An orthotopic model of papillary thyroid carcinoma in athymic nude mice

An orthotopic model of papillary thyroid carcinoma in athymic nude mice
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DOI:
10.1001/archoto.2007.36
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发表时间:
2008-02-01
影响因子:
--
通讯作者:
Clayman, Gary L.
Clayman, Gary L.
中科院分区:
其他
文献类型:
--
作者:
Ahn, Soon-Hyun;Henderson, Ying;Clayman, Gary L.

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目的:为了建立一个可重复的原位甲状腺乳头状癌模型,用于BRAF(V600 E)突变(GenBank NM 004333)和RET/PTC重排(GenBank M31213),以重现人类的临床表现。D.安德森癌症中心。干预:将BRAF突变或RET/PTC 1重排的乳头状甲状腺癌细胞注射到无胸腺雌性裸鼠的甲状腺中。当肿瘤负荷超过1.0 cm或当它们表现出显着的morbidity.Main结果Measures:致瘤性,肿瘤侵袭和转移,细胞侵袭和迁移的程度,和中位数survival.Results:所有的BRAF突变的细胞系和1个选择的RET/PTC 1重排细胞系在小鼠中的致瘤性为100%。这些小鼠肿瘤模型表现出广泛的生物学潜能,包括喉浸润,淋巴结转移,肺转移,从而反映了临床谱的乳头状carcinoma.Conclusions:原位模型的乳头状甲状腺癌成功地建立在裸鼠中使用BRAF突变和RET/PTC 1重排细胞系。这些模型模拟了人类疾病,因此将有助于评估新型靶向治疗的临床潜力。
Objective: To develop a reproducible orthotopic model of papillary thyroid carcinoma for the BRAF(V600E) mutation (GenBank NM004333) and an RET/PTC rearrangement (GenBank M31213) that recapitulates the clinical picture in humans.Design: In vitro and in vivo study.Setting: Department of Head and Neck Surgery, M. D. Anderson Cancer Center.Subjects: Eight- to 12-week-old athymic female nude mice.Intervention: Either BRAF-mutated or RET/PTC1-rearranged papillary thyroid carcinoma cells were injected into the thyroid glands of athymic female nude mice. The mice were euthanized when the tumor burden exceeded 1.0 cm or when they exhibited significant morbidity.Main Outcome Measures: Tumorigenicity, extent of tumor invasion and metastasis, cell invasion and migration, and median survival.Results: All the BRAF-mutated cell lines and 1 selected RET/PTC1-rearranged cell line were 100% tumorigenic in mice. These mouse tumor models exhibited a wide range of biological potential, including laryngeal invasion, lymph node metastasis, and pulmonary metastasis, thus reflecting the clinical spectrum of papillary carcinoma.Conclusions: An orthotopic model of papillary thyroid carcinoma was successfully established in nude mice using BRAF-mutated and RET/PTC1-rearranged cell lines. These models mimic the human disease and will thus be useful for evaluating the clinical potential of novel targeted therapies.