Biochemistry and clinical role of trypsinogens and pancreatic secretory trypsin inhibitor

Critical Reviews in Clinical Laboratory Sciences

Volumn 43, Issue 2, 2006, Pages 103-142

  Paju, Annukka ^a,b   Stenman, Ulf Håkan ^a  

^a HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

^b UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Gastrointestinal cancer; Gynecological cancer; Immunoassay; Pancreatitis; Prognosis; Proteinase; Serum marker; Tumor marker; Urological cancer

Indexed keywords

ALPHA 1 ANTITRYPSIN; ALPHA 2 MACROGLOBULIN; ALPHA FETOPROTEIN; APROTININ; C REACTIVE PROTEIN; CA 19-9 ANTIGEN; CARCINOEMBRYONIC ANTIGEN; CHORIONIC GONADOTROPIN; CHORIONIC GONADOTROPIN BETA SUBUNIT; CYTOKINE; EPIDERMAL GROWTH FACTOR RECEPTOR; KALLIKREIN; MATRIX METALLOPROTEINASE; NEURON SPECIFIC ENOLASE; PROSTATE SPECIFIC ANTIGEN; PROTEINASE ACTIVATED RECEPTOR 2; PROUROKINASE; SERINE PROTEINASE INHIBITOR; TISSUE POLYPEPTIDE ANTIGEN; TRANSFORMING GROWTH FACTOR ALPHA; TRYPSIN INHIBITOR; TRYPSINOGEN; TUMOR NECROSIS FACTOR ALPHA;

ACUTE PANCREATITIS; AMINO ACID SEQUENCE; BODY FLUID; DIGESTIVE SYSTEM CANCER; ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY; ENZYME ACTIVATION; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME METABOLISM; ENZYME REGULATION; ENZYME SPECIFICITY; ENZYME SUBSTRATE; EXTRACELLULAR MATRIX; GYNECOLOGIC CANCER; HUMAN; NUCLEOTIDE SEQUENCE; PANCREAS SECRETION; PANCREATITIS; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN STRUCTURE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; REVIEW; SQUAMOUS CELL CARCINOMA; URINARY TRACT CANCER;

HUMANS; NEOPLASMS; PANCREAS; PANCREATIC NEOPLASMS; PANCREATITIS; TRYPSIN; TRYPSIN INHIBITOR, KAZAL PANCREATIC; TRYPSINOGEN; TUMOR MARKERS, BIOLOGICAL;

EID: 33745000756     PISSN: 10408363     EISSN: 1549781X     Source Type: Journal    
DOI: 10.1080/10408360500523852     Document Type: Review

References (245)

1. Kunitz M, Northrop JH. Isolation from beef pancreas of crystalline trypsinogen, trypsin, a trypsin inhibitor, and an inhibitor-trypsin compound. J Gen Physiol 1936; 19: 991-1007.
2. Haverback BJ, Dyce B, Bundy H, Edmonson HA. Trypsin, trypsinogen, and trypsin inhibitor in human pancreatic juice. Am J Med 1960; 29: 424-433.
3. Buck FF, Bier M, Nord FF. Some properties of human trypsin. Arch Biochem Biophys 1962; 98: 528-530.
4. Scheele G, Bartelt D, Bieger W. Characterization of human exocrine pancreatic proteins by two-dimensional isoelectric focusing/sodium dodecyl sulfate gel electrophoresis. Gastroenterology 1981; 80: 461-473.
5. Figarella C, Clemente F, Guy O. On zymogens of human pancreatic juice. FEBS Lett 1969; 3: 351-353.
6. Rinderknecht H, Renner IG, Carmack C. Trypsinogen variants in pancreatic juice of healthy volunteers, chronic alcoholics, and patients with pancreatitis and cancer of the pancreas. Gut 1979; 20: 886-891.
7. Rinderknecht H, Renner IG, Abramson SB, Carmack C. Mesotrypsin: A new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid. Gastroenterology 1984; 86: 681-692.
8. Wiegand U, Corbach S, Minn A, Kang J, Muller-Hill B. Cloning of the cdna encoding human brain trypsinogen and characterization of its product. Gene 1993; 136: 167-175.
9. Stenman UH, Koivunen E, Vuento M. Characterization of a tumor-associated serine protease. Biol Chem Hoppe Seyler 1988; 369 (Suppl): S9-14.
10. Koivunen E, Huhtala ML, Stenman UH. Human ovarian tumor-associated trypsin. Its purification and characterization from mucinous cyst fluid and identification as an activator of pro-urokinase. J Biol Chem 1989; 264: 14095-14099.
11. Sorsa T, Salo T, Koivunen E, Tyynelä J, Konttinen YT, Bergmann U, Tuuttila A, Niemi E, Teronen O, Heikkila P, Tschesche H, Leinonen J, Osman S, Stenman UH. Activation of type IV procollagenases by human tumor-associated trypsin-2. J Biol Chem 1997; 272: 21067-21074.
12. Rowen L, Koop BF, Hood L. The complete 685-kilobase DNA sequence of the human beta t cell receptor locus. Science 1996; 272: 1755-1762.
13. Chen J, Ferec C. Genes, cloned cdnas, and proteins of human trypsinogens and pancreatitis-associated cationic trypsinogen mutations. Pancreas 2000; 21: 57-62.
14. Cockell M, Stevenson BJ, Strubin M, Hagenbuchle O, Wellauer PK. Identification of a cell-specific DNA-binding activity that interacts with a transcriptional activator of genes expressed in the acinar pancreas. Mol Cell Biol 1989; 9: 2464-2476.
15. Walker MD, Edlund T, Boulet AM, Rutter WJ. Cell-specific expression controlled by the 5′-flanking region of insulin and chymotrypsin genes. Nature 1983; 306: 557-561.
16. Fodor E, Weinrich SL, Meister A, Mermod N, Rutter WJ. A pancreatic exocrine cell factor and AP4 bind overlapping sites in the amylase 2A enhancer. Biochemistry 1991; 30: 8102-8108.
17. Guy O, Lombardo D, Bartelt DC, Amic J, Figarella C. Two human trypsinogens. Purification, molecular properties, and n-terminal sequences. Biochemistry 1978; 17: 1669-1675.
18. Emi M, Nakamura Y, Ogawa M, Yamamoto T, Nishide T, Mori T, Matsubara K. Cloning, characterization and nucleotide sequences of two cDNAs encoding human pancreatic trypsinogens. Gene 1986; 41: 305-310.
19. Nyaruhucha CN, Kito M, Fukuoka SI. Identification and expression of the cDNA-encoding human mesotrypsin(ogen), an isoform of trypsin with inhibitor resistance. J Biol Chem 1997; 272: 10573-10578.
20. Craik CS, Largman C, Fletcher T, Roczniak S, Barr PJ, Fletterick R, Rutter WJ. Redesigning trypsin: Alteration of substrate specificity. Science 1985; 228: 291-297.
21. Guy O, Bartelt DC, Amic J, Colomb E, Figarella C. Activation peptide of human trypsinogen 2. FEBS Lett 1976; 62: 150-153.
22. Hermon-Taylor J, Perrin J, Grant DA, Appleyard A, Bubel M, Magee AI. Immunofluorescent localisation of enterokinase in human small intestine. Gut 1977; 18: 259-265.
23. Imamura T, Kitamoto Y. Expression of enteropeptidase in differentiated enterocytes, goblet cells, and the tumor cells in human duodenum. Am J Physiol Gastrointest Liver Physiol 2003; 285: G1235-G1241.
24. Greenbaum LM, Hirshkowitz A, Shoichet. The activation of trypsinogen by cathepsin b. J Biol Chem 1959; 234: 2885-2890.
25. Figarella C, Miszczuk-Jamska B, Barrett AJ. Possible lysosomal activation of pancreatic zymogens. Activation of both human trypsinogens by cathepsin b and spontaneous acid. Activation of human trypsinogen 1. Biol Chem Hoppe Seyler 1988; 369 (Suppl): S293-298.
26. Halangk W, Lerch MM, Brandt-Nedelev B, Roth W, Ruthenbuerger M, Reinheckel T, Domschke W, Lippert H, Peters C, Deussing J. Role of cathepsin b in intracellular trypsinogen activation and the onset of acute pancreatitis. J Clin Invest 2000; 106: 773-781.
27. Kukor Z, Mayerle J, Kruger B, Toth M, Steed PM, Halangk W, Lerch MM, Sahin-Tóth M. Presence of cathepsin b in the human pancreatic secretory pathway and its role in trypsinogen activation during hereditary pancreatitis. J Biol Chem 2002; 277: 21389-21396.
28. Szmola R, Kukor Z, Sahin-Tóth M. Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors. J Biol Chem 2003; 278: 48580-48589.
29. Colomb E, Figarella C. Comparative studies on the mechanism of activation of the two human trypsinogens. Biochim Biophys Acta 1979; 571: 343-351.
30. Sarkany RP, Moreland BH. Enhancement of the autocatalytic activation of trypsinogen to trypsin by bile and bile acids. Biochim Biophys Acta 1985; 839: 262-267.
31. Kukor Z, Toth M, Sahin-Tóth M. Human anionic trypsinogen: Properties of autocatalytic activation and degradation and implications in pancreatic diseases. Eur J Biochem 2003; 270: 2047-2058.
32. Rinderknecht H, Stace NH, Renner IG. Effects of chronic alcohol abuse on exocrine pancreatic secretion in man. Dig Dis Sci 1985; 30: 65-71.
33. Kazal LA, Spicer DS, Brahinsky RA. Isolation of a crystalline trypsin inhibitor-anticoagulant proteim from pancreas. J Am Chem Soc 1948; 70: 3034-3040.
34. Pubols MH, Bartelt DC, Greene LJ. Trypsin inhibitor from human pancreas and pancreatic juice. J Biol Chem 1974; 249: 2235-2242.
35. Huhtala ML, Pesonen K, Kalkkinen N, Stenman UH. Purification and characterization of a tumor-associated trypsin inhibitor from the urine of a patient with ovarian cancer. J Biol Chem 1982; 257: 13713-13716.
36. Barrett AJ, Starkey PM. The interaction of alpha 2-macroglobulin with proteinases. Characteristics and specificity of the reaction, and a hypothesis concerning its molecular mechanism. Biochem J 1973; 133: 709-724.
37. Ohlsson K. Acute pancreatitis. Biochemical, pathophysiological and therapeutics aspects. Acta Gastroenterol Belg 1988; 51: 3-12.
38. Laurell C-B, Jeppson J-O. Protease inhibitors in plasma. New York, Academic Press, 1975
39. Hovi T, Mosher D, Vaheri A. Cultured human monocytes synthesize and secrete alpha2-macroglobulin. J Exp Med 1977; 145: 1580-1589.
40. White R, Janoff A, Godfrey HP. Secretion of alpha-2-macroglobulin by human alveolar macrophages. Lung 1980; 158: 9-14.
41. Ganrot PO. Inhibition of plasmin activity by alpha-2-macroglobulin. Clin Chim Acta 1967; 16: 328-329.
42. Birkenmeier G, Stigbrand T. Production of conformation-specific monoclonal antibodies against alpha 2 macroglobulin and their use for quantitation of total and transformed alpha 2 macroglobulin in human blood. J Immunol Methods 1993; 162: 59-67.
43. Carrell RW, Jeppsson JO, Laurell CB, Brennan SO, Owen MC, Vaughan L, Boswell DR. Structure and variation of human alpha 1-antitrypsin. Nature 1982; 298: 329-334.
44. Greene LJ, Pubols MH, Bartelt DC. Human pancreatic secretory trypsin inhibitor. Methods Enzymol 1976; 45: 813-25.
45. Stenman UH, Koivunen E, Itkonen O. Biology and function of tumor-associated trypsin inhibitor, TATI. Scand J Clin Lab Invest 1991; 207 (Suppl): S5-9.
46. Perona JJ, Tsu CA, Craik CS, Fletterick RJ. Crystal structures of rat anionic trypsin complexed with the protein inhibitors APPI and BPTI. J Mol Biol 1993; 230: 919-933.
47. Eddeland A, Wehlin L. Secretin/cholecystokinin-stimulated secretion of trypsinogen and trypsin inhibitor in pure human pancreatic juice collected by endoscopic retrograde catheterization. Hoppe Seylers Z Physiol Chem 1978; 359: 1653-1658.
48. Dooley CP, Valenzuela JE. Duodenal volume and osmoreceptors in the stimulation of human pancreatic secretion. Gastroenterology 1984; 86: 23-7.
49. Owyang C, May D, Louie DS. Trypsin suppression of pancreatic enzyme secretion. Differential effect on cholecystokinin release and the enteropancreatic reflex. Gastroenterology 1986; 91: 637-643.
50. Bohe M, Borgström A, Lindström C, Ohlsson K. Pancreatic endoproteases and pancreatic secretory trypsin inhibitor immunoreactivity in human Paneth cells. J Clin Pathol 1986; 39: 786-793.
51. Ghosh D, Porter E, Shen B, Lee SK, Wilk D, Drazba J, Yadav SP, Crabb JW, Ganz T, Bevins CL. Paneth cell trypsin is the processing enzyme for human defensin-5. Nat Immunol 2002; 3: 583-590.
52. Koshikawa N, Nagashima Y, Miyagi Y, Mizushima H, Yanoma S, Yasumitsu H, Miyazaki K. Expression of trypsin in vascular endothelial cells. FEBS Lett 1997; 409: 442-448.
53. Koshikawa N, Hasegawa S, Nagashima Y, Mitsuhashi K, Tsubota Y, Miyata S, Miyagi Y, Yasumitsu H, Miyazaki K. Expression of trypsin by epithelial cells of various tissues, leukocytes, and neurons in human and mouse. Am J Pathol 1998; 153: 937-944.
54. Paju A, Bjartell A, Zhang W-M, Nordling S, Borgström A, Hansson J, Stenman U-H. Expression and characterization of trypsinogen produced in the male genital tract. Am J Pathol 2000; 157: 2011-2021.
55. Cottrell GS, Amadesi S, Grady EF, Bunnett NW. Trypsin IV, a novel agonist of protease-activated receptors 2 and 4. J Biol Chem 2004; 279: 13532-13539.
56. Fujimura T, Ohta T, Kitagawa H, Fushida S, Nishimura GI, Yonemura Y, Elnemr A, Miwa K, Nakanuma Y. Trypsinogen expression and early detection for peritoneal dissemination in gastric cancer. J Surg Oncol 1998; 69: 71-75.
57. Oyama K, Ohta T, Nishimura GI, Elnemr A, Yasui T, Fujimura T, Fushida S, Kitagawa H, Kayahara M, Terada T, Miwa K. Trypsinogen expression in colorectal cancers. Int J Mol Med 2000; 6: 543-548.
58. Williams SJ, Gotley DC, Antalis TM. Human trypsinogen in colorectal cancer. Int J Cancer 2001; 93: 67-73.
59. Hirahara F, Miyagi Y, Miyagi E, Yasumitsu H, Koshikawa N, Nagashima Y, Kitamura H, Minaguchi H, Umeda M, Miyazaki K. Trypsinogen expression in human ovarian carcinomas. Int J Cancer 1995; 63: 176-181.
60. Hirahara F, Miyagi E, Nagashima Y, Miyagi Y, Yasumitsu H, Koshikawa N, Nakatani Y, Nakazawa T, Udagawa K, Kitamura H, Minaguchi H, Miyazaki K. Differential expression of trypsin in human ovarian carcinomas and low-malignant-potential tumors. Gynecol Oncol 1998; 68: 162-165.
61. Ohta T, Terada T, Nagakawa T, Tajima H, Itoh H, Fonseca L, Miyazaki I. Pancreatic trypsinogen and cathepsin b in human pancreatic carcinomas and associated metastatic lesions. Br J Cancer 1994; 69: 152-156.
62. Yamashita K, Mimori K, Inoue H, Mori M, Sidransky D. A tumor-suppressive role for trypsin in human cancer progression. Cancer Res 2003; 63: 6575-6578.
63. Terada T, Ohta T, Minato H, Nakanuma Y. Expression of pancreatic trypsinogen/trypsin and cathepsin b in human cholangiocarcinomas and hepatocellular carcinomas. Hum Pathol 1995; 26: 746-752.
64. Kawano N, Osawa H, Ito T, Nagashima Y, Hirahara F, Inayama Y, Nakatani Y, Kimura S, Kitajima H, Koshikawa N, Miyazaki K, Kitamura H. Expression of gelatinase A, tissue inhibitor of metalloproteinases-2, matrilysin, and trypsin(ogen) in lung neoplasms: An immunohistochemical study. Hum Pathol 1997; 28: 613-622.
65. Diederichs S, Bulk E, Steffen B, Ji P, Tickenbrock L, Lang K, Zanker KS, Metzger R, Schneider PM, Gerke V, Thomas M, Berdel WE, Serve H, Muller-Tidow C. S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer. Cancer Res 2004; 64: 5564-5569.
66. Link CJ Jr, Reed E, Sarosy G, Kohn EC. Borderline ovarian tumors. Am J Med 1996; 101: 217-225.
67. Paju A, Vartiainen J, Haglund C, Itkonen O, von Boguslawski K, Leminen A, Wahlström T, Stenman UH. Expression of trypsinogen-1, trypsinogen-2, and tumor-associated trypsin inhibitor in ovarian cancer: Prognostic study on tissue and serum. Clin Cancer Res 2004; 10: 4761-4768.
68. Yamamoto H, Iku S, Adachi Y, Imsumran A, Taniguchi H, Nosho K, Min Y, Horiuchi S, Yoshida M, Itoh F, Imai K. Association of trypsin expression with tumour progression and matrilysin expression in human colorectal cancer. J Pathol 2003; 199: 176-184.
69. Bjartell A, Paju A, Zhang WM, Gadaleanu V, Hansson J, Landberg G, Stenman UH. Expression of tumor-associated trypsinogens (TAT-1 and TAT-2) in prostate cancer. Prostate 2005; 64: 29-39.
70. Koivunen E, Saksela O, Itkonen O, Osman S, Huhtala ML, Stenman UH. Human colon carcinoma, fibrosarcoma and leukemia cell lines produce tumor-associated trypsinogen. Int J Cancer 1991; 47: 592-596.
71. Miszczuk-Jamska B, Merten M, Guy-Crotte O, Amouric M, Clemente F, Schoumacher RA, Figarella C. Characterization of trypsinogens 1 and 2 in two human pancreatic adenocarcinoma cell lines; cfpac-1 and capan-1. FEBS Lett 1991; 294: 175-178.
72. Ohta T, Tajima H, Fushida S, Kitagawa H, Kayahara M, Nagakawa T, Miwa K, Yamamoto M, Numata M, Nakanuma Y, Kitamura Y, Terada T. Cationic trypsinogen produced by human pancreatic ductal cancer has the characteristics of spontaneous activation and gelatinolytic activity in the presence of proton. Int J Mol Med 1998; 1: 689-692.
73. Koshikawa N, Yasumitsu H, Umeda M, Miyazaki K. Multiple secretion of matrix serine proteinases by human gastric carcinoma cell lines. Cancer Res 1992; 52: 5046-5053.
74. Koshikawa N, Yasumitsu H, Nagashima Y, Umeda M, Miyazaki K. Identification of one- and two-chain forms of trypsinogen 1 produced by a human gastric adenocarcinoma cell line. Biochem J 1994; 303: 187-190.
75. Miyata S, Miyagi Y, Koshikawa N, Nagashima Y, Kato Y, Yasumitsu H, Hirahara F, Misugi K, Miyazaki K. Stimulation of cellular growth and adhesion to fibronectin and vitronectin in culture and tumorigenicity in nude mice by overexpression of trypsinogen in human gastric cancer cells. Clin Exp Methods 1998; 16: 613-622.
76. Kato Y, Nagashima Y, Koshikawa N, Miyagi Y, Yasumitsu H, Miyazaki K. Production of trypsins by human gastric cancer cells correlates with their malignant phenotype. Eur J Cancer 1998; 34: 1117-1123.
77. Angel P, Imagawa M, Chiu R, Stein B, Imbra RJ, Rahmsdorf HJ, Jonat C, Herrlich P, Karin M. Phorbol ester-inducible genes contain a common cis element recognized by a tpa-modulated trans-acting factor. Cell 1987; 49: 729-739.
78. Jonat C, Rahmsdorf HJ, Park KK, Cato AC, Gebel S, Ponta H, Herrlich P. Antitumor promotion and antiinflammation: Down-modulation of ap-1 (fos/jun) activity by glucocorticoid hormone. Cell 1990; 62: 1189-1204.
79. Birkedal-Hansen H, Moore WG, Bodden MK, Windsor LJ, Birkedal-Hansen B, DeCarlo A, Engler JA. Matrix metalloproteinases: A review. Crit Rev Oral Biol Med 1993; 4: 197-250.
80. Lukkonen A, Sorsa T, Salo T, Tervahartiala T, Koivunen E, Golub L, Simon S, Stenman UH. Down-regulation of trypsinogen-2 expression by chemically modified tetracyclines: Association with reduced cancer cell migration. Int J Cancer 2000; 86: 577-581.
81. Moilanen M, Sorsa T, Stenman M, Nyberg P, Lindy O, Vesterinen J, Paju A, Konttinen Y, Stenman U-H, Salo T. Tumor-associated trypsinogen-2 (trypsinogen-2) activates procollagenases (MMP-1, -8, -13) and stromelysin-1 (MMP-13) and degrades type I collagen. Biochemistry 2003; 42: 5414-5420.
82. Andreasen PA, Kjoller L, Christensen L, Duffy MJ. The urokinase-type plasminogen activator system in cancer metastasis: A review. Int J Cancer 1997; 72: 1-22.
83. Westermarck J, Kähäri VM. Regulation of matrix metalloproteinase expression in tumor invasion. FASEB J 1999; 13: 781-792.
84. Koivunen E, Ristimäki A, Itkonen O, Osman S, Vuento M, Stenman UH. Tumor-associated trypsin participates in cancer cell-mediated degradation of extracellular matrix. Cancer Res 1991; 51: 2107-2112.
85. Tajima H, Ohta T, Elnemr A, Yasui T, Kitagawa H, Fushida S, Kayahara M, Miwa K, Wakayama T, Iseki S, Yokoyama S. Enhanced invasiveness of pancreatic adenocarcinoma cells stably transfected with cationic trypsinogen cDNA. Int J Cancer 2001; 94: 699-704.
86. Nyberg P, Moilanen M, Paju A, Sarin A, Stenman U-H, Sorsa T, Salo T. MMP-9 activation by tumor trypsin-2 enhances in vivo invasion of human tongue carcinoma cells. J Dent Res 2002; 81: 831-835.
87. Geokas MC, Largman C, Brodrick JW, Johnson JH. Determination of human pancreatic cationic trypsinogen in serum by radioimmunoassay. Am J Physiol 1979; 236: E77-83.
88. Florholmen J, Jorde R, Olsen RL, Kolmannskog S, Burhol PG. Radioimmunoassay of cationic trypsin-like immunoreactivity in man. Scand J Gastroenterol 1984; 19: 613-621.
89. Borgström A, Ohlsson K. Radioimmunological determination and characterization of cathodal trypsin-like immunoreactivity in normal human plasma. Scand J Clin Lab Invest 1976; 36: 809-814.
90. Largman C, Brodrick JW, Geokas MC, Johnson JH. Demonstration of human pancreatic anionic trypsinogen in normal serum by radioimmunoassay. Biochim Biophys Acta 1978; 543: 450-454.
91. Koivunen E, Itkonen O, Halila H, Stenman UH. Cyst fluid of ovarian cancer patients contains high concentrations of trypsinogen-2. Cancer Res 1990; 50: 2375-2378.
92. Itkonen O, Stenman UH, Osman S, Koivunen E, Halila H, Schroder T. Serum samples from pancreatectomized patients contain trypsinogen immunoreactivity. J Lab Clin Med 1996; 128: 98-102.
93. Critchley G, Sumar N, O'Neill K, Hermon-Taylor J, Bell BA. Cerebral trypsinogen expression in human and rat cerebrospinal fluid. Neurosci Lett 2000; 283: 13-16.
94. Wilhelm SM, Eisen AZ, Teter M, Clark SD, Kronberger A, Goldberg G. Human fibroblast collagenase: Glycosylation and tissue-specific levels of enzyme synthesis. Proc Natl Acad Sci USA 1986; 83: 3756-3760.
95. Liotta LA, Tryggvason K, Garbisa S, Robey PG, Abe S. Partial purification and characterization of a neutral protease which cleaves type IV collagen. Biochemistry 1981; 20: 100-104.
96. Wilhelm SM, Collier IE, Kronberger A, Eisen AZ, Marmer BL, Grant GA, Bauer EA, Goldberg GI. Human skin fibroblast stromelysin: Structure, glycosylation, substrate specificity, and differential expression in normal and tumorigenic cells. Proc Natl Acad Sci USA 1987; 84: 6725-6729.
97. Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, Okada Y. Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymic properties. J Biol Chem 1995; 270: 6691-6697.
98. Duncan ME, Richardson JP, Murray GI, Melvin WT, Fothergill JE. Human matrix metalloproteinase-9: Activation by limited trypsin treatment and generation of monoclonal antibodies specific for the activated form. Eur J Biochem 1998; 258: 37-43.
99. Will H, Atkinson SJ, Butler GS, Smith B, Murphy G. The soluble catalytic domain of membrane type 1 matrix metalloproteinase cleaves the propeptide of progelatinase a and initiates autoproteolytic activation. Regulation by timp-2 and timp-3. J Biol Chem 1996; 271: 17119-17123.
100. Takayama TK, Fujikawa K, Davie EW. Characterization of the precursor of prostate-specific antigen. Activation by trypsin and by human glandular kallikrein. J Biol Chem 1997; 272: 21582-21588.
101. Christensson A, Lilja H. Complex formation between protein c inhibitor and prostate-specific antigen in vitro and in human semen. Eur J Biochem 1994; 220: 45-53.
102. Lilja H. A kallikrein-like serine protease in prostatic fluid cleaves the predominant seminal vesicle protein. J Clin Invest 1985; 76: 1899-1903.
103. Zhang WM, Leinonen J, Kalkkinen N, Dowell B, Stenman UH. Purification and characterization of different molecular forms of prostate-specific antigen in human seminal fluid. Clin Chem 1995; 41: 1567-1573.
104. Watt KW, Lee PJ, M'Timkulu T, Chan WP, Loor R. Human prostate-specific antigen: Structural and functional similarity with serine proteases. Proc Natl Acad Sci USA 1986; 83: 3166-3170.
105. Christensson A, Laurell CB, Lilja H. Enzymatic activity of prostate-specific antigen and its reactions with extracellular serine proteinase inhibitors. Eur J Biochem 1990; 194: 755-763.
106. Lövgren J, Rajakoski K, Karp M, Lundwall A, Lilja H. Activation of the zymogen form of prostate-specific antigen by human glandular kallikrein 2. Biochem Biophys Res Commun 1997; 238: 549-555.
107. Lövgren J, Valtonen-André C, Marsal K, Lilja H, Lundwall A. Measurement of prostate-specific antigen and human glandular kallikrein 2 in different body fluids. J Androl 1999; 20: 348-355.
108. Kong W, McConalogue K, Khitin LM, Hollenberg MD, Payan DG, Bohm SK, Bunnett NW. Luminal trypsin may regulate enterocytes through proteinase-activated receptor 2. Proc Natl Acad Sci USA 1997; 94: 8884-8889.
109. Nguyen TD, Moody MW, Steinhoff M, Okolo C, Koh DS, Bunnett NW. Trypsin activates pancreatic duct epithelial cell ion channels through proteinase-activated receptor-2. J Clin Invest 1999; 103: 261-269.
110. Miyata S, Koshikawa N, Yasumitsu H, Miyazaki K. Trypsin stimulates integrin alpha(5)beta(1)-dependent adhesion to fibronectin and proliferation of human gastric carcinoma cells through activation of proteinase-activated receptor-2. J Biol Chem 2000; 275: 4592-4598.
111. Alm AK, Gagnemo-Persson R, Sorsa T, Sundelin J. Extrapancreatic trypsin-2 cleaves proteinase-activated receptor-2. Biochem Biophys Res Commun 2000; 275: 77-83.
112. Nystedt S, Emilsson K, Larsson AK, Strombeck B, Sundelin J. Molecular cloning and functional expression of the gene encoding the human proteinase-activated receptor 2. Eur J Biochem 1995; 232: 84-89.
113. Santulli RJ, Derian CK, Darrow AL, Tomko KA, Eckardt AJ, Seiberg M, Scarborough RM, Andrade-Gordon P. Evidence for the presence of a protease-activated receptor distinct from the thrombin receptor in human keratinocytes. Proc Natl Acad Sci USA 1995; 92: 9151-9155.
114. Bohm SK, Kong W, Bromme D, Smeekens SP, Anderson DC, Connolly A, Kahn M, Nelken NA, Coughlin SR, Payan DG, Bunnett NW. Molecular cloning, expression and potential functions of the human proteinase-activated receptor-2. Biochem J 1996; 314: 1009-1016.
115. Dery O, Corvera CU, Steinhoff M, Bunnett NW. Proteinase-activated receptors: Novel mechanisms of signaling by serine proteases. Am J Physiol 1998; 274: C1429-1452.
116. Ducroc R, Bontemps C, Marazova K, Devaud H, Darmoul D, Laburthe M. Trypsin is produced by and activates protease-activated receptor-2 in human cancer colon cells: Evidence for new autocrine loop. Life Sci 2002; 70: 1359-1367.
117. Shimamoto R, Sawada T, Uchima Y, Inoue M, Kimura K, Yamashita Y, Yamada N, Nishihara T, Ohira M, Hirakawa K. A role for protease-activated receptor-2 in pancreatic cancer cell proliferation. Int J Oncol 2004; 24: 1401-1406.
118. Yada K, Shibata K, Matsumoto T, Ohta M, Yokoyama S, Kitano S. Protease-activated receptor-2 regulates cell proliferation and enhances cyclooxygenase-2 mRNA expression in human pancreatic cancer cells. J Surg Oncol 2005; 89: 79-85.
119. Shpacovitch VM, Brzoska T, Buddenkotte J, Stroh C, Sommerhoff CP, Ansel JC, Schulze-Osthoff K, Bunnett NW, Luger TA, Steinhoff M. Agonists of proteinase-activated receptor 2 induce cytokine release and activation of nuclear transcription factor kappaB in human dermal microvascular endothelial cells. J Invest Dermatol 2002; 118: 380-385.
120. Lehrer RI, Ganz T. Endogenous vertebrate antibiotics. Defensins, protegrins, and other cysteine-rich antimicrobial peptides. Ann NY Acad Sci 1998; 797: 228-239.
121. Ouellette AJ, Selsted ME. Paneth cell defensins: Endogenous peptide components of intestinal host defense. FASEB J 1996; 10: 1280-1289.
122. Lundberg AH, Eubanks JW, 3rd, Henry J, Sabek O, Kotb M, Gaber L, Norby-Teglund A, Gaber AO. Trypsin stimulates production of cytokines from peritoneal macrophages in vitro and in vivo. Pancreas 2000; 21: 41-51.
123. Whitcomb DC. Hereditary pancreatitis: New insights into acute and chronic pancreatitis. Gut 1999; 45: 317-322.
124. Steer ML, Meldolesi J. Pathogenesis of acute pancreatitis. Annu Rev Med 1988; 39: 95-105.
125. Whitcomb D, Gorry M, Preston R, Furey W, Sossenheimer M, Ulrich C. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nat Genet 1996; 14: 141-145.
126. Gorry M, Gabbaizedeh D, Furey W, Gates L, Preston R, Aston C, Zhang Y, Ulrich C, Ehrlich G, Whitcomb D. Mutations in the cationic trypsinogen gene are associated with recurrent acute and chronic pancreatitis. Gastroenterology 1997; 113: 1063-1068.
127. Gaiser S, Ahler A, Gundling F, Kruse ML, Savkovic V, Selig L, Teich N, Tomasini R, Dagorn JC, Mossner J, Keim V, Bodeker H. Expression of mutated cationic trypsinogen reduces cellular viability in AR4-2J cells. Biochem Biophys Res Commun 2005; 334: 721-728.
128. Lundh G. Current status of pancreatic function tests. Surg Annu 1977; 9: 133-145.
129. Elias E, Redshaw M, Wood T. Diagnostic importance of changes in circulating concentrations of immunoreactive trypsin. Lancet 1977; 2: 66-68.
130. Crossley JR, Smith PA, Edgar BW, Gluckman PD, Elliott RB. Neonatal screening for cystic fibrosis, using immunoreactive trypsin assay in dried blood spots. Clin Chim Acta 1981; 113: 111-121.
131. Borgström A, Ohlsson K. Immunoreactive trypsin in serum and peritoneal fluid in acute pancreatitis. Hoppe Seylers Z Physiol Chem 1978; 359: 677-681.
132. Borgström A, Lasson A. Trypsin-alpha 1-protease inhibitor complexes in serum and clinical course of acute pancreatitis. Scand J Gastroenterol 1984; 19: 1119-1122.
133. Borgström A, Ohlsson K. Do trypsin 2-alpha-1-antitrypsin complexes occur naturally in the circulation? Gut 1998; 43: 861.
134. Kimland M, Russick C, Marks WH, Borgström A. Immunoreactive anionic and cationic trypsin in human serum. Clin Chim Acta 1989; 184: 31-46.
135. Itkonen O, Koivunen E, Hurme M, Alfthan H, Schröder T, Stenman UH. Time-resolved immunofluorometric assays for trypsinogen-1 and 2 in serum reveal preferential elevation of trypsinogen-2 in pancreatitis. J Lab Clin Med 1990; 115: 712-718.
136. Hedström J, Leinonen J, Sainio V, Stenman U-H. Time-resolved immunofluorometric assay of trypsin-2 complexed with α-1-antitrypsin in serum. Clin Chem 1994; 40: 1761-1765.
137. 1 antitrypsin as diagnostic and prognostic marker of acute pancreatitis: Clinical study in consecutive patients. BMJ 1996; 313: 333-337.
138. Hedström J, Sainio V, Kemppainen V, Puolakkainen P, Haapiainen R, Kivilaakso E, Schauman K-O, Stenman U-H. Urine trypsinogen-2 as a marker of acute pancreatitis. Clin Chem 1996; 42: 685-690.
139. Hedström J, Korvuo A, Kenkimäki P, Tikanoja S, Haapiainen R, Kivilaakso E, Stenman U-H. Urinary trypsinogen-2 test strip for acute pancreatitis. Lancet 1996; 347: 729-730.
140. Kemppainen E, Hedström J, Puolakkainen P, Sainio V, Haapiainen R, Perhoniemi V, Osman S, Kivilaakso E, Stenman UH. Rapid measurement of urinary trypsinogen-2 as a screening test for acute pancreatitis. N Engl J Med 1997; 336: 1788-1793.
141. Kylänpää-Bäck M, Kemppainen E, Puolakkainen P, Hedström J, Haapiainen R, Perhoniemi V, Kivilaakso E, Korvuo A, Stenman UH. Reliable screening for acute pancreatitis with rapid urine trypsinogen-2 test strip. Br J Surg 2000; 87: 49-52.
142. Kemppainen E, Hedström J, Puolakkainen P, Halttunen J, Sainio V, Haapiainen R, Kivilaakso E, Stenman UH. Increased serum trypsinogen 2 and trypsin 2-alpha 1 antitrypsin complex values identify endoscopic retrograde cholangiopancreatography induced pancreatitis with high accuracy. Gut 1997; 41: 690-695.
143. Lempinen M, Stenman UH, Halttunen J, Puolakkainen P, Haapiainen R, Kemppainen E. Early sequential changes in serum markers of acute pancreatitis induced by endoscopic retrograde cholangiopancreatography. Pancreatology 2005; 5: 157-164.
144. Lempinen M, Stenman UH, Puolakkainen P, Hietaranta A, Haapiainen R, Kemppainen E. Sequential changes in pancreatic markers in acute pancreatitis. Scand J Gastroenterol 2003; 38: 666-675.
145. Andersen JM, Hedstrom J, Kemppainen E, Finne P, Puolakkainen P, Stenman UH. The ratio of trypsin-2-alpha(1)-antitrypsin to trypsinogen-1 discriminates biliary and alcohol-induced acute pancreatitis. Clin Chem 2001; 47: 231-236.
146. Andersen MJ, Hedstrom J, Tikanoja T, Leijala M, Rautiainen P, Stenman UH. Elevated levels of trypsinogen-2 and trypsin-2-alpha1-antitrypsin in sera of infants and children after cardiac surgery. Scand J Clin Lab Invest 2002; 62: 89-96.
147. Crossley JR, Elliott RB, Smith PA. Dried-blood spot screening for cystic fibrosis in the newborn. Lancet 1979; 1: 472-474.
148. Wilcken B, Wiley V. Newborn screening methods for cystic fibrosis. Paediatr Respir Rev 2003; 4: 272-277.
149. Yamamoto H, Iku S, Itoh F, Tang X, Hosokawa M, Imai K. Association of trypsin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma. Cancer 2001; 91: 1324-1331.
150. Paju A, Sorsa T, Tervahartiala T, Koivunen E, Haglund C, Leminen A, Wahlstrom T, Salo T, Stenman UH. The levels of trypsinogen isoenzymes in ovarian tumour cyst fluids are associated with promatrix metalloproteinase-9 but not promatrix metalloproteinase-2 activation. Br J Cancer 2001; 84: 1363-1371.
151. Vergote IB, Kaern J, Abeler VM, Pettersen EO, De Vos LN, Trope CG. Analysis of prognostic factors in stage I epithelial ovarian carcinoma: Importance of degree of differentiation and deoxyribonucleic acid ploidy in predicting relapse. Am J Obstet Gynecol 1993; 169: 40-52.
152. Ichikawa Y, Koshikawa N, Hasegawa S, Ishikawa T, Momiyama N, Kunizaki C, Takahashi M, Moriwaki Y, Akiyama H, Yamaoka H, Yanoma S, Tsuburaya A, Nagashima Y, Shimada H, Miyazaki K. Marked increase of trypsin(ogen) in serum of linitis plastica (gastric cancer, borrmann 4) patients. Clin Cancer Res 2000; 6: 1385-1388.
153. Hedström J, Haglund C, Haapiainen R, Stenman UH. Serum trypsinogen-2 and trypsin-2-alpha(1)-antitrypsin complex in malignant and benign digestive-tract diseases. Preferential elevation in patients with cholangiocarcinomas. Int J Cancer 1996; 66: 326-331.
154. Hedström J, Haglund C, Kemppainen E, Leinimaa M, Leinonen J, Stenman UH. Time-resolved immunofluorometric assay of trypsin-1 complexed with alpha(1)-antitrypsin in serum: Increased immunoreactivity in patients with biliary tract cancer. Clin Chem 1999; 45: 1768-1773.
155. Stenman UH, Huhtala ML, Koistinen R, Seppälä M. Immunochemical demonstration of an ovarian cancer-associated urinary peptide. Int J Cancer 1982; 30: 53-57.
156. Horii A, Kobayashi T, Tomita N, Yamamoto T, Fukushige S, Murotsu T, Ogawa M, Mori T, Matsubara K. Primary structure of human pancreatic secretory trypsin inhibitor (PSTI) gene. Biochem Biophys Res Commun 1987; 149: 635-641.
157. Yamamoto T, Nakamura Y, Nishide J, Emi M, Ogawa M, Mori T, Matsubara K. Molecular cloning and nucleotide sequence of human pancreatic secretory trypsin inhibitor (PSTI) cDNA. Biochem Biophys Res Commun 1985; 132: 605-612.
158. Tomita N, Horii A, Yamamoto T, Ogawa M, Mori T, Matsubara K. Expression of pancreatic secretory trypsin inhibitor gene in neoplastic tissues. FEBS Lett 1987; 225: 113-139.
159. Yasuda T, Ohmachi Y, Katsuki M, Yokoyama M, Murata A, Monden M, Matsubara K. Identification of novel pancreas-specific regulatory sequences in the promoter region of human pancreatic secretory trypsin inhibitor gene. J Biol Chem 1998; 273: 34413-34421.
160. Yasuda T, Ogawa M, Murata A, Ohmachi Y, Mori T, Matsubara K. Identification of the IL-6-responsive element in an acute-phase-responsive human pancreatic secretory trypsin inhibitor-encoding gene. Gene 1993; 131: 275-280.
161. Ohmachi Y, Murata A, Matsuura N, Yasuda T, Monden M, Mori T, Ogawa M, Matsubara K. Specific expression of the pancreatic-secretory-trypsin-inhibitor (PSTI) gene in hepatocellular carcinoma. Int J Cancer 1993; 55: 728-734.
162. Bartelt DC, Shapanka R, Greene LJ. The primary structure of the human pancreatic secretory trypsin inhibitor. Amino acid sequence of the reduced s-aminoethylated protein. Arch Biochem Biophys 1977; 179: 189-199.
163. Greene LJ, Rigbi M, Fackre DS. Trypsin inhibitor from bovine pancreatic juice. J Biol Chem 1966; 241: 5610-5618.
164. Fritz H, Hüller I, Wiedemann M, Werle E. On protease inhibitors, V. On the chemistry and physiology of the specific trypsin inhibitors from the ox, dog, pig and human pancreas. Hoppe Seylers Z Physiol Chem 1967; 348: 405-418.
165. Kikuchi N, Nagata K, Shin M, Mitsushima K, Teraoka H, Yoshida N. Site-directed mutagenesis of human pancreatic secretory trypsin inhibitor. J Biochem (Tokyo) 1989; 106: 1059-1063.
166. Eddeland A, Ohlsson K. Studies on the pancreatic secretory trypsin inhibitor in plasma and its complex with trypsin in vivo and in vitro. Scand J Clin Lab Invest 1978; 38: 507-515.
167. Freeman TC, Playford RJ, Quinn C, Beardshall K, Poulter L, Young J, Calam J. Pancreatic secretory trypsin inhibitor in gastrointestinal mucosa and gastric juice. Gut 1990; 31: 1318-1323.
168. Playford RJ, Batten JJ, Freeman TC, Beardshall K, Vesey DA, Fenn GC, Baron JH, Calam J. Gastric output of pancreatic secretory trypsin inhibitor is increased by misoprostol. Gut 1991; 32: 1396-1400.
169. Marchbank T, Chinery R, Hanby AM, Poulsom R, Elia G, Playford RJ. Distribution and expression of pancreatic secretory trypsin inhibitor and its possible role in epithelial restitution. Am J Pathol 1996; 148: 715-722.
170. Ohmuraya M, Hirota M, Araki M, Mizushima N, Matsui M, Mizumoto T, Haruna K, Kume S, Takeya M, Ogawa M, Araki K, Yamamura K. Autophagic cell death of pancreatic acinar cells in serine protease inhibitor Kazal type 3-deficient mice. Gastroenterology 2005; 129: 696-705.
171. Marchbank T, Freeman TC, Playford RJ. Human pancreatic secretory trypsin inhibitor. Distribution, actions and possible role in mucosal integrity and repair. Digestion 1998; 59: 167-174.
172. Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R, Matsuura N, Murata A, Tomita N, Monden T, Ogawa M. Immunohistochemical analysis of pancreatic secretory trypsin inhibitor expression in pulmonary adenocarcinoma: Its possible participation in scar formation of the tumor tissues. Tumour Biol 1992; 13: 299-307.
173. Honda A, Siruntawineti J, Baba T. Role of acrosomal matrix proteases in sperm-zona pellucida interactions. Hum Reprod Update 2002; 8: 405-412.
174. Huhtala ML. Demonstration of a new acrosin inhibitor in human seminal plasma. Hoppe Seylers Z Physiol Chan 1984; 365: 819-825.
175. Venesmaa P, Stenman UH, Forss M, Leminen A, Lehtovirta P, Vartiainen J, Paavonen J. Preoperative serum level of tumour-associated trypsin inhibitor and residual tumour size as prognostic indicators in stage III epithelial ovarian cancer. Br J Obstet Gynaecol 1998; 105: 508-511.
176. Hunt LT, Barker WC, Dayhoff MO. Epidermal growth factor: Internal duplication and probable relationship to pancreatic secretory trypsin inhibitor. Biochem Biophys Res Commun 1974; 60: 1020-1028.
177. Scheving LA. Primary amino acid sequence similarity between human epidermal growth factor-urogastrone, human pancreatic secretory trypsin inhibitor, and members of porcine secretin family. Arch Biochem Biophys 1983; 226: 411-413.
178. Niinobu T, Ogawa M, Shibata T, Murata A, Nishibe S, Mori T, Ogata N. Specific binding of human pancreatic secretory trypsin inhibitor to various cultured cells. Res Commun Chem Pathol Pharmacol 1986; 53: 245-248.
179. Niinobu T, Ogawa M, Murata A, Nishijima J, Mori T. Identification and characterization of receptors specific for human pancreatic secretory trypsin inhibitor. J Exp Med 1990; 172: 1133-1142.
180. Ogawa M, Tsushima T, Ohba Y, Ogawa N, Tanaka S, Ishida M, Mori T. Stimulation of DNA synthesis in human fibroblasts by human pancreatic secretory trypsin inhibitor. Res Commun Chem Pathol Pharmacol 1985; 50: 155-158.
181. McKeehan WL, Sakagami Y, Hoshi H, McKeehan KA. Two apparent human endothelial cell growth factors from human hepatoma cells are tumor-associated proteinase inhibitors. J Biol Chem 1986; 261: 5378-5383.
182. Freeman TC, Curry BJ, Calam J, Woodburn JR. Pancreatic secretory trypsin inhibitor stimulates the growth of rat pancreatic carcinoma cells. Gastroenterology 1990; 99: 1414-1420.
183. Ohmachi Y, Murata A, Matsuura N, Yasuda T, Uda K, Mori T. Overexpression of pancreatic secretory trypsin inhibitor in pancreatic cancer. Evaluation of its biological function as a growth factor. Int J Pancreatol 1994; 15: 65-73.
184. Ogawa M, Kitahara T, Fujimoto K, Tanaka S, Takatsuka Y, Kosaki G. Serum pancreatic secretory trypsin inhibitor in acute pancreatitis. Lancet 1980; 2: 205.
185. Lasson A, Borgström A, Ohlsson K. Elevated pancreatic secretory trypsin inhibitor levels during severe inflammatory disease, renal insufficiency, and after various surgical procedures. Scand J Gastroenterol 1986; 21: 1275-1280.
186. Ogawa M, Matsuda K, Shibata T, Matsuda Y, Ukai T, Ohta M, Mori T. Elevation of serum pancreatic secretory trypsin inhibitor (PSTI) in patients with serious injury. Res Commun Chem Pathol Pharmacol 1985; 50: 259-266.
187. Matsuda K, Ogawa M, Shibata T, Nishibe S, Miyauchi K, Matsuda Y, Mori T. Postoperative elevation of serum pancreatic secretory trypsin inhibitor. Am J Gastroenterol 1985; 80: 694-698.
188. Roberts RM, Mathialagan N, Duffy JY, Smith GW. Regulation and regulatory role of proteinase inhibitors. Crit Rev Eukaryot Gene Expr 1995; 5: 385-436.
189. Yasuda T, Ogawa M, Murata A, Oka Y, Uda K, Mori T. Response to Il-6 stimulation of human hepatoblastoma cells: Production of pancreatic secretory trypsin inhibitor. Biological Chemistry Hoppe-Seyler 1990; 371 (Suppl): S95-100.
190. Jönsson P, Linder C, Genell S, Ohlsson K. Extrapancreatic origin of the pancreatic secretory trypsin inhibitor as an acute-phase reactant. Pancreas 1996; 12: 303-307.
191. Fukayama M, Hayashi Y, Koike M, Ogawa M, Kosaki G. Immunohistochemical localization of pancreatic secretory trypsin inhibitor in fetal and adult pancreatic and extrapancreatic tissues. J Histochem Cytochem 1986; 34: 227-235.
192. Bohe H, Bohe M, Lindström C, Ohlsson K. Immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in normal and neoplastic colonic mucosa. J Clin Pathol 1990; 43: 901-904.
193. Shibata T, Ogawa M, Matsuda K, Miyauchi K, Yamamoto T, Mori T. Purification and characterization of pancreatic secretory trypsin inhibitor in human gastric mucosa. Clin Chim Acta 1986; 159: 27-36.
194. Shibata T, Ogawa M, Takata N, Matsuda K, Niinobu T, Uda K, Wakasugi C, Mori T. Distribution of pancreatic secretory trypsin inhibitor in various human tissues and its inactivation in the gastric mucosa. Res Commun Chem Pathol Pharmacol 1987; 55: 243-248.
195. Lukkonen A, Lintula S, von Boguslawski K, Carpen O, Ljungberg B, Landberg G, Stenman UH. Tumor-associated trypsin inhibitor in normal and malignant renal tissue and in serum of renal-cell carcinoma patients. Int J Cancer 1999; 83: 486-490.
196. Hotakainen K, Bjartell A, Sankila A, Järvinen R, Paju A, Rintala E, Haglund C, Stenman U-H. Differential expression of trypsinogen and tumor-associated trypsin inhibitor (TATI) in bladder cancer. Int J Oncol 2006; 28: 95-101.
197. Huhtala ML, Kahanpaa K, Seppälä M, Halila H, Stenman UH. Excretion of a tumor-associated trypsin inhibitor (TATI) in urine of patients with gynecological malignancy. Int J Cancer 1983; 31: 711-714.
198. Ogawa M, Matsuura N, Higashiyama K, Mori T. Expression of pancreatic secretory trypsin inhibitor in various cancer cells. Res Commun Chem Pathol Pharmacol 1987; 55: 137-140.
199. Tomita N, Doi S, Higashiyama M, Morimoto H, Murotani M, Kawasaki Y, Monden T, Shimano T, Horii A, Yokouchi H. Expression of pancreatic secretory trypsin inhibitor gene in human colorectal tumor. Cancer 1990; 66: 2144-2149.
200. Higashiyama M, Monden T, Tomita N, Murotani M, Kawasaki Y, Morimoto H, Murata A, Shimano T, Ogawa M, Mori T. Expression of pancreatic secretory trypsin inhibitor (PSTI) in colorectal cancer. Br J Cancer 1990; 62: 954-958.
201. Higashiyama M, Monden T, Ogawa M, Matsuura N, Murotani M, Kawasaki Y, Tomita N, Murata A, Shimano T, Mori T. Immunohistochemical study on pancreatic secretory trypsin inhibitor (PSTI) in gastric carcinomas. Am J Clin Pathol 1990; 93: 8-13.
202. Ueda G, Shimizu C, Tanaka Y, Inoue M, Tanizawa O, Ogawa M, Mori T. Immunohistochemical demonstration of pancreatic secretory trypsin inhibitor in gynecologic tumors. Gynecol Oncol 1989; 32: 37-40.
203. Bohe H, Bohe M, Lindström C, Ohlsson K. Immunoreactive pancreatic secretory trypsin inhibitor in normal, inflammatory and neoplastic gallbladders. Gastroenterol Japon 1991; 26: 95-98.
204. Diggle CP, Cruickshank S, Olsburgh JD, Pellegrin S, Smith B, Banks RE, Selby PJ, Knowles MA, Southgate J, Harnden P. Identification of genes up-regulated in urothelial tumors: The 67-kd laminin receptor and tumor-associated trypsin inhibitor. Am J Pathol 2003; 163: 493-504.
205. Ogata N, Murata A. Pancreatic secretory trypsin inhibitor immunoreactivity detected in serum-free culture medium of human pancreatic carcinoma cell line, CAPAN-1. Res Commun Chem Pathol Pharmacol 1988; 59: 233-244.
206. Lauren P. The two histological main types of gastric carcinoma: Diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand 1965; 64: 31-49.
207. Ming SC. Cellular and molecular pathology of gastric carcinoma and precursor lesions: A critical review. Gastric Cancer 1998; 1: 31-50.
208. Wiksten JP, Lundin J, Nordling S, Kokkola A, Stenman UH, Haglund C. High tissue expression of tumour-associated trypsin inhibitor (TATI) associates with a more favourable prognosis in gastric cancer. Histopathology 2005; 46: 380-388.
209. Solakidi S, Tiniakos DG, Petraki K, Stathopoulos GP, Markaki I, Androulakis G, Sekeris CE. Co-expression of trypsin and tumour-associated trypsin inhibitor (TATI) in colorectal adenocarcinomas. Histol Histopathol 2003; 18: 1181-1188.
210. Stenman UH. Tumor-associated trypsin inhibitor. Clin Chem 2002; 48: 1206-1209.
211. Osman S, Turpeinen U, Itkonen O, Stenman UH. Optimization of a time-resolved immunofluorometric assay for tumor-associated trypsin inhibitor (TATI) using the streptavidin-biotin system. J Immunol Methods 1993; 161: 97-106.
212. Eddeland A, Ohlsson K. A radioimmunoassay for measurement of human pancreatic secretory trypsin inhibitor in different body fluids. Hoppe Seylers Z Physiol Chem 1978; 359: 671-675.
213. Halila H, Huhtala ML, Schröder T, Kiviluoto T, Stenman UH. Pancreatic secretory trypsin inhibitor-like immunoreactivity in pancreatectomized patients. Clin Chim Acta 1985; 153: 209-216.
214. Kolho KL, Huhtala ML, Jalanko H, Rauramo I, Stenman UH. Pancreatic secretory trypsin inhibitor from human amniotic fluid and fetal and neonatal urine: Concentrations and physicochemical characterization. Clin Chim Acta 1986; 156: 123-129.
215. Marks WH, Ohlsson K. Elimination of pancreatic secretory trypsin inhibitor from the circulation. A study in man. Scand J Gastroenterol 1983; 18: 955-959.
216. Witt H, Luck W, Hennies H, Classen M, Kage A, Lass U, Landt O, Becker M. Mutations in the gene encoding the serine protease inhibitor, Kazal type 1 are associated with chronic pancreatitis. Nat Genet 2000; 25: 213-216.
217. Gomez-Lira M, Bonamini D, Castellani C, Unis L, Cavallini G, Assael B, Pignatti P. Mutations in the spink1 gene in idiopathic pancreatitis Italian patients. Eur J Hum Genet 2003; 11: 543-546.
218. Threadgold J, Greenhalf W, Ellis I, Howes N, Lerch MM, Simon P, Jansen J, Charnley R, Laugier R, Frulloni L, Olah A, Delhaye M, Ihse I, Schaffalitzky de Muckadell OB, Andren-Sandberg A, Imrie CW, Martinek J, Gress TM, Mountford R, Whitcomb D, Neoptolemos JP. The N34S mutation of SPINK1 (PSTI) is associated with a familial pattern of idiopathic chronic pancreatitis but does not cause the disease. Gut 2002; 50: 675-681.
219. Witt H, Luck W, Becker M, Bohmig M, Kage A, Truninger K, Ammann RW, O'Reilly D, Kingsnorth A, Schulz H-U, Halangk W, Kielstein V, Knoefel WT, Teich N, Keim V. Mutation in the SPINK1 trypsin inhibitor gene, alcohol use, and chronic pancreatitis. JAMA 2001; 285: 2716-2717.
220. Lempinen M, Paju A, Kemppainen E, Smura T, Kylänpää ML, Nevanlinna H, Stenman J, Stenman UH. Mutations N34S and P55S of the SPINK1 gene in patients with chronic pancreatitis or pancreatic cancer and in healthy subjects: A report from Finland. Scand J Gastroenterol 2005; 40: 225-230.
221. Schneider A. Serine protease inhibitor Kazal type 1 mutations and pancreatitis. Clin Lab Med 2005; 25: 61-78.
222. Le Marechal C, Chen JM, Le Gall C, Plessis G, Chipponi J, Chuzhanova NA, Raguenes O, Ferec C. Two novel severe mutations in the pancreatic secretory trypsin inhibitor gene (SPINK1) cause familial and/or hereditary pancreatitis. Hum Mutat 2004; 23: 205.
223. Kuwata K, Hirota M, Shimizu H, Nakae M, Nishihara S, Takimoto A, Mitsushima K, Kikuchi N, Endo K, Inoue M, Ogawa M. Functional analysis of recombinant pancreatic secretory trypsin inhibitor protein with amino-acid substitution. J Gastroenterol 2002; 37: 928-934.
224. Paavonen J, Lehtinen M, Lehto M, Laine S, Aine R, Räsänen L, Stenman UH. Concentrations of tumor-associated trypsin inhibitor and C-reactive protein in serum in acute pelvic inflammatory disease. Clin Chem 1989; 35: 869-871.
225. Kobayashi K, Horiuchi M, Saheki T. Pancreatic secretory trypsin inhibitor as a diagnostic marker for adult-onset type II citrullinemia. Hepatology 1997; 25: 1160-1165.
226. Haglund C, Huhtala ML, Halila H, Nordling S, Roberts PJ, Scheinin TM, Stenman UH. Tumour-associated trypsin inhibitor, TATI, in patients with pancreatic cancer, pancreatitis and benign biliary diseases. Br J Cancer 1986; 54: 297-303.
227. Halila H, Lehtovirta P, Stenman UH, Seppälä M. CA 125 in the follow-up of patients with ovarian cancer. Acta Obstet Gynecol Scand 1988; 67: 53-58.
228. Peters-Engl C, Medl M, Ogris E, Leodolter S. Tumor-associated trypsin inhibitor (TATI) and cancer antigen 125 (CA125) in patients with epithelial ovarian cancer. Anticancer Res 1995; 15: 2727-2730.
229. Venesmaa P, Lehtovirta P, Stenman UH, Leminen A, Forss M, Ylikorkala O. Tumour-associated trypsin inhibitor (TATI): Comparison with CA125 as a preoperative prognostic indicator in advanced ovarian cancer. Br J Cancer 1994; 70: 1188-1190.
230. Stenman U-H, Koivunen E, Itkonen O, Halila H. Clinical use and biological function of tumor-associated trypsin inhibitor (TATI). In Ballesta AM, Torre GC, Bombardieri E, Gion M, Molina R, Eds. Up dating on tumor markers in tissues and biological fluids. Pp 351-361. Torino: Edizioni Minerva Medica, 1993.
231. Peters-Engl C, Buxbaum P, Ogris E, Sevelda P, Medl M. TATI (tumor associated trypsin inhibitor) and cancer antigen 125 (CA 125) in patients with early-stage endometrial cancer. Anticancer Res 1998; 18: 4635-4639.
232. Pectasides D, Economides N, Bourazanis J, Pozadzizou P, Gogou L, Koutsiouba P, Athanassiou A. Squamous cell carcinoma antigen, tumor-associated trypsin inhibitor, and carcinoembryonic antigen for monitoring cervical cancer. Am J Clin Oncol 1994; 17: 307-312.
233. Loizate Toricaguena A, Lamiquiz Vallejo A, Dominguez Merru-Urrutia MJ, Legorburu Escudero JF. Tumor-associated trypsin inhibitor (TATI) in benign and malignant gastric disease. Scand J Clin Lab Invest Suppl 1991; 207: 59-62.
234. Piantino P, Arosaio E. Tumor-associated trypsin inhibitor, TATI, in gastrointestinal cancer and related benign diseases. Scand J Clin Lab Invest 1991; 207 (Suppls): S67-69.
235. Pasanen PA, Eskelinen M, Partanen K, Pikkarainen P, Penttila I, Alhava E. Multivariate analysis of six serum tumor markers (CEA, CA 50, CA 242, TPA, TPS, TATI) and conventional laboratory tests in the diagnosis of hepatopancreatobiliary malignancy. Anticancer Res 1995; 15: 2731-2737.
236. Hedström J, Haglund C, Leinonen J, Nordling S, Stenman UH. Trypsinogen-1, -2 and tumour-associated trypsin-inhibitor in bile and biliary tract tissues from patients with biliary tract diseases and pancreatic carcinomas. Scand J Clin Lab Invest 2001; 61: 111-118.
237. Pasanen P, Eskelinen M, Kulju A, Penttila I, Janatuinen E, Alhava E. Tumour-associated trypsin inhibitor (TATI) in patients with colorectal cancer: A comparison with CEA, CA 50 and CA 242. Scand J Clin Lab Invest 1995; 55: 119-124.
238. Pectasides D, Bafaloucos D, Antoniou F, Gogou L, Economides N, Varthalitis J, Dimitriades M, Kosmidis P, Athanassiou A. TPA, TATI, CEA, AFP, beta-hCG, PSA, SCC, and CA 19-9 for monitoring transitional cell carcinoma of the bladder. Am J Clin Oncol 1996; 19: 271-277.
239. Kelloniemi E, Rintala E, Finne P, Stenman U-H, Group F. Tumor-associated trypsin inhibitor (TATI) as a prognostic marker during follow-up of bladder cancer. Urology 2003; 62: 249-253.
240. Shariat SF, Herman M, Casella R, Lotan Y, Karam J, U-H. S. Urinary levels of tumor-associated trypsin inhibitor (TATI) in the detection of transitional cell carcinoma of the urinary bladder. Eur Urol 2005; 48: 424-431.
241. Meria P, Toubert ME, Cussenot O, Bassi S, Janssen T, Desgrandchamps F, Cortesse A, Schlageter MH, Teillac P, Le Duc A. Tumour-associated trypsin inhibitor and renal cell carcinoma. Eur Urol 1995; 27: 223-226.
242. Paju A, Jacobsen J, Rasmuson T, Stenman U-H, Ljungberg B. Tumor-associated trypsin inhibitor as a prognostic factor in renal cell carcinoma. J Urol 2001; 165: 959-962.
243. Järvisalo J, Hakama M, Knekt P, Stenman UH, Leino A, Teppo L, Maatela J, Aromaa A. Serum tumor markers CEA, CA 50, TATI, and NSE in lung cancer screening. Cancer 1993; 71: 1982-1988.
244. Sjöström J, Alfthan H, Joensuu H, Stenman UH, Lundin J, Blomqvist C. Serum tumour markers CA 15-3, TPA, TPS, hCG-beta and TATI in the monitoring of chemotherapy response in metastatic breast cancer. Scand J Clin Lab Invest 2001; 61: 431-441.
245. Goumas PD, Mastronikolis NS, Mastorakou AN, Vassilakos PJ, Nikiforidis GC. Evaluation of TATI and cyfra 21-1 in patients with head and neck squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec 1997; 59: 106-114.