New pancreatic carcinoma model for studying oncolytic adenoviruses in the permissive Syrian hamster.

New pancreatic carcinoma model for studying oncolytic adenoviruses in the permissive Syrian hamster.
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DOI:
10.1038/cgt.2009.36
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发表时间:
2009-12
影响因子:
6.4
通讯作者:
--
中科院分区:
医学3区
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--
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叙利亚仓鼠是研究5型腺病毒溶瘤载体系统作用的实用动物模型。Ad5在叙利亚仓鼠组织中复制良好,并且已知叙利亚仓鼠细胞系支持Ad5复制。在这项研究中,我们从可移植的胰腺、肾脏、肝脏和肺部肿瘤中建立了四种新的叙利亚仓鼠细胞系。胰腺细胞系(SHPC 6)和肾细胞系对Ad5复制是高度允许的。当细胞被注射到腹腔中时,SHPC 6细胞系形成播散性腹膜内肿瘤。INGN 007是一种基于溶瘤Ad5的载体,在腹膜内注射该载体后,完全逆转了播散性腹膜内SHPC 6肿瘤结节的生长,导致治疗动物的100%存活。SHPC 6细胞也形成皮下肿瘤,其生长在瘤内注射后被INGN 007抑制。INGN 007在腹膜内和皮下SHPC 6肿瘤中复制。腹膜内注射后,INGN 007在具有腹膜内SHPC 6肿瘤的仓鼠的肝脏中未复制,并且无肝毒性。这些研究表明,SHPC 6细胞系可能是一个有用的模型,为播散性胰腺癌,INGN 007可能是一个安全和有效的载体来治疗这些肿瘤。
Syrian hamster is a practical animal model for studying the systemic effects of oncolytic vectors derived from adenovirus serotype 5 (Ad5). Ad5 replicates well in Syrian hamster tissues, and Syrian hamster cell lines are available that are known to support Ad5 replication. In this study, we established four new Syrian hamster cell lines from transplantable pancreatic, renal, hepatic and lung tumors. The pancreatic cell line (SHPC6) and the renal cell line were highly permissive for Ad5 replication. The SHPC6 cell line formed disseminated intraperitoneal tumors when cells were injected into the peritoneal cavity. INGN 007, an oncolytic Ad5-based vector, completely reversed the growth of disseminated intraperitoneal SHPC6 tumor nodules following intraperitoneal injection of the vector, leading to 100% survival of the treated animals. SHPC6 cells also formed subcutaneous tumors, whose growth was suppressed by INGN 007 following intratumoral injection. INGN 007 replicated in both the intraperitoneal and subcutaneous SHPC6 tumors. Following intraperitoneal injection, INGN 007 did not replicate in the livers of hamsters with intraperitoneal SHPC6 tumors, and was not hepatotoxic. These studies suggest that the SHPC6 cell line may be useful as a model for disseminated pancreatic cancer, and that INGN 007 may be a safe and effective vector to treat these tumors.
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