Establishment of patient-derived cancer xenografts in immunodeficient NOG mice.

Establishment of patient-derived cancer xenografts in immunodeficient NOG mice.
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DOI:
10.3892/ijo.2015.2997
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发表时间:
2015-07
影响因子:
5.2
通讯作者:
Nakamura M
Nakamura M
中科院分区:
医学2区
文献类型:
--
作者:
Chijiwa T;Kawai K;Noguchi A;Sato H;Hayashi A;Cho H;Shiozawa M;Kishida T;Morinaga S;Yokose T;Katayama M;Takenaka N;Suemizu H;Yamada R;Nakamura Y;Ohtsu T;Takano Y;Imai K;Miyagi Y;Nakamura M

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可行和稳定的人类癌细胞系和动物模型与充分的临床信息相结合,对癌症研究和患者护理的未来进展至关重要。常规的体外癌细胞系是常见的;然而,它们缺乏患者的详细信息,包括疾病表型和药物敏感性。具有临床信息的患者来源的异种移植物(PDX)(所谓的“癌症异种患者”)是一个有希望的进步,可能会加速抗癌治疗的发展。我们将116个手术切除的肿瘤组织皮下接种于NOG小鼠,建立了61个PDX细胞系(成功率53%)。PDX细胞系是在各种类型的上皮肿瘤和肉瘤中建立的,包括胃肠道间质瘤和Ewing/PNET肉瘤。转移性肿瘤产生PDX细胞系的效率(65%)高于原发肿瘤(27%,P<0.001)。在我们的PDX模型中,形态特征、基因表达谱和遗传改变模式都得到了很好的保存。在8例(7%)中,几代可移植的异种移植物由来自人类的大而单调的非上皮细胞组成,显示为爱泼斯坦-巴尔病毒感染相关的淋巴增生性病变。尽管如此,与临床信息相联系的PDX为研究新的抗癌药物的临床前研究提供了许多优势。快速有效地建立个体PDX也可能有助于未来的个性化抗癌治疗。
Viable and stable human cancer cell lines and animal models combined with adequate clinical information are essential for future advances in cancer research and patient care. Conventional in vitro cancer cell lines are commonly available; however, they lack detailed information on the patient from which they originate, including disease phenotype and drug sensitivity. Patient-derived xenografts (PDX) with clinical information (so-called ‘cancer xenopatients’) are a promising advance that may accelerate the development of anticancer therapies. We established 61 PDX lines from 116 surgically removed tumor tissues inoculated subcutaneously into NOG mice (53% success rate). PDX lines were established from various types of epithelial tumors and also from sarcomas, including gastrointestinal stromal tumors and Ewing/PNET sarcomas. The metastatic tumors yielded PDX lines more effectively (65%) than the primary tumors (27%, P<0.001). In our PDX models, morphological characteristics, gene expression profiles, and genetic alteration patterns were all well preserved. In eight cases (7%), the transplantable xenografts for several generations were composed of large monotonous nonepithelial cells of human origin, revealed to be Epstein-Barr virus infection-associated lymphoproliferative lesions. Despite this, PDX linked with clinical information offer many advantages for preclinical studies investigating new anticancer drugs. The fast and efficient establishment of individual PDX may also contribute to future personalized anticancer therapies.
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