| Literature DB >> 29435042 |
Tamami Higuchi1,2, Takehiko Yokobori3,4, Tomoharu Naito2, Chihaya Kakinuma2, Shinji Hagiwara2, Masahiko Nishiyama1,4, Takayuki Asao5.
Abstract
Prognosis of pancreatic cancer is poor, thus the development of novel therapeutic drugs is necessary. During preclinical studies, appropriate models are essential for evaluating drug efficacy. The present study sought to determine the ideal pancreatic cancer mouse model for reliable preclinical testing. Such a model could accurately reflect human pancreatic cancer phenotypes and predict future clinical trial results. Systemic pathology analysis was performed in an orthotopic transplantation model to prepare model mice for use in preclinical studies, mimicking the progress of human pancreatic cancer. The location and the timing of inoculated cancer cell metastases, pathogenesis and cause of fatality were analyzed. Furthermore, the efficacy of gemcitabine, a key pancreatic cancer drug, was evaluated in this model where liver metastasis and peritoneal dissemination occur. Results indicated that the SUIT-2 orthotopic pancreatic cancer model was similar to the phenotypic sequential progression of human pancreatic cancer, with extra-pancreatic invasion, intra-peritoneal dissemination and other hematogenous organ metastases. Notably, survival was prolonged by administering gemcitabine to mice with metastasized pancreatic cancer. Furthermore, the detailed effects of gemcitabine on the primary tumor and metastatic tumor lesions were pathologically evaluated in mice. The present study indicated the model accurately depicted pancreatic cancer development and metastasis. Furthermore, the detailed effects of pancreatic cancer drugs on the primary tumor and on metastatic tumor lesions. We present this model as a potential new standard for new drug development in pancreatic cancer.Entities:
Keywords: chemotherapy; gemcitabine; metastasis; orthotopic mouse model; pancreatic cancer; pathology; survival prolongation effects
Year: 2017 PMID: 29435042 PMCID: PMC5778887 DOI: 10.3892/ol.2017.7722
Source DB: PubMed Journal: Oncol Lett ISSN: 1792-1074 Impact factor: 2.967