ABSTRACT
Background: Despite several therapeutic options available for bladder cancer, the outcomes are less satisfactory. To find a more effective modality, we were interested in the bioactive mushroom extract, PDF, which has been shown to sensitize certain anticancer drugs. Accordingly, we investigated if cytotoxic effects of several anticancer drugs used on bladder cancer patients could be enhanced with PDF in vitro.Methods: Human bladder cancer T24 cells were treated with four anticancer drugs, carmustine (BCNU), 5-fluorouracil (5FU), cisplatin (CPL), and doxorubicin (DOX) alone, their combinations, or in combination with PDF, and cell viability was determined. To explore the anticancer mechanism, the status of glyoxalase I (Gly-I), an enzyme involved in the drug resistance of cancer cells, and oxidative stress that can cause severe cellular injury/damage was also assessed.Results: BCNU and 5FU alone resulted in a >50% reduction in cell viability but CPL and DOX had no such effects. Only a combination of BCNU and PDF led to a drastic (~90%) cell viability reduction, accompanied by inactivation of Gly-I and an increase in oxidative stress. However, any combinations of other drugs and PDF had little effects on cell viability, Gly-I activity, or severity of oxidative stress.Conclusions: This study shows that anticancer activity of BCNU is significantly potentiated with PDF in T24 cells. This is rather attributed to inactivated Gly-I and increased oxidative stress. Therefore, PDF appears to have a chemosensitizing effect capable of enhancing BCNU cytotoxicity, which may offer an alternative, improved therapeutic option for bladder cancer.
ABSTRACT
Advanced Glycation End Products (AGEs), their receptor (RAGE) and their detoxifying enzyme Glyoxalase-I (GLO-I) have been implicated in the development of experimental diabetic peripheral neuropathy (DPN). However, few studies have assessed their role in the tissues of diabetic patients. We have assessed the relationship between skin expression of AGEs, RAGE, GLO-I and diabetic neuropathy in patients with type 1 diabetes. Sixty-two patients with type 1 diabetes mellitus (16 with and 46 without DPN) and 30 age-matched control subjects underwent detailed assessment of neurologic deficits, quantitative sensory testing, electrophysiology, corneal confocal microscopy (CCM), intraepidermal nerve fibre density (IENFD) and AGEs, RAGE and GLO1-I expression in foot skin biopsies. Skin AGEs and RAGE expression was significantly higher and GLO-I was significantly lower in the 16 epidermis, microvessels and reticular extracellular matrix of patients with diabeticneuropathy as compared to diabetic patients without neuropathy and control subjects. Skin AGEs and RAGE expression was also moderately but significantly increased and GLO-I expression was decreased in some skin structures in patients without diabetic neuropathy as compared to control subjects. Skin AGEs and RAGE expression correlated negatively and GLO-I expression correlated positively with sural nerve amplitude and velocity, IENFD and corneal nerve pathology. These findings suggest that AGEs, RAGE and GLO-I may play an important role in the etiology of human diabetic neuropathy. Retraction Notice: This paper has been retracted from the journal after receipt of written complains regarding authorship dispute. This journal is determined to promote integrity in research publication. This retraction is in spirit of the same. After formal procedures editor(s) and publisher have retracted this paper on 5th April-2016. Related policy is available here: http://goo.gl/lI77Nn
ABSTRACT
Background: Metabolism of methylglyoxal by the glyoxalase system may be linked to the development of diabetic complications. It was considered worthwhile to find out whether changes observed in the levels of glyoxalase I, glyoxalase II, aldose reductase & D-lactate are prognostic indicators for the development of complications of diabetes or merely reflect the result of changes associated with complications. Methods: The glyoxalase system was characterized in erythrocytes of blood samples from patients with type II diabetes mellitus (n=177), and normal healthy control subjects (n=40). Diabetics were divided into 3 main groups based on presence or absence of complications. Results: The concentrations of RBC glyoxalase I, glyoxalase II, aldose reductase, and D-lactate were significantly increased in all groups of diabetic patients, (P <0.001) relative to controls. Comparison between groups showed maximum rise of enzymes in group I and group III (P <0.001); and maximum rise of D-lactate in group III (P <0.001). Within the groups of patients with complications, enzyme levels were markedly increased in patients with IHD/PVD (ischaemic heart disease/peripheral vascular disease) and decreased in patients with nephropathy. Conclusion: Results of this study suggests a positive relationship between increased activity of erythrocyte enzymes of glyoxalase system and poor or moderate glycemic control. The increased enzyme levels in patients without complications indicate their role as prognostic markers for development of complications. Molecular mechanisms for development of Nephropathy appear to be different from those of Neuropathy and Retinopathy.
ABSTRACT
Glyoxalase system,a most effective defence system is present in cytosol of cells to scavenge ?-oxoaldehydes,which are reactive intermediates of AGEs formation.Glyoxalase Ⅰ is the key enzyme of this system.?-oxoaldehydes and AGEs are involved in the development of Alzheimer′s disease (AD). Therefore,the expression level and activity of glyoxalase I are essential to pathogenesis of AD.
ABSTRACT
It has been reported earlier that nucleotides, nucleosides and a series of structurally related compounds as well as compounds based on transition state analogy inhibit yeast glyoxalase I. In our study on the metabolic regulation of glyoxalase I, we have found that nucleotides such as ATP, GTP and different classes of other reagents based on transition state analogy (D-isoascorbate, dihydroxyfumaric acid, rhodizonic acid) do not inhibit yeast or goat liver glyoxalase I. The reported inhibition of glyoxalase I by these compounds has been found to be due to the interference of these compounds with the absorbancy at 240 nm of S-D-lactoylglutathione formed by the glyoxalase I reaction. Glyoxalase I from goat liver has been found to be strongly and competitively inhibited by lactaldehyde. But, lactaldehyde has very little inhibitory effect on yeast glyoxalase I. Lactaldehyde is formed from methylglyoxal, the substrate for glyoxalase I by the enzyme methylglyoxal reductase. D-Lactaldehyde inhibits the liver enzyme more strongly than Llactaldehyde.
ABSTRACT
A method of typing of EsD-PCM_1-CLOI on the same gel electrophoresis has been devel- oped by improving and mixing the individual tests of typing EsD, PGM_1and GLOI. The method supplies a reliable, economical and practical means for more wide-spread use of EsD, PGM_1 and GLOI in the forensic medicine field.
ABSTRACT
The polymorphic variants of HLA-linked genetic markers GLO, Bf, C2 and C4 were determined in Koreans. The GLO2 allele was found at a similar frequency as compared with other orientals and at higher frequency than in Caucasians. The gene frequencies of BfS and BfF showed different figures from those in other orientals and were similar to Caucasians. The C2C allele was the highest variant as in other populations. The rare variant C2A was not observed in this study. The common variants of C4A alleles are C4A*3 and C4A*4. Among the C4B variants, C4B*1, C4B*2 and C4B* QO are common in that order. Several undefined electrophoretic variants C4A and C4B were observed in this study. These findings suggest that the frequencies of various HLA-linked genetic markers can be used in anthropological studies.