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Ribonuclease C and pancreatic secretory proteins in the peripheral circulation before and after pancreatectomy for pancreatic cancer

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Abstract

Increases in the activities of human circulatory ribonucleases have been associated with malignancies and other pathological conditions. To elucidate the relationship between circulatory ribonuclease and pancreatic malignancy, we have determined the activities in serum of ribonucleases selective for polycytidylic acid (ribonuclease C) and of α-amylase before and after surgery for pancreatic cancer and for several malignant and nonmalignant disorders unrelated to the pancreas. Prior to pancreatectomy, the activity of ribonuclease C in the serum of three pancreatic cancer patients was within the range of values obtained for healthy subjects. Unexpectedly, ribonuclease C began to increase within 2 hr after surgery, and amounts of ribonuclease C more than threefold higher than preoperative levels were found for at least 3 weeks after pancreatectomy. Variations in the serum concentrations of urea nitrogen and creatinine followed time courses which differed from those of ribonuclease C; thus the increases in the activity of ribonuclease C could not be attributed to renal impairment. The concentrations of α-amylase and trypsinogen in the blood of two of the pancreatic cancer patients were considerably higher than those of healthy subjects and declined rapidly to subnormal levels after pancreatectomy. Only a small amount of α-amylase and no trypsinogen were found in the blood of the third patient both before and after surgery, and samples of pure pancreatic juice obtained preoperatively after sequential intravenous administration of secretin and cholecystokinin-pancreozymin were negative for α-amylase and three proteolytic zymogens; nevertheless, the presurgical level of ribonuclease C in his serum was within the normal range. For all of the patients treated for nonpancreatic disorders, the concentrations of ribonuclease C and α-amylase in serum were not significantly altered by surgery. The rate and ultimate extent of the decrease in circulatory α-amylase following pancreatectomy indicate that ≈-80% of the α-amylase in blood is pancreatic in origin and that the half-life of pancreatic α-amylase in the peripheral circulation ≈-15 hr. From the highly significant increases in circulatory ribonuclease C which followed pancreatectomy for pancreatic cancer, we conclude that the exocrine pancreas is neither the sole nor the principal source of ribonuclease C in the peripheral circulation.

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References

  1. Warshaw AL, Lee K-H: Serum ribonuclease elevations and pancreatic necrosis in acute pancreatitis. Surgery 86:227–234, 1979

    Google Scholar 

  2. Rabinovitch M, Liberman B, Fausto N: Plasma ribonuclease activity in human uremia. J Lab Clin Med 53:563–568, 1959

    Google Scholar 

  3. Peterson LM: Serum RNase in the diagnosis of pancreatic carcinoma. Proc Natl Acad Sci USA 76:2630–2634, 1979

    Google Scholar 

  4. Akagi K, Yamanaka M, Murai K, Omae T: Purification and properties of acid ribonucleases in human serum and leukocytes. Cancer Res 38:2163–2167, 1978

    Google Scholar 

  5. Sheid B, Lu T, Pedrinan L, Nelson JH: Plasma ribonuclease. A marker for the detection of ovarian cancer. Cancer 39:2204–2208, 1978

    Google Scholar 

  6. Reddi KK, Holland JF: Elevated serum ribonuclease in patients with pancreatic cancer. Proc Natl Acad Sci USA 73:2308–2310, 1976

    Google Scholar 

  7. Warshaw AL, Lee K-H, Wood WC, Cohen AM: Sensitivity and specificity of serum ribonuclease in the diagnosis of pancreatic cancer. Am J Surg 139:27–32, 1980

    Google Scholar 

  8. Reddi KK: Nature and possible origin of human serum ribonuclease. Biochem Biophys Res Commun 67:110–118, 1975

    Google Scholar 

  9. Isaacs P: Serum ribonuclease (c-RNase): Evidence against pancreatic tumor specificity. Ir J Med Sci 146(suppl 1):38–39, 1977

    Google Scholar 

  10. Abramson SB, Renner IG: Human ribonucleases selective for polycytidylic acid: Evidence for catalytic heterogeneity and nonpancreatic origin of ribonucleases in human serum. J Cell Biol 87:327a, 1980 (abstract)

    Google Scholar 

  11. Zimmerman SB, Sandeen G: A sensitive assay for pancreatic ribonuclease. Anal Biochem 10:444–449, 1965

    Google Scholar 

  12. Rinderknecht H: A rapid, simple method for estimating plasma trypsinogen. Clin Res 28:631A, 1980 (abstract)

    Google Scholar 

  13. Rinderknecht H, Renner IG, Carmack C: Activation of human pancreatic juice. Clin Chim Acta 73:369–372, 1976

    Google Scholar 

  14. Rinderknecht H, Fleming RM: A new, highly sensitive and specific assay for chymotrypsin. Clin Chim Acta 59:139–146, 1975

    Google Scholar 

  15. Rinderknecht H, Renner IG, Douglas AP, Adham NF: Profiles of pure pancreatic secretions obtained by direct pancreatic duct cannulation in normal healthy human subjects. Gastroenterology 75:1083–1089, 1978

    Google Scholar 

  16. Dixon WJ, Massey FJ Jr: Introduction to Statistical Analysis, 3rd ed., New York, McGraw-Hill, 1969

    Google Scholar 

  17. Migliarese JF: Serum ribonuclease in the cancer patient. Proc Am Assoc Cancer Res 2:327, 1958 (abstract)

    Google Scholar 

  18. Maor D, Mardiney MR Jr: Alteration of human serum ribonuclease activity in malignancy. CRC Rev Clin Lab Sci 10:89–111, 1979

    Google Scholar 

  19. Daoust R, Amano H: Ribonuclease and deoxyribonuclease activities in experimental and human tumors by the histochemical substrate film method. Cancer Res 23:131–134, 1963

    Google Scholar 

  20. Taper HS, Brucher J-M, Fort L: Activity of alkaline and acid nucleases in tumors of the nervous system. Cancer 28:482–490, 1971

    Google Scholar 

  21. Fontaniére B, Daoust R: Histochemical studies on nuclease activity and neoplastic transformation in rat liver during diethylnitrosamine carcinogenesis. Cancer Res 33:3108–3111, 1973

    Google Scholar 

  22. Roth JS, Hilton S, Morris HP: Ribonuclease activity in some transplantable rat hepatomas. Cancer Res 24:294–301, 1964

    Google Scholar 

  23. Chakravorty AK, Busch H: Alkaline ribonuclease and ribonuclease inhibitor in nuclear and nucleolar preparations from normal and neoplastic tissue. Cancer Res 27:789–792, 1967

    Google Scholar 

  24. Ambellan E, Hollander VP: The role of ribonuclease in regression of lymphoma P1798, Cancer Res 26:903–909, 1966

    Google Scholar 

  25. Graffi A, Arnold W: Inhibition by pancreatic ribonuclease of experimental tumor metastisizing in mice. Acta Biol Med Ger 30:K15-K18, 1973

    Google Scholar 

  26. Erbe W, Preiss J, Siefert R, Hilz H: Increase in RNase and DPNase activities in ascites tumor cells induced by various cytostatic agents. Biochem Biophys Res Commun 23:392–397, 1966

    Google Scholar 

  27. Goldberg DM, Ayre HA, Pitts JF: Effect of radium treatment on activity and distribution of some enzymes in cancers of the human cervix uteri. Cancer 20:1388–1394, 1967

    Google Scholar 

  28. Zigman S, Allison JB: Ribonuclease activity of protein-depleted and tumor-bearing rats. Cancer Res 10:1105–1108, 1959

    Google Scholar 

  29. Allison JB, Wannemacher RW Jr, Banks WL, Wunner WH, Gomez-Brenes RA: Dietary proteins correlated with ribonuclease, ribonucleic acid and tissue proteins. J Nutr 78:333–337, 1962

    Google Scholar 

  30. Albanese AA, Orto LA, Zavarotto DN, De Carlo R: Protein metabolic significance of blood ribonuclease levels in man. Nutr Rep Int 4:151–164, 1971

    Google Scholar 

  31. Scott PH, Berger HM, Kenward C, Scott P, Wharton BA: Plasma alkaline ribonuclease (EC 3.1.4.22) and nitrogen retention in low-birth-weight infants. Br J Nutr 40:459–464, 1978

    Google Scholar 

  32. Levy AL, Rottino A: Effect of disease states on the ribonuclease concentration of body fluids. Clin Chem 6:43–51, 1960

    Google Scholar 

  33. Zytko J, Cantero A: Serum ribonuclease in patients with malignant disease. Can Med Assoc J 86:482–485, 1962

    Google Scholar 

  34. Shenkin A, Citrin DL, Rowan RM: An assessment of the clinical usefulness of plasma ribonuclease assays. Clin Chim Acta 72:223–231, 1976

    Google Scholar 

  35. Kottel RH, Hoch SO, Parsons RG, Hoch JA: Serum ribonuclease activity in cancer patients. Br J Cancer 38:280–286, 1978

    Google Scholar 

  36. Mackie CR, Moossa AR, Go VLW, Noble G, Sizemore G, Cooper MJ, Wood RAB, Hall AW, Waldmann T, Gelder F, Rubenstein AH: Prospective evaluation of some candidate tumor markers in the diagnosis of pancreatic cancer. Dig Dis Sci 25:161–172, 1980

    Google Scholar 

  37. Duane WC, Frerichs R, Levitt MD: Simultaneous study of the metabolic turnover and renal excretion of salivary amylase-125I and pancreatic amylase-131I in the baboon. J clin Invest 51:1504–1513, 1972

    Google Scholar 

  38. Duane WC, Frerichs R, Levitt MD: Distribution, turnover and mechanism of renal excretion of amylase in the baboon. J Clin Invest 50:156–165, 1971

    Google Scholar 

  39. Skude G: Human amylase isoenzymes. Scand J Gastroenterol 12(suppl 44), 1977

  40. O'Donnell MD, McGeeney KF: Purification and properties of an α-amylase inhibitor from wheat. Biochim Biophys Acta 422:159–169, 1976

    Google Scholar 

  41. O'Donnell MD, FitzGerald O, McGeeney KF: Differential serum amylase determination by use of an inhibitor, and design of a routine procedure. Clin Chem 23:560–566, 1977

    Google Scholar 

  42. O'Donnell MD, Miller MJ: Plasma pancreatic and salivary type amylase and immunoreactive trypsin concentrations: Variations with age and reference ranges for children. Clin Chim Acta 104:265–273, 1980

    Google Scholar 

  43. Lorentz K: Salivary isoamylases: Deamidation products of amylase. Clin Chim Acta 93:161–162, 1979

    Google Scholar 

  44. Abramson SB, Renner IG, Douglas AP: Multiple molecular forms of α-amylase from pure human pancreatic juice: Kinetics and possible mechanisms of generation. ASCB Methods Perspectives Cell Biol Proc Symp 1979, in press (abstract)

  45. Warshaw AL, Lee K-H: Aging changes of pancreatic isoamylases and the appearance of “old amylase” in the serum of patients with pancreatic pseudocysts. Gastroenterology 79:1246–1251, 1980

    Google Scholar 

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This work was supported in part by a grant from the Robert E. and May R. Wright Foundation and by grant CA 20222 from the National Pancreatic Cancer Project, National Cancer Institute, Department of Health and Human Services.

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Abramson, S.B., Rinderknecht, H. & Renner, I.G. Ribonuclease C and pancreatic secretory proteins in the peripheral circulation before and after pancreatectomy for pancreatic cancer. Digest Dis Sci 27, 889–896 (1982). https://doi.org/10.1007/BF01316572

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