Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

5-Aza-2'-deoxycytidine (5-AZA-CdR) is an inhibitor of DNA methylation, and its antileukemic activity has been shown in preclinical and clinical studies. This paper describes the ability of 5-AZA-CdR to inhibit DNA methylation, DNA synthesis and cell growth in several human neuroblastoma cell lines. The stability of cell growth inhibition was ascertained, as well as the ability of the metabolite thymidine to enhance the antiproliferative effect of 5-AZA-CdR. The activity of phosphorylating enzyme deoxycytidine kinase (dCK) was correlated to different levels of sensitivity in several cell lines. The results obtained indicate that 5-AZA-CdR may be an agent for the chemotherapy of neuroblastoma.
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PMID:Antiproliferative effects and DNA hypomethylation by 5-aza-2'-deoxycytidine in human neuroblastoma cell lines. 750 41

Additive to synergistic induction of apoptosis has been reported as a result of sequential incubation of cancer cells with a histone deacetylase inhibitor (HDACi) and gemcitabine (dFdC), a deoxycytidine analogue with proven anti-tumour activity. This study shows that sequential treatment of two neuroblastoma cell lines with BL1521, an HDACi, and dFdC resulted in strong antagonism despite a minor increase of dFdCTP incorporation into the DNA of one cell line. Furthermore, no difference in the deoxycytidine kinase activity was observed in response to BL1521. In conclusion, cancer cells that respond to HDACi with a cell cycle arrest and differentiation may no longer be sensitive to dFdC.
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PMID:Antagonistic effects of sequential administration of BL1521, a histone deacetylase inhibitor, and gemcitabine to neuroblastoma cells. 1590 66

The effect of the CTP synthetase inhibitor cyclopentenyl cytosine (CPEC) on the metabolism and cytotoxicity of 2',2'-difluorodeoxycytidine (dFdC, gemcitabine) and the expression and activity of deoxycytidine kinase (dCK) was studied in human neuroblastoma cell lines. The cytotoxicity of dFdC and CPEC was studied in a panel of MYCN-amplified and MYCN-single-copy neuroblastoma cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide-assays. dFdC-metabolism was studied in SK-N-BE(2)c cells using [3H]-radiolabeled dFdC. dCK activity and expression were measured using enzyme assays, immunoblot and quantitative PCR, respectively. Both MYCN-amplified and MYCN-single-copy neuroblastoma cell lines were highly sensitive to dFdC, with concentration of the drug resulting in 50% effect when compared to untreated controls (ED50) values in the nanomolar range after a 3-h exposure to dFdC. There was no correlation of the observed ED50 with the dCK activity. Treatment with dFdC induced cell death in MYCN-amplified cells whereas MYCN-single-copy-cell lines underwent neuronal differentiation. Pre-incubation with CPEC significantly increased dFdC-cytotoxicity from 1.3 to 5.3-fold in 13 out of 15 cell lines. [3H]dFdC-anabolism increased 6-44 fold in SK-N-BE(2)c cells after incubation with CPEC and was paralleled by a significant increase in expression and activity of dCK. In conclusion, the combination of dFdC and CPEC is highly toxic to neuroblastoma in vitro.
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PMID:Cyclopentenyl cytosine-induced activation of deoxycytidine kinase increases gemcitabine anabolism and cytotoxicity in neuroblastoma. 1613 34