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.
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 humanuveal melanoma xenografts transplanted into immunodeficientmice. EXPERIMENTAL DESIGN: Ninety tumor specimens were grafted into severe combined immunodeficientmice, 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 humanuveal 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.
Authors: Clemens Krepler; Katrin Sproesser; Patricia Brafford; Marilda Beqiri; Bradley Garman; Min Xiao; Batool Shannan; Andrea Watters; Michela Perego; Gao Zhang; Adina Vultur; Xiangfan Yin; Qin Liu; Ioannis N Anastopoulos; Bradley Wubbenhorst; Melissa A Wilson; Wei Xu; Giorgos Karakousis; Michael Feldman; Xiaowei Xu; Ravi Amaravadi; Tara C Gangadhar; David E Elder; Lauren E Haydu; Jennifer A Wargo; Michael A Davies; Yiling Lu; Gordon B Mills; Dennie T Frederick; Michal Barzily-Rokni; Keith T Flaherty; Dave S Hoon; Michael Guarino; Joseph J Bennett; Randall W Ryan; Nicholas J Petrelli; Carol L Shields; Mizue Terai; Takami Sato; Andrew E Aplin; Alexander Roesch; David Darr; Steve Angus; Rakesh Kumar; Ensar Halilovic; Giordano Caponigro; Sebastien Jeay; Jens Wuerthner; Annette Walter; Matthias Ocker; Matthew B Boxer; Lynn Schuchter; Katherine L Nathanson; Meenhard Herlyn Journal: Cell Rep Date: 2017-11-14 Impact factor: 9.423
Authors: Ignacio Garrido-Laguna; Maria Uson; N V Rajeshkumar; Aik Choon Tan; Elizabeth de Oliveira; Collins Karikari; Maria C Villaroel; Ana Salomon; Gretchen Taylor; Rajni Sharma; Ralph H Hruban; Anirban Maitra; Daniel Laheru; Belén Rubio-Viqueira; Antonio Jimeno; Manuel Hidalgo Journal: Clin Cancer Res Date: 2011-07-08 Impact factor: 12.531
Authors: Mariana Varna; Guilhem Bousquet; Irmine Ferreira; Marie Goulard; Morad El-Bouchtaoui; Pierre Mongiat Artus; Jérome Verine; Eric de Kerviler; Lucie Hernandez; Christophe Leboeuf; Bernard Escudier; Luc Legrès; Niclas Setterblad; Hany Soliman; Jean-Paul Feugeas; Anne Janin; Philippe Bertheau Journal: Int J Clin Exp Pathol Date: 2014-05-15