Author's response to reviews Title: Dimethylaminoparthenolide and gemcitabine: a survival study using a genetically engineered mouse model of pancreatic cancer Authors:

Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer

OBJECTIVE Pancreatic ductal adenocarcinoma (PDA) is characterised by stromal desmoplasia and vascular dysfunction, which critically impair drug delivery. This study examines the role of an abundant extracellular matrix component, the megadalton glycosaminoglycan hyaluronan (HA), as a novel therapeutic target in PDA. METHODS Using a genetically engineered mouse model of PDA, the authors enzyma...

Author's response to reviews Title: Enhancing chemosensitivity to gemcitabine via RNA interference targeting the catalytic subunits of protein kinase CK2 in human pancreatic cancer cells Authors:

Modeling targeted inhibition of MEK and PI3 kinase in human pancreatic cancer.

Activating mutations in the KRAS oncogene occur in approximately 90% of pancreatic cancers, resulting in aberrant activation of the MAPK and the PI3K pathways, driving malignant progression. Significant efforts to develop targeted inhibitors of nodes within these pathways are underway and several are currently in clinical trials for patients with KRAS-mutant tumors, including patients with panc...

Chronic Pancreatitis and Systemic Inflammatory Response Syndrome Prevent Impact of Chemotherapy with Gemcitabine in a Genetically Engineered Mouse Model of Pancreatic Cancer12

BACKGROUND AND AIMS BACKGROUND AND AIMSGemcitabine is the standard therapy for patients with pancreatic cancer with metastatic disease. Patients with metastatic pancreatic cancer presenting with increased values of C-reactive protein do not respond to gemcitabine. So far, no studies have evaluated the correlation between chronic pancreatitis, systemic inflammatory response syndrome, and the los...

Utilizing Genetically Engineered Mouse Models of Pancreatic Cancer: Evaluating the Role of Cathepsin B and the Efficacy of Farnesyl Thiosalicylic Acid

I have utilized genetically engineered mouse models of pancreatic cancer to identify a potential new therapeutic target, and to test the efficacy of a putative ras inhibitor. In the first part, I show that cathepsin B is upregulated during disease progression in the mouse pancreas, as is overall cathepsin activity. Loss of cathepsin B decreases preinvasive disease burden and imparts a significa...