Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001430 (adenoma)
 21,222 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Lipid peroxide production, antioxidant contents and activities of antioxidative protective enzymes were examined in lungs of rats exposed to clean air (control group), 0.05 ppm O3, 0.05 ppm O3 + 0.04 ppm NO2 and 0.05 ppm O3 + 0.4 ppm NO2 for 22 months. The results were compared with our previous data in rats exposed to 0.04 ppm NO2, 0.4 ppm NO2 and 4 ppm NO2 for their life span (Sagai et al., Toxicol. Appl. Pharmacol., 73, (1984) 444-456). TBA values used as an index of lipid peroxidation in the lungs were increased maximally at 9 months, but were decreased below control values in animals exposed for 18 and 22 months. Nonprotein sulfhydryl (NPSH) contents were increased maximally at 9 months, and after 18 and 22 months were decreased significantly below control values. Vitamin E (VE) contents showed a similar trend. On the other hand, enzyme activities of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), glutathione reductase (GR), glutathione peroxidase measured by using cumene hydroperoxide (cum.OOH) substrate (GPx-cum.OOH), glutathione peroxidase measured by using H2O2 as a substrate (GPx-H2O2), glutathione S-transferase (GSH-Tase) and superoxide dismutase (SOD) did not show any significant changes during this experiment. The results show that lipid peroxidation in lungs was increased synergistically by a combination of NO2 and O3 at ambient levels, and that the time of maximum lipid peroxide production was shorter than with NO2 alone. The protective ability against lipid peroxides was higher with increased lipid peroxide levels, but the inducibility was not maintained through a life span exposure to the combined gases. Additionally, two small adenomas were observed in 2 out of 18 rats in the 0.05 ppm O3 + 0.04 ppm NO2 group and a large adenoma was observed in 1 out of 18 animals in the 0.05 ppm + 0.4 ppm NO2 group exposed for 22 months.
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PMID:Biochemical effects of combined gases of nitrogen dioxide and ozone. IV. Changes of lipid peroxidation and antioxidative protective systems in rat lungs upon life span exposure. 201 15

The coupling of iodotyrosine (coupling reaction) is one of the least studied in the formation of thyroid hormone, particularly in human thyroid diseases. This paper describes a method of measuring iodotyrosine coupling catalyzed by human thyroid peroxidase (TPO) in vitro. There were two important requirements to demonstrate the coupling reaction: 1) thyroglobulin with a low thyroid hormone content, and 2) partially purified TPO. Thyroglobulin with low thyroid hormone content was obtained from Grave's and follicular adenoma tissues after propylthiouracil (PTU) therapy and L-T4 therapy, respectively. TPO was prepared from Graves' thyroid by solubilizing the 100,000 X g pellet of thyroid homogenate with sodium deoxycholate and trypsin, followed by Sephacryl S-300 gel filtration. Before the coupling reaction, thyroglobulin was iodinated with chloramine-T and potassium iodide, followed by dialysis. The coupling reaction was carried out by incubating newly iodinated thyroglobulin with TPO, diiodotyrosine, a coupling stimulator, and a H2O2-generating system (glucose and glucose oxidase) for 20 min at 37 C. After thyroglobulin was digested with Pronase, the thyroid hormone content of the thyroid digest was measured by RIA. Coupling activity was measured by the amount of newly formed T3 (nanograms of T3 per mg thyroglobulin). The time course of coupling reaction showed a progressive increase in coupling activity up to 30 min, and the reaction was temperature and pH dependent, with a pH optimum of 7.0. Coupling activity in the presence of H2O2 and TPO was 43 +/- 5.0 ng T3/mg thyroglobulin (mean +/- SD of triplicate samples), and addition of diiodotyrosine to the H2O2-TPO system caused a nearly 3-fold increase in coupling activity. This method has potential utilization for measurement of peroxidase coupling activity, since there was a linear relationship between the measured coupling activity and the amount of added TPO when the TPO concentration was over 3 micrograms/300 microliter. Methimazole (MMI) and PTU had similar potencies in inhibiting the TPO-catalyzed coupling reaction, whereas MMI was distinctly more potent than PTU as an inhibitor of TPO-mediated iodination in vitro. The different potencies of MMI in the two reactions suggest that different inhibitory mechanisms may be involved in iodination and coupling. The reducing agent, sodium metabisulfite, was also found to be a more potent inhibitor of the TPO-mediated coupling reaction than of the TPO-mediated iodination reaction. The method of iodotyrosine coupling described here may be useful to investigate the coupling step of thyroid hormone formation in human thyroid diseases.
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PMID:Coupling of iodotyrosine catalyzed by human thyroid peroxidase in vitro. 383 97

A follicular adenoma of the thyroid was 'hot' one hour after 99mTc pertechnetate administration, but 'cold' 24 h after 131I iodide administration. Incubation of the tissue in vitro demonstrated a defect in iodide binding to proteins that was abolished by addition of an H2O2 generating system. In this tissue iodide failed to inhibit TSH-induced cyclic AMP accumulation. The results show that iodide oxidation is required for its inhibitory action on cyclic AMP accumulation in human thyroid.
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PMID:Iodide organification defect in a cold thyroid nodule: absence of iodide effect on cyclic AMP accumulation. 632 51

The intracellular localization of Cu/Zn- and Mn-superoxide dismutase (SOD), which catalyze the dismutation of superoxide radicals (O2-) to O2 and H2O2, was studied in the thyroid tissue of various thyroid disorders by an immunohistochemical technique. The concentrations of both SODs in those tissues were measured also by a sandwich enzyme immunoassay technique. Copper/zinc-SOD in thyroid tissues were identified by immunocytochemical staining in most cases of papillary carcinoma and in some cases of other thyroid disorders. In normal follicular cells this enzyme is localized in the perinuclear cytoplasm, whereas in thyroid tumor or hyperplastic follicular cells it exists homogeneously in cytoplasm. Manganese-SOD stained strongly in papillary carcinoma and papillary-growing cells in the thyroid tissue of adenoma and Graves' disease. The concentrations of Cu/Zn-and Mn-SOD in thyroid tumor tissues and hyperplastic follicular disorders were significantly higher than those in normal thyroid tissue when they were compared as a function of protein or deoxyribonucleic acid contents. The ratio of Mn-SOD to Cu/Zn-SOD was significantly higher only in papillary carcinoma, except for other thyroid disorders as compared with that in the normal thyroid. In conclusion, SOD seems to be related to cell proliferation and differentiation in the thyroid follicular cell because Cu/Zn-SOD changes its localization in tumor and hyperplastic follicular cells and because the Mn-SOD concentration is increased in papillary carcinoma or papillary-growing cells.
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PMID:Localization of Cu/Zn and Mn superoxide dismutase in various thyroid disorders. 750 2

Several biochemical and functional modifications demonstrated in goitrous tissues could reflect the effect of goitrogenic factors. Growth-enhancing agents, including TSH itself, have been involved in goitrogenesis. To study comparatively the variation patterns of some TSH-dependent enzymes within single goitrous tissues, we measured the activities of peroxidase (TPO), NADPH-cytochrome-c (cyt-c) reductase, and monoamine oxidase (MAO) in tissues from cold follicular adenoma and multinodular goiter. Iodide transport and organification were also evaluated. Perinodular and necropsy tissues were used as controls. The mean TPO activity measured by guaiacol as well as triiodide assays was significantly increased in multinodular goiter, whereas a nonsignificant increment was observed in cold adenoma. NADPH-cyt-c reductase and MAO were markedly increased in the two types of pathological tissues. The individual activities of the three enzymes showed dissimilar modifications within single samples and among different tissues. There was no correlation in the activities of the enzymes within single specimens from cold adenoma and multinodular goiter, except for MAO and NADPH-cyt-c reductase in multinodular goiter, for which a significant correlation was obtained. In this tissue, MAO and TPO measured by guaiacol assay were weakly correlated. TPO activity evaluated by guaiacol oxidation was correlated with that measured by triiodide formation in cold adenoma, but not in multinodular goiter. The mean iodide organification values assayed by iodotyrosine formation in the absence of exogenous H2O2 in particulate fractions from cold adenoma and multinodular goiter were within the normal range. A reduced iodide transport, evaluated as the thyroid/medium ratio, was observed in slices from these tissues. The dissociation of the three enzyme activities in single specimens from cold adenoma and multinodular goiter along with the reduced iodide transport in these tissues support the hypothesis that factors other than TSH or with TSH-like effects could be involved in the abnormal thyroid growth.
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PMID:Dissociation of thyrotropin-dependent enzyme activities, reduced iodide transport, and preserved iodide organification in nonfunctioning thyroid adenoma and multinodular goiter. 802 49

The localization of Cu/Zn and Mn superoxide dismutase (SOD), which catalyzes the dismutation of superoxide radicals (O2-) to O2 and H2O2, in various thyroid disorders was studied by an immunohistochemical technique in 20% formalin fixed paraffin embedded thin sections using anti-human Cu/Zn and Mn-SOD antibodies. The concentrations of both SODs in those tissues were also measured by a sandwich enzyme immunoassay technique. Cu/Zn SOD was immunocytochemically stained in most of papillary carcinoma, and some of other disorders. In the normal follicular cells it localized in the perinuclear cytoplasm, whereas in the tumor or hyperplastic cells it was in the cytoplasm homogeneously. Mn SOD was strongly stained in papillary carcinoma and papillary growing cells in adenoma and Graves' disease. The concentrations of Cu/Zn and Mn SOD in every thyroid disorder were higher than those in normal thyroid, and it was much higher in the malignant tumors. The ratio of the concentration of Mn SOD against Cu/Zn SOD in the tissues was higher only in papillary carcinoma compared with that in normal thyroid. In conclusion, SOD seems to be relating to the cell proliferation and differentiation in the thyroid since both SODs increased in tumors and hyperplastic disorders, and Cu/Zn SOD changed its localization and Mn SOD existed predominantly in papillary carcinoma or papillary growing cells.
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PMID:[Study of the localization and the concentration of superoxide dismutase in various thyroid disorders]. 823 85

Although attention has focused on the chemopreventive action of retinoic acid (RA) in hepatocarcinogenesis, the functional role of RA in the liver has yet to be clarified. To explore the role of RA in the liver, we developed transgenic mice expressing RA receptor (RAR) alpha- dominant negative form in hepatocytes using albumin promoter and enhancer. At 4 months of age, the RAR alpha- dominant negative form transgenic mice developed microvesicular steatosis and spotty focal necrosis. Mitochondrial beta-oxidation activity of fatty acids and expression of its related enzymes, including VLCAD, LCAD, and HCD, were down-regulated; on the other hand, peroxisomal beta-oxidation and its related enzymes, including AOX and BFE, were up-regulated. Expression of cytochrome p4504a10, cytochrome p4504a12, and cytochrome p4504a14 was increased, suggesting that omega-oxidation of fatty acids in microsomes was accelerated. In addition, formation of H2O2 and 8-hydroxy-2'-deoxyguanosine was increased. After 12 months of age, these mice developed hepatocellular carcinoma and adenoma of the liver. The incidence of tumor formation increased with age. Expression of beta-catenin and cyclin D1 was enhanced and the TCF-4/beta-catenin complex was increased, whereas the RAR alpha/ beta-catenin complex was decreased. Feeding on a high-RA diet reversed histological and biochemical abnormalities and inhibited the occurrence of liver tumors. These results suggest that hepatic loss of RA function leads to the development of steatohepatitis and liver tumors. In conclusion, RA plays an important role in preventing hepatocarcinogenesis in association with fatty acid metabolism and Wnt signaling.
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PMID:Retinoic acid receptor alpha dominant negative form causes steatohepatitis and liver tumors in transgenic mice. 1536 41

Cold thyroid nodules (CTNs) represent a frequent endocrine disorder accounting for up to 85% of thyroid nodules in a population living in an iodine-deficient area. Benign CTNs need to be distinguished from thyroid cancer, which is relatively rare. The molecular etiology of benign CTNs is unresolved. To obtain novel insights into their pathogenesis, protein expression profiling was performed in a series of 27 solitary CTNs (10 follicular adenoma and 20 adenomatous nodules) and surrounding normal thyroid tissues using two-dimensional gel electrophoresis combined with mass spectrometry analysis, Western blotting, and immunohistochemistry. The proteome analysis revealed a specific fingerprint of CTNs with up-regulation of three functional systems: 1) thyroid cell proliferation, 2) turnover of thyroglobulin, and 3) H2O2 detoxification. Western blot analysis and immunohistochemistry confirmed the proteome data and showed that CTNs exhibit significant up-regulation of proteins involved in thyroid hormone synthesis yet are deficient in T4-containing thyroglobulin. This is consequential to intranodular iodide deficiency, mainly due to cytoplasmic sodium iodide symporter localization, and portrays the CTN as an activated proliferating lesion with an intranodular hypothyroid milieu. Furthermore, we provide preliminary evidence that up-regulation of H2O2 generation in CTNs could override the antioxidative system resulting in oxidative stress, which is suggested by the finding of raised 8-oxo-guanidine DNA adduct formation in CTNs.
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PMID:Proteomic profiling of cold thyroid nodules. 1719 41

In the colorectal epithelium oxidative stress is observed endogenously in premalignant adenoma cells or induced by nutritional factors like fatty acid hydroperoxides (LOOH). Bioactive phenols like resveratrol and quercetin can quench reactive oxygen species and protect from pro-oxidative damage. Our study used colorectal adenoma and carcinoma cell lines to assess antioxidant protective effects of resveratrol and quercetin. It demonstrated that both compounds efficiently protect from oxidative stress induced by LOOH. Effective concentrations (10 microM resveratrol and 1 microM quercetin) can easily be reached in the intestinal lumen after consumption of plant foods or food supplements. Both compounds prevent LOOH-induced formation of intracellular H2O2, stimulation of cyclooxygenase-2 and vascular endothelial growth factor. For reduction of endogenous H2O2 levels in colorectal tumor cells higher antioxidant-concentrations are needed in all cell lines. Quercetin (10 microM) alone even increased H2O2 in LT97 adenoma cells and stimulated VEGF production. Resveratrol and quercetin also induced 10-30% and 40-60% cell loss respectively by apoptosis. In summary, this indicates that resveratrol and quercetin have little protective capacity in absence of exogenous stress. They are however highly efficient in protecting against nutrition induced oxidative stress damage suggesting that this constitutes the major part of their tumor protective activity.
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PMID:The dietary antioxidants resveratrol and quercetin protect cells from exogenous pro-oxidative damage. 1793 64

An extract of the Mediterranean carob (Ceratonia siliqua L.) pod (carob fibre extract), products formed after its fermentation by the gut flora and the major phenolic ingredient gallic acid (GA), were comparatively investigated for their influence on survival and growth parameters of colon adenocarcinoma HT29 cells and adenoma LT97 cells. Hydrogen peroxide (H2O2) formation in the cell culture media was quantified. After 1h 97+/-4 microM or 70+/-15 microM were found in HT29 medium and 6+/-1 microM or 3+/-3 microM in LT97 medium for carob fibre extract or GA, respectively. After 72 h carob fibre extract reduced survival of rapidly proliferating HT29 cells (by 76.4+/-12.9%) whereas metabolic activity and DNA-synthesis were only transiently impaired. Survival of slower growing LT97 cells was less decreased (by 21.5+/-12.9%), but there were marked effects on DNA-synthesis (reduction by 95.6+/-7%, 72 h). GA and fermented carob fibre did not have comparable effects. Thus, carob fibre extract resulted in H2O2 formation, which, however, could not explain impairment of cell growth. The differently modulated growth of human colon cell lines was more related to proliferation rates and impairment of DNA-synthesis than to H2O2 formation.
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PMID:Carob fibre compounds modulate parameters of cell growth differently in human HT29 colon adenocarcinoma cells than in LT97 colon adenoma cells. 1795 May 17


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