关键词: Experimental carcinogenesis angiogenesis angiogenic switch hamster cheek pouch microvasculature oral cancer

Mesh : 9,10-Dimethyl-1,2-benzanthracene / toxicity Animals Apoptosis Biomarkers, Tumor / metabolism Carcinogens / toxicity Cell Proliferation Cheek / pathology Cricetinae Disease Models, Animal Endothelium, Vascular / metabolism pathology Immunoenzyme Techniques Mesocricetus Mouth Neoplasms / blood supply chemically induced metabolism pathology Neovascularization, Pathologic / pathology Tumor Cells, Cultured Vascular Endothelial Growth Factor A / metabolism

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Abstract:
OBJECTIVE: To evaluate vascular morphology and density, angiogenic switch activation, vascular endothelial growth factor (VEGF) expression, and endothelial cell (EC) proliferation in the hamster cheek pouch (HCP) model of oral cancer.
METHODS: Immunohistochemical detection of factor VIII, 5\'-Bromo-2\'-Deoxyuridine (BrdU) and VEGF was performed in pre-malignant and tumoral tissues.
RESULTS: Activation of angiogenesis was detected adjacent to epithelial dysplasia. Vascularized area and perimeter (p<0.001) increased in dysplasias and tumors. Tumor blood vessels exhibited an enhanced vascular compression (p<0.001) and structural alterations. EC proliferation was similar in dysplasias and carcinomas. An increase in vascular density, EC proliferation and VEGF expression was found in potentially malignant tissues but not in carcinomas.
CONCLUSIONS: The angiogenic switch occurs in the dysplastic stage preceding tumor development in the HCP model of oral cancer. In potentially malignant tissues, increased VEGF expression favors EC proliferation and an increase in vascular density. Conversely, in tumors, VEGF is no longer of pivotal importance.
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