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BMC Cancer Nov 2021Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that...
BACKGROUND
Malignant glioma cell line models are integral to pre-clinical testing of novel potential therapies. Accurate prediction of likely efficacy in the clinic requires that these models are reliable and consistent. We assessed this by examining the reporting of experimental conditions and sensitivity to temozolomide in glioma cells lines.
METHODS
We searched Medline and Embase (Jan 1994-Jan 2021) for studies evaluating the effect of temozolomide monotherapy on cell viability of at least one malignant glioma cell line. Key data items included type of cell lines, temozolomide exposure duration in hours (hr), and cell viability measure (IC).
RESULTS
We included 212 studies from 2789 non-duplicate records that reported 248 distinct cell lines. The commonest cell line was U87 (60.4%). Only 10.4% studies used a patient-derived cell line. The proportion of studies not reporting each experimental condition ranged from 8.0-27.4%, including base medium (8.0%), serum supplementation (9.9%) and number of replicates (27.4%). In studies reporting IC, the median value for U87 at 24 h, 48 h and 72 h was 123.9 μM (IQR 75.3-277.7 μM), 223.1 μM (IQR 92.0-590.1 μM) and 230.0 μM (IQR 34.1-650.0 μM), respectively. The median IC at 72 h for patient-derived cell lines was 220 μM (IQR 81.1-800.0 μM).
CONCLUSION
Temozolomide sensitivity reported in comparable studies was not consistent between or within malignant glioma cell lines. Drug discovery science performed on these models cannot reliably inform clinical translation. A consensus model of reporting can maximise reproducibility and consistency among in vitro studies.
Topics: Animals; Antineoplastic Agents, Alkylating; Bias; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Glioma; Humans; In Vitro Techniques; Mice; Temozolomide
PubMed: 34794398
DOI: 10.1186/s12885-021-08972-5 -
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 -
Frontiers in Neurology 2021Clinical presentations and treatment programs about anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis still remain incompletely understood. This study...
Clinical presentations and treatment programs about anti-leucine-rich glioma inactivated 1 (LGI1) encephalitis still remain incompletely understood. This study analyzed the clinical features and therapeutic effects of anti-LGI1 encephalitis. PubMed, EMBASE, and the Cochrane Library were searched to identify published English and Chinese articles until April 2021. Data were extracted, analyzed, and recorded in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. A total of 80 publications detailing 485 subjects matched our inclusion criteria. Short-term memory loss (75.22%), faciobrachial dystonic seizures (FBDS) (52.53%), other seizures excluding FBDS (68.48%), psychiatric symptoms (57.67%), and sleep disturbances (34.30%) were the most frequently described symptoms in anti-LGI1 encephalitis. Hyponatremia (54.90%) was the most common hematologic examination change. The risk of incidence rate of malignant tumors was higher than in healthy people. The positive rate of anti-LGI1 in serum (99.79%) was higher than CSF (77.38%). Steroids (93.02%), IVIG (87.50%), and combined use (96.67%) all had a high remission rate in the initial visit. A total of 35 of 215 cases relapsed, of which 6/35 (17.14%) did not use first-line treatment, and 21 (60.00%) did not maintain long-term treatment. Plasma exchange (PE) could be combined in severe patients, immunosuppressant could be used for refractory patients or for recurrence and using an anti-epileptic drug to control seizures may benefit cognition. Short-term memory loss, FBDS, psychiatric symptoms, and hyponatremia were key features in identifying anti-LGI1 encephalitis. Serum and CSF antibody tests should be considered in diagnosis criteria. Steroids with IVIG should be recommended, PE was combined for use in severe patients, immunosuppressant therapy might improve outcomes if recurrence or progression occurred, and control seizures might benefit cognition. The useful ways to reduce relapse rate were early identification, clear diagnosis, rapid treatment, and maintaining long-term treatment. The follow-up advice was suggested according to the research of paraneoplastic syndrome, and concern about tumors was vital as well.
PubMed: 35095736
DOI: 10.3389/fneur.2021.791014 -
BMJ Open Dec 2021To assess the efficacy and safety of bevacizumab (BEV) in patients with glioma. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the efficacy and safety of bevacizumab (BEV) in patients with glioma.
DESIGN
Systematic review and meta-analysis.
PARTICIPANTS
Adults aged 18 years and above, whose histology was confirmed to be malignant glioma.
PRIMARY AND SECONDARY OUTCOME MEASURES
The main indicators included progression-free survival (PFS) rate and overall survival (OS) rate, and the secondary indicators were adverse reactions.
RESULTS
A total of 11 clinical centre trials were included in this study for meta-analysis, including 2392 patients. The results of the meta-analysis showed that the median PFS rate of the BEV group was significantly higher than that of the non-BEV group (p<0.00001). When comparing PFS between two groups, we found that the PFS in the BEV group was higher than that in the non-BEV group at 6 months (OR 3.31, 95% CI 2.74 to 4.00, p<0.00001), 12 months (OR 2.05, 95% CI 1.70 to 2.49, p<0.00001) and 18 months (OR 1.31, 95% CI 1.02 to 1.69, p=0.03). But at 24 months (OR 0.83, 95% CI 0.50 to 1.37, p=0.47), there was no significant difference between the two groups. At 30 months (OR 0.62, 95% CI 0.39 to 0.97, p=0.04), the PFS of the BEV group was lower than that of the non-BEV group. Moreover, The results showed that BEV had no significant effect on improving OS, but the adverse reaction in BEV group was significantly higher than that in non-BEV group.
CONCLUSION
The evidence suggests that BEV can significantly prolong the PFS of patients with glioma within 18 months and shorten the PFS of patients after 30 months. This limitation may be related to the subgroup of patients, the change of recurrence mode, the optimal dose of drug, the increase of hypoxia, the enhancement of invasiveness and so on. Therefore, it is necessary to carry out more samples and higher quality large-scale research in the future.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Glioma; Humans; Progression-Free Survival
PubMed: 34857558
DOI: 10.1136/bmjopen-2021-048975 -
International Journal of Molecular... Apr 2022The invasive capabilities of glioblastoma (GBM) define the cancer's aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences... (Review)
Review
The invasive capabilities of glioblastoma (GBM) define the cancer's aggressiveness, treatment resistance, and overall mortality. The tumor microenvironment influences the molecular behavior of cells, both epigenetically and genetically. Current forces being studied include properties of the extracellular matrix (ECM), such as stiffness and "sensing" capabilities. There is currently limited data on the physical forces in GBM-both relating to how they influence their environment and how their environment influences them. This review outlines the advances that have been made in the field. It is our hope that further investigation of the physical forces involved in GBM will highlight new therapeutic options and increase patient survival. A search of the PubMed database was conducted through to 23 March 2022 with the following search terms: (glioblastoma) AND (physical forces OR pressure OR shear forces OR compression OR tension OR torsion) AND (migration OR invasion). Our review yielded 11 external/applied/mechanical forces and 2 tumor microenvironment (TME) forces that affect the ability of GBM to locally migrate and invade. Both external forces and forces within the tumor microenvironment have been implicated in GBM migration, invasion, and treatment resistance. We endorse further research in this area to target the physical forces affecting the migration and invasion of GBM.
Topics: Brain Neoplasms; Cell Line, Tumor; Cell Movement; Extracellular Matrix; Glioblastoma; Humans; Mechanical Phenomena; Tumor Microenvironment
PubMed: 35409420
DOI: 10.3390/ijms23074055 -
Surgical Neurology International 2023Awake craniotomy (AC) aims to minimize postoperative neurological complications while allowing maximum safe resection. Intraoperative seizures (IOSs) have been a... (Review)
Review
BACKGROUND
Awake craniotomy (AC) aims to minimize postoperative neurological complications while allowing maximum safe resection. Intraoperative seizures (IOSs) have been a reported complication during AC; however, literature delving into the predictors of IOS remains limited. Therefore, we planned a systematic review and meta-analysis of existing literature to explore predictors of IOS during AC.
METHODS
From the inception until June 1, 2022, systematic searches of PubMed, Scopus, the Cochrane Library, CINAHL, and Cochrane's Central Register of Controlled Trials were conducted to look for published studies reporting IOS predictors during AC.
RESULTS
We found 83 different studies in total; included were six studies with a total of 1815 patients, and 8.4% of them experienced IOSs. The mean age of included patients was 45.3 years, and 38% of the sample was female. Glioma was the most common diagnosis among the patients. A pooled random effect odds ratio (OR) of frontal lobe lesions was 2.42 (95% confidence intervals [CI]: 1.10-5.33, = 0.03). Those with a pre-existing history of seizures had an OR of 1.80 (95% CI: 1.13-2.87, = 0.01), and patients on antiepileptic drugs (AEDs) had a pooled OR of 2.47 (95% CI: 1.59-3.85, < 0.001).
CONCLUSION
Patients with lesions of the frontal lobe, a prior history of seizures, and patients on AEDs are at higher risk of IOSs. These factors should be taken into consideration during the patient's preparation for an AC to avoid an intractable seizure and consequently a failed AC.
PubMed: 37404511
DOI: 10.25259/SNI_135_2023 -
Biomedicines Feb 2023(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of... (Review)
Review
(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6-12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11-52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.
PubMed: 36979629
DOI: 10.3390/biomedicines11030651 -
IScience Jun 2023This study aims to evaluate deep learning (DL) performance in differentiating low- and high-grade glioma. Search online database for studies continuously published from...
This study aims to evaluate deep learning (DL) performance in differentiating low- and high-grade glioma. Search online database for studies continuously published from 1st January 2015 until 16th August 2022. The random-effects model was used for synthesis, based on pooled sensitivity (SE), specificity (SP), and area under the curve (AUC). Heterogeneity was estimated using the Higgins inconsistency index (I). 33 were ultimately included in the meta-analysis. The overall pooled SE and SP were 94% and 93%, with an AUC of 0.98. There was great heterogeneity in this field. Our evidence-based study shows DL achieves high accuracy in glioma grading. Subgroup analysis reveals several limitations in this field: 1) Diagnostic trials require standard method for data merging for AI; 2) small sample size; 3) poor-quality image preprocessing; 4) not standard algorithm development; 5) not standard data report; 6) different definition of HGG and LGG; and 7) poor extrapolation.
PubMed: 37250800
DOI: 10.1016/j.isci.2023.106815 -
Neurologia Medico-chirurgica Apr 2022Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent... (Meta-Analysis)
Meta-Analysis
Malignant progression of diffuse low-grade glioma (LGG) is a critical event affecting patient survival; however, the incidence and related factors have been inconsistent in literature. According to the PRISMA guidelines, we systematically reviewed articles from 2009, meta-analyzed the incidence of malignant progression, and clarified factors related to the transformation. Forty-one articles were included in this study (n = 7,122; n, number of patients). We identified two definitions of malignant progression: histologically proven (Htrans) and clinically defined (Ctrans). The malignant progression rate curves of Htrans and Ctrans were almost in parallel when constructed from the results of meta-regression by the mean follow-up time. The true transformation rate was supposed to lie between the two curves, approximately 40% at the 10-year mean follow-up. Risk of malignant progression was evaluated using hazard ratio (HR). Pooled HRs were significantly higher in tumors with a larger pre- and postoperative tumor volume, lower degree of resection, and notable preoperative contrast enhancement on magnetic resonance imaging than in others. Oligodendroglial histology and IDH mutation (IDHm) with 1p/19q codeletion (Codel) also significantly reduced the HRs. Using Kaplan-Meier curves from eight studies with molecular data, we extracted data and calculated the 10-year malignant progression-free survival (10yMPFS). The 10yMPFS in patients with IDHm without Codel was 30.4% (95% confidence interval [95% CI]: 22.2-39.0) in Htrans and 38.3% (95% CI: 32.3-44.3) in Ctrans, and that with IDHm with Codel was 71.7% (95% CI: 61.7-79.5) in Htrans and 62.5% (95% CI: 55.9-68.5) in Ctrans. The effect of adjuvant radiotherapy or chemotherapy could not be determined.
Topics: Brain Neoplasms; Glioma; Humans; Incidence; Isocitrate Dehydrogenase; Mutation
PubMed: 35197400
DOI: 10.2176/jns-nmc.2021-0313 -
Neuro-oncology Advances 2022In patients with high-grade glioma (HGG), true disease progression and treatment-related changes often appear similar on magnetic resonance imaging (MRI), making it... (Review)
Review
BACKGROUND
In patients with high-grade glioma (HGG), true disease progression and treatment-related changes often appear similar on magnetic resonance imaging (MRI), making it challenging to evaluate therapeutic response. Dynamic susceptibility contrast (DSC) MRI has been extensively studied to differentiate between disease progression and treatment-related changes. This systematic review evaluated and synthesized the evidence for using DSC MRI to distinguish true progression from treatment-related changes.
METHODS
We searched Ovid MEDLINE and the Ovid MEDLINE in-process file (January 2005-October 2019) and the reference lists. Studies on test performance of DSC MRI using relative cerebral blood volume in HGG patients were included. One investigator abstracted data, and a second investigator confirmed them; two investigators independently assessed study quality. Meta-analyses were conducted to quantitatively synthesize area under the receiver operating curve (AUROC), sensitivity, and specificity.
RESULTS
We screened 1177 citations and included 28 studies with 638 patients with true tumor progression, and 430 patients with treatment-related changes. Nineteen studies reported AUROC and the combined AUROC is 0.85 (95% CI, 0.81-0.90). All studies contributed data for sensitivity and specificity, and the pooled sensitivity and specificity are 0.84 (95% CI, 0.80-0.88), and 0.78 (95% CI, 0.72-0.83). Extensive subgroup analyses based on study, treatment, and imaging characteristics generally showed similar results.
CONCLUSIONS
There is moderate strength of evidence that relative cerebral blood volume obtained from DSC imaging demonstrated "excellent" ability to discriminate true tumor progression from treatment-related changes, with robust sensitivity and specificity.
PubMed: 35386567
DOI: 10.1093/noajnl/vdac027