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International Journal of Molecular... Mar 2024Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular... (Review)
Review
Glioblastoma multiforme (GBM) is the most common and malignant type of primary brain tumor in adults. Despite important advances in understanding the molecular pathogenesis and biology of this tumor in the past decade, the prognosis for GBM patients remains poor. GBM is characterized by aggressive biological behavior and high degrees of inter-tumor and intra-tumor heterogeneity. Increased understanding of the molecular and cellular heterogeneity of GBM may not only help more accurately define specific subgroups for precise diagnosis but also lay the groundwork for the successful implementation of targeted therapy. Herein, we systematically review the key achievements in the understanding of GBM molecular pathogenesis, mechanisms, and biomarkers in the past decade. We discuss the advances in the molecular pathology of GBM, including genetics, epigenetics, transcriptomics, and signaling pathways. We also review the molecular biomarkers that have potential clinical roles. Finally, new strategies, current challenges, and future directions for discovering new biomarkers and therapeutic targets for GBM will be discussed.
Topics: Humans; Glioblastoma; Pathology, Molecular; Brain Neoplasms; Biomarkers; Gene Expression Profiling; Biomarkers, Tumor
PubMed: 38474286
DOI: 10.3390/ijms25053040 -
Cancer Control : Journal of the Moffitt... 2022Glioblastoma multiforme (GBM) makes 60-70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Glioblastoma multiforme (GBM) makes 60-70% of gliomas and 15% of primary brain tumors. Despite the availability of standard multimodal therapy, 2 years, 3 years, and 5 years survival rate of GBM are still low. Active immunotherapy is a relatively new treatment option for GBM that seems promising.
METHODS
An electronic database search on PubMed, Cochrane, Scopus, and clinicaltrials.gov was performed to include all relevant studies. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Reported parameters are OS, PFS, AEs, post treatment KPS, and 2 year mortality.
RESULTS
Active immunotherapy provided better OS (HR = .85; 95% CI = .71-1.01; = .06) and PFS (HS = .83; 95% CI= .66 - 1.03; = .11) side albeit not statistically significant. Active immunotherapy reduces the risk of 2 year mortality as much as 2.5% compared to control group (NNT and RRR was 56.7078 and 0,0258, respectively).
CONCLUSION
Active immunotherapy might be beneficial in terms of survival rate in patients with GBM although not statistically significant. It could be a treatment option for GBM in the future.
Topics: Humans; Glioblastoma; Brain Neoplasms; Glioma; Combined Modality Therapy; Immunotherapy, Active; Immunotherapy
PubMed: 36748348
DOI: 10.1177/10732748221079474 -
Cancers Apr 2022Proline has attracted growing interest because of its diverse influence on tumor metabolism and the discovery of the regulatory mechanisms that appear to be involved. In... (Review)
Review
BACKGROUND
Proline has attracted growing interest because of its diverse influence on tumor metabolism and the discovery of the regulatory mechanisms that appear to be involved. In contrast to general oncology, data on proline metabolism in central nervous system malignancies are limited.
MATERIALS AND METHODS
We performed a systematic literature review of the MEDLINE and EMBASE databases according to PRISMA guidelines, searching for articles concerning proline metabolism in malignant glial tumors. From 815 search results, we identified 14 studies pertaining to this topic.
RESULTS
The role of the proline cycle in maintaining redox balance in IDH-mutated gliomas has been convincingly demonstrated. Proline is involved in restoring levels of glutamate, the main glial excitatory neurotransmitter. Proline oxidase influences two major signaling pathways: p53 and NF- κB. In metabolomics studies, the metabolism of proline and its link to the urea cycle was found to be a prognostic factor for survival and a marker of malignancy. Data on the prolidase concentration in the serum of glioblastoma patients are contradictory.
CONCLUSIONS
Despite a paucity of studies in the literature, the available data are interesting enough to encourage further research, especially in terms of extrapolating what we have learned of proline functions from other neoplasms to malignant gliomas.
PubMed: 35454935
DOI: 10.3390/cancers14082030 -
European Review For Medical and... Nov 2021The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The phenomenon is that few randomized control trials (RCTs) directly compared the effects of bevacizumab with other types of standard treatments for recurrent glioblastoma (GBM). We conducted a systematic review and meta-analysis to assess the efficacy of bevacizumab in recurrent GBM patients.
MATERIALS AND METHODS
We searched electronic databases (Medline, Embase, and Web of Science) contrasting the bevacizumab with standard treatments up to May 2021. For the continuous outcomes of median progression-free survival (PFS) and median overall survival (OS), we summarized the mean difference (MD) as the effective index. We used relative risk (RR) to estimate the data with a random-effects model to get the outcomes of objective response rate (ORR), 12-month OS, 6-month PFS, and any mentioned adverse events.
RESULTS
A total of 807 patients in 5 RCTs included into our systematic review and meta-analysis. The results showed bevacizumab could provide benefits of the ORR (RR, 2.67; 95% CI: 1.14-6.26, p = 0.02), median PFS (MD, 1.12 months; 95% CI: 0.35-1.90 months, p = 0.005), but not the median OS (MD, -0.19 months; 95% CI: -1.37-0.99 months, p = 0.75). Whereas the rates of the secondary outcomes of interest were similar between the bevacizumab group and control group, including 6 month-PFS (RR, 1.23; 95% CI, 0.82-1.84, p = 0.32) and 12 month-OS (RR, 0.93; 95% CI, 0.79-1.09, p = 0.36). As for adverse events, patients with bevacizumab showed higher rates of grade 3/4 and any grade hypertension compared with those with standard treatments (RR, 3.71; 95% CI: 1.17-11.76, p = 0.03; RR, 2.68; 95% CI: 1.26-5.76, p = 0.01, respectively).
CONCLUSIONS
This study provides clear proof of the beneficial effects of bevacizumab treatment in recurrent GBM patients. The only observed adverse event was grade 3/4 or any grade hypertension.
Topics: Angiogenesis Inhibitors; Bevacizumab; Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 34787852
DOI: 10.26355/eurrev_202111_27092 -
Frontiers in Surgery 2022Hemorrhage into optic pathway-hypothalamic glioma (OPHG) is rare. Variable clinical presentations and outcomes are associated with such pathology. We aim to present two... (Review)
Review
BACKGROUND
Hemorrhage into optic pathway-hypothalamic glioma (OPHG) is rare. Variable clinical presentations and outcomes are associated with such pathology. We aim to present two infants presented with OPHG and a systematic review of the literature.
METHODS
We describe two cases of infants presenting with sudden decreased vision, poor feeding, and irritability due to OPHG. Both patients underwent urgent craniotomy and subtotal resection followed by chemotherapy. We systematically reviewed the literature using PubMed, Google Scholar, and Embase. In addition, we included all English published reports for all ages discussing the optic pathway (optic nerve and optic chiasm) or hypothalamic glioma associated with hemorrhage from the year of the first reported case (1970) to January 2022.
RESULTS
Of 17,949, 44 articles met the inclusion criteria of this review. A total of 56 cases were described with a mean of 21.35 years (0.5-70), with the male gender 52% and the female gender 45%. The hemorrhage location was sellar/suprasellar in 43% cases. Histopathology of included cases was pilocytic astrocytoma in 41%, followed by pilomyxoid astrocytoma in 16% cases. The outcome was unfavorable; 37.5% cases showed improvement, whereas 18% cases resulted in death.
CONCLUSION
Apoplexy of the OPHG can be fatal and associated with poor outcomes. A systematic review of the literature has shown that younger age, pilocytic or pilomexyoid astrocytoma histopathology, and chiasmal/hypothalamic locations are associated with a higher risk of intertumoral hemorrhage and poor prognosis. Further genetic studies for OPHG may provide information for high-risk patients.
PubMed: 35733436
DOI: 10.3389/fsurg.2022.891556 -
Journal of Clinical Medicine Jun 2024Pilocytic astrocytoma (PCA) are commonly observed as slow-growing noncancerous brain tumors in pediatric populations, but they can also occur in adults, albeit rarely.... (Review)
Review
Pilocytic astrocytoma (PCA) are commonly observed as slow-growing noncancerous brain tumors in pediatric populations, but they can also occur in adults, albeit rarely. When located in diencephalic regions, particularly in the hypothalamus, they present unique diagnostic and management challenges due to their rarity and overlapping clinical and radiological features with other intracranial pathologies. This systematic review aims to provide a comprehensive understanding of hypothalamic PCA in adults, focusing on their differential diagnosis, neurological presentation, diagnostic modalities, treatment strategies. A case illustration is also described in order to better underline all the difficulties related to the diagnostic process. A systematic literature search was conducted in the PubMed/MEDLINE, Embase, and Scopus databases up to November 2023 to identify studies. The systematic literature search identified a total of 214 articles. Following screening by title and abstract and full-text review, 12 studies were deemed eligible and are included here. Adult-onset PCA in diencephalic regions pose diagnostic challenges due to their rarity and overlapping features with other intracranial lesions. Advanced imaging techniques play a crucial role in diagnosis, while surgery remains the cornerstone of treatment. Multidisciplinary collaboration is essential for the optimal management and long-term follow-up of these patients.
PubMed: 38930064
DOI: 10.3390/jcm13123536 -
Neurosurgical Review Oct 2022The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the... (Review)
Review
The development of minimally invasive neuroendoscopy has advanced in recent years. The introduction of the neuroendoscopic ultrasonic aspirator (NUA) increased the treatment spectrum of neuroendoscopy. This review aimed to present a systematic overview of the extent of resection, lesion characteristics, technical aspects, complications, and clinical outcomes related to using the NUA. Articles were identified by searching the PubMed/Medline, Embase, and Web of Science database through June 2022 with restriction to the last 20 years. We included case series, case reports, clinical trials, controlled clinical trials, meta-analyses, randomized controlled trials, reviews, and systematic reviews written in English. Studies reporting on endonasal approach or hematoma evacuation using the NUA were excluded. The references of the identified studies were reviewed as well. Nine full-text articles were included in the analysis, with a total of 40 patients who underwent surgery for a brain tumor using NUA. The most common underlying pathology treated by NUA was colloid cyst (17.5%), pilocytic astrocytoma (12.5%), subependymal giant cell astrocytoma (7.5%), subependymoma (7.5%), and craniopharyngioma (7.5%). Complete or near-total resection was achieved in 62.5%. The most frequently reported postoperative complication was secondary hydrocephalus (10%), meningitis/-encephalitis (7.5%), cognitive impairment (7.5%), and subdural hygroma (7.5%). In one case (2.5%), surgery-related death occurred due to a severe course of meningoencephalitis. According to the preliminary data, NUA seems to be a safe and efficient minimally invasive alternative to conventional microscopic resection of brain tumors. Further studies to investigate advantages and disadvantages of using the NUA are needed.
Topics: Astrocytoma; Brain; Brain Neoplasms; Colloid Cysts; Humans; Neuroendoscopy; Pituitary Neoplasms; Ultrasonics
PubMed: 35896917
DOI: 10.1007/s10143-022-01837-w -
European Journal of Cancer (Oxford,... Nov 2022Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review,... (Review)
Review
BACKGROUND
Grading and classification of IDH-mutant astrocytomas has shifted from solely histology towards histology combined with molecular diagnostics. In this systematic review, we give an overview of all currently known clinically relevant molecular markers within IDH-mutant astrocytomas grade 2 to 4.
METHODS
A literature search was performed in five electronic databases for English original papers on patient outcome with respect to a molecular marker as determined by DNA/RNA sequencing, micro-arrays, or DNA methylation profiling in IDH-mutant astrocytomas grade 2 to 4. Papers were included if molecular diagnostics were performed on tumour tissue of at least 15 IDH-mutant astrocytoma patients, and if the investigated molecular markers were not limited to the diagnostic markers MGMT, ATRX, TERT, and/or TP53.
RESULTS
The literature search identified 4508 unique articles, published between August 2012 and December 2021, of which ultimately 44 articles were included. Numerous molecular markers from these papers were significantly correlated to patient outcome. The associations between patient outcome and non-canonical IDH mutations, PI3K mutations, high expression of MSH2, high expression of RAD18, homozygous deletion of CDKN2A/B, amplification of PDGFRA, copy number neutral loss of chromosomal arm 17p, loss of chromosomal arm 19q, the G-CIMP-low DNA methylation cluster, high total CNV, and high tumour mutation burden were confirmed in multiple studies.
CONCLUSIONS
Multiple genetic and epigenetic markers are associated with survival in IDH-mutant astrocytoma patients. Commonly affected are the RB signalling pathway, the RTK-PI3K-mTOR signalling pathway, genomic stability markers, and (epigenetic) gene regulation.
Topics: Astrocytoma; Biomarkers, Tumor; Brain Neoplasms; DNA; DNA-Binding Proteins; Homozygote; Humans; Isocitrate Dehydrogenase; Lymphoma, Follicular; MutS Homolog 2 Protein; Mutation; Phosphatidylinositol 3-Kinases; Sequence Deletion; TOR Serine-Threonine Kinases; Ubiquitin-Protein Ligases
PubMed: 36152406
DOI: 10.1016/j.ejca.2022.08.016 -
Glia Aug 2019Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and...
Gliomas are a heterogenous group of malignant primary brain tumors that arise from glia cells or their progenitors and rely on accurate diagnosis for prognosis and treatment strategies. Although recent developments in the molecular biology of glioma have improved diagnosis, classical histological methods and biomarkers are still being used. The glial fibrillary acidic protein (GFAP) is a classical marker of astrocytoma, both in clinical and experimental settings. GFAP is used to determine glial differentiation, which is associated with a less malignant tumor. However, since GFAP is not only expressed by mature astrocytes but also by radial glia during development and neural stem cells in the adult brain, we hypothesized that GFAP expression in astrocytoma might not be a direct indication of glial differentiation and a less malignant phenotype. Therefore, we here review all existing literature from 1972 up to 2018 on GFAP expression in astrocytoma patient material to revisit GFAP as a marker of lower grade, more differentiated astrocytoma. We conclude that GFAP is heterogeneously expressed in astrocytoma, which most likely masks a consistent correlation of GFAP expression to astrocytoma malignancy grade. The GFAP positive cell population contains cells with differences in morphology, function, and differentiation state showing that GFAP is not merely a marker of less malignant and more differentiated astrocytoma. We suggest that discriminating between the GFAP isoforms GFAPδ and GFAPα will improve the accuracy of assessing the differentiation state of astrocytoma in clinical and experimental settings and will benefit glioma classification.
Topics: Animals; Astrocytoma; Biomarkers, Tumor; Central Nervous System Neoplasms; Glial Fibrillary Acidic Protein; Humans; Protein Isoforms
PubMed: 30667110
DOI: 10.1002/glia.23594 -
Chinese Clinical Oncology Aug 2022Glioma is the most common intracranial primary malignant tumor, and half of it is glioblastoma. Despite receiving the standard treatment, the prognosis of glioblastoma...
BACKGROUND AND OBJECTIVE
Glioma is the most common intracranial primary malignant tumor, and half of it is glioblastoma. Despite receiving the standard treatment, the prognosis of glioblastoma is still poor and its 5-year survival rate in China is only 9%. In addition, new targeted and immunotherapy therapy and tumor treating fields also have certain curative effects on glioblastoma. To help clinicians and patients make appropriate treatment based on current evidences, we summarize the Chinese guidelines on the management of glioma and review the recent management of glioblastoma.
METHODS
We systematically searched PubMed, China National Knowledge Infrastructure (CNKI) and Wanfang databases to retrieve guidelines on glioma in China published from the establishment of the database to 24 January 2022. We performed a narrative review of current clinical study related to the management of glioblastoma, especially in the surgical, targeted and immunotherapy therapy and tumor treating fields.
KEY CONTENT AND FINDINGS
In this review, 19 guidelines were included, including 8 subclassified as the guideline, 8 subclassified as the consensus and 3 subclassified as the standard. Two guidelines reported the contents of the system search, 4 guidelines are updated, and 9 guidelines reported the source of funding. At present, most clinical trials on the immune and targeted therapy of glioblastoma are ongoing in China.
CONCLUSIONS
China's guidelines still need to be improved in terms of preciseness, applicability and editorial independence. In addition, the cooperation in clinical research of glioblastoma in multiple centers needs to be strengthened in China.
Topics: Brain Neoplasms; China; Databases, Factual; Glioblastoma; Glioma; Humans
PubMed: 36098100
DOI: 10.21037/cco-22-18