Decreased oxidant profile and increased antioxidant capacity in naturally postmenopausal women.

Recent works have shown a dual side of estrogens, and research on the relationship between oxidative stress and menopausal status remains unclear and has produced controversial results. In this work, we aimed to evaluate by sensitive methods the oxidant and antioxidant changes that develop after natural menopause. Thirty premenopausal and 28 naturally postmenopausal women volunteered for this study. Blood was collected and plasma used. 17-OH estradiol levels in plasma were estimated. Plasma levels of advanced oxidation protein products (AOPP), lipid peroxidation products (such as hydroperoxides and malondialdehyde (MDA)), and nitrites were measured, and total radical antioxidant parameter testing was performed to determine the oxidant and antioxidant profiles, respectively. Estrogen levels were significantly increased (p < 0.02) in premenopausal women (54.28 ± 9.34 pg/mL) as compared with postmenopausal women (18.10 ± 1.49 pg/mL). Postmenopausal women had lower levels of lipid hydroperoxide oxidation (p < 0.0001), lipid hydroperoxide levels evaluated by the area under the curve (AUC; 1,366,000 ± 179,400 AUC; p < 0.01), and hydroperoxides as measured by the ferrous oxidation-xylenol orange method (31.48 ± 2.7 µM; p < 0.0001). The MDA levels did not differ between pre- and postmenopausal women whether measured by thiobarbituric acid-reactive substances or high-performance liquid chromatography assays. No differences in AOPP and nitrite levels were observed between pre- and postmenopausal women. Postmenopausal women also exhibited a higher total radical antioxidant level (0.89 ± 0.08 µM Trolox; p < 0.0001). Postmenopausal women demonstrated lower levels of oxidative damage and a higher antioxidant capacity than premenopausal women.

Molecular subtype is determinant on inflammatory status and immunological profile from invasive breast cancer patients.

Breast cancer consists in a chronic inflammatory disease with multiple biological and clinical behaviors. Based on high throughput technologies data, this disease is currently classified according to the molecular expression of estrogen (ER), progesterone (PR) and human epidermal growth factor (HER-2) receptors. In this study, we defined the inflammatory profile of the main molecular subtypes of breast cancer patients: luminal (ER and PR positive, HER-2 negative), HER-2 enriched (HER-2 positive) and triple negative (ER, PR and HER-2 negative). Cytokines panel was assessed by measurement of TNF-α, TGF-ß, IL-1, IL-10 and IL-12 plasmatic levels. Oxidative profile was assessed by determination of lipid peroxidation, total antioxidant capacity of plasma, malondialdehyde levels, carbonyl content and nitric oxide (NO). Clinical data were correlated with inflammatory findings. Our findings demonstrated that patients bearing the luminal subtype displayed high TNF-α, TGF-ß and enhanced oxidative stress levels associated with reduced IL-12. HER-2-enriched group exhibited higher levels of TNF-α, IL-12 and TGF-ß associated with enhanced oxidative stress. Triple-negative subtype exhibited the most aggressive profile of disease behavior, with reduction in both TNF-α and TGF-ß, with high levels of lipid peroxidation and NO. The clinical importance of our findings lies in the fact that the inflammatory status varies in distinct ways due to molecular subtype of breast cancer, opening potential therapeutic targets to future therapies.

Immunological effects of taxol and adryamicin in breast cancer patients.

Antineoplastic chemotherapy still consists in the major first-line therapeutics against cancer. Several reports have described the immunomodulatory effects of these drugs based on in vitro treatment, but no previous data are known about these effects in patients and its association with immunological-mediated toxicity. In this study, we first characterize the immunological profile of advanced breast cancer patients treated with doxorubicin and paclitaxel protocols, immediately after chemotherapy infusion. Our findings included an immediate plasmatic reduction in IL-1, IL-10, and TNF-α levels in doxorubicin-treated patients, as well as high levels of IL-10 in paclitaxel patients. Further, it was demonstrated that both drugs led to leukocytes oxidative burst impairment. In vitro analysis was performed exposing healthy blood to both chemotherapics in the same concentration and time of exposition of patients, resulting in low IL-10 and high IL-1ß in doxorubicin exposition, as low TNF-α and high IL-1 in paclitaxel treatment. Nitric oxide levels were not altered in both in vivo and in vitro treatments. In conclusion, our data revealed for the first time that the immediate effects of chemotherapy could be mediated by cytokines signaling in patients and that the results observed in patients could be a resultant of host immune cells activation.

Oxidative stress and hematological profiles of advanced breast cancer patients subjected to paclitaxel or doxorubicin chemotherapy.

Several adverse effects of chemotherapy treatments have been described, and most of these effects are associated with direct interactions between blood cells and indirect effects generated during the oxidative metabolism of antineoplastic drugs. In this study we evaluated the oxidative systemic status and hematological profiles of breast cancer patients with advanced ductal infiltrative carcinoma treated with doxorubicin (DOX) or paclitaxel (PTX) within 1 h after chemotherapy. Blood analyses included evaluation of hemogram, pro-oxidative markers, and antioxidant status. The results showed that advanced breast cancer diseased (AD) patients without previous chemotherapy presented anemia and high oxidative stress status characterized by elevated levels of lipid peroxidation and nitric oxide, and reduced catalase activity when compared with controls. DOX-treated patients exhibited increased anemia and reduced antioxidant status, which was revealed by decreases in reduced glutathione levels and the total antioxidant capacity of plasma; however, these changes did not lead to further increases in lipid peroxidation or carbonyl proteins when compared with the AD group. PTX-treated patients also showed increased anemia, lactate dehydrogenase leakage, and enhanced lipid peroxidation. These data reveal for the first time that patients subjected to chemotherapy with DOX or PTX present immediate systemic oxidative stress and red blood cell oxidative injury with anemia development. These findings provide a new perspective on the systemic redox state of AD and patients subjected to chemotherapy regarding oxidative stress enhancement and its possible involvement in the aggravation of chronic anemia.

Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1ß, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators.

Breathing pattern and thoracoabdominal motion during exercise in chronic obstructive pulmonary disease.

Subjects with chronic obstructive pulmonary disease (COPD) present breathing pattern and thoracoabdominal motion abnormalities that may contribute to exercise limitation. Twenty-two men with stable COPD (FEV1 = 42.6 +/- 13.5% predicted; age 68 +/- 8 years; mean +/- SD) on usual medication and with at least 5 years of diagnosis were evaluated at rest and during an incremental cycle exercise test (10 watts/2 min). Changes in respiratory frequency, tidal volume, rib cage and abdominal motion contribution to tidal volume and the phase angle that measures the asynchrony were analyzed by inductive respiratory plethysmography at rest and during three levels of exercise (30-50, 70-80, and 100% maximal work load). Repeated measures ANOVA followed by pre-planned contrasts and Bonferroni corrections were used for analyses. As expected, the greater the exercise intensity the higher the tidal volume and respiratory frequency. Abdominal motion contributed to the tidal volume increase (rest: 49.82 +/- 11.19% vs exercise: 64.15 +/- 9.7%, 63.41 +/- 10%, and 65.56 +/- 10.2%, respectively, P < 0.001) as well as the asynchrony [phase angle: 11.95 +/- 7.24 degrees at rest vs 22.2 +/- 15 degrees (P = 0.002), 22.6 +/- 9 degrees (P < 0.001), and 22.7 +/- 8 degrees (P < 0.001), respectively, at the three levels of exercise]. In conclusion, the increase in ventilation during exercise in COPD patients was associated with the major motion of the abdominal compartment and with an increase in the asynchrony independent of exercise intensity. It suggests that cycling exercise is an effective way of enhancing ventilation in COPD patients.

Breathing pattern and thoracoabdominal motion during exercise in chronic obstructive pulmonary disease

Subjects with chronic obstructive pulmonary disease (COPD) present breathing pattern and thoracoabdominal motion abnormalities that may contribute to exercise limitation. Twenty-two men with stable COPD (FEV1 = 42.6 ± 13.5 percent predicted; age 68 ± 8 years; mean ± SD) on usual medication and with at least 5 years of diagnosis were evaluated at rest and during an incremental cycle exercise test (10 watts/2 min). Changes in respiratory frequency, tidal volume, rib cage and abdominal motion contribution to tidal volume and the phase angle that measures the asynchrony were analyzed by inductive respiratory plethysmography at rest and during three levels of exercise (30-50, 70-80, and 100 percent maximal work load). Repeated measures ANOVA followed by pre-planned contrasts and Bonferroni corrections were used for analyses. As expected, the greater the exercise intensity the higher the tidal volume and respiratory frequency. Abdominal motion contributed to the tidal volume increase (rest: 49.82 ± 11.19 percent vs exercise: 64.15 ± 9.7 percent, 63.41 ± 10 percent, and 65.56 ± 10.2 percent, respectively, P < 0.001) as well as the asynchrony [phase angle: 11.95 ± 7.24° at rest vs 22.2 ± 15° (P = 0.002), 22.6 ± 9° (P < 0.001), and 22.7 ± 8° (P < 0.001), respectively, at the three levels of exercise]. In conclusion, the increase in ventilation during exercise in COPD patients was associated with the major motion of the abdominal compartment and with an increase in the asynchrony independent of exercise intensity. It suggests that cycling exercise is an effective way of enhancing ventilation in COPD patients.