RESUMO
Background This study was performed to assess adhesion molecules in systemic lupus erythematosus (SLE). Methods This case-control study examined 126 SLE patients and 48 healthy individuals. Blood levels of six adhesion molecules, cortisol, nuclear autoantibody (ANA) and anti-double stranded DNA (anti-dsDNA) titers were measured, while disease activity was assessed using the SLE Disease Activity Index (SLEDAI) score. Results Platelet endothelial cell adhesion molecule 1 (PECAM-1), vascular cell adhesion molecule 1 (VCAM-1), E-selectin, P-selectin, and plasminogen activator inhibitor type-1 (PAI-1) were significantly higher in SLE patients than in controls. Binary logistic regression analysis showed that PECAM-1 and PAI-1 predicted SLE with a sensitivity of 86.5% and a specificity of 81.3%. ANA titers were significantly and positively associated with PECAM-1, VCAM-1, E-selectin, and PAI-1, whereas there were no associations between anti-dsDNA titers and adhesion molecules. Cortisol was negatively associated with PCAM-1 and ICAM-1. There were significant associations between metabolic syndrome (MetS) and E-selectin and PAI-1. 14.8% of the variance in the SLEDAI score was explained by the regression on PECAM-1 and MetS. Conclusions Our data show that adhesion molecules, especially PECAM-1, are significantly associated with SLE and disease activity, suggesting that they play a role in SLE pathophysiology. While MetS, ANA titers and cortisol levels modulate adhesion molecule levels, these associations do not explain the increased levels of adhesion molecules in SLE. Increased levels of adhesion molecules are new drug targets in SLE.
Assuntos
Anticorpos Antinucleares/sangue , Autoimunidade , Moléculas de Adesão Celular/sangue , Hidrocortisona/sangue , Lúpus Eritematoso Sistêmico/sangue , Síndrome Metabólica/complicações , Adulto , Biomarcadores/sangue , Índice de Massa Corporal , Brasil , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Lúpus Eritematoso Sistêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Índice de Gravidade de DoençaRESUMO
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.
Assuntos
Neoplasias da Mama/patologia , Inflamação/patologia , Adulto , Antineoplásicos/uso terapêutico , Antioxidantes/análise , Neoplasias da Mama/sangue , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/imunologia , Citocinas/sangue , Doxorrubicina/uso terapêutico , Feminino , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Peroxidação de Lipídeos , Malondialdeído/sangue , Pessoa de Meia-Idade , Invasividade Neoplásica , Óxido Nítrico/sangue , Estresse Oxidativo , Paclitaxel/uso terapêutico , Prognóstico , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
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.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma/tratamento farmacológico , Doxorrubicina/administração & dosagem , Paclitaxel/administração & dosagem , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Carcinoma/diagnóstico , Carcinoma/imunologia , Carcinoma/patologia , Citocinas/sangue , Doxorrubicina/efeitos adversos , Feminino , Humanos , Imunomodulação , Pessoa de Meia-Idade , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Paclitaxel/efeitos adversosRESUMO
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.
Assuntos
Neoplasias da Mama/sangue , Carcinoma Ductal de Mama/sangue , Estresse Oxidativo , Adulto , Idoso , Antioxidantes/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/patologia , Catalase/metabolismo , Eritrócitos/enzimologia , Eritrócitos/metabolismo , Feminino , Glutationa/metabolismo , Humanos , Peroxidação de Lipídeos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Nitritos/metabolismo , Carbonilação Proteica , Superóxido Dismutase/metabolismo , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
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.