Response of Estrogen Receptor-Positive Breast Cancer Tumorspheres to Antiestrogen Treatments

Estrogen signaling plays a critical role in the pathogenesis of breast cancer. Because the majority of breast carcinomas express the estrogen receptor ERα, endocrine therapy that impedes estrogen-ER signaling reduces breast cancer mortality and has become a mainstay of breast cancer treatment. However, patients remain at continued risk of relapse for many years after endocrine treatment. It has been proposed that cancer recurrence may be attributed to cancer stem cells (CSCs)/tumor-initiating cells (TICs). Previous studies in breast cancer have shown that such cells can be enriched and propagated in vitro by culturing the cells in suspension as mammospheres/tumorspheres. Here we established tumorspheres from ERα-positive human breast cancer cell line MCF7 and investigated their response to antiestrogens Tamoxifen and Fulvestrant. The tumorsphere cells express lower levels of ERα and are more tumorigenic in xenograft assays than the parental cells. Both 4-hydroxytamoxifen (4-OHT) and Fulvestrant attenuate tumorsphere cell proliferation, but only 4-OHT at high concentrations interferes with sphere formation. However, treated tumorsphere cells retain the self-renewal capacity. Upon withdrawal of antiestrogens, the treated cells resume tumorsphere formation and their tumorigenic potential remains undamaged. Depletion of ERα shows that ERα is dispensable for tumorsphere formation and xenograft tumor growth in mice. Surprisingly, ERα-depleted tumorspheres display heightened sensitivity to 4-OHT and their sphere-forming capacity is diminished after the drug is removed. These results imply that 4-OHT may inhibit cellular targets besides ERα that are essential for tumorsphere growth, and provide a potential strategy to sensitize tumorspheres to endocrine treatment

Medical advice and diabetes self-management reported by Mexican-American, Black- and White-non-Hispanic adults across the United States

<p>Abstract</p> <p>Background</p> <p>Diabetes has reached epidemic proportions in the United States, particularly among minorities, and if improperly managed can lead to medical complications and death. Healthcare providers play vital roles in communicating standards of care, which include guidance on diabetes self-management. The background of the client may play a role in the patient-provider communication process. The aim of this study was to determine the association between medical advice and diabetes self care management behaviors for a nationally representative sample of adults with diabetes. Moreover, we sought to establish whether or not race/ethnicity was a modifier for reported medical advice received and diabetes self-management behaviors.</p> <p>Methods</p> <p>We analyzed data from 654 adults aged 21 years and over with diagnosed diabetes [130 Mexican-Americans; 224 Black non-Hispanics; and, 300 White non-Hispanics] and an additional 161 with 'undiagnosed diabetes' [N = 815(171 MA, 281 BNH and 364 WNH)] who participated in the National Health and Nutrition Examination Survey (NHANES) 2007-2008. Logistic regression models were used to evaluate whether medical advice to engage in particular self-management behaviors (reduce fat or calories, increase physical activity or exercise, and control or lose weight) predicted actually engaging in the particular behavior and whether the impact of medical advice on engaging in the behavior differed by race/ethnicity. Additional analyses examined whether these relationships were maintained when other factors potentially related to engaging in diabetes self management such as participants' diabetes education, sociodemographics and physical characteristics were controlled. Sample weights were used to account for the complex sample design.</p> <p>Results</p> <p>Although medical advice to the patient is considered a standard of care for diabetes, approximately one-third of the sample reported not receiving dietary, weight management, or physical activity self-management advice. Participants who reported being given medical advice for each specific diabetes self-management behaviors were 4-8 times more likely to report performing the corresponding behaviors, independent of race. These results supported the ecological model with certain caveats.</p> <p>Conclusions</p> <p>Providing standard medical advice appears to lead to diabetes self-management behaviors as reported by adults across the United States. Moreover, it does not appear that race/ethnicity influenced reporting performance of the standard diabetes self-management behavior. Longitudinal studies evaluating patient-provider communication, medical advice and diabetes self-management behaviors are needed to clarify our findings.</p

Does rapid HIV disease progression prior to combination antiretroviral therapy hinder optimal CD4 + T-cell recovery once HIV-1 suppression is achieved?

Objective: This article compares trends in CD4+ T-cell recovery and proportions achieving optimal restoration (>=500 cells/µl) after viral suppression following combination antiretroviral therapy (cART) initiation between rapid and nonrapid progressors. Methods: We included HIV-1 seroconverters achieving viral suppression within 6 months of cART. Rapid progressors were individuals experiencing at least one CD4+ less than 200 cells/µl within 12 months of seroconverters before cART. We used piecewise linear mixed models and logistic regression for optimal restoration. Results: Of 4024 individuals, 294 (7.3%) were classified as rapid progressors. At the same CD4+ T-cell count at cART start (baseline), rapid progressors experienced faster CD4+ T-cell increases than nonrapid progressors in first month [difference (95% confidence interval) in mean increase/month (square root scale): 1.82 (1.61; 2.04)], which reversed to slightly slower increases in months 1–18 [-0.05 (-0.06; -0.03)] and no significant differences in 18–60 months [-0.003 (-0.01; 0.01)]. Percentage achieving optimal restoration was significantly lower for rapid progressors than nonrapid progressors at months 12 (29.2 vs. 62.5%) and 36 (47.1 vs. 72.4%) but not at month 60 (70.4 vs. 71.8%). These differences disappeared after adjusting for baseline CD4+ T-cell count: odds ratio (95% confidence interval) 0.86 (0.61; 1.20), 0.90 (0.38; 2.17) and 1.56 (0.55; 4.46) at months 12, 36 and 60, respectively. Conclusion: Among people on suppressive antiretroviral therapy, rapid progressors experience faster initial increases of CD4+ T-cell counts than nonrapid progressors, but are less likely to achieve optimal restoration during the first 36 months after cART, mainly because of lower CD4+ T-cell counts at cART initiation

Promoter methylation correlates with reduced NDRG2 expression in advanced colon tumour

<p>Abstract</p> <p>Background</p> <p>Aberrant DNA methylation of CpG islands of cancer-related genes is among the earliest and most frequent alterations in cancerogenesis and might be of value for either diagnosing cancer or evaluating recurrent disease. This mechanism usually leads to inactivation of tumour-suppressor genes. We have designed the current study to validate our previous microarray data and to identify novel hypermethylated gene promoters.</p> <p>Methods</p> <p>The validation assay was performed in a different set of 8 patients with colorectal cancer (CRC) by means quantitative reverse-transcriptase polymerase chain reaction analysis. The differential RNA expression profiles of three CRC cell lines before and after 5-aza-2'-deoxycytidine treatment were compared to identify the hypermethylated genes. The DNA methylation status of these genes was evaluated by means of bisulphite genomic sequencing and methylation-specific polymerase chain reaction (MSP) in the 3 cell lines and in tumour tissues from 30 patients with CRC.</p> <p>Results</p> <p>Data from our previous genome search have received confirmation in the new set of 8 patients with CRC. In this validation set six genes showed a high induction after drug treatment in at least two of three CRC cell lines. Among them, the N-myc downstream-regulated gene 2 (<it>NDRG2) </it>promoter was found methylated in all CRC cell lines. <it>NDRG2 </it>hypermethylation was also detected in 8 out of 30 (27%) primary CRC tissues and was significantly associated with advanced AJCC stage IV. Normal colon tissues were not methylated.</p> <p>Conclusion</p> <p>The findings highlight the usefulness of combining gene expression patterns and epigenetic data to identify tumour biomarkers, and suggest that NDRG2 silencing might bear influence on tumour invasiveness, being associated with a more advanced stage.</p

Patterns and universals of mate poaching across 53 nations : the effects of sex, culture, and personality on romantically attracting another person’s partner

As part of the International Sexuality Description Project, 16,954 participants from 53 nations were administered an anonymous survey about experiences with romantic attraction. Mate poaching--romantically attracting someone who is already in a relationship--was most common in Southern Europe, South America, Western Europe, and Eastern Europe and was relatively infrequent in Africa, South/Southeast Asia, and East Asia. Evolutionary and social-role hypotheses received empirical support. Men were more likely than women to report having made and succumbed to short-term poaching across all regions, but differences between men and women were often smaller in more gender-egalitarian regions. People who try to steal another's mate possess similar personality traits across all regions, as do those who frequently receive and succumb to the poaching attempts by others. The authors conclude that human mate-poaching experiences are universally linked to sex, culture, and the robust influence of personal dispositions.peer-reviewe

Are men universally more dismissing than women? Gender differences in romantic attachment across 62 cultural regions

The authors thank Susan Sprecher (USA), Del Paulhus (Canada), Glenn D. Wilson (England), Qazi Rahman (England), Alois Angleitner (Germany), Angelika Hofhansl (Austria), Tamio Imagawa (Japan), Minoru Wada (Japan), Junichi Taniguchi (Japan), and Yuji Kanemasa (Japan) for helping with data collection and contributing significantly to the samples used in this study.Gender differences in the dismissing form of adult romantic attachment were investigated as part of the International Sexuality Description Project—a survey study of 17,804 people from 62 cultural regions. Contrary to research findings previously reported in Western cultures, we found that men were not significantly more dismissing than women across all cultural regions. Gender differences in dismissing romantic attachment were evident in most cultures, but were typically only small to moderate in magnitude. Looking across cultures, the degree of gender differentiation in dismissing romantic attachment was predictably associated with sociocultural indicators. Generally, these associations supported evolutionary theories of romantic attachment, with smaller gender differences evident in cultures with high–stress and high–fertility reproductive environments. Social role theories of human sexuality received less support in that more progressive sex–role ideologies and national gender equity indexes were not cross–culturally linked as expected to smaller gender differences in dismissing romantic attachment.peer-reviewe

Differential cross section measurements for the production of a W boson in association with jets in proton–proton collisions at √s = 7 TeV

Measurements are reported of differential cross sections for the production of a W boson, which decays into a muon and a neutrino, in association with jets, as a function of several variables, including the transverse momenta (pT) and pseudorapidities of the four leading jets, the scalar sum of jet transverse momenta (HT), and the difference in azimuthal angle between the directions of each jet and the muon. The data sample of pp collisions at a centre-of-mass energy of 7 TeV was collected with the CMS detector at the LHC and corresponds to an integrated luminosity of 5.0 fb[superscript −1]. The measured cross sections are compared to predictions from Monte Carlo generators, MadGraph + pythia and sherpa, and to next-to-leading-order calculations from BlackHat + sherpa. The differential cross sections are found to be in agreement with the predictions, apart from the pT distributions of the leading jets at high pT values, the distributions of the HT at high-HT and low jet multiplicity, and the distribution of the difference in azimuthal angle between the leading jet and the muon at low values.United States. Dept. of EnergyNational Science Foundation (U.S.)Alfred P. Sloan Foundatio

Penilaian Kinerja Keuangan Koperasi di Kabupaten Pelalawan

This paper describe development and financial performance of cooperative in District Pelalawan among 2007 - 2008. Studies on primary and secondary cooperative in 12 sub-districts. Method in this stady use performance measuring of productivity, efficiency, growth, liquidity, and solvability of cooperative. Productivity of cooperative in Pelalawan was highly but efficiency still low. Profit and income were highly, even liquidity of cooperative very high, and solvability was good