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International Journal of Molecular... Jun 2023Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state... (Review)
Review
Gliomas are the most common brain tumor in adults, and molecularly targeted therapies to treat gliomas are becoming a frequent topic of investigation. The current state of molecular targeted therapy research for adult-type diffuse gliomas has yet to be characterized, particularly following the 2021 WHO guideline changes for classifying gliomas using molecular subtypes. This systematic review sought to characterize the current state of molecular target therapy research for adult-type diffuse glioma to better inform scientific progress and guide next steps in this field of study. A systematic review was conducted in accordance with PRISMA guidelines. Studies meeting inclusion criteria were queried for study design, subject (patients, human cell lines, mice, etc.), type of tumor studied, molecular target, respective molecular pathway, and details pertaining to the molecular targeted therapy-namely the modality, dose, and duration of treatment. A total of 350 studies met the inclusion criteria. A total of 52 of these were clinical studies, 190 were laboratory studies investigating existing molecular therapies, and 108 were laboratory studies investigating new molecular targets. Further, a total of 119 ongoing clinical trials are also underway, per a detailed query on clinicaltrials.gov. GBM was the predominant tumor studied in both ongoing and published clinical studies as well as in laboratory analyses. A few studies mentioned IDH-mutant astrocytomas or oligodendrogliomas. The most common molecular targets in published clinical studies and clinical trials were protein kinase pathways, followed by microenvironmental targets, immunotherapy, and cell cycle/apoptosis pathways. The most common molecular targets in laboratory studies were also protein kinase pathways; however, cell cycle/apoptosis pathways were the next most frequent target, followed by microenvironmental targets, then immunotherapy pathways, with the wnt/β-catenin pathway arising in the cohort of novel targets. In this systematic review, we examined the current evidence on molecular targeted therapy for adult-type diffuse glioma and discussed its implications for clinical practice and future research. Ultimately, published research falls broadly into three categories-clinical studies, laboratory testing of existing therapies, and laboratory identification of novel targets-and heavily centers on GBM rather than IDH-mutant astrocytoma or oligodendroglioma. Ongoing clinical trials are numerous in this area of research as well and follow a similar pattern in tumor type and targeted pathways as published clinical studies. The most common molecular targets in all study types were protein kinase pathways. Microenvironmental targets were more numerous in clinical studies, whereas cell cycle/apoptosis were more numerous in laboratory studies. Immunotherapy pathways are on the rise in all study types, and the wnt/β-catenin pathway is increasingly identified as a novel target.
Topics: Adult; Humans; Animals; Mice; Molecular Targeted Therapy; beta Catenin; Mutation; Glioma; Brain Neoplasms; Oligodendroglioma; Isocitrate Dehydrogenase
PubMed: 37445633
DOI: 10.3390/ijms241310456 -
Brain and Behavior Aug 2023Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions. (Review)
Review
Tumoral parkinsonism-Parkinsonism secondary to brain tumors, paraneoplastic syndromes, intracranial malformations, or oncological intervention, and the effect of dopaminergic treatment.
INTRODUCTION
Secondary tumoral parkinsonism is a rare phenomenon that develops as a direct or indirect result of brain neoplasms or related conditions.
OBJECTIVES
The first objective was to explore to what extent brain neoplasms, cavernomas, cysts, paraneoplastic syndromes (PNSs), and oncological treatment methods cause parkinsonism. The second objective was to investigate the effect of dopaminergic therapy on the symptomatology in patients with tumoral parkinsonism.
METHODS
A systematic literature review was conducted in the databases PubMed and Embase. Search terms like "secondary parkinsonism," "astrocytoma," and "cranial irradiation" were used. Articles fulfilling inclusion criteria were included in the review.
RESULTS
Out of 316 identified articles from the defined database search strategies, 56 were included in the detailed review. The studies, which were mostly case reports, provided research concerning tumoral parkinsonism and related conditions. It was found that various types of primary brain tumors, such as astrocytoma and meningioma, and more seldom brain metastases, can cause tumoral parkinsonism. Parkinsonism secondary to PNSs, cavernomas, cysts, as well as oncological treatments was reported. Twenty-five of the 56 included studies had tried initiating dopaminergic therapy, and of these 44% reported no, 48% low to moderate, and 8% excellent effect on motor symptomatology.
CONCLUSION
Brain neoplasms, PNSs, certain intracranial malformations, and oncological treatments can cause parkinsonism. Dopaminergic therapy has relatively benign side effects and may relieve motor and nonmotor symptomatology in patients with tumoral parkinsonism. Dopaminergic therapy, particularly levodopa, should therefore be considered in patients with tumoral parkinsonism.
Topics: Humans; Parkinsonian Disorders; Brain Neoplasms; Dopamine; Astrocytoma; Paraneoplastic Syndromes; Meningeal Neoplasms; Cysts
PubMed: 37433071
DOI: 10.1002/brb3.3151 -
Clinical & Translational Oncology :... Feb 2024Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal... (Review)
Review
Glioblastoma (GBM) constitutes the most common primary brain tumor in adults. The challenges in GBM therapeutics have shed light on zebrafish used as a promising animal model for preclinical GBM xenograft studies without a standardized methodology. This systematic review aims to summarize the advances in zebrafish GBM xenografting, compare research protocols to pinpoint advantages and underlying limitations, and designate the predominant xenografting parameters. Based on the PRISMA checklist, we systematically searched PubMed, Scopus, and ZFIN using the keywords "glioblastoma," "xenotransplantation," and "zebrafish" for papers published from 2005 to 2022, available in English. 46 articles meeting the review criteria were examined for the zebrafish strain, cancer cell line, cell labeling technique, injected cell number, time and site of injection, and maintenance temperature. Our review designated that AB wild-type zebrafish, Casper transparent mutants, transgenic Tg(fli1:EGFP), or crossbreeding of these predominate among the zebrafish strains. Orthotopic transplantation is more commonly employed. A number of 50-100 cells injected at 48 h post-fertilization in high density and low infusion volume is considered as an effective xenografting approach. U87 cells are used for GBM angiogenesis studies, U251 for GBM proliferation studies, and patient-derived xenograft (PDX) to achieve clinical relevance. Gradual acclimatization to 32-33 °C can partly address the temperature differential between the zebrafish and the GBM cells. Zebrafish xenograft models constitute valuable tools for preclinical studies with clinical relevance regarding PDX. The GBM xenografting research requires modification based on the objective of each research team. Automation and further optimization of the protocol parameters could scale up the anticancer drug trials.
Topics: Animals; Humans; Glioblastoma; Transplantation, Heterologous; Zebrafish; Heterografts; Brain Neoplasms; Cell Line, Tumor; Xenograft Model Antitumor Assays; Disease Models, Animal
PubMed: 37400666
DOI: 10.1007/s12094-023-03258-7 -
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 -
Scientific Reports Mar 2023Glioblastomas presenting topographically at the cerebellopontine angle (CPA) are exceedingly rare. Given the specific anatomical considerations and their rarity, overall...
Glioblastomas presenting topographically at the cerebellopontine angle (CPA) are exceedingly rare. Given the specific anatomical considerations and their rarity, overall survival (OS) and management are not discussed in detail. The authors performed an integrative survival analysis of CPA glioblastomas. A literature search of PubMed, Scopus, and Web of Science databases was performed per PRISMA guidelines. Patient data including demographics, clinical features, neuroimaging, management, follow-up, and OS were extracted. The mean age was 39 ± 26.2 years. The mean OS was 8.9 months. Kaplan-Meier log-rank test and univariate Cox proportional-hazards model identified hydrocephalus (log-rank, p = 0.034; HR 0.34; 95% CI 0.12-0.94; p = 0.038), chemotherapy (log-rank, p < 0.005; HR 5.66; 95% CI 1.53-20.88; p = 0.009), and radiotherapy (log-rank, p < 0.0001; HR 12.01; 95% CI 3.44-41.89; p < 0.001) as factors influencing OS. Hydrocephalus (HR 3.57; 95% CI 1.07-11.1; p = 0.038) and no adjuvant radiotherapy (HR 0.12; 95% CI 0.02-0.59; p < 0.01) remained prognostic on multivariable analysis with fourfold and twofold higher risk for the time-related onset of death, respectively. This should be considered when assessing the risk-to-benefit ratio for patients undergoing surgery for CPA glioblastoma.
Topics: Humans; Child; Adolescent; Young Adult; Adult; Middle Aged; Aged; Glioblastoma; Cerebellopontine Angle; Survival Analysis; Prognosis; Proportional Hazards Models; Kaplan-Meier Estimate; Retrospective Studies
PubMed: 36932101
DOI: 10.1038/s41598-023-30677-x -
World Neurosurgery Jul 2023Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications....
BACKGROUND
Staged surgery for skull base lesions has been utilized to facilitate maximal safe resection and optimize outcomes while minimizing morbidity and complications. Conversely, staged surgery for primary intraparenchymal neoplasms is less commonly performed and has not been reported as extensively within the literature. As such, we performed a systematic review to examine the unique surgical indications for staging, timing between stages, specific surgical approaches utilized, and postoperative complications of staged surgery for primary intra-axial neoplasms.
METHODS
A literature search was conducted in August 2021 using PubMed, Web of Science, and Cochrane databases using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) recommendations. Titles and abstracts were evaluated independently by 2 authors, after which articles were selected for final analysis based on application of strict inclusion criteria during full text screen. Each included article was then qualitatively assessed and relevant variables-including operative approaches, timing, and outcomes-were extracted for synthesis.
RESULTS
Of 115 results, 7 articles were included for final analysis and consisted of 17 pediatric and 4 adult patients. Staged approaches were more commonly utilized in the pediatric patient population for resection of astrocytoma and glioma. Pediatric patients had a timing of surgeries ranging from 5-10 days between operations, compared with 18 days to 4 months in adult patients. Complications in pediatric patients were most commonly hemiparesis, hydrocephalus, cranial nerve VI and VII palsies, truncal ataxia, and cerebellar mutism, while complications in adult patients included language and abstract thinking deficits, respiratory failure, and motor weakness.
CONCLUSIONS
This study reports the first comprehensive review of staged surgical procedures for primary, intra-axial cranial neoplasms. There exists a large degree of heterogeneity in complications resulting from staged surgeries for intra-axial neoplasms, which are similar to complications associated with single-stage surgery for intraparenchymal lesions as well as multi-stage surgeries for skull base lesions.
Topics: Adult; Humans; Child; Skull Base; Glioma; Astrocytoma; Postoperative Complications
PubMed: 36924887
DOI: 10.1016/j.wneu.2023.03.046 -
Cureus Feb 2023Subependymal giant cell astrocytoma (SEGA) is the most common intracranial tumor in tuberous sclerosis (TS) patients. The tumor generally localizes in the proximity of...
Subependymal giant cell astrocytoma (SEGA) is the most common intracranial tumor in tuberous sclerosis (TS) patients. The tumor generally localizes in the proximity of Monro's foramen; as it grows, it subsequently causes hydrocephalus and increases intracranial pressure (ICP). However, acute symptoms of increased ICP due to intratumoral bleeding rarely manifest in SEGA patients. We present a 27-year-old male with TS who presented due to hemorrhagic complications of SEGA with intratumoral bleeding and vitreous orbital hemorrhage. We then conducted a systematic review with four databases (PubMed, Web of Science, Google Scholar, and Cochrane) to identify similar cases using the following keywords: "Subependymal giant cell astrocytoma," "Hemorrhage," "Haemorrhage," and "Bleeding." Our review identified 12 articles reporting 14 cases of hemorrhagic complications of SEGA in addition to our case report. The median age of diagnosis was 21 (range 5-79) years with unequal gender distribution (M:F ratio, 11:4). Headache was the most presented symptom, followed by hemiparesis, seizure, altered mental status, visual deterioration, and headache accompanied by seizure. TS was seen in most of the cases (80%). Gross total resection (GTR) was achieved in 53.5% of the patients. Regarding the clinical outcome, 66.7% had a good outcome, 20% died, and 13.3% had no report of their outcomes. No tumor recurrence was seen in the cases with a reported duration of follow-up. Catastrophic presentation of SEGA apoplexy is a rare occurrence. We present a case report with a systematic review and discuss SEGA apoplexy's possible pathophysiology and outcome.
PubMed: 36915840
DOI: 10.7759/cureus.34784 -
BMC Cancer Feb 2023Glioblastoma, the most common primary malignant brain tumour in adults, is a highly vascular tumour characterised by abnormal angiogenesis. Additional mechanisms of...
BACKGROUND
Glioblastoma, the most common primary malignant brain tumour in adults, is a highly vascular tumour characterised by abnormal angiogenesis. Additional mechanisms of tumour vascularisation have also been reported in glioblastoma, including the formation of tumour cell-derived vessels by vasculogenic mimicry (VM) or the transdifferentiation of tumour cells to endothelial cells. VM and endothelial transdifferentiation have frequently been reported as distinct processes, however, the use of both terms to describe a single process of vascularisation also occurs. Some overlapping characteristics have also been reported when identifying each process. We therefore aimed to determine the markers consistently attributed to VM and endothelial transdifferentiation in the glioblastoma literature.
METHODS
Ovid MEDLINE and Ovid Embase were searched for studies published between January 1999 and July 2021 that assessed VM or tumour to endothelial transdifferentiation in human glioblastoma. The online systematic review tool Covidence was used for screening and data extraction. Extracted data included type of tumour-derived vasculature reported, methods and techniques used, and markers investigated. Studies were grouped based on type of vasculature reported for further assessment.
RESULTS
One hundred and thirteen of the 419 unique records identified were included for analysis. VM was reported in 64/113 studies, while tumour to endothelial transdifferentiation was reported in 16/113 studies. The remaining studies used both terms to describe a single process, did not define the process that occurred, or concluded that neither VM nor endothelial transdifferentiation occurred. Absence of CD34 and/or CD31 in vascular structures was the most common indicator of VM, while expression of CD34 and/or CD31, in addition to various other endothelial, stem cell or tumour cell markers, indicated tumour to endothelial transdifferentiation.
CONCLUSION
Cells derived from tumour to endothelial transdifferentiation express typical endothelial markers including CD34 and CD31, while tumour cells contributing to VM lack CD34 and CD31 expression. Additional tumour markers are required to identify transdifferentiation in glioblastoma tissue, and this process requires further characterisation.
Topics: Adult; Humans; Glioblastoma; Endothelial Cells; Cell Transdifferentiation; Neovascularization, Pathologic; Cell Differentiation; Biomarkers, Tumor
PubMed: 36823554
DOI: 10.1186/s12885-023-10659-y -
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 -
European Journal of Medical Research Jan 2023Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Primary central nervous system (CNS) tumors are a heterogeneous group of neoplasms, including benign and malignant tumors. Since there are many heterogeneities in the prevalence reported in previous studies on this type of tumor, this study was performed to determine the overall prevalence of different primary CNS tumors.
METHOD
The study was conducted as a systematic review and meta-analysis by searching international databases, including PubMed, Scopus, Science Direct, Web of science, and the Google Scholar search engine until August 2020. After transferring the studies to information management software (EndNote) and eliminating duplicate studies, the remaining studies were reviewed based on inclusion and exclusion criteria according to three stages of primary and secondary evaluation and qualitative evaluation. Comprehensive Meta-Analysis software, Begg, Mazumdar, and I tests were used for data analysis, publication bias analysis, and heterogeneity analysis, respectively.
RESULTS
After performing the systematic review steps, 80 studies were included for final analysis. Based on 8 studies, the prevalence of brain tumors was 70.9%. Also, studies on 7 other studies showed that the prevalence of spinal tumors was 12.2%. A review of 14 studies showed that the prevalence of neuroepithelial tumors was 34.7%. The analysis of 27 studies reported a prevalence of glioma tumors of 42.8%. Analyses performed on other studies showed that the prevalence of pituitary adenomas was 12.2%, embryonal tumors 3.1%, ependymal tumors 3.2%, meningiomas 24.1%, glial tumors 0.8%, astrocytic 20.3%, oligodendroglial 3.9%, glioblastoma 17.7%, schwannoma 6.7%, medulloblastoma 7.7% and Polycystic astrocytomas 3.8%.
CONCLUSION
As a result, it can be stated that brain tumors are the most common type of primary CNS tumors. It was also observed that tumors involving neuroepithelial cells are more common in patients than other types of tumors.
Topics: Humans; Prevalence; Central Nervous System Neoplasms; Brain Neoplasms; Glioblastoma
PubMed: 36670466
DOI: 10.1186/s40001-023-01011-y