Clinicopathological characteristics and survival outcomes in Paget disease: a SEER populationâ based study

The objective of this study was to investigate the clinicopathological characteristics and survival outcomes of Paget disease (PD), Paget disease concomitant infiltrating duct carcinoma (PDâ IDC), and Paget disease concomitant intraductal carcinoma (PDâ DCIS). We identified 501,631 female patients from 2000 to 2013 in the Surveillance, Epidemiology, and End Results (SEER) database. These identified patients included patients with PD (n = 469), patients with PDâ IDC (n = 1832), and patients with PDâ DCIS (n = 1130) and infiltrating ductal carcinoma (IDC) (n = 498,076). Then, we compared the clinical characteristics of these patients with those who were diagnosed with IDC during the same period. The outcomes of these subtypes of breast carcinoma were different. Based on the overall survival, the patients with PDâ IDC had the worst prognosis (5â year survival rate = 84.1%). The PDâ DCIS had the best prognosis (5â year survival rate = 97.5%). Besides, among patients with Paget disease, the one who was married had a better prognosis than who were not. And, according to our research, the marital status was associated with the hormone receptor status in patients with PDâ IDC. Among three subtypes of Paget disease, patients with PDâ IDC had the worst prognosis. Besides, patients who were unmarried had worse outcomes. And the marital status of patients with PDâ IDC is associated with hormone status. The observation underscores the importance of individualized treatment.Patients with PDâ IDC have the worst prognosis. And the marital status of PDâ IDC patients is associated with hormone status and HER2 status. The observation underscores the importance of individualized treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144702/1/cam41475.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144702/2/cam41475_am.pd

Inactivation and unfolding of protein tyrosine phosphatase from Thermus thermophilus HB27 during urea and guanidine hydrochloride denaturation.

The effects of urea and guanidine hydrochloride (GdnHCl) on the activity, conformation and unfolding process of protein tyrosine phosphatase (PTPase), a thermostable low molecular weight protein from Thermus thermophilus HB27, have been studied. Enzymatic activity assays showed both urea and GdnHCl resulted in the inactivation of PTPase in a concentration and time-dependent manner. Inactivation kinetics analysis suggested that the inactivation of PTPase induced by urea and GdnHCl were both monophasic and reversible processes, and the effects of urea and GdnHCl on PTPase were similar to that of mixed-type reversible inhibitors. Far-ultraviolet (UV) circular dichroism (CD), Tryptophan and 1-anilinonaphthalene -8-sulfonic acid (ANS) fluorescence spectral analyses indicated the existence of a partially active and an inactive molten globule-like intermediate during the unfolding processes induced by urea and GdnHCl, respectively. Based on the sequence alignment and the homolog Tt1001 protein structure, we discussed the possible conformational transitions of PTPase induced by urea and GdnHCl and compared the conformations of these unfolding intermediates with the transient states in bovine PTPase and its complex structures in detail. Our results may be able to provide some valuable clues to reveal the relationship between the structure and enzymatic activity, and the unfolding pathway and mechanism of PTPase

Down-Regulation of NDUFB9 Promotes Breast Cancer Cell Proliferation, Metastasis by Mediating Mitochondrial Metabolism.

Despite advances in basic and clinical research, metastasis remains the leading cause of death in breast cancer patients. Genetic abnormalities in mitochondria, including mutations affecting complex I and oxidative phosphorylation, are found in breast cancers and might facilitate metastasis. Genes encoding complex I components have significant breast cancer prognostic value. In this study, we used quantitative proteomic analyses to compare a highly metastatic cancer cell line and a parental breast cancer cell line; and observed that NDUFB9, an accessory subunit of the mitochondrial membrane respiratory chain NADH dehydrogenase (complex I), was down-regulated in highly metastatic breast cancer cells. Furthermore, we demonstrated that loss of NDUFB9 promotes MDA-MB-231 cells proliferation, migration, and invasion because of elevated levels of mtROS, disturbance of the NAD+/NADH balance, and depletion of mtDNA. We also showed that, the Akt/mTOR/p70S6K signaling pathway and EMT might be involved in this mechanism. Thus, our findings contribute novel data to support the hypothesis that misregulation of mitochondrial complex I NADH dehydrogenase activity can profoundly enhance the aggressiveness of human breast cancer cells, suggesting that complex I deficiency is a potential and important biomarker for further basic research or clinical application

The inactivation rate constants and residual activity of PTPase in the presence of different concentrations of urea.

<p>The inactivation rate constants and residual activity of PTPase in the presence of different concentrations of urea.</p

Intrinsic fluorescence spectra of PTPase in the presence of different concentrations of urea and GdnHCl.

<p>(A) Urea concentrations for the labels 1–9 were 0, 1, 2, 3, 4, 5, 6, 7 and 8 M, respectively. (B) GdnHCl concentrations for the labels 1–7 were 0, 0.5, 1, 1.25, 1.5, 2 and 2.5 M, respectively. (C–D) The relative changes of Imax value as a function of [urea] and [GdnHCl], respectively. (E–F) The relative changes of λmax value as a function of [urea] and [GdnHCl], respectively.</p

The inactivation rate constants and residual activity of PTPase in the presence of different concentrations of GdnHCl.

<p>The inactivation rate constants and residual activity of PTPase in the presence of different concentrations of GdnHCl.</p

The inhibition and inactivation kinetic parameters of PTPase in the presence of urea and GdnHCl.

<p>The inhibition and inactivation kinetic parameters of PTPase in the presence of urea and GdnHCl.</p