RESUMO
<p><b>OBJECTIVE</b>To establish and characterize imatinib-resistant gastrointestinal stromal tumor (GIST) xenografts. Further provided an ideal experimental platform through the imatinib-resistant GIST xenografts to investigate the mechanism of resistance to imatinib.</p><p><b>METHODS</b>Imatinib-resistant GIST cells were injected under the skin of athymic nude mice to establish animal models of human imatinib-resistant GIST. The molecular and histopathologic features of GIST xenografts were also analysed and compared with their counterpart of cell lines.</p><p><b>RESULTS</b>The xenograft tumor models had been established by subcutaneously injection of GIST cells into nude mice. Immunohistochemistry results showed CD117 expression was positive in GIST-PR2 xenograft tumor, but negative in GIST-R. In GIST-PR1, tumor areas showing rhabdomyoblastic differentiation were presented next to areas with classic GIST morphology. The rhabdomyoblastic component demonstrated consistently positivity for desmin and myogenin, whereas CD117 was completely negative. The mutation profiles of these xenograft tumors were the same as their counterpart of cell lines.</p><p><b>CONCLUSIONS</b>Human GIST xenografts with mutation in c-kit have been established from imatinib-resistant GIST lines. Those models will enable further studies on mechanisms of resistance, combination therapies and allow testing of novel targeted therapies.</p>
Assuntos
Animais , Feminino , Humanos , Masculino , Camundongos , Antineoplásicos , Farmacologia , Benzamidas , Diferenciação Celular , Linhagem Celular Tumoral , Desmina , Metabolismo , Resistencia a Medicamentos Antineoplásicos , Neoplasias Gastrointestinais , Genética , Metabolismo , Patologia , Tumores do Estroma Gastrointestinal , Genética , Metabolismo , Patologia , Mesilato de Imatinib , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação , Miogenina , Metabolismo , Piperazinas , Farmacologia , Proteínas Proto-Oncogênicas c-kit , Genética , Metabolismo , Pirimidinas , Farmacologia , Rabdomiossarcoma , Metabolismo , Patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
<p><b>OBJECTIVE</b>To investigate the effects of microencapsulated Chinese hamster ovary (CHO) cells modified with maspin gene on the motility and adhesiveness of breast carcinoma cells Bcap37 and to explore the possibility and feasibility of its clinical application in treatment of malignant tumors.</p><p><b>METHODS</b>After the Bcap37 cells were co-cultured with the microencapsulated CHO cells modified with maspin gene, their motility and adhesion to vascular endothelial cells (ECV304), changes in CD44v6 and E-cadherin expression were examined.</p><p><b>RESULTS</b>After the treatment, the motility of Bcap37 cells, their adhesion to vascular endothelial cells ECV304 and the CD44v6 expression were significantly reduced. The adhesiveness of Bcap37 cells and their E-cadherin expression were significantly enhanced.</p><p><b>CONCLUSION</b>The microencapsulated CHO cells modified with maspin gene decrease motility and adhesiveness of breast carcinoma cells Bcap37, which help explain the anti-metastatic effects of maspin.</p>