scholarly journals Edge Contrast of the FLAIR Hyperintense Region Predicts Survival in Patients with High-Grade Gliomas following Treatment with Bevacizumab

2018 ◽  
Vol 39 (6) ◽  
pp. 1017-1024 ◽  
Author(s):  
N. Bahrami ◽  
D. Piccioni ◽  
R. Karunamuni ◽  
Y.-H. Chang ◽  
N. White ◽  
...  
Keyword(s):  
High Grade ◽  
Edge Contrast ◽  
High Grade Gliomas

Venous Thromboembolism and High Grade Gliomas

1993 ◽  
Vol 70 (03) ◽  
pp. 393-396 ◽  
Author(s):  
Mandeep S Dhami ◽  
Robert D Bona ◽  
John A Calogero ◽  
Richard M Hellman
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Medical Center ◽  
Significant Risk ◽  
Bleeding Complications ◽  
Fisher Exact Test ◽  
High Grade ◽  
Chi Square ◽  
Exact Test ◽  
High Grade Gliomas

SummaryA retrospective study was done to determine the incidence of and the risk factors predisposing to clinical venous thromboembolism (VTE) in patients treated for high grade gliomas. Medical records of 68 consecutive patients diagnosed and treated at Saint Francis Hospital and Medical Center from January 1986 to June 1991 were reviewed. The follow up was to time of death or at least 6 months (up to December 1991). All clinically suspected episodes of VTE were confirmed by objective tests. Sixteen episodes of VTE were detected in 13 patients for an overall episode rate of 23.5%. Administration of chemotherapy (p = 0.027, two tailed Fisher exact test) and presence of paresis (p = 0.031, two tailed Fisher exact test) were statistically significant risk factors for the development of VTE. Thrombotic events were more likely to occur in the paretic limb and this difference was statistically significant (p = 0.00049, chi square test, with Yates correction). No major bleeding complications were seen in the nine episodes treated with long term anticoagulation.We conclude that venous thromboembolic complications are frequently encountered in patients being treated for high grade gliomas and the presence of paresis and the administration of chemotherapy increases the risk of such complications.

A Prospective Validation Study of the First 3D Digital Exoscope for Visualization of 5-ALA–Induced Fluorescence in High-Grade Gliomas

2021 ◽  
Author(s):  
Michael A. Vogelbaum ◽  
Derek Kroll ◽  
Arnold Etame ◽  
Nam Tran ◽  
James Liu ◽  
...  
Keyword(s):  
Validation Study ◽  
High Grade ◽  
High Grade Gliomas

scholarly journals TMOD-18. TARGETING THE PI3K/AKT PATHWAY IN MYCN AMPLIFIED HIGH GRADE GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii231-ii232
Author(s):  
Katharine Halligan ◽  
Ann-Catherine Stanton ◽  
Matthew Halbert ◽  
Brian Golbourn ◽  
Stephen Mack ◽  
...  
Keyword(s):  
Stem Cells ◽  
Tumor Suppressor ◽  
Mouse Model ◽  
Protein Expression ◽  
Neural Stem Cells ◽  
Tumor Suppressor Genes ◽  
Akt Pathway ◽  
High Grade ◽  
Suppressor Genes ◽  
High Grade Gliomas

Abstract Pediatric glioblastoma (pGBM) are incurable brain tumors with overall poor prognosis and response to treatments due to molecular and epigenetic heterogeneity. In particular, the MYCN subtype of pGBM are a highly aggressive form of GBM with a dismal median survival of only 14 months. Furthermore, this subtype is enriched with loss of the tumor suppressor genes TP53 and PTEN, leading to aberrantly active PI3K-AKT signaling pathway and DNA-checkpoint abnormalities. Here, we report the generation of a novel syngeneic mouse model that recapitulates the features of the MYCN subtype of pGBM. We isolated Sox2-Cre neural stem cells from C57BL/6 mice and transduced inverted retroviral-cassettes of the murine Mycn oncogene simultaneously with shRNA targeting tumor suppressor genes p53 and Pten. Retroviral-cassettes are flanked by tandem LoxP sites arranged so that Cre recombinase expression inverts the cassettes in frame allowing for MYCN protein expression and loss of the P53/PTEN proteins. Transgene activation is accompanied with selectable cell surface markers and fluorescent tags enabling for fluorescent activated cell sorting (FACS) of the desired cell populations. Neural stem cells with MYCN protein expression and concurrent silencing of P53 and PTEN protein (NPP cells) result in significantly increased proliferation and activation of PI3K-AKT pathway as compared to control neural stem cells and have. Injection of NPP cells into the forebrain of immune competent C57BL/6 mice result in the formation of invasive high-grade gliomas with a lethal phenotype at ~50 days post injection. Using several next generation brain penetrant small molecule inhibitors of the PI3K-AKT pathway, we show inhibition of tumorigenesis in vitro. Moreover, we have identified several novel mechanisms of PI3KAKT treatment resistance and are currently identifying therapies that may overcome this resistance through RNA seq analysis. In summary, well defined genetic drivers of GBM can lead to informed mouse model generation to test promising therapies.

scholarly journals Mebendazole and temozolomide in patients with newly diagnosed high-grade gliomas: Results of a phase 1 clinical trial

2020 ◽  
Author(s):  
Gary L Gallia ◽  
Matthias Holdhoff ◽  
Henry Brem ◽  
Avadhut D Joshi ◽  
Christine L Hann ◽  
...  
Keyword(s):  
Dose Escalation ◽  
Plasma Levels ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Maximum Tolerated Dose ◽  
High Grade ◽  
Newly Diagnosed ◽  
Kaplan Meier ◽  
High Grade Gliomas ◽  
Expansion Cohort

Abstract Background Mebendazole is an anthelmintic drug introduced for human use in 1971 that extends survival in preclinical models of glioblastoma and other brain cancers. Methods A single center dose escalation and safety study of mebendazole in 24 patients with newly diagnosed high-grade gliomas (HGG) in combination with temozolomide was conducted. Patients received mebendazole in combination with adjuvant temozolomide after completing concurrent radiation plus temozolomide. Dose escalation levels were 25, 50, 100 and 200 mg/kg/day of oral mebendazole. A 15-patient expansion cohort was conducted at the maximum tolerated dose of 200 mg/kg/day. Trough plasma levels of mebendazole were measured at 4, 8 and 16 weeks. Results Twenty-four patients (18 glioblastoma, 6 anaplastic astrocytoma) were enrolled with median age of 49.9 years. Four patients (at 200 mg/kg) developed elevated grade 3 ALT and/or AST after one month, which reversed with lower dosing or discontinuation. Plasma levels of mebendazole were variable but generally increased with dose. Kaplan Meier analysis showed a 21-month median survival with 43% of patients alive at two years and 25% at 3 and 4 years. Median progression free survival (PFS) from the date of diagnosis for 17 patients taking more than one month of mebendazole was 13.1 months (95% Confidence Interval: 8.8 to 14.6 months) but for seven patients who received less than one month of mebendazole PFS was 9.2 months (95% CI: 5.8 -13.0 months). Conclusion Mebendazole at doses up to 200 mg/kg demonstrated long-term safety and acceptable toxicity. Further studies are needed to determine mebendazole’s efficacy in patients with HGG.

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