Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single dose of cis-dichloro(dipyridine)platinum(II) (cis-PPC), when given to BDF1 mice bearing 1-day-old L1210 leukemia, suppressed the increase of spleen and liver ornithine decarboxylase (ODC) activity which occurs concomitantly with development of the leukemia. The inhibition of ODC, the rate-limiting enzyme in polyamine synthesis, appeared to correlate with the prolonged chemotherapeutic efficacy of a single dose of the platinum complex. These observations suggest an additional mechanism by which platinum complexes express their antitumor actions and, in addition, support the view that polyamine synthesis and excretion patterns can be used as predictors of chemotherapeutic response.
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PMID:The effects of single administration of an antitumor platinum compound on ornithine decarboxylase activity in certain tissues of mice bearing L1210 leukemia. 107 May 17

The Odc-rs8 locus belongs to a family of mouse DNA sequences related to the gene encoding ornithine decarboxylase (ODC). Odc-rs8 was mapped by recombinant inbred (RI) strain analysis to the region of Chromosome (Chr) 12 occupied by the variable region genes of the immunoglobulin heavy chain (Igh) complex. In the present study, alleles at Odc-rs8 were shown to cosegregate with those for Igh variable region (Igh-V or VH) genes among 37 inbred mouse strains that had been characterized previously for their haplotypes at Igh. For a more precise definition of the location of Odc-rs8 relative to Igh-V, DNAs from 17 Abelson murine leukemia virus (A-MuLV)-transformed pre-B cell lines cultured from mice heterozygous at Igh and Odc-rs8 were analyzed for the presence of DNA restriction fragments (RFs) derived from each parental Odc-rs8 allele. These cell lines, each of which has rearranged one or both Igh genes, previously were employed in mapping members of nine VH gene families by deletion analysis (Brodeur et al. 1988). Comparing the deletion profiles of the cell lines for Odc-rs8 with those for the VH gene families has located Odc-rs8b within the VHJ558/VH3609 gene cluster and Odc-rs8c either within or upstream of the 5'-most 9% of VHJ558, identifying Odc-rs8 as a potentially useful marker for the 5' end of the Igh complex.
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PMID:Deletion mapping of the mouse ornithine decarboxylase-related locus Odc-rs8 within Igh-V. 142 65

Overexpression of the ornithine decarboxylase (ODC) gene may be important to the development and maintenance of colonic neoplasms, as well as tumors in general. In this study, we examined the promoter elements governing constitutive expression of the human ODC gene in HCT 116 human colon carcinoma cells and, for comparison, K562 human erythro-leukemia cells. It was determined by functional analysis that the promoter elements responsible reside within the 378 bp immediately upstream from the transcription start site. Within this sequence, there are at least three regions that modulate the efficiency of the ODC promoter cooperatively. Both DNA bandshift and footprint assays demonstrated all three regions to be rich in sites that bind to nuclear proteins isolated from HCT 116 and K562 cells; the protein binding pattern of non-transformed, diploid fibroblasts was found to be much less complex. Several of the protein binding sequences have little or no homology to common regulatory elements. We suggest that the constitutive activity of the ODC gene in HCT 116 colon carcinoma cells, and perhaps transformed cells in general, involves a complex interaction of multiple regulatory sequences and their associated nuclear proteins. Finally, the saturation of the promoter in these transformed cell lines suggests that high levels of protein binding in the ODC promoter may contribute to elevated constitutive expression of this gene.
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PMID:Multiple promoter elements govern expression of the human ornithine decarboxylase gene in colon carcinoma cells. 159 17

Sequence analysis of the first 549 nucleotides (nt) of the non-translated 5' end of the cloned mouse ornithine decarboxylase (ODC; L-ornithine carboxy-lyase, EC 4.1.1.17)-encoding sequence shows that this sequence is closely related to nt 1946-1395 of Moloney murine leukemia virus (MuLV). The viral sequence, however, is oriented anti-sense relative to the ODC sequence. This orientation makes it unlikely to be a cloning artifact mediated by reverse transcriptase, but rather a recombination between genomic DNA and a MuLV-like provirus. In the cell line, from which the cDNA clone originated, Katz and Kahana [EMBO J. 8 (1989) 1163-1167] have shown that an intragenic deletion and amplification of the ODC gene had taken place. We believe that an additional recombination also has occurred in this cell line. The cDNA clone studied was obtained after selecting for high ODC expression. It is conceivable that the retroviral sequence contains an intragenic enhancer which is also functional in the anti-sense orientation. The inserted sequence contains two repeats which share homology with known enhancer elements. The reported recombination event shows that caution is needed when selective pressure is applied for the isolation and characterization of genes.
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PMID:The long leader sequence of the mouse ornithine decarboxylase mRNA, previously suspected to be a cloning artifact, is probably a product of recombination with MuLV-like retrovirus. 176 76

We have examined the effects of Cyclosporin A (CsA) on growth and polyamine metabolism of MOLT-4, human T lymphoblastic leukaemia cells to ascertain the role of the polyamine biosynthetic pathway in the antitumour action of CsA. We observed that CsA had a dose-dependent inhibitory effect on growth of the cells in vitro, decreasing protein content, cell number and the rate of incorporation of 3H-thymidine into the cells. However, CsA treatment had no significant effect on intracellular polyamine levels in the cells. Contrary to previous reports, simultaneous addition of the diamine, putrescine, with CsA did not block or lessen the growth inhibitory effects of CsA. On the other hand, ornithine decarboxylase activity, the rate limiting enzyme of polyamine biosynthesis which converts ornithine to putrescine, was decreased by CsA treatment. This decrease appeared to be reversible and contrasts with the inhibition by alpha-difluoromethyl-ornithine, which is irreversible and can be overcome by addition of putrescine. This suppression of ornithine decarboxylase by CsA is more likely to occur by indirect effects on translation and/or transcription rather than a direct effect on the enzyme. It may be a contributory factor in the overall antiproliferative effects of CsA but is more likely to be a response to these growth inhibitory effects rather than a direct effect of the drug.
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PMID:Effects of cyclosporin A on growth and polyamine metabolism of MOLT-4 T-lymphoblastic leukaemia cells. 189 53

Previous studies have demonstrated that BR-931, a hepatic peroxisome proliferator, can induce liver tumours in mice and rats. Since alterations in gene expression may play a critical role in multistage hepatocarcinogenesis, the present studies examined the expression of the c-myc, c-H-ras, epidermal growth factor (EGF) receptor and ODC (ornithine decarboxylase) genes, as well as endogenous retrovirus-like sequences, in F344 rat liver during the first 8 weeks of feeding a 0.16% Br931 diet and in liver tumours induced by chronic feeding of this diet. Northern blot analysis of poly A + liver RNA samples showed an increase in the level of RNAs homologous to rat leukaemia virus (RaLV) but no significant change in the level of 30S-retrovirus related RNAs in the liver RNA samples obtained from rats during the first 8 weeks of feeding the diet containing BR931. An increase in the levels of c-myc, c-H-ras and ODC transcripts was also seen in the liver RNA samples from the treated rats. Of particular interest was a decrease in the abundance of EGF receptor transcripts in the liver RNA samples from rats fed the BR931 diet. Increased levels of RaLV, c-myc, and ODC RNAs were also seen in the tumours induced by BR931, but this was not the case for 30S and c-H-ras. The liver tumour samples also showed a decrease in EGF receptor RNA. These changes in cellular levels of specific RNAs resemble, in several respect, those we previously described in rodent liver during regeneration and tumour promotion, and also those seen in rodent hepatomas induced by other agents. Therefore, they may reflect a common profile of gene expression relevant to liver proliferation and carcinogenesis.
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PMID:Changes in expression of cellular oncogenes and endogenous retrovirus-like sequences during hepatocarcinogenesis induced by a peroxisome proliferator. 193

In this study, 13 heteroarotinoids were synthesized. The key step in each preparation was the condensation of the appropriate chroman-, thiochroman-, or benzothienyl-substituted phosphorus ylide, obtained from the independent synthesis of the corresponding phosphonium salts, with selected polyene-substituted aldehyde esters. Nine of these heterocycles contained a thiochroman group, two had a chroman group, and two others had a benzothienyl system. Screening of the compounds was with one of two assays. One assay measured the ability of a retinoid to inhibit the phorbol ester induced increase of mouse epidermal ornithine decarboxylase (ODC) activity. The other assay measured retinoid-induced differentiation of the human myoloid leukemia cell line HL-60. In the ODC assay, all thirteen compounds were screened. The most active heteroarotinoids were ester 10 [methyl (E)-4-[2-(2,2,4,4-tetramethylthiochroman-6-yl)-1- propenyl]benzoate] and acid 11 [(E)-4-[2-(2,2,4,4-tetramethyl-3,4- dihydro-2H-1- benzothiopyran-6-yl)-1-propenyl]benzoic acid]. Both of these retinoids had ID50 values (dose required for half-maximal inhibition of phorbol ester induced ODC activity) of about 0.3 nmol. In comparison, the ID50 value for trans-retinoic acid (1) was 0.12 nmol while the ID50 values for acids 7 and 9, namely (2Z,4E,6E)-3,7-dimethyl-7-(4,4-dimethyl-thiochroman -6-yl)-2,4,6-heptatrienoic acid and (2E,4E,6E)-3,7-dimethyl-7-(2,2,4,4-tetramethylthiochroman -6-yl)-2,4,6- heptatrienoic acid, respectively, were about 3.5 nmol. Heteroarotinoids 8 and 12-17 had ID50 values of 35 nmol or greater. With a thiochroman unit, the most active acids in decreasing order of activity in the ODC assay were 7 greater than 9 greater than 8. Thus, simple replacement of the terminal propenyl system [C(16,17,18)] in 7 with a cyclopropyl group produced acid 8 [(2E,4E,6E)-7-methyl-7-(4,4-dimethylthiochroman-6-yl)- 2,3-methylene-4,6-heptadienoic acid with markedly reduced activity. With a benzoic acid group as part of the structure attached to the thiochroman unit, the ODC activity was enhanced as shown in 10 and 11. The combination of the 2,2,4,4-tetramethylthiochroman group and the benzoic acid (or ester) terminal group seemed to enhance the biological action which resembles that found with (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)- 1-propenyl]benzoic acid (TTNPB, 6b), a well-known model system.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Novel heteroarotinoids: synthesis and biological activity. 199 44

The mechanism of the antitumor action of 15-deoxyspergualin (DSG) was investigated. DSG inhibited spermidine synthase noncompetitively with putrescine, spermine synthase competitively with spermidine and polyamine oxidase in vitro. Induction of ornithine decarboxylase (ODC) activity observed after subculture of human leukemia cells was blocked by the addition of DSG to the culture medium. In DSG-treated leukemia cells, putrescine, spermidine and spermine levels were markedly depressed. The synthesis of protein was also greatly diminished in these polyamine-depleted leukemic cells, whereas the depressions of DNA and RNA syntheses were minimum. In in vivo experiments, DSG depressed polyamine levels in P388 leukemic ascites cells, and prolonged the survival times of mice bearing the leukemia cells. These results suggest that inhibition of polyamine and protein biosyntheses by DSG is substantially responsible for its antitumor action on the tumor cells.
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PMID:15-Deoxyspergualin, an antiproliferative agent for human and mouse leukemia cells shows inhibitory effects on the synthetic pathway of polyamines. 201 67

Calvatic acid (p-carboxyphenylazoxycyanide) is an antibiotic containing an azoxycyano group that displays carcinostatic activity. In the present work it has been shown that in AH-130 hepatoma and K562 leukemia cells the antibiotic, at low concentration, decreases ornithine decarboxylase (ODC) levels. The change depends on two summative effects of the drug, impairment of overall protein synthesis and inhibition of enzyme activity. Some analogs of calvatic acid have been tested in order to gain more insight into the structure-activity relationship. The decarboxylated derivative phenylazoxycyanide proved to be more effective in reducing protein synthesis and ODC activity in the whole tumor cells. The rapidly growing K562 cells displayed high sensitivity to this compound. Calvatic acid analogs devoid of the cyano group were less effective on the same parameters.
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PMID:Effect of calvatic acid and its analogs on ornithine decarboxylase activity in tumour cells. 227 63

The administration of 1 mM sodium butyrate induced the phenotypic differentiation of human promonocytic leukemia U937 cells, as judged by the expression of cD11b and cD11c antigens, two differentiation-specific surface markers. At the same time, butyrate greatly induced the expression at the mRNA level of the vimentin gene. The increase in the level of this RNA started at 6 h of treatment and reached the maximum at Hour 24. Such an increase was caused at least in part by a stimulation in the rate of gene transcription, as suggested by transcription assays in isolated nuclei. Experiments in the presence of cycloheximide suggested that vimentin induction is probably a direct response to the action of butyrate, not mediated by the prior induction of other gene products. Unlike the case of vimentin, the levels of other RNAs, namely beta-actin, ornithine decarboxylase, and c-myc, were not enhanced, but they decreased at different times of treatment with butyrate. Finally, we observed that butyrate induced also the differentiation of HL60 cells, another human myeloid cell type. Nevertheless, the drug failed to stimulate the expression of vimentin in this cell line.
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PMID:The induction of vimentin gene expression by sodium butyrate in human promonocytic leukemia U937 cells. 232 71


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