OBJECTIVE: The biological features of malignant gliomas include high cell proliferation, extensive local infiltration of tumor cells into normal brain, and marked neovascularization. alphavbeta3 integrin is highly expressed in malignant gliomas and plays a role in glioma growth. This article investigates, the in vitro and in vivo effects of a synthetic alphavbeta3 integrin inhibitor called IS201 on human malignant gliomas. METHODS: The in vitro effects of IS201. were studied by performing adhesion assays, competition studies, semi-in vivo angiogenic assays, and migration and proliferation assays. For the in vivo experiments, IS201 was administered systemically in nude mouse intracranial and subcutaneous malignant glioma models. RESULTS: IS201 reacted selectively to alphavbeta3 integrin in glioma cells and tissues. In vitro, IS201 strongly inhibited angiogenesis and simultaneously exhibited potent antimitotic and antimigratory effects on numerous tumor and endothelial cell lines. In addition, at high concentrations, IS201 induced endothelial and tumor cell apoptosis. In vivo, when IS201 was administered intraperitoneally in subcutaneous and intracranial nude mouse glioma models, it potently reduced malignant glioma growth. Inhibition levels of 76 and 82% were observed at concentrations of 1 and 5 mg/kg, respectively, in the U87 intracranial model. The suppression of tumor growth is associated with a decrease in tumor vascularity, an increase in apoptosis, and a decrease in tumor cell proliferation. CONCLUSION: This work expands the understanding of the effects of anti-alphavbeta3 integrin inhibitors on malignant gliomas. In addition to direct proapoptotic and antiangiogenic effects, IS201 inhibits tumor and endothelial cell proliferation and migration, resulting in a potent inhibition of glioma growth in vivo

Bello, L., Lucini, V., Giussani, C., Carrabba, G., Pluderi, M., Scaglione, F., et al. (2003). IS20I, a specific alphavbeta3 integrin inhibitor, reduces glioma growth in vivo. NEUROSURGERY, 52(1), 177-185 [10.1097/00006123-200301000-00023].

IS20I, a specific alphavbeta3 integrin inhibitor, reduces glioma growth in vivo

Giussani, CG;Carrabba, G;
2003

Abstract

OBJECTIVE: The biological features of malignant gliomas include high cell proliferation, extensive local infiltration of tumor cells into normal brain, and marked neovascularization. alphavbeta3 integrin is highly expressed in malignant gliomas and plays a role in glioma growth. This article investigates, the in vitro and in vivo effects of a synthetic alphavbeta3 integrin inhibitor called IS201 on human malignant gliomas. METHODS: The in vitro effects of IS201. were studied by performing adhesion assays, competition studies, semi-in vivo angiogenic assays, and migration and proliferation assays. For the in vivo experiments, IS201 was administered systemically in nude mouse intracranial and subcutaneous malignant glioma models. RESULTS: IS201 reacted selectively to alphavbeta3 integrin in glioma cells and tissues. In vitro, IS201 strongly inhibited angiogenesis and simultaneously exhibited potent antimitotic and antimigratory effects on numerous tumor and endothelial cell lines. In addition, at high concentrations, IS201 induced endothelial and tumor cell apoptosis. In vivo, when IS201 was administered intraperitoneally in subcutaneous and intracranial nude mouse glioma models, it potently reduced malignant glioma growth. Inhibition levels of 76 and 82% were observed at concentrations of 1 and 5 mg/kg, respectively, in the U87 intracranial model. The suppression of tumor growth is associated with a decrease in tumor vascularity, an increase in apoptosis, and a decrease in tumor cell proliferation. CONCLUSION: This work expands the understanding of the effects of anti-alphavbeta3 integrin inhibitors on malignant gliomas. In addition to direct proapoptotic and antiangiogenic effects, IS201 inhibits tumor and endothelial cell proliferation and migration, resulting in a potent inhibition of glioma growth in vivo
Articolo in rivista - Articolo scientifico
Animals; Antineoplastic Agents; Brain Neoplasms; Cell Adhesion; Cell Division; Cell Movement; Cell Survival; Endothelium, Vascular; Glioma; Humans; Integrin alphaVbeta3; Mice; Mice, Nude; Neoplasm Invasiveness; Neoplasm Transplantation; Neovascularization, Pathologic; Oligopeptides; Peptides, Cyclic; Tumor Cells, Cultured
English
2003
52
1
177
185
reserved
Bello, L., Lucini, V., Giussani, C., Carrabba, G., Pluderi, M., Scaglione, F., et al. (2003). IS20I, a specific alphavbeta3 integrin inhibitor, reduces glioma growth in vivo. NEUROSURGERY, 52(1), 177-185 [10.1097/00006123-200301000-00023].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/148275
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