Induction of pancreatic neoplasia in the KRAS/TP53 Oncopig.
Induction of pancreatic neoplasia in the KRAS/TP53 Oncopig.
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DOI：
10.1242/dmm.049699
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发表时间：
2023-01-01
影响因子：
4.3
通讯作者：
中科院分区：
文献类型：
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作者：
胰腺癌（PC）的5年生存率仍然很低。小鼠模型可能无法充分模拟人类PC，并且对于医疗器械开发来说可能太小。大型动物PC模型可以解决这些问题。我们在Oncopigs（含有KRASG 12 D和TP 53 R167 H的转基因猪）中诱导和表征胰腺肿瘤。将表达Cre重组酶的腺病毒（AdCre）注射到一个主胰管中。通过组织学、细胞因子表达、外显子组测序和转录组分析来表征所得肿瘤。10/14头肿瘤猪（71%）在3周内出现大体肿瘤。尸检时，所有这些受试者均出现继发于胰腺肿瘤和胰头癌的胃出口梗阻。用不含Cre重组酶的注射液注射的肿瘤猪和用AdCre注射的野生型猪没有显示出显著的效果。猪胰腺肿瘤的外显子组和转录组分析揭示了与人PC的分子特征和途径的相似性。尽管进一步优化和验证该猪PC模型将是有益的，但预计该模型将有助于集中研究和开发PC的诊断和治疗技术。.总结：我们在Oncopigs中诱导和表征胰腺肿瘤，观察与人胰腺癌的相似性，并表明该模型在胰腺癌诊断和治疗开发中的潜在用途。
The 5-year survival of pancreatic cancer (PC) remains low. Murine models may not adequately mimic human PC and can be too small for medical device development. A large-animal PC model could address these issues. We induced and characterized pancreatic tumors in Oncopigs (transgenic swine containing KRASG12D and TP53R167H). The oncopigs underwent injection of adenovirus expressing Cre recombinase (AdCre) into one of the main pancreatic ducts. Resultant tumors were characterized by histology, cytokine expression, exome sequencing and transcriptome analysis. Ten of 14 Oncopigs (71%) had gross tumor within 3 weeks. At necropsy, all of these subjects had gastric outlet obstruction secondary to pancreatic tumor and phlegmon. Oncopigs with injections without Cre recombinase and wild-type pigs with AdCre injection did not show notable effect. Exome and transcriptome analysis of the porcine pancreatic tumors revealed similarity to the molecular signatures and pathways of human PC. Although further optimization and validation of this porcine PC model would be beneficial, it is anticipated that this model will be useful for focused research and development of diagnostic and therapeutic technologies for PC. . Summary: We induced and characterized pancreatic neoplasms in Oncopigs, observing similarities with human pancreatic cancer, and indicating potential use of the model in the development of diagnostics and therapeutics for pancreatic cancer.
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影响因子：
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