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71.
Madhura S. Mehta Sonia C. Dolfi Roman Bronfenbrener Erhan Bilal Chunxia Chen Dirk Moore Yong Lin Hussein Rahim Seena Aisner Romona D. Kersellius Jessica Teh Suzie Chen Deborah L. Toppmeyer Dan J. Medina Shridar Ganesan Alexei Vazquez Kim M. Hirshfield 《PloS one》2013,8(7)
Several epidemiological studies have suggested a link between melanoma and breast cancer. Metabotropic glutamate receptor 1 (GRM1), which is involved in many cellular processes including proliferation and differentiation, has been implicated in melanomagenesis, with ectopic expression of GRM1 causing malignant transformation of melanocytes. This study was undertaken to evaluate GRM1 expression and polymorphic variants in GRM1 for associations with breast cancer phenotypes. Three single nucleotide polymorphisms (SNPs) in GRM1 were evaluated for associations with breast cancer clinicopathologic variables. GRM1 expression was evaluated in human normal and cancerous breast tissue and for in vitro response to hormonal manipulation. Genotyping was performed on genomic DNA from over 1,000 breast cancer patients. Rs6923492 and rs362962 genotypes associated with age at diagnosis that was highly dependent upon the breast cancer molecular phenotype. The rs362962 TT genotype also associated with risk of estrogen receptor or progesterone receptor positive breast cancer. In vitro analysis showed increased GRM1 expression in breast cancer cells treated with estrogen or the combination of estrogen and progesterone, but reduced GRM1 expression with tamoxifen treatment. Evaluation of GRM1 expression in human breast tumor specimens demonstrated significant correlations between GRM1 staining with tissue type and molecular features. Furthermore, analysis of gene expression data from primary breast tumors showed that high GRM1 expression correlated with a shorter distant metastasis-free survival as compared to low GRM1 expression in tamoxifen-treated patients. Additionally, induced knockdown of GRM1 in an estrogen receptor positive breast cancer cell line correlated with reduced cell proliferation. Taken together, these findings suggest a functional role for GRM1 in breast cancer. 相似文献
72.
Wan C. Tan Jean Bourbeau Paul Hernandez Kenneth R. Chapman Robert Cowie J. Mark FitzGerald Shawn Aaron Darcy D. Marciniuk Francois Maltais A. Sonia Buist Denis E. O’Donnell Don D. Sin 《PloS one》2013,8(3)
Background
The relationship between patient-reported symptoms and objective measures of lung function is poorly understood.Aim
To determine the association between responsiveness to bronchodilator and respiratory symptoms in random population samples.Methods
4669 people aged 40 years and older from 8 sites in Canada completed interviewer-administered respiratory questionnaires and performed spirometry before and after administration of 200 ug of inhaled salbutamol. The effect of anthropometric variables, smoking exposure and doctor-diagnosed asthma (DDA) on bronchodilator responsiveness in forced expiratory volume in 1 second (FEV1) and in forced vital capacity (FVC) were evaluated. Multiple logistic regression was used to test for association between quintiles of increasing changes in FEV1 and in FVC after bronchodilator and several respiratory symptoms.Results
Determinants of bronchodilator change in FEV1 and FVC included age, DDA, smoking, respiratory drug use and female gender [p<0.005 to p<0.0001 ]. In subjects without doctor-diagnosed asthma or COPD, bronchodilator response in FEV1 was associated with wheezing [p for trend<0.0001], while bronchodilator response for FVC was associated with breathlessness. [p for trend <0.0001].Conclusions
Bronchodilator responsiveness in FEV1 or FVC are associated with different respiratory symptoms in the community. Both flow and volume bronchodilator responses are useful parameters which together can be predictive of both wheezing and breathlessness in the general population. 相似文献73.
John J. Openshaw Sonia Hegde Hossain M. S. Sazzad Salah Uddin Khan M. Jahangir Hossain Jonathan H. Epstein Peter Daszak Emily S. Gurley Stephen P. Luby 《EcoHealth》2016,13(1):39-48
We used data on feeding practices and domestic animal health gathered from 207 Bangladeshi villages to identify any association between grazing dropped fruit found on the ground or owners directly feeding bat- or bird-bitten fruit and animal health. We compared mortality and morbidity in domestic animals using a mixed effects model controlling for village clustering, herd size, and proxy measures of household wealth. Thirty percent of household heads reported that their animals grazed on dropped fruit and 20% reported that they actively fed bitten fruit to their domestic herds. Household heads allowing their cattle to graze on dropped fruit were more likely to report an illness within their herd (adjusted prevalence ratio 1.17, 95% CI 1.02–1.31). Household heads directly feeding goats bitten fruit were more likely to report illness (adjusted prevalence ratio 1.35, 95% CI 1.16–1.57) and deaths (adjusted prevalence ratio 1.64, 95% CI 1.13–2.4). Reporting of illnesses and deaths among goats rose as the frequency of feeding bitten fruit increased. One possible explanation for this finding is the transmission of bat pathogens to domestic animals via bitten fruit consumption. 相似文献
74.
75.
Ecosystems may exhibit catastrophic shifts, i.e. abrupt and irreversible responses of ecosystem functions and services to continuous changes in external conditions. The search for early warning signs of approaching shifts has so far mainly been conducted on theoretical models assuming spatially-homogeneous external pressures (e.g. climatic). Here, we investigate how a spatially explicit pressure may affect ecosystems’ risk of catastrophic shifts and the associated spatial early-warning signs. As a case study, we studied a dryland vegetation model assuming ‘associational resistance’, i.e. the mutual reduction of local grazing impact by neighboring plants sharing the investment in defensive traits. Consequently, grazing pressure depends on the local density of plants and is thus spatially-explicit. We focus on the distribution of vegetation patch sizes, which can be assessed using remote sensing and are candidate early warning signs of catastrophic shifts in drylands. We found that spatially explicit grazing affected both the resilience and the spatial patterns of the landscape. Grazing impact became self-enhancing in more fragmented landscapes, disrupted patch growth and put apparently ‘healthy’ drylands under high risks of catastrophic shifts. Our study highlights that a spatially explicit pressure may affect the nature of the spatial pattern observed and thereby change the interpretation of the early warning signs. This may generalize to other ecosystems exhibiting self-organized spatial patterns, where a spatially-explicit pressure may interfere with pattern formation. 相似文献
76.
77.
Meriam Denguezli Hager Daldoul Imed Harrabi Louisa Gnatiuc Sonia Coton Peter Burney Zouhair Tabka 《PloS one》2016,11(3)
Background
It’s currently well known that smoking and increasing age constitute the most important risk factors for chronic obstructive pulmonary disease (COPD). However, little is known about COPD among nonsmokers. The present study aimed to investigate prevalence, risk factors and the profiles of COPD among nonsmokers based on the Tunisian Burden of Obstructive Lung Disease (BOLD) study.Methods
807 adults aged 40 years+ were randomly selected from the general population. We collected information about history of respiratory disease, risk factors for COPD and quality of life. Post-bronchodilator spirometry was performed for assessment of COPD. COPD diagnostic was based on the post-bronchodilator FEV1/FVC ratio, according to the Global Initiative for Obstructive Lung Disease (GOLD) guidelines. The lower limit of normal (LLN) was determined as an alternative threshold for the FEV1/FVC ratio.Results and Conclusions
Among 485 nonsmokers, 4.7% met the criteria for GOLD grade I and higher COPD. These proportions were similar even when the LLN was used as a threshold. None of the nonsmokers with COPD reported a previous doctor diagnosis of COPD compared to 7.1% of smokers. Nonsmokers accounted for 45.1% of the subjects fulfilling the GOLD spirometric criteria of COPD. Nonsmokers were predominately men and reported more asthma problems than obstructed smokers. Among nonsmokers significantly more symptoms and higher co-morbidity were found among those with COPD. Increasing age, male gender, occupational exposure, lower body mass index and a previous diagnosis of asthma are associated with increased risk for COPD in nonsmokers. This study confirms previous evidence that nonsmokers comprise a substantial proportion of individuals with COPD. Nonsmokers with COPD have a specific profile and should, thus, receive far greater attention to prevent and treat chronic airway obstruction. 相似文献78.
Sonia Vallet Muhammad Hasan Bashari Feng-Juan Fan Stefano Malvestiti Andreas Schneeweiss Patrick Wuchter Dirk J?ger Klaus Podar 《PloS one》2016,11(3)
Introduction
The occurrence of skeletal metastases in cancer, e.g. breast cancer (BC), deteriorates patient life expectancy and quality-of-life. Current treatment options against tumor-associated bone disease are limited to anti-resorptive therapies and aimed towards palliation. There remains a lack of therapeutic approaches, which reverse or even prevent the development of bone metastases. Recent studies demonstrate that not only osteoclasts (OCs), but also osteoblasts (OBs) play a central role in the pathogenesis of skeletal metastases, partly by producing hepatocyte growth factor (HGF), which promotes tumor cell migration and seeding into the bone. OBs consist of a heterogeneous cell pool with respect to their maturation stage and function. Recent studies highlight the critical role of pre-OBs in hematopoiesis. Whether the development of bone metastases can be attributed to a particular OB maturation stage is currently unknown.Methods and Results
Pre-OBs were generated from healthy donor (HD)-derived bone marrow stromal cells (BMSC) as well as the BMSC line KM105 and defined as ALPlow OPNlow RUNX2high OSX high CD166high. Conditioned media (CM) of pre-OBs, but not of undifferentiated cells or mature OBs, enhanced migration of metastatic BC cells. Importantly, HGF mRNA was significantly up-regulated in pre-OBs versus mature OBs, and CM of pre-OBs activated the MET signaling pathway. Highlighting a key role for HGF, CM from HGF-negative pre-OBs derived from the BMSC line HS27A did not support migration of BC cells. Genetically (siMET) or pharmacologically (INCB28060) targeting MET inhibited both HGF- and pre-OB CM- mediated BC cell migration.Conclusions
Our data demonstrate for the first time a role for pre-OBs in mediating HGF/MET- dependent migration of BC cells and strongly support the clinical evaluation of INCB28060 and other MET inhibitors to limit and/or prevent BC-associated bone metastases. 相似文献79.
Sonia Gaucher Isabelle Boutron Florence Marchand-Maillet Gabriel Baron Richard Douard Jean-Pierre Béthoux AMBUPROG Group Investigators 《PloS one》2016,11(2)