A miRNA signature of chemoresistant mesenchymal phenotype identifies novel molecular targets associated with advanced pancreatic cancer.

In this study a microRNA (miRNA) signature was identified in a gemcitabine resistant pancreatic ductal adenocarcinoma (PDAC) cell line model (BxPC3-GZR) and this signature was further examined in advanced PDAC tumor specimens from The Cancer Genome Atlas (TCGA) database. BxPC3-GZR showed a mesenchymal phenotype, expressed high levels of CD44 and showed a highly significant deregulation of 17 miRNAs. Based on relevance to cancer, a seven-miRNA signature (miR-100, miR-125b, miR-155, miR-21, miR-205, miR-27b and miR-455-3p) was selected for further studies.

Inhibiting signal transducer and activator of transcription-3 increases response to gemcitabine and delays progression of pancreatic cancer.

Background: Among the solid tumors, human pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis. Gemcitabine is the standard first line of therapy for pancreatic cancer but has limited efficacy due to inherent or rapid development of resistance and combining EGFR inhibitors with this regimen results in only a modest clinical benefit. The goal of this study was to identify molecular targets that are activated during gemcitabine therapy alone or in combination with an EGFR inhibitor.

Role of the ferroportin iron-responsive element in iron and nitric oxide dependent gene regulation.

The newly described iron transporter, ferroportin (MTP1, IREG1), is expressed in a variety of tissues including the duodenum and cells of the mononuclear phagocyte system (MPS). In the MPS, ferroportin is hypothesized to be a major exporter of iron scavenged from senescent erythrocytes. Changes in iron metabolism, including the sequestration of iron in the MPS, are characteristic of both acute and chronic inflammation and these conditions induce changes in ferroportin expression.