Experimental Animal Models of Pancreatic Carcinogenesis for Prevention Studies and Their Relevance to Human Disease

Abstract

Pancreatic cancer is difficult to cure, so its prevention is very important. For this purpose, animal model studies are necessary to develop effective methods. Injection of N-nitrosobis(2-oxopropyl)amine (BOP) into Syrian golden hamsters is known to induce pancreatic ductal adenocarcinomas, the histology of which is similar to human tumors. Moreover, K-ras activation by point mutations and p16 inactivation by aberrant methylation of 5′ CpG islands or by homozygous deletions have been frequently observed in common in both the hamster and humans. Thus, this chemical carcinogenesis model has an advantage of histopathological and genetic similarity to human pancreatic cancer, and it is useful to study promotive and suppressive factors. Syrian golden hamsters are in a hyperlipidemic state even under normal dietary conditions, and a ligand of peroxizome proliferator-activated receptor gamma was found to improve the hyperlipidemia and suppress pancreatic carcinogenesis. Chronic inflammation is a known important risk factor, and selective inhibitors of inducible nitric oxide synthase and cyclooxygenase-2 also have protective effects against pancreatic cancer development. Anti-inflammatory and anti-hyperlipidemic agents can thus be considered candidate chemopreventive agents deserving more attention.

Doxorubicin-loaded polysaccharide nanoparticles suppress the growth of murine colorectal carcinoma and inhibit the metastasis of murine mammary carcinoma in rodent models

“…Especially, carcinogeninduced models can effectively recapitulate the time-dependent and multistage progression of tumor pathogenesis in response to environmental carcinogens and tumor-promoting agents [17]. Their molecular, biochemical, and histopathological characteristics are similar to the developmental consequences of specific human cancers, from hyperplasias, pre-malignant lesions, low grade welldifferentiated carcinomas, and ultimately to invasive and more poorly differentiated carcinomas [20,21]. Consequently, carcinogen-induced primary tumor models have been used as a general class of preclinical cancer models to offer various distinct advantages and clinical relevance to human cancers.…”

Modifying effects of 1,2-dichloropropane on N-nitrosobis(2-oxopropyl)amine-induced cholangiocarcinogenesis in male Syrian hamsters

“…While a specific animal model capable of predicting cholangiocarcinogenicity of chemicals in humans has not been established, the present BOP-induced multi-organ hamster carcinogenesis model is well established as a bioassay for evaluating the effects of chemicals in multiple organs/tissues including hepatobiliary system and pancreas (Pour et al, 1978;Furukawa et al, 2003;Takahashi et al, 2008Takahashi et al, , 2011Okamura et al, 2013). To the best of our knowledge, this is the first study to determine the carcinogenic effects of 1,2-DCP in hamsters.…”

“…N-nitrosobis(2-oxopropyl)amine (BOP) is a wellknown multiorgan carcinogen in hamsters, inducing tumors in the pancreas, liver, lung, and kidneys (Pour et al, 1978;Furukawa et al, 2003;Takahashi et al, 2008Takahashi et al, , 2011Okamura et al, 2013). The main purpose of the present study was to determine the modifying effects of 1,2-DCP on BOP-induced cholangiocarcinogenesis in male Syrian hamsters.…”

Pathogenesis of Pancreatic Cancer

“…Indeed, the Syrian hamster provides independent validation of additional non-genetic risk factors for PDAC, and ought not be neglected in the GEM model era (Takahashi et al 2011). Among these epidemiologically-identified risk factors are obesity and type-2 diabetes, which are themselves linked and which may promote PDAC through elevated systemic inflammation (Greer and Whitcomb 2009).…”