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Cells Apr 2022Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival.... (Review)
Review
Glioblastoma and neuroblastoma are the most common central nervous system malignant tumors in adult and pediatric populations. Both are associated with poor survival. These tumors are highly heterogeneous, having complex interactions among different cells within the tumor and with the tumor microenvironment. One of the main challenges in the neuro-oncology field is achieving optimal conditions to evaluate a tumor's molecular genotype and phenotype. In this respect, the zebrafish biological model is becoming an excellent alternative for studying carcinogenic processes and discovering new treatments. This review aimed to describe the results of xenotransplantation of patient-derived CNS tumors in zebrafish models. The reviewed studies show that it is possible to maintain glioblastoma and neuroblastoma primary cell cultures and transplant the cells into zebrafish embryos. The zebrafish is a suitable biological model for understanding tumor progression and the effects of different treatments. This model offers new perspectives in providing personalized care and improving outcomes for patients living with central nervous system tumors.
Topics: Animals; Central Nervous System Neoplasms; Glioblastoma; Humans; Neuroblastoma; Tumor Microenvironment; Zebrafish
PubMed: 35406768
DOI: 10.3390/cells11071204 -
Journal of Clinical Neuroscience :... Jan 2021Multiple glioblastoma multiforme (GBM) is classified as multifocal and multicentric GBM according to whether there is communication between the lesions. Multiple GBM is...
Multiple glioblastoma multiforme (GBM) is classified as multifocal and multicentric GBM according to whether there is communication between the lesions. Multiple GBM is more genetically heterogeneous, aggressive and resistant to chemoradiotherapy than unifocal GBM, and has a worse prognosis. There is no international consensus on the treatment of multiple GBM. This review discusses some paradigms of multiple GBM and focuses on the heterogeneity spread pathway, imaging diagnosis, pathology, molecular characterization and prognosis of multifocal and multicentric GBM. Several promising therapeutic methods of multiple GBM are also recommended.
Topics: Brain Neoplasms; Glioblastoma; Humans
PubMed: 33358091
DOI: 10.1016/j.jocn.2020.11.025 -
Oncology (Williston Park, N.Y.) Mar 2023Glioblastoma is the most common primary neoplasm of the central nervous system. Standard treatment includes surgery with maximum safe resection and radiotherapy plus...
BACKGROUND
Glioblastoma is the most common primary neoplasm of the central nervous system. Standard treatment includes surgery with maximum safe resection and radiotherapy plus concomitant and adjuvant chemotherapy; however, almost invariably, tumor relapse occurs. We aimed to describe signaling pathways and molecular mechanisms present in tumor relapse of glioblastoma.
METHODS
This systematic review followed the PRISMA guidelines. We searched the PubMed, EMBASE and Web of Science databases. We included studies that enrolled patients 15 years or older with a diagnosis of glioblastoma according to Louis criteria and focused on signaling pathways and molecular mechanisms present in tumor relapse of glioblastoma. The outcome of interest was progression-free survival.
RESULTS
We identified 1470 articles; 31 met the inclusion criteria. From each publication, we obtained the associated markers O-6-methylguanine-DNA methyltransferase, isocitrate dehydrogenase, mRNA, epidermal growth factor receptor (EGFR), p53, and others. All publications were evaluated with the Q-Genie checklist tool for quality assessment.
CONCLUSIONS
We identified a wide variety of signaling pathways and molecular processes that are involved in glioblastoma relapse. This diversity would explain intra- and intertumor heterogeneity, treatment evasion, and relapse. However, only a few molecular processes have robust evidence for clinical utility.
Topics: Humans; Glioblastoma; Brain Neoplasms; Chemotherapy, Adjuvant; Recurrence; Signal Transduction
PubMed: 36961958
DOI: 10.46883/2023.25920986 -
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 -
Critical Reviews in Oncology/hematology Apr 2021Glioblastoma, the most common primary brain malignancy, is an exceptionally fatal cancer. Lack of suitable biomarkers and efficient treatment largely contribute to the... (Review)
Review
Glioblastoma, the most common primary brain malignancy, is an exceptionally fatal cancer. Lack of suitable biomarkers and efficient treatment largely contribute to the therapy failure. Cytoskeletal proteins are crucial proteins in glioblastoma pathogenesis and can potentially serve as biomarkers and therapeutic targets. Among them, GFAP, has gained most attention as potential diagnostic biomarker, while vimentin and microtubules are considered as prospective therapeutic targets. Microtubules represent one of the best anti-cancer targets due to their critical role in cell proliferation. Despite testing in clinical trials, the efficiency of taxanes, epothilones, vinca-domain binding drugs, colchicine-domain binding drugs and γ-tubulin binding drugs remains to be confirmed. Moreover, tumor treating field that disrupts microtubules draw attention because of its high efficiency and is called "the fourth cancer treatment modality". Thereby, because of the involvement of cytoskeleton in key physiological and pathological processes, its therapeutic potential in glioblastoma is currently extensively investigated.
Topics: Biomarkers; Cytoskeletal Proteins; Glioblastoma; Humans; Prospective Studies; Tubulin
PubMed: 33667657
DOI: 10.1016/j.critrevonc.2021.103283 -
World Neurosurgery Jul 2018Glioblastoma (GBM) is a dismal disease managed in the first instance by surgical resection, temozolomide, and radiation. The role of repeat surgery at recurrence remains... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glioblastoma (GBM) is a dismal disease managed in the first instance by surgical resection, temozolomide, and radiation. The role of repeat surgery at recurrence remains ill defined. This study aims to quantify the effect of repeat surgery in recurrent GBM on overall survival and determine if a trend in reported effect over time exists.
METHODS
Searches of 7 electronic databases from inception to January 2018 were conducted following PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) guidelines. There were 2692 articles identified for screening. Prognostic hazard ratios (HRs) derived from multivariate regression analysis were extracted and analyzed using meta-analysis of proportions and linear regression.
RESULTS
Eight observational studies reporting prognostic HRs in 10 cohorts were included. They described 1906 recurrent GBM diagnoses, managed by surgery at primary diagnosis, with 709 (37%) undergoing further repeat surgery at recurrence. Repeat surgery was shown to confer a statistically significant survival advantage compared with no surgery at recurrence in the pooled cohort (HR, 0.722; P < 0.001). Newer studies trended toward a more superior prognostic advantage of repeat surgery compared with earlier studies (effect coefficient, 0.856; P = 0.012).
CONCLUSIONS
This meta-analysis of contemporary literature suggests that repeat surgery at GBM recurrence in select patients confers a significant, prognostic overall survival advantage independent of other prognostic factors. Furthermore, newer studies are significantly more likely to suggest greater benefit than are older studies. The main limitation is the selection bias inherent in the cohorts pooled for analysis. Larger prospective randomized controlled studies are needed to validate the findings of this study and provide stratification for such benefit justified by quality of life metrics.
Topics: Brain Neoplasms; Glioblastoma; Humans; Neoplasm Recurrence, Local; Observational Studies as Topic; Second-Look Surgery; Survival Rate
PubMed: 29654958
DOI: 10.1016/j.wneu.2018.04.016 -
Neurosurgical Review Dec 2023Intradural spinal tumors present significant challenges due to involvement of critical motor and sensory tracts. Achieving maximal resection while preserving functional... (Meta-Analysis)
Meta-Analysis Review
Intradural spinal tumors present significant challenges due to involvement of critical motor and sensory tracts. Achieving maximal resection while preserving functional tissue is therefore crucial. Fluorescence-guided surgery aims to improve resection accuracy and is well studied for brain tumors, but its efficacy has not been fully assessed for spinal tumors. This meta-analysis aims to delineate the efficacy of fluorescence guidance in intradural spinal tumor resection. The authors performed a systematic review in four databases. We included studies that have utilized fluorescence agents, 5-aminolevulinic acid (5-ALA) or sodium fluorescein, for the resection of intradural spinal tumors. A meta-analysis was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 12 studies involving 552 patients undergoing fluorescence-guided intradural spinal tumor resection were included. Meningiomas demonstrated a 98% fluorescence rate and were associated with a homogenous florescence pattern; however, astrocytomas had variable fluorescence rate with pooled proportion of 70%. There was no significant difference in gross total resection (GTR) rates between fluorescein and 5-ALA (94% vs 84%, p = .22). Pre-operative contrast enhancement was significantly associated with intraoperative fluorescence with fluorescein. Intramedullary tumors with positive intraoperative fluorescence were significantly associated with higher GTR rates (96% vs 73%, p = .03). Utilizing fluorescence guidance during intradural spinal tumor resection holds promise of improving intraoperative visualization for specific intradural spinal tumors. Meningiomas and ependymomas have the highest fluorescence rates especially with sodium fluorescein; on the other hand, astrocytomas have variable fluorescence rates with no superiority of either agent. Positive fluorescence of intramedullary tumors is associated with a higher degree of resection.
Topics: Humans; Spinal Neoplasms; Fluorescein; Fluorescence; Meningioma; Spinal Cord Neoplasms; Astrocytoma; Aminolevulinic Acid; Meningeal Neoplasms
PubMed: 38085385
DOI: 10.1007/s10143-023-02230-x -
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 -
Journal of Cancer Survivorship :... Aug 2017The median survival of glioblastoma is 12-14 months with less than 10% of patients surviving at least 2 years from diagnosis. Patients diagnosed with glioblastoma face... (Review)
Review
BACKGROUND
The median survival of glioblastoma is 12-14 months with less than 10% of patients surviving at least 2 years from diagnosis. Patients diagnosed with glioblastoma face poor prognosis, significant symptom burden, and high care needs. The aim of this study is to undertake a literature review to document the issues encountered by long-term survivors of glioblastoma, a small but important subset of patients.
METHODS
MEDLINE, PsychInfo, and EMBASE were searched with core concepts: (1) glioblastoma, (2) survivor, and (3) terms pertaining to survivorship issues. A thematic analysis was undertaken of the three included studies.
RESULTS
Long-term survivors of glioblastoma encounter neurologic deficits, impairment in cognition, psychological distress, reduced social function, and future uncertainty. These issues result in the inability to return to work and financial difficulties. Independence in activities of daily living, working memory, and overall quality of life appears to be preserved.
CONCLUSIONS
Long-term survivors of glioblastoma continue to have significant symptom burden and care needs. There is currently a paucity of literature surrounding this topic. Further research is required to accurately describe these issues in order for improved supportive care to be implemented in the community and the outpatient setting.
IMPLICATIONS FOR CANCER SURVIVORS
Understanding the issues faced by long-term survivor of glioblastoma will provide insight into the care needs of patients as well as support networks required for patients and their carers.
Topics: Adult; Female; Glioblastoma; Humans; Male; Middle Aged; Quality of Life; Survivors
PubMed: 28194640
DOI: 10.1007/s11764-017-0602-7 -
World Neurosurgery Mar 2024Glioblastoma (GBM) is an aggressive tumor known for its poor prognosis. Despite extensive research into its molecular and clinical aspects, the current management... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Glioblastoma (GBM) is an aggressive tumor known for its poor prognosis. Despite extensive research into its molecular and clinical aspects, the current management strategies have shown limited efficacy in improving survival rate. Despite some preclinical studies exploring the combination of temozolomide (TMZ) with biguanides such as metformin (MET) and others, the potential benefits of this combination remain uncertain. The aim of this study is to evaluate the overall survival (OS) in GBM murine-models treated with a combination of TMZ + biguanide compared to those treated with TMZ alone.
METHODS
We systematically searched Medline, Embase, and Lilacs databases for studies comparing TMZ + biguanide versus TMZ alone in GBM models and reporting OS data. The mean difference (MD) with 95% confidence interval and random-effects model was adopted.
RESULTS
Nine studies were included in this systematic review. The meta-analysis comprised 6 studies involving 85 rat-models, with 45 subjects undergoing combined-treatment. GBM-murine models treated with TMZ + biguanide exhibited notably superior OS rates compared to those who received TMZ alone, showing an MD of 21.0 days (6.9-35.0). Within the subgroup of orthotopic models, the OS was also significantly better in combination-therapy with an MD of 23.7 days (6.5-40.9). Similarly, in the subgroup where MET was used as biguanide therapy, TMZ + MET demonstrated a significant increase in OS, with an MD of 27.4 days (6.0-48.8). In immunocompromised models, the combination-therapy also exhibited higher survival rates, with an MD of 13 days (9.4-16.6).
CONCLUSIONS
This systematic review and meta-analysis provide compelling evidence regarding the beneficial effects of TMZ + biguanide in GBM models compared with TMZ alone, resulting in a significant improvement in OS.
Topics: Humans; Mice; Rats; Animals; Temozolomide; Glioblastoma; Antineoplastic Agents, Alkylating; Brain Neoplasms; Metformin
PubMed: 38184227
DOI: 10.1016/j.wneu.2024.01.006