RESUMEN
BACKGROUND: The ARTemis trial previously reported that addition of neoadjuvant bevacizumab (Bev) to docetaxel (D) followed by fluorouracil, epirubicin and cyclophosphamide (D-FEC) in HER2 negative breast cancer improved the pathological complete response (pCR) rate. We present disease-free survival (DFS) and overall survival (OS) with central pathology review. PATIENTS AND METHODS: Patients were randomized to 3 cycles of D followed by 3 cycles of FEC (D-FEC), ±4 cycles of Bev (Bev + D-FEC). DFS and OS were analyzed by treatment and by central pathology reviewed pCR and Residual Cancer Burden (RCB) class. RESULTS: A total of 800 patients were randomized [median follow-up 3.5 years (IQR 3.2-4.4)]. DFS and OS were similar across treatment arms [DFS hazard ratio (HR)=1.18 (95% CI 0.89-1.57), P = 0.25; OS HR = 1.26 (95% CI 0.90-1.76), P = 0.19). Both local pathology report review and central histopathology review confirmed a significant improvement in DFS and OS for patients who achieved a pCR [DFS HR = 0.38 (95% CI 0.23-0.63), P < 0.001; OS HR = 0.43 (95% CI 0.24-0.75), P = 0.003]. However, significant heterogeneity was observed (P = 0.02); larger improvements in DFS were obtained with a pCR achieved with D-FEC than a pCR achieved with Bev + D-FEC. As RCB class increased, significantly worse DFS and OS was observed (P for trend <0.0001), which effect was most marked in the ER negative group. CONCLUSIONS: The addition of short course neoadjuvant Bev to standard chemotherapy did not demonstrate a DFS or OS benefit. Achieving a pCR with D-FEC is associated with improved DFS and OS but not when pCR is achieved with Bev + D-FEC. At the present time therefore, Bev is not recommended in early breast cancer. CLINICALTRIALS.GOV NUMBER: NCT01093235.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bevacizumab/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Taxoides/uso terapéutico , Neoplasias de la Mama/patología , Ciclofosfamida/uso terapéutico , Docetaxel , Diagnóstico Precoz , Epirrubicina/uso terapéutico , Femenino , Fluorouracilo/uso terapéutico , Genes erbB-2 , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Inducción de Remisión , Análisis de SupervivenciaRESUMEN
A facial image was reconstructed from the skull, part of a complete skeleton found in woodland, of a male person who hanged himself from a tree. In addition, video superimposition was carried out with antemortem photographs of a person suspected of being the victim, and a good match was obtained. In a further case, a cheaper video-transparency superimposition was carried out, with identity later being confirmed on the basis of dental records. The techniques and the problems encountered are discussed. According to our experience, 3D computer reconstruction and video superimposition have a useful role in the process of identification, particularly in the early stages of an investigation and when other more definitive methods may not be available.
Asunto(s)
Cefalometría , Computadores , Cara/anatomía & histología , Antropología Forense/métodos , Grabación de Cinta de Video , Adulto , Pueblo Asiatico , Humanos , Masculino , Fotograbar , Población BlancaRESUMEN
The paramagnetic species in human metHb and horse metmyoglobin (metMb) have been studied at low temperature using EPR spectroscopy. The high-spin (HS) haem signal in aquometMb has a greater rhombic distortion than the HS metHb signal. Nevertheless, the individual line width (g=6) is smaller in metMb than in metHb, consistent with non-identical signals from the alpha and beta Hb subunits. Three low-spin (LS) haem forms are present in metHb, while metMb has only two. The major LS form in both proteins is the alkaline species (with OH(-) at the sixth co-ordination position). The minor LS forms are assigned to different histidine hemichromes in equilibrium with the normal HS species at low temperature. LS forms disappear when the haem is bound by a ligand, such as fluoride, which ensures 100% occupancy of the HS state both at room temperature and at 25 K. The small differences in effective g-factors of the histidine hemichromes are interpreted in terms of different distances between the distal histidine and haem iron. The pH dependence of the inter-conversion of the different paramagnetic species is consistent with a model whereby protonation of a residue with a pK of 5.69 (metHb) or 6.12 (metMb), affects ligand binding and transformation from the HS to the LS form. Chemical and spectroscopic considerations suggest that the residue is unlikely to be the proximal or distal histidine. We therefore propose a model where protonation of this distant amino acid causes a conformational change at the iron site. Identical effects are seen in frozen human blood, suggesting that this effect may have physiological significance.