Establishment of murine basal cell carcinoma allografts: a potential model for preclinical drug testing and for molecular analysis.

Establishment of murine basal cell carcinoma allografts: a potential model for preclinical drug testing and for molecular analysis.
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DOI:
10.1038/jid.2011.204
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发表时间:
2011-11
影响因子:
6.5
通讯作者:
Epstein, Ervin H., Jr.
Epstein, Ervin H., Jr.
中科院分区:
医学1区
文献类型:
--
作者:
Wang, Grace Ying;So, Po-Lin;Wang, Lynn;Libove, Eileen;Wang, Joy;Epstein, Ervin H., Jr.

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在许多癌症中发现了刺猬(HH)信号传导失调,这表明针对该途径的治疗可能对多种癌症有用。基底细胞癌(BCC)是研究HH信号通路在癌变过程中的作用的理想模型系统,因为HH信号通路的异常激活不仅对BCC的发生发展至关重要,而且对BCC的维持也至关重要。基因工程BCC小鼠模型提供了一个重要的工具,用于研究人类BCC的生物学和评估治疗干预,因为这些小鼠在相对较短的时间内产生多种遗传定义的肿瘤。然而,这些模型用于大规模临床前药物测试仍然昂贵且繁琐。在这里,我们报告了一种从NOD/SCID小鼠的小鼠BCC肿瘤中生长同种异体移植物的方法。这些同种异体移植物发育更快,并复制了它们所产生的亲本自体肿瘤的组织学、免疫表型和对至少一种抗BCC药物的反应。因此,同种异体移植物模型为(i)研究BCC致癌作用和(ii)抗HH途径和其他抗BCC药物的初步临床前筛选提供了实用模型。
Dysregulated hedgehog (HH) signaling has been found in numerous cancers, suggesting that therapeutic targeting of this pathway may be useful vs. a wide range of cancers. Basal cell carcinoma (BCC) is an excellent model system for studying the influence of the HH pathway on carcinogenesis because aberrant activation of HH signaling not only is crucial for the development but also for the maintenance of BCC. Genetically engineered BCC mouse models provide one important tool for the study of the biology of human BCCs and for evaluating therapeutic interventions since these mice produce multiple genetically defined tumors within a relatively short period of time. However, these models remain expensive and cumbersome to use for large-scale pre-clinical drug testing. Here we report a method for growing allografts from murine BCC tumors in NOD/SCID mice. These allografts develop faster and reproduce the histology, immunophenotypes and response to at least one anti-BCC drug of the parental autochthonous tumors from which they arise. Therefore, the allograft model provides a practical model for (i) studying BCC carcinogenesis and (ii) initial pre-clinical screening for anti-HH pathway and other anti-BCC drugs.
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影响因子: 50.3
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影响因子: 64.8
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