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同基因原位小鼠膀胱癌模型的组织病理学特征

Histopathological characterization of a syngeneic orthotopic murine bladder cancer model.

作者信息

Chade Daher C, Andrade Priscila M, Borra Ricardo C, Leite Katia R, Andrade Enrico, Villanova Fabiola E, Srougi Miguel

机构信息

Division of Urology, University of Sao Paulo Medical School, Sao Paulo, Brazil.

出版信息

Int Braz J Urol. 2008 Mar-Apr;34(2):220-6; discussion 226-9. doi: 10.1590/s1677-55382008000200013.

Abstract

PURPOSE

We developed and characterized by histopathology and immunohistochemistry a syngeneic murine bladder tumor model derived from the MB49 tumor cell line.

MATERIALS AND METHODS

Bladder tumor implantation was achieved by intravesical instillation of 5 x 105 MB49 tumor cells in C57BL/6 mice. A chemical lesion of the bladder was performed in order to promote intravesical tumor implantation. The bladder wall lesion was accomplished by transurethral instillation of silver nitrate (AgNO3). After 15 days, the animals were sacrificed, examined macroscopically for intravesical tumor and bladder weight. Histology and immunohistochemistry were performed using cytokeratin 7 (CK7), carcinoembrionic antigen (Dako-CEA), p53 and c-erbB2 oncoprotein (Her2/neu).

RESULTS

Twenty-nine out of 30 animals (96.7%) developed intravesical tumors in a 15-day period. Macroscopically, the mean bladder weight was 0.196g (0.069-0.538g), 10 to 15 times the normal bladder weight. The immunohistochemical analysis showed significant membrane expression of CEA and CK7: a similar finding for human urothelial cancer. We also characterized absence of expression of p53 and anti-Her2/neu in the murine model.

CONCLUSIONS

High tumor take rates were achieved by using the chemical induction of the bladder tumor. Although electric cauterization is widely described in the literature for syngeneic orthotopic animal models, the technique described in this study represents an alternative for intravesical bladder tumor implantation. Moreover, the histopathology and immunohistochemical analysis of the murine bladder tumor model derived from the MB49 cell line showed a resemblance to human infiltrating urothelial carcinoma, allowing clinical inference from experimental immunotherapy testing.

摘要

目的

我们通过组织病理学和免疫组织化学方法建立并鉴定了一种源自MB49肿瘤细胞系的同基因小鼠膀胱肿瘤模型。

材料与方法

通过向C57BL/6小鼠膀胱内灌注5×105个MB49肿瘤细胞来实现膀胱肿瘤植入。为促进膀胱内肿瘤植入,对膀胱进行化学损伤。膀胱壁损伤通过经尿道灌注硝酸银(AgNO3)完成。15天后,处死动物,肉眼检查膀胱内肿瘤及膀胱重量。使用细胞角蛋白7(CK7)、癌胚抗原(Dako-CEA)、p53和c-erbB2癌蛋白(Her2/neu)进行组织学和免疫组织化学分析。

结果

30只动物中有29只(96.7%)在15天内发生了膀胱内肿瘤。肉眼可见,平均膀胱重量为0.196g(0.069 - 0.538g),是正常膀胱重量的10至15倍。免疫组织化学分析显示CEA和CK7有明显的膜表达:这与人类尿路上皮癌的情况相似。我们还鉴定了该小鼠模型中p53和抗Her2/neu无表达。

结论

通过化学诱导膀胱肿瘤实现了高肿瘤接种率。尽管文献中广泛描述了电灼术用于同基因原位动物模型,但本研究中描述的技术是膀胱内肿瘤植入的一种替代方法。此外,源自MB49细胞系的小鼠膀胱肿瘤模型的组织病理学和免疫组织化学分析显示与人类浸润性尿路上皮癌相似,这使得能够从实验性免疫治疗测试中进行临床推断。

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