Establishment of a patient-derived orthotopic Xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern.

Establishment of a patient-derived orthotopic Xenograft (PDOX) model of HER-2-positive cervical cancer expressing the clinical metastatic pattern.
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DOI:
10.1371/journal.pone.0117417
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Hoffman RM
Hoffman RM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hiroshima Y;Zhang Y;Zhang N;Maawy A;Mii S;Yamamoto M;Uehara F;Miwa S;Yano S;Murakami T;Momiyama M;Chishima T;Tanaka K;Ichikawa Y;Bouvet M;Murata T;Endo I;Hoffman RM

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宫颈鳞状细胞癌在发展中国家非常普遍,通常具有转移性和治疗抗性,没有标准的治疗方案。本实验室率先采用外科原位移植(SOI)技术建立了患者源性原位异种移植(PDOX)裸鼠模型。与皮下移植患者来源的异种移植物(PDX)模型不同,PDOX模型转移。最重要的是,转移模式与患者相关。在本报告中,我们描述了HER-2阳性宫颈癌的PDOX模型的发展。裸鼠SOI后的转移包括腹膜播散、肝转移、肺转移和淋巴结转移,反映了供体患者的转移模式。6只裸鼠原发瘤中有4只发现转移。裸鼠中的原发性肿瘤和转移瘤具有与原始肿瘤相似的组织学结构,并且被抗HER-2抗体以与患者癌症相同的模式染色。因此,在PDOX模型中保留了患者的转移模式、组织学和HER-2肿瘤表达。相反,皮下移植患者的颈部肿瘤导致原发性生长,但没有转移。
Squamous cell carcinoma of the cervix, highly prevalent in the developing world, is often metastatic and treatment resistant with no standard treatment protocol. Our laboratory pioneered the patient-derived orthotopic xenograft (PDOX) nude mouse model with the technique of surgical orthotopic implantation (SOI). Unlike subcutaneous transplant patient-derived xenograft (PDX) models, PDOX models metastasize. Most importantly, the metastasis pattern correlates to the patient. In the present report, we describe the development of a PDOX model of HER-2-positive cervical cancer. Metastasis after SOI in nude mice included peritoneal dissemination, liver metastasis, lung metastasis as well as lymph node metastasis reflecting the metastatic pattern in the donor patient. Metastasis was detected in 4 of 6 nude mice with primary tumors. Primary tumors and metastases in the nude mice had histological structures similar to the original tumor and were stained by an anti-HER-2 antibody in the same pattern as the patient’s cancer. The metastatic pattern, histology and HER-2 tumor expression of the patient were thus preserved in the PDOX model. In contrast, subcutaneous transplantation of the patient’s cervical tumors resulted in primary growth but not metastasis.
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