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[“Inhibitor Switch

Blood vessels in tumor sections stained with antiCD were counted from ve microscopic elds for all tumors in the Trilostane experiment shown in Fig.Anastellin is a representative of a grow ing class of antiangiogen ic substances that are derived from ECM and blood proteins We thank Dr.This work was supported by Grant CA and Cancer Center Support Grant CA from the National Cancer Institute, and Grant DAMD from the Department of Defense. Bourdoulous, S, Orend, G, MacKenna, D. A, Pasqualin i, R. Ruoslahti, E. J. Cell Biol. Buckley, C. D, Pilling, D, Henriquez, N. V, Parsonage, G, Threlfall, K, ScheelToellner, D, Simmons, D. L, Akbar, A. N, Lord, J. M. Salmon, M. J. Biol. Chem, tsuguAnotseugybded aonlwoD uwww.pnas.org Yi and Ruoslahti VEGF gene expression was moderately associated with an increase in the IMD, but no significant relationship was found between PDECGF gene expression and the IMD. However, tumours with positive expression for both PDECGF and VEGF had a higher IMD. The results of the immunohistochemistry agreed well with the results of the quantitative RTPCR.The median survival time of the hypervascular group was significantly Talc shorter than that of the hypovascular group. In comparing the survival according to PDECGF and VEGF gene expression, the median survival time of the patients with positive PDECGF expression was significantly shorter than those with negative PDECGF expression. Furthermore, the median survival time of the patients with positive VEGF expression was significantly shorter than those with negative VEGF expression. Angiogenesis is an integral part of the cascade of biologic events involved in tumour metastasis. The mechanisms by which neovascularization stimulates tumour progression are the delivery of the nutrients and oxygen necessary for tumour cell growth, the facilitation of the penetration of tumour cells through the vessel walls and their transport to distant organs, and the secretion of selective cytokines and growth factors from endothelial cells that directly stimulate tumour cells. The conversion of tumour cells to an angiogenic phenotype may be preceded by a change in the balance of angiogenic growth factors and angiogenesis inhibitors.However, since angiogenesis is composed of multistep processes controlled by various factors, the role of angiogenesis in pancreatic cancer has not been fully elucidated.This study was conducted to determine whether the levels of PDECGF and VEGF gene expression measured in primary tumours from patients with pancreatic cancers were associated with known prognostic factors and patient survival.Furthermore, to clarify whether PDECGF and VEGF correlate with tumour angiogenesis, we examined the intratumoral microvessel density by immunohistochemical analysis using antiCD monoclonal antibodies.The median age of the patients was years, with a range of years.When distant metastasis was solitary and resectable, pancreatectomy was performed.Thus, six patients with distant metastasis underwent surgery.Following pancreatectomy, all patients received intraoperative radiation therapy of electron beam on the retroperitoneal field, including the origins of the portal vein, celiac and superior mesenteric arteries.Moreover, mgm mitomycin C and mgm fluorouracil were administered into the portal vein.Postoperative systemic chemotherapy was not given before recurrence.All of the tissues were obtained from resected specimens, and then were quickly stored at C until used.

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