Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The stability of solutions of the antitumour antimetabolites, vinca alkaloids, podophyllotoxins, interferons, steroids and platinum drugs as well as maytansine, asparaginase, amsacrine, flavone-8-acetic acid, mitoguazone, and N-phosphonoacetyl-L-aspartate (PALA) is reviewed. Much of the published work has been done with biological, not stability-indicating, assays; thus, the relevant results should be used with caution. With this proviso, almost all of these drugs can be stored in solution for several days at room temperature or 4 degrees C. Most reports also suggest that the drugs that have been tested are stable when frozen in solution. For a number of the drugs, particular precautions are required; for instance, amsacrine should not be mixed with chloride-containing solutions, whereas cisplatin is most stable in solutions containing greater than 0.1 M chloride.
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PMID:Stability of solutions of antineoplastic agents during preparation and storage for in vitro assays. III. Antimetabolites, tubulin-binding agents, platinum drugs, amsacrine, L-asparaginase, interferons, steroids and other miscellaneous antitumor agents. 246 80

We recently used RNA interference to show that a negative correlation of L-asparaginase (L-ASP) chemotherapeutic activity with asparagine synthetase (ASNS) expression in the ovarian subset of the NCI-60 cell line panel is causal. To determine whether that relationship would be sustained in a larger, more diverse set of ovarian cell lines, we have now measured ASNS mRNA expression using microarrays and a branched-DNA RNA assay, ASNS protein expression using an electrochemiluminescent immunoassay, and L-ASP activity using an MTS assay on 19 human ovarian cancer cell lines. Contrary to our previous findings, L-ASP activity was only weakly correlated with ASNS mRNA expression; Pearson's correlation coefficients were r = -0.21 for microarray data and r = -0.39 for the branched-DNA RNA assay, with just the latter being marginally statistically significant (P = 0.047, one-tailed). ASNS protein expression measured by liquid-phase immunoassay exhibited a much stronger correlation (r = -0.65; P = 0.0014, one-tailed). We conclude that ASNS protein expression measured by immunoassay is a strong univariate predictor of L-ASP activity in ovarian cancer cell lines. These findings provide rationale for evaluation of ASNS protein expression as a predictive biomarker of clinical L-ASP activity in ovarian cancer.
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PMID:Asparagine synthetase is a predictive biomarker of L-asparaginase activity in ovarian cancer cell lines. 1885 15

Childhood acute lymphoblastic leukemia (ALL) is treated with combined chemotherapy, including L-asparaginase (L-asp). Recent studies question the traditional view that the level of asparagine synthetase (ASNS), an enzyme producing the intracellular asparagine, correlates with the response to L-asp treatment. However, the importance of ASNS in response to L-asp has neither been confirmed nor refuted so far. In this study, we wanted to elucidate the effect of ASNS expression level on the sensitivity of ALL cells to L-asp treatment. We used four ALL cell lines (NALM-6, RS4;11, REH, and UOCB6) and 30 diagnostic bone marrow samples of ALL patients to study the relationship between ASNS expression and sensitivity to L-asp using MTS proliferation assay. RNA interference was used to study the effect of a range of ASNS levels on the response to L-asp treatment. Using a cell line model with a gradually knocked-down ASNS gene, we defined a cutoff level below which ASNS gene expression does not correlate with sensitivity to L-asp. Importantly, ASNS gene expression in patients' ALL blasts is below this level. We confirmed that there was no correlation between ASNS gene expression and sensitivity to L-asp in ALL blasts. In addition, we show that cells with low ASNS expression level do not respond to asparagine deprivation by upregulation of ASNS gene expression. In conclusion, the ASNS expression level does not predict sensitivity to L-asp in leukemic blasts. Moreover, cell lines with high basal expression of ASNS cannot serve as a valid model for studies on the relationship between the ASNS and L-asp cytotoxic effect.
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PMID:Low expression of asparagine synthetase in lymphoid blasts precludes its role in sensitivity to L-asparaginase. 2254 78