Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultured mouse blastocysts produce plasminogen activator, a protease that converts the zymogen plasminogen into the trypsin-like enzyme, plasmin. We have fractionated the blastocyst and cultured the constituent cell types. Trophoblast outgrowths free of inner cell mass derivatives secrete plasminogen activator during a time period that closely parallels the invasive phase of trophoblast cells in utero. Isolated inner cell masses also produce plasminogen activator; further fractionation of the inner cell mass as well as studies with primary cultures obtained from midgestation tissues demonstrate that enzyme formation is restricted entirely to parietal endoderm cells. Secretion of the enzyme may facilitate the migration of parietal endoderm cells along the trophoblast layer as the yolk sac cavity enlarges during gestation. F9 embryonal carcinoma cells do not secrete detectable amounts of plasminogen activator. However, when these cells are induced to differentiate, the resulting parietal endoderm-like cells are capable of producing the enzyme. These results are consistent with previous findings suggesting that plasminogen activator production may be a characteristic of invasive and/or migratory cells.
Cancer Res 1976 Nov
PMID:Differentiation of early mouse embryonic and teratocarcinoma cells in vitro: plasminogen activator production. 97 58

Insulin, a mitogen for cultured chick embryo fibroblasts (Temin, H.M. (1968) Cancer 3, 771-787), has been employed to characterize the effects of mitogen/cell membrane interactions as it relates to growth. The specific binding of 125I-insulin to substratum-attached cells is time- and temperature dependent and is optimum at a pH of 7.0. Fetal calf and chicken sera, somatomedin "A/C mixed," and desalanine or native porcine insulin compete with 125I-insulin for membrane-binding sites. Proinsulin, although competing less effectively than native insulin for binding, is more effective than desoctapeptide insulin. Unrelated polypeptide hormones do not compete for 125I-insulin binding. The lowest concentration of insulin at which specific binding is detected is 0.1 nM. Scatchard plot analysis of the binding data indicates that there are two types of binding sites in confluent cultures of fibroblasts: one of high affinity (K1 = 2 to 6 X 10(8) M-1) and low capacity, the other of low affinity (K2 = 0.8 to 3.0 X 10(7) M-1) and high capacity. Approximately 1.9 and 7.1 X 10(3) molecules of insulin are bound at each site, respectively. A 10-min incubation at 24 degrees of the fibroblasts with 10 mug/ml of trypsin causes a 2-fold stimulation of specific 125I-insulin binding and a similar 2-fold increase in insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation. Neuraminidase treatment also produces a 37% increase in specific 125I-insulin binding but treatment with alpha-chymotrypsin or phospholipase C are without significant effect. The results of this and additional experiments support the hypothesis that trypsin treatment of chick embryo fibroblasts leads to an unmasking of 125I-insulin binding sites. Serum starvation of fibroblasts for 12 or 24 h produces a 2.5- to 5-fold increase in specific 125I-insulin binding. This increase is the result of an increase in the number of hormone-binding sites from 9 X 10(3) to 6 X 10(4) per cell which are predominantly of the low affinity type. There is no change in the affinity constants. The presence of camptothecin, or cordycepin, or cycloheximide in the incubation medium completely blocks the increase in number of 125I-insulin-binding sites resulting from serum starvation. The addition of native insulin to the medium of serum-starved cultures also blocks this increase. The magnitude of insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation correlates with the levels of occupancy of the low affinity 125I-insulin-binding sites in untreated fibroblasts. In fibroblasts cultured in the absence of serum, the marked increase in insulin-stimulated 2-deoxy-D-glucose uptake and thymidine incorporation parallels the increase in number of mitogen receptors. The concentration of insulin that produces a half-maximum stimulation of thymidine incorporation is calculated to be 5 X 10(-8) M. At this concentration of insulin, 42% of the receptor sites are occupied.
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PMID:Mitogen receptors in chick embryo fibroblasts. Kinetics, specificity, unmasking, and synthesis of 125I-insulin binding sites. 98 22

Glycopeptides suggesting a complex oligosaccharide composition are present on the surface of cells from human neuroblastoma tumors and several cell lines derived from the tumors. The glycopeptides, labeled with radioactive L-fucose, were removed from the cell surface with trypsin, digested with Pronase, and examined by chromatography on Sephadex G-50. Human skin fibroblasts, brain cells, and a fibroblast line derived from neuroblastoma tumor tissue show less complex glycopeptides. Although some differences exist between the cell lines and the primary tumor cells, the similarities between these human tumors and animal tumors examined previously are striking.
Cancer Res 1976 Dec
PMID:Glycopeptides from the surgace of human neuroblastoma cells. 100 Apr 97

A serum factor (SF), isolated from acidified sera of normal donors, inhibited phytohemagglutinin (PHA) stimulation of lymphocytes isolated from patients with chronic lymphocytic leukemia (CLL),but had no effect on those from healthy donors. An SF isolated by an identical procedure from the sera of patients with CLL had essentially no inhibitory effect on DNA synthesis in normal or leukemic lymphocytes. The SF was isolated from sera or plasma by ammonium sulfate precipitation, acidification to pH 1.5, and chromatography on DEAE-cellulose. The SF was heat labile and sensitive to digestion by trypsin. Maximum inhibition was obtained when the factor was added within 24 hours after the cells were stimulated with PHA.
J Natl Cancer Inst 1976 Jul
PMID:Serum factor: the inhibition of phytohemagglutinin-induced blastogenesis of chronic lymphocytic leukemia lymphocytes. 100 3

Incubation of 20,000 X g supernatant proteins of rat liver with benzo]a]pyrene (BP) and appropriate cofactors produced metabolites of BP covalently bound at the 4,5- position to protein. After being incubated, protein samples were freed from noncovalently bound metabolites and hydrolyzed chemically or both enzymatically and chemically. All steps were performed under minimum exposure to light and air; benzene extracts were prepared during hydrolysis. Chemical hydrolysis released the K-region metabolite BP-4,5-dihydrodiol (identified by UV and mass spectra) and BP. Hydrolysis with trypsin and pronase gave products with the characteristic UV spectrum of substituted chrysene. Chemical hydrolysis of these products released BP and BP-4,5-dihydrodiol.
J Natl Cancer Inst 1976 Jul
PMID:Covalent binding to protein of the K-region oxide of benzo(a)pyrene formed by microsome incubation. 100 7

A simple liquid culture technique has been used to study peripheral blood from patients with acute myelogenous leukaemia. Evidence is presented that cells from morphologically identical types of leukaemia have differing capacity for "differentiation" from free floating blast cells into plastic-adherent phagocytic, trypsin-resistant macrophage-like cells with Fc and C3 receptors. Preliminary analysis suggests that patients whose cells have the greatest capacity for "differentiation" have a better chance of achieving complete remission.
Br J Cancer 1976 Apr
PMID:Diagnostic and prognostic significance of peripheral blood cultural characteristics in adult acute leukaemia. 106 91

Immunological studies are presented on a patient with a long clinical history suggesting the existence of a tumor-specific immune response. His tumor, first considered benign, progressed to a highly malignant osteosarcoma. Cell-mediated immune reactivity against biopsy cells and against tumor extract was detected in vitro by the autologous tumor stimulation test (ATS) and in vivo by the skin test. In one ATS-test with tumor extract, blastogenesis of T-cells was demonstrated. The amount of Ig(s) in consecutive biopsies increased. Biopsies taken in the later period of the disease stimulated only after trypsin treatment. This stimulation was inhibited by autologous serum or acid eluate of the biopsy. The inhibitory factor in the serum was not intact immunoglobin. Blood lymphocytes did not show a discriminatory or disease-related cytotoxicity, either directly or after co-cultivation with the tumor material. Lymphocytes isolated from one biopsy were non-reactive in both the ATS and the cytotoxicity test.
Int J Cancer 1976 Sep 15
PMID:Search for anti-tumor response in a bone tumor patient with a long clinical history. 106 20

Peripheral blood leukocytes from 31 out of 48 patients with acute myelogenous leukemia grew in short-term liquid culture. Two distinct types of growth occurred. The first type was dimorphic with supernatant free-floating ("non-sticker") cells and, in addition, a plastic/glass adherent, trypsin resistant, phagocytic population ("stickers"). The second type which occurred less frequently than the first consisted almost entirely of free-floating "non-sticker" cells. Although patients with this second type of growth pattern almost invariably had AML, 44% of AML's produced monocytoid "sticker" cells in culture. Cells from the majority of patients with ALL did not grow in culture.
Recent Results Cancer Res 1976
PMID:Morphological characterisation of adult acute leukaemia in short-term liquid culture. 107 63

Regressing and progressing Moloney sarcomas, induced in BALB/c mice by the injection of cultured sarcoma cells (MSC)1, were sampled for histologic analysis and then disaggregated using mixtures of trypsin, collagenase and DNAse or collagenase and DNAse alone. The types of inflammatory cells (IC) found in resultant cell suspensions were determined 6, 11, 14 and 18 days post inoculation. Inflammatory infiltrates were composed almost exclusively of three cell types; neutrophils, T lymphocytes and macrophages. The extent to which each was found in tumors was related to the time post inoculation. Neutrophils were part of an early acute inflammatory response seen in both developing regressing and progressing sarcomas. The onset of regression was associated histologically with the appearance within tumors of a mononuclear inflammatory infiltrate. T lymphocytes and macrophages were the principal constituents. A higher percentage of T lymphocytes was recovered at all sampling times from regressing, compared to progressing, sarcomas. During development of the mononuclear inflammatory infiltrate there were relatively more large T cells in regressing, than in progressing tumors, and the percentage of macrophages was higher. Thereafter, the proportion of macrophages in the recovered cell population was approximately the same for both types of tumor. Such equality was more apparent than real, however, since IC were restricted to the peripheries of progressing sarcomas after the acute inflammatory phase, but continued to be found throughout regressing neoplasms. The effective ratio of macrophages and T lymphocytes to tumor cells therefore was much lower in progressing sarcomas than was suggested by percentage figures. The data presented support the concept that T lymphocytes are instrumental in causing the regression of Moloney sarcomas, possibly through interactions with macrophages.
Int J Cancer 1976 Sep 15
PMID:Inflammatory cells in solid murine neoplasms. II. Cell types found throughout the course of Moloney sarcoma regression or progression. 108 89

Serum alpha1-antitrypsin Pi types and trypsin inhibitory capacity (TIC) were measured in 72 patients with lung cancer and in 196 patients with abnormal sputum cytology but no clinical evidence of lung cancer to determine if a genetic deficiency of alpha1-antitrypsin (AAT) predisposes to lung cancer. The distributions of Pi types in these two groups of patients and healthy adults are similar. Serum TIC and AAT concentrations are elevated in lung cancer patients. However, patients with abnormal sputum cytology and no clinical lung cancer have normal levels of serum TIC and AAT. A genetic deficiency of AAT probably does not produce a state of increased susceptibility to the carcinogenic effects of respiratory carcinogens such as tobacco smoke.
Cancer 1976 Oct
PMID:Serum alpha1-antitrypsin in patients with lung cancer or abnormal sputum cytology. 108 7


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