Orthotopic Patient-Derived Pancreatic Cancer Xenografts Engraft Into the Pancreatic Parenchyma, Metastasize, and Induce Muscle Wasting to Recapitulate the Human Disease.
Orthotopic Patient-Derived Pancreatic Cancer Xenografts Engraft Into the Pancreatic Parenchyma, Metastasize, and Induce Muscle Wasting to Recapitulate the Human Disease.
复制标题
DOI：
10.1097/mpa.0000000000000843
复制
发表时间：
2017-07
期刊：
影响因子：
2.9
通讯作者：
Trevino JG
中科院分区：
文献类型：
--
作者：
Go KL;Delitto D;Judge SM;Gerber MH;George TJ Jr;Behrns KE;Hughes SJ;Judge AR;Trevino JG
与当前动物模型相关的局限性是胰腺癌（PC）治疗的可靠临床前评价的主要障碍。为了开发更可靠的临床前模型，我们最近建立了皮下患者来源的异种移植物（PDX）模型。然而，负责其高致死性的PC的关键方面，如远处转移和癌症恶病质的发展，在侧翼PDX模型中仍然代表不足。本研究的目的是评估胰腺癌（PC）原位患者来源的异种移植物（PDX）模型重现人类疾病这些方面的程度。将人PDX衍生的PC肿瘤直接植入NOD.Cg-Prkdcscid Il 2 rgtm 1 Wjl/SzJ（NSG）小鼠的胰腺中。然后评估肿瘤生长、转移和肌肉萎缩。原位植入的PDX衍生的肿瘤一致地并入鼠胰腺实质中，转移到肝和肺两者，并且诱导与肿瘤大小成正比的肌肉消耗，与癌症恶病质综合征一致。通过原位植入技术的描述，我们证明了一个高度可重复的模型，概括了人类PC的局部和全身方面。
Limitations associated with current animal models serve as a major obstacle to reliable preclinical evaluation of therapies in pancreatic cancer (PC). In an effort to develop more reliable preclinical models, we have recently established a subcutaneous patient-derived xenograft (PDX) model. However, critical aspects of PC responsible for its highly lethal nature, such as the development of distant metastasis and cancer cachexia, remain underrepresented in the flank PDX model. The purpose of this study was to evaluate the degree to which an orthotopic patient-derived xenograft (PDX) model of pancreatic cancer (PC) recapitulates these aspects of the human disease. Human PDX-derived PC tumors were implanted directly into the pancreas of NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ (NSG) mice. Tumor growth, metastasis and muscle wasting were then evaluated. Orthotopically implanted PDX-derived tumors consistently incorporated into the murine pancreatic parenchyma, metastasized to both the liver and lungs and induced muscle wasting directly proportional to the size of the tumor, consistent of the cancer cachexia syndrome. Through the orthotopic implantation technique described, we demonstrate a highly reproducible model that recapitulates both local and systemic aspects of human PC.