Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Methylazoxymethanol is a potent carcinogen and induces tumors predominantly of the small intestine and colon following a single injection. Previous data indicated that alcohol dehydrogenase could convert this carcinogen to a reactive alkylating agent. Rats were treated with an inhibitor of this enzyme, pyrazole, 2 hr prior to their receiving the carcinogen. The development of intestinal and colonic tumors was prevented. The rats did, however, develop numerous tumors of the skin and kidney. Analyses of the complete autopsies are presented. The data indicate that intestinal and colonic alcohol dehydrogenase plays a role in the tumorigenic effects of methylazoxymethanol and that other non-pyrazole-sensitive enzymes exist in other organs that can also activate this carcinogen.
Cancer Res 1982 May
PMID:Inhibition of methylazoxymethanol-induced intestinal tumors in the rat by pyrazole with paradoxical effects on skin and kidney. 703 19

Human brain contains four forms of aldehyde reducing enzymes. One major activity, designated AR3, has properties indicating its identity with the NADPH-dependent aldehyde reductase, EC 1.1.1.2. The other major form of human brain enzyme, AR1, which is also NADPH-dependent, reduces both aldehyde and ketone-containing substrates, including vitamin K3 (menadione) and daunorubicin, a cancer chemotherapeutic agent. This enzyme is very sensitive to inhibition by the flavonoids quercitrin and quercetine, and may be analogous to a daunorubicin reductase previously described in liver of other species. One minor form of human brain aldehyde reductase, AR2, demonstrates substrate specificity and inhibitor sensitivity which suggest its similarity to aldose reductases found in lens and other tissues of many species. This enzyme, which can also use NADH as cofactor to some extent, is the most active in reducing the aldehyde derivatives of the biogenic amines. The fourth human brain enzyme ("SSA reductase") differs from the other forms in its ability to use NADH as well as or better than NADPH as cofactor, and in its molecular weight, which is nearly twice that of the other forms. It is quite specific for succinic semialdehyde (SSA) as substrate, and was found to be significantly inhibited only by quercetine and quercitrin. AR3 can also reduce SSA, and both enzymes may contribute to the production of gamma-hydroxybutyric acid in vivo. These results indicate that the human brain aldehyde reductases can play relatively specific physiologic roles.
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PMID:Multiple aldehyde reductases of human brain. 742 38

Aldose reductase and aldehyde reductase are members of the aldo-keto reductase superfamily, and participate in the reduction of a wide range of carbonyl compounds. We have purified aldose reductase from rat lens and raised antiserum against it in rabbits. Immunoblot analyses using this antibody showed that a significant amount of aldose reductase was expressed in cell lines derived from hepatomas while it was negligible in normal hepatocytes. Elevated expression of aldose reductase was also observed in cancerous lesions of 3'-methyl-4-dimethyl-aminoazobenzene (3'-Me-DAB)-induced hepatocarcinomas. Expression of aldose reductase mRNA was confirmed in these cells by Northern-blot analysis, suggesting that the induction occurred at the stage of gene transcription. The level of aldehyde reductase, however, did not change in cancerous tissue or in the cell lines. The viability of hepatoma cells in the presence of 3-deoxyglucosone and glyceraldehyde was decreased by an aldose reductase inhibitor, ONO-2235 (5-[1Z,2E)-2-methyl-3-phenylpropenylidene]-4-oxo-2-thioxo -3- thiazolidineacetic acid). Taken together, induction of aldose reductase gene expression during hepatocarcinogenesis may render cancer cells resistant to various toxic carbonyl compounds produced during metabolism or administered as anti-cancer drugs.
Int J Cancer 1995 Sep 15
PMID:Elevation of aldose reductase gene expression in rat primary hepatoma and hepatoma cell lines: implication in detoxification of cytotoxic aldehydes. 755 25

Despite modern therapy, one third to one half of patients who get breast cancer will eventually die from it. This disconcerting circumstance has focused attention on prevention, and preventing breast cancer will require a much better understanding of the biological abnormalities underlying its development and progression. Many studies into the mechanisms of invasive breast cancer evolution have evaluated presumed precursor lesions (e.g. proliferative disease without atypia, atypical ductal hyperplasia, and ductal carcinoma in-situ) for genetic alterations known to occur in fully developed invasive carcinomas. This approach has shed some light on events which may be important in early malignant transformation, including the observations that overexpression of the c-erbB-2 oncogene and mutations of the p53 tumor suppressor gene are present in significant subsets of DCIS, but not PDWA or ADH. Although this approach is limited by our incomplete knowledge of cancer genetics, there is still a great deal to learn about breast cancer evolution by evaluating cancer-associated genes in potential precursor lesions using established techniques such as immunohistochemistry and in situ hybridization.
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PMID:Immunohistochemical studies of early breast cancer evolution. 781 82

We report an 82-year-old retired man who developed syndrome of inappropriate secretion of ADH (SIADH) caused by sodium valproate (VPA). He had been taking VPA for treatment of symptomatic epilepsy due to cardioembolic stroke. Although he was clinically asymptomatic, he was found to have decreased level of serum sodium concentration (128 mEq/l). Association of hyponatremia, normal urinary sodium concentration, high urine osmolality and increased concentration of serum ADH strongly suggested the presence of SIADH. There were no underlying disorders which can cause SIADH, such as malignant neoplasm with autonomous ADH release, non-malignant pulmonary diseases and active disorders of the central nervous system. Eight days after discontinuation of VPA administration serum sodium level increased (142 mEq/l) to the normal level. Then, we started the administration of VPA again to confirm that VPA was responsible for developing hyponatremia. As a result, he developed SIADH with hyponatremia (128 mEq/l) again, which improved after discontinuation of the administration. Therefore, we concluded that the SIADH might have been caused by administration of VPA. This is the first report on adverse effect of VPA causing SIADH.
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PMID:[Valproate related syndrome of inappropriate secretion of antidiuretic hormone (SIADH)--a case report]. 782 Sep 67

Human intercellular adhesion molecule-1 (ICAM-1), a specific ligand for the lymphocyte-function-associated antigen-1, plays an important role in immune responses. ICAM-1 expression is regulated by various proinflammatory cytokines, by PMA, and by retinoic acid. In this study, we have investigated the mechanisms of transcriptional control involved in the stimulation of ICAM-1 gene expression by retinoic acid in SK-N-SH cells. Northern-blot analysis demonstrated that ICAM-1 mRNA is maximally induced at 24 hr, suggesting that it is not an early-response gene with respect to retinoic-acid responsiveness, whereas the retinoic acid receptor-beta mRNA level was maximal 12 hr following retinoic acid treatment. To analyze the 5'-regulatory region of the ICAM-1 gene, an EcoRI/SaII fragment spanning the first 1.3 kb upstream of the translational start site was used to direct the expression of a linked luciferase reporter gene in transient transfection assays in SK-N-SH cells. A 24-hr treatment of transfected cells with 10 microM retinoic acid resulted in a 10- to 13-fold increase in luciferase activity compared with untreated cells. Deletion mutant analysis revealed that a region located between -393 and -176 bp from the translational start site is critical for retinoic acid stimulation of luciferase activity. This region harbors a consensus sequence for a retinoic-acid-responsive element (RARE) homologous to the element found upstream of the alcohol dehydrogenase-3 gene. Co-transfection of expression vectors encoding the retinoic acid receptor-alpha, -beta, or -gamma, with reporter plasmids harboring the putative RARE, confirmed that the ICAM-1 gene is regulated by retinoic acid in a retinoic acid receptor-dependent fashion.
Int J Cancer 1994 Aug 15
PMID:Regulation of intercellular adhesion molecule-1 expression by retinoic acid: analysis of the 5' regulatory region of the gene. 791 15

Early breast neoplasia may be defined in many ways. Any non-invasive or invasive but nonmetastatic breast cancer qualifies as early neoplasia in the sense that they are non-lethal. Before we can prevent lethal breast cancer, we must gain a better understanding of the biological abnormalities underlying its development and progression. Many studies into the mechanisms of breast cancer evolution have evaluated potential precursor lesions (e.g., proliferative disease without atypia [PDWA], atypical ductal hyperplasia [ADH], and ductal carcinoma in situ [DCIS]) for genetic alterations known to occur in fully developed invasive carcinomas. This approach has shed some light on events which may be important in early malignant transformation, including the observations that overexpression of the c-erbB-2 oncogene and mutations of the p53 tumor suppressor gene are present in significant subsets of DCIS, but not PDWA or ADH. This approach is limited by our incomplete knowledge of cancer genetics. However, there is more to learn by evaluating known cancer-associated genes in potential precursor lesions using established techniques such as immunohistochemistry and in situ hybridization. Until recently, technology could not detect unknown genetic abnormalities in microscopic lesions such as PDWA, ADH, or DCIS. Now, PCR-based techniques have the theoretical ability to detect novel tumor promoter and suppressor genes in clinical samples of these very small lesions. For example, suppressor-type genes may be detected using comprehensive mapping probes to identify loss of heterozygosity in PCR-amplified DNA extracted from a few hundred cells microdissected from either fresh or archival tissue.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biomarkers in early breast neoplasia. 800 90

A new cancer cell line (Lu-165) producing a large amount of anti-diuretic hormone (ADH, 2.8 micrograms/g protein) was established from a 50-year-old small cell lung cancer patient presenting with a syndrome of inappropriate anti-diuretic hormone secretion. These cells grew well in serum-supplemented medium and during more than 100 passages they continued producing a large amount of this hormone. This cell line will be a useful tool for studies of the biochemistry and pathology of ADH-producing cancer.
Jpn J Cancer Res 1994 Jul
PMID:Establishment of a human small cell lung cancer cell line producing a large amount of anti-diuretic hormone. 807 Nov 14

Several enzymes metabolize the toxic aldehydes produced during lipid peroxidation, such as 4-hydroxynonenal. During carcinogenesis induced by diethylnitrosamine in rat liver, an increase in aldehyde dehydrogenase, in comparison with normal liver, has already been shown. This paper demonstrates that, although to a lesser extent than aldehyde dehydrogenase, aldehyde reductase and glutathione-S-transferase also increase during carcinogenesis. Of the latter two enzymes, aldehyde reductase increases more markedly in a progressive fashion during the months of development of nodules and hepatoma. The increase of enzymes able to metabolize 4-hydroxynonenal, as well as other aldehydes, is certainly important in protecting tumour cells against cytotoxic effect of aldehydes.
Cancer Lett 1993 Feb
PMID:Glutathione-S-transferase, alcohol dehydrogenase and aldehyde reductase activities during diethylnitrosamine-carcinogenesis in rat liver. 844 90

Seventy-five percent of esophageal cancers are alcohol related, yet alcohol is not a carcinogen. Ethanol may promote carcinogenesis via increased free radical products during its metabolism, as indicated by data from this and other studies. Ethanol is oxidized to acetaldehyde by alcohol dehydrogenase, catalase and the microsomal ethanol oxidizing system (MEOS). Free radicals (FR) are released during the oxidation of ethanol by the MEOS. An increased formation of FR in tissues would increase their oxidative stress and may increase their susceptibility for developing chemically induced cancers. FR and some FR products can rapidly react with biological materials, i.e. lipids, proteins and nucleic acids, forming toxic products. This study focuses on the effects of FR and/or FR products on cancer promotion during alcohol metabolism. Eight groups of mice were fed nutritionally adequate diets supplemented with vitamin E and/or ethanol. Some groups of mice were also orally gavaged with N-nitrosomethylbenzylamine (NMBzA), an esophageal carcinogen. Following the feeding of the various diets for 22 weeks, livers and esophagi were removed and the FR burden in the liver measured by the presence of lipid peroxide products and the number of tumors in each esophagus determined. These studies indicate that a linear relationship exists between the increasing number of esophageal tumors and increasing levels of lipid peroxide products that are formed during FR activity. These results show that FR and/or FR products are the cancer promoters during ethanol metabolism, since diets supplemented with high levels of vitamin E, which inhibits ethanol-induced FR activity and the formation of FR products, suppress the promotion of cancer by ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of cancer growth by vitamin E and alcohol. 847 Oct 82


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