SU6668, a multiple tyrosine kinase inhibitor, inhibits progression of human malignant pleural mesothelioma in an orthotopic model
| Autor: | TRUNG THE VAN, MASAKI HANIBUCHI, HISATSUGU GOTO, TAKUYA KURAMOTO, SAWAKA YUKISHIGE, SOJI KAKIUCHI, SEIDAI SATO, SATOSHI SAKAGUCHI, LE TAN DAT, YASUHIKO NISHIOKA, SHIN-ICHI AKIYAMA, SABURO SONE |
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| Rok vydání: | 2012 |
| Předmět: |
Pulmonary and Respiratory Medicine
Pathology medicine.medical_specialty Severe combined immunodeficiency Pleural effusion medicine.drug_class business.industry Basic fibroblast growth factor medicine.disease Tyrosine-kinase inhibitor Vascular endothelial growth factor Mesothelium chemistry.chemical_compound medicine.anatomical_structure chemistry medicine Neoplasm Mesothelioma business |
| Zdroj: | Respirology. 17:984-990 |
| ISSN: | 1323-7799 |
| Popis: | Background and objective: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm of the mesothelium with high chemotherapeutic resistance. In this study, the preclinical therapeutic activity of the multiple tyrosine kinase inhibitor, SU6668, against MPM was examined. Methods: Two human MPM cell lines with different pro-angiogenic cytokine expression, Y-MESO-14 cells that express high levels of vascular endothelial growth factor (VEGF) and MSTO-211H cells that express high levels of basic fibroblast growth factor (bFGF), were orthotopically inoculated into the thoracic cavities of mice with severe combined immunodeficiency. The mice with MPM were treated or not treated with SU6668 (200 mg/kg/day). Results: SU6668 abrogated the proliferation of endothelial cells stimulated by VEGF or bFGF, but did not directly affect the growth of human MPM cells in vitro. In this orthotopic implantation model, treatment with SU6668 effectively reduced tumour weight and pleural effusion volumes, in association with inhibition of the growth of tumour vasculature. More importantly, treatment with SU6668 significantly prolonged survival time in mice with MPM. Conclusions: These findings suggest that SU6668 has a promising therapeutic effect on the progression of MPM in vivo through its anti-angiogenic effects. |
| Databáze: | OpenAIRE |
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