Inhibitors of a, integrins have been developed as anti-angiogenic agents for cancer therapy and, among them, cyclic RGD-containing pentapeptides, such as cilengitide, are the most commonly used integrin antagonists. In this study, cilengitide was tested in combination with the methylating agent temozolomide (TMZ), a well-tolerated anticancer drug with favourable pharmacokinetic properties currently used for the therapy of metastatic melanoma. To this end, the influence of cilengitide and TMZ on malignant melanoma growth and endothelial cell proliferation were investigated, using in vitro and in vivo models. The results indicated that cilengitide and TMZ exerted synergistic antiproliferative effects against melanoma and endothelial cells in vitro and induced a statistically significant reduction of in vivo melanoma growth with respect to treatment with the methylating agent only. In conclusion, this study proposes the use of cilengitide in combination with TMZ for the treatment of metastatic melanoma, thereby opening novel perspectives for the use of integrin inhibitors to enhance the efficacy of chemotherapy.

Tentori, L., Dorio, A.s., Muzi, A., Lacal, P.m., Ruffini, F., Navarra, P., et al. (2008). The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. ONCOLOGY REPORTS, 19(4), 1039-1043.

The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma

TENTORI, LUCIO;DORIO, ANNALISA SUSANNA;MUZI, ALESSIA;GRAZIANI, GRAZIA
2008-04-01

Abstract

Inhibitors of a, integrins have been developed as anti-angiogenic agents for cancer therapy and, among them, cyclic RGD-containing pentapeptides, such as cilengitide, are the most commonly used integrin antagonists. In this study, cilengitide was tested in combination with the methylating agent temozolomide (TMZ), a well-tolerated anticancer drug with favourable pharmacokinetic properties currently used for the therapy of metastatic melanoma. To this end, the influence of cilengitide and TMZ on malignant melanoma growth and endothelial cell proliferation were investigated, using in vitro and in vivo models. The results indicated that cilengitide and TMZ exerted synergistic antiproliferative effects against melanoma and endothelial cells in vitro and induced a statistically significant reduction of in vivo melanoma growth with respect to treatment with the methylating agent only. In conclusion, this study proposes the use of cilengitide in combination with TMZ for the treatment of metastatic melanoma, thereby opening novel perspectives for the use of integrin inhibitors to enhance the efficacy of chemotherapy.
apr-2008
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore BIO/14
English
Con Impact Factor ISI
antineoplastic agent; cilengitide; temozolomide; dacarbazine; drug derivative; integrin; snake venom; animal cell; animal experiment; animal model; antineoplastic activity; article; cancer inhibition; cell proliferation; combination chemotherapy; concentration response; controlled study; drug efficacy; drug potentiation; drug safety; drug tolerability; endothelium cell; human; human cell; in vitro study; in vivo study; melanoma; metastasis potential; monotherapy; mouse; nonhuman; priority journal; animal; C57BL mouse; drug antagonism; drug effect; genetics; male; mismatch repair; pathology; tumor cell line; Animals; Antineoplastic Agents; Cell Line, Tumor; Dacarbazine; DNA Mismatch Repair; Drug Synergism; Endothelial Cells; Integrins; Male; Melanoma; Mice; Mice, Inbred C57BL; Snake Venoms
Tentori, L., Dorio, A.s., Muzi, A., Lacal, P.m., Ruffini, F., Navarra, P., et al. (2008). The integrin antagonist cilengitide increases the antitumor activity of temozolomide against malignant melanoma. ONCOLOGY REPORTS, 19(4), 1039-1043.
Tentori, L; Dorio, As; Muzi, A; Lacal, Pm; Ruffini, F; Navarra, P; Graziani, G
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/46314
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