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Brain Pathology (Zurich, Switzerland) Jul 2008The description of neuroglia by Virchow in 1848 may be considered the starting point of our understanding of primary brain tumors. At the beginning of the 20th century,... (Review)
Review
The description of neuroglia by Virchow in 1848 may be considered the starting point of our understanding of primary brain tumors. At the beginning of the 20th century, surgical removal of primary brain tumors became possible, and therefore, tissue for microscopic analysis and clinical data on survival became available. During this time, research on gliomas beyond improving surgical procedures focused on their classification. The classification schemes developed emphasized parameters for sorting tumors with regard to (i) cytological aspects; (ii) presumed tumor cell origin; (iii) histological appearance of the tissue; or (iv) clinical outcome. Over the years, experimental studies have greatly improved our knowledge on gliomas. Gliomas induced by viruses, chemicals, radiation, transgenes and knock-out technology contributed to the understanding of their pathogenesis and still serve as preclinical models for the testing of novel therapies. Recent advances in developmental neurobiology and the identification of stem cells provided new insights into the origin of brain tumors and the molecular mechanisms of tumor formation. This review briefly compiles the evolution of our concepts on gliomas, focusing on the latest developments.
Topics: Animals; Brain Neoplasms; Glioma; Humans
PubMed: 18371180
DOI: 10.1111/j.1750-3639.2008.00136.x -
Cancer Control : Journal of the Moffitt... Apr 2015Progress in molecular oncology during the last decade has enabled investigators to more precisely define and group gliomas. The impacts of isocitrate dehydrogenase (IDH)... (Review)
Review
BACKGROUND
Progress in molecular oncology during the last decade has enabled investigators to more precisely define and group gliomas. The impacts of isocitrate dehydrogenase (IDH) mutation (mut) status and other molecular markers on the classification, prognostication, and management of diffuse gliomas are likely to be far-reaching.
METHODS
Clinical experience and the medical literature were used to assess the current status of glioma categorization and the likely impact of the pending revision of the classification scheme of the World Health Organization (WHO).
RESULTS
IDH-mut is a defining event in most adult fibrillary astrocytomas (FAs) and nearly all oligodendrogliomas (ODs). The IDH-mut status of most gliomas can be established by immunohistochemistry for the most common mutant of IDH1 (R132H). IDH wild-type (wt) diffuse gliomas include several familiar entities -- in particular, glioblastoma (GBM) and most pediatric gliomas -- as well as an assortment of less well-defined entities. The codeletion of 1p/19q distinguishes OD from FA, which, by contrast, shows frequent loss of the α thalassemia/mental retardation syndrome X-linked protein. Mixed oligoastrocytomas are typically classifiable as either OD or FA using molecular testing.
CONCLUSIONS
The current practice of designating IDH-mut WHO grade 4 astrocytoma as secondary GBM will likely be discouraged, and primary or de novo GBM, which is always IDH-wt, may lose this qualification. Histologically, low- or intermediate-grade IDH-wt gliomas with molecular changes characteristic of GBM might justify the designation of GBM WHO grade 3. Mixed oligoastrocytoma is losing popularity as a diagnostic term because most cases will fall into either the FA or OD category. Distinguishing IDH-mut from IDH-wt tumors in clinical trials is likely to clarify sensitivity rates or tumor resistance among subgroups, thus suggesting opportunities for targeted therapy.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA Helicases; Genes, p53; Glioma; Glutarates; Humans; Immunohistochemistry; Isocitrate Dehydrogenase; Mutation; Nuclear Proteins; Oligodendroglioma; Prognosis; X-linked Nuclear Protein
PubMed: 26068765
DOI: 10.1177/107327481502200211 -
European Journal of Cancer (Oxford,... Sep 2023In an international randomised controlled phase II study of temozolomide (TMZ) versus TMZ in combination with bevacizumab (BEV) in locally diagnosed non-1p/19q... (Randomized Controlled Trial)
Randomized Controlled Trial
Health-related quality-of-life results from the randomised phase II TAVAREC trial on temozolomide with or without bevacizumab in 1p/19q intact first-recurrence World Health Organization grade 2 and 3 glioma (European Organization for Research and Treatment of Cancer 26091).
BACKGROUND
In an international randomised controlled phase II study of temozolomide (TMZ) versus TMZ in combination with bevacizumab (BEV) in locally diagnosed non-1p/19q co-deleted World Health Organization grade 2 or 3 gliomas with a first and contrast-enhancing recurrence after initial radiotherapy, and overall survival at 12 months was not significantly different (61% in the TMZ arm and 55% in the TMZ + BEV arm).
OBJECTIVES
Health-related quality of life (HRQoL) was a key secondary end-point in this trial, and the main objective of this study was to determine the impact of the addition of BEV to TMZ on HRQoL.
METHODS
HRQoL was assessed using the European Organization for Research and Treatment of Cancer QLQ-C30 (version 3) and QLQ-BN20 at baseline, and then every 12 weeks until disease progression. The pre-selected primary HRQoL end-point was the QLQ-C30 global health scale, with self-perceived cognitive functioning and pain selected as secondary HRQoL issues. Analysis was undertaken using linear mixed modelling and complemented with sensitivity analyses using summary statistics. A difference was considered clinically relevant with ≥10 points difference on a 100-point scale.
RESULTS
Baseline compliance was high at 94% and remained above 60% until 72 weeks, limiting the analysis to 60 weeks. Compliance was similar in both arms. We found no statistically significant or clinically significant differences between the primary HRQoL end-point in both treatment arms (p = 0.2642). The sensitivity analyses confirmed this finding. The overall test for post-baseline differences between the two treatment arms also showed no statistically or clinically significant differences regarding the selected secondary end-point scales.
INTERPRETATION
The addition of BEV to TMZ in this patient group neither improves nor negatively impacts HRQoL.
Topics: Humans; Temozolomide; Bevacizumab; Quality of Life; Brain Neoplasms; Glioma; World Health Organization
PubMed: 37453240
DOI: 10.1016/j.ejca.2023.112946 -
JNCI Cancer Spectrum Jan 2022Population-based analyses of patterns of care and survival of older patients diagnosed with grade II-III oligodendroglioma (OLI) or astrocytoma (AST) can aid clinicians...
BACKGROUND
Population-based analyses of patterns of care and survival of older patients diagnosed with grade II-III oligodendroglioma (OLI) or astrocytoma (AST) can aid clinicians in their understanding and care of these patients.
METHODS
We identified patients diagnosed between 2006 and 2015 with primary glioma diagnoses (OLI or AST) who were older than 65 years using the latest release of the Surveillance, Epidemiology, and End Results-Medicare-linked database. Medicare claims were used to identify cancer treatments (surgery, chemotherapy, and radiation therapy) from 2006 to 2016. Kaplan-Meier methodology was used to describe overall survival (OS). Cox proportional hazards regression was used to associate variables of interest, including treatments in a time-dependent manner, with OS. Hazard ratios (HRs) and 95% confidence intervals (CIs) from multivariable, cause-specific competing risk models identified associations with treatments. All statistical tests were 2-sided.
RESULTS
We identified 1291 patients comprising 158 with OLI, 1043 with AST, and 90 with mixed histologies. Median OS was 6.5 (95% CI = 6.1 to 7.3) months for the overall cohort, 22.6 (95% CI = 13.9 to 33.1) months for OLI, and 5.8 (95% CI = 5.3 to 6.4) months for AST. Patients who received surgery and patients who received both chemotherapy and radiation therapy in combination experienced better OS (HR = 0.87, 95% CI = 0.79 to 0.96, and HR = 0.58, 95% CI = 0.35 to 0.96, respectively). Over the time frame studied, there was a 4.0% increase per year in prescription of chemotherapy (P = .03) and a 2.0% improvement in OS for each calendar year (P = .003).
CONCLUSIONS
We provide population-based evidence that patients older than 65 years with grade II-III glioma have experienced increased chemotherapy use as well as improvement in survival over time.
Topics: Aged; Astrocytoma; Glioma; Humans; Medicare; Oligodendroglioma; Proportional Hazards Models; United States
PubMed: 35699501
DOI: 10.1093/jncics/pkac010 -
Medicine Sep 2022We aimed to evaluate the differences in dynamic susceptibility contrast (DSC)- magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) parameters between...
We aimed to evaluate the differences in dynamic susceptibility contrast (DSC)- magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI) parameters between the pre- and postbiopsy MRI obtained before treatment in patients with diffuse midline glioma, H3K27-altered. The data of 25 patients with pathologically proven diffuse midline glioma, H3K27-altered, were extracted from our hospital's database between January 2017 and August 2021. Twenty (median age, 13 years; range, 3-52 years; 12 women) and 8 (13.5 years; 5-68 years; 1 woman) patients underwent preoperative DSC-MRI and DWI before and after biopsy, respectively. The normalized corrected relative cerebral blood volume (ncrCBV), normalized relative cerebral blood flow (nrCBF), and normalized maximum, mean, and minimum apparent diffusion coefficient (ADC) were calculated using the volumes-of-interest of the tumor and normal-appearing reference region. The macroscopic postbiopsy changes (i.e., biopsy tract, tissue defect, and hemorrhage) were meticulously excluded from the postbiopsy measurements. The DSC-MRI and DWI parameters of the pre- and postbiopsy groups were compared using the Mann-Whitney U test. The ncrCBV was significantly lower in the postbiopsy group than in the prebiopsy group [prebiopsy group: median 1.293 (range, 0.513 to 2.547) versus postbiopsy group: 0.877 (0.748 to 1.205), P = .016]. No significant difference was observed in the nrCBF and normalized ADC values, although the median nrCBF was lower in the postbiopsy group. The DSC-MRI parameters differed between the pre- and postbiopsy MRI obtained pretreatment, although the macroscopic postbiopsy changes were carefully excluded from the analysis. The results emphasize the potential danger of integrating and analyzing DSC-MRI parameters derived from pre- and postbiopsy MRI.
Topics: Adolescent; Cerebrovascular Circulation; Diffusion Magnetic Resonance Imaging; Female; Glioma; Humans; Magnetic Resonance Imaging; Perfusion
PubMed: 36107564
DOI: 10.1097/MD.0000000000030183 -
Clinical Neuroradiology Dec 2021To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in...
PURPOSE
To explore the focal predictability of vascular growth factor expression and neovascularization using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in glioma.
METHODS
120 brain biopsies were taken in vital tumor, infiltration zone and normal brain tissue of 30 glioma patients: 17 IDH(isocitrate dehydrogenase)-wildtype glioblastoma (GBM), 1 IDH-wildtype astrocytoma °III (together prognostic group 1), 3 IDH-mutated GBM (group 2), 3 anaplastic astrocytomas IDH-mutated (group 3), 4 anaplastic oligodendrogliomas and 2 low-grade oligodendrogliomas (together prognostic group 4). A mixed linear model evaluated the predictabilities of microvessel density (MVD), vascular area ratio (VAR), mean vessel size (MVS), vascular endothelial growth factor and receptors (VEGF-A, VEGFR‑2) and vascular endothelial-protein tyrosine phosphatase (VE-PTP) expression from Tofts model kinetic and model-free curve parameters.
RESULTS
All kinetic parameters were associated with VEGF‑A (all p < 0.001) expression. K, k and v were associated with VAR (p = 0.006, 0.004 and 0.01, respectively) and MVS (p = 0.0001, 0.02 and 0.003, respectively) but not MVD (p = 0.84, 0.74 and 0.73, respectively). Prognostic groups differed in K (p = 0.007) and v (p = 0.004) values measured in the infiltration zone. Despite significant differences of VAR, MVS, VEGF‑A, VEGFR‑2, and VE-PTP in vital tumor tissue and the infiltration zone (p = 0.0001 for all), there was no significant difference between kinetic parameters measured in these zones.
CONCLUSION
The DCE-MRI kinetic parameters show correlations with microvascular parameters in vital tissue and also reveal blood-brain barrier abnormalities in the infiltration zones adequate to differentiate glioma prognostic groups.
Topics: Biopsy; Brain; Brain Neoplasms; Contrast Media; Glioma; Humans; Magnetic Resonance Imaging; Vascular Endothelial Growth Factor A
PubMed: 33900414
DOI: 10.1007/s00062-021-01015-3 -
Neuro-oncology Aug 2022
Topics: Circulating Tumor DNA; Glioma; Humans; Imidazoles; Liquid Biopsy; Pyridines; Pyrimidines
PubMed: 35323938
DOI: 10.1093/neuonc/noac076 -
International Journal of Molecular... Jan 2018The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise... (Review)
Review
The invasion properties of glioblastoma hamper a radical surgery and are responsible for its recurrence. Understanding the invasion mechanisms is thus critical to devise new therapeutic strategies. Therefore, the creation of in vitro models that enable these mechanisms to be studied represents a crucial step. Since in vitro models represent an over-simplification of the in vivo system, in these years it has been attempted to increase the level of complexity of in vitro assays to create models that could better mimic the behaviour of the cells in vivo. These levels of complexity involved: 1. The dimension of the system, moving from two-dimensional to three-dimensional models; 2. The use of microfluidic systems; 3. The use of mixed cultures of tumour cells and cells of the tumour micro-environment in order to mimic the complex cross-talk between tumour cells and their micro-environment; 4. And the source of cells used in an attempt to move from commercial lines to patient-based models. In this review, we will summarize the evidence obtained exploring these different levels of complexity and highlighting advantages and limitations of each system used.
Topics: Brain Neoplasms; Cell Communication; Glioma; Humans; Models, Biological; Neoplasm Invasiveness; Tumor Microenvironment
PubMed: 29300332
DOI: 10.3390/ijms19010147 -
Neuro-oncology Jan 2021
Topics: Glioma; Humans; Neural Networks, Computer
PubMed: 33180900
DOI: 10.1093/neuonc/noaa262 -
Computational Intelligence and... 2022Aldo-keto reductase family 1 member B1 (AKR1B1) plays a vital role in tumor development and is involved in the tumor immune process. However, its role in glioma cell is...
Aldo-keto reductase family 1 member B1 (AKR1B1) plays a vital role in tumor development and is involved in the tumor immune process. However, its role in glioma cell is poorly studied. This study's aim was to assess the role of AKR1B1 in glioma through bioinformatics analysis. The AKR1B1 expression data and corresponding clinical data of glioma were collected from the Cancer Genome Atlas (TCGA) database. The R packages were used for data integration, extraction, analysis, and visualization. According to the median value of the risk score, all patients were divided into high-risk and low-risk groups to draw the Kaplan-Meier (KM) survival curves and to explore the level of immune infiltration. The expression of AKR1B1 was significantly elevated in glioma tissues compared to normal tissues ( < 0.001). The high expression of AKR1B1 was significantly associated with WHO grade ( < 0.001), IDH status ( < 0.001), 1p/19q codeletion ( < 0.001), primary therapy outcome ( = 0.004), and age ( < 0.05). Kaplan-Meier survival analysis found that OS (HR = 3.75, < 0.001), DSS (HR = 3.85, < 0.001), and PFI (HR = 2.76, < 0.001) were lower in patients with glioma with high AKR1B1 expression than in the group with low AKR1B1 expression. Based on GESA, six pathways (including interferon gamma signaling, signaling by interleukins, cell cycle checkpoints, cytokine receptor interaction, cell adhesion molecules (CAMs), and cell surface interactions) at the vascular wall were identified as significantly different between the two groups. Moreover, highly expressed AKR1B1 was associated with immune cell infiltration. AKR1B1 plays a key role in glioma progression and prognosis and, therefore, serves as a potential biomarker for prediction of patients' survival.
Topics: Databases, Factual; Glioma; Humans; Prognosis
PubMed: 35341178
DOI: 10.1155/2022/9979200