Erythropoietin drives breast cancer progression by activation of its receptor EPOR

YesBreast cancer is a leading cause of cancer-related deaths. Anemia is common in breast cancer patients and can be treated with blood transfusions or with recombinant erythropoietin (EPO) to stimulate red blood cell production. Clinical studies have indicated decreased survival in some groups of cancer patients treated with EPO. Numerous tumor cells express the EPO receptor (EPOR), posing a risk that EPO treatment would enhance tumor growth, but the mechanisms involved in breast tumor progression are poorly understood. Here, we have examined the functional role of the EPO-EPOR axis in preclinical models of breast cancer. EPO induced the activation of PI3K/AKT and MAPK pathways in human breast cancer cell lines. EPOR knockdown abrogated human tumor cell growth, induced apoptosis through Bim, reduced invasiveness, and caused downregulation of MYC expression. EPO-induced MYC expression is mediated through the PI3K/AKT and MAPK pathways, and overexpression of MYC partially rescued loss of cell proliferation caused by EPOR downregulation. In a xenotransplantation model, designed to simulate recombinant EPO therapy in breast cancer patients, knockdown of EPOR markedly reduced tumor growth. Thus, our experiments in vitro and in vivo demonstrate that functional EPOR signaling is essential for the tumor-promoting effects of EPO and underline the importance of the EPO-EPOR axis in breast tumor progression.Cancer Research UK - C10141/A9977 (TRL, MET, KKC). European Commission FP7 (EpoCan) 282551 (TRL, KBM); Invest NI RD0914223 (TRL, KBM)

Vascular co-option

Vascular co-option is an alternative mechanism to interact with blood vessels used by normal cells and hijacked by cancer cells. Functional experiments using in vivo models have demonstrated that co-option of pre-existing capillary networks is a critical step for the initiation of multiorgan metastases from different cancer types. Thus targeting this process pharmacologically is a very promising strategy to prevent metastases. Vascular co-option supports the viability of disseminated tumor cells, even when they remain dormant. Additionally, targeting vascular co-option could be a valuable strategy to challenge the emergence of resistance to more conventional therapies.S

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Union Membership, Economic Rents, and Migration Behavior

This study represents an extension of the human capital paradigm as it relates to an individual’s decision to migrate. It differs from previous studies by incorporating union membership, a labor market variable, into the model. In effect, the National Labor Relations Act of 1935 granted a monopoly bargaining position to unions. The theoretical implication of a union’s monopoly bargaining position is that union wage levels will increase relative to nonunion wages. The increase of relative wages results in union membership granting a property right that possesses positive net present value and hence reduces an employed union member’s probability of migrating. Additionally, the supra-competitive remuneration of union members results in a surplus of labor supplied to union firms. Employers respond by using quality screening to hire workers from the larger labor pool. As a result, unemployed union members will on average possess higher levels of human capital, which will increase their probability of migrating above that of their unemployed nonunion cohorts

The Use of Spreadsheet Packages in Industrial Engineering: The Case of Regression Analysis with Binary Dependent Variables

Industrial engineers often rely upon multiple regressions in forecasting. However, in the case where the dependent variable is binary, the use of ordinary least squares regression, as provided by spreadsheet packages, introduces serious problems. This study provides an easily implemented alternative technique which solves these problems. The technique is implemented by adding a logit regression template to Lotus 1-2-3

Age and Work Experience in the Decision to Migrate

This study concludes that past migration research studies, by failing to control for years of work experience, have computed a coefficient for the age variable that is the summation of two oppositely signed factors. On the one hand, age increases the psychic cost of moving and decreases the length of the accrual period for benefits thus inhibiting geographic mobility. On the other, age increases the general skill level thus stimulating geographic mobility. By controlling for years of experience, this study more accurately measures the impact of age on the migration decision and introduces a modification to the standard human capital model as presented in migration literature.

Search Time, Unemployment, and the Migration Decision

Several studies have shown that the unemployed in distressed regions of the U.S. have been reluctant to move to areas of greater employment opportunities. By establishing a negative correlation between weeks of job search and the probability of migration, this study is able to provide a partial explanation for the lack of a positive and statistically significant relationship between out-migration rates and the unemployment rate in the local labor market. It is our contention here that those regions that have experienced long periods of high unemployment possess a long-term unemployed population that is less likely to undertake a geographic move.