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Growth inhibition of orthotopic anaplastic thyroid carcinoma xenografts in nude mice by PTK787/ZK222584 and CPT-11
- Source :
- Headneck. 28(5)
- Publication Year :
- 2006
-
Abstract
- 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. © 2005 Wiley Periodicals, Inc. Head Neck27: 389–399, 2006
- Subjects :
- Male
medicine.drug_class
Angiogenesis
Pyridines
Cell Culture Techniques
Mice, Nude
Apoptosis
Irinotecan
Tyrosine-kinase inhibitor
Thyroid carcinoma
chemistry.chemical_compound
Mice
In vivo
Cell Line, Tumor
medicine
Animals
heterocyclic compounds
Anaplastic carcinoma
Thyroid Neoplasms
neoplasms
Protein Kinase Inhibitors
Cell Proliferation
business.industry
Carcinoma
medicine.disease
Antineoplastic Agents, Phytogenic
Otorhinolaryngology
chemistry
Cancer research
Phthalazines
Camptothecin
Drug Therapy, Combination
Growth inhibition
business
Neoplasm Transplantation
medicine.drug
Subjects
Details
- ISSN :
- 10433074
- Volume :
- 28
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Headneck
- Accession number :
- edsair.doi.dedup.....7941dda3f938d2650620c4e2d8e4652e