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Pancreatic adenocarcinoma causes diabetes mellitus by releasing factors interfering with glucose metabolism.We verified in isolated rat hepatocytes the molecular weight (MW) of the fraction from pancreatic cancer cell conditioned media (CM) that altered glucose metabolism and ascertained, using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) analysis, whether there is any common peptide in CM and in the sera of patients with pancreatic cancer.Sera was obtained from patients with pancreatic cancer ( n = 14) and chronic pancreatitis ( n = 9) and healthy control subjects ( n = 10). Conditioned medium (CM) was obtained from the following cell lines: MIA PaCa 2, PSK-1, PANC-1, and CAPAN-1. Two fractions (MW of less than 30,000 Da and less than 10,000 Da) were obtained from patients' sera, from CM, and from non-CM (NCM) after two-step ultrafiltration. Rat hepatocytes were incubated with CM and NCM. The peptide profile of patients' sera, CM, and NCM were analyzed using MALDI-MS.In rat hepatocytes, glucose metabolism was impaired by CM from all the pancreatic cancer cell lines and by CM with an MW of less than 10,000 Da. Two peptides (m/z 2030 and 2726) were found in CM and patients' sera. Only the peptide at m/z 2030 was found to be associated with the presence of diabetes.A peptide at m/z 2030 may be a putative pancreatic cancer-associated diabetogenic factor.

Our aim was to assess the clinical reliability of mutated K-ras detection in serum or bile for the diagnosis of pancreatic cancer using ME-PCR. DNA was extracted from 1 ml serum obtained from 29 patients with pancreatic cancer and 12 control subjects. ME-PCR was optimized using a mixture of normal DNA added with different amounts of mutated DNA. The analysis of sera obtained from the 29 patients and of bile obtained from 11 pancreatic cancer patients demonstrated the presence of mutated K-ras in two (6.9%) and four cases (36%). By contrast K-ras was not amplifiable in any of the 12 serum samples obtained from healthy controls. In conclusion the DNA obtained from pancreatic cancer patients' sera is suitable for K-ras amplification and for the identification of codon 12 point mutations. However ME-PCR alone has an unsatisfactory sensitivity for the detection of pancreatic cancer using serum DNA as starting template.

Interleukin 6 (IL-6), an autocrine growth factor for many tumors, seems to favour tumor spread to the liver. Our aims were first to evaluate the pattern of portal and systemic IL-6 levels in patients with pancreatic cancer (PC, n =18) and chronic pancreatitis (CP, n =22) compared with controls (CS, n =20); and second, to ascertain whether there was any relation between IL-6 levels and tumor spread or PC-associated Diabetes mellitus. For all subjects, a fasting serum sample was obtained from a cubital vein; a portal serum sample was obtained from nine PC and three CP patients. In cubital and portal sera we measured IL-6, interleukin 1 beta (IL-1b), CA 19-9, c-reactive protein (CRP) and amylase. Systemic IL-6 levels were significantly higher in PC patients than in CS. In PC, portal IL-6 levels were significantly higher than the corresponding systemic values. The same pattern was found in the three CP patients, whereas IL-1b, CA 19-9, CRP and amylase portal levels were the same as systemic values. No correlation was found between PC stage and systemic or portal IL-6 levels. Portal IL-6 levels were correlated with the corresponding fasting serum glucose values. A significant correlation was found between IL-6 values and CRP, ALT, total bilirubin, GGT and creatinine, but not amylase. In conclusion: (1) Portal IL-6, which is partly of pancreatic origin, is first metabolised in the liver; (2) Systemic IL-6 reflects hepatic and renal functions rather than local conditions in the pancreas; (3) IL-6 does not appear to influence PC spread; (4) IL-6, which is released in large amounts by the inflamed pancreas, may contribute to determining diabetes, thus interfering with the signal transducing pathways involved in glucose metabolism in liver cells.