Common Malignant Central Nervous System Research Articles

Glioblastoma: a comprehensive approach combining bibliometric analysis, Latent Dirichlet Allocation, and HJ-Biplot : Glioblastoma insights and trends: a 49-year bibliometric analysis.

Glioblastoma is a common and aggressive malignant central nervous system tumor in adults. This study aims to evaluate and analyze the scientific results, collaboration countries, main research topics, and topics over time reported about glioblastoma. A bibliometric analysis of glioblastoma publications was performed mainly using R and Multbiplot software for author, journal, and resume. Associated statistic methods Latent Dirichlet Allocation (LDA) and HJ-Biplot. Inclusion criteria were research articles from the PubMed database published in English between 1973 and December 2022. A total of 64,823 documents with an annual growth rate of 8.27% indicates a consistent increase in research output over time. The results for the number of citations and significant publications showed Cancer Res, J Neuro-Oncol, and Neuro-Oncology are the most influential journals in the field of glioblastoma. The countries that concentrated research were the tumor United States, China, Germany, and Italy. Finally, there has been a marked growth in studies on prognosis and patient survival, therapies, and treatments for glioblastoma. These findings reinforce the need for increased global resources to address glioblastoma, particularly in underdeveloped countries. Glioblastoma research's exponential growth reflects sustained interest in early diagnosis and patient survival.

Abstract LB200: Defining the mechanisms of cancer specific transcription factor, tGLI1

Abstract Glioblastoma (GBM) is the most common malignant central nervous system tumor in adults with a five-year survival rate of less than 7%. First identified in GBM, truncated GLI1 (tGLI1), an alternative splicing isoform of GLI1, has emerged as a cancer specific GLI1 variant as tGLI1 is highly expressed in both GBM cell lines and primary specimens but not in normal tissue. Despite an in-frame loss of 41 amino acids, the tGLI1 protein has retained all known GLI1 functional domains and appears to respond to sonic hedgehog in a similar manner as GLI1. However, tGLI1 operates as a gain of function transcription factor with the ability to bind to and activate genes unique from GLI1 to promote invasion, migration, angiogenesis, and stemness in both GBM and breast cancer. Despite the advancements in our understanding of tGLI1, a genome wide DNA binding pattern of tGLI1 has not been established and the mechanism by which tGLI1 gains access to these genes is unknown. To establish a more robust understanding of the differential DNA binding patterns of GLI1 and tGLI1, we carried out ChIP-sequencing (ChIP-seq) and found only 14% of GLI1 and tGLI1 binding sites are shared. These results suggest GLI1 and tGLI1 have even more unique binding pattens across the entire genome that previously thought. However, the underlying mechanism for why GLI1 and tGLI1 bind different regions of the genome remains elusive. To determine whether variations in protein interactions of GLI1 and tGLI1 contribute to the unique binding pattern of tGLI1, we carried out immunoprecipitation (IP) followed by mass spectrometry (mass spec). Results identified 45 GLI1 associated proteins and 52 tGLI1 associated proteins with only a 29% overlap between the two. Furthermore, gene ontology analysis revealed 43% of the tGLI1-specific associated proteins are involved in processes related to RNA binding, processing, and metabolism. From these RNA-related proteins, we validated an interaction between tGLI1 and the protein NONO. NONO, which can bind both RNA and DNA, is involved in a range of molecular processes including paraspeckle formation and transcriptional regulation. In GBM, high NONO expression correlated with poor patient outcomes and the mesenchymal subtype. Interestingly, we observed that NONO, along with another essential paraspeckle component, SFPQ, had a greater interaction with tGLI1 compared to GLI1. Furthermore, co-expressing NONO with tGLI1 significantly increased clonogenic growth as well as CD44 gene transactivation using a luciferase reporter, suggesting it may play a role in tGLI1-driven stem-like properties. Furthermore, co-expression of NONO and tGLI1 increased the nuclear localization of both proteins. Together, these results show NONO may enhance tGLI1 nuclear localization, transcriptional activity, and exacerbate tGLI1-driven phenotypes. These effects of NONO could also contribute to the differential binding pattern between GLI1 and tGLI1. Citation Format: Haddie DeHart, Nolan Gregg, Richard Carpenter. Defining the mechanisms of cancer specific transcription factor, tGLI1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB200.

Molecular characterization and survival analysis of a cohort of glioblastoma, IDH-wildtype

Glioblastoma, IDH-wild type, the most common malignant primary central nervous system tumor, represents a formidable challenge in clinical management due to its poor prognosis and limited therapeutic responses. With an evolving understanding of its underlying biology, there is an urgent need to identify prognostic molecular groups that can be subject to targeted therapy. This study established a cohort of 124 sequential glioblastomas from a tertiary hospital and aimed to find correlations between molecular features and survival outcomes. Comprehensive molecular characterization of the cohort revealed prevalent alterations as previously described, such as TERT promoter mutations and involvement of the PI3K-Akt-mTOR, CK4/6-CDKN2A/B-RB1, and p14ARF-MDM2-MDM4-p53 pathways. MGMT promoter methylation is a significant predictor of improved overall survival, aligned with previous data. Conversely, age showed a marginal association with higher mortality. Multivariate analysis to account for the effect of MGMT promoter methylation and age showed that, in contrast to other published series, this cohort demonstrated improved survival for tumors harboring PTEN mutations, and that there was no observed difference for most other molecular alterations, including EGFR amplification, RB1 loss, or the coexistence of EGFR amplification and deletion/exon skipping (EGFRvIII). Despite limitations in sample size, this study contributes data to the molecular landscape of glioblastomas, prompting further investigations to examine these findings more closely in larger cohorts.

Abstract 1174: Incorporation of multisector analysis into the design of personalized DNA vaccines for patients with newly diagnosed glioblastoma

Abstract Glioblastoma (GBM) is the most common malignant central nervous system (CNS) tumor in adults. Despite multimodality treatment including surgery, radiation, and chemotherapy, patients with GBM have a median survival of less than 2 years. Recent clinical trials have reported promising results using cancer vaccines to stimulate a tumor-directed immune response in several histologies. The majority of trials targeted tumor neoantigens derived from a single tumor sample, which limits the antigen pool in spatially heterogeneous cancers like GBM. Our group previously implemented multisector sequencing into the design of personalized peptide vaccines to increase the candidate pool of targetable neoantigens (NCT03422094). Although the peptide vaccine treatment was successful in stimulating an effector T cell response, it was limited by a long turnaround time from vaccine design to administration and a low peptide production rate. Therefore, we incorporated multisector sampling into the design of a personalized DNA-based GBM vaccine (NCT04015700). An average of 33% of the candidate targetable neoantigens were spatially restricted to a single sampled region, which would have been missed without multisector sequencing. DNA-based vaccines are potentially advantageous over peptide-based vaccines because they enable a higher neoantigen payload and faster manufacturing time with potent immunogenicity. Here, we report the results from 9 subjects enrolled onto the study. Spatially distinct tumor regions were subjected to whole exome sequencing (WES) and RNA-sequencing (RNA-seq), data from which were used to identify neoantigens through the pVACseq algorithm (http://pvactools.org). An average of 32 neoantigens were included in each DNA vaccine, compared to an average of only 9 for the peptide vaccine, and the turnaround time from date of surgery to administration of the DNA vaccine was about half the time. Three subjects had radiographic evidence of tumor progression prior to vaccination, highlighting the aggressive nature of GBM and the need for short manufacturing timeframes. PBMCs pre- and post-DNA vaccination were collected from 7/9 subjects. All subjects presented detectable responses and 6/7 tested revealed a sustained increment in T cell reactivity against tumor neoantigens post-treatment by IFN-γ ELISpot. Intracellular staining showed a neoantigen-specific antitumor CD8/CD4 T cell cytolytic (CD69+, CD107a+) and proliferative (Ki67+) profile. Post-vaccination tumor resections were performed for 2 subjects who also were treated with PD1 blockade upon progression, providing an opportunity to explore vaccine-induced changes in the tumor microenvironment. Herein, we demonstrate the advantages of incorporating multisector sequencing into the development of DNA-based GBM vaccines and provide insights into the resulting immune responses. Citation Format: Elizabeth A. Garfinkle, Katherine E. Miller, Alexandra J. Livingstone, Renzo Perales-Linares, Neil Cooch, Alfredo Perales-Puchalt, Sarah Rochestie, Joann Peters, Niranjan Y. Sardesai, William E. Gillanders, Elaine R. Mardis, Gavin P. Dunn, Tanner M. Johanns. Incorporation of multisector analysis into the design of personalized DNA vaccines for patients with newly diagnosed glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1174.

Prognostic value of indoleamine 2, 3-dioxygenase-1 expression in glial tumors.

<p>Gliomas are the most common primary malignant central nervous system tumors in adults, exhibiting a poor prognosis. Indoleamine 2, 3-dioxygenase-1 (IDO-1) has important functions in cancer immunotherapy due to its role in escaping cancer cells from the immune system. In this study we purposed to evaluate the correlation between IDO-1 expression and clinicopathological parameters in gliomas, and whether IDO-1 can be a prognostic marker.</p>. <p>n=75 patients in total, n=25 patients with low grade glial tumors (LGG, grade 1-2), n=25 patients with high grade glial tumors (HGG, grade 3-4), and n=25 persons with normal brain tissue as control group were included in this study. IDO-1 expression was categorized by using immunohistochemical staining in biopsy specimens as high (H) and low (L) groups among the patients with gliomas. We used a 95% percent confidence interval and p &lt;0.05 to analyze the association between the degree of IDO-1 expression, clinicopathological characteristics, and survival rates in glioma patients.&nbsp;</p>. <p>In HGG, IDO-1 levels were higher than in control brain tissue and LGG (p&lt; 0.001). The mean overall survival (OS) was longer in the L-IDO-1 group (64.53 &plusmn; 3.34) in months (95% CI: 57.969-71.098) compared to the H-IDO-1 group (43.74 &plusmn; 4.36) in months, (95% CI: 35.218-52.330) (p&lt; 0.05).</p>. <p>IDO-1 expression is an in&shy;de&shy;pendent prognostic biomarker to predict&nbsp;<br>OS and progression in HGG. IDO-1 can be&nbsp;evaluated as an alternative instrument for precision medicine in the treatment of gliomas.</p>.

Current Strategies for Management of Medulloblastoma.

Medulloblastoma (MB) is the most common malignant central nervous system tumor of childhood, which includes multiple molecular subgroups (4) and subtypes (8 to 12), each with different outcomes and potential therapy options. Long-term survival remains poor for many of the subtypes, with high late mortality risks and poor health-related quality of life. Initial treatment strategies integrate molecular subgroup information with more standard clinical and phenotypic factors to risk stratify newly diagnosed patients. Clinical trials treating relapsed disease, often incurable, now include multiple new approaches in an attempt to improve progression-free and overall survival.

Glioblastoma in elderly patients: A retrospective analysis of survival and response based on molecular and clinical characteristics—Experience in our centre.

e14054 Background: Glioblastoma (GBM) is the most lethal and the most common malignant central nervous system tumor in adults. The standard treatment includes surgery, radiotherapy (Rt) and temozolomide based chemotherapy (Qt). However, compared with younger population, overall survival (OS) is worse in elderly patients and, additionally, this group is not usually included in clinical trials. Retrospective studies have shown, among other factors, tumor biology and performance status with poorer survival in older population, but it is necessary further research in order to discover prognostic factors and optimize management in this group. Methods: In this retrospective study we analyzed clinical and tumor biology characteristics in older population (≥ 70 years) and we also compared these results with younger population (&lt; 70 years) for the purpose of enhance clinical outcomes. From November-2016 to October-2022, we analyzed 111 patients in our hospital: group A (&lt; 70 years): 80 patients, group B (≥ 70 years): 31 patients. The tumor biology and patient characteristics are described in the table. Results: OS was statistically better in group A (A 13.93 +/- 1.28 months versus B 9.39 +/- 1.45 months; p=0.035). In contrast of A, in B no differences in OS were observed related with type of surgery (p=0.78), MGMT status (p=0.4) or p53 status (p=0.75). However, significant differences in OS were observed in B in multivariate analysis according to modality of adjuvant treatment (greater OS in Qt-Rt+ Qt &gt; Qt-Rt &gt; Rt exclusively &gt; no treatment; p&lt;0.001) and performance status (greater OS in PS 0 &gt; PS 1 &gt; PS 2 &gt; PS 3; p=0.001). There was no differences of OS between A and B if the adjuvant treatment was concomitant Qt-Rt +/- Qt (p=0.81), but with this therapy there was a toxic death (infection Grade 5) in B group. Other relevant toxicities Grade 3/4 in this group with Qt-Rt +/-Qt were: infection 3.2%, thrombocytopenia 12.9%, neutropenia 12.9%, leukopenia 6.45%, anemia 3.2%, thrombosis 3.2% Conclusions: Temozolomide based therapy is an effective and safe option for the treatment of patients ≥ 70 years with GBM. We need to perform prospective trials in this population in order to recognize prognostic and predictive factors to allow better treatment selection.[Table: see text]

Fatostatin induces ferroptosis through inhibition of the AKT/mTORC1/GPX4 signaling pathway in glioblastoma

Glioblastoma multiforme (GBM) is the most common and fatal primary malignant central nervous system tumor in adults. Although there are multiple treatments, the median survival of GBM patients is unsatisfactory, which has prompted us to continuously investigate new therapeutic strategies, including new drugs and drug delivery approaches. Ferroptosis, a kind of regulated cell death (RCD), has been shown to be dysregulated in various tumors, including GBM. Fatostatin, a specific inhibitor of sterol regulatory element binding proteins (SREBPs), is involved in lipid and cholesterol synthesis and has antitumor effects in a variety of tumors. However, the effect of fatostatin has not been explored in the field of ferroptosis or GBM. In our study, through transcriptome sequencing, in vivo experiments, and in vitro experiments, we found that fatostatin induces ferroptosis by inhibiting the AKT/mTORC1/GPX4 signaling pathway in glioblastoma. In addition, fatostatin inhibits cell proliferation and the EMT process through the AKT/mTORC1 signaling pathway. We also designed a p28-functionalized PLGA nanoparticle loaded with fatostatin, which could better cross the blood-brain barrier (BBB) and be targeted to GBM. Our research identified the unprecedented effects of fatostatin in GBM and presented a novel drug-targeted delivery vehicle capable of penetrating the BBB in GBM.

Combination of Caffeic Acid Phenethyl Ester and Crocin Realign Potential Molecular Markers in U87-MG Glioma Cells

Glial tumors are the most common primary malignant central nervous system tumors. They are hard to treat, not only because of the deregulation in multiple pathways but also because they are not contained in a well-defined mass with clear borders. The use of a single therapeutic agent to target gliomas has yielded unsatisfactory results. A combination of molecules targeting multiple pathways may prove to be a better alternative. The effect of caffeic acid phenethyl ester and crocin on the proliferation and death of U87-MG cells over a concentration range was analyzed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays. A colony formation assay was used to measure the effect of caffeic acid phenethyl ester and crocin on contact inhibition and anchorage independence ability of U87-MG cells. Furthermore, apoptosis in U87-MG cells was analyzed by propidium iodide assay. Real-time polymerase chain reaction and Western blotting were performed to determine the expression level of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen. Caffeic acid phenethyl ester and crocin when used in combination present an anticancer potential for glioma. These molecules, in combination, inhibit proliferation and induce apoptosis in U87-MG glioma cells. Our results provide evidence that combination treatment realigns the expression paradigm of p53, epidermal growth factor receptor, and proliferating cell nuclear antigen in cotreated U87-MG cells. The combination of caffeic acid phenethyl ester and crocin led to inhibition in glioma cell proliferation and might prove to be an effective adjunct to the therapies in vogue.

Current studies and future directions for medulloblastoma: A review from the pacific pediatric neuro-oncology consortium (PNOC) disease working group

Medulloblastoma (MB) is the most common malignant central nervous system tumor of childhood, comprising a heterogenous group of tumors each with distinct biology, clinical behavior, and prognosis. Long-term survival remains unacceptable, and those who do survive face high late mortality risk, new chronic treatment-related medical conditions, neurocognitive impairments, and poor health-related quality of life. Up-front treatment strategies now integrate molecular subgrouping with standard clinico-radiological factors to more actually risk stratify newly-diagnosed patients. To what extent this new stratification will lead to improvements in treatment outcome will be determined in the coming years. In parallel, discovery and appreciation for medulloblastoma's inter- and intra-tumoral heterogeneity continues growing. Clinical trials treating relapsed disease now encompass precision medicine, epigenetic modification, and immune therapy approaches. The Pacific Pediatric Neuro-Oncology (PNOC) Medulloblastoma Working Group is committed to developing clinical trials based on these evolving therapeutic strategies and supports translational efforts by PNOC researchers and the multi-stakeholder medulloblastoma community at large.

BIOS-02. CLINICAL OUTCOMES OF OVER 600 PATIENTS WITH GLIOBLASTOMA TREATED AT A CANADIAN TERTIARY CENTER IN THE PAST 15 YEARS: A COMPARATIVE ANALYSIS WITH THE PIVOTAL STUPP TRIAL

Abstract Glioblastoma is the most common malignant primary central nervous system tumor in adults and is associated with a poor prognosis. The benefit of adding concomitant followed by adjuvant temozolomide to radiotherapy after maximal safe resection was demonstrated by Stupp and colleagues in 2005 and has since remained the standard of care. This regimen conferred a statistically significant benefit with a 2-year survival rate of 26.5% compared to 10.4% in patients treated with radiotherapy alone. Our primary goal was to retrospectively assess the clinical outcomes of patients with glioblastoma treated at our institution over the past 15 years by comparing the overall survival (OS) and progression-free survival (PFS) from our cohort to data from the pivotal trial. Our secondary objective was to create a comprehensive database with clinical and pathological information in order to identify predictive and prognostic factors. We reviewed the clinical records of patients treated for glioblastoma from January 2005 to November 2019 at our center. We extracted data on survival and calculated OS and PFS using the Kaplan-Meier method. 617 patient charts were reviewed, out of which 17 were excluded because of missing data. The remaining 600 patients were included. Baseline demographic information was similar to that of the Stupp cohort, with the exception of a larger proportion of patients aged 50 or above (76% versus 69%, respectively). The median OS at our center was 14.3 months, 95% confidence interval [12.8-15.2], which was comparable to that of the original trial (14.6 months [13.2-16.8]). PFS was better in our cohort at 6 months (74.2% [70.7-77.7] versus 53.9% [48.1-59.6]) and 12 months (36.3% [32.5-40.2] versus 26.9% [21.8-32.1]), and comparable thereafter. Our study confirms that the data from the Stupp trial are reproducible in a Canadian academic center setting. Our database will allow us to explore potentially new predictive factors.

The differential usage of molecular machinery in brain cancer patients with iron-enriched glioma environments.

Gliomas are neuroepithelial tumors in the brain or spinal cord that arise from glial or precursor cells and include astrocytomas, oligodendrogliomas, and ependymomas. They are the most common malignant primary central nervous system tumors, representing 75% of cases in adults and 24% of all cases of primary brain and CNS tumors [1,2].

P02.04.A Preoperative neutrophil, thrombocyte and monocyte to lymphocyte ratios as independent prognostic factors for patient survival in WHO 2021 glioblastoma multiforme

Abstract Background Glioblastoma (GBM) is the most common malignant primary central nervous system (CNS) tumor. It is a fast-growing and extremely aggressive malignancy with a short postoperative survival time of little more than a year. The tumor-immune system interactions are complex and can be measured as local phenomena - e.g., tumor-infiltrating lymphocytes, or as systemic events - e.g., lymphopenia, neutropenia, etc. with cell numbers allowing for estimation of the type of immune reaction against the tumor. Material and Methods A retrospective non-clinical approach was utilized for the means of the study. Patients with a histologically and molecular verified GBM, corresponding to the guidelines of 2021 WHO CNS tumor classification, diagnosed in a three-year interval (February 2018-2021) in a single tertiary healthcare institution were included. Patients with infectious, inflammatory, autoimmune, and hematological diseases, as well as those with malignancy in another location, were excluded. Data regarding patient demographics, and preoperative peripheral blood cell counts (neutrophils, platelets, and monocytes in a ratio to lymphocytes) were compared with postoperative patient survival. Preoperative ratios were calculated as absolute values. For cutoff values we used generally accepted ones - &amp;gt;4 for neutrophil to lymphocyte (NLR), &amp;gt;200 for thrombocyte to lymphocyte (TLR), and &amp;gt;0.25 for monocyte to lymphocyte ratios (MLR). Results were statistically analyzed with MedCalc version 19.7.1 and the Kaplan-Meier method. Results A total of 22 patients fit the established criteria, with a male to female ratio of 2.14:1, mean age of 66.23 years, and mean survival of 255.72 days (8.04 months, range 24-801 days). Eight patients had an elevation of NLR and five of PLR, with no statistical correlation to survival. Six patients had an increase in MLR with a statistically significant (p=0.0044) shorter postoperative survival. Synergic increase in NLR and PLR did not show significance, while synergic increase with MLR showed no added benefit, as did comparison within MGMT promoter methylation groups. Conclusion Elevation in NLR, PLR, and MLR is a good independent prognostic marker for postoperative patient survival in histologically and mutationally verified GBM. Acknowledgments * contributed equally to the work and should be considered co-first authors.Financing: Medical University - Varna Scientific Fund, grant number 19010 and National scientific fund - young researchers (Republic of Bulgaria) grant number 2990/07.06.2021 Ethical approval: Medical University - Varna committee on scientific ethics approval protocol number 93/21.05.2020

Multi-Arm GlioblastoMa Australasia (MAGMA): protocol for a multiarm randomised clinical trial for people affected by glioblastoma

IntroductionGlioblastoma (GBM) is the most common malignant primary central nervous system cancer in adults. The objective of the Multi-Arm GlioblastoMa Australasia (MAGMA) trial is to test hypotheses in real world...

Weighted Gene Co-Expression Network Analysis and Support Vector Machine Learning in the Proteomic Profiling of Cerebrospinal Fluid from Extraventricular Drainage in Child Medulloblastoma.

Medulloblastoma (MB) is the most common pediatric malignant central nervous system tumor. Overall survival in MB depends on treatment tuning. There is aneed for biomarkers of residual disease and recurrence. We analyzed the proteome of waste cerebrospinal fluid (CSF) from extraventricular drainage (EVD) from six children bearing various subtypes of MB and six controls needing EVD insertion for unrelated causes. Samples included total CSF, microvesicles, exosomes, and proteins captured by combinatorial peptide ligand library (CPLL). Liquid chromatography-coupled tandem mass spectrometry proteomics identified 3560 proteins in CSF from control and MB patients, 2412 (67.7%) of which were overlapping, and 346 (9.7%) and 805 (22.6%) were exclusive. Multidimensional scaling analysis discriminated samples. The weighted gene co-expression network analysis (WGCNA) identified those modules functionally associated with the samples. A ranked core of 192 proteins allowed distinguishing between control and MB samples. Machine learning highlighted long-chain fatty acid transport protein 4 (SLC27A4) and laminin B-type (LMNB1) as proteins that maximized the discrimination between control and MB samples. Machine learning WGCNA and support vector machine learning were able to distinguish between MB versus non-tumor/hemorrhagic controls. The two potential protein biomarkers for the discrimination between control and MB may guide therapy and predict recurrences, improving the MB patients’ quality of life.

Alarm Signal S100-Related Signature Is Correlated with Tumor Microenvironment and Predicts Prognosis in Glioma.

Glioma are the most common malignant central nervous system tumor and are characterized by uncontrolled proliferation and resistance to therapy. Dysregulation of S100 proteins may augment tumor initiation, proliferation, and metastasis by modulating immune response. However, the comprehensive function and prognostic value of S100 proteins in glioma remain unclear. Here, we explored the expression profiles of 17 S100 family genes and constructed a high-efficient prediction model for glioma based on CGGA and TCGA datasets. Immune landscape analysis displayed that the distribution of immune scores, ESTIMATE scores, and stromal scores, as well as infiltrating immune cells (macrophages M0/M1/M2, T cell CD4+ naïve, Tregs, monocyte, neutrophil, and NK activated), were significant different between risk-score subgroups. Overall, we demonstrated the value of S100 protein-related signature in the prediction of glioma patients' prognosis and determined its relationship with the tumor microenvironment (TME) in glioma.

Glioblastoma: Changing concepts in the WHO CNS5 classification.

Glioblastoma is the most common malignant central nervous system (CNS) tumor in adults. Acute common clinical symptoms include headache, seizure, behavior changes, focal neurological deficits, and signs of increased intracranial pressure. The classic MRI finding of glioblastoma is an irregularly shaped, rim-enhancing or ring-enhancing lesion with a central dark area of necrosis. This constellation of features correlates with microscopic findings of tumor necrosis and microvascular proliferation. Besides these common features, several well-recognized histological subtypes include giant cell glioblastoma, granular cell glioblastoma, gliosarcoma, glioblastoma with a primitive neuronal component, small cell glioblastoma, and epithelioid glioblastoma. While glioblastoma was historically classified as isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant groups, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and the fifth edition of the WHO Classification of Tumors of the Central Nervous System clearly updated the nomenclature to reflect glioblastoma to be compatible with wildtype IDH status only. Therefore, glioblastoma is now defined as "a diffuse, astrocytic glioma that is IDH-wildtype and H3-wildtype and has one or more of the following histological or genetic features: microvascular proliferation, necrosis, Telomerase reverse transcriptase promoter mutation, Epidermal growth factor receptor gene amplification, +7/-10 chromosome copy-number changes (CNS WHO grade 4)."

Regional Development of Glioblastoma: The Anatomical Conundrum of Cancer Biology and Its Surgical Implication.

Glioblastoma (GBM) are among the most common malignant central nervous system (CNS) cancers, they are relatively rare. This evidence suggests that the CNS microenvironment is naturally equipped to control proliferative cells, although, rarely, failure of this system can lead to cancer development. Moreover, the adult CNS is innately non-permissive to glioma cell invasion. Thus, glioma etiology remains largely unknown. In this review, we analyze the anatomical and biological basis of gliomagenesis considering neural stem cells, the spatiotemporal diversity of astrocytes, microglia, neurons and glutamate transporters, extracellular matrix and the peritumoral environment. The precise understanding of subpopulations constituting GBM, particularly astrocytes, is not limited to glioma stem cells (GSC) and could help in the understanding of tumor pathophysiology. The anatomical fingerprint is essential for non-invasive assessment of patients’ prognosis and correct surgical/radiotherapy planning.

Efficacy of Cytokine-Induced Killer Cell Immunotherapy for Patients With Pathologically Pure Glioblastoma.

The most common malignant central nervous system tumor is glioblastoma multiforme (GBM). Cytokine-induced killer (CIK) cell therapy is a promising type of adoptive cell immunotherapy for various cancers. We previously conducted a randomized clinical trial on CIK cell therapy in patients with GBM. The aim of this study was to evaluate the efficacy of CIK immunotherapy for patients with pathologically pure GBM, using data from our previous randomized clinical trial. The difference between overall survival (OS) and progression-free survival (PFS) according to CIK immunotherapy was analyzed using the Kaplan–Meier method. Hazard ratios were calculated using univariate and multivariate Cox regression analyses to determine whether CIK cell immunotherapy was independently associated with higher OS and PFS in patients with pure GBM. A total of 156 eligible patients were included in the modified intention-to-treat (mITT) population. We confirmed that 125 (80.1%) GBM samples were pure GBM tumors without the presence of other types of tumors. For patients with pure GBM, Kaplan-Meier analysis showed no significant difference in OS between the CIK cell treatment and control groups. However, multivariate Cox regression demonstrated CIK cell immunotherapy as an independent predictor of greater OS (hazard ratio, 0.59; 95% CI, 0.36–0.97; p = 0.038) and PFS (hazard ratio, 0.55; 95% CI, 0.36–0.84; p = 0.001) in patients with pathologically pure GBM in the mITT population. This study showed that CIK cell immunotherapy combined with conventional temozolomide chemoradiotherapy could prolong OS and PFS in patients with newly diagnosed pathologically pure GBM, with no significant adverse events related to treatment. However, unlike the results of multivariate Cox analysis, no statistical significance of CIK cell immunotherapy in OS in Kaplan-Meier analysis raises a question. Further studies are required to validate these results.

Omega-3 fatty acids decrease CRYAB, production of oncogenic prostaglandin E2 and suppress tumor growth in medulloblastoma

AimsMedulloblastoma (MB) is one of the most common malignant central nervous system tumors of childhood. Despite intensive treatments that often leads to severe neurological sequelae, the risk for resistant relapses remains significant. In this study we have evaluated the effects of the ω3-long chain polyunsaturated fatty acids (ω3-LCPUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on MB cell lines and in a MB xenograft model. Main methodsEffects of ω3-LCPUFA treatment of MB cells were assessed using the following: WST-1 assay, cell death probes, clonogenic assay, ELISA and western blot. MB cells were implanted into nude mice and the mice were randomized to DHA, or a combination of DHA and EPA treatment, or to control group. Treatment effects in tumor tissues were evaluated with: LC-MS/MS, RNA-sequencing and immunohistochemistry, and tumors, erythrocytes and brain tissues were analyzed with gas chromatography. Key findingsω3-LCPUFA decreased prostaglandin E2 (PGE2) secretion from MB cells, and impaired MB cell viability and colony forming ability and increased apoptosis in a dose-dependent manner. DHA reduced tumor growth in vivo, and both PGE2 and prostacyclin were significantly decreased in tumor tissue from treated mice compared to control animals. All ω3-LCPUFA and dihomo-γ-linolenic acid increased in tumors from treated mice. RNA-sequencing revealed 10 downregulated genes in common among ω3-LCPUFA treated tumors. CRYAB was the most significantly altered gene and the downregulation was confirmed by immunohistochemistry. SignificanceOur findings suggest that addition of DHA and EPA to the standard MB treatment regimen might be a novel approach to target inflammation in the tumor microenvironment.