Development of induced glioblastoma by implantation of a human xenograft in Yucatan minipig as a large animal model

被引:26
作者
Khoshnevis, Mehrdad [1 ]
Carozzo, Claude [1 ]
Bonnefont-Rebeix, Catherine [1 ]
Belluco, Sara [1 ]
Leveneur, Olivia [3 ]
Chuzel, Thomas [4 ]
Pillet-Michelland, Elodie [1 ]
Dreyfus, Matthieu [5 ]
Roger, Thierry [1 ]
Berger, Francois [5 ]
Ponce, Frederique [1 ,2 ]
机构
[1] VetAgro Sup, UPSP 2016 A104, ICE, Campus Vet Lyon,1 Ave Bourgelat, F-69280 Marcy Letoile, France
[2] VetAgro Sup, Clin Oncol Unit, Campus Vet Lyon,1 Ave Bourgelat, F-69280 Marcy Letoile, France
[3] VetAgro Sup, Inst Claude Bourgelat, BIOVIVO, Campus Vet Lyon,1 Ave Bourgelat, F-69280 Marcy Letoile, France
[4] Voxcan, 1 Ave Bourgelat, F-69280 Marcy Letoile, France
[5] Grenoble Alpes Univ, Inserm Unit 1205, 17 Rue Martyrs Bat, F-38054 Grenoble, France
关键词
Minipig; Yucatan; Glioblastoma; U87; Cyclosporine; Animal model; CONVECTION-ENHANCED DELIVERY; CENTRAL-NERVOUS-SYSTEM; MALIGNANT GLIOMAS; BRAIN-TUMORS; CELL XENOGRAFTS; MURINE MODELS; UNITED-STATES; RAT BRAINS; RADIOTHERAPY; IMMUNOTHERAPY;
D O I
10.1016/j.jneumeth.2017.03.007
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background: Glioblastoma is the most common and deadliest primary brain tumor for humans. Despite many efforts toward the improvement of therapeutic methods, prognosis is poor and the disease remains incurable with a median survival of 12-14.5 months after an optimal treatment. To develop novel treatment modalities for this fatal disease, new devices must be tested on an ideal animal model before performing clinical trials in humans. New method: A new model of induced glioblastoma in Yucatan minipigs was developed. Nine immunosuppressed minipigs were implanted with the U87 human glioblastoma cell line in both the left and right hemispheres. Computed tomography (CT) acquisitions were performed once a week to monitor tumor growth. Results: Among the 9 implanted animals, 8 minipigs showed significant macroscopic tumors on CT acquisitions. Histological examination of the brain after euthanasia confirmed the CT imaging findings with the presence of an undifferentiated glioma. Comparison with existing method: Yucatan minipig, given its brain size and anatomy (gyrencephalic structure) which are comparable to humans, provides a reliable brain tumor model for preclinical studies of different therapeutic Methods: in realistic conditions. Moreover, the short development time, the lower cyclosporine and caring cost and the compatibility with the size of commercialized stereotactic frames make it an affordable and practical animal model, especially in comparison with large breed pigs. Conclusion: This reproducible glioma model could simulate human anatomical conditions in preclinical studies and facilitate the improvement of novel therapeutic devices, designed at the human scale from the outset. (C) 2017 Elsevier B.V. All rights reserved.
引用
收藏
页码:61 / 68
页数:8
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