Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have evaluated tumor-associated trypsin inhibitor (TATI) as a marker for pancreatic and hepatic cancer. Of the patients studied 52 had pancreatic cancer, 30 primary liver cancer, 32 chronic pancreatitis, 25 biliary tract inflammatory disease, and 28 liver cirrhosis. A considerable number of falsely elevated values were observed in benign biliary diseases and in chronic relapsing pancreatitis. In pancreatic cancer the sensitivity of TATI was 63% while that of CEA was 40% and of CA19-9 77%. TATI is a marker of pancreatic disease but it does not differentiate between pancreatitis and pancreatic cancer. In liver cancer TATI and AFP has similar sensitivity and specificity.
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PMID:Tumor-associated trypsin inhibitor in pancreatic diseases. 172 34

Tumor-associated trypsin inhibitor (TATI) is a 6,000 Daltons peptide, which is synthesized by several tumors and cell lines. TATI is identical to pancreatic secretory trypsin inhibitor (PSTI). This peptide is also produced by the mucosa of the gastrointestinal tract, where it is thought to protect the mucosal cells from proteolytic breakdown. Elevated serum and urine levels of TATI occur in connection with many types of cancer, especially mucinous ovarian cancer. Elevated levels may also occur in nonmalignant diseases, e.g. in pancreatitis, severe infections and tissue destruction. Thus TATI may behave as an acute phase reactant. Tumors producing TATI often express tumor-associated trypsinogen. Elevation of TATI in cancer and pancreatic disease is therefore associated with expression of trypsin, but such a connection has not been demonstrated in inflammatory disease. TATI can inhibit trypsin-mediated degradation of extracellular matrix by tumor cells. Therefore its role may be to control the activation of tumor-associated trypsinogen. TATI has also been shown to possess growth factor activity in vitro, but it is not known whether this is a physiological function.
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PMID:Biology and function of tumor-associated trypsin inhibitor, TATI. 178 Jun 91

Tumor-associated trypsin inhibitor (TATI) is a 6 K dalton protease inhibitor, that was isolated from urine of a patient with ovarian cancer. In our experience, mean serum level of TATI in healthy subjects (n. 120), is 13 micrograms/l (range 5.1-42 micrograms/l). The cut-off point is established in 32 micrograms/l (mean +/- 3 SD). We have examined 357 patients with gastrointestinal diseases: 98 gastric cancer, 50 colon cancers, 52 pancreatic cancers, 32 chronic pancreatitis, 38 IBD, 28 colon polyps, 40 gastric ulcers and 25 non-neoplastic biliary tree diseases. TATI may be a good tumor marker only in gastric cancer. Elevated levels of TATI also occur in obstructive hepatobiliary disease and active pancreatitis or IBD.
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PMID:[Determination of tumor-associated trypsin inhibitor (TATI) in subjects with gastrointestinal diseases. Preliminary data]. 271 42

Pancreatic secretory trypsin inhibitor (PSTI) is a 6000-dalton peptide, that occurs in high concentrations in the pancreas and in pancreatic juice. It is thought to be synthesized by pancreatic acinar cells. We have recently reported the findings of an identical trypsin inhibitor at high concentrations in the urine of patients with gynecological malignancy. Therefore, we have named the inhibitor tumor-associated trypsin inhibitor (TATI). We have now studied patients who have undergone total pancreatoduodenectomy for pancreatic cancer or chronic pancreatitis. By radioimmunoassay (RIA), we found normal levels of this inhibitor in the serum and urine of pancreatectomized patients. The absence of pancreas was confirmed by measuring serum trypsin. By gel filtration and HPLC it was found that PSTI/TATI occurring in pancreatectomized patients was indistinguishable from that found in connection with pancreatitis and ovarian cancer.
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PMID:Pancreatic secretory trypsin inhibitor-like immunoreactivity in pancreatectomized patients. 393 45

In earlier studies we reported the finding of a tumor-associated peptide that also occurred at high concentrations in early amniotic fluid. Determination of the N-terminal sequence of this peptide revealed that it is closely related or identical to the pancreatic secretory trypsin inhibitor. Therefore, the peptide is called tumor-associated trypsin inhibitor (TATI). The concentration of TATI was determined by radioimmunoassay in the urine of 148 patients with various forms of gynecologic malignancy and in a reference population consisting of 98 patients with non-malignant gynecologic disease, and also in 40 patients with severe infections or inflammatory disease. In the reference population, the median urinary concentration of TATI was 22 micrograms/g creatinine and the central 95% reference interval was 7-50 micrograms/g creatinine. Elevated urinary levels were observed in 53% of all patients with gynecologic cancer, in 63% of those with active disease and 26% of those in clinical remission. The highest urinary TATI level (11,000 micrograms/g creatinine) was over 200 times the upper limit of the reference range. Patients with cervical cancer had the highest frequency of elevated values. Increased excretion of TATI was also observed in patients with severe bronchopulmonary infections and pancreatitis. Although increased excretion of TATI is not cancer-specific, the distinction by elevated levels of TATI between malignant and nonmalignant gynecologic disease is better than by most other putative tumor markers, and the increased excretion of TATI in patients with active disease can be important for the understanding of tumor biology.
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PMID:Excretion of a tumor-associated trypsin inhibitor (TATI) in urine of patients with gynecological malignancy. 619 Jul 63

Mutations in the serine protease inhibitor Kazal type 1 gene (SPINK1) encoding pancreatic secretory trypsin inhibitor (PSTI) have recently been found to be associated with chronic pancreatitis. Nevertheless, knowledge of severe mutations is particularly scarce, both in terms of number and in the extent of clinical information. The aim of this study was to expand the known spectrum of such mutations. 46 unrelated families, each including at least two pancreatitis patients and carrying neither cationic trypsinogen (PRSS1) mutations nor the frequent SPINK1 N34S mutation, participated in this study. The four exons and their flanking sequences of the SPINK1 gene were screened by denaturing high performance liquid chromatography analysis (DHPLC); and mutations were identified by direct sequencing. A heterozygous microdeletion mutation (c.27delC), which occurs within a symmetric element, was identified in two families. In one family, c.27delC showed segregation with the disease across two generations, with a penetrance of up to 75%. But in the other family, however, the same mutation manifested as a low-penetrance susceptibility factor. In addition, a novel heterozygous splicing mutation, c.87+1G>A (G>A substitution at nucleotide +1 of intron 2) was found in one family with familial pancreatitis. Our results also helped to resolve the sharply differing views about PSTI's role in pancreatitis.
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PMID:Two novel severe mutations in the pancreatic secretory trypsin inhibitor gene (SPINK1) cause familial and/or hereditary pancreatitis. 1472 25

Mutations in the cationic trypsinogen gene are acknowledged as a risk factor for pancreatic cancer in patients with hereditary pancreatitis. However, whether patients with mutations in other genes, such as the serine protease inhibitor Kazal type 1 (SPINK1) gene, are also at a higher risk of pancreatic cancer remains unknown. We report a case of pancreatic cancer associated with chronic calcifying pancreatitis in a patient with a homozygous N34S mutation in the SPINK1 gene. A 44-year-old woman was hospitalized due to obstructive jaundice. Preoperative examination showed a tumor in the head of the pancreas and multiple pancreatic stones; pancreatoduodenectomy revealed a solid tumor, 3.0 x 2.5 cm in size, in the head of the pancreas, and numerous pancreatic stones throughout the pancreas. Pathologic studies revealed moderately differentiated tubular adenocarcinoma. Mutational analyses of the SPINK1 and PRSS1 genes in members of the patient's family were carried out. The homozygous N34S mutation in the SPINK1 gene was found in the patient and her older sister, who was previously diagnosed with chronic calcific pancreatitis and had undergone the Frey operation. The patient's parents and brother were unaffected carriers of the N34S heterozygous mutation. No family members had any mutations in the cationic trypsinogen gene. To our knowledge, this is the first reported case of chronic pancreatitis accompanied by pancreatic cancer in a patient with the SPINK1 N34S mutation. Although this case does not meet the classic criteria of hereditary pancreatitis, it does suggest that the SPINK1 N34S mutation may be associated with cancer development in patients with hereditary pancreatitis. Further prospective, multicenter trials investigating secondary screening for pancreatic cancer in hereditary pancreatitis are necessary to clarify the role of SPINK1 mutations in the development of pancreatic cancer.
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PMID:Hereditary pancreatitis as the premalignant disease: a Japanese case of pancreatic cancer involving the SPINK1 gene mutation N34S. 1508 77

Trypsin activity is properly suppressed by pancreatic secretory trypsin inhibitor (PSTI), which is also known as serine protease inhibitor Kazal type 1 (SPINK1), thereby preventing damage to pancreatic acinar cells as a first line of defence. However, if trypsin activation exceeds the capacity of PSTI/SPINK1, a subsequent cascade of events leads to the activation of various proteases that damage cells. Five mutations (R122H, N29I, A16V, D22G and K23R) in cationic trypsinogen and two mutations (N34S and M1T) in the PSTI/SPINK1 gene have been found to correlate significantly with the onset of pancreatitis. From analyses of hereditary pancreatitis and the phenotype of PSTI/SPINK1 (Spink3) knockout mice, we showed that the imbalance of trypsin activation and its inhibition by PSTI/SPINK1 would lead to the development of pancreatitis.
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PMID:Genetic background of pancreatitis. 1714 97

The proteins expressed in pancreatic acinar cells during the initiation of acute pancreatitis may determine the severity of the disease. Cerulein pancreatitis is one of the best characterized models for acute pancreatitis. Present study aims to determine the differentially expressed proteins in cerulein-stimulated pancreatic acinar cells as an in vitro model for acute pancreatitis. Rat pancreatic acinar AR42J cells were treated with 10(-8)M cerulein for 12h. The protein patterns separated by two-dimensional electrophoresis using pH gradients of 5-8 were compared between the cells treated without cerulein and those with cerulein. The changed proteins were conclusively identified by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis of the peptide digests. As a result, 10 proteins (Orp150 protein, protein disulfide isomerase related protein, dnaK-type molecular chaperone hsp72-ps1, mitochondrial glutamate dehydrogenase, similar to chaperonin containing TCP-1 beta subunit, RuvB-like protein 1, heterogeneous nuclear ribonucleoprotein H1, aldehyde reductase 1, triosephosphate isomerase 1, peroxiredoxin 2) were up-regulated while four proteins (vasolin-containing protein, 78 kDa glucose-regulated protein precursor, heat shock protein 8, adenosylhomocysteinase) were down-regulated by cerulein in pancreatic acinar AR42J cells. These proteins are related to chaperone, cell defense mechanism against oxidative stress or DNA damage, anti-apoptosis and energy generation. The differentially expressed proteins by ceruein share their functional roles in pancreatic acinar cells, suggesting the possible involvement of oxidative stress, DNA damage, and anti-apoptosis in pathogenesis of acute pancreatitis. Proteins involved in cellular defense mechanism and energy production may protect pancreatic acinar cells during the development of pancreatitis.
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PMID:Differentially expressed proteins in cerulein-stimulated pancreatic acinar cells: implication for acute pancreatitis. 1802 78

The serine protease inhibitor Kazal type 1 (SPINK1) is a potent antiprotease and an important inactivation factor of intrapancreatic trypsin activity. Loss of function by the SPINK1 mutations leads to decreased inhibitory capacity. The significance of SPINK1 mutations in alcoholic chronic pancreatitis (CP) in Japan and its functional role remain unclear. The aim of the present study was to clarify the incidence of SPINK1, alcohol dehydrogenase 2 (ADH2) and aldehyde dehydrogenase 2 (ALDH2) variants in CP patients in Japan. One hundred and 86 patients with CP, and 527 healthy volunteers were enrolled. Mutational analyses were performed by polymerase chain reaction-restriction fragment length polymorphism and direct sequencing. Serum pancreatic secretory trypsin inhibitor (PSTI) level was measured by radioimmunoassay. The frequencies of N34S and IVS3 + 2T > C in the SPINK1 gene were significantly higher in patients with non-alcoholic CP (12.9% and 8.6%, respectively) than in normal subjects (0.37% and 0%). In total, 18 of 93 (19.4%) patients with non-alcoholic CP had at least one SPINK1 mutation. Concerning alcoholic CP, we found IVS3 + 2T > C in a small number of patients (3.9%). Serum PSTI concentration was decreased in patients with the IVS3 + 2T > C mutation. The frequency of the ADH2*2 allele in the alcoholic CP group was significantly higher than that in alcoholics without pancreatitis. The frequency of the ALDH2*2 allele was significantly low in patients with alcoholic CP compared with healthy controls. In conclusion, SPINK1 mutations were associated with non-alcoholic CP. Furthermore, we revealed the amount of wild-type PSTI was decreased in patients with IVS3 + 2T > C mutation. Variants of alcohol-metabolizing enzymes appeared in the relation to alcoholic CP.
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PMID:SPINK1, ADH2, and ALDH2 gene variants and alcoholic chronic pancreatitis in Japan. 1833 71


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