Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.11.2 (prolyl hydroxylase)
 1,814 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A staging scheme for hepatocellular carcinoma was presented at an International Symposium on Liver Cancer in Kampala, Uganda in 1971. Historical, clinical, and laboratory aspects of that staging scheme were examined for prognostic significance in 72 untreated patients with this disease studied at the Uganda Cancer Institute. The median survival for the entire group was 1 month. The presence of a serum bilirubin concentration of greater than 2 mg/100 ml or weight loss greater than 25 percent of body weight were the poorest prognostic features. Other factors with prognostic significance were visible abdominal collateral circulation, ascites, tumor differentiation, and serum levels of alkaline phosphatase, SGOT, alpha fetoprotein, and proline hydroxylase. A modified staging scheme is presented which defines three prognostically different groups of Ugandan patients. It is hoped this staging scheme will serve as a stimulus for analysis of similar prognostic features in other populations of patients with hepatocellular carcinoma.
Cancer 1975 May
PMID:A staging system for hepatocellular carcinoma: prognostic factors in Ugandan patients. 4 61

A sensitive assay system, optimally supplemented with tritiated protocollagen substrate and cofactors, is described which is suitable for determining the peptidyl proline hydroxylase (PPH) content of a wide spectrum of rat tissues. In most tissues, less than 50 percent of the total activity was soluble; the particulate portion of the activity (concentrated in the mitochondrial and microsomal fractions) was doubled by pretreatment with Triton X-100. Among normal adult tissues, lung had the highest total PPH activity (2.4 times that of liver) and small intestine had the lowest (25 percent that of liver). In brain and lactating mammary gland, the activity was similar to that in skin (60 percent of that in liver). Fetal tissues contained 3 to 8 times more PPH than the corresponding adult tissues, and a much lower portion of the total activity was soluble. In four tissues studied in detail (lung, liver, kidney, and brain), the total PPH declined rapidly during the last few days of gestation; brain attained its low adult value before term, whereas the other three tissues continued to decrease in the course of postnatal development. An injection of cortisol to fetal rats enhanced the decline of PPH in lung, liver, and skull. These experiments suggest that during normal differentiation the decline in collagen synthesis is initiated by fetal glucocorticoid secretion which is maximal on the 19th gestational day. PPH activity appears to be a sensitive indicator of neoplastic growth. In renal, mammary, muscle, and hepatic tumors, the PPH activities were 4 to 10 times higher than in the cognate adult tissue. Even in well-differentiated, slowgrowing tumors, the activity was considerably higher than in any normal, mature, or immature tissue, with the exception of the skull and lung of the 19-day-old fetus.
Cancer Res 1975 Apr
PMID:Peptidyl proline hydroxylase in adult, developing, and neoplastic rat tissues. 16 93

Thirty-two scirrhous cancers of breast have been examined to determine the origin of the collagen stroma in these tumours. Employing two immunohistochemical techniques it has been shown that the malignant epithelial cells in 30 of these tumours contain not only collagen but also prolyl hydroxylase, a key enzyme in collagen biosynthesis. Neither this enzyme nor collagen was detectable in the spindle cells in the stroma of these tumours. Neither the epithelium in normal breast, that in fibrocystic disease and in fibroadenomata, nor the malignant epithelium in two medullary cancers of breast contained either collagen or prolyl hydroxylase. These results strongly suggest that the malignant epithelium of scirrhous breast cancers produces its own collagen stroma and that the scirrhous reaction in these tumours is not a host response to tumour invasion. The production of collagen and prolyl hydroxylase by breast cancer cells (of the scirrhous type) therefore represents another example of inappropriate protein production by a human tumour.
Br J Cancer 1975 Jun
PMID:Inappropriate production of collagen and prolyl hydroxylase by human breast cancer cells in vivo. 16 65

Transformation of chick embryo fibroblasts by Rous sarcoma virus inhibited their ability to synthesize collagen. Kinetic experiments showed that 72 hours after infection, collagen synthesis was reduced by 90%. Nontransforming Rous-associated viruses did not inhibit collagen synthesis. The inhibition resulted from the failure of the cells to synthesize collagen polypeptides rather than from a decrease in the activity of prolyl hydroxylase; the levels of prolyl hydroxylase were fourfold those in uninfected cells. The addition of dibutyryl cyclic AMP and theophylline, alone or together, did not restore collagen synthesis.
J Natl Cancer Inst 1975 Oct
PMID:Loss of ability to synthesize collagen in fibroblasts transformed by rous sarcoma virus. 17 26

Considerable thymidine kinase and pyrroline-5-carboxylate reductase activities were found in the plasma of rats bearing a transplanted lymphoma; neither activity was detected in plasma of hosts carrying hepatic, renal, mammary, or submaxillary gland tumors. All host livers exhibited signs of biochemical immaturity as indicated by the appropriate increases or decreases in the concentrations of the nine enzymes measured. The extent and time schedule of the changes in host liver varied with the enzyme and with the tumor that caused them. The hepatic concentrations of ornithine aminotransferase, arginase, pyrroline-5-carboxylate reductase, and glucokinase (all diminished), and of peptidyl proline hydroxylase and hexokinase (increased) were sensitive indicators of tumor growth in general. The concentration of ornithine aminotransferase decreased before the tumors became palpable. At more advanced stages, the high hepatic thymidine kinase activity distinguished the presence of hepatoma and lymphoma from those of all other equally fast-growing tumors. However, only in lymphoma-bearing rats did a fivefold elevation of hepatic thymidine kinase occur as early as 4 days after implantation. Additional observations on the lymphoma itself, on blood cells, and on the involuting thymus of normal rats indicate that the striking systemic effects of this tumor cannot be explained by a release of enzymes from the thymus or by the increased number of lymphoma cells present in blood or liver.
Cancer Res 1977 Jan
PMID:The effect of lymphoma and other neoplasms on hepatic and plasma enzymes of the host rat. 18 34

The concentrations of 16 to 21 enzymes, representing various metabolic pathways, have been determined in human adult, fetal, and neoplastic lung. At midgestation, 12 enzymes (among them, several that metabolize amino acids) were above their adult values while 3 other enzymes were still at low concentrations. These signs of biochemical immaturity are contrasted and compared with those in fetal human liver and rat lung. The enzymic composition of the 11 human pulmonary tumors studied resembled that of the normal fetal lungs closely; the same 12 enzymes were elevated and the same 2 were decreased (compared to nonneoplastic adult lung) in both. The characteristic abnormality in the overall pattern of enzymes, in the concentrations of individual ones, and in the quality of pyrroline-5-carboxylate reductase was clearly evident in both primary and metastatic tumors. The mean concentrations of 10 enzymes in the tumors were significantly different (higher or lower) from those in the control lungs (p less than 0.001 to less than 0.05). The best markers of neoplasticity were thymidine kinase, peptidyl proline hydroxylase, phosphoserine phosphatase, hexokinase, and pyrroline-5-carboxylate reductase. The results demonstrate that quantification of a small battery of enzymes, none of them tissue specific, can distinguish adult human lung from its neoplasms.
Cancer Res 1977 Mar
PMID:The undifferentiated enzymic composition of human fetal lung and pulmonary tumors. 18 17

The effect of the potent tumor promoter phorbol 12-myristate 13-acetate (PMA) on collagen synthesis, a differentiated property of chick embryo fibroblasts, was examined. Collagen synthesis, as measured by the rate of formation of [3H]hydroxyproline from [3H]proline, was found to be decreased in cells treated with PMA but not in cells treated with the parent alcohol phorbol. The decrease in collagenase-sensitive proteins was confirmed by polyacrylamide gel electrophoresis of cell lysates, indicating that the decrease could not be ascribed simply to an effect on prolyl hydroxylase. Although a decrease in collagen synthesis was observed after one day, five days were required for a maximal reduction to 20% of that of dimethyl sulfoxide-treated controls. The effect of PMA on collagen synthesis was reversible. It was therefore not the result of a permanent transformation of the cells or of the selection of a population of cells with a reduced capacity for collagen synthesis. Collagen synthesis was decreased in chick embryo fibroblasts transformed by Rous sarcoma virus. Treatment of these cells with PMA for 5 days brought about a further decrease to 50% of the level in dimethyl sulfoxide-treated transformed controls.
Cancer Res 1979 May
PMID:Decrease in collagen production in normal and Rous sarcoma virus-transformed chick embryo fibroblasts induced by phorbol myristate acetate. 21 32

The enzymic composition of 7 human mesothelioma lines propagated in nude mice was compared with 4 of the original and 15 additional mesotheliomas sampled during the patients' surgery. The xenografts exhibited several-fold higher thymidine kinase (TK), uridine kinase (UK), phosphoserine phosphatase (PSP) and peptidyl proline hydroxylase (PPH) concentrations than the fresh human samples, while their DNA, gamma-glutamyl transpeptidase (GGT) and beta-galactosidase (Bgal) contents remained similar. The volume growth rate of the xenografts (doubling time, DT = 9.23 +/- 1.25 days) was much faster than that of tumors in the human host, and the decline of this rate with increasing nodule size was accompanied by decreases in TK and PSP concentrations. This first quantitative biochemical study of xenografted human neoplasms indicates that 1) pleural mesotheliomas, though preserving their histological characteristics after heterotransplantation, show considerable increases of enzymes in nucleic acid, collagen, and nonessential amino acid synthesis, and that 2) the concentration of TK is a good indicator of the different growth properties of tumors in a mouse rather than in the human host.
Cancer Biochem Biophys 1991 Aug
PMID:Enzymic composition and growth rate of human pleural mesothelioma transplants in nude mice. 176 9

Cancer's random, reversible, unstable transitions to "normal" structures imply their functional relation. Similar random, continuous, reversible oncogene "mutational transformation" also lacks a consistent hybrid. Positing cancer's "mutationally altered genotype" leads to medically foreign causes, qualities, inducers, suppressors, immune proteins, and viruses. Its random variation, however, opposes the functionally discrete, ordered, stable, irreversible hybrid variation and single-valued transforms of molecular genetics. There, "causal mutational operators" remain unspecified; only consistent single-valued DNA base and amino acid change, as "transform operand", are made explicit. A mitotically "blocked" (normal) and "unblocked" (malignant) stem cell "phenotype", operationally constructed from microscopic data, is therefore viewed within the homeostatic context of open-system enzyme-regulatory equilibrium. This functional, stochastic field distribution between "structurally bound" and "freely dividing" stem cell number discloses their putative regulatory mitotic-blocking factor. A tyrosinase complex, interacting by Cu2+-Fe2+ chelation with a proline hydroxylase divisional enzyme near stem cell ribosomes, maintains steady-state mitotic equilibrium. Based upon familiar medical, biochemical, and energy principles this confronts cancer's pigmentary-depigmentary signs, glycolytic metabolism, elevated serum tyrosinase, defective collagen production, exposed membrane binding sites, and tyrosine's recent growth control role.
 ...
PMID:A membrane-specific tyrosinase chelate: the mitotic regulator? 311 30

Male Fischer 344 rats were given a single lung instillation of bleomycin sulfate (0.6 units/100 g). some animals were treated 24 hr after bleomycin administration with triamcinolone diacetate. Steroid treatment was continued on alternate days for 4 weeks. At the end of 4 weeks, the lungs of rats receiving bleomycin alone had two-fold increases of both prolyl hydroxylase activity and proteinaceous hydroxyproline as compared to control values. The lungs of bleomycin-treated rats which received 4 mg of triamcinolone diacetate per kg on alternate days had a 33% increase of prolyl hydroxylase activity and proteinaceous hydroxyproline content of bleomycin-treated animals receiving glucocorticoid (8 mg/kg) on alternate days were the same as control values. The results indicate that alternate day administration of the synthetic glucocorticoid triamcinolone diacetate blocks lung collagen accumulation following a single intratracheal dose of bleomycin to rats.
Cancer Res 1982 Feb
PMID:Inhibition of collagen accumulation by glucocorticoids in rat lung after intratracheal bleomycin instillation. 617 11


1 2 3 4 5 6 7 8 9 10 Next >>