Journal of Neuro-Oncology最新文献

{"title":"Treatment-induced ripple effect: a systematic review exploring the abscopal phenomenon in Glioblastoma multiforme.","authors":"Ali Haider Bangash, Prabhat Poudel, Khalid M Alshuqayfi, Mudassir Ahmed, Oluwaseun O Akinduro, Walid Ibn Essayed, Afshin Salehi, Rafael De la Garza Ramos, Reza Yassari, Harminder Singh, Jason P Sheehan, Yoshua Esquenazi","doi":"10.1007/s11060-024-04912-y","DOIUrl":"10.1007/s11060-024-04912-y","url":null,"abstract":"<p><strong>Purpose: </strong>This systematic review aimed to collate and synthesize the available literature on the abscopal effect in Glioblastoma multiforme (GBM) neoplasms, focusing on the reported biochemical mechanisms driving the abscopal effect.</p><p><strong>Methods: </strong>A systematic search was conducted in PubMed, Cochrane Database of Systematic Reviews, and Epistemonikos from inception to May 1, 2023. Studies exploring the abscopal effect in GBM were included. The Clinical Relevance Assessment of Animal Preclinical research (RAA) tool was used to assess methodological quality of preclinical studies. Data on preclinical models, biochemical mechanisms, and outcomes were extracted and synthesized systrmatically.</p><p><strong>Results: </strong>Out of a total of 7 studies, five preclinical studies met the inclusion criteria. The studies utilized various in vivo mouse models, including bilateral tumor models and immunohumanized mice. Key biochemical mechanisms identified included immunogenic cell death, danger-associated molecular pattern release, macrophage activation, and enhanced T cell responses. Combinatorial approaches involving oncolytic virotherapy, nanoparticle-based treatments, radiation therapy, and immune checkpoint inhibitors showed promise in inducing abscopal effects. Significant tumor growth inhibition and improved survival were reported in treated animals. However, the RAA analysis highlighted concerns regarding research transparency and internal validity across studies.</p><p><strong>Conclusions: </strong>This systematic review highlighted the potential of the abscopal effect in GBM, demonstrating its ability to enhance anti-tumor immune responses both locally and systemically. The synergistic effects of combinatorial approaches showed promise for improving outcomes. However, the low methodological quality of existing studies underscored the need for more rigorous preclinical research. Future studies should focus on improving research transparency, exploring the abscopal effect in other primary CNS neoplasms, and translating these findings into clinical trials to assess safety and efficacy in humans.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"77-87"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854465","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":"Bevacizumab exerts dose-dependent risk for intracranial hemorrhage in patients with malignant gliomas.","authors":"Sanghee Lim, Nathan H Clarke, Sara L Maloney, Ugur T Sener, Samantha J Caron, Sani H Kizilbash, Jian L Campian, Bryan J Neth, Ivan D Carabenciov, Joon Uhm, Michael W Ruff","doi":"10.1007/s11060-024-04916-8","DOIUrl":"10.1007/s11060-024-04916-8","url":null,"abstract":"<p><strong>Purpose: </strong>Bevacizumab, an anti-VEGF monoclonal antibody, has become a mainstay therapeutic in the management of malignant glioma. It is unknown if the risk of intracranial hemorrhage (ICH), a major complication associated with bevacizumab use, is dose-dependent.</p><p><strong>Methods: </strong>This was a single institution retrospective analysis of patients treated with bevacizumab for the management of gliomas between 2009 and 2022. Incidence rates of ICH between patients receiving low-dose (< 5 mg/kg/week) and conventional-dose (5 mg/kg/week) bevacizumab regimens were compared via competing risk analysis over time. We evaluated post-progression survival (PPS) as a secondary outcome using multivariate Cox regression.</p><p><strong>Results: </strong>One hundred and seventy-three patients were identified (low-dose group, n = 51, conventional-dose group, n = 122) for inclusion in our analysis. Cumulative incidence rates of all cases of ICH and clinically symptomatic cases of ICH were higher in the conventional-dose (17.2% for all cases, 13.7% for symptomatic) relative to the low-dose group (3.9% for all cases, 2.0% for symptomatic); p-value 0.0296 for all cases, p-value 0.0274 for symptomatic cases. On multivariate Fine-Gray regression, conventional-dose bevacizumab therapy remained significantly associated with increased risk for symptomatic ICH (SHR 8.0560; p-value 0.0442). No difference in PPS was observed between the low-dose versus conventional-dose groups.</p><p><strong>Conclusions: </strong>Conventional-dose bevacizumab therapy (5 mg/kg/week) is associated with increased incidence of ICH in patients with malignant glioma compared to lower dose bevacizumab (< 5 mg/kg/week) in this single center retrospective cohort. No difference in PPS was observed between the low-dose versus conventional-dose groups.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"273-280"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921140","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":"A phase I study of convection-enhanced delivery (CED) of liposomal-irinotecan using real-time magnetic resonance imaging in patients with recurrent high-grade glioma.","authors":"Kazim H Narsinh, Karishma Kumar, Krystof Bankiewicz, Alastair J Martin, Mitchell Berger, Jennifer Clarke, Jennie Taylor, Nancy Ann Oberheim Bush, Annette M Molinaro, Manish Aghi, Nicholas Butowski","doi":"10.1007/s11060-024-04904-y","DOIUrl":"10.1007/s11060-024-04904-y","url":null,"abstract":"<p><strong>Background: </strong>Irinotecan demonstrates anti-tumor efficacy in preclinical glioma models but clinical results are modest due to drug delivery limitations. Convection enhanced delivery (CED) improves drug delivery by increasing intratumoral drug concentration. Real-time magnetic resonance imaging of infusate delivery during CED may optimize tumor coverage. This phase 1 trial examines the safety and tolerability of liposomal irinotecan and gadolinium delivered via CED using real-time MRI guidance in recurrent high-grade glioma patients.</p><p><strong>Methods: </strong>Initially, a 3 + 3 dose-escalating, single dose trial was planned with 4 cohorts based on a fixed drug dose and volume. After 9 patients, a protocol amendment allowed for variable volume and dose of the study agent based on tumor size. The amended design specified 'personalized' drug volume but fixed concentration of 20 mg/mL of liposomal irinotecan in the first cohort escalating to 40 mg/mL in the second cohort.</p><p><strong>Results: </strong>Eighteen patients with recurrent WHO grade 3 or 4 gliomas (diameter 1-4 cm) were treated. Based on the tumor volume, the total dose of liposomal irinotecan was 20-680 mg in a total volume of 2-17 ml. Technical challenges were overcome by real-time MRI guidance and protocol amendment. The only dose-limiting toxicity (DLT) was a grade 3 stroke. Safety and survival information is presented.</p><p><strong>Conclusions: </strong>CED of liposomal irinotecan using real-time MRI in patients with recurrent high-grade glioma is feasible. Image-guidance allowed for improved placement of CED cannulas and optimal tumor coverage. Our results warrant further study with repeat CED dosing.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"219-227"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832582/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systematic review of stereotactic radiosurgery for metastatic spinal sarcomas.","authors":"Trent Kite, Stephen Jaffe, Vineetha Yadlapalli, Rhea Verma, Jenna Li, Stephen Karlovits, Rodney E Wegner, Matthew J Shepard","doi":"10.1007/s11060-024-04892-z","DOIUrl":"10.1007/s11060-024-04892-z","url":null,"abstract":"<p><strong>Purpose: </strong>Sarcomas metastasizing to the spine are a rare entity. Ideally an En-bloc resection is necessary to achieve durable local control (LC) rates. However, anatomical constraints often limit the degree of tumor resection. Because of this, other therapeutic modalities either replacing or as an adjuvant to resection are necessary. Stereotactic radiosurgery (SRS) is a reasonable candidate therapy.</p><p><strong>Methods: </strong>We conducted a systematic review of the literature using the following databases: PubMed, Science Direct, and Cochrane library. We used a combination of the following terms connected by boolean operators: \"Metastatic Sarcoma, Sarcoma of the Spine, Spine Sarcoma, Metastasis, stereotactic radiosurgery, SRS.\" All retrospective and prospective cohorts, as well as randomized control trials reporting on patients with histopathologically confirmed metastatic sarcomas of the bony elements of the vertebrae, thecal sac, cord, or associated soft tissues of the spine were included. We excluded animal studies, case reports, case series, patients < 18 (pediatric cohorts), review articles and meta-analyses. No date filters were applied to our search.</p><p><strong>Results: </strong>Our final analysis included 5 studies ranging from 2009 to 2024 reporting on 260 patients and 371 associated lesions. Leiomyosarcoma was the most frequently reported histologic subtype (60%). Most lesions were localized to the thoracic spine (48.6%). 75% of studies reported a median dose < 30 Gy, and achieved biologically equivalent doses (BEDs) ranging from < 50-100. Pooled 1-year median survival was 64.5% (IQR: 61.8-75.10). Pooled 1-year median LC was 86% (IQR: 79.4-88.5). Three of five studies (60%) for OS and 4/5 (80%) for LC had data availability suitable for meta-analysis. The 1-year OS and LC rates proportions across these studies were 67% (proportion = 0.67, 95% CI: 0.57-0.75, p = 0.07, I² = 63%), and 84% (proportion = 0.84, 95% CI: 0.78-0.89, p = 0.10, I² = 52%) respectively. Median follow up across all studies was 18 months (IQR:12.7-31.3).</p><p><strong>Conclusions: </strong>SRS is a reasonable alternative therapy in either the up front, salvage or adjuvant setting which can facilitate durable LC.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"153-162"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142739669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrine effects of MEK and BRAF inhibitor therapy in paediatric patients: a tertiary centre experience.","authors":"Arif Hanafi Bin Jalal, Harriet Gunn, Buddhi Gunasekara, Hoong-Wei Gan","doi":"10.1007/s11060-024-04896-9","DOIUrl":"10.1007/s11060-024-04896-9","url":null,"abstract":"<p><strong>Purpose: </strong>BRAF and MEK inhibitors are used to treat a range of paediatric tumours including low-grade gliomas. The ubiquitous nature of the BRAF/MAPK/MEK pathway means such treatments are not without side effects such as renal tubulopathies and hyperglycaemia. This study aims to describe the endocrine dysfunction observed in a cohort of children treated with BRAF and MEK inhibitors at the largest paediatric centre in the UK utilising these treatments.</p><p><strong>Methods: </strong>Electronic data for patients treated with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) from January 2019 to May 2022 were retrospectively reviewed. Outcomes included diagnosis of glucose dysregulation, the presence of hyponatraemia (< 135 mmol/l) and sodium nadir during treatment.</p><p><strong>Results: </strong>A total of 55 patients were included for analysis. Nine patients had at least one hyponatraemic episode during treatment of whom three had coexisting central diabetes insipidus. A statistically significant difference (p-value = 0.037) with regards to the plasma sodium nadir during treatment was observed between patients with diabetes insipidus (median = 134 (132-137) mmol/l) and patients without (median = 137 (127-141 mmol/l). Six patients were diagnosed with a form of glucose dysregulation (e.g. insulin resistance, type 2 diabetes), of whom four were diagnosed during treatment with dabrafenib, all with hypothalamo-pituitary lesions.</p><p><strong>Conclusion: </strong>Clinicians using such treatments need to be aware of these potential effects, particularly the risk of hyponatraemia in patients with pre-existing central diabetes insipidus and monitor for these accordingly, including performing measurements of sodium and glucose prior to, during and after treatment.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"257-263"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817909","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating biomarkers in high-grade gliomas: current insights and future perspectives.","authors":"Suchet Taori, Ahmed Habib, Samuel Adida, Neslihan Nisa Gecici, Nikhil Sharma, Michael Calcaterra, Anthony Tang, Sumaarg Pandya, Arnav Mehra, Hansen Deng, Hayat Elidrissy, Yassine Alami Idrissi, Mohammadreza Amjadzadeh, Pascal O Zinn","doi":"10.1007/s11060-024-04903-z","DOIUrl":"10.1007/s11060-024-04903-z","url":null,"abstract":"<p><strong>Purpose: </strong>High-grade gliomas (HGG) represent a challenging subset of brain tumors characterized by aggressive nature and poor prognosis. Histopathology remains to be the standard for diagnosis, however, it is invasive, prone to sampling errors, and may not capture the full tumor heterogeneity and evolution over time. In recent years, there has been a growing interest in the potential utility of circulating biomarkers, obtained through minimally-invasive liquid biopsies, providing an opportunity for diagnosis, prognostication, monitoring treatment response and developing targeted therapies.</p><p><strong>Methods: </strong>We have reviewed the literature on circulating biomarkers for HGG, including circulating tumor cells (CTCs), circulating tumor-derived exosomes/extracellular vesicles (ctEVs), circulating tumor-derived DNA (ctDNA), circulating tumor-derived miRNA (ctmiRNA), and circulating tumor-derived proteins.</p><p><strong>Results: </strong>CTCs provide real-time information about tumor characteristics for molecular profiling and monitoring treatment response, yet their low numbers in circulation makes detection challenging. ctEVs carry a range of biomolecules and are easily detectable. However, they are not exclusively released from tumor cells and heterogeneity in their content requires standardized isolation and analysis methods. ctDNA is another promising biomarker with its levels correlating with the disease stage. However, its low concentration in blood requires highly sensitive techniques for identification and differentiation from normal cell-free DNA. ctmiRNA and tumor-derived proteins show promise but are limited by their susceptibility to dilution and lack of specificity in current technology.</p><p><strong>Conclusion: </strong>This review highlights the transformative potential of circulating biomarkers in the management of HGG, with implications for improving patient outcomes, optimizing treatment strategies, and advancing precision oncology in neuro-oncology practice.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"41-49"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142817895","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":"Cerebral spinal fluid analyses and therapeutic implications for leptomeningeal metastatic disease.","authors":"Jie Wei Zhu, Megan Shum, Maleeha A Qazi, Arjun Sahgal, Sunit Das, Matthew Dankner, Ines Menjak, Mary Jane Lim-Fat, Katarzyna J Jerzak","doi":"10.1007/s11060-024-04902-0","DOIUrl":"10.1007/s11060-024-04902-0","url":null,"abstract":"<p><strong>Purpose: </strong>To review applications of cerebral spinal fluid (CSF) biomarkers for the diagnosis, monitoring and treatment of leptomeningeal metastatic disease (LMD) among patients with metastatic solid tumors.</p><p><strong>Methods: </strong>A narrative review identified original research related to CSF biomarkers among patients with metastatic solid tumors and LMD. Pre-clinical research (e.g. studies conducted in animal models) was not included. A descriptive analysis of literature was undertaken, with a focus on clinical applications related to the diagnosis, monitoring and treatment of LMD.</p><p><strong>Results: </strong>The low cellularity of CSF in comparison to plasma is an advantage for liquid biopsy, given that circulating tumor DNA (ctDNA) is not significantly diluted by genomic DNA from non-cancer cells. This results in higher variant allelic frequencies and increased sensitivity in detecting ctDNA compared to plasma. However, the clinical significance of positive ctDNA and/or circulating tumor cells (CTCs) in the CSF, particularly in the absence of other signs of LMD (either clinical and/or radiological), remains unclear. While the use of CSF liquid biopsy to monitor treatment response is promising, this approach requires prospective validation using larger sample sizes prior to adoption in routine clinical care. Discovery efforts involving proteomics and metabolomics have potential to identify proteins involved in the regulation of energy metabolism, vasculature, and inflammation in LMD, which in turn, may offer insights into novel treatment approaches.</p><p><strong>Conclusion: </strong>CSF liquid biopsy should be incorporated in prospective studies for patients with LMD to validate promising diagnostic and/or predictive biomarkers of treatment response, as well as new therapeutic targets.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"31-40"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142864542","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":"Precision radiotherapy with molecular-profiling of CNS tumours.","authors":"Deepak Dinakaran, Daniel Moore-Palhares, Fan Yang, Jordan B Hill","doi":"10.1007/s11060-024-04911-z","DOIUrl":"10.1007/s11060-024-04911-z","url":null,"abstract":"<p><p>Diagnoses of CNS malignancies in the primary and metastatic setting have significantly advanced in the last decade with the advent of molecular pathology. Using a combination of immunohistochemistry, next-generation sequencing, and methylation profiling integrated with traditional histopathology, patient prognosis and disease characteristics can be understood to a much greater extent. This has recently manifested in predicting response to targeted drug therapies that are redefining management practices of CNS tumours. Radiotherapy, along with surgery, still remains an integral part of treating the majority of CNS tumours. However, the rapid advances in CNS molecular diagnostics have not yet been effectively translated into improving CNS radiotherapy. We explore several promising strategies under development to integrate molecular oncology into radiotherapy, and explore future directions that can serve to use molecular diagnostics to personalize radiotherapy. Evolving the management of CNS tumours with molecular profiling will be integral to supporting the future of precision radiotherapy.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"51-75"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142854418","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 value of immunohistochemical staining for H3K27me3 and EZH2 in astrocytoma, IDH-mutant.","authors":"Shumpei Onishi, Fumiyuki Yamasaki, Vishwa Jeet Amatya, Ushio Yonezawa, Akira Taguchi, Iori Ozono, Novita Ikbar Khairunnisa, Yukari Go, Yukio Takeshima, Nobutaka Horie","doi":"10.1007/s11060-024-04897-8","DOIUrl":"10.1007/s11060-024-04897-8","url":null,"abstract":"<p><strong>Background: </strong>H3 histone 27 lysine (H3K27) trimethylation (H3K27me3), which is catalyzed by enhancer of zeste homolog 2 (EZH2), regulates gene expression through epigenetic mechanisms. H3K27me3 is used as a diagnostic marker for diffuse midline glioma and as a surrogate marker to distinguish posterior fossa ependymoma A and B. However, the clinical significance of the EZH2-H3K27me3 axis in astrocytoma, IDH-mutant has not been reported, prompting this investigation.</p><p><strong>Methods: </strong>Thirty-three patients with astrocytoma, IDH-mutant treated at our institute were included in this study. Immunohistochemistry (IHC) targeting H3K27me3, H3K27M, EZH2, EZH inhibitory protein, IDH1-R132H, p53, ATRX, Ki-67, and MTAP was performed. Kaplan-Meier analysis and Cox regression analysis were performed to analyze the correlations of overall survival (OS) and progression-free survival (PFS) with various factors, including age, World Health Organization (WHO) grade, the extent of resection, and immunohistochemical results.</p><p><strong>Results: </strong>The mean patient age was 40.6 ± 11.0 years. IHC for H3K27me3 was positive in 19 patients and negative in 14 patients. The WHO grade and Ki-67 index were significantly higher in the H3K27me3-positive group (p = 0.004 and p = 0.024, respectively). OS and PFS were significantly shorter in the H3K27me3-positive group (p = 0.002 and p = 0.026, respectively). Furthermore, the H3K27me3 and EZH2 double-positive group was associated with a higher WHO grade and higher Ki-67 index (p = 0.001 and p = 0.024, respectively). In the analysis of patients with WHO grade 2/3, double positivity for H3K27me3 and EZH2 was linked to significantly shorter OS and PFS (p = 0.0053 and p = 0.0048, respectively).</p><p><strong>Conclusion: </strong>Positivity for H3K27me3, especially double positivity for H3K27me3 and EZH2, could be a poor prognostic factor for astrocytoma, IDH-mutant. These results suggest the utility of H3K27me3 and EZH2 as candidate markers for estimating the malignancy of astrocytoma, IDH-mutant.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"185-194"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11832638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell RNA-seq reveals diverse molecular signatures associated with Methotrexate resistance in primary central nervous system lymphoma cells.","authors":"Ryosuke Osako, Azusa Hayano, Atsushi Kawaguchi, Ryuya Yamanaka","doi":"10.1007/s11060-024-04893-y","DOIUrl":"10.1007/s11060-024-04893-y","url":null,"abstract":"<p><strong>Purpose: </strong>Methotrexate is one of the most essential single agents in patients with primary central nervous system lymphoma (PCNSL). However, 25-50% result in relapse with a poor prognosis. Therefore, studies on methotrexate resistance are warranted to explore salvage chemotherapy for recurrent PCNSL. Single-cell sequence analysis enables the characterization of novel cell types and provides a precise understanding of cancer biology.</p><p><strong>Methods: </strong>Single-cell sequence analysis of parental and methotrexate-resistant PCNSL cells was performed. We used a Weighted Gene Co-expression Network Analysis to identify groups of significantly connected genes.</p><p><strong>Results: </strong>We identified consensus modules in both the HKBML and TK datasets. HLA-DRβ1, HLA-DQβ1,and SNRPG were hub genes those detected in both datasets revealed by network analysis. Cyclosporine A was selected as the candidate drug for treating methotrexate-resistant cells.</p><p><strong>Conclusion: </strong>The results of the present study characterized the methotrexate resistance-related signaling pathways in cultured PCNSL cells. Overall, these results may account for variations in treatment responses and lead potential novel therapeutic strategies for patients with PCNSL.</p>","PeriodicalId":16425,"journal":{"name":"Journal of Neuro-Oncology","volume":" ","pages":"163-173"},"PeriodicalIF":3.2,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142785997","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}