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Changes in Tumor Vascularization after Irradiation, Anthracyclin, or Antiangiogenic Treatment in Nitrosomethyl Ureas-Induced Rat Mammary Tumors

Institut National de la Santé et de la Recherche Médicale E 0211 [F. D., S. C., P. L., O. l. F., P. B.], and Institut National de la Santé et de la Recherche Médicale U316 [L. C., F. T.], IFR 120, CHU Bretonneau, Tours, France

Purpose: Changes in tumor vascularization may be involved in tumor regression after anticancer treatments. We therefore studied the relationship between tumor vascularization and tumor response according to treatment by irradiation (RT), epirubicin (EPI), or antiangiogenic agent TNP-470 in a nitrosomethyl-ureas-induced rat mammary tumor model by measuring the changes in tumor blood flow using high-frequency Power-Doppler sonography.

Experimental Design: Mammary tumors were induced in female Sprague-Dawley rats by a single s.c. injection of nitrosomethyl-ureas. After tumor areas reached 2 cm², the animals received four weekly injections of epirubicin (EPI group), or a single fraction of 18 Gy (RT group), or six injections of TNP-470 within 12 days (TNP group), or both (RT combined with TNP-470, RT+TNP group). Power-Doppler sonography quantification of tumor vascularization (PDI) was performed before and 12 days after initiation of treatment. Tumor shrinkage was later evaluated and compared with the early changes in PDI values.

Results: Compared with the control group, EPI induced an arrest in tumor growth. A similar effect was obtained with TNP-470. There was a decrease in tumor area after RT, but administration of TNP-470 combined with RT did not further enhance this effect. Changes in tumor area paralleled changes in PDI in the EPI group. Furthermore, changes in PDI 7 days after RT were associated with further tumor change in the RT groups, whereas they were independent of the antitumor effect of TNP-470.

Conclusions: Changes in functional tumor vascularization evolution appeared to be closely associated with tumor regression after anticancer treatment.

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