Our findings suggest a possible role of the glyoxalase system enzymes in the chemoresistance displayed by the kidney tumor. In fact, such a refractory behavior involves a decrease in the methylglyoxal level, a potent apoptosis activator. In addition, glyoxalase II activity decrease in the adenocarcinoma tissue suggests a likely role of the intermediate S-D-lactoylglutathione by supplying energy in actively proliferating cells. Finally, we point out a possible use of glyoxalase I inhibitors as anticancer drugs.
SummaryMicroarray platforms, enabling simultaneous measurement of many allergens with a small serum sample, are potentially powerful tools in allergy diagnostics. We report here the first study comparing a fully automated microarray system, the Microtest allergy system, with a manual microarray platform, Immuno-Solid phase Allergen Chip (ISAC), and two wellestablished singleplex allergy tests, skin prick test (SPT) and ImmunoCAP, all tested on the same patients. One hundred and three adult allergic patients attending the allergy clinic were included into the study. All patients were tested with four allergy test methods (SPT, ImmunoCAP, Microtest and ISAC 112) and a total of 3485 pairwise test results were analysed and compared. The four methods showed comparable results with a positive/negative agreement of 81-88% for any pair of test methods compared, which is in line with data in the literature. The most prevalent allergens (cat, dog, mite, timothy, birch and peanut) and their individual allergen components revealed an agreement between methods with correlation coefficients between 0Á73 and 0Á95. All four methods revealed deviating individual patient results for a minority of patients. These results indicate that microarray platforms are efficient and useful tools to characterize the specific immunoglobulin (Ig)E profile of allergic patients using a small volume of serum sample. The results produced by the Microtest system were in agreement with diagnostic tests in current use. Further data collection and evaluation are needed for other populations, geographical regions and allergens.
The glutathione-dependent glyoxalases system, composed of glyoxalase I (GloI) and glyoxalase II (GloII) enzymes, is involved in the detoxification of methylglyoxal, a by-product of cell metabolism. Aberrations in the expression of glyoxalase genes in several human cancers have been reported. Sometimes, these aberrations seem to differ depending on the organs and on the sensitivity of the tumours to estrogens, as we previously detected in the hormone-responsive breast cancer compared to the hormone-independent bladder cancer. To investigate a possible regulatory role of estrogens, as well as antiestrogens, on glyoxalases system, estrogen receptor (ER)-positive MCF7 and ER-negative BT20 human breast cancer cells were cultured in the presence of 17beta-estradiol (E2) and tamoxifen (TAM) performing two independent experiments. After a 24 h or 4 days treatment, we evaluated GloI and GloII mRNA levels, by Ribonuclease Protection Assay (RPA), enzymatic activities spectrophotometrically and cell proliferation by [3H]thymidine incorporation. We found that both steroid molecules affected glyoxalases gene expression and proliferation in a different manner in the cell lines. The modifications in mRNA levels were accompanied by parallel changes in the enzymatic activities. The possibility that modulation of glyoxalase genes by E2 and TAM are due to the presence of estrogen response elements (ERE) or cross-talk mechanisms by proteins of the estrogen signal transduction pathways are discussed. Knowledge regarding the regulation of glyoxalases by E2 and TAM may provide insights into the importance of this enzymes in human breast carcinomas in vivo.
The high prevalence of food and respiratory sensitization supports the clinical guideline recommendation that allergies should be evaluated in all children with suspected asthma. The microarray platforms studied here demonstrated acceptable accuracy and provided refined IgE characterization in 47% of the patients compared to standard extract-based methods.
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