Establishment of a Non-Invasive Semi-Quantitative Bioluminescent Imaging Method for Monitoring of an Orthotopic Esophageal Cancer Mouse Model.

Establishment of a Non-Invasive Semi-Quantitative Bioluminescent Imaging Method for Monitoring of an Orthotopic Esophageal Cancer Mouse Model.
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建立一种非侵入性半定量生物发光成像方法,用于监测原位食管癌小鼠模型。

DOI:
10.1371/journal.pone.0114562
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Fujiwara T
Fujiwara T
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Kuroda S;Kubota T;Aoyama K;Kikuchi S;Tazawa H;Nishizaki M;Kagawa S;Fujiwara T

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各类肿瘤原位模型广泛应用于临床前抗肿瘤治疗实验。然而,在原位肿瘤模型中,特别是对于外部看不见的肿瘤,缺乏适当的治疗效果监测方法。在本研究中,我们旨在建立一种无创的半定量生物发光成像方法来监测原位食管癌小鼠模型。我们证实,原位植入nu/nu小鼠(n = 5)腹腔食管的TE8食管癌细胞系在接种后6周内不仅在植入部位出现主要肿瘤,而且出现局部淋巴结转移和腹膜传播。建立了稳定表达萤火虫荧光素酶基因(TE8- luc)的TE8细胞系。我们发现皮下植入nu/nu小鼠(n = 5)的TE8-Luc细胞在接种后5周持续生长。肿瘤体积与肿瘤发出的发光强度密切相关,使用IVIS成像系统对其进行量化。然后我们发现,将TE8-Luc细胞原位植入小鼠腹部食道(n = 8)也形成了肿瘤,并且通过IVIS检测,该肿瘤的发光强度随着时间的推移而增加,直到接种后7周,因此可能反映了肿瘤的进展。因此,我们建议使用无创半定量IVIS成像系统监测这种原位食管癌模型,将有助于食管癌的体内治疗实验。该实验环境有望促进食管癌临床前研究中新型治疗技术的发展。
Orthotopic models of various types of tumors are widely used in anti-tumor therapeutic experiments in preclinical studies. However, there are few ways to appropriately monitor therapeutic effect in orthotopic tumor models, especially for tumors invisible from the outside. In this study we aimed to establish a non-invasive semi-quantitative bioluminescent imaging method of monitoring an orthotopic esophageal cancer mouse model. We confirmed that the TE8 esophageal cancer cell line implanted orthotopically into the abdominal esophagus of nu/nu mice (n = 5) developed not only a main tumor at the implanted site, but also local lymph node metastases and peritoneal disseminations within 6 weeks after inoculation. We established a TE8 cell line that stably expressed the firefly luciferase gene (TE8-Luc). We showed that TE8-Luc cells implanted subcutaneously into nu/nu mice (n = 5) grew over time until 5 weeks after inoculation. Tumor volume was strongly correlated with luminescent intensity emitted from the tumor, which was quantified using the IVIS imaging system. We then showed that TE8-Luc cells implanted orthotopically into the mouse abdominal esophagus (n = 8) also formed a tumor and that the luminescent intensity of such a tumor, as detected by IVIS, increased over time until 7 weeks after inoculation and was therefore likely to reflect tumor progression. We therefore propose that this orthotopic esophageal cancer model, monitored using the non-invasive semi-quantitative IVIS imaging system, will be useful for in vivo therapeutic experiments against esophageal cancer. This experimental setting is expected to contribute to the development of novel therapeutic technologies for esophageal cancer in preclinical studies.
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