Phosphorylation of estrogen receptor α serine 167 is predictive of response to endocrine therapy and increases postrelapse survival in metastatic breast cancer

INTRODUCTION: Endocrine therapy is the most important treatment option for women with hormone-receptor-positive breast cancer. The potential mechanisms for endocrine resistance involve estrogen receptor (ER)-coregulatory proteins and crosstalk between ER and other growth factor signaling networks. However, the factors and pathways responsible for endocrine resistance are still poorly identified. METHODS: Using immunohistochemical techniques, we focused on the expression and phosphorylation of hormone receptors themselves and examined the phosphorylation of ER-α Ser118 and ER-α Ser167 and the expression of ER-α, ER-β1, ER-βcx/β2, progesterone receptor (PR), PRA, and PRB in the primary breast carcinomas of 75 patients with metastatic breast cancer who received first-line treatment with endocrine therapy after relapse. RESULTS: Phosphorylation of ER-α Ser118, but not Ser167, was positively associated with overexpression of HER2, and HER2-positive tumors showed resistance to endocrine therapy. The present study has shown for the first time that phosphorylation of ER-α Ser167, but not Ser118, and expression of PRA and PRB, as well as ER-α and PR in primary breast tumors are predictive of response to endocrine therapy, whereas expression of ER-β1 and ER-βcx/β2 did not affect response to the therapy. In addition, patients with either high phosphorylation of ER-α Ser167, or high expression of ER-α, PR, PRA, or PRB had a significantly longer survival after relapse. CONCLUSION: These data suggest that phosphorylation of ER-α Ser167 is helpful in selecting patients who may benefit from endocrine therapy and is a prognostic marker in metastatic breast cancer

Formation and Thermal Behaviors of Ternary Silicon Oxycarbides derived from Silsesquioxane Derivatives

Silsesquioxane (SQ) derivatives possessing intramolecular H2C = CH- groups and Si-H groups were designed as precursors for ternary silicon oxycarbide (SiOC). By using R-Si(OMe)3, H-Si(OEt)3 and (H-Si(Me)2)2O as starting compounds, SQ derivatives of VH-SQ (R = vinyl) and St-H-SQ (R = stylyl) were successfully synthesized through the conventional sol-gel route. Simultaneous thermogravimetric and mass spectroscopic analyses up to 1000 °C revealed that in situ cross-linking via hydrosilylation and demethanation of VH-SQ suppressed the evolution of gaseous hydrocarbon species to afford amorphous SiOC having a composition close to the desired stoichiometric SiO2(1−x)Cx (x = ca. 0.3) with a high yield. The effect of carbon content on the phase separation and crystallization of the SQ-derived amorphous SiOC was studied by several spectroscopic analyses and TEM observation. The results were discussed aiming to develop a novel polymer-derived ceramics (PDCs) route for in situ formation of binary β-SiC-amorphous SiO2 nanocomposites with enhanced thermal and mechanical stability

Pulsed neutron spectroscopic imaging for crystallographic texture and microstructure

A time-of-flight (TOF) spectroscopic neutron imaging at a pulsed neutron source is expected to be a new material analysis tool because this method can non-destructively investigate the spatial dependence of the crystallographic and metallographic information in a bulk material. For quantitative evaluation of such information, a spectral analysis code for the transmission data is necessary. Therefore, we have developed a Rietveld-like analysis code, RITS. Furthermore, we have applied the RITS code to evaluation of the position dependence of the crystal orientation anisotropy, the preferred orientation and the crystallite size of a welded α-iron plate, and we have successfully obtained the information on the texture and the microstructure. However, the reliability of the values given by the RITS code has not been evaluated yet in detail. For this reason, we compared the parameters provided by the RITS code with the parameters obtained by the neutron TOF powder diffractometry and its Rietveld analysis. Both the RITS code and the Rietveld analysis software indicated values close to each other, but there were systematic differences on the preferred orientation and the crystallite size

Teaching a Mobile Robot to Take Elevators

The ability of moving between floors by using elevators is indispensable for mobile robots operating in office environments to expand their work areas. This paper describes a method of interactively teaching the task of taking elevators for making it easier for the user to use such robots for various elevators. The necessary knowledge of the task is organized as the task model. The robot examines the task model and determines what are missing in the model, and then asks the user to teach them. This enables the user to teach the necessary knowledge easily and efficiently. Experimental results show the potential usefulness of our approach.

Simultaneous Broadening Analysis of Multiple Bragg Edges Observed by Wavelength-resolved Neutron Transmission Imaging of Deformed Low-carbon Ferritic Steel

With the goal of real-space mapping of dislocation information using a wavelength-resolved (spectroscopic) neutron transmission imaging method, broadenings of multiple Bragg-edges in neutron transmission spectrum were investigated in detail for the first time. Data of time-of-flight (TOF) neutron transmission imaging and diffraction experiments on a polycrystalline low-carbon ferritic steel sample while undergoing tensile testing were analysed. The Bragg-edge neutron transmission spectroscopy was combined with the classical Williamson-Hall method corrected by the crystal elastic anisotropy using the ratio of diffraction Young's modulus, namely, the corrected classical Williamson-Hall (ccWH) method. As a result, the broadening values evaluated from the ccWH analysis of Bragg-edge data were consistent with results of both our TOF neutron diffraction experiments and previous reports. In addition, it was deduced that the line-broadenings appearing in the plastic deformation condition during tensile testing in our experiment were mainly caused by micro-strain (dislocation density) effect and not by crystallite size effect. Finally, a Bragg-edge broadening mapping method, using a simultaneous multiple Bragg-edges profile analysis based on the ccWH method, could identify plastically deformed zones in the sample more clearly than a traditional single Bragg-edge broadening analysis method