RESUMO
BACKGROUND: Preoperative chemotherapy (PCT) allows for in vivo testing of treatment effects on tumor and its microenvironment. Aim of this analysis was to evaluate the effect of PCT on tumor biomarker expression and to evaluate the prognostic role of treatment-induced variation of these biomarkers (molecular response). METHODS: Two hundred and twenty-one stage II-III breast cancer patients were included. The following parameters were evaluated at baseline and on surgical specimens after PCT: estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, human epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor 2 (VEGFR2), and apoptosis. RESULTS: A pathological complete response was observed in 8.8% of the patients. PCT induced a significant reduction in the expression of ER, PgR, Ki-67, and apoptosis. As by multivariable model, Ki-67 > or = 15% and nodal positivity after preoperative chemotherapy (PCT) were significant predictors of worse disease-free survival [hazard ratio (HR) 3.79, P < 0.0001 and HR 2.31, P = 0.037, respectively]. Ki-67 > or = 15% after PCT was also a significant predictor of overall survival (HR 3.75, P = 0.013). On the basis of these two parameters, patients were classified into three groups: (i) low risk (negative nodes and Ki-67 <15%), (ii) intermediate risk (nodal positivity or Ki-67 > or = 15%), and (iii) high risk (nodal positivity and Ki-67 > or = 15%). As compared with the low-risk group, the HRs for recurrence were 3.1 and 9.3 for the intermediate- and high-risk group, respectively (P = 0.0001); the HRs for death were 2.4 and 6.5 for the intermediate- and high-risk group, respectively (P = 0.042). CONCLUSIONS: Ki-67 and nodal status have been used to generate a simple and easily reproducible prognostic model, able to discriminate patients with worse prognosis among the heterogeneous group of women with residual disease after PCT.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/análise , Neoplasia Residual/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Pessoa de Meia-Idade , Modelos Teóricos , Neoplasia Residual/patologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios , Prognóstico , Estudos Prospectivos , Recidiva , RiscoRESUMO
Zn2+ appears to stabilize the myelin sheath but the mechanism of this effect is unknown. In a previous report we have shown that zinc binds to CNS myelin basic protein (MBP) in the presence of phosphate and this results in MBP aggregation. For this paper we used a solid phase zinc blotting assay to identify which myelin proteins bind zinc. MBP and a 58 kDa band were found to be the major targets of 65Zn binding. Moreover, using fluorescence, light scattering and electron microscopy we investigated the binding of zinc and other cations to purified MBP in solution. Among the cations tested for their ability to interfere with the binding of zinc, the most effective were cadmium, mercury and copper, but only cadmium and mercury increased the scattering intensity, whereas MBP aggregation was not inhibited by copper ions. Thus, the effect of zinc on the formation of MBP clusters seems to be specific.
Assuntos
Cátions Bivalentes/metabolismo , Proteína Básica da Mielina/metabolismo , Zinco/metabolismo , Animais , Autorradiografia , Bovinos , Colódio , Luz , Microscopia Eletrônica , Ligação Proteica , Espalhamento de Radiação , Espectrometria de FluorescênciaAssuntos
Côndilo Mandibular/fisiopatologia , Neoplasias Mandibulares/cirurgia , Osteocondroma/cirurgia , Contenções , Adulto , Feminino , Humanos , Neoplasias Mandibulares/fisiopatologia , Boca , Osteocondroma/fisiopatologia , Amplitude de Movimento Articular , Articulação Temporomandibular/fisiopatologia , Trismo/terapiaRESUMO
Authors value the resistance given from biological tissues in brachifacial, mormofacial and dolicofacial patients to know current intensity used during orthodontic therapy for bone remodelling. This study shows that a thicker biological structure gives more resistance to the current flow than other tipologies.