Trefoil factors (TFFs) gene expression was analyzed in publicly available cancer genome datasets, followed by assessment of their expression in genetically engineered spontaneous mouse model (GEM) of PC (KrasG12D; Pdx1-Cre (KC)) and in human tissue microarray consisting of normal pancreas adjacent to tumor (NAT), precursor lesions (PanIN), and various pathological grades of PC by immunohistochemistry (IHC).
The ROC curves indicate a sensitivity and specificity of 80% for PDX1 and 86% for MSX2.Gene expression of MSX2 in tissue samples obtained by EUS-FNA and serum expression of MSX2 and PDX1 were higher in patients with PC.
Experiments were performed in a genetically engineered mouse model of pancreatic cancer (KPC mice: LSL-Kras<sup>G12D/+</sup>; LSL-Trp53<sup>R172H/+</sup>; Pdx-1-Cre).
K-ras<sup>LSL-G12D/+</sup>:: p53<sup>LSL-R172H/+</sup>:: Pdx-1-Cre (KPC) mice are an established model of pancreatic cancer that specifically express mutants of both K-ras and p53 in the pancreas by using Pdx-1-Cre.
The LSL-Kras<sup>G12D/+</sup>; LSL-Trp53<sup>R172H/+</sup>; Pdx-1-Cre (KPC) mouse model represents an established and frequently used transgenic model to evaluate novel therapies in pancreatic cancer.
Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-Kras<sup>G12D/+</sup>;Tp53<sup>R172H/+</sup> (KPC) mice, a genetically engineered model of pancreatic cancer.
We utilized human tissue microarrays and different PC mouse models (Pdx1-cre; LSL- Kras<sup>(G12D)</sup>, Pdx1-Cre; LSL-Kras<sup>(G12D)</sup>; LSL-p53<sup>(R172H)</sup> and RIP1-Tag2) to analyze SEMA5A expression during PC progression.
Treatment with metformin also suppressed tumor growth, invasion and EMT in LSL‑KrasG12D/+, Trp53fl/+and Pdx1‑Cre (KPC) transgenic mice that harbor spontaneous pancreatic cancer.
In all but two patients with pancreatic cancer, PDX-1 was expressed and was found positive in 7 patients with pancreatic cancer in which cytology was negative.
Moreover, expression of miR-146a in eight PC cell lines, and in pancreatic tissues obtained from transgenic mouse models of K-Ras (K), Pdx1-Cre (C), K-Ras;Pdx1-Cre (KC) and K-Ras;Pdx1-Cre;INK4a/Arf (KCI), showed down-regulation of miR-146a expression in KCI mice which was in part led to over-expression of its target gene, epidermal growth factor receptor (EGFR).
Our aim is to review the process of identifying PDX1 as a specific, potential RNAi target in pancreatic cancer, as well as the underlying mechanisms and various forms of RNAi, with subsequent testing and development of PDX1-targeted bifunctional shRNA therapy.
In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (Kras(G12D);Pdx1-Cre (KC)) murine PC model from pancreatic intraepithelial neoplasia (PanIN) to pancreatic ductal adenocarcinoma (PDAC) by immunohistochemistry and quantitative real-time PCR.
Down-regulation of PDX-1 expression inhibits pancreatic cancer cell growth in vitro and in vivo, implying its use as a potential therapeutic target for the treatment of pancreatic cancer.
To further explore the oncogenic activity of Aurora A kinase while attempting to develop a useful mouse model for pancreatic cancer, Aurora A kinase was targeted to pancreatic duodenal homeobox gene-1 (Pdx-1)-positive cells.
Furthermore, PDX-1 protein was found in all six freshly isolated human pancreas cancer specimens and two liver metastasis samples that were group-tested, suggesting the feasibility of using RIP-TK gene therapy in humans.