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)

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.
Cancer Res 1988 Feb 15
PMID:Suppressor lymphokine produced by rat T-cells in response to syngeneic mammary adenocarcinoma 13762A. 296 35

Monoclonal antibodies (MAbs) were generated by immunizing mice with the mesothelioma cell line SPC111 and selected by indirect immunofluorescence on viable cells. Indirect immunofluorescence staining and radioimmunoassays demonstrated selective binding of the antibodies ME1 and ME2 with the surface membrane of mesothelioma, but not with lung adenocarcinoma cell lines. Lung small-cell carcinoma cell lines were unreactive, while staining was seen in a proportion of lung squamous-cell carcinoma cell lines. The antibodies were unreactive with other cell lines, including breast, colon, ovarian, and renal-cell carcinoma, leukemia, and lung fibroblast. The antibodies stained normal mesothelial cells, but were unreactive with normal bronchial epithelial cells in primary cultures, or peripheral blood cells. Immunohistochemical staining of cryostat sections of tumor tissues confirmed the ability of the antibodies to distinguish between mesothelioma and lung adenocarcinoma. All 12 mesothelioma tissues, but none of 9 lung adenocarcinomas or large-cell carcinomas, stained with the MAbs. Staining of malignant mesothelioma tissues was very homogeneous. Some lung squamous-cell carcinomas and breast carcinomas were stained focally by both, and some ovarian carcinomas by one antibody. Solid-phase radioimmunoassays demonstrated antigen sensitivity to chymotrypsin digestion and binding competition between the antibodies. The antibodies ME1 and ME2 identify a surface membrane antigen with preferential expression on normal and malignant mesothelial cells. They distinguish malignant mesothelioma from lung adenocarcinoma on cryostat sections and promise to be useful tools in biological studies of mesothelial cells.
Int J Cancer 1988 Feb 15
PMID:Monoclonal antibodies against mesothelial membrane antigen discriminate between malignant mesothelioma and lung adenocarcinoma. 327 35

Protease inhibitors are synthesized in biological systems and play a critical role in controlling a number of diverse physiological functions. They participate in blood clotting and lysis of clots, in growth processes by modulation of proteolytic digestion of proteins and thus availability of amino acids, and in the induction of selective DNA amplification. When incorporated into the diet, protease inhibitors appear to suppress many types of cancer. In vitro, they suppress neoplastic transformation caused by chemical carcinogens, ionizing radiation, and oncogenes. These observations offer the hope that judiciously applied protease inhibitors in small concentrations may prevent a wide range of human cancers. This hope is further supported by epidemiological studies which show that populations consuming relatively large amounts of protease inhibitors have a lower occurrence of cancer. The tasks remaining are to determine the kind and the level of protease inhibitors that are most effective in preventing cancer without also having toxic side effects and to incorporate them into our diet. Perhaps the most encouraging investigations are those using small nontoxic protease inhibitors available in pure form (epsilon-aminocaproic acid, a trypsin plasminogen activator inhibitor, and nicotinamide, a chymotrypsin inhibitor and known vitamin). Both agents have been shown to be preventive agents of cancer in animals and in vitro models. Further studies with natural protease inhibitors may yield even more effective agents which when incorporated into our diet will prevent the development of many types of cancer.
Adv Cancer Res 1987
PMID:Anticarcinogenic action of protease inhibitors. 331 95

Induction of a microsomal Ca2+-dependent serine protease by hepatic tumor promoters was studied. Male F344 rats were fed a diet containing one of the following promoting agents: phenobarbital (CAS: 50-06-6), dichlorophenyltrichloroethane (CAS: 50-29-3), butylated hydroxytoluene, ethyl-alpha-chlorophenoxyisobutyrate (CAS: 128-95-0), or 17-alpha-ethynylestradiol (CAS: 57-63-6) or a nonpromoting agent, diphenylhydantoin (CAS: 57-41-0), for 1 week. By treatment with promoters, the protease activity in the microsomal fraction was increased to threefold to fivefold that of control, whereas only a slight increase of activity was found after diphenylhydantoin treatment. The Ca2+-dependent protease activity was determined with the use of N-benzoyl-L-tyrosine ethyl ester as the substrate in a medium containing 50 mM CaCl2 for its maximal activity. This protease was preferentially localized in the smooth microsomal membrane and strongly inhibited by diisopropyl phosphorofluoridate (CAS: 55-91-4), and the optimum pH of the activity was 7.8. It appears that the Ca2+-dependent serine protease measured by using a chymotrypsin substrate is a novel protease, and induction of its activity by hepatic tumor-promoting agents is a common and specific phenomenon.
J Natl Cancer Inst 1986 Jul
PMID:Induction of a novel Ca2+-dependent chymotrypsin-like serine protease by tumor promoters in rat livers. 352 96

The legume-derived Bowman-Birk trypsin and chymotrypsin protease inhibitors (BBI) are effective anticarcinogens in vivo and in vitro. The chymotrypsin-inhibitory domain has been shown to be responsible for this anticarcinogenic action. In this study we identify hydrolytic enzymes by their ability to hydrolyze the relatively specific chymotrypsin substrate succinyl-Ala-Ala-Pro-Phe-aminomethyl coumarin. Results presented in this study show: there is an approximately 2-fold increase in the activity of these enzyme(s) between normal and transformed C3H/10T1/2 cells; there are five such enzymes associated with transformed cells (separated by diethylaminoethyl-cellulose chromatography); only two of these enzymes are inhibited by BBI; the BBI-inhibitable enzymes are membrane associated; the BBI-inhibitable enzymes are similar to each other but different from pancreatic chymotrypsin. BBI has thus distinguished a subpopulation of enzymes capable of hydrolyzing succinyl-Ala-Ala-Pro-Phe-aminomethyl coumarin which may mediate the transformation of C3H/10T1/2 cells.
Cancer Res 1987 Mar 15
PMID:Proteases occurring in the cell membrane: a possible cell receptor for the Bowman-Birk type of protease inhibitors. 354 48

Acid stable trypsin inhibitor having the same antigenicity as urinary trypsin inhibitor was first identified in the bile of patients with malignant tumors (biliary tract carcinoma or pancreas head carcinoma) and gallstones. Bile trypsin inhibitor from malignant tumor patients was partially purified by DEAE cellulose ion exchange column chromatography. Two molecular forms of the inhibitor were identified. The main form had a molecular weight of about 86,000 and the minor one a molecular weight of 31,000 as determined by gel filtration. Using isoelectric focussing, the larger molecular form gave a pI value of 2.0 and the smaller form, a pI value of 5.1. The isolated larger form migrated on the slightly cationic side of human serum albumin by analytical polyacrylamide gel electrophoresis. The larger form reacted and fused with anti-urinary trypsin inhibitor serum and strongly inhibited trypsin, partially inhibited chymotrypsin and plasmin, but did not inhibit urokinase. The clinical significance of acid stable trypsin inhibitor is discussed.
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PMID:Acid stable trypsin inhibitor in bile. 374 18

The Baumgartner perfusion apparatus has been used for quantitative comparison of the interaction of platelets with subendothelium in the presence of microvesicles derived from SKNMC (human neuroblastoma) cells, which aggregate platelets by an adenosine diphosphate (ADP)-dependent mechanism, and U87MG (human glioblastoma) cells, which function by a thrombin-dependent mechanism. The derived microvesicles from each line were as effective as the intact cells in inducing thrombogenesis on both undigested and alpha-chymotrypsin-digested subendothelium. Thrombus size on digested vessels was greater than on undigested vessels by fivefold for SKNMC cells and microvesicles and by 20-fold for U87MG cells and sevenfold for U87MG microvesicles. The results show that microvesicles from both cell lines initiate interactions between platelets and subendothelium identical to those caused by intact tumor cells. The results also demonstrate that intact tumor cells in the circulation may not be necessary for the thromboembolic complications of malignancy.
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PMID:Morphometric evaluation of thrombogenesis by microvesicles from human tumor cell lines with thrombin-dependent (U87MG) and adenosine diphosphate-dependent (SKNMC) platelet-activating mechanisms. 378 31

Solid and papillary epithelial neoplasms of the pancreas from six female patients were studied using immunohistochemistry and electron microscopy to define better their histogenesis. The tumors ranged in diameter from 5 to 15 cm (average: 9 cm), and, on cross section, most had areas of hemorrhage and necrosis, sometimes extensive. Microscopically, there was a solid and pseudopapillary pattern, with tumor cells typically having ovoid nuclei with delicate folding and indistinct nucleoli. Of note were the following: a relatively low mitotic rate (range: 0-6/20 hpf), the presence of hyaline globules (four of six cases), and collections of foam cells (three of six cases). Staining for cytoplasmic argyrophil granules was negative in each case. Ultrastructurally, the solid and papillary epithelial neoplasms of the pancreas showed evidence of acinar or ductular differentiation. Two contained zymogen granules, one had intermediate filaments (probably keratin), and three had abundant rough endoplasmic reticulum and mitochondria. Immunostaining was positive for chymotrypsin (six of six cases), trypsin (four of six), and amylase (three of six). None was positive for alpha-1-antitrypsin, neuron-specific enolase, pancreatic polypeptide, gastrin, glucagon, somatostatin, or insulin. The findings support an origin from exocrine pancreas, and follow-up indicates a low rate of malignancy, with local recurrence in two of the six patients.
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PMID:Solid and papillary epithelial neoplasm of the pancreas. An ultrastructural and immunocytochemical study of six cases. 381 76

We have previously shown, in the estrogen-unresponsive C3H mouse mammary tumor that the affinity of the estrogen receptor (ER) for calf thymus DNA in vitro is four-times higher than that of uterine ER [Baskevitch, P. P., Vignon, F., Bousquet, C. and Rochefort, H. (1983) Cancer Res. 43, 2290]. By mixing cytosols from this tumor and uterus, we describe a tumor factor capable of increasing ER affinity for DNA, as assayed by DNA-cellulose chromatography and saturation studies. The activity of this factor was inhibited by alpha-chymotrypsin-inhibitors such as N-tosylphenylalanylchloromethane and chymostatin. Using the fluorogenic substrate glutarylglycylglycylphenylalanyl-N-naphthylamide, we assayed such a protease in the C3H mammary tumor cytosol. This protease and the factor altering ER-DNA binding were eluted together from chromatography on DEAE-cellulose, AcA 44, and carboline-agarose and were sensitive to the same inhibitors. The partially purified factor decreases the molecular mass of the estrogen receptor as seen by denaturing electrophoresis after covalent labelling of the ER with [3H]tamoxifen aziridine. We suggest that the increase of ER affinity for DNA and the decrease of ER molecular size are due to the same protease with an alpha-chymotrypsin-like specificity.
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PMID:A cytosol protease from the estrogen-resistant C3H mammary carcinoma increases the affinity of the estrogen receptor for DNA in vitro. 388 20

Phosphoribosylglycineamide formyltransferase levels were studied in several mammalian tissues and were found to be elevated 3- to 6-fold in some anaplastic cells, including rat hepatoma H-35 and mouse leukemia L1210, as compared to their corresponding normal tissues. The enzyme was found to reside in the cytosol of chicken liver and L1210 cells. The enzyme was purified to near homogeneity, as judged by a single band on polyacrylamide gels after electrophoresis in the presence of sodium dodecyl sulfate, from two mammalian sources, mouse L1210 and mouse Sarcoma 180. Comparison of the digestion patterns of L1210 enzyme and chicken liver enzyme upon exposure to chymotrypsin showed some similarity between the two, as did cross-reactivity in Western blots of the chicken enzyme with antibodies raised to the L1210 enzyme. Subunit molecular weight of the L1210 and Sarcoma 180 phosphoribosylglycineamide formyltransferases is about 117,000. Steady-state kinetics was performed with the purified murine enzyme in the presence of 5'-phosphoribosyl-N-glycineamide and 10-formyltetrahydrofolate and with 5'-phosphoribosyl-N-glycineamide and 10-formyl-5,8-deazafolate, establishing that these mammalian enzymes utilize 10-formyltetrahydrofolate as the actual cofactor. 11-Formyltetrahydrohomofolate was found to be an inhibitor of the murine and human (HeLa) enzymes, competitive with respect to 10-formyltetrahydrofolate, with KiS of 1 and 3 microM, respectively. 11-Formyldihydrohomofolate was an inhibitor of HeLa cell growth with a 50% effective dose of 8-11 microM.
Cancer Res 1985 Oct
PMID:Characterization of mammalian phosphoribosylglycineamide formyltransferase from transformed cells. 402 81


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