Therapeutic management of gliosarcoma in the temozolomide era

McAleer, M.F.; Brown, Paul D.

doi:10.2217/cns.14.61

Cited by 18 publications

(7 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evaluation of gliosarcoma response to therapy is limited due to its rarity. As most chemotherapeutic agents demonstrate limited efficacy in CNS malignancies, gliosarcoma treatments generally parallel that of glioblastoma, consisting of maximal surgical resection, temozolomide (TMZ), and radiotherapy (8). Some studies demonstrate a possible benefit associated with TMZ and radiotherapy (9,10); however, prospective evidence is sorely lacking (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma

et al. 2020

View full text Add to dashboard Cite

Introduction: Gliosarcomas are clinically aggressive tumors, histologically distinct from glioblastoma. Data regarding the impact of extent of resection and post-operative adjuvant therapy on gliosarcoma outcomes are limited.Methods: Patients with histologically confirmed gliosarcoma diagnosed between 1999 and 2019 were identified. Clinical, molecular, and radiographic data were assembled based on historical records. Comparisons of categorical variables used Pearson's Chi-square and Fisher's exact test while continuous values were compared using the Wilcoxon signed-rank test. Survival comparisons were assessed using Kaplan-Meier statistics and Cox regressions.Results: Seventy-one gliosarcoma patients were identified. Secondary gliosarcoma was not associated with worse survival when compared to recurrent primary gliosarcoma (median survival 9.8 [3.8 to 21.0] months vs. 7.6 [1.0 to 35.7], p = 0.7493). On multivariable analysis, receipt of temozolomide (HR = 0.02, 95% CI 0.001-0.21) and achievement of gross total resection (GTR; HR = 0.13, 95% CI 0.02-0.77) were independently prognostic for improved progression-free survival (PFS) while only receipt of temozolomide was independently associated with extended overall survival (OS) (HR = 0.03, 95% CI 0.001-0.89). In patients receiving surgical resection followed by radiotherapy and concomitant temozolomide, achievement of GTR was significantly associated with improved PFS (median 32.97 [7.1-79.6] months vs. 5.45 [1.8-26.3], p = 0.0092) and OS (median 56.73 months [7.8-104.5] vs. 14.83 [3.8 to 29.1], p = 0.0252). Conclusion:Multimodal therapy is associated with improved survival in gliosarcoma. Even in patients receiving aggressive post-operative multimodal management, total surgical removal of macroscopic disease remains important for optimal outcomes.

show abstract

Section: Introductionmentioning

confidence: 99%

Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma

et al. 2020

View full text Add to dashboard Cite

show abstract

“…In recent years, combined treatment using radiotherapy plus temozolomide (TMZ) becomes the standard treatment for GBM [28]. TMZ is a DNA-alkylating agent that adds a methyl group to the O6 position of guanine in genomic DNA to result in tumor cell death [29]. Compared with radiotherapy alone, TMZ addition increased the median survival from 15.3 months to 21.7 months in patients [30].…”

Section: Introductionmentioning

confidence: 99%

Inhibitor of Nicotinamide Phosphoribosyltransferase Sensitizes Glioblastoma Cells to Temozolomide via Activating ROS/JNK Signaling Pathway

Feng

Yan

Zhao

et al. 2016

BioMed Research International

View full text Add to dashboard Cite

Overcoming temozolomide (TMZ) resistance is a great challenge in glioblastoma (GBM) treatment. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the biosynthesis of nicotinamide adenine dinucleotide and has a crucial role in cancer cell metabolism. In this study, we investigated whether FK866 and CHS828, two specific NAMPT inhibitors, could sensitize GBM cells to TMZ. Low doses of FK866 and CHS828 (5 nM and 10 nM, resp.) alone did not significantly decrease cell viability in U251-MG and T98 GBM cells. However, they significantly increased the antitumor action of TMZ in these cells. In U251-MG cells, administration of NAMPT inhibitors increased the TMZ (100 μM)-induced apoptosis and LDH release from GBM cells. NAMPT inhibitors remarkably enhanced the activities of caspase-1, caspase-3, and caspase-9. Moreover, NAMPT inhibitors increased reactive oxygen species (ROS) production and superoxide anion level but reduced the SOD activity and total antioxidative capacity in GBM cells. Treatment of NAMPT inhibitors increased phosphorylation of c-Jun and JNK. Administration of JNK inhibitor SP600125 or ROS scavenger tocopherol with TMZ and NAMPT inhibitors substantially attenuated the sensitization of NAMPT inhibitor on TMZ antitumor action. Our data indicate a potential value of NAMPT inhibitors in combined use with TMZ for GBM treatment.

show abstract

“…Temozolomide is included in the standard care for patients with glioblastoma multiforme after maximal safe surgical resection followed by adjuvant partial brain radiation ( 27 ). The therapeutic benefit of TMZ depends on its capability to alkylate/methylate DNA, which damages the DNA and triggers the death of tumor cells ( 28 ). However, the interaction between TMZ and the Livin gene is unclear.…”

Section: Discussionmentioning

confidence: 99%

Difference in the Inhibitory Effect of Temozolomide on TJ905 Glioma Cells and Stem Cells

et al. 2017

View full text Add to dashboard Cite

This study aims to determine the difference in the inhibitory effect of temozolomide (TMZ) on TJ905 glioma cells and stem cells. TJ905 cancer stem cells were isolated. Livin is a member of the inhibitor of apoptosis protein family. The TJ905 cells and cancer stem cells were transfected with a Livin-shRNA and negative-shRNA, respectively, and then treated with TMZ. At 48 h post-transfection, a cell counting kit 8 assay, flow cytometry, and real-time qPCR were performed to detect cell proliferation, the cell cycle, and the expression of the Caspase-3, -7, and -9 mRNAs, respectively. As a result, the suppressive effect of TMZ on TJ905 cells was more significant than its effect on TJ905 cancer stem cells. TMZ exerted an inhibitory effect on the growth of TJ905 glioma cells by arresting them at G0/G1 phase and arresting cancer stem cells at S phase in a dose-dependent manner. TMZ inhibited Livin mRNA expression and increased the expression of the Caspase-3, -7, and -9 mRNAs. Low Livin mRNA expression induced high levels of Caspase-3, -7, and -9 expressions, thus promoting the apoptosis of both TJ905 cells and cancer stem cells in response to TMZ treatment. The TJ905 cells transfected with the Livin-shRNA were more sensitive to TMZ, whereas the TJ905 glioma stem cells transfected with the Livin-shRNA showed no significant changes in their sensitivity to TMZ. In conclusion, the Livin gene may play an important role in the resistance mechanisms of TJ905 glioma cells and cancer stem cells. However, Livin had a more distinct role in TMZ resistance, cell proliferation, and the cell cycle in TJ905 glioma cells than in cancer stem cells.

show abstract

Therapeutic management of gliosarcoma in the temozolomide era

Cited by 18 publications

References 27 publications

Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma

Evaluating Surgical Resection Extent and Adjuvant Therapy in the Management of Gliosarcoma

Inhibitor of Nicotinamide Phosphoribosyltransferase Sensitizes Glioblastoma Cells to Temozolomide via Activating ROS/JNK Signaling Pathway

Difference in the Inhibitory Effect of Temozolomide on TJ905 Glioma Cells and Stem Cells

Contact Info

Product

Resources

About