PDF(Pubmed)
Abstract：
Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5-7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining growth parameter-based stages of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future.
摘要：
胰腺导管腺癌(PDAC),以血管不足为特征，缺氧,增生性基质是人类最致命的恶性肿瘤之一，5年生存率仅为7%。在疾病早期发作的患者中，胰腺的解剖位置和缺乏症状是晚期诊断的原因。因此,85%的患者出现不可切除，本地先进,或晚期转移性疾病在诊断和依赖替代疗法，如化疗，免疫疗法，和其他人。对这些疗法的反应高度取决于治疗开始时的疾病阶段。是的,因此,在测试新疗法和治疗方式时，在临床前研究中考虑PDAC模型的阶段至关重要。我们报告了小鼠基于细胞的原位胰腺癌模型的标准化诱导，并通过超声成像和胰腺星状细胞水平的组织学分析来鉴定其进展的重要特征。成熟成纤维细胞，和胶原蛋白。结果突出表明,在所研究的BxPC-3和Panc-1模型的植入后第5-7周,早期原发性肿瘤在胰腺中被隔离,并向浸润网膜前进。后期表现出广泛的增长，网膜和/或胃壁的浸润，转移,增强的成纤维细胞，和胶原蛋白水平。这些发现可以作为定义基于生长参数的原位胰腺癌模型阶段的建议，用于未来药物疗效的临床前测试。
