Large Animal Models of Breast Cancer.

In this mini review the status, advantages, and disadvantages of large animal modeling of breast cancer (BC) will be discussed. While most older studies of large animal BC models utilized canine and feline subjects, more recently there has been interest in development of porcine BC models, with some early promising results for modeling human disease. Widely used rodent models of BC were briefly reviewed to give context to the work on the large animal BC models.

Porcine pancreatic ductal epithelial cells transformed with KRAS and SV40T are tumorigenic.

We describe our initial studies in the development of an orthotopic, genetically defined, large animal model of pancreatic cancer. Primary pancreatic epithelial cells were isolated from pancreatic duct of domestic pigs. A transformed cell line was generated from these primary cells with oncogenic KRAS and SV40T.

Porcine Models of Pancreatic Cancer.

Pancreatic cancer is the fourth most common cause of cancer-related deaths in both men and women. The 5-year survival rate for metastatic pancreatic cancer is only 8%. There remains a need for improved early diagnosis and therapy for pancreatic cancer.

Enhancing responsiveness of pancreatic cancer cells to gemcitabine treatment under hypoxia by heme oxygenase-1 inhibition.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive malignancies and has one of the worst prognoses leading to a meager 5-year survival rate of ∼8%. Chemotherapy has had limited success in extending the life span of patients with advanced PDAC due to poor tumor perfusion and hypoxia-induced resistance. Hypoxia reprograms the gene expression profile and upregulates the expression of multiple genes including heme oxygenase-1 (HO-1), which provide survival advantage to PDAC cells.

TGFβ/Smad3 regulates proliferation and apoptosis through IRS-1 inhibition in colon cancer cells.

In this study, we have uncovered a novel crosstalk between TGFβ and IGF-1R signaling pathways. We show for the first time that expression and activation of IRS-1, an IGF-1R adaptor protein, is decreased by TGFβ/Smad3 signaling. Loss or attenuation of TGFβ activation leads to elevated expression and phosphorylation of IRS-1 in colon cancer cells, resulting in enhanced cell proliferation, decreased apoptosis and increased tumor growth in vitro and in vivo.