Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic secretory abnormalities develop in most persons with pancreatic cancer and have been attributed to ductal obstruction. These experiments investigated whether abnormal secretion results instead from carcinogen-induced changes in the secreting cells. Fifty male Syrian Golden hamsters (40 to 100 grams) received weekly injections of di-isopropyl-nitrosamine (250 mg/kg, subcutaneously), and survivors and age-matched controls were studied after 3.5 to 6.5 months of treatment. Pancreatic secretion was stimulated by secretin or cholecystokinin (2 units/kg, intravenously, as a bolus). After each stimulus four 15-minute collections of pancreatic juice were analyzed for HCO3- and Cl- or total protein, amylase, trypsin, and chymotrypsin. The organs were examined histologically. Pancreatic ductal adenocarcinoma developed in 30% of the animals at 5 months, 56% at 5.5 months, and 100% at 6.5 months. The animals without cancer either had hyperplasia of the duct epithelium or were histologically normal. The histologic appearance of acinar tissue and protein secretion were normal in all groups. The tumors did not obstruct the major ducts. In all treated animals the pancreatic secretory response to secretin was of low volume, low maximal [HCO3-] and HCO3- output, and low [Cl- + HCO3-]; these changes progressed with time. The secretory abnormalities antedated the appearance of the neoplasms and were not caused by obstruction.
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PMID:Pancreatic secretion in hamsters with pancreatic cancer. 87 54

A rare autopsy case, in which pleural malignant fibrous histiocytoma (MFH) and peripheral pulmonary adenocarcinoma were present concurrently in the right thorax, is described. Clinically, only a pleural mass was detected because of massive pleural effusion. Since cytologic examination of the effusion showed only adenocarcinoma cells, the pleural mass was considered to be enlarged mediastinal lymph nodes due to metastasis of adenocarcinoma. Histopathologically, the pleural mass showed the features of a common type of MFH, accompanied by metastatic adenocarcinoma cells in the pleural lymphatics. No mixture of MFH and adenocarcinoma cells was present. Immunohistochemically, the MFH lesion showed positive staining for alpha-1-antitrypsin, alpha-1-chymotrypsin, and factor XIIIa, but no reactivity for cytokeratins. The adenocarcinoma lesion showed positive staining for carcinoembryonic antigen (CEA), and contained hyaluronidase-resistant mucin. To our knowledge, this is the second reported case of pleural MFH with pulmonary adenocarcinoma.
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PMID:Pleural malignant fibrous histiocytoma concomitant with pulmonary adenocarcinoma. 133 5

In two cases of solid and papillary neoplasm of the pancreas (SPN), positive staining for argyrophil granules, chromogranin-A, neuron-specific enolase, chymotrypsin, alpha 1-antitrypsin, vimentin, cytokeratin, and estrogen receptors was present. Ultrastructurally, neurosecretory as well as zymogenlike granules were demonstrated. Measurements of mean nuclear volume and volume-corrected mitotic index discriminated between SPN and well-differentiated ductal adenocarcinoma of the pancreas, with notably lower values being seen in SPN. Silver-stained nucleolar organizer region counts showed wide overlaps. The results suggest that SPN is a tumor with mixed endocrine and exocrine features. Its low malignant potential compared to ductal adenocarcinoma is reflected in the mean nuclear volume and volume-corrected mitotic index. The presence of estrogen receptors may prove therapeutically useful.
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PMID:Solid and papillary neoplasm of the pancreas. 144 85

The ability of tumor cells to express elevated levels of proteinases capable of degrading tissue matrix and basement membrane components in vitro has been correlated to their invasive and metastatic potential. Many in vitro invasion assays have been performed either in the presence of serum or with tumor cells that had been previously grown in serum. Since serum contains large amounts of active proteinase inhibitors, their presence could complicate interpretations. We have, therefore, attempted to measure the amounts of serine proteinase inhibitors released into culture medium by two rat mammary adenocarcinoma metastatic variants selected in vitro for serum-independent growth and differing in their in vivo metastatic behavior. Concentrated spent media (CSM) derived from cultures of poorly metastatic MTLn2(T42D) and highly metastatic MTLn3(T17D) tumor cells, grown in the presence and absence of fetal bovine serum (FBS) for 20-24 h, were compared for the presence of serine proteinase inhibitors capable of inactivating alpha-chymotrypsin. Our results show that when MTLn2(T42D) and MTLn3(T17D) tumor cells were exposed to FBS, the CSM of MTLn2(T42D) exhibited nearly 5-fold greater amounts of active proteinase inhibitors than that of MTLn3(T17D). The amount of proteinase inhibitory activity detected in the CSM of tumor cells not exposed to FBS was not eliminated but declined by 82% and 37% for MTLn2(T42D) and MTLn3(T17D), respectively. Analysis for enzyme-inhibitor (E-I) complex formation by nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography confirmed the kinetic results and revealed that the major inhibitor present in CSM/FBS of both variants forms a heat- and sodium dodecyl sulfate-stable E-I complex with an apparent molecular weight of approximately 79,000, identical to that formed when FBS or purified alpha 1-proteinase inhibitor is incubated with [alpha-125I]chymotrypsin. E-I complexes with apparent molecular weights of 44,000 and 50,000 were formed from CSM/bovine serum albumin of MTLn3(T17D) and MTLn2(T42D), respectively, that were not detected when [alpha-125I]chymotrypsin was incubated with bovine serum albumin. We infer from these observations that, in culture, poorly metastatic MTLn2(T42D) tumor cells, as compared to their highly metastatic MTLn3(T17D) counterparts, exhibit an increased capacity to retain and subsequently release significantly greater amounts of serum-derived active proteinase inhibitors. Moreover, the detection of proteinase activity by kinetic analysis and E-I complexes by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and autoradiography in CSM prepared from cultures not exposed to FBS indicates that both variants have the capacity to produce their own inhibitors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Differential release of active proteinase inhibitors by two rat mammary adenocarcinoma variants possessing different metastatic potentials. 199 70

Two new human cell lines, RCM-1 and CoCM-1, have been established from primary colorectal adenocarcinomas. Both cell lines were unique in that the cultures secreted trypsin inhibitors in vitro. The activities of these inhibitors were accumulated in serum-free media of both cell lines over a period of several days. Two inhibitors (PI-1 and PI-2) were isolated from serum-free conditioned medium in which RCM-1 was grown by anion-exchange and gel filtration high-performance liquid chromatography. PI-1 inhibited trypsin and chymotrypsin strongly, and pancreatic elastase weakly. Its molecular weight was about 57 kilodaltons (Kd) as determined by gel filtration chromatography. It cross-reacted with the antiserum elicited against human alpha 1-antitrypsin in double immunodiffusion. PI-1 corresponding to alpha 1-antitrypsin was also demonstrated immunohistochemically in both cell lines. PI-2 inhibited trypsin strongly, and chymotrypsin, kallikrein and plasmin weakly. It had higher molecular weight (200-300 Kd) than that of PI-1, and did not cross-react with antisera against human alpha 1-antitrypsin, alpha 2-macroglobulin, alpha 1-antichymotrypsin, alpha 2-plasmin inhibitor, inter-alpha-trypsin inhibitor and urinary trypsin inhibitor. RCM-1 and CoCM-1 are the first colorectal adenocarcinoma cell lines that secrete functionally active trypsin inhibitors, including alpha 1-antitrypsin in vitro, and are useful for the study of tumor-cell derived proteinase inhibitors.
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PMID:New human colorectal carcinoma cell lines that secrete proteinase inhibitors in vitro. 257 Apr 82

Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad range of biological activities in various tissues. After interaction with its membrane receptor, VIP generally induces a very large increase in the intracellular cyclic AMP level. Receptors for VIP have been described in numerous tissues and cell lines. The first results on VIP receptor structure have been obtained by covalent cross-linking using bifunctional reagents. The molecular mass of the different components characterized in this way differs greatly according to the species and the tissue used. This heterogeneity may reflect either a difference in the length of the cross-linked polypeptide backbone or differently glycosylated forms of the same polypeptide. The VIP binding site of intact human adenocarcinoma cells (HT29 cells) is an Mr 64,000 glycoprotein with 20kDa of N-linked oligosaccharide side chains containing sialic acid. The structure of the VIP binding site from HT29 cell is compared, first to the structure of the VIP receptor from other tissues, particularly that from rat liver, and second to the structure of the hepatic glucagon binding site. Recently, solubilization of the VIP receptor in an active form has provided a new way of studying this receptor. The HT29 cell line is an appropriate model to study the dynamics of the VIP receptor. After binding to its receptor, VIP is rapidly internalized, probably by receptor-mediated endocytosis. This internalization leads to a decrease in the cell surface receptor number and simultaneously to a homologous desensitization of adenylate cyclase. VIP is then degraded in the lysosomes, while most of the receptors are recycled back to the cell surface. The presence of an intracellular pool of unoccupied VIP receptors has been demonstrated after inactivation of the cell surface receptors by chymotrypsin. The kinetics of the receptor reappearance at the cell surface, after inactivation by chymotrypsin or after receptor-mediated endocytosis, indicate 2 possible intracellular pathways for occupied and unoccupied VIP receptors.
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PMID:The vasoactive intestinal peptide (VIP) receptor: recent data and hypothesis. 285 63

Microvilli isolated from the MAT-C1 ascites subline of the 13762 rat mammary adenocarcinoma contain a major calcium-sensitive microfilament-binding protein, AMV-p35 (ascites microvillar p35). Association of AMV-p35 with microfilament cores during Triton X-100 extraction of the microvilli is half-maximal at 0.1-0.2 mM calcium. The protein, which comprises 6% of the total microvillar protein, can be isolated from microfilament cores prepared in the presence of calcium by extraction with EGTA and purification by ion-exchange chromatography. Alternatively, the protein can be isolated from Triton extracts of microvilli prepared in the absence of calcium by precipitation with calcium, solubilization of the precipitate with EGTA, and chromatography on an ion-exchange column. AMV-p35 binds to phosphatidylserine liposomes and F-actin with half-maximal calcium concentrations of about 10 microM and 0.2 mM, respectively. Treatment of AMV-p35 with chymotrypsin yields a 33,000-dalton fragment, behavior similar to the tyrosine kinase substrates calpactins I and II and lipocortins I and II. Immunoblot analyses using antibodies directed against calpactin I, lipocortin I, and lipocortin II showed strong reactivity of AMV-p35 with anti-calpactin I and anti-lipocortin II, but little reactivity toward anti-lipocortin I. The close relationship between AMV-p35 and calpactin I was verified by amino acid sequence analyses of peptides isolated from cyanogen bromide digests of AMV-p35. By gel filtration and velocity sedimentation analyses purified AMV-p35 is a 35,000-dalton monomer. Moreover, AMV-p35 extracted directly from microvilli in Triton/EGTA also behaves as a 35,000-dalton menomer. These findings indicate that AMV-p35 is closely related to the pp60src kinase substrate calpactin I (p36). However, AMV-p35 occurs in the microvilli as a monomer rather than as the heterotetrameric calpactin found in several other cell types.
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PMID:Isolation of a calcium-sensitive, 35,000-dalton microfilament- and liposome-binding protein from ascites tumor cell microvilli: identification as monomeric calpactin. 296 74

An antiproliferative suppressor lymphokine was produced from rat T-cells specifically in response to the poorly immunogenic syngeneic mammary adenocarcinoma 13762A. The tumor-induced suppressor lymphokine (TISL) was produced late in culture (peak production on Days 4 and 5) and showed strong but selective inhibitory activity on a variety of immune responses. The immune peritoneal exudate cell response to a highly immunogenic clone from the parental tumor (clone 18A) and the concanavalin A-stimulated response of nonimmune spleen cells were inhibited strongly by TISL. In contrast, the immune spleen cell response to 13762A and the lipopolysaccharide response of nonimmume spleen cells were unaffected. Preliminary molecular weight and physicochemical analysis of TISL indicated that the molecule was large (Mr greater than 350,000); partially sensitive to 75 degrees C treatment for 15 min and to pH 2.0 treatment; only partly degraded by the enzymes trypsin, chymotrypsin, and proteinase K; and completely destroyed by boiling. Although TISL was produced specifically in response to 13762A tumor, prior immunization in vivo was not necessary for the induction of the suppressor lymphokine. These results indicate that populations of rat lymphocytes contain naturally occurring TISL secreting cells, which can be activated specifically by tumor antigens such as those expressed by 13762A.
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PMID:Suppressor lymphokine produced by rat T-cells in response to syngeneic mammary adenocarcinoma 13762A. 296 35

Incubation of monolayers of HT29-D4 cells (a clone of the human colonic adenocarcinoma cell line HT29) in the presence of 17.5 microM cycloheximide resulted in an increase in the number of vasoactive intestinal peptide (VIP) binding sites at the cell surface without any change in the affinity of receptor for its ligand. The increase in 125I-VIP-binding capacity was dose-dependent between 0.35 microM and 17.5 microM cycloheximide and was correlated with the inhibition of protein biosynthesis. At higher concentrations of drug (17.5-100 microM) a plateau corresponding to a twofold increase in VIP-binding capacity was reached independently of the extent of protein synthesis inhibition. We found that VIP receptors of HT29-D4 cells with such an enhanced binding capacity behaved like those of control cells with respect to receptor internalization and recycling (i.e. the cycle of occupied receptors was insensitive to cycloheximide). After inactivation of 90% of cell-surface VIP receptors by alpha-chymotrypsin, we observed a biphasic kinetic of reappearance of VIP-binding sites. 40% of VIP-binding sites reappeared very quickly (less than 5 min) and 100% within 17 h. The fast recovery of VIP receptors was probably due to the deployment of new binding sites from an intracellular pool. The rate and extent of recovery of these receptors were similar in control cells and in cycloheximide-treated cells. However, the slow recovery was inhibited in cycloheximide-treated cells probably because a pool of immature receptors was depleted by the drug before the alpha-chymotrypsin treatment. Our data are consistent with the existence of two different intracellular pathways of occupied and unoccupied VIP receptors.
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PMID:Cycloheximide induces accumulation of vasoactive intestinal peptide (VIP) binding sites at the cell surface of a human colonic adenocarcinoma cell line (HT29-D4). Evidence for the presence of an intracellular pool of VIP receptors. 304 Apr 9

Incorporation of alpha-1-antichymotrypsin (ACT) into human stomach adenocarcinoma cell nuclei and the effect of ACT on DNA primase from the same carcinoma cells were studied. ACT or [125I]-ACT were observed in carcinoma cell nuclei and high specific radioactivity was detected in washed nuclear fraction when 0.4 mg of ACT or [125I] ACT (8 x 10(7) cpm) was intravenously injected into carcinoma bearing nude mice 2 h before killing. The molecular weight of radioactivity presented in cell nuclei was same as the intact ACT on SDS-polyacrylamide gel electrophoresis. ACT inhibited DNA primase activity and this inhibiting activity was stable than its chymotrypsin inhibiting activity. The results presented here show ACT is incorporated into carcinoma cell nuclei without modification of its molecular weight and may inhibit DNA primase activity.
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PMID:Incorporation of alpha-1-antichymotrypsin into human stomach adenocarcinoma cell nuclei and inhibition of DNA primase activity. 327 74


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