Establishment and characterization of a panel of human uveal melanoma xenografts derived from primary and/or metastatic tumors
| Autor: | Sergio Roman-Roman, Jérôme Couturier, Marie-Hélène Donnadieu, Fariba Nemati, Corine Plancher, Bernard Asselain, Didier Decaudin, Isabelle Peguillet, Delphine Robert, Xavier Sastre-Garau, Laurence Desjardins, Cécile Reyes, Olivier Lantz, Marie-Andrée Bessard, Sophie Piperno-Neumann, Simon Saule, David Gentien, Ahmed Dahmani, Cécile Laurent, Emmanuel Barillot, Pascale Mariani |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Uveal Neoplasms Cancer Research Pathology medicine.medical_specialty Mice SCID Polymorphism Single Nucleotide Nitrosourea Compounds Metastasis Mice Organophosphorus Compounds Antineoplastic Combined Chemotherapy Protocols medicine Biomarkers Tumor Temozolomide Tumor Cells Cultured Animals Humans Neoplasm Metastasis Melanoma In Situ Hybridization Fluorescence Oligonucleotide Array Sequence Analysis business.industry Gene Expression Profiling Cancer Middle Aged medicine.disease Xenograft Model Antitumor Assays Tumor antigen Transplantation Dacarbazine Oncology Cancer research Fotemustine Female business medicine.drug Tumor Graft |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 16(8) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: Uveal melanoma is the most common primary intraocular malignant tumor in adults and is defined by a poor natural outcome, as 50% of patients die from metastases. The aim of this study was to develop and characterize a panel of human uveal melanoma xenografts transplanted into immunodeficient mice. Experimental Design: Ninety tumor specimens were grafted into severe combined immunodeficient mice, and 25 transplantable xenografts were then established (28%). Relationship between tumor graft and clinical, biological, and therapeutic features of the patients included were investigated. Characterization of 16 xenografts included histology, molecular analyses by immunohistochemistry, genetic alteration analysis (single-nucleotide polymorphism), and specific tumor antigen expression by quantitative reverse transcription-PCR. Pharmacologic characterization (chemosensitivity) was also done in four models using two drugs, temozolomide and fotemustine, currently used in the clinical management of uveal melanoma. Results: Take rate of human uveal melanoma was 28% (25 of 90). Tumor take was independent of size, histologic parameters, or chromosome 3 monosomy but was significantly higher in metastatic tumors. Interestingly, in vivo tumor growth was prognostic for a lower metastasis-free survival in patients with primary tumors. A high concordance between the patients' tumors and their corresponding xenografts was found for all parameters tested (histology, genetic profile, and tumor antigen expression). Finally, the four xenografts studied displayed different response profiles to chemotherapeutic agents. Conclusions: Based on these results, this panel of 16 uveal melanoma xenografts represents a useful preclinical tool for both pharmacologic and biological assessments. Clin Cancer Res; 16(8); 2352–62. ©2010 AACR. |
| Databáze: | OpenAIRE |
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