Journal of Neuro-Oncology最新文献

{"title":"The association between postoperative photon radiotherapy dose and disease control and salvage treatment in pediatric and adolescent ependymoma: a multi-institutional investigation.","authors":"Kevin X Liu, Mia Salans, Teresa P Easwaran, Christina Phuong, Kee Kiat Yeo, Hesham Elhalawani, Paul J Catalano, Kathryn Dusenbery, Karen J Marcus, Stephanie A Terezakis, Daphne A Haas-Kogan, Steve E Braunstein","doi":"10.1007/s11060-025-04975-5","DOIUrl":"https://doi.org/10.1007/s11060-025-04975-5","url":null,"abstract":"<p><strong>Purpose: </strong>We characterized the association between photon radiation dose (< 59.4 versus ≥ 59.4 Gy) and outcomes in intracranial ependymoma. We also examined factors associated with survival after relapse.</p><p><strong>Methods: </strong>This multi-institutional retrospective study included patients age ≤ 21 years who received postoperative definitive-intent photon radiotherapy for posterior fossa ependymoma between 1997 and 2021. Clinical characteristics were obtained from medical records. Five-year overall (OS) and progression-free (PFS) survival were estimated using the Kaplan-Meier method. Factors associated with progression after radiotherapy, including dose < 59.4 versus ≥ 59.4 Gy, were analyzed using Fine and Gray's proportional subhazards model. Factors associated with post-relapse survival were explored using the Cox proportional-hazards model.</p><p><strong>Results: </strong>We identified 45 patients meeting inclusion criteria; 48.9% received ≥ 59.4 Gy. There was no difference in 5-year OS or PFS between those who received < 59.4 Gy versus ≥ 59.4 (OS 49.0% vs. 82.9%, p = 0.11; PFS 36.4% vs. 63.9%, p = 0.08); however, there was a trend towards worse 5-year OS and PFS among patients with grade 2 ependymoma who received < 59.4 Gy (OS 48.8% vs. 88.9%, p = 0.06, PFS 40.0% vs. 83.1%, p = 0.08). Only age > 4 years at diagnosis (subdistribution hazard ratio [SHR]: 0.40, p = 0.03) was associated lower risk of progression. Following radiotherapy, 24 patients relapsed. Receipt of salvage systemic therapy was associated with worse post-relapse OS on multivariable analysis (HR = 2.84, p = 0.04).</p><p><strong>Conclusion: </strong>Underlying biological factors such as age and molecular subtype may hold greater prognostic significance than radiation dose in pediatric ependymoma. Regardless, recurrences are common and outcomes remain poor. Further research into optimal management of relapsed disease is critical.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492411","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RAPID, a multicenter collaboration for the study of craniopharyngiomas: challenges, opportunities, and future directions.","authors":"Michael Karsy, Varun R Kshettry, Andrew S Little","doi":"10.1007/s11060-025-04981-7","DOIUrl":"https://doi.org/10.1007/s11060-025-04981-7","url":null,"abstract":"","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of LSR suppresses glioma proliferation and invasion via regulating FOXO3a.","authors":"Jinlong Zhu, Tong Wang, Xi Liu, Ting Lu, Jianwei Zhuo, Xiangying Li, Zhengquan Yu, Gang Cui, Haitao Shen","doi":"10.1007/s11060-025-04976-4","DOIUrl":"https://doi.org/10.1007/s11060-025-04976-4","url":null,"abstract":"<p><strong>Purpose: </strong>Gliomas, the most prevalent type of central nervous system tumors, currently lack effective therapeutic options. Lipolysis-stimulated lipoprotein receptors (LSR) have been implicated in tumor development and progression. This study aims to investigate the influence of LSR on gliomas and elucidate the underlying mechanisms.</p><p><strong>Methods: </strong>We analyze LSR expression in gliomas and its association with patient prognosis using bioinformatics tools. Western blotting and immunohistochemistry revealed differential expression of LSR across different grades of glioma. The effects of LSR on glioma cell proliferation and invasion are evaluated through a series of cellular assays. Subcutaneous xenografts in nude mice are utilized to assess the impact of LSR on gliomas in vivo. Additionally, western blotting is employed to detect changes in protein levels related to the FOXO3a signaling pathway following LSR overexpression.</p><p><strong>Results: </strong>LSR expression is higher in tissues from low-grade gliomas compared to those from glioblastomas. Patients with low LSR expression exhibit poorer prognoses. Overexpression of LSR inhibit glioma cell proliferation and invasion. The protein levels of PCNA, Cyclin D1, MMP2, and MMP9 are significantly decreased in the OE-LSR group. Tumor volume is reduced in nude mice injected subcutaneously with LSR-overexpressing glioma cells. Overexpression of LSR increases nuclear FOXO3a level while reduces p-FOXO3a and p-14-3-3 levels. Knockdown of FOXO3a reverse the inhibitory effects of LSR overexpression on glioma cell proliferation and invasion.</p><p><strong>Conclusion: </strong>Low LSR expression is associated with adverse prognosis in glioma patients. By modulating FOXO3a, LSR overexpression suppresses glioma cell proliferation and invasion.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic revalidation of RANO categories for extent of resection in glioblastoma: a reconstruction of individual patient data.","authors":"Johannes Wach, Martin Vychopen, Erdem Güresir","doi":"10.1007/s11060-025-04950-0","DOIUrl":"https://doi.org/10.1007/s11060-025-04950-0","url":null,"abstract":"<p><strong>Background: </strong>The RANO classification for glioblastoma defines resection categories based on volumetric tumor assessments, aiming to standardize outcomes related to extent of resection (EOR). This study revalidates the prognostic impact of RANO classes by reconstructing individual patient data (IPD).</p><p><strong>Methods: </strong>A systematic review and meta-analysis were performed, including three studies comprising 580 glioblastoma patients. Included studies reported or allowed conversion to RANO classes for glioblastoma resection extent, with detailed OS data and numbers at risk. Overall survival (OS) data were extracted from Kaplan-Meier survival curves, and IPD were reconstructed using Digitizelt and the R package IPDfromKM. Survival analyses were conducted using Kaplan-Meier estimates and Cox regression models.</p><p><strong>Results: </strong>Median follow-up was 15.6 months (IQR: 10.1-28.8). Patients undergoing supramaximal resection (RANO class 1, n = 163) had the highest median OS (35.6 months; 95% CI: 30.9-40.4), significantly outperforming non-class 1 resections (median OS: 13.9 months; 95% CI: 13.0-14.7; p < 0.001). Subgroup analysis revealed superior OS for class 2a (19.0 months) over class 2b (14.1 months; p < 0.001), while class 3 and 4 resections demonstrated progressively poorer outcomes. Hazard ratios consistently favored class 1 versus all other classes (HR: 0.28; 95% CI: 0.23-0.37).</p><p><strong>Conclusions: </strong>Supramaximal (class 1) resection provides a significant survival benefit in glioblastoma, underscoring its critical role in surgical management. The RANO classification stratifies resection outcomes effectively, supporting its use as a prognostic tool. These findings advocate for resection strategies targeting maximal tumor removal.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurocognitive function in lower grade glioma patients selected for proton radiotherapy: real-world data from a prospective cohort study.","authors":"Hiska L van der Weide, Anne M Buunk, Femke F Siebenga, Johannes A Langendijk, Agata Bannink-Gawryszuk, Ingeborg Bosma, Roelien H Enting, Anouk van der Hoorn, Hanne-Rinck Jeltema, Michiel Wagemakers, Rob J M Groen, Annemiek M E Walenkamp-Hageman, Janine Nuver, Miranda C A Kramer, Jacoba M Spikman","doi":"10.1007/s11060-025-04973-7","DOIUrl":"https://doi.org/10.1007/s11060-025-04973-7","url":null,"abstract":"<p><strong>Purpose: </strong>To determine neurocognitive function (NCF) profiles of patients with lower grade glioma (LGG) eligible to undergo proton radiotherapy (PRT), and how these relate to clinical and radiological characteristics. PRT is offered to those patients for whom sparing of NCF is considered important given their favorable prognosis. To date it is unknown to which extent their NCF profiles are favorable as well.</p><p><strong>Methods: </strong>A consecutive cohort of 151 LGG patients eligible for PRT according to prevailing Dutch criteria, referred between 2018 and 2023, were assessed with standardized neuropsychological tests prior to PRT. Scores were compared to norm-scores. Composite scores were calculated for the total NCF and 6 separate cognitive domains, and profiles were related to tumor location. Clinical and radiological factors characterizing overall NCF impaired patients were investigated, comparing 3 definitions for impairment.</p><p><strong>Results: </strong>Patients had on average significantly lower NCF than their norm-group, but interindividual variability was large. For 100/151 patients (66.2%), all cognitive domains were intact, whereas 15/151 patients (9.9%) displayed multiple domain impairments. Poorer NCF was related to right-sided LGG laterality, larger PRT target volume, no Wait & Scan policy, worse neurological function and worse radiological indices (Fazekas and global cortical atrophy, respectively). LGG involvement of the left temporal and occipital lobes was associated with, respectively, lower verbal memory and processing speed.</p><p><strong>Conclusion: </strong>Prior to PRT, the majority of selected LGG patients display favorable NCF profiles. However, a subgroup showed NCF impairments, with multiple relevant clinical and radiological covariates.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Papillary craniopharyngioma management in the era of BRAF and MEK inhibition.","authors":"Mark Damante, Santino Cua, Daniel Kreatsoulas, Pierre Giglio, Luma Ghalib, Chandrima Biswas, Kyle C Wu, Daniel M Prevedello","doi":"10.1007/s11060-025-04969-3","DOIUrl":"https://doi.org/10.1007/s11060-025-04969-3","url":null,"abstract":"<p><strong>Purpose: </strong>Papillary craniopharyngioma is a rare entity, demonstrating BRAF-V600E mutations in approximately 95% of patients. Recently, a phase 2 trial of patients treated with surgery and BRAF/MEKi demonstrated 91% reduction in residual tumor volume. This study allowed for additional treatments at the discretion of the treatment team without reporting subsequent rates of endocrinopathy or visual decline. We aimed to evaluate the possibility of employing BRAF/MEKi without the need for adjuvant radiotherapy therapies.</p><p><strong>Methods: </strong>A retrospective report of two patients treated with resection and BRAF/MEKi without additional treatment were analyzed. Patient demographics, treatment characteristics, pre- and post-treatment radiographic volumes, adverse events, and endocrinologic and visual outcomes, were recorded and analyzed.</p><p><strong>Results: </strong>Two patients underwent subtotal resection followed by BRAF/MEKi without adjuvant treatment. Mean length of BRAF therapy was 21.4 months and MEKi therapy was 12.94 months. Mean preoperative nodule volume was 0.33 cm [3] and 2.29 cm [3] and cystic volume was 5.04 cm [3] and 6.18 cm [3] in case 1 and case 2, respectively. Neither patient received radiation. Grade 3 cardiotoxicity developed in case 1 after 6.5 months, with function recovering completely following discontinuation of MEKi. BRAF therapy was discontinued electively after 23.5 months. The second patient remains on dual inhibition therapy without toxicity. For these cases, post-treatment nodule volumes are 0.07 cm [3] (98.4% reduction) and 0.04 cm [3] (99.2% reduction), respectively, and cystic volume 0.0 cm [3] in both patients. Progression free survival is 100% with a mean follow up of 36-months.</p><p><strong>Conclusions: </strong>Utilizing surgery and BRAF/MEKi without adjuvant radiation, we demonstrate excellent disease control with reversible toxicity. Avoiding additional treatments may spare vital functions and unnecessary procedures.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The skull base chordoma patient reported outcome survey (sbCPROS): a patient-centered, disease-specific tool for assessing quality of life in chordoma patients.","authors":"Saket Myneni, Linda Tang, Hanan Akbari, Raquel Mayne, A Karim Ahmed, Foad Kazemi, Nicolas Dea, Nathan T Zwagerman, Shirley Y Su, Garret Choby, Eric W Wang, Kristin J Redmond, Erin L McKean, Carl H Snyderman, Nicholas R Rowan, Debraj Mukherjee","doi":"10.1007/s11060-025-04974-6","DOIUrl":"https://doi.org/10.1007/s11060-025-04974-6","url":null,"abstract":"<p><strong>Purpose: </strong>Chordomas are rare malignant tumors arising from the embryological notochord that present most frequently in the lumbosacral spine, followed by the skull base, with an overall 1/1,000,000 incidence. These tumors and their treatment significantly affect quality of life (QOL) due to intricate anatomical locations and aggressive treatment regimens. Despite these challenges, there are currently no disease-specific patient-reported outcome (PRO) surveys for chordomas. We aimed to develop a tool to assess QOL in patients with skull base chordomas (sbCs).</p><p><strong>Methods: </strong>Twenty-seven patients who underwent sbC resection were interviewed on QOL throughout their care. Grounded-theory analysis of interview transcripts generated 7 themes. We developed an initial survey with 79 items from existing general and anatomic-specific QOL assessment tools addressing these themes. Ten chordoma providers and 10 new patients completed an anonymous Qualtrics survey, rating items' relevance on a 5-point Likert scale to validate survey content. An a priori cutoff of > 3.0 was used for significant relevance. Mean relevance scores for each item were compared between providers and patients as well as between skull base respondents and 5 control patients with lumbar spine and sacral chordomas, using two-sided Mann-Whitney U-tests.</p><p><strong>Results: </strong>Seventy-four items reached the relevance threshold. These were consolidated to create the final 42-item Skull Base Chordoma Patient Reported Outcome Survey (sbCPROS). Providers significantly overvalued items related to the themes of pain (73%), sleep changes (60%), and sensory & motor symptoms (43%) relative to patients. Ten items were more relevant to skull base patients than patients with spinal tumors (p < 0.05).</p><p><strong>Conclusion: </strong>The authors developed a novel patient-centered, disease-specific PRO instrument to assess change in QOL for sbC patients over time. sbCPROS may provide significant insight into the delivery of high quality care for patients with sbCs and guide patient-physician discussions about care decision-making.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143458383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distribution and failure patterns of primary central nervous system lymphoma related to the hippocampus: implications for hippocampal avoidance irradiation.","authors":"Hyejo Ryu, Xue Li, Tae Hoon Lee, Tae Min Kim, Seung Hong Choi, Chul-Kee Park, Soon Tae Lee, Sung-Hye Park, Jae-Kyung Won, Bum-Sup Jang, Il Han Kim, Joo Ho Lee","doi":"10.1007/s11060-025-04965-7","DOIUrl":"https://doi.org/10.1007/s11060-025-04965-7","url":null,"abstract":"<p><strong>Purpose: </strong>Hippocampal injury from WBRT contributes to neurocognitive decline in brain malignancy patients. HA-WBRT may mitigate this by reducing hippocampal radiation exposure, but its feasibility in PCNSL remains unassessed regarding hippocampal involvement and failure rates. This study evaluates hippocampal involvement at diagnosis and after treatment in PCNSL patients.</p><p><strong>Materials and methods: </strong>We conducted a retrospective analysis of 278 immunocompetent PCNSL patients diagnosed between 2000 and 2021. Following high-dose methotrexate-based induction chemotherapy, patients either received consolidation therapy, including RT, cytarabine alone, or autologous stem cell transplantation or underwent observation. Hippocampus was outlined on T1 MRI images and expanded by a 5 mm margin to create the hippocampal avoidance region (HAR). Hippocampal failure was defined as recurrence or progression at HAR. The median follow-up was 38.7 months (range 3.1-239.4 months).</p><p><strong>Results: </strong>Of the 278 patients diagnosed with PCNSL, 39.9% presented initial lesions at HAR. After induction therapy, 212 evaluable patients received consolidation treatments or observation. Intracranial failures occurred in 47.6% (n = 101), with 66.3% (n = 67) occurring outside the HAR and 33.7% (n = 34) inside the HAR. Unifocal disease (HR 0.61, 95% CI 0.39-0.96, p = 0.025) was associated with a lower risk of hippocampal failures, while initial HAR involvement significantly increased the risk (HR 2.26, 95% CI 1.18-4.47, p = 0.018). Patients with unifocal disease outside the HAR had the lowest 3-year hippocampal failure rate (6.2%). RT that included the hippocampus did not significantly affect hippocampal failure rates in patients without initial HAR lesions (p = 0.282), with three-year rates of 9.2 vs. 14.6% for other treatments. However, among patients with initial HAR involvement, RT including the hippocampus significantly reduced hippocampal failure rates compared to other approaches (p = 0.002). Hippocampal failure rates were comparable, with conventional WBRT at 14.6% and HA-WBRT at 19% in patients without initial HAR lesions (p = 0.734).</p><p><strong>Conclusion: </strong>The routine application of the HA-WBRT strategy is not supported due to the high risk of hippocampal failures in general and requires further investigation to establish its feasibility and safety in well-defined subgroups. Our results suggest that the HA-WBRT strategy could be evaluated for select PCNSL patients with unifocal lesions or those located outside the HAR.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143449365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Establishment of xenografts and methods to evaluate tumor burden for the three most frequent subclasses of pediatric-type diffuse high grade gliomas.","authors":"Leire Balaguer-Lluna, Nagore G Olaciregui, Rosario Aschero, Claudia Resa-Pares, Sonia Paco, Maria Cuadrado-Vilanova, Victor Burgueño, Merce Baulenas-Farres, Carles Monterrubio, Alejandro Manzanares, Eva Rodríguez, Cinzia Lavarino, Jaume Mora, Angel M Carcaboso","doi":"10.1007/s11060-025-04954-w","DOIUrl":"https://doi.org/10.1007/s11060-025-04954-w","url":null,"abstract":"<p><strong>Purpose: </strong>We aimed to expand and refine the experimental models for pediatric-type diffuse high grade gliomas (pHGG) and the methods to follow up disease progression in mouse pHGG xenografts.</p><p><strong>Methods: </strong>Using whole exome sequencing and immunoassays we characterized pHGG primary cultures and xenografts established at hospital SJD Barcelona. We obtained tumor samples and serial CSF samples from mouse xenografts. To assess tumor progression, we evaluated: (1) mouse weight, (2) human cell counts in brain paraffin sections, and (3) tumor DNA amount, quantified through droplet digital polymerase chain reaction (ddPCR) in paraffin sections and cerebrospinal fluid (CSF).</p><p><strong>Results: </strong>We established 15 experimental models of three pHGG subclasses, four of which engrafted in mice. Xenografts HSJD-DIPG-007 and HSJD-DMG-005 are diffuse midline glioma (DMG) H3 K27-altered, HSJD-GBM-002 is an H3 G34-mutant diffuse hemispheric glioma, and HSJD-GBM-001 is an H3-wildtype and IDH-wildtype pHGG. ddPCR quantification of human H3F3A K27M, H3F3A G34R, and ACVR1 R206H in paraffin samples is linear and sufficiently sensitive. We required a preamplification step to detect H3F3A K27M in CSF. In HSJD-DIPG-007 xenografts, human cell counts correlated with H3F3A amounts in paraffin for the whole engraftment period. Weight loss correlated with human cell counts and H3F3A amounts in paraffin. Serial collection of CSF was feasible, but H3F3A amounts in the CSF correlated only with weight loss.</p><p><strong>Conclusion: </strong>The developed methods contribute to the preclinical field of pHGG and introduce for the first time the concept of liquid biopsy in mice, which still needs improvement regarding its use as a preclinical biomarker.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T-type calcium channels regulate medulloblastoma and can be targeted for therapy.","authors":"Collin J Dube, Michelle Lai, Ying Zhang, Shekhar Saha, Ulas Yener, Farina Hanif, Kadie Hudson, Myron K Gibert, Pawel Marcinkiewicz, Yunan Sun, Tanvika Vegiraju, Esther Xu, Aditya Sorot, Rosa I Gallagher, Julia D Wulfkuhle, Ashley Vernon, Lily Dell'Olio, Rajitha Anbu, Elizabeth Mulcahy, Benjamin Kefas, Fadila Guessous, Emanuel F Petricoin, Roger Abounader","doi":"10.1007/s11060-025-04967-5","DOIUrl":"10.1007/s11060-025-04967-5","url":null,"abstract":"<p><strong>Purpose: </strong>The goal of this study was to investigate the role and therapeutic targeting of T-type calcium channels in medulloblastoma, a common and deadly pediatric brain tumor that arises in the cerebellum.</p><p><strong>Methods: </strong>T-type calcium channel expression was assessed in publicly available bulk and single cell RNA-seq datasets. The effects of T-type calcium channel blocker mibefradil on cell growth, death and invasion were assessed with cell counting, alamar blue, trypan blue and transwell assays. Proteomic-based drug target and signaling pathway mapping was performed with Reverse Phase Protein Arrays (RPPA). Co-expression modules of single cell RNA-seq data were generated using high dimensional weighted gene co-expression network analysis (hdWGCNA). Orthotopic xenografts were used for therapeutic studies with the T-Type calcium channel blocker mibefradil.</p><p><strong>Results: </strong>T-type calcium channels were upregulated in more than 30% of medulloblastoma tumors and patients with high expression associated with a worse prognosis. T-type calcium channels had variable expression across all the subgroups of medulloblastoma at the bulk RNA-seq and single-cell RNA-seq level. Mibefradil treatment or siRNA mediated silencing of T-type calcium channels inhibited tumor cell growth, viability and invasion. RPPA-based protein/phosphoprotein signal pathway activation mapping of T-type calcium channel inhibition and single cell hdWGCNA identified altered cancer signaling pathways. Oral administration of mibefradil inhibited medulloblastoma xenograft growth and prolonged animal survival.</p><p><strong>Conclusion: </strong>Our results represent a first comprehensive multi-omic characterization of T-type calcium channels in medulloblastoma and provide preclinical data for repurposing mibefradil as a treatment strategy for these relatively common pediatric brain tumors.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}