RESUMO
INTRODUCTION AND OBJECTIVES: The heterogenous nature of hepatocellular carcinoma (HCC) motivated this attempt at developing and validating a model based on combined biomarkers for improving early HCC detection. PATIENTS/MATERIALS AND METHODS: This study examined 196 patients for an estimation study (104 patients with HCC, 52 with liver cirrhosis and 40 with liver fibrosis) and 122 patients for the validation study (80 patients with HCC, 42 with liver cirrhosis). All patients were positive for hepatitis C virus. Four markers were measured: Midkine and thioredoxin using ELISA, 1-methyladenosine and 1-methylguanosine using a gas chromatography-mass spectrometry (GC-MS). The results were compared with alpha-fetoprotein (AFP). The performance of the model was estimated in BCLC, CLIP and Okuda staging systems of HCC. RESULTS: The model yielded high performance with an area under ROC (AUC) of 0.94 for predicting HCC in patients with liver cirrhosis, compared with AUC of 0.69 for AFP. This model had AUCs of 0.93, 0.94 and 0.94 in patients who had only one single nodule, absent macrovascular invasion and tumor size <2cm, respectively, compared with AUCs of 0.71, 0.6 and 0.59 for AFP. The model produced AUCs of 0.91 for BCLC (0-A), 0.92 for CLIP (0-1) and 0.94 for Okuda (stage I) compared with AUCs of 0.56, 0.58 and 0.64 for AFP. No significant difference was found between AUC in the estimation and the validation groups. CONCLUSION: This model may enhance early-stage HCC detection and help to overcome insufficient sensitivity of AFP.
Assuntos
Adenosina/análogos & derivados , Carcinoma Hepatocelular/sangue , Guanosina/análogos & derivados , Cirrose Hepática/sangue , Neoplasias Hepáticas/sangue , Midkina/sangue , Tiorredoxinas/sangue , alfa-Fetoproteínas/metabolismo , Adenosina/sangue , Idoso , Área Sob a Curva , Biomarcadores Tumorais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico , Estudos de Casos e Controles , Detecção Precoce de Câncer , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Guanosina/sangue , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In-stent restenosis and poor re-endothelization usually follow percutaneous transluminal coronary angioplasty, even using drug-eluting stents, due to inflammation and oxidative stress. Medical ozone has antioxidant and anti-inflammatory properties and has not been evaluated in this context. OBJECTIVES: To evaluate whether ozonotherapy might reduce restenosis following bare metal stents implantation in relation to the redoxin system in pigs. METHODS: Twelve male Landrace pigs (51±9kg) underwent percutaneous transluminal circumflex coronary arteries bare metal stent implantation under heparine infusion and fluoroscopical guidance, using standard techniques. Pigs were randomized to ozonetherapy (n=6) or placebo (n=6) treatment. Before stenting (24h) and twice a week for 30days post-stenting, venous blood was collected, ozonized and reinfused. Same procedure was performed in placebo group except for ozonation. Both groups received antiplatelet treatment. Histopathology and immunohistochemistry studies were performed. RESULTS: Severe inflammatory reaction and restenosis with increase in the immunohistochemical expression of thioredoxin-1 were observed in placebo group 30days after surgery. Oppositely, ozonetherapy drastically reduced inflammatory reaction and restenosis, and showed no increase in the Trx-1 immunohistochemical expression 30days after surgery. Immunolabeling for Prx-2 was negative in both groups. Ozonated autohemotherapy strikingly reduced restenosis 30days following PTCA with BMS implantation in pigs. CONCLUSIONS: Stimulation of the redoxin system by ozone pretreatment might neutralize oxidative damage from the start and increase antioxidative buffering capacity post-injury, reducing further damage and so the demand for antioxidant enzymes. Our interpretation agrees with the ozone oxidative preconditioning mechanism, extensively investigated.
Assuntos
Neointima/sangue , Neointima/prevenção & controle , Ozônio/administração & dosagem , Stents/efeitos adversos , Tiorredoxinas/sangue , Animais , Reestenose Coronária/sangue , Reestenose Coronária/etiologia , Reestenose Coronária/prevenção & controle , Masculino , Neointima/etiologia , Estudos Prospectivos , Distribuição Aleatória , Método Simples-Cego , SuínosRESUMO
Peroxiredoxin 2 (Prx2) is a 2-Cys peroxiredoxin extremely abundant in the erythrocyte. The peroxidase activity was studied in a steady-state approach yielding an apparent K(M) of 2.4 microM for human thioredoxin and a very low K(M) for H2O2 (0.7 microM). Rate constants for the reaction of peroxidatic cysteine with the peroxide substrate, H2O2 or peroxynitrite, were determined by competition kinetics, k(2) = 1.0 x 10(8) and 1.4 x 10(7) M(-1) s(-1) at 25 degrees C and pH 7.4, respectively. Excess of both oxidants inactivated the enzyme by overoxidation and also tyrosine nitration and dityrosine were observed with peroxynitrite treatment. Prx2 associates into decamers (5 homodimers) and we estimated a dissociation constant K(d) < 10(-23) M(4) which confirms the enzyme exists as a decamer in vivo. Our kinetic results indicate Prx2 is a key antioxidant enzyme for the erythrocyte and reveal red blood cells as active oxidant scrubbers in the bloodstream.