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2 "Angiogenesis Factor"
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Original Articles
Role of Angiogenesis and Expression of Vascular Endothelial Growth Factor in Mouse Skin Carcinogenesis .
Aeree Kim, Byoung Kook Kim, Hosu Chun, Ju Han Lee, Jong Sang Choi
Korean J Pathol. 2002;36(2):106-111.
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AbstractAbstract PDF
BACKGROUND
Angiogenesis is crucial for many biological processes such as embryogenesis, cyclic changes in the endometrium and wound healing. It is also critical for the growth, invasion and metastasis of solid tumors. Vascular endothelial growth factor (VEGF) acts as a mitogen for endothelial cells and is expressed by the presence of various tumor cells. The objective of this study is to evaluate if angiogenesis is involved in the mouse skin carcinogenesis and if VEGF is related to angiogenesis.
METHODS
We induced premalignant and malignant lesions on mouse (BALB/c) skin using the two stage chemical carcinogenesis moedl, DMBA (7,12-dimethylbenzanthracene) initiation and TPA (tetra decanoyl-phorbol-acetate) promotion. And we analysed the microvessel densities (MVD) and expression of VEGF in various stages of premalignant and malignant lesions by immunohistochemical studies.
RESULTS
Squamous papillomas, keratoacanthoma, dermatofibroma, and squamous cell carcinomas were developed in 20 weeks. There were no differences in the incidence of benign and malignant tumors between 10-week and 20-week promotion groups. There were significant increases in MVD from normal and hyperplastic skin through premalignant lesion to invasive squamous cell carcinoma (p<0.0005). But the degree of VEGF expression neither correlated with neither MVD nor the tumor groups.
CONCLUSIONS
Increased angiogenesis begins from the hyperplastic stage. VEGF produced by tumor cells may not play major roles in the angiogenesis in the two stage chemical carcinogenesis model of the mouse skin.
Expression of Nitric Oxide Synthase Isotypes in Advanced Gastric Carcinoma.
Kyong Mee Kwon, Young Chae Chu, Tae Sook Hwang
Korean J Pathol. 2002;36(6):374-371.
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  • 11 Download
AbstractAbstract PDF
BACKGROUND
Increased expression of nitric oxide synthase (NOS) isotypes is present in human tumor cell lines and solid tumor tissues. Hypoxia upregulates NOS expression, and nitric oxide (NO) induces mitogenesis among endothelial cells. NO has been known to induce vascular endothelial growth factor (VEGF) expression in carcinoma cells and to induce neovascularization in tumors.
METHODS
The expression and cellular localization of 3 isotypes of NOS was detected by immunohistochemistry in 73 advanced gastric carcinoma tissues along with adjacent normal gastric mucosa; and the relationship to known clinicopathologic parameters, microvascular density, and VEGF expression was analysed.
RESULTS
Forty-four (60.3%), 56 (76.7%), and 52 (71.2%) of the 73 cases revealed eNOS, nNOS, and iNOS expression, respectively. Intestinal type adenocarcinomas tended to have higher activity of eNOS (p=0.000) and nNOS (p=0.001) activities than did the diffuse type adenocarcinomas. All isotypes of NOS (eNOS, p=0.001; nNOS, p=0.005; iNOS, p=0.044) tended to be highly expressed when the tumor was differentiated. There was no significant relationship between any of the 3 NOS isotypes and microvascular density, whereas VEGF was closely related with microvascular density (p=0.000). The expression of VEGF was not related to with any of the NOS isotype expressions.
CONCLUSIONS
From the above results, we speculated that NO may be implicated in the early stage of the gastric carcinogenesis rather than the growth and progression stages, and NO does not appear to affect angiogenesis or VEGF expression in the advanced gastric carcinoma.

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