BACKGROUND: A preclinical evaluation of CPT-1 (Camptosar, irinotecan) and PTK787/ZK222584, a vascular endothelial growth factor receptor (VEGFR-2) tyrosine kinase inhibitor, as therapeutic agents against anaplastic thyroid carcinoma (ATC) was performed in vitro and in an orthotopic model of ATC in nude mice. METHODS: The cytotoxic and cytostatic effects of CPT-11 on ATC cell lines were evaluated. The antitumor effects of CPT-11 in combination with PTK787/ZK222584 on orthotopic ATC xenografts in nude mice were also studied. RESULTS: CPT-11 demonstrated significant antiproliferative effects on ATC cell lines. In vivo, PTK787/ZK222584, CPT-11, and the two agents together produced 61%, 82%, and 89% decrease in tumor growth, respectively. The differences in tumor volume between CPT-11 and CPT-11 + PTK787/ZK222584 groups were not statistically significant. PTK787/ZK222584 inhibited the phosphorylation of VEGFR-2 on tumor endothelium and decrease the tumor microvessel density. CONCLUSIONS: The camptothecin class of chemotherapeutic agents and antiangiogenic agents such as PTK787/ZK222584 warrant further study as novel therapeutic agents against ATC. Copyright 2005 Wiley Periodicals, Inc.
BACKGROUND: A preclinical evaluation of CPT-1 (Camptosar, irinotecan) and PTK787/ZK222584, a vascular endothelial growth factor receptor (VEGFR-2) tyrosine kinase inhibitor, as therapeutic agents against anaplastic thyroid carcinoma (ATC) was performed in vitro and in an orthotopic model of ATC in nude mice. METHODS: The cytotoxic and cytostatic effects of CPT-11 on ATC cell lines were evaluated. The antitumor effects of CPT-11 in combination with PTK787/ZK222584 on orthotopic ATC xenografts in nude mice were also studied. RESULTS:CPT-11 demonstrated significant antiproliferative effects on ATC cell lines. In vivo, PTK787/ZK222584, CPT-11, and the two agents together produced 61%, 82%, and 89% decrease in tumor growth, respectively. The differences in tumor volume between CPT-11 and CPT-11 + PTK787/ZK222584 groups were not statistically significant. PTK787/ZK222584 inhibited the phosphorylation of VEGFR-2 on tumor endothelium and decrease the tumor microvessel density. CONCLUSIONS: The camptothecin class of chemotherapeutic agents and antiangiogenic agents such as PTK787/ZK222584 warrant further study as novel therapeutic agents against ATC. Copyright 2005 Wiley Periodicals, Inc.
Authors: Hop S Tran Cao; Sharmeela Kaushal; Cynthia S Snyder; Weg M Ongkeko; Robert M Hoffman; Michael Bouvet Journal: Anticancer Res Date: 2010-11 Impact factor: 2.480
Authors: Carmelo Nucera; Matthew A Nehs; Michal Mekel; Xuefeng Zhang; Richard Hodin; Jack Lawler; Vânia Nose; Sareh Parangi Journal: Thyroid Date: 2009-10 Impact factor: 6.568