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Division of Hematology and Oncology, Department of Internal Medicine, Wayne State University School of Medicine, Detroit, Michigan 48202 [R. M. M., A. A-K., L. L. S.], and Cancer Research Institute and Department of Chemistry, Arizona State University, Tempe, Arizona 85287-1604 [G. R. P.]
2 To whom requests for reprints should be addressed, at Division of Hematology and Oncology, Wayne State University School of Medicine, P. O. Box 02143, Detroit, MI 48202.
The immunomodulating effects and antitumor activity of two biological agents, bryostatin 1 (Bryo1) and 
-interferon, were tested in vitro and in vivo either alone or prior to chemotherapy agents, against a Waldenström's macroglobulinemia tumor line (WSU-WM). Bryo1 caused a decrease in the expression of CD10, CD19, IgM, Leu10, and CD22 and a temporary growth inhibition as measured by cell cycle analysis. -Interferon did not show any major effects. In vivo, severe combined immunodeficient mice were used to test the activity of the agents against WSU-WM. Bryo1 (i.p.) was given either alone or sequentially with doxorubicin (i.v.), vincristine (i.v.), melphalan (i.v.), and -interferon (i.v.). Bryo1 given 24 h before vincristine or melphalan resulted in the highest tumor growth inhibition, tumor growth delay, and tumor cell kill. Two of five mice receiving Bryo1/vincristine combination were free of tumors >200 days after treatment and were considered cured. In light of our findings, we recommend that Bryo1 be considered for clinical investigation in human B-cell tumors and might best be given combined with other chemotherapy agents used in the treatment of that disease. Whether Bryo1 is acting as a differentiating agent or as a direct anti-Waldenström's macroglobulinemia tumor agent, remains unclear.
1 This publication was made possible by Grant R29 CA50715-01A1 from the National Cancer Institute and also was supported by the Dennis Shea and Stephen Brandt Funds for Cancer Research and by the Ayad Al-Katib Cancer Research Funds of Harper Hospital. Flow cytometry was performed at the Ben Kasle Cytometry Facility of the Meyer L. Prentis Comprehensive Cancer Center of Metropolitan Detroit supported by Department of Health and Human Services Grant CA 22453.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 7/12/93. Accepted 10/22/93.
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