This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gee, M. S. Articles by Lee, W. M. F. Search for Related Content PubMed PubMed Citation Articles by Gee, M. S. Articles by Lee, W. M. F.

Selective Cytokine Inhibitory Drugs with Enhanced Antiangiogenic Activity Control Tumor Growth through Vascular Inhibition

¹ Biomedical Graduate Program,
² Department of Medicine and the Cancer Center, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania;
³ Electrical and Computer Science Engineering Department, Rensselaer Polytechnic Institute, Troy, New York; and
⁴ Celgene Corporation, Warren, New Jersey

Selective cytokine inhibitory drugs (SelCIDs) are a novel class of phosphodiesterase 4 inhibitors discovered during a thalidomide analog discovery program. These analogs were evaluated for their ability to inhibit tumor angiogenesis, vascularity, and growth. Two analogs (CC-7034 and CC-9088) were identified that had enhanced antiangiogenic activity in Matrigel assays compared with parental thalidomide. These analogs also inhibited the growth of established K1735 and RENCA murine tumors. Tumors whose growth was suppressed by SelCID treatment exhibited decreased vessel density together with increased tumor cell hypoxia and death. The decrease in vascularity produced by SelCID treatment is attributed to a selective loss of vessels devoid of pericyte coverage, suggesting that these agents target immature tumor vessels. That tumor cell death was localized to relatively avascular or hypoxic areas, coupled with the fact that none of the analogs was cytotoxic in vitro against the tumor cells, demonstrates that these analogs are novel antivascular agents with potent antitumor activity.

This article has been cited by other articles:

				D. A. Murphy, S. Makonnen, W. Lassoued, M. D. Feldman, C. Carter, and W. M.F. Lee Inhibition of Tumor Endothelial ERK Activation, Angiogenesis, and Tumor Growth by Sorafenib (BAY43-9006) Am. J. Pathol., November 1, 2006; 169(5): 1875 - 1885. [Abstract] [Full Text] [PDF]

				H. Kobayashi, T. Yagyu, T. Kondo, N. Kurita, K. Inagaki, S. Haruta, R. Kawaguchi, T. Kitanaka, Y. Sakamoto, Y. Yamada, et al. Suppression of Urokinase Receptor Expression by Thalidomide Is Associated with Inhibition of Nuclear Factor {kappa}B Activation and Subsequently Suppressed Ovarian Cancer Dissemination Cancer Res., November 15, 2005; 65(22): 10464 - 10471. [Abstract] [Full Text] [PDF]

				L. S. Ziemer, W. M. F. Lee, S. A. Vinogradov, C. Sehgal, and D. F. Wilson Oxygen distribution in murine tumors: characterization using oxygen-dependent quenching of phosphorescence J Appl Physiol, April 1, 2005; 98(4): 1503 - 1510. [Abstract] [Full Text] [PDF]