NgBR is a type I receptor with a single transmembrane domain and was identified as a specific receptor for Nogo-B. Our recent findings demonstrated that NgBR binds farnesylated Ras and recruits Ras to the plasma membrane, which is a critical step required for the activation of Ras signaling in human breast cancer cells and tumorigenesis. Here, we first use immunohistochemistry and real-time PCR approaches to examine the expression patterns of Nogo-B and NgBR in both normal and breast tumor tissues. Then, we examine the relationship between NgBR expression and molecular subtypes of breast cancer, and the roles of NgBR in estrogen-dependent survivin signaling pathway. Results showed that NgBR and Nogo-B protein were detected in both normal and breast tumor tissues. However, the expression of Nogo-B and NgBR in breast tumor tissue was much stronger than in normal breast tissue. The statistical analysis demonstrated that NgBR is highly associated with ER-positive/HER2-negative breast cancer. We also found that the expression of NgBR has a strong correlation with the expression of survivin, which is a well-known apoptosis inhibitor. The correlation between NgBR and survivin gene expression was further confirmed by real-time PCR. In vitro results also demonstrated that estradiol induces the expression of survivin in ER-positive T47D breast tumor cells but not in ER-negative MDA-MB-468 breast tumor cells. NgBR knockdown with siRNA abolishes estradiol-induced survivin expression in ER-positive T47D cells but not in ER-negative MDA-MB-468 cells. In addition, estradiol increases the expression of survivin and cell growth in ER-positive MCF-7 and T47D cells whereas knockdown of NgBR with siRNA reduces estradiol-induced survivin expression and cell growth. In summary, these results indicate that NgBR is a new molecular marker for breast cancer. The data suggest that the expression of NgBR may be essential in promoting ER-positive tumor cell proliferation via survivin induction in breast cancer.
This article presents an overview of the benign conditions that affect the breast for the practicing surgeon. The authors discuss the diagnosis and management of a variety of breast pathologic conditions, including those associated with infection and inflammation as well as proliferative and nonproliferative disorders. The authors also offer their experience with the integration of nurse practitioners in the care of patients with benign breast disease.
Purpose
Population-based studies have revealed higher mortality among breast cancer patients treated in low-volume hospitals. Other studies have demonstrated disparities in race and socioeconomic status (SES) in breast cancer survival. The purpose of our study was to determine whether nonwhite or low-SES patients are disproportionately treated in low-volume hospitals.
Methods
A population-based cohort of 2,777 Medicare breast cancer patients who underwent breast cancer surgery in 2003 participated in a survey study examining breast cancer outcomes. Information was obtained from survey responses, Medicare claims, and state tumor registry data.
Results
On univariate analysis, patients treated at low-volume hospitals were less likely to be white, less likely to live in an urban location, and more likely to have a low SES with less social support and live a greater distance from a high-volume hospital. Education, marital status, total household income, having additional insurance besides Medicare, population density of primary residence, and tangible support were associated with distance to the nearest high-volume hospital. On multivariate analysis, the independent predictors of treatment at a low-volume hospital were being nonwhite (P = 0.003), having a lower household income (P < 0.0001), residence in a rural location (P = 0.01), and living a greater distance from a high-volume hospital (P < 0.0001).
Conclusions
In this large population-based cohort, women who were poorer, nonwhite, and who lived in a rural location or at a greater distance from a high-volume hospital were more likely to be treated at low-volume hospitals. These differences may partially explain racial and SES disparities in breast cancer outcomes.
Chemotherapy (CT) is a necessary treatment to prevent the growth and survival of cancer cells. However, CT has a well-established adverse impact on the cardiovascular (CV) system, even years after cessation of treatment. The effects of CT drugs on tumor vasculature have been the focus of much research, but little evidence exists showing the effects on the host microcirculation. Microvascular (MV) dysfunction is an early indicator of numerous CV disease phenotypes, including heart failure. The goal of this study was to evaluate the direct effect of doxorubicin (Dox) on human coronary MV function. To study the effect of CT on the cardiac MV function, flow-mediated dilation (FMD), pharmacologically-induced endothelial dependent dilation to acetylcholine (ACh), and smooth muscle-dependent dilation to papaverine were investigated. Vessels were freshly isolated from atrial appendages of adult patients undergoing cardiopulmonary bypass surgery or from cardiac tissue of pediatric patients, collected at the time of surgery to repair congenital heart defects. Isolated vessels were incubated in endothelial culture medium containing vehicle or Dox (100 nm, 15–20 h) and used to measure dilator function by video microscopy. Ex vivo treatment of adult human coronary microvessels with Dox significantly impaired flow-mediated dilation (FMD). Conversely, in pediatric coronary microvessels, Dox-induced impairment of FMD was significantly reduced in comparison with adult subjects. In both adult and pediatric coronary microvessels, ACh-induced constriction was reversed into dilation in the presence of Dox. Smooth muscle-dependent dilation remained unchanged in all groups tested. In vessels from adult subjects, acute treatment with Dox in clinically relevant doses caused significant impairment of coronary arteriolar function, whereas vessels from pediatric subjects showed only marginal impairment to the same stressor. This interesting finding might explain the delayed onset of future adverse CV events in children compared with adults after anthracycline therapy. NEW & NOTEWORTHY We have characterized, for the first time, human microvascular responses to acute ex vivo exposure to doxorubicin in coronary vessels from patients without cancer. Our data show an augmented impairment of endothelial function in vessels from adult subjects compared with pediatric samples.
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