Dual effects of TGF-β on ERα-mediated estrogenic transcriptional activity in breast cancer

<p>Abstract</p> <p>Background</p> <p>TGF-β resistance often develops in breast cancer cells that in turn overproduce this cytokine to create a local immunosuppressive environment that fosters tumor growth and exacerbates the invasive and metastatic behavior of the tumor cells themselves. Smads-mediated cross-talk with the estrogen receptor has been implied to play an important role in development and/or progression of breast cancer. We investigated how TGF-β regulates ERα-induced gene transcription and potential mechanisms of frequent TGF-β resistance in breast cancer.</p> <p>Methods</p> <p>Effect of TGF-β on ERα-mediated gene transcription was investigated in breast cancer cell lines using transient transfection, real-time PCR, sequential DNA precipitation, and small interfering RNA assays. The expression of Smads on both human breast cancer cell lines and ERα-positive human breast cancer tissue was evaluated by immunofluorescence and immunohistochemical assays.</p> <p>Results</p> <p>A complex of Smad3/4 mediates TGF-β inhibition of ERα-mediated estrogenic activity of gene transcription in breast cancer cells, and Smad4 is essential and sufficient for such repression. Either overexpression of Smad3 or inhibition of Smad4 leads to the "switch" of TGF-β from a repressor to an activator. Down-regulation and abnormal cellular distribution of Smad4 were associated with some ERα-positive infiltrating human breast carcinoma. There appears a dynamic change of Smad4 expression from benign breast ductal tissue to infiltrating ductal carcinoma.</p> <p>Conclusion</p> <p>These results suggest that aberrant expression of Smad4 or disruption of Smad4 activity lead to the loss of TGF-β suppression of ERα transactivity in breast cancer cells.</p

Axiomatic Bargaining Theory on Opportunity Assignments

This paper discusses issues of axiomatic bargaining problems over opportunity assignments. The fair arbitrator uses the principle of "equal opportunity" for all players to make the recommendation on re- source allocations. A framework in such a context is developed and several classical solutions to standard bargaining problems are reformulated and axiomatically characterized. Working Paper 06-4

Multi-Objective Optimization of Transonic Compressor Blade Using Evolutionary Algorithm

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/77106/1/AIAA-14667-294.pd

Enhanced tensile ductility and strength of electrodeposited ultrafine-grained nickel with a desired bimodal microstructure

This work aims to use surfactant-assisted direct current electrodeposition technique to prepare four types of bimodal nickel, under different current densities. Bimodal Ni is obtained with different grain size and spatial distribution of CG and UFG areas showing a big disparity in mechanical properties. As a result of small population of coarse-grained surrounded by quite a lot of ultrafine-grained forming a unique shell-and-core bimodal structure, bimodal one present the best comprehensive mechanical properties with an ultrahigh tensile strength (similar to 847 MPa) and a considerable plastic strain (similar to 16.7%). Deformation initial, bimodal structures display more positive strain hardening to meaningful strains than unimodal structure of UFG and CG. Particularly bimodal one work-hardening rate is the highest thanks to its structure (UFG occupy 76.7% in total number fraction) and the distribution of growth twins. Growth twins in this article are referred to Sigma 3(111) coherent twins playing an important role in improving high strength, enhancing uniform plastic deformation ability

Brachial Artery Responses to Ambient Pollution, Temperature, and Humidity in People with Type 2 Diabetes: A Repeated-Measures Study

Background: Extreme weather and air pollution are associated with increased cardiovascular risk in people with diabetes. Objectives: In a population with diabetes, we conducted a novel assessment of vascular brachial artery responses both to ambient pollution and to weather (temperature and water vapor pressure, a measure of humidity). Methods: Sixty-four 49- to 85-year-old Boston residents with type 2 diabetes completed up to five study visits (279 repeated measures). Brachial artery diameter (BAD) was measured by ultrasound before and after brachial artery occlusion [i.e., flow-mediated dilation (FMD)] and before and after nitroglycerin-mediated dilation (NMD). Ambient concentrations of fine particulate mass (PM2.5), black carbon (BC), organic carbon (OC), elemental carbon, particle number, and sulfate were measured at our monitoring site; ambient concentrations of carbon monoxide, nitrogen dioxide, and ozone were obtained from state monitors. Particle exposure in the home and during each trip to the clinic (home/trip exposure) was measured continuously and as a 5-day integrated sample. We used linear models with fixed effects for participants, adjusting for date, season, temperature, and water vapor pressure on the day of each visit, to estimate associations between our outcomes and interquartile range increases in exposure. Results: Baseline BAD was negatively associated with particle pollution, including home/trip–integrated BC (–0.02 mm; 95% CI: –0.04, –0.003, for a 0.28 μg/m3 increase in BC), OC (–0.08 mm; 95% CI: –0.14, –0.03, for a 1.61 μg/m3 increase) as well as PM2.5, 5-day average ambient PM2.5, and BC. BAD was positively associated with ambient temperature and water vapor pressure. However, exposures were not consistently associated with FMD or NMD. Conclusion: Brachial artery diameter, a predictor of cardiovascular risk, decreased in association with particle pollution and increased in association with ambient temperature in our study population of adults with type 2 diabetes. Citation: Zanobetti A, Luttmann-Gibson H, Horton ES, Cohen A, Coull BA, Hoffmann B, Schwartz JD, Mittleman MA, Li Y, Stone PH, de Souza C, Lamparello B, Koutrakis P, Gold DR. 2014. Brachial artery responses to ambient pollution, temperature, and humidity in people with type 2 diabetes: a repeated-measures study. Environ Health Perspect 122:242–248; http://dx.doi.org/10.1289/ehp.120613

5-FU-hydrogel inhibits colorectal peritoneal carcinomatosis and tumor growth in mice

<p>Abstract</p> <p>Background</p> <p>Colorectal peritoneal carcinomatosis (CRPC) is a common form of systemic metastasis of intra-abdominal cancers. Intraperitoneal chemotherapy is a preferable option for colorectal cancer. Here we reported that a new system, 5-FU-loaded hydrogel system, can improve the therapeutic effects of intraperitoneal chemotherapy.</p> <p>Methods</p> <p>A biodegradable PEG-PCL-PEG (PECE) triblock copolymer was successfully synthesized. The biodegradable and temperature sensitive hydrogel was developed to load 5-FU. Methylene blue-loaded hydrogel were also developed for visible observation of the drug release. The effects and toxicity of the 5-FU-hydrogel system were evaluated in a murine CRPC model.</p> <p>Results</p> <p>The hydrogel system is an injectable flowing solution at ambient temperature and forms a non-flowing gel depot at physiological temperature. 5-FU-hydrogel was subsequently injected into abdominal cavity in mice with CT26 cancer cells peritoneal dissemination. The results showed that the hydrogel delivery system prolonged the release of methylene blue; the 5-FU-hydrogel significantly inhibited the peritoneal dissemination and growth of CT26 cells. Furthermore, intraperitoneal administration of the 5-FU-hydrogel was well tolerated and showed less hematologic toxicity.</p> <p>Conclusions</p> <p>Our data indicate that the 5-FU-hydrogel system can be considered as a new strategy for peritoneal carcinomatosis, and the hydrogel may provide a potential delivery system to load different chemotherapeutic drugs for peritoneal carcinomatosis of cancers.</p