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Antitumor Activity of Endostatin against Carcinogen-induced Rat Primary Mammary Tumors¹

Dipartimento di Biologia Strutturale e Funzionale, Università degli Studi dell’Insubria, 21100 Varese, Italy [G. P., P. C., E. M., F. P.]; Divisione di Anatomia Patologica, Istituto Nazionale per lo Studio e la Cura dei Tumori, 20133 Milano, Italy [R. G.]; Department of Surgery, Children’s Hospital, Harvard Medical School, Boston, Massachusetts 02115 [J. F., L. C.]

Endostatin, a M_r 20,000 fragment of collagen XVIII, potently inhibits the growth of experimental tumors implanted in mice. Here we report the cloning, expression, and antitumor activity of the rat form of endostatin. When tested on breast carcinomas arising in female virgin rats after intragastric administration of 9,10-dimethyl-1,2-benzanthracene (DMBA), endostatin induced significant inhibition of mammary tumor growth in all of the treated rats during a 4-week treatment period without signs of systemic toxicity. Interestingly, this arrest of tumor growth persisted throughout a four-week off-therapy period. Moreover, endostatin was effective in counteracting the development of multiple primary tumors. These results confirm that rat endostatin is a potent anticancer agent in a carcinogen-induced, spontaneously arising rat breast cancer model. It not only stops the growth of existing tumors but also decreases the incidence of the development of multiple neoplastic lesions.

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