Neuro-oncology advances最新文献

{"title":"Erratum to: Evolutionary evidence precludes <i>ELP1</i> as a high-penetrance pediatric cancer predisposition syndrome gene.","authors":"","doi":"10.1093/noajnl/vdae213","DOIUrl":"https://doi.org/10.1093/noajnl/vdae213","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/noajnl/vdae165.].</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdae213"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11843024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484783","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A comparative study of preclinical and clinical molecular imaging response to EGFR inhibition using osimertinib in glioblastoma.","authors":"Benjamin M Ellingson, Qunicy Okobi, Robert Chong, Rhea Plawat, Eva Zhao, Andrei Gafita, Ida Sonni, Saewon Chun, Emese Filka, Jingwen Yao, Donatello Telesca, Shanpeng Li, Gang Li, Albert Lai, Phioanh Nghiemphu, Johannes Czernin, David A Nathanson, Timothy F Cloughesy","doi":"10.1093/noajnl/vdaf022","DOIUrl":"10.1093/noajnl/vdaf022","url":null,"abstract":"<p><strong>Background: </strong>To demonstrate the potential value of ¹⁸F-fluorodeoxyglucose positron emission tomography (¹⁸F-FDG PET) as a rapid, non-invasive metabolic imaging surrogate for pharmacological modulation of EGFR signaling in EGFR-driven GBM, we synchronously conducted a preclinical imaging study using patient-derived orthotopic xenograft (PDOX) models and validated it in a phase II molecular imaging study in recurrent GBM (rGBM) patients using osimertinib.</p><p><strong>Methods: </strong>A GBM PDOX mouse model study was performed concurrently with an open-label, single-arm, single-center, phase II study of osimertinib (NCT03732352) that enrolled 12 patients with rGBM with EGFR alterations. Patients received osimertinib daily and 3 ¹⁸F-FDG PET scans: two 24 h apart prior to dosing, and one 48 h after dosing.</p><p><strong>Results: </strong>GBM PDOX models suggest osimertinib has limited impact on both ¹⁸F-FDG uptake (+ 9.8%-+25.9%) and survival (+ 15.5%; <i>P</i> = .01), which may be explained by insufficient exposure in the brain (Kp_uu: 0.30) required to robustly inhibit the EGFR alterations found in GBM. Treatment with osimertinib had subtle, but measurable decreases in the linear rate of change of ¹⁸F-FDG nSUV growth rate averaging -4.5% per day (<i>P</i> = .01) and change in ¹⁸F-FDG uptake was correlated with change in tumor growth rate (R² = 0.4719, <i>P = </i>.0195). No metabolic (PERCIST) or radiographic (RANO) responses were seen, and no improvements in PFS or OS were observed.</p><p><strong>Conclusions: </strong>This study demonstrated the feasibility of using FDG PET as a clinically reliable imaging biomarker for assessing EGFR inhibition in GBM, while revealing osimertinib's limited impact on both metabolic activity and tumor growth in GBM, findings that were concordant between preclinical and clinical observations.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf022"},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883343/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Size matters: Early progression of melanoma brain metastases after treatment with immune checkpoint inhibitors.","authors":"Sophie H A E Derks, Li Shen Ho, Stephan R Koene, Martijn P A Starmans, Esther Oomen-de Hoop, Arjen Joosse, Maja J A de Jonge, Kishan A T Naipal, Joost L M Jongen, Martin J van den Bent, Marion Smits, Astrid A M van der Veldt","doi":"10.1093/noajnl/vdaf026","DOIUrl":"10.1093/noajnl/vdaf026","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs) are effective treatments for patients with metastatic melanoma, including patients with brain metastasis (BM). However, half of patients with melanoma BM have intracranial progression within 6 months after the start of ICIs. We investigated whether size affects response to ICIs in patients with melanoma BM.</p><p><strong>Methods: </strong>In this single-center cohort study, patients with melanoma BM who were treated with ICIs between 2012 and 2021 were included. Clinical and radiologic features were collected at baseline. Longest axial diameter of all BMs was measured on baseline and follow-up MRI, and segmentation was performed for all BMs on baseline MRI. Lesion-level logistic regression analysis and patient-level survival analysis were performed for early BM progression (ie, within 6 months after start of ICIs) and intracranial progression-free survival (PFS), respectively.</p><p><strong>Results: </strong>A total of 82 patients were included with a total of 464 BMs. At baseline, 37.8% of patients had ≥ 4 BMs and 53.7% of patients had at least one BM with a diameter ≥ 10 mm. In multivariable analysis on the lesion level, baseline BM diameter was associated with early BM progression (odds ratio 1.10, 95%CI 1.05-1.15, <i>P</i> < .001). On the patient level, having at least one BM ≥ 10mm was associated with shorter intracranial PFS (hazard ratio 2.08, 95%CI 1.64-5.56, <i>P</i> < .001).</p><p><strong>Conclusions: </strong>Large BM diameter was associated with a higher risk of early progression after the start of ICIs. Therefore, local therapy should be considered for patients who are treated with ICIs and who have melanoma BMs ≥ 10 mm.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf026"},"PeriodicalIF":3.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Distant brain failure after stereotactic radiosurgery for brain metastases in patients receiving novel systemic treatments.","authors":"Paul van Schie, Ruben G Huisman, Terry Wiersma, Joost L Knegjens, Edwin P M Jansen, Dieta Brandsma, Annette Compter, Philip C de Witt Hamer, René Post, Gerben R Borst","doi":"10.1093/noajnl/vdaf027","DOIUrl":"10.1093/noajnl/vdaf027","url":null,"abstract":"<p><strong>Background: </strong>Novel systemic therapies, such as immunotherapy and targeted therapies, have shown better systemic disease control in the last decennium. However, the effect of these treatments on distant brain failure (DBF) in patients with brain metastases (BM) remains a topic of discussion. Improving time to DBF leads to longer overall survival (OS), as is reflected in the brain metastasis velocity (BMV). This study presents real world data about the combined effects of local and systemic treatments on DBF and survival.</p><p><strong>Methods: </strong>A retrospective consecutive cohort study was conducted. Patients with newly diagnosed BM were included between June 2018 and May 2020. Factors associated with DBF were analyzed in multivariate models. The association between BMV and overall survival was analyzed with linear regression analysis.</p><p><strong>Results: </strong>Three hundred and three patients were included. Two hundred and sixty-two (86%) patients received stereotactic radiotherapy, 41 (14%) awaited in first instance the intracranial effect of newly started or switched systemic treatment. Median time to DBF after radiotherapy was 21 months (95% CI 15-27), median OS was 20 months (IQR 10-36). Receiving immunotherapy or targeted therapy were associated with a lower hazard of DBF, compared with chemotherapy. The presence of > 5 initial BM and progressive or stable extracranial disease were associated with increased DBF. BMV was significantly associated with overall survival.</p><p><strong>Conclusions: </strong>In this retrospective cohort, patients who received immunotherapy or targeted therapy experienced a reduced risk of DBF in comparison to those treated with chemotherapy. A higher BMV was associated with a decreased OS.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf027"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883346/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carboplatin and vinblastine monthly in the optic pathway and hypothalamic gliomas: A retrospective analysis in a single institute.","authors":"Ting-Bin Lin, Chao-Yang Kuo, Feng-Chi Chang, Shih-Chieh Lin, Yi-Wei Chen, Muh-Lii Liang, Yi-Yen Lee","doi":"10.1093/noajnl/vdaf020","DOIUrl":"10.1093/noajnl/vdaf020","url":null,"abstract":"<p><strong>Background: </strong>Chemotherapy plays an important role in the treatment of optic pathway hypothalamic gliomas (OPHGs). Commonly used regimens include carboplatin and vincristine and monotherapy with vinblastine weekly. In this retrospective study, we used a monthly regimen of carboplatin and vinblastine to treat progressive/recurrent OPHGs and evaluated their effectiveness, visual preservation, and toxicity.</p><p><strong>Methods: </strong>The study involved patients with OPGH who were treated with carboplatin and vinblastine once per month. The response, disease progression, overall survival, vision changes, and toxicity were recorded according to their medical charts at our institute, and survival was analyzed.</p><p><strong>Results: </strong>A total of 25 patients were included, including 15 males (60%) and 10 females (40%). The response rate was 11/25 (44%), and the stabilization rate (complete response rate + partial response rate + minor response rate + and stable disease rate) was 21/25 (84%). The 3-year progression-free survival (PFS) rate was 54.6%, and the 5-year PFS rate was 46.8%. The 5-year overall survival rate was 100%. There were 6 patients who showed improved visual acuity (28.6%). Stable vision was found in 52.4% of patients. Only 2 patients experienced severe allergic reactions to carboplatin.</p><p><strong>Conclusions: </strong>The results showed that extending the dosing interval of carboplatin and vinblastine to every month can be seen as a similar response compared with previous regimens. The toxicity of this regimen is milder, and patients benefit from a lower frequency of hospital visits. The regimen can be considered as a choice of the first line of chemotherapy for OPHG patients.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf020"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575071","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal profiling of IDH-mutant astrocytomas reveals acquired RAS-MAPK pathway mutations associated with inferior survival.","authors":"Eduardo Rodriguez Almaraz, Geno A Guerra, Nadeem N Al-Adli, Jacob S Young, Abraham Dada, Daniel Quintana, Jennie W Taylor, Nancy Ann Oberheim Bush, Jennifer L Clarke, Nicholas A Butowski, John de Groot, Melike Pekmezci, Arie Perry, Andrew W Bollen, Aaron W Scheffler, David V Glidden, Joanna J Phillips, Joseph F Costello, Edward F Chang, Shawn Hervey-Jumper, Mitchel S Berger, Stephen S Francis, Susan M Chang, David A Solomon","doi":"10.1093/noajnl/vdaf024","DOIUrl":"10.1093/noajnl/vdaf024","url":null,"abstract":"<p><strong>Background: </strong>Isocitrate dehydrogenase (IDH)-mutant astrocytomas represent the most frequent primary intraparenchymal brain tumor in young adults, which typically arise as low-grade neoplasms that often progress and transform to higher grade despite current therapeutic approaches. However, the genetic alterations underlying high-grade transformation and disease progression of IDH-mutant astrocytomas remain inadequately defined.</p><p><strong>Methods: </strong>Genomic profiling was performed on 205 IDH-mutant astrocytomas from 172 patients from both initial treatment-naive and recurrent post-treatment tumor specimens. Molecular findings were integrated with clinical outcomes and pathologic features to define the associations of novel genetic alterations in the RAS-MAPK signaling pathway.</p><p><strong>Results: </strong>Likely oncogenic alterations within the RAS-MAPK mitogenic signaling pathway were identified in 13% of IDH-mutant astrocytomas, which involved the <i>KRAS, NRAS, BRAF, NF1</i>, <i>SPRED1</i>, and <i>LZTR1</i> genes. These included focal amplifications and known activating mutations in oncogenic components (e.g. <i>KRAS</i>, <i>BRAF</i>), as well as deletions and truncating mutations in negative regulatory components (e.g. <i>NF1</i>, <i>SPRED1</i>). These RAS-MAPK pathway alterations were enriched in recurrent tumors and occurred nearly always in high-grade tumors, often co-occurring with <i>CDKN2A</i> homozygous deletion. Patients whose IDH-mutant astrocytomas harbored these oncogenic RAS-MAPK pathway alterations had inferior survival compared to those with RAS-MAPK wild-type tumors.</p><p><strong>Conclusions: </strong>These findings highlight novel genetic perturbations in the RAS-MAPK pathway as a likely mechanism contributing to the high-grade transformation and treatment resistance of IDH-mutant astrocytomas that may be a potential therapeutic target for affected patients and used for future risk stratification.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf024"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575061","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring adult glioma through MRI: A review of publicly available datasets to guide efficient image analysis.","authors":"Meryem Abbad Andaloussi, Raphael Maser, Frank Hertel, François Lamoline, Andreas Dominik Husch","doi":"10.1093/noajnl/vdae197","DOIUrl":"10.1093/noajnl/vdae197","url":null,"abstract":"<p><strong>Background: </strong>Publicly available data are essential for the progress of medical image analysis, in particular for crafting machine learning models. Glioma is the most common group of primary brain tumors, and magnetic resonance imaging (MRI) is a widely used modality in their diagnosis and treatment. However, the availability and quality of public datasets for glioma MRI are not well known.</p><p><strong>Methods: </strong>In this review, we searched for public datasets of glioma MRI using Google Dataset Search, The Cancer Imaging Archive, and Synapse.</p><p><strong>Results: </strong>A total of 28 datasets published between 2005 and May 2024 were found, containing 62 019 images from 5515 patients. We analyzed the characteristics of these datasets, such as the origin, size, format, annotation, and accessibility. Additionally, we examined the distribution of tumor types, grades, and stages among the datasets. The implications of the evolution of the World Health Organization (WHO) classification on tumors of the brain are discussed, in particular the 2021 update that significantly changed the definition of glioblastoma.</p><p><strong>Conclusions: </strong>Potential research questions that could be explored using these datasets were highlighted, such as tumor evolution through malignant transformation, MRI normalization, and tumor segmentation. Interestingly, only 2 datasets among the 28 studied reflect the current WHO classification. This review provides a comprehensive overview of the publicly available datasets for glioma MRI currently at our disposal, providing aid to medical image analysis researchers in their decision-making on efficient dataset choice.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdae197"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lack of ST2 aggravates glioma invasiveness, vascular abnormality, and immune suppression.","authors":"Grzegorz Wicher, Ananya Roy, Alessandra Vaccaro, Kalyani Vemuri, Mohanraj Ramachandran, Tommie Olofsson, Rebeca-Noemi Imbria, Mattias Belting, Gunnar Nilsson, Anna Dimberg, Karin Forsberg-Nilsson","doi":"10.1093/noajnl/vdaf010","DOIUrl":"10.1093/noajnl/vdaf010","url":null,"abstract":"<p><strong>Background: </strong>Glioblastoma (GBM) is the most common primary malignant brain tumor in adults, characterized by aggressive growth and a dismal prognosis. Interleukin-33 (IL-33) and its receptor ST2 have emerged as regulators of glioma growth, but their exact function in tumorigenesis has not been deciphered. Indeed, previous studies on IL-33 in cancer have yielded somewhat opposing results as to whether it is pro- or anti-tumorigenic.</p><p><strong>Methods: </strong>IL-33 expression was assessed in a GBM tissue microarray and public databases. As in vivo models we used orthotopic xenografts of patient-derived GBM cells, and syngenic models with grafted mouse glioma cells.</p><p><strong>Results: </strong>We analyzed the role of IL-33 and its receptor ST2 in nonmalignant cells of the glioma microenvironment and found that IL-33 levels are increased in cells surrounding the tumor. Protein complexes of IL-33 and ST2 are mainly found outside of the tumor core. The IL-33-producing cells consist primarily of oligodendrocytes. To determine the function of IL-33 in the tumor microenvironment, we used mice lacking the ST2 receptor. When glioma cells were grafted to ST2-deficient mouse brains, the resulting tumors exhibited a more invasive growth pattern, and are associated with poorer survival, compared to <i>wild-type</i> mice. Tumors in ST2-deficient hosts are more invasive, with increased expression of extracellular matrix remodeling enzymes and enhanced tumor angiogenesis. Furthermore, the absence of ST2 leads to a more immunosuppressive environment.</p><p><strong>Conclusions: </strong>Our findings reveal that glia-derived IL-33 and its receptor ST2 participate in modulating tumor invasiveness, tumor vasculature, and immunosuppression in glioma.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf010"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11808570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392464","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rise in post-resection neutrophil-to-lymphocyte ratio correlates with decreased survival in glioblastoma patients.","authors":"Amro H Mohammad, Rawan Sakalla, William Davalan, Miguel Angel Ruiz-Barerra, Sukhdeep Jatana, Roy Khalaf, Hongda Li, Rebecca Aberra, Tariq Al-Saadi, Roberto J Diaz","doi":"10.1093/noajnl/vdaf014","DOIUrl":"10.1093/noajnl/vdaf014","url":null,"abstract":"<p><strong>Background: </strong>Neutrophil-to-lymphocyte ratio (NLR) is used in the prognostication of multiple malignancies. However, the NLR value in glioblastoma (GBM) is controversial. This controversy may be due to the unaccounted effect of dexamethasone on NLR. Using retrospective data from 230 isocitrate dehydrogenase-1 (<i>IDH</i>) wild-type GBM patients, we studied the prognostic value of NLR in relation to dexamethasone treatment in GBM.</p><p><strong>Methods: </strong>We retrospectively analyzed 230 patients with GBM. NLR and dexamethasone use were used as dichotomous variables with cutoff values of 9.5 and 8 mg, respectively. Correlations between high NLR, as well as NLR change after surgery, and patient outcome measures, including post-surgical complications and survival, were assessed using Kaplan-Meier curves, logistic, and Cox regression analyses.</p><p><strong>Results: </strong>We demonstrate in this study that high perioperative NLR (≥9.5 NLR) does not associate with survival of GBM patients (274 days, 95% confidence interval [CI] 211-337, vs. 229 days, 95% CI 52-406, <i>P</i> = .9). However, high positive change in NLR (≥6 units) (higher postoperative NLR relative to preoperative NLR) has a significant association with decreased survival in GBM patients (196 days, 95% CI 121-270, vs. 304 days, 95% CI 223-384, <i>P</i> = .01). High preoperative and perioperative average dexamethasone (≥8 mg) treatment did not change the perioperative NLR trend and were not associated with decreased survival.</p><p><strong>Conclusions: </strong>We demonstrate that an increase in NLR after surgery associates with decreased GBM patient survival.</p>","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf014"},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11883344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143573790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Slovenian translational platform GlioBank for brain tumor research: Identification of molecular signatures of glioblastoma progression.","authors":"Metka Novak, Bernarda Majc, Marta Malavolta, Andrej Porčnik, Jernej Mlakar, Matjaž Hren, Anamarija Habič, Mateja Mlinar, Ivana Jovčevska, Neja Šamec, Alja Zottel, Marija Skoblar Vidmar, Tina Vipotnik Vesnaver, Andrej Zupan, Alenka Matjašič, Saša Trkov Bobnar, Dejan Georgiev, Aleksander Sadikov, Roman Bošnjak, Borut Prestor, Radovan Komel, Tamara Lah Turnšek, Barbara Breznik","doi":"10.1093/noajnl/vdaf015","DOIUrl":"10.1093/noajnl/vdaf015","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Glioblastoma (GB) is one of the most lethal solid tumors in humans, with an average patient life expectancy of 15 months and a 5-year survival rate of 5%-10%. GB is still uncurable due to tumor heterogeneity and invasive nature as well as therapy-resistant cancer cells. Centralized biobanks with clinical data and corresponding biological material of GB patients facilitate the development of new treatment approaches and the search for clinically relevant biomarkers, with the goal of improving outcomes for GB patients. The aim of this study was firstly to establish a Slovenian translation platform, GlioBank, and secondly to demonstrate its utility through the identification of molecular signatures associated with GB progression and patient survival.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;GlioBank contains tissue samples and corresponding tumor models as well as clinical data from patients diagnosed with glioma, with a focus on GB. Primary GB cells, glioblastoma stem cells (GSCs), and organoids have been established from fresh tumor biopsies. We performed expression analyses of genes associated with GB progression and bioinformatics analyses of available clinical and research data obtained from a subset of 91 GB patients. qPCR was performed to determine the expression of genes associated with therapy resistance and cancer cell invasion, including markers of different GB subtypes, GSCs, epithelial-to-mesenchymal transition, and immunomodulation/chemokine signaling in tumor tissues and corresponding cellular models.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;GlioBank contains biological material and research, and clinical data collected in the SciNote electronic laboratory notebook. To date, more than 240 glioma tissue samples have been collected and stored in GlioBank, most of which are GB tissues (205) and were further processed to establish primary GB cells (&lt;i&gt;n&lt;/i&gt; = 64), GSCs (&lt;i&gt;n&lt;/i&gt; = 14), and GB organoids (&lt;i&gt;n&lt;/i&gt; = 17). Corresponding blood plasma (&lt;i&gt;n&lt;/i&gt; = 103) and peripheral blood mononuclear cells (&lt;i&gt;n&lt;/i&gt; = 101) are also stored. GB tumors were classified into 4 different subtypes that differed regarding patient survival; the mixed subtype exhibited the longest patient survival. High &lt;i&gt;DAB2, S100A4&lt;/i&gt;, and &lt;i&gt;STAT3&lt;/i&gt; expression were associated with poor overall patient survival, and &lt;i&gt;DAB2&lt;/i&gt; was found to be an independent prognostic marker for GB survival. We analyzed the molecular signatures between different tumor regions (core vs. rim). &lt;i&gt;STMN4, ERBB3&lt;/i&gt;, and &lt;i&gt;ACSBG1&lt;/i&gt; were upregulated in the tumor rim, suggesting that these genes are associated with the invasive nature of GB.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;GlioBank is a centralized biobank that has been built by a multidisciplinary network with the aim of facilitating disease-oriented basic and clinical research. The advantages of GlioBank include the molecular characterization of GB based on targeted gene expression, the availability of diverse cel","PeriodicalId":94157,"journal":{"name":"Neuro-oncology advances","volume":"7 1","pages":"vdaf015"},"PeriodicalIF":3.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11831694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}