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The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model.

Sandström M, Johansson M, Andersson U, Bergh A, Bergenheim AT, Henriksson R - Br. J. Cancer (2004)

Bottom Line: ZD6474 significantly decreased tumour volume compared to controls.In vitro, the growth of both cell lines was significantly reduced.The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Sciences, Oncology, Umeå University, S-901 85 Umeå, Sweden. maria.sandstrom@onkologi.umu.se

ABSTRACT
Malignant glioma is characterised by extensive neovascularisation, principally influenced by vascular endothelial growth factor (VEGF). ZD6474 is a potent inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory effects on other growth factors. In this study, we have investigated the effects of ZD6474 with regard to tumour growth, neovascularisation, proliferation and apoptosis in the intracerebral rat glioma model, BT4C. ZD6474 (50 and 100 mg kg(-1)) was given as a daily oral gavage. Animals were killed on day 19 and tumour volume was measured. Sections were stained for factor VIII, Ki-67 and for apoptosis. The ability of ZD6474 to inhibit cell growth directly was examined in vitro, using the glioma cell line BT4C and the transformed rat brain endothelial cell line RBE4. Cell growth was analysed with fluorometric microculture cytotoxicity assay to quantify the cytotoxic effects. ZD6474 significantly decreased tumour volume compared to controls. Microvascular density increased after treatment with ZD6474, and tumour cell proliferation index was reduced. There was also an increase in tumour cell apoptosis. In vitro, the growth of both cell lines was significantly reduced. The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities.

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An intracerebral BT4C tumour in the right hemisphere from an animal in the control group, stained with haematoxylin–eosin. Scale bar, 2 mm.
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fig1: An intracerebral BT4C tumour in the right hemisphere from an animal in the control group, stained with haematoxylin–eosin. Scale bar, 2 mm.

Mentions: The previously characterised syngenic intracerebral BT4C rat glioma model was used for the in vivo experiments in this study (Bergenheim et al, 1994; Johansson et al, 2000) (Figure 1Figure 1


The tyrosine kinase inhibitor ZD6474 inhibits tumour growth in an intracerebral rat glioma model.

Sandström M, Johansson M, Andersson U, Bergh A, Bergenheim AT, Henriksson R - Br. J. Cancer (2004)

An intracerebral BT4C tumour in the right hemisphere from an animal in the control group, stained with haematoxylin–eosin. Scale bar, 2 mm.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747688&req=5

fig1: An intracerebral BT4C tumour in the right hemisphere from an animal in the control group, stained with haematoxylin–eosin. Scale bar, 2 mm.
Mentions: The previously characterised syngenic intracerebral BT4C rat glioma model was used for the in vivo experiments in this study (Bergenheim et al, 1994; Johansson et al, 2000) (Figure 1Figure 1

Bottom Line: ZD6474 significantly decreased tumour volume compared to controls.In vitro, the growth of both cell lines was significantly reduced.The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities.

View Article: PubMed Central - PubMed

Affiliation: Department of Radiation Sciences, Oncology, Umeå University, S-901 85 Umeå, Sweden. maria.sandstrom@onkologi.umu.se

ABSTRACT
Malignant glioma is characterised by extensive neovascularisation, principally influenced by vascular endothelial growth factor (VEGF). ZD6474 is a potent inhibitor of VEGF-R2 tyrosine kinase activity, but with additional inhibitory effects on other growth factors. In this study, we have investigated the effects of ZD6474 with regard to tumour growth, neovascularisation, proliferation and apoptosis in the intracerebral rat glioma model, BT4C. ZD6474 (50 and 100 mg kg(-1)) was given as a daily oral gavage. Animals were killed on day 19 and tumour volume was measured. Sections were stained for factor VIII, Ki-67 and for apoptosis. The ability of ZD6474 to inhibit cell growth directly was examined in vitro, using the glioma cell line BT4C and the transformed rat brain endothelial cell line RBE4. Cell growth was analysed with fluorometric microculture cytotoxicity assay to quantify the cytotoxic effects. ZD6474 significantly decreased tumour volume compared to controls. Microvascular density increased after treatment with ZD6474, and tumour cell proliferation index was reduced. There was also an increase in tumour cell apoptosis. In vitro, the growth of both cell lines was significantly reduced. The results reported justify further experimental investigations concerning the effects of ZD6474 in malignant glioma alone or in combination with other modalities.

Show MeSH
Related in: MedlinePlus