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转基因Lewis大鼠中的前列腺癌——一种用于评估免疫治疗的肿瘤模型。

Prostate carcinoma in transgenic Lewis rats - a tumor model for evaluation of immunological treatments.

作者信息

Johnson Laura E, Becker Jordan T, Dubovsky Jason A, Olson Brian M, McNeel Douglas G

机构信息

University of Wisconsin Carbone Cancer Center, Madison, WI 53705, USA.

出版信息

Chin Clin Oncol. 2013 Mar 1;2(1). doi: 10.3978/j.issn.2304-3865.2012.11.06.

Abstract

Transgenic rodent models of prostate cancer have served as valuable preclinical models to evaluate novel treatments and understand malignant disease progression. In particular, a transgenic rat autochthonous model of prostate cancer using the SV40 large T antigen expressed under a prostate-specific probasin promoter was previously developed as a model of androgen-dependent prostate cancer (TRAP). In the current report, we backcrossed this strain to the Lewis strain, an inbred rat strain better characterized for immunological analyses. We demonstrate that Lewis transgenic rats (Lew-TRAP) developed prostate adenocarcinomas with 100% penetrance by 25 weeks of age. Tumors were predominantly androgen-dependent, as castration prevented tumor growth in the majority of animals. Finally, we demonstrate that Lew-TRAP rats could be immunized with a DNA vaccine encoding a human prostate tumor antigen (prostatic acid phosphatase) with the development of Lewis strain-specific T-cell responses. We propose that this Lew-TRAP strain, and prostate tumor cell lines derived from this strain, can be used as a future prostate cancer immunotherapy model.

摘要

前列腺癌的转基因啮齿动物模型已成为评估新疗法和了解恶性疾病进展的重要临床前模型。特别是,先前已开发出一种使用在前列腺特异性前列腺素启动子下表达的SV40大T抗原的前列腺癌转基因大鼠原位模型,作为雄激素依赖性前列腺癌(TRAP)的模型。在本报告中,我们将该品系回交到Lewis品系,这是一种在免疫分析方面特征更明确的近交大鼠品系。我们证明,Lewis转基因大鼠(Lew-TRAP)在25周龄时100%发生前列腺腺癌。肿瘤主要是雄激素依赖性的,因为去势可阻止大多数动物的肿瘤生长。最后,我们证明用编码人前列腺肿瘤抗原(前列腺酸性磷酸酶)的DNA疫苗免疫Lew-TRAP大鼠可产生Lewis品系特异性T细胞反应。我们提出,这种Lew-TRAP品系以及源自该品系的前列腺肿瘤细胞系可作为未来前列腺癌免疫治疗模型。

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