Combination celecoxib and temozolomide in C6 rat glioma orthotopic model

Kang, Seok‐Gu; Kim, Jong Soo; Park, Kwan; Groves, Morris D.; Nam, Do Hyun

doi:10.3892/or.15.1.7

Cited by 29 publications

(31 citation statements)

References 27 publications

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“…Because of the radiosensitizing potential of meloxicam and in view of the recently reported interaction between irradiation and celecoxib [40] as well as between temozolomide and celecoxib [43] in experimental gliomas, selective COX-2 inhibitors yield promising perspective to further improve the therapy of glioma patients.…”

Section: Discussionmentioning

confidence: 99%

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

et al. 2007

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The COX-2 protein is frequently overexpressed in human malignant gliomas. This expression has been associated with their aggressive growth characteristics and poor prognosis for patients. Targeting the COX-2 pathway might improve glioma therapy. In this study, the effects of the selective COX-2 inhibitor meloxicam alone and in combination with irradiation were investigated on human glioma cells in vitro. A panel of three glioma cell lines (D384, U87 and U251) was used in the experiments from which U87 cells expressed constitutive COX-2. The response to meloxicam and irradiation (dose-range of 0-6 Gy) was determined by the clonogenic assay, cell proliferation was evaluated by growth analysis and cell cycle distribution by FACS. 24-72 h exposure to 250-750 lM meloxicam resulted in a time and dose dependent growth inhibition with an almost complete inhibition after 24 h for all cell lines. Exposure to 750 lM meloxicam for 24 h increased the fraction of cells in the radiosensitive G 2 /M cell cycle phase in D384 (18-27%) and U251 (17-41%) cells. 750 lM meloxicam resulted in radiosensitization of D384 (DMF:2.19) and U87 (DMF:1.25) cells, but not U251 cells (DMF:1.08). The selective COX-2 inhibitor meloxicam exerted COX-2 independent growth inhibition and radiosensitization of human glioma cells.

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Section: Discussionmentioning

confidence: 99%

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

et al. 2007

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“…Yet, the median survival remains less than 2 years and novel therapeutic approaches, such as immunotherapy, gene therapy, antiangiogenic agents and growth factor inhibitors, are being pursued at the pre-clinical and clinical levels. Furthermore, to maximize the anticancer effects, combination therapy of two or more therapeutics with independent modes of action are being actively evaluated (10)(11)(12).…”

Section: Discussionmentioning

confidence: 99%

Combined therapy of temozolomide and ZD6474 (vandetanib) effectively reduces glioblastoma tumor volume through anti-angiogenic and anti-proliferative mechanisms

Kim

et al. 2012

Mol Med Report

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Abstract. Currently, clinically available options for treating glioblastoma (GBM) are quite limited, and there is a clear need to develop novel treatment strategies that can more effectively manage tumors. Here, we present a combination treatment of temozolomide (TMZ), a blood-brain barrier penetrating DNA alkylating agent, and ZD6474 (vandetanib), a VEGFR2 and EGFR dual-targeting anti-angiogenic agent, as a novel treatment strategy for GBM. In a U-87MG orthotopic xenograft model, the combination treatment provided a marked 94% tumor volume reduction. This reduction was greater than that achieved by monotherapy of either agent, and was correlated with a statistically significant reduction in microvessel density (CD31 + cells) and proliferation (PCNA + cells). These results confirm the necessity to target angiogenesis in addition to utilizing cytotoxic approaches, and provide the rationale for application of TMZ + ZD6474 combination therapy for treating GBM patients in the clinical setting.

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“…22 Early-phase clinical studies of celecoxib have been promising in some solid tumors. [23][24][25][26] Preclinical data have shown promising results using combinations of cytotoxic and anti-angiogenic therapies in animal models of solid tumors.…”

mentioning

confidence: 99%

“…19,20 COX-2 is highly expressed in glioma cells and tumor vasculature, 21 and inhibition of COX-2 has shown efficacy in preclinical rat models of solid tumors. 22 Early-phase clinical studies of celecoxib have been promising in some solid tumors. [23][24][25][26] Preclinical data have shown promising results using combinations of cytotoxic and anti-angiogenic therapies in animal models of solid tumors.…”

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confidence: 99%

Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults

et al. 2008

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We conducted a phase II study of the combination of temozolomide and angiogenesis inhibitors for treating adult patients with newly diagnosed glioblastoma. Patients who had stable disease following standard radiation therapy received temozolomide for 5 days in 28-day cycles, in combination with daily thalidomide and celecoxib. Patients were treated until tumor progression or development of unacceptable toxicity. Four-month progression-free survival (PFS) from study enrollment was the primary end point, and overall survival (OS) was the secondary end point. In addition, we sought to correlate response with O 6 -methylguanine-DNA methyltransferase promoter methylation status and serum levels of angiogenic peptides. Fifty patients with glioblastoma were enrolled (18 women, 32 men). Median age Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults Santosh Kesari, David Schiff, John W. Henson, Alona Muzikansky, Debra C. Gigas, Lisa Doherty, Tracy T. Batchelor, Janina A. Longtine, Keith L. Ligon, Susan Weaver, Andrea Laforme, Naren Ramakrishna, Peter McL. Black, Jan Drappatz, Abigail Ciampa, Judah Folkman, Mark Kieran, and Patrick Y. Wen Dana-Farber/Brigham and Women's Cancer Center, Center for Neuro-Oncology, Boston, MA (S.K., D.C.G., L.D., N.R., P.M.B., J.D., A.C., P.Y.W.); Departments of Neurology (S.K., J.D., P.Y.W.), Pathology (J.A.L., K.L.L.), Radiation Oncology (N.R.), and Neurosurgery (P.M.B.), Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA (S.K., J.W.H., A.M., T.T.B., J.A.L., K.L.L., N.R., P.M.B., J.D., J.F., M.K., P.Y.W.) was 54 years (range, 29-78) and median KPS score was 90 (range, 70-100). From study enrollment, median PFS was 5.9 months (95% confidence interval [CI]: 4.2-8.0) and 4-month PFS was 63% (95% CI: 46%-75%). Median OS was 12.6 months (95% CI: 8.5-16.4) and 1-year OS was 47%. Of the 47 patients evaluable for best response, none had a complete response, five (11%) had partial response, four (9%) had minor response, 22 (47%) had stable disease, and 16 (34%) had progressive disease. Analysis of serial serum samples obtained from 47 patients for four angiogenic peptides failed to show a significant correlation with response or survival for three of the peptides; higher vascular endothelial growth factor levels showed a trend toward correlation with decreased OS (p 5 0.07) and PFS (p 5 0.09). The addition of celecoxib and thalidomide to adjuvant temozolomide was well tolerated but did not meet the primary end point of improvement of 4-month PFS from study enrollment. Neuro-Oncology 10, 300-308, 2008 (Posted to NeuroOncology [serial online], Doc. D06-00231, April 10, 2008 DOI: 10.1215 DOI: 10. /15228517-2008 Copyright 2008 by the Society for Neuro-Oncology D espite optimal treatment with surgery, radiation, and chemotherapy, the prognosis for patients with malignant gliomas remains poor. First-line chemotherapy with temozolomide has been shown to improve survival when given with radiotherapy.1 Because gliomas are highl...

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Combination celecoxib and temozolomide in C6 rat glioma orthotopic model

Cited by 29 publications

References 27 publications

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

Radiosensitizing potential of the selective cyclooygenase-2 (COX-2) inhibitor meloxicam on human glioma cells

Combined therapy of temozolomide and ZD6474 (vandetanib) effectively reduces glioblastoma tumor volume through anti-angiogenic and anti-proliferative mechanisms

Phase II study of temozolomide, thalidomide, and celecoxib for newly diagnosed glioblastoma in adults

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