Breast cancer: Pretreatment drug resistance parameters (GSH-system, ATase, P-glycoprotein) in tumor tissue and their correlation with clinical and prognostic characteristics

Background: The identification of new factors predicting relapse,outcome and response to systemic therapy in breast cancer is warranted. Themeasurement of biological markers such as drug resistance parameters (DRPs),which are part of the phenotype of malignant cells and contribute toresistance to anti-cancer drugs may be a possibility, which may ultimatelylead to improvement of therapeutic results.Patients and methods: The level of glutathione (GSH), activities ofglutathione-S-transferase (GST), glutathione-peroxidase (GPx),06-alkylguanine-DNA-alkyltransferase (ATase), and P-glycoprotein (PGP) weremeasured in tumor and adjacent tumor free tissue samples from 89 consecutive,untreated females with breast cancer and correlated with clinical andprognostic factors. Early breast cancer (EBC) was diagnosed in 56 patients,22 patients had locally advanced (LABC) and 11 patients metastatic breastcancer.Results: All DRPs showed significantly higher expression in tumorthan in tumor free tissues. GPx was positively correlated with GST (R = 0.3, P = 0.0048) and with GSH (R = 0.5, P = 0.0001) in tumor as wellas in normal tissue. GST activity was significantly higher in EBC than in LABCor metastatic breast cancer ( P = 0.02). GSH level was significantlyhigher in grade 1 than in grade 2 or grade 3 tumors ( P = 0.01). Whenclinical characteristics were related to the level of DRP, high GSH wasassociated with age >60 years ( P = 0.01) in EBC, and with grade1–2 tumors ( P = 0.05) in LABC. No differences in OS were apparentbetween groups of high and low DRP-expression. However, the four-yearestimated disease-free survival of EBC tended to be higher in patients withhigh GST ( P = 0.10) and of LABC in patients with high GPx levels( P = 0.06).Conclusion: We conclude that high levels of DRP in tumor tissue ofbreast cancer patients are part of the initial phenotype of the malignantcells. Due to its high prevalence (83% in EBC, 100% in primarilymetastatic breast cancer), PGP did not add to prognostic information. Highlevels of GSH, GST and and GPx were associated with favorable clinicalcharacteristics and good prognosis, whereas low levels of GSH and GST activitywere associated with more aggressive or more advanced disease.     

Consumption of cranberry beverage improved endogenous antioxidant status and protected against bacteria adhesion in healthy humans: a randomized controlled trial

Consumption of polyphenol-rich foods is associated with lower risk from many chronic diseases. We hypothesized that a single dose of cranberry beverage would improve indices of oxidative stress, inflammation, and urinary antibacterial adhesion activity in healthy humans. Six males and 6 females (18-35 years; body mass index, 19-25 kg/m²) consumed placebo, cranberry leaf extract beverage, or low-calorie cranberry juice cocktail (LCJC) once in a randomized, double-blind, placebo-controlled cross-over experimental design trial. The washout period between beverages was 1 week. Blood was collected 0, 2, 4, 8, and 24 hours after beverage consumption for measuring oxidative and inflammatory biomarkers. Urine was collected at 0, 0 to 3, 3 to 6, 6 to 9, 9 to 12, and 24 hours postintervention to assess antibacterial adhesion activity. Consumption of cranberry leaf extract beverage elevated (P < .05) blood glutathione peroxidase activity, whereas LCJC consumption increased (P < .05) glutathione concentrations and superoxide dismutase activity compared with placebo. Cranberry leaf extract beverage and LCJC consumption had no effect on the inflammatory biomarkers measured as compared with placebo. At 0 to 3 hours postconsumption, urine from participants who consumed cranberry beverages had higher (P < .05) ex vivo antiadhesion activity against P-fimbriated Escherichia coli compared with placebo. An acute dose of cranberry beverages improved biomarkers of antioxidant status and inhibition of bacterial adhesion in urine.     

Effect of Moderate Wine Consumption on Oxidative Stress Markers in Coronary Heart Disease Patients

Evidence from research studies reports that wine consumption is associated with lower cardiovascular disease risk, partly through the amelioration of oxidative stress. The aim of the present study was to examine the effect of regular light to moderate wine consumption from coronary heart disease (CHD) patients compared to the effect induced by alcohol intake without the presence of wine microconstituents, on oxidation-induced macromolecular damage as well as on endogenous antioxidant enzyme activity. A randomized, single-blind, controlled, three-arm parallel intervention was carried out, in which 64 CHD patients were allocated to three intervention groups. Group A consumed no alcohol, and Group B (wine) and Group C (ethanol) consumed 27 g of alcohol/day for 8 weeks. Blood and urine samples were collected at baseline and at 4 and 8 weeks. Urine oxidized guanine species levels, protein carbonyls, thiobarbituric acid substances (TBARS) levels, as well as superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities, were measured. Oxidized guanine species and protein carbonyl levels were significantly increased in the ethanol group during the intervention and were significantly decreased in the wine group. These results support the idea that wine’s bioactive compounds may exert antioxidant actions that counteract the macromolecular oxidative damage induced by alcohol in CHD patients.     

SIRT3 regulation of mitochondrial oxidative stress

Mitochondria play a central role in the production of reactive oxygen species as byproducts of metabolism and energy production. In order to protect cellular structures from oxidative stress-induced damage, cells have evolved elegant mechanisms for mitochondrial ROS detoxification. The mitochondrial sirtuin, SIRT3, is emerging as a pivotal regulator of oxidative stress by deacetylation of substrates involved in both ROS production and detoxification. This review will summarize recent findings on the regulation of mitochondrial ROS homeostasis by SIRT3.     

Chemoprevention of liver cancer by plant polyphenols

Primary liver cancer or hepatocellular carcinoma (HCC) is one of the most frequent tumors representing the fifth commonest malignancy worldwide and the third cause of mortality from cancer. Currently, the treatments for HCC are not so effective and new strategies are needed for its fight. Chemoprevention, the use of natural or synthetic chemical agents to reverse, suppress or prevent carcinogenesis is considered an important way for confronting HCC. Many of the chemopreventive agents are phytochemicals, namely non-nutritive plant chemicals with protective or disease preventive properties. In this review, we focus on plant polyphenols, one of the most important classes of phytochemicals, their chemopreventive properties against HCC and discuss the molecular mechanisms accounting for this activity.     

硒的化学形式对人血中含硒组分的影响

在低膳食硒地区的农村,对健康男性受试者进行了为期一年的补硒干预试验。所有受试者每天服硒200μg,以硒酸钠或硒蛋氨酸形式供给。血样分析结果表明,这两种形式的硒均能有效地提高低硒人体的谷胱甘肽过氧化物酶(GPx)活力,因而在预防克山病工作中可采用较为经济的硒酸钠;但补硒蛋氨酸后可见“富裕”硒进入了红细胞的Hb和血浆的白蛋白中,而补硒酸钠后未见“富裕”硒,因而为提高人体硒营养水平,以补充硒蛋氨酸形式的硒为宜。     

Dietary clofibrate inhibits induction of hepatic antioxidant enzymes by chronic estradiol in female ACI rats

Excess production of H₂O₂ has been implicated in oncogenesis. The object of the present study was twofold: first, to determine the influence of chronic estradiol (E₂) on the activities of selected hepatic antioxidant enzymes in female ACI rats, a strain that is highly sensitive to the induction of estrogen dependent mammary tumors; secondly, to evaluate the actions of dietary clofibrate, a peroxisome proliferator, on activities of these enzymes in control and E₂-treated ACI rats. Enzymes selected for study were: NAD(P)H quinone oxidoreductase (NQO1), glutathione S-transferase (GST) and glutathione peroxidase (GPx). Cytosolic catalase (CAT) was also measured as an index of peroxisome proferation in control and E_2- treated animals. E₂ was administered chronically over 6 and 12 week periods from cholesterol pellet implants containing either 1 or 3 mg E₂. Animals were fed AIN-76A diets with or without 0.4% clofibrate over the experimental period. NQO1 and GST but not GPx were induced to varying degrees (NQO1 about 300%, and GST about 45–97%) by chronic E₂-treatment. E₂-induced increases in these activities were completely prevented in rats exposed to dietary clofibrate. Dietary clofibrate also caused slight but significant reductions in baseline activities of NQO1, GST and GPx in control animals. Serum E₂ levels, increased approximately 540% in a dose-dependent manner, and were not altered by dietary clofibrate. It is concluded that chronic E2 treatment markedly induces several important hepatic antioxidant enzymes in female ACI rats, and induction of these activities by E2 is inhibited completely by dietary clofibrate. Both of these actions have the potential to markedly influence the profile of E₂ metabolites exported from the liver to E₂ sensitive extrahepatic tissues and influence the initiation and progression of hormone-dependent tumors.     

The combination of α-lipoic acid supplementation and aerobic exercise inhibits lipid peroxidation in rat skeletal muscles

We investigated the effect of dl-α-lipoic acid (LA) supplementation and regular aerobic exercise on the concentrations of malondialdehyde (MDA) and vitamin E, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx), and the levels of glutathione (GSH) in rat skeletal muscles (soleus and red gastrocnemius). For 8 weeks, rats (n = 7 per group) were (1) exercised on a treadmill for 30 min d⁻¹, (2) treated with supplemental LA, or (3) exercised and treated with supplemental LA. Control rats (n = 7) did not receive LA and were not exercised. dl-α-Lipoic acid (100 mg kg⁻¹) was administered daily as an oral supplement. The rats were exercised in a graded manner for 5 d wk⁻¹. The concentration of MDA in the soleus and red gastrocnemius was significantly lower in rats that exercised and received LA than in the other groups. Compared with the other groups, rats that exercised and received LA had a significantly higher vitamin E concentration in the soleus. The SOD and GPx activities in the soleus and red gastrocnemius were significantly higher in rats that exercised and received LA. These results suggest that LA supplementation combined with aerobic treadmill exercise inhibits lipid peroxidation in skeletal muscles. This effect was especially remarkable in the soleus, which is particularly sensitive to oxidative stress, as revealed by the increased vitamin E level and SOD and GPx activities.