Novel Models of Myxoid Liposarcoma Xenografts Mimicking the Biological and Pharmacologic Features of Human Tumors
| Autor: | Juan Carlos Tercero, Roberta Frapolli, Sergio Marchini, Ezia Bello, Paolo G. Casali, Maurizio D'Incalci, G. Peloso, Roberta Sanfilippo, Eva Tarantino, Emanuela Virdis, Silvana Pilotti, Federica Grosso, Alessandro Gronchi, Elena Tamborini |
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| Rok vydání: | 2010 |
| Předmět: |
Adult
Male Cancer Research Pathology medicine.medical_specialty Transplantation Heterologous Mice Nude Cell Growth Processes Dioxoles Liposarcoma Fusion gene Mice Tetrahydroisoquinolines medicine Animals Humans Antineoplastic Agents Alkylating In Situ Hybridization Fluorescence Trabectedin Aged Aged 80 and over Myxoid liposarcoma medicine.diagnostic_test Reverse Transcriptase Polymerase Chain Reaction business.industry Soft tissue sarcoma Cancer Middle Aged medicine.disease Liposarcoma Myxoid body regions Transplantation Oncology Female business Neoplasm Transplantation medicine.drug Fluorescence in situ hybridization |
| Zdroj: | Clinical Cancer Research. 16:4958-4967 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-10-0317 |
| Popis: | Purpose: Myxoid liposarcoma is a common subtype of liposarcoma. It is associated in more than 90% of cases with the chromosomal translocation t(12;16)(q13;p11) leading to the fusion FUS-CHOP gene that is responsible for the oncogenic transformation of preadipocytes. Recently the marine natural product trabectedin has shown highly selective activity for myxoid liposarcoma, even in the most aggressive round-cell subtype. Experimental Design: Fragments of 17 sarcomas were transplanted s.c. in female athymic NCr-nu/nu mice. Xenografts were established and characterized by morphology, fluorescence in situ hybridization analysis for the translocation and reverse transcriptase-PCR analysis for fusion transcripts. Trabectedin was injected i.v. Results: Seven of 17 tumors grew as continuous xenografts, five of them being myxoid liposarcoma of the round-cell subtype. The chromosomal rearrangement and fusion transcripts in different passages were the same as in the human tumors from which they were derived. The responsiveness to trabectedin in type II myxoid liposarcoma xenografts was as high as in patients. The pathologic response was associated with the presence of the FUS-CHOP fusion gene, indicating that the drug does not totally eradicate the disease. Type III myxoid liposarcoma xenografts seemed much less sensitive to trabectedin, confirming previous clinical observations. Conclusions: This study reports for the first time the characterization of human myxoid liposarcoma xenografts that adequately mimic the biological and pharmacologic features of the human tumor. These models offer a useful tool for investigating the mechanism of selectivity of trabectedin, testing new combinations with this drug and evaluating novel therapies for myxoid liposarcoma. Clin Cancer Res; 16(20); 4958–67. ©2010 AACR. |
| Databáze: | OpenAIRE |
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