The DESTINY-Breast04 clinical trial is currently investigating whether trastuzumab deruxtecan (T-DXd) is effective in HER2-low as well as HER2-positive breast cancer. This highlights the interest in treatment strategies for patients with HER2-low breast cancer. The current study was therefore designed to determine the frequency of HER2-low among all breast cancers, and to compare the prognosis of HER2low patients with that of HER2-negative patients. MethodsWe retrospectively reviewed the biological data from 4,918 of 4,977 primary breast cancer patients who attended our institute. We quanti ed the overall frequency of breast cancer patients with a new HER2-low subtype that was de ned by an immunohistochemistry score of IHC1+ or IHC2+/ISH-. We then compared the clinical characteristics and prognosis of HER2-low patients with that of patients who did not have HER2 ampli cation (HER2-0). ResultsLow HER2 expression was found in 3169 (64.4%) patients; 2860 (58.1%) were HR-positive and 309(6.3%) were HR-negative. Among HER2-0 patients, 681(13.9%) were HR-positive and 157(3.2%) were HRnegative. The HER2-0 group tended to have more poor prognostic factors than the HER2-low group, irrespective of HR status. There were no statistically signi cant differences between the prognosis of HER2-low and HER2-0 patients, regardless of HR status. However, patients in the HER2-low group tended to have better prognosis than those in the HER2-0 group. ConclusionHER2-low patients did not have a signi cantly different prognosis than HER2-0 patients, regardless of HR status. However, we should consider tailoring therapies for patients with HRE2-low early breast cancer according to their HR status.
Objective. To assess levels of soluble Fas (sFas) and soluble Fas ligand (sFas‐L) in sera from patients with various rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), mixed connective tissue disease (MCTD), and Sjögren's syndrome (SS). Methods. Levels of sFas and sFas‐L were determined by a sandwich enzyme‐linked immunosorbent assay. Results. In SLE, PM/DM, MCTD, and SS, sFas levels were significantly higher compared with normal controls. Levels of sFas in the SLE patients were significantly higher than in patients with other rheumatic diseases. Levels of sFas‐L were significantly increased in SS patients. SLE and RA patients with high levels sFas‐L tended to have high levels of sFas, while sFas and sFasL levels did not correlate in patients with other diseases. In some of the SLE patients, sFas and sFas‐L levels decreased following steroid therapy. Conclusion. Serum sFas and sFas‐L levels were significantly higher in some rheumatic disease patients. Since these changes are complex in these rheumatic diseases, it may be difficult to directly relate sFas and sFasL to their pathogenesis.
IL-12 is a cytokine that induces Th1-derived cytokines (interferon-gamma (IFN-gamma) and IL-2). The significance of IL-12 in human autoimmunity is no clear, and the serum levels of IL-12 in SLE are not clearly established. Therefore, we examined the levels of IL-12 in 39 patients with active SLE, with sandwich ELISA. The levels of IL-12 in patients were significantly higher than in normal subjects. Patients with high levels of IL-12 also had high levels of IFN-gamma, while their levels of IL-13 were significantly lower than in patients with normal levels of IL-12. Patients with pulmonary involvement had high levels of IL-12, and steroid therapy decreased the IL-12 level in three patients. In a retrospective study of seven patients, various changes of IL-12 and IL-13 were recognized before disease flare. Thus, in SLE patients, the level of IL-12 was increased and this increase was related to the change of Th1- or Th2-derived cytokines with some organ involvement.
A clear correlation between electronic structure and CO selectivity for steam reforming of methanol (SRM) was obtained with PdZn, PtZn, NiZn, and PdCd intermetallics on the basis of experiments and calculations. In order to rule out the effects of oxide supports, the intermetallic powders were simply prepared by alloying in an arc furnace followed by crushing in a mortar. PdZn and PdCd exhibit valence electronic densities of states similar to that of Cu and significant chemical shifts (larger than 1 eV) of Pd 3d states with respect to pure Pd, as verified by high-resolution hard X-ray photoelectron spectroscopy (HXPS) measurements and density functional theory (DFT) calculations. Consequently, they show the similar high selectivity of CO for the SRM reaction. However, this is not the case for PtZn and NiZn because of the slight differences in their valence electronic structures from that of PdZn. The interval between the Fermi level and the top of the d band is closely related to the selectivity of CO for the SRM: the larger the interval is, the higher is the selectivity of CO. According to DFT calculations for bulk PdZn performed by Chen et al. ( Phys. Rev. B 2003 , 68 , 075417 ), the (111) and (100) surfaces exposing Zn and Pd in an equimolar ratio are more stable than the (001) or (110) surfaces terminated by alternative Zn or Pd layers. First-principles slab calculations for PdZn, PtZn, and NiZn show that bond breaking on the surface leads to a reduction in the d bandwidth but that the d band for stable (111) or (100) surfaces remains essentially unchanged from that of the bulk. It is intriguing that PdZn and PdCd do not contain Cu but show similar valence electronic structure and catalytic selectivity, and hence, a concept is proposed where PdZn and PdCd are regarded as pseudoelements of Cu. The basis of this concept is like electronic structure, like catalysis, which has been demonstrated by experiments and calculations. This is a logical way to enable us to look for new catalysts in which precious metals are partially or completely replaced by base metals. We do not expect that this concept can be applied to all catalytic reactions, but this approach is one of most promising ways to derive a better understanding of the origin of catalytic mechanisms and eventually allow us to design useful catalysts intentionally in the future. This Account reviews the authors' published works on this topic.
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