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Blood, 15 December 2004, Vol. 104, No. 13, pp. 4181-4187. Prepublished online as a Blood First Edition Paper on August 10, 2004; DOI 10.1182/blood-2004-03-1153. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-03-1153v1 104/13/4181    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Frost, P. Articles by Lichtenstein, A. Search for Related Content PubMed PubMed Citation Articles by Frost, P. Articles by Lichtenstein, A. Related Collections Neoplasia Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA In vivo antitumor effects of the mTOR inhibitor CCI-779 against human multiple myeloma cells in a xenograft model Patrick Frost, Farhad Moatamed, Bao Hoang, Yijiang Shi, Joseph Gera, Huajun Yan, Philip Frost, Jay Gibbons, and Alan Lichtenstein From the Departments of Medicine and Pathology, UCLA-West Los Angeles VA Medical Center, Los Angeles, CA; and Wyeth-Ayerst, Pearl River, NY. In vitro studies indicate the therapeutic potential of mTOR inhibitors in treating multiple myeloma. To provide further support for this potential, we used the rapamycin analog CCI-779 in a myeloma xenograft model. CCI-779, given as 10 intraperitoneal injections, induced significant dose-dependent, antitumor responses against subcutaneous growth of 8226, OPM-2, and U266 cell lines. Effective doses of CCI-779 were associated with modest toxicity, inducing only transient thrombocytopenia and leukopenia. Immunohistochemical studies demonstrated the antitumor responses were associated with inhibited proliferation and angiogenesis, induction of apoptosis, and reduction in tumor cell size. Although CCI-779-mediated inhibition of the p70 mTOR substrate was equal in 8226 and OPM-2 tumor nodules, OPM-2 tumor growth was considerably more sensitive to inhibition of proliferation, angiogenesis, and induction of apoptosis. Furthermore, the OPM-2 tumors from treated mice were more likely to show down-regulated expression of cyclin D1 and c-myc and up-regulated p27 expression. Because earlier work suggested heightened AKT activity in OPM-2 tumors might induce hypersensitivity to mTOR inhibition, we directly tested this by stably transfecting a constitutively active AKT allele into U266 cells. The in vivo growth of the latter cells was remarkably more sensitive to CCI-779 than the growth of control U266 cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Toward a rational combinaTORial therapy for multiple myeloma Helena Jernberg-Wiklund and Kenneth Nilsson Blood 2004 104: 3845-3846. [Full Text] [PDF] This article has been cited by other articles: A. S. Fung, L. Wu, and I. F. Tannock Concurrent and Sequential Administration of Chemotherapy and the Mammalian Target of Rapamycin Inhibitor Temsirolimus in Human Cancer Cells and Xenografts Clin. Cancer Res., September 1, 2009; 15(17): 5389 - 5395. [Abstract] [Full Text] [PDF] B. Hoang, A. Benavides, Y. Shi, P. Frost, and A. Lichtenstein Effect of autophagy on multiple myeloma cell viability Mol. Cancer Ther., July 1, 2009; 8(7): 1974 - 1984. [Abstract] [Full Text] [PDF] P. Frost, Y. Shi, B. Hoang, J. Gera, and A. 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