Objectives: Evaluation of glutathione (GSH) system in different tumors to reveal its potential usefulness in a clinical setting.
Design and methods: In addition to 10 normal controls, blood and tissue samples (85 benign and 109 malignant) from patients with breast, ovarian, prostatic, and liver neoplasms were investigated. The GSH concentration, glutathione S-transferase, glutathione peroxidase, and glutathione reductase activities were biochemically measured.
Results: Whereas all the components of the GSH system increased in patients with breast tumors, few components were significantly changed in patients with malignant ovarian, prostatic as well as metastatic liver diseases. GSH had the highest Z scores in ovarian and breast tumors. It was correlated (p < 0.05) with both glutathione S-transferase, glutathione peroxidase in breast cancer and with glutathione S-transferase only in prostate cancer. No correlation could be found in the expression of the GSH system in the blood and tissues of the same group of patients.
Conclusion: This work revealed that measurement of some and/or all components of the GSH system might be of clinical value in some malignant cases. 相似文献
The Combi-Targeting concept postulates that a molecule termed combi-molecule (C-molecule) with binary epidermal growth factor receptor (EGFR) targeting/DNA-damaging properties and with the ability to be hydrolyzed to another EGFR inhibitor should induce sustained antiproliferative activity in cells overexpressing EGFR. Because we postulate that the EGFR affinity of the C-molecule and that of its hydrolytic metabolites are critical parameters for sustained potency against EGFR-overexpressing cells, we synthesized BJ2000 (IC(50) = 0.1 microM, competitive binding at ATP site), a novel C-molecule that can decompose into a 6-amino-4-anilinoquinazoline FD105 (IC(50) = 0.2 microM). Studies using the EGFR-overexpressing A431 cells revealed that BJ2000 could damage DNA and block epidermal growth factor-stimulated EGFR autophosphorylation by a partially irreversible mechanism. Blockade of EGFR autophosphorylation subsequently induced inhibition of mitogen-activated protein kinase activation and c-fos gene expression. Enzyme-linked immunosorbent assay and growth factor-mediated stimulation of proliferation assays in the EGFR-expressing NIH3T3HER14 demonstrated the preferential EGFR-targeting properties of BJ2000, and more importantly suggest that blockade of EGFR phosphorylation by this drug translate into significant growth inhibitory effects. These properties culminated into irreversible antiproliferative effects as confirmed by a sulforhodamine B assay. Five days after a 2-h treatment, BJ2000 retained significant antiproliferative effect in A431 cells, whereas its reversible metabolite FD105 almost completely lost its activity. This result in toto lend support to the Combi-Targeting concept according to which a molecular conjugate kept small enough to interact with EGFR and designed to degrade into another inhibitor of the same target plus a DNA-damaging species may induce sustained growth inhibitory effect in EGFR-overexpressing cells. 相似文献