Pancreatic cancer is associated with profound insulin resistance, resulting in diabetes in up to 80% of patients. This metabolic abnormality is tumor dependent and disappears after tumor resection, despite the loss of islets. Amylin is a pancreatic hormone that inhibits muscle glycogen synthesis and reduces food intake. In most pancreatic cancer patients, amylin levels are elevated in the fasting state. Even though diabetes may not be a major problem for the management of patients with pancreatic cancer, measurement of amylin may be a valuable marker for the early diagnosis of the disease, at least in a proportion of patients. Furthermore, the increased amylin levels appear to result from stimulation of peri-tumoral islets by a tumor-derived peptide (amylin releasing peptide of ARP). It is likely that, compared with amylin, circulating ARP levels are elevated in an even higher proportion of pancreatic cancer patients. The major goals of this proposal are as follows: 1. To investigate the specificity of elevated circulating amylin in pancreatic cancer, by investigating patients with pancreatitis, biliary obstruction, newly diagnosed diabetes, pancreatic cancer or other malignancies. 2. To purify and sequence ARP and develop a radioimmunoassay to measure this peptide. 3. To establish whether ARP is a better marker for pancreatic cancer than amylin, by measurement in the above groups of patients. 4. To determine the value of amylin and ARP as early indicators of pancreatic cancer, by measuring the peptides in families with a high risk of developing the disease, and by measuring them in samples from pancreatic cancer patient collected several years prior to their cancer diagnosis. This study may aid in the development of an early screening technique for detecting pancreatic cancer at an early, curable stage. In addition, it will improve our understanding of the role played by the islets in this disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA072712-03
Application #
6103309
Study Section
Project Start
1999-03-25
Project End
2003-01-31
Budget Start
1998-10-01
Budget End
1999-09-30
Support Year
3
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Type
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198
Chan, June M; Gong, Zhihong; Holly, Elizabeth A et al. (2013) Dietary patterns and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Nutr Cancer 65:157-64
Mutolo, Michael J; Morris, Kirsten J; Leir, Shih-Hsing et al. (2012) Tumor suppression by collagen XV is independent of the restin domain. Matrix Biol 31:285-9
Pour, Parviz M (2012) A novel tissue for islet transplantation in diabetics. Pancreatology 12:57-60
Sherman, Simon; Shats, Oleg; Ketcham, Marsha A et al. (2011) PCCR: Pancreatic Cancer Collaborative Registry. Cancer Inform 10:83-91
Chan, June M; Wang, Furong; Holly, Elizabeth A (2009) Sweets, sweetened beverages, and risk of pancreatic cancer in a large population-based case-control study. Cancer Causes Control 20:835-46
Moniaux, Nicolas; Nemos, Christophe; Deb, Shonali et al. (2009) The human RNA polymerase II-associated factor 1 (hPaf1): a new regulator of cell-cycle progression. PLoS One 4:e7077
Mimeault, M; Hauke, R; Batra, S K (2008) Recent advances on the molecular mechanisms involved in the drug resistance of cancer cells and novel targeting therapies. Clin Pharmacol Ther 83:673-91
Hennig, R; Osman, T; Esposito, I et al. (2008) BLT2 is expressed in PanINs, IPMNs, pancreatic cancer and stimulates tumour cell proliferation. Br J Cancer 99:1064-73
Davda, Jasmine P; Jain, Maneesh; Batra, Surinder K et al. (2008) A physiologically based pharmacokinetic (PBPK) model to characterize and predict the disposition of monoclonal antibody CC49 and its single chain Fv constructs. Int Immunopharmacol 8:401-13
Hennig, Rene; Kehl, Timo; Noor, Seema et al. (2007) 15-lipoxygenase-1 production is lost in pancreatic cancer and overexpression of the gene inhibits tumor cell growth. Neoplasia 9:917-26

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