Hormones and breast and endometrial cancers: preventive strategies and future research.

A number of hormonal approaches for prevention of endometrial and breast cancers have been proposed. Because of the hormonal responsiveness of both tumors, much attention has focused on effects of exogenous hormone use. Although estrogens in hormone replacement therapy increase the risk of endometrial cancer, the disease is substantially reduced by long-term use of oral contraceptives. The issues with breast cancer are more complex, mainly because of a variety of unresolved effects. Long-term estrogen use is associated with some increase in breast cancer risk, and certain patterns of oral contraceptives appear to predispose to early-onset disease. With respect to estrogens, preventive approaches for both tumors would include use for as limited periods of time as possible. Addition of a progestin appears to lower estrogen-associated endometrial disease, but its effect on breast cancer risk remains less clear. Additional studies on effects of detailed usage parameters should provide useful insights into etiologic mechanisms. Other preventive approaches for endometrial cancer that may work through hormonal mechanisms include staying thin, being physically active, and maintaining a vegetarian diet. Breast cancer risk may possibly be reduced by extended periods of breastfeeding, restriction of intake of alcoholic beverages, remaining thin later in life, and being physically active. Additional research is needed to clarify the biologic mechanisms of these associations. The bridging of epidemiology with the biologic sciences should clarify many unresolved issues and lead to better preventive approaches

Effect of Injector Exit Geometry on Atomization of a Liquid-Liquid Double Swirl Coaxial Injector using Non-Invasive Laser, Optical, and X-ray Techniques

The spray characteristics of a liquid-liquid double swirl coaxial injector were studied using non-invasive optical, laser, and X-ray diagnostics. Phase Doppler interferometry was used to characterize droplet statistics and non-dimensional droplet parameters over a range of inlet conditions and for various fluids allowing for a study on the role of fluid properties on atomization. Based on the atomization statistics and observed trends from high-speed images, a description of breakup regimes over a range of Reynolds and Weber numbers was created. Next, X-ray computed tomography scans revealed that the spray cone was distinctively non-uniform and comprised of several pockets of increased mass concentration which varied with injection pressure. Finally, a parametric study of injector exit geometry demonstrated that spray breakup time, breakup type, and sheet stability could be controlled with exit geometry. Implications for these data on injector stability and atomization efficiency are discussed considering the desired performance characteristics of liquid-liquid rocket injectors

Human tissue monitoring and specimen banking: opportunities for exposure assessment, risk assessment, and epidemiologic research

A symposium on Human Tissue Monitoring and Specimen Banking: Opportunities for Exposure Assessment, Risk Assessment, and Epidemiologic Research was held from 30 March to 1 April 1993 in Research Triangle Park, North Carolina. There were 117 registered participants from 18 states and 5 foreign countries. The first 2 days featured 21 invited speakers from the U.S. Environmental Protection Agency, the Centers for Disease Control and Prevention, the National Institute of Environmental Health Sciences, various other government agencies, and universities in the United States, Canada, Germany, and Norway. The speakers provided a state-of-the-art overview of human exposure assessment techniques (especially applications of biological markers) and their relevance to human tissue specimen banking. Issues relevant to large-scale specimen banking were discussed, including program design, sample design, data collection, tissue collection, and ethical ramifications. The final group of presentations concerned practical experiences of major specimen banking and human tissue monitoring programs in the United States and Europe. The symposium addressed the utility and research opportunities afforded by specimen banking programs for future research needs in the areas of human exposure assessment, risk assessment, and environmental epidemiology. The third day of the symposium consisted of a small workshop convened to discuss and develop recommendations to the U.S. Environmental Protection Agency regarding applications and utility of large-scale specimen banking, biological monitoring, and biological markers for risk assessment activities

Design and Fabrication of Oxygen/RP-2 Multi-Element Oxidizer-Rich Staged Combustion Thrust Chamber Injectors

As part of the Combustion Stability Tool Development project funded by the Air Force Space and Missile Systems Center, the NASA Marshall Space Flight Center was contracted to assemble and hot-fire test a multi-element integrated test article demonstrating combustion characteristics of an oxygen/hydrocarbon propellant oxidizer-rich staged-combustion engine thrust chamber. Such a test article simulates flow through the main injectors of oxygen/kerosene oxidizer-rich staged combustion engines such as the Russian RD-180 or NK-33 engines, or future U.S.-built engine systems such as the Aerojet-Rocketdyne AR-1 engine or the Hydrocarbon Boost program demonstration engine. On the current project, several configurations of new main injectors were considered for the thrust chamber assembly of the integrated test article. All the injector elements were of the gas-centered swirl coaxial type, similar to those used on the Russian oxidizer-rich staged-combustion rocket engines. In such elements, oxidizer-rich combustion products from the preburner/turbine exhaust flow through a straight tube, and fuel exiting from the combustion chamber and nozzle regenerative cooling circuits is injected near the exit of the oxidizer tube through tangentially oriented orifices that impart a swirl motion such that the fuel flows along the wall of the oxidizer tube in a thin film. In some elements there is an orifice at the inlet to the oxidizer tube, and in some elements there is a sleeve or "shield" inside the oxidizer tube where the fuel enters. In the current project, several variations of element geometries were created, including element size (i.e., number of elements or pattern density), the distance from the exit of the sleeve to the injector face, the width of the gap between the oxidizer tube inner wall and the outer wall of the sleeve, and excluding the sleeve entirely. This paper discusses the design rationale for each of these element variations, including hydraulic, structural, thermal, combustion performance, and combustion stability considerations. This paper also discusses the fabrication and assembly of the injector components, including the injector body/interpropellant plate, the additive manufactured GRCop-84 faceplate, and the pieces that make up the injector elements including the oxidizer tube, an inlet to the oxidizer tube, and a facenut that includes the fuel tangential inlets and forms the initial recessed volume where oxidizer and fuel first interact. Hot-fire test results of these main injector designs in an integrated test article that includes an oxidizer-rich preburner are described in companion papers at this JANNAF meeting

Cotinine concentrations in semen, urine, and blood of smokers and nonsmokers.

Cotinine levels in the semen, urine, and blood of 88 male smokers and nonsmokers, aged 18 and 35, were analyzed via radioimmunoassay. Detectable cotinine levels were found in all three body fluids, and cotinine levels in all three fluids were highly correlated. Cotinine levels in semen and blood were of similar magnitude; cotinine levels in urine were an order of magnitude or more higher. In all three fluids, cotinine levels increased with an increase in cigarette smoke exposure.Cotinine levels in the semen, urine, and blood of 88 male smokers and nonsmokers, aged 18 and 35, were analyzed via radioimmunoassay. Detectable cotinine levels were found in all three body fluids, and cotinine levels in all three fluids were highly correlated. Cotinine levels in semen and blood were of similar magnitude; cotinine levels in urine were an order of magnitude or more higher. In all three fluids, cotinine levels increased with an increase in cigarette smoke exposure

DNA repair genes XRCC1 and XRCC3 polymorphisms and their relationship with the level of micronuclei in breast cancer patients

Breast cancer (BC) is the most prevalent type worldwide, besides being one of the most common causes of death among women. It has been suggested that sporadic BC is most likely caused by low-penetrance genes, including those involved in DNA repair mechanisms. Furthermore, the accumulation of DNA damage may contribute to breast carcinogenesis. In the present study, the relationship between two DNA repair genes, viz., XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms, and the levels of chromosome damage detected in 65 untreated BC women and 85 healthy controls, was investigated. Chromosome damage was evaluated through micronucleus assaying, and genotypes determined by PCR-RFLP methodology. The results showed no alteration in the risk of BC and DNA damage brought about by either XRCC1 (Arg399Gln) or XRCC3 (Thr241Met) action in either of the two groups. Nevertheless, on evaluating BC risk in women presenting levels of chromosome damage above the mean, the XRCC3Thr241Met polymorphism was found to be more frequent in the BC group than in the control, thereby leading to the conclusion that there is a slight association between XRCC3 (241 C/T) genotypes and BC risk in the subgroups with higher levels of chromosome damage

In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

© 2008 Garvin and Dabrosin; licensee BioMed Central Ltd

Assessment of health care needs and utilization in a mixed public-private system: the case of the Athens area

BACKGROUND: Given the public-private mix of the Greek health system, the purpose of this study was to assess whether variations in the utilisation of health services, both primary and inpatient care, were associated with underlying health care needs and/or various socio-economic factors. METHODS: Data was obtained from a representative sample (N = 1426) residing in the broader Athens area (response rate 70.6%). Perceived health-related quality of life (HRQOL), as measured by the physical and mental summary component scores of the SF-36 Health Survey, was used as a proxy of health care need. Health care utilization was measured by a) last-month visits to public sector physicians, b) last-month visits to private sector physicians, c) last-year visits to hospital emergency departments and d) last-year hospital admissions. Statistical analysis involved the implementation of logistic regression models. RESULTS: Health care need was the factor most strongly associated with all measures of health care utilization, except for visits to public physicians. Women, elderly, less wealthy and individuals of lower physical health status visited physicians contracted to their insurance fund (public sector). Women, well educated and those once again of lower physical health status were more likely to visit private providers. Visits to hospital emergency departments and hospital admissions were related to need and no socio-economic factor was related to the use of those types of care. CONCLUSION: This study has demonstrated a positive relationship between health care need and utilisation of health services within a mixed public-private health care system. Concurrently, interesting differences are evident in the utilization of various types of services. The results have potential implications in health policy-making and particularly in the proper allocation of scarce health resources

Withaferin a-induced apoptosis in human breast cancer cells is mediated by reactive oxygen species

Withaferin A (WA), a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera, inhibits growth of MDA-MB-231 and MCF-7 human breast cancer cells in culture and MDA-MB-231 xenografts in vivo in association with apoptosis induction, but the mechanism of cell death is not fully understood. We now demonstrate, for the first time, that WA-induced apoptosis is mediated by reactive oxygen species (ROS) production due to inhibition of mitochondrial respiration. WA treatment caused ROS production in MDA-MB-231 and MCF-7 cells, but not in a normal human mammary epithelial cell line (HMEC). The HMEC was also resistant to WA-induced apoptosis. WA-mediated ROS production as well as apoptotic histone-associated DNA fragment release into the cytosol was significantly attenuated by ectopic expression of Cu,Zn-superoxide dismutase in both MDA-MB-231 and MCF-7 cells. ROS production resulting from WA exposure was accompanied by inhibition of oxidative phosphorylation and inhibition of complex III activity. Mitochondrial DNA-deficient Rho-0 variants of MDA-MB-231 and MCF-7 cells were resistant to WA-induced ROS production, collapse of mitochondrial membrane potential, and apoptosis compared with respective wild-type cells. WA treatment resulted in activation of Bax and Bak in MDA-MB-231 and MCF-7 cells, and SV40 immortalized embryonic fibroblasts derived from Bax and Bak double knockout mouse were significantly more resistant to WA-induced apoptosis compared with fibroblasts derived from wild-type mouse. In conclusion, the present study provides novel insight into the molecular circuitry of WA-induced apoptosis involving ROS production and activation of Bax/Bak. © 2011 Hahm et al