ro-28-2653 and Adenocarcinoma

ro-28-2653 has been researched along with Adenocarcinoma* in 1 studies

Other Studies

1 other study(ies) available for ro-28-2653 and Adenocarcinoma

ArticleYear
Anti-invasive, antitumoral, and antiangiogenic efficacy of a pyrimidine-2,4,6-trione derivative, an orally active and selective matrix metalloproteinases inhibitor.
    Clinical cancer research : an official journal of the American Association for Cancer Research, 2004, Jun-15, Volume: 10, Issue:12 Pt 1

    The implication of matrix metalloproteinases (MMPs) in the major stages of cancer progression has fueled interest in the design of synthetic MMP inhibitors (MMPIs) as a novel anticancer therapy. Thus far, drugs used in clinical trials are broad-spectrum MMPIs the therapeutic index of which proved disappointingly low. The development of selective MMPIs for tumor progression-associated MMPs is, thus, likely to offer improved therapeutic possibilities.. The anti-invasive capacity of a series of pyrimidine-trione derivatives was tested in vitro in a chemoinvasion assay, and the most potent compound was further evaluated in vivo in different human tumor xenograft models. The activity of this novel selective MMPI was compared with BB-94, a broad-spectrum inhibitor.. Ro-28-2653, an inhibitor with high selectivity for MMP-2, MMP-9, and membrane type 1 (MT1)-MMP, showed the highest anti-invasive activity in vitro. In vivo, Ro-28-2653 reduced the growth of tumors induced by the inoculation of different cell lines producing MMPs and inhibited the tumor-promoting effect of fibroblasts on breast adenocarcinoma cells. Furthermore, Ro-28-2653 reduced tumor vascularization and blocked angiogenesis in a rat aortic ring assay. In contrast, BB-94 up-regulated MMP-9 expression in tumor cells and promoted angiogenesis in the aortic ring assay.. Ro-28-2653, a selective and orally bioavailable MMPI with inhibitory activity against MMPs expressed by tumor and/or stromal cells, is a potent antitumor and antiangiogenic agent. In contrast to broad-spectrum inhibitors, the administration of Ro-28-2653 was not associated with the occurrence of adverse side effects that might hamper the therapeutic potential of these drugs.

    Topics: Adenocarcinoma; Administration, Oral; Animals; Antineoplastic Agents; Aorta; Breast Neoplasms; Cell Line, Tumor; Disease Progression; DNA, Complementary; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fibroblasts; Humans; Inhibitory Concentration 50; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Microscopy, Fluorescence; Models, Chemical; Neoplasm Invasiveness; Neoplasm Transplantation; Neovascularization, Pathologic; Phenylalanine; Piperazines; Protease Inhibitors; Pyrimidines; Rats; Thiophenes; Time Factors; Up-Regulation

2004
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