Rainov N G, Koch S, Sena-Esteves M, Berens M E
Department of Neurosurgery, Faculty of Medicine, Martin-Luther-University Halle-Wittenberg, Halle, Germany.
J Neuropathol Exp Neurol. 2000 Jul;59(7):607-13. doi: 10.1093/jnen/59.7.607.
A large animal tumor model for anaplastic glioma has been recently developed using immunotolerant allogeneic Beagle dogs and an established canine glioma cell line, J3T. This model offers advantages in terms of tumor morphology and similarity to human anaplastic glioma. The present study was aimed at evaluating the biological characteristics of the J3T canine glioma cell line as related to experimental gene therapy studies. Furthermore, development and morphology of canine brain tumors in a xenogeneic immunodeficient SCID mouse model was investigated. It was demonstrated that cultured J3T cells can be efficiently infected by adenovirus (AV), herpes-simplex type I (HSV), or retrovirus (RV) vectors, as well as by non-virus vectors such as cationic liposome/DNA complexes. Thus, in terms of infectability and transfectability, J3T cells seem to be closer to human glioma than the 9L rodent gliosarcoma. Cytotoxicity of selection antibiotics such as G418, puromycin, and hygromycin on J3T cells essentially resemble cytotoxicity seen with other established glioma lines, for example, 9L, U87, or U343. RV-mediated HSV-TK/GCV gene therapy demonstrated comparable LD50 for TK-expressing and control (non-expressing) J3T and 9L cells treated with Ganciclovir. Further, it was proven that J3T cells are tumorigenic and may grow heterotopically and orthotopically in a xenogeneic immunodeficient host, the SCID mouse, although morphology and growth pattern of these xenogeneic tumors differ from the demonstrated invasive phenotype in the Beagle dog.
最近利用免疫耐受的同种异体比格犬和已建立的犬胶质瘤细胞系J3T开发了一种间变性胶质瘤的大型动物肿瘤模型。该模型在肿瘤形态和与人类间变性胶质瘤的相似性方面具有优势。本研究旨在评估J3T犬胶质瘤细胞系与实验性基因治疗研究相关的生物学特性。此外，还研究了异种免疫缺陷SCID小鼠模型中犬脑肿瘤的发生和形态。结果表明，培养的J3T细胞可被腺病毒（AV）、I型单纯疱疹病毒（HSV）或逆转录病毒（RV）载体以及阳离子脂质体/DNA复合物等非病毒载体有效感染。因此，就感染性和转染性而言，J3T细胞似乎比9L啮齿动物胶质肉瘤更接近人类胶质瘤。选择抗生素如G418、嘌呤霉素和潮霉素对J3T细胞的细胞毒性与其他已建立的胶质瘤细胞系（如9L、U87或U343）所观察到的细胞毒性基本相似。RV介导的HSV-TK/GCV基因治疗显示，用更昔洛韦处理的表达TK的J3T和9L细胞与对照（不表达）细胞的LD50相当。此外，已证明J3T细胞具有致瘤性，并且可以在异种免疫缺陷宿主SCID小鼠中异位和原位生长，尽管这些异种肿瘤的形态和生长模式与比格犬中显示的侵袭性表型不同。
