatial habitats.</p><p><strong>Results: </strong>Increases in hypervascular and hypovascular cellular habitats and habitat risk scores were associated with shorter TTP and OS (all p < .05). Hypovascular cellular habitat and habitat risk scores 1 and 2 independently predicted TTP (hazard ratio [HR], 4.14; p=.03, HR, 4.51; p=.001 and HR, 10.02; p<.001, respectively). Hypovascular cellular habitat and habitat risk score 2 independently predicted OS (HR, 4.01, p=.003; and HR, 3.27, p<.001, respectively). Habitat risk score outperformed tumor volume in predicting TTP (12-month AUC, 0.762 vs. 0.646, p=.048). Hypovascular cellular habitat predicted progression sites (mean Dice index: 0.31).</p><p><strong>Conclusions: </strong>Multiparametric physiologic MRI-based spatiotemporal tumor habitats and habitat risk scores are useful biomarkers for early tumor progression and outcomes in IDH-wildtype glioblastoma patients.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504991","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining Risk Features for Medulloblastoma in the Molecular Era.","authors":"Nicholas G Gottardo, Amar Gajjar","doi":"10.1093/neuonc/noae223","DOIUrl":"https://doi.org/10.1093/neuonc/noae223","url":null,"abstract":"","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504988","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GDH1-catalytic glutaminolysis feedback activate EGFR/PI3K/AKT pathway and reprogram glioblastoma metabolism.","authors":"Rui Yang, Guanghui Zhang, Zhen Meng, Li Wang, Yanping Li, Haibin Li, Siyuan Yan, Xiaonan Wei, Shanshan Wang, Hongjuan Cui","doi":"10.1093/neuonc/noae222","DOIUrl":"https://doi.org/10.1093/neuonc/noae222","url":null,"abstract":"<p><strong>Background: </strong>Glutamine is an important nutriment for cancer cell growth that provides biological sources for nucleic acid and fatty acid synthesis, but the role of glutaminolysis in signal transduction and glioblastoma (GBM) progression remains little known.</p><p><strong>Methods: </strong>Knockdown and overexpression cells were obtained to explore the functional roles of GDH1 in cell proliferation, tumor formation and aerobic glycolysis. RNA-seq, Chromatin immunoprecipitation, luciferase assay and western blot were performed to verify the regulation of EGFR-AKT pathway by the glutamate dehydrogenase 1 (GDH1, also known as GLUD1) and KDM6A. Metabolite-level measurements and Seahorse Assay were performed to assess the functional role of GHD1 in reprogramming glycolysis.</p><p><strong>Results: </strong>Here, we report that GDH1 catalytic glutaminolysis is essential for GBM cell line proliferation and brain tumorigenesis even in high-glucose conditions. Glutamine is metabolized through glutaminolysis to produce α-ketoglutarate (α-KG). We demonstrate that glutamine in combination with leucine activates mammalian TORC1 by enhancing glutaminolysis and α-KG production. α-KG increases the transcription of PDPK1 by reducing the suppressive histone modification H3K27me3, and then promotes the activation of PI3K/AKT/mTOR pathway. This transcriptional activation induced by α-KG requires histone demethylase KDM6A, which is a 2-oxoglutarate oxygenase that plays important roles in converting α-KG to succinate. Furthermore, we show that GDH1-catalytic glutaminolysis also increases the expression of HK2 and promotes glycolysis in high-glucose condition dependent on KDM6A-mediated demethylation of H3K27.</p><p><strong>Conclusion: </strong>These findings suggest a novel function of glutaminolysis in regulation of signal transduction and metabolism reprograming, provide further evidence for unique role of glutaminolysis in GBM progression.</p>","PeriodicalId":19377,"journal":{"name":"Neuro-oncology","volume":" ","pages":""},"PeriodicalIF":16.4,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}