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溶瘤麻疹病毒对犬膀胱移行细胞癌细胞的抗肿瘤活性。

Antitumor activity of an oncolytic measles virus against canine urinary bladder transitional cell carcinoma cells.

机构信息

Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Japan; Institute of Industrial Science, The University of Tokyo, 4-6-1, Komaba, Meguro-ku, Tokyo 153-8505, Japan; Laboratory of Veterinary Surgery, Department of Veterinary Medicine, College of Bioresource Sciences, Nihon University, 1866 Kameino, Fujisawa, Kanagawa 252-0880, Japan.

Laboratory Animal Research Center, The Institute of Medical Science, The University of Tokyo, Japan.

出版信息

Res Vet Sci. 2020 Dec;133:313-317. doi: 10.1016/j.rvsc.2020.10.016. Epub 2020 Oct 22.

Abstract

The prognosis of canine transitional cell carcinoma (TCC) of urinary bladder is generally poor because it is difficult to diagnose at early stages and conventional therapies, such as surgical resection and/or chemotherapy, are often not curative treatments. Based on our previous report that recombinant measles virus (rMV-SLAMblind) therapy could be a new treatment for canine mammary tumor, the applicability of rMV-SLAMblind in canine urinary bladder TCC was examined in this study. A canine TCC cell line was established from a TCC patient dog by transplanting a piece of the tumor mass into an immunodeficient mouse and then isolating the primary TCC cells from the grown tumor mass. The primary cultured cells, named TCC-NU1, express nectin-4, a receptor for rMV-SLAMblind infection. The rMV-SLAMblind infected TCC-NU1 cells, and dose-dependently showed cell cytotoxicity. Moreover, intratumoral administration of rMV-SLAMblind in a xenograft model bearing TCC-NU1 cells significantly suppressed the tumor growth reducing the endpoint mass of tumors in treated mice compared to control mice. These results suggest that virotherapy with rMV-SLAMblind be a new candidate therapy for canine TCC.

摘要

犬膀胱癌移行细胞癌(TCC)的预后通常较差,因为早期诊断困难,手术切除和/或化疗等常规治疗往往不是治愈性治疗。基于我们之前关于重组麻疹病毒(rMV-SLAMblind)治疗可能是犬乳腺肿瘤的一种新治疗方法的报告,本研究检查了 rMV-SLAMblind 在犬膀胱癌 TCC 中的适用性。通过将肿瘤块移植到免疫缺陷小鼠中,然后从生长的肿瘤块中分离原发性 TCC 细胞,从患有 TCC 的犬患者中建立了犬 TCC 细胞系。原代培养的细胞命名为 TCC-NU1,表达了 rMV-SLAMblind 感染的受体 nectin-4。rMV-SLAMblind 感染 TCC-NU1 细胞,并呈剂量依赖性显示细胞毒性。此外,在携带 TCC-NU1 细胞的异种移植模型中瘤内给予 rMV-SLAMblind 显著抑制了肿瘤生长,与对照组小鼠相比,治疗组小鼠的肿瘤终末质量减少。这些结果表明,rMV-SLAMblind 的病毒疗法可能是犬 TCC 的一种新的候选治疗方法。

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