دورية أكاديمية
Anti-invasive, antitumoral, and antiangiogenic efficacy of a pyrimidine-2,4,6-trione derivative, an orally active and selective matrix metalloproteinases inhibitor
| العنوان: | Anti-invasive, antitumoral, and antiangiogenic efficacy of a pyrimidine-2,4,6-trione derivative, an orally active and selective matrix metalloproteinases inhibitor |
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| المؤلفون: | Maquoi, Erik, Sounni, Nor Eddine, Devy, L., Olivier, Fabrice, Frankenne, Francis, Krell, H. W., Grams, F., Foidart, Jean-Michel, Noël, Agnès |
| المصدر: | Clinical Cancer Research, 10 (12, Pt 1), 4038-4047 (2004-06-15) |
| بيانات النشر: | American Association for Cancer Research, Inc. (AACR), 2004. |
| سنة النشر: | 2004 |
| مصطلحات موضوعية: | Human health sciences, Oncology, Sciences de la santé humaine, Oncologie |
| الوصف: | Purpose: 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. Experimental Design: 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. Results: 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. Conclusion: 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. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article peer reviewed |
| اللغة: | English |
| Relation: | urn:issn:1078-0432; urn:issn:1557-3265 |
| DOI: | 10.1158/1078-0432.CCR-04-0125 |
| URL الوصول: | https://orbi.uliege.be/handle/2268/12043 |
| حقوق: | open access http://purl.org/coar/access_right/c_abf2 info:eu-repo/semantics/openAccess |
| رقم الأكسشن: | edsorb.12043 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1158/1078-0432.CCR-04-0125 |
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