尿激酶特异性溶瘤仙台病毒诱导原位荷瘤鼠模型中间变性甲状腺癌的细胞融合/凋亡。

Induction of cell fusion/apoptosis in anaplastic thyroid carcinoma in orthotopic mouse model by urokinase-specific oncolytic Sendai virus.

机构信息

Department of Otolaryngology - Head and Neck Surgery, National Defense Medical College, Saitama, Japan.

Department of Otolaryngology - Head and Neck Surgery, Kitasato University School of Medicine, Sagamihara, Japan.

出版信息

Head Neck. 2019 Sep;41(9):2873-2882. doi: 10.1002/hed.25769. Epub 2019 Apr 10.

DOI:10.1002/hed.25769

PMID:30969451

Abstract

BACKGROUND

This study was designed to assess the therapeutic effect of urokinase-targeted recombinant oncolytic Sendai virus, termed "BioKnife," on anaplastic thyroid carcinoma (ATC).

METHODS

Urokinase activity was investigated in human ATC cell lines, and BioKnife cytotoxicity against the cell lines was evaluated in vitro. Orthotopic mouse models of ATC were treated with three intratumoral injections of BioKnife, control virus, or phosphate-buffered saline (PBS) and were observed daily until >20% weight loss occurred.

RESULTS

All three ATC cell lines showed a high level of urokinase activity. BioKnife induced urokinase-dependent cell fusion and cytotoxicity in all cell lines. Orthotopic models treated with BioKnife showed significantly prolonged survival compared with models treated with control virus or PBS (BioKnife 41.6 ± 15.0, control virus 17.0 ± 2.9, PBS 17.7 ± 6.3 days).

CONCLUSIONS

BioKnife exerted therapeutic effects in orthotopic ATC mouse models. Thus, BioKnife represents a possible treatment option for ATC.

摘要

背景

本研究旨在评估尿激酶靶向重组溶瘤单纯疱疹病毒（称为“BioKnife”）对间变性甲状腺癌（ATC）的治疗效果。

方法

研究了尿激酶活性在人 ATC 细胞系中的作用，并评估了 BioKnife 对细胞系的体外细胞毒性。用三种肿瘤内注射 BioKnife、对照病毒或磷酸盐缓冲盐水（PBS）治疗 ATC 原位小鼠模型，并每天观察，直到体重损失超过 20%。

结果

所有三种 ATC 细胞系均显示高水平的尿激酶活性。BioKnife 诱导所有细胞系中尿激酶依赖性细胞融合和细胞毒性。与对照病毒或 PBS 治疗的模型相比，用 BioKnife 治疗的原位模型显示出显著延长的存活时间（BioKnife 41.6±15.0、对照病毒 17.0±2.9、PBS 17.7±6.3 天）。