Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.49 (reverse transcriptase)
 31,746 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The high event-free survival rates of Down syndrome (DS) children with acute myeloid leukemia (AML) are due, in part, to increased in vitro sensitivity of DS myeloblasts to cytosine arabinoside (ara-C) and daunorubicin and the greater generation of ara-C triphosphate (ara-CTP) from ara-C compared with myeloblasts from non-DS patients (Taub et al, Blood 87:3395, 1996). This study further explores the molecular basis of chemotherapy sensitivity of DS AML patients by examining the expression of chromosome 21-localized genes in myeloblasts from newly diagnosed AML patients. Transcript levels of two chromosome 21-localized genes, cystathionine-beta-synthase (CBS) and superoxide dismutase (SOD), measured by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), were 12.0- and 3. 8-fold higher in DS compared with non-DS myeloblasts (P <.0001 and P <.0001, respectively). Conversely, there were no significant increases in transcripts for 2 other chromosome 21-localized genes, carbonyl reductase and the reduced folate carrier. CBS transcript levels correlated with both in vitro ara-C sensitivity measured by the 3-[4,5-dimethyl-thiazol-2-yl]-2,5-diphenyltetrazolium-bro mid e (MTT) assay (P =.003) and the generation of (3)H-ara-C triphosphate (ara-CTP) after in vitro incubations with 5 micromol/L (3)H-ara-C (P =.0003). Transcripts of deoxycytidine kinase were 2.6-fold higher in DS compared with non-DS cells and may be a factor in the enhanced metabolism of ara-C in DS cells. There was no significant correlation of SOD transcripts with in vitro ara-C and daunorubicin sensitivities. Increased CBS transcripts could result in elevated CBS activity, which modulates ara-C metabolism by altering reduced folate pools, deoxycytidine triphosphate pools, S-adenosylmethionine levels, and/or methylation of the deoxycytidine kinase gene. The further identification of the molecular mechanisms of chemotherapy sensitivity of DS AML patients may lead to significant improvements in the treatment and cure of AML.
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PMID:Expression of chromosome 21-localized genes in acute myeloid leukemia: differences between Down syndrome and non-Down syndrome blast cells and relationship to in vitro sensitivity to cytosine arabinoside and daunorubicin. 1043 27

Cynomolgus and Japanese monkey kidneys, dog and pig livers and rabbit lens contain dimeric dihydrodiol dehydrogenase (EC 1.3.1.20) associated with high carbonyl reductase activity. Here we have isolated cDNA species for the dimeric enzymes by reverse transcriptase-PCR from human intestine in addition to the above five animal tissues. The amino acid sequences deduced from the monkey, pig and dog cDNA species perfectly matched the partial sequences of peptides digested from the respective enzymes of these animal tissues, and active recombinant proteins were expressed in a bacterial system from the monkey and human cDNA species. Northern blot analysis revealed the existence of a single 1.3 kb mRNA species for the enzyme in these animal tissues. The human enzyme shared 94%, 85%, 84% and 82% amino acid identity with the enzymes of the two monkey strains (their sequences were identical), the dog, the pig and the rabbit respectively. The sequences of the primate enzymes consisted of 335 amino acid residues and lacked one amino acid compared with the other animal enzymes. In contrast with previous reports that other types of dihydrodiol dehydrogenase, carbonyl reductases and enzymes with either activity belong to the aldo-keto reductase family or the short-chain dehydrogenase/reductase family, dimeric dihydrodiol dehydrogenase showed no sequence similarity with the members of the two protein families. The dimeric enzyme aligned with low degrees of identity (14-25%) with several prokaryotic proteins, in which 47 residues are strictly or highly conserved. Thus dimeric dihydrodiol dehydrogenase has a primary structure distinct from the previously known mammalian enzymes and is suggested to constitute a novel protein family with the prokaryotic proteins.
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PMID:Cloning and sequencing of the cDNA species for mammalian dimeric dihydrodiol dehydrogenases. 1047 85

Increasing evidence suggests that altered gene expression is associated with the induction and maintenance of malignancy in various organs including mouse lung adenocarcinomas. A competitive cDNA library screening (CCLS) was used to examine gene expression in 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone-induced lung adenocarcinomas from (C3H/HeJ x A/J])F1 mice. Comparisons of RNA expression in lung adenocarcinomas to those of normal surrounding lung tissue revealed altered expression in 220 clones from more than 50,000 clones screened. Fifty clones were selected for quantitative reverse transcriptase-polymerase chain reaction (PCR) analysis to verify altered expression. PCR primers were designed based on partial sequence analysis of the clones. Twenty-two clones were found to be differentially expressed in lung adenocarcinomas compared with normal lungs. GenBank database analysis showed that 14 of the 22 clones were homologous with known genes, whereas 8 clones contained novel sequences. Thirteen clones were down regulated in tumors compared to normal lung tissues, and 9 were overexpressed. The clones underexpressed or absent include adipocyte p27, carbonic anhydrase III, carbonyl reductase, cytochrome CYP2E1, skelemin, myosin, major urinary protein, and contrapsin. Overexpressed clones include Bruton's tyrosine kinase, cyclin D3, poly(A)-binding protein, alpha-fetoprotein, transferrin, and mouse B2 family repetitive sequence. Further examination of biologic implications of the differentially expressed genes in lung adenocarcinomas is necessary to understand their role(s) in mouse lung carcinogenesis.
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PMID:Detection of differentially expressed genes in mouse lung adenocarcinomas. 1129 25