{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:56:19Z","timestamp":1793404579419,"version":"4.5.0"},"reference-count":49,"publisher":"National Academy of Sciences","issue":"23","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2000,11,7]]},"abstract":"<jats:p>\n                    Targeting the endothelial cell cycle as an antiangiogenic strategy\n has been difficult given the ubiquitous expression of critical cell\n cycle regulators. Here, we show that the antiangiogenic drug TNP-470\n displays striking cell-type specificity insofar as it induces the\n expression of p21\n                    <jats:sup>CIP\/WAF<\/jats:sup>\n                    , a cyclin-dependent kinase\n inhibitor, in endothelial cells but not in embryonic or adult\n fibroblasts. Moreover, primary endothelial cells isolated from\n p53\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    and p21\n                    <jats:sup>CIP\/WAF\u2212\/\u2212<\/jats:sup>\n                    mice are\n resistant to the cytostatic activity of TNP-470. We also demonstrate\n that p21\n                    <jats:sup>CIP\/WAF\u2212\/\u2212<\/jats:sup>\n                    mice are resistant to the\n antiangiogenic activity of TNP-470 in the basic fibroblast growth\n factor corneal micropocket angiogenesis assay. We conclude that TNP-470\n induces p53 activation through a unique mechanism in endothelial cells\n leading to p21\n                    <jats:sup>CIP\/WAF<\/jats:sup>\n                    expression and subsequent growth\n arrest.\n                  <\/jats:p>","DOI":"10.1073\/pnas.97.23.12782","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:45:09Z","timestamp":1027680309000},"page":"12782-12787","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":101,"title":["The antiangiogenic agent TNP-470 requires p53 and p21\n                    <sup>CIP\/WAF<\/sup>\n                    for endothelial cell growth arrest"],"prefix":"10.1073","volume":"97","author":[{"given":"Jing-Ruey J.","family":"Yeh","sequence":"first","affiliation":[{"name":"Departments of Molecular, Cellular, and Developmental Biology, and\r Pharmacology, Yale University, New Haven, CT 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