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Anticancer Activity of Bisphosphonic Acids in Methylnitrosourea-induced Mammary Carcinoma of the Rat — Benefit of Combining Bisphosphonates with Cytostatic Agents by F. Wingen; B. L. Pool; P. Klein; T. Klenner; D. Schmähl is a Medicine article available to read on EtoBox.

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This study primarily describes the cytostatic activity of a bisphosphonate and of an alkylating agent linked bisphosphonate toward mammary carcinomas in vivo. Bisphosphonates had been shown to be therapeutically active in bone metastases. There is no animal tumor model available in which both primary mammary carcinomas and bone metastases can be studied simultaneously. Therefore, the Walker carcinosarcoma model, which was used as a model for bone metastasis in earlier studies, was combined with the M-methyl-Nnitrosourea (MNU) induced mammary carcinoma as a model for the primary tumor. Four-, or six-week treatment of MNU-induced mammary carcinomas in Sprague-Dawley rats with the new aromatic bisphosphonate 4[4-[bis(2-chloroethyl)-amino]-phenyl]-l-hydroxybutane-l,l-bisphosphonate (BAD) showed higher antitumor activity than treatment with melphalan or with 3-amino-l-hydroxypropylidene-l,l-bisphosphonate (APD) alone. BAD is the APD moiety covalently bound to a molecule derived from melphalan. A combination therapy with 11.75 mg/kg/day APD and 0.6 mg/kg/day melphalan showed the best therapeutic efficacy in this tumor model. In comparison to monotherapy with BAD, APD, or melphalan, a sig

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Author

F. Wingen; B. L. Pool; P. Klein; T. Klenner; D. Schmähl

Publisher

Springer US; Springer-Verlag; Kluwer Academic Publishers; Springer Science and Business Media LLC (ISSN 0167-6997)

Published

1988

Language

EN

Field

Medicine (Health Sciences)