Sample records for ecsc
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Tsuno, Akitoshi; Nasu, Kaei; Kawano, Yukie; Yuge, Akitoshi; Li, Haili; Abe, Wakana; Narahara, Hisashi
2011-12-01
During the development of endometriotic lesions, excess fibrosis may lead to scarring and to the alterations of tissue function that are the characteristic features of this disease. Enhanced extracellular matrix contractility of endometriotic stromal cells (ECSC) mediated by the mevalonate-Ras homology (Rho)/Rho-associated coiled-coil-forming protein kinase (ROCK) pathway has been shown to contribute to the pathogenesis of endometriosis. To assess the use of fasudil, a selective ROCK inhibitor, for the medical treatment of endometriosis-associated fibrosis, the effects of this agent on the cell proliferation, apoptosis, cell cycle, morphology, cell density, and contractility of ECSC were investigated. The effects of fasudil on the expression of contractility-related, apoptosis-related, and cell cycle-related molecules in ECSC were also evaluated. Fasudil significantly inhibited the proliferation and contractility of ECSC and induced the cell cycle arrest in the G2/M phase and apoptosis of these cells. Morphological observation revealed the suppression of ECSC attachment to collagen fibers and decrease of cell density by fasudil. The expression of α-smooth muscle actin, RhoA, ROCK-I, and ROCK-II proteins was inhibited by fasudil administration. The expression of the antiapoptotic factors, Bcl-2 and Bcl-X(L), in two-dimensional cultured ECSC were down-regulated by the addition of fasudil, whereas, the expression of p16(INK4a) and p21(Waf1/Cip1) was up-regulated by the addition of fasudil. The present findings suggest that fasudil is a promising agent for the treatment of endometriosis. The inhibition of cell proliferation, contractility, and myofibroblastic differentiation, the attenuation of attachment to collagen fibers, the decrease of cell density, and the induction of cell cycle arrest and apoptosis of ECSC are involved in the active mechanisms of fasudil.
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Zheng, Qiaomei; Xu, Ying; Lu, Jingjing; Zhao, Jing; Wei, Xuan; Liu, Peishu
2016-11-01
To determine whether emodin facilitates the mesenchymal-epithelial transition (MET) of endometrial stromal cells (ESCs) as well as to explore the mechanism through which emodin favored the MET of ESCs. Cell viability was tested by methyl thiazolyl tetrazolium assay. Cell migration and invasion abilities were detected by transwell assays. Levels of integrin-linked kinase (ILK) and epithelial-mesenchymal transition (EMT)-related proteins were detected by Western blot. Upregulated ILK and increased abilities of migration and invasion were confirmed in the eutopic and ectopic ESCs (EuSCs and EcSCs), especially in the EcSCs. After treated with emodin, the expression of ILK was statistically downregulated in EcSCs, resulting in the MET and decreased migration and invasion abilities of EcSCs. Additionally, silencing of the ILK gene in EcSCs also achieved the above-mentioned effects, which were strengthened by emodin. Furthermore, exogenous expression of ILK in control ESCs (CSCs) resulted in the EMT and increased abilities of migration and invasion of CSCs, which can be abrogated by emodin. Besides, exogenous expression of ILK also abrogated the effects of emodin on CSCs. Emodin inhibits the migration and invasion abilities of human ESCs by facilitating the MET through targeting ILK. © The Author(s) 2016.
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Ramke, Jacqueline; Zwi, Anthony B; Lee, Arier C; Blignault, Ilse; Gilbert, Clare E
2017-04-01
Inequalities in cataract blindness are well known, but data are rarely disaggregated to explore the combined effects of a range of axes describing social disadvantage. We examined inequalities in cataract blindness and services at the intersection of three social axes. Three dichotomous social variables (sex (male/female); place of residence (urban/rural); literacy (literate/illiterate)) from cross-sectional national blindness surveys in Pakistan (2001-2004; n=16 507) and Nigeria (2005-2007; n=13 591) were used to construct eight subgroups, with disadvantaged subgroups selected a priori (ie, women, rural dwellers, illiterate). In each data set, the social distribution of cataract blindness, cataract surgical coverage (CSC) and effective cataract surgical coverage (eCSC) were examined. Inequalities were assessed comparing the best-off and worst-off subgroups using rate differences and rate ratios (RRs). Logistic regression was used to assess cumulative effects of multiple disadvantage. Disadvantaged subgroups experienced higher prevalence of cataract blindness, lower CSC and lower eCSC in both countries. A social gradient was present for CSC and eCSC, with coverage increasing as social position improved. Relative inequality in eCSC was approximately twice as high as CSC (Pakistan: eCSC RR 2.7 vs CSC RR 1.3; Nigeria: eCSC RR 8.7 vs CSC RR 4.1). Cumulative disadvantage was observed for all outcomes, deteriorating further with each additional axis along which disadvantage was experienced. Each outcome tended to be worse with the addition of each layer of social disadvantage. Illiterate, rural women fared worst in both settings. Moving beyond unidimensional analyses of social position identified subgroups in most need; this permits a more nuanced response to addressing the inequitable distribution of cataract blindness. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.
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Euroscepticism in Britain and France: Implications for NATO and the European Union
2016-03-01
establishment BBC British Broadcasting Corporation CSDP Common Security and Defence Policy ECSC European Coal and Steel Community EDC European Defense...existed since the formation of collective European international organizations such as the European Coal and Steel Community (ECSC) and the European...external coercion or aggression.”142 The EU was formed after a progression of economic and political treaties beginning with the European Coal and
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Spectra of confined positronium
NASA Astrophysics Data System (ADS)
Munjal, D.; Silotia, P.; Prasad, V.
2017-12-01
Positronium is studied under the effect of spherically confined plasma environment. Exponentially Cosine Screened Coulomb potential (ECSC) has been used to include the dense plasma screening effect on positronium. Time independent Schrodinger equation is solved numerically. Various physical parameters such as energy eigenvalues, radial matrix elements, oscillator strengths, and polarizability are well explored as a function of confinement parameters. Oscillator strength gets drastically modified under confinement. We have also obtained the results for Ps confined under spherically confined Debye potential and compared with results of ECSC potential. Also incidental degeneracy for different values of confinement parameters has been reported for the first time for positronium.
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Aguilar, Esther; de Mas, Igor Marin; Zodda, Erika; Marin, Silvia; Morrish, Fionnuala; Selivanov, Vitaly; Meca-Cortés, Óscar; Delowar, Hossain; Pons, Mònica; Izquierdo, Inés; Celià-Terrassa, Toni; de Atauri, Pedro; Centelles, Josep J; Hockenbery, David; Thomson, Timothy M; Cascante, Marta
2016-01-01
In solid tumors, cancer stem cells (CSCs) can arise independently of epithelial-mesenchymal transition (EMT). In spite of recent efforts, the metabolic reprogramming associated with CSC phenotypes uncoupled from EMT is poorly understood. Here, by using metabolomic and fluxomic approaches, we identify major metabolic profiles that differentiate metastatic prostate epithelial CSCs (e-CSCs) from non-CSCs expressing a stable EMT. We have found that the e-CSC program in our cellular model is characterized by a high plasticity in energy substrate metabolism, including an enhanced Warburg effect, a greater carbon and energy source flexibility driven by fatty acids and amino acid metabolism and an essential reliance on the proton buffering capacity conferred by glutamine metabolism. An analysis of transcriptomic data yielded a metabolic gene signature for our e-CSCs consistent with the metabolomics and fluxomics analysis that correlated with tumor progression and metastasis in prostate cancer and in 11 additional cancer types. Interestingly, an integrated metabolomics, fluxomics and transcriptomics analysis allowed us to identify key metabolic players regulated at the post-transcriptional level, suggesting potential biomarkers and therapeutic targets to effectively forestall metastasis. PMID:27146024
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El Attar, Mohamed Nour; Hadj Mabrouk, Khaoula; Ben Abdelaziz, Ahmed; Abdelghani, Ahmed; Bousarssar, Mohamed; Limam, Khélifa; Maatoug, Chiraz; Bouslah, Hmida; Charrada, Ameur; Rouatbi, Sonia; Ben Saad, Helmi
2014-01-01
Tunisian pulmonary functional laboratories accept the default settings for reference equations (European Respiratory Society/European Community for Steel and Coal (ERS/ECSC1983) offered by the manufacturer even though adult Tunisian reference equations (Tunisian1995) are available. To compare the spirometric profile of Tunisian subjects, according to the two reference equations. Spirometric data were recorded from 1192 consecutive spirometry procedures in adults aged 18-60 years. Reference values and lower limits of normality (LLN) were calculated using the two reference equations. Applied definitions: large airway obstructive ventilatory defect (LAOVD): ratio between the 1st second expiratory volume and forced vital capacity (FEV1/FVC) < LLN. Small AOVD (SAOVD): FEV1/FVC > LLN and FVC > LLN and maximal midexpiratory flow < LLN. Tendency through a restrictive ventilatory defect (TRVD): FEV1 and FVC < LLN. The spirometric profile, according the two reference equations, was determined. Using Tunisian1995 reference equations, 34%, 7%, 37% and 19% of spirometry records were interpreted as normal, and as having, LAOVD, SAOVD and TRVD, respectively. Using ERS/ECSC1983 reference equations, 85%, 3%, 9% and 2% of spirometry records were interpreted as normal, and as having, LAOVD, SAOVD and TRVD, respectively. Using the ERS/ECSC1983 reference equations, misclassification was worse for LAOVD, for SAOVD and for TRVD, respectively, 68%, 94% and 89%. Our results showed that the use of the old Caucasian reference equations resulted in misinterpretation of spirometry data in a significant proportion of subjects. This could result in inappropriate diagnosis and/or management.
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Tang, Ya-Bin; Teng, Lin; Sun, Fan; Wang, Xiao-Lin; Peng, Liang; Cui, Yong-Yao; Hu, Jin-Jia; Luan, Xin; Zhu, Liang; Chen, Hong-Zhuan
2012-09-15
Because glycine plays a prominent role in living creatures, an accurate and precise quantitative analysis method for the compound is needed. Herein, a new approach to analyze glycine by hydrophilic interaction chromatography (HILIC) coupled with electrospray ionization tandem mass spectrometry (ESI-MS/MS) was developed. This method avoids the use of derivatization and/or ion-pairing reagents. N-methyl-D-aspartate (NMDA) is used as the internal standard (IS). The mobile phase for the isocratic elution consisted of 10 mM ammonium formate in acetonitrile-water (70:30, v/v, adjusted to pH 2.8 with formic acid), and a flow rate of 250 μL/min was used. Two microliters of sample was injected for analysis. The signal was monitored in the positive multiple reaction monitoring (MRM) mode. The total run time was 5 min. The dynamic range was 40-2000 ng/mL for glycine in the biological matrix. The LLOQ (lower limit of quantification) of this method was 40 ng/mL (80 pg on column). The validated method was applied to determine the dynamic release of glycine from P19 embryonal carcinoma stem cells (ECSCs). Glycine spontaneously released from the ECSCs into the intercellular space gradually increased from 331.02±60.36 ng/mL at 2 min in the beginning to 963.52±283.80 ng/mL at 60 min and 948.27±235.09 ng/mL at 120 min, finally reaching a plateau, indicating that ECSCs consecutively release glycine until achieving equilibration between the release and the reuptake of the compound; on the contrary, the negative control NIH/3T3 embryonic fibroblast cells did not release glycine. This finding will help to improve our understanding of the novel effects of neurotransmitters, including glycine, on non-neural systems. Copyright © 2012 Elsevier B.V. All rights reserved.
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Waring, Cheryl D; Henning, Beverley J; Smith, Andrew J; Nadal-Ginard, Bernardo; Torella, Daniele; Ellison, Georgina M
2015-01-01
Intensity-controlled (relative to VO2max) treadmill exercise training in adult rats results in the activation and ensuing differentiation of endogenous c-kitpos cardiac stem/progenitor cells (eCSCs) into newly formed cardiomyocytes and capillaries. Whether these training-induced adaptations persist following detraining is undetermined. Twelve male Wistar rats (∼230 g) were exercised at 80–85% of their VO2max for 30 min day−1, 4 days week−1 for 4 weeks (TR;n = 6), followed by 4 weeks of detraining (DTR; n = 6). Twelve untrained rats acted as controls (CTRL). Exercise training significantly enhanced VO2max (11.34 mL kg−1 min−1) and wet heart weight (29%) above CTRL (P < 0.05). Echocardiography revealed that exercise training increased LV mass (∼32%), posterior and septal wall thickness (∼15%), ejection fraction and fractional shortening (∼10%) compared to CTRL (P < 0.05). Cardiomyocyte diameter (17.9 ± 0.1 μm vs. 14.9 ± 0.6 μm), newly formed (BrdUpos/Ki67pos) cardiomyocytes (7.2 ± 1.3%/1.9 ± 0.7% vs. 0.2 ± 0.1%/0.1 ± 0.1%), total cardiomyocyte number (45.6 ± 0.6 × 106 vs. 42.5 ± 0.4 × 106), c-kitpos eCSC number (884 ± 112 per 106 cardiomyocytes vs. 482 ± 132 per 106 cardiomyocytes), and capillary density (4123 ± 227 per mm2 vs. 2117 ± 118 per mm2) were significantly greater in the LV of trained animals (P < 0.05) than CTRL. Detraining removed the stimulus for c-kitpos eCSC activation (640 ± 98 per 106 cardiomyocytes) and resultant cardiomyocyte hyperplasia (0.4 ± 0.3% BrdUpos/0.2 ± 0.2% Ki67pos cardiomyocytes). Capillary density (3673 ± 374 per mm2) and total myocyte number (44.7 ± 0.5 × 106) remained elevated following detraining, but cardiomyocyte hypertrophy (15.0 ± 0.4 μm) was lost, resulting in a reduction of anatomical (wall thickness ∼4%; LV mass ∼10% and cardiac mass ∼8%, above CTRL) and functional (EF & FS ∼2% above CTRL) parameters gained through exercise training. These findings demonstrate that cardiac adaptations, produced by 4 weeks of intensity-controlled exercise training are lost after a similar period of detraining. PMID:25713328
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Carresi, Cristina; Musolino, Vincenzo; Gliozzi, Micaela; Maiuolo, Jessica; Mollace, Rocco; Nucera, Saverio; Maretta, Alessia; Sergi, Domenico; Muscoli, Saverio; Gratteri, Santo; Palma, Ernesto; Bosco, Francesca; Giancotta, Caterina; Muscoli, Carolina; Marino, Fabiola; Aquila, Iolanda; Torella, Daniele; Romeo, Franco; Mollace, Vincenzo
2018-04-12
Doxorubicin (DOXO) is one of the most widely used antineoplastic drugs. Despite its highly beneficial effects against several malignancies, the clinical use of DOXO is often associated to cardiomyopathy that leads to congestive heart failure. Here we investigated the antioxidant and cardioprotective effects of a polyphenol-rich fraction of citrus bergamot (BPF), in DOXO-induced cardiac damage in rats. Moreover, we evaluated the effect of BPF on cardiomyocyte survival and resident endogenous cardiac stem/progenitor cell (eCSC) activation. Adult male Wistar rats were i.p. injected with saline (serving as controls, CTRL, n = 10), BPF (20 mg/kg daily for 14 consecutive days, n = 10), DOXO (6 doses of 2,5 mg/Kg from day 1 to day 14, n = 10), and DOXO + BPF (n = 10). Animals were then sacrificed 7 days later (i.e., at 21 days). DOXO administration reduced cardiac function at 21 days, an adverse effect significantly attenuated in animals receiving DOXO + BPF. No changes were detected in rats receiving just saline or BPF alone. The cardioprotective effect of BPF on DOXO acute toxicity was also associated with a significant antioxidant effect coupled with protective autophagy restoration, and attenuation of cardiomyocyte apoptosis and reactive hypertrophy. Finally, treatment of rats with BPF prevented eCSCs attrition by DOXO which was followed by a limited but significant increase of newly-formed BrdU + cardiomyocytes. In conclusion, BPF reduces DOXO-induced cardiotoxicity by counteracting reactive oxygen species (ROS) overproduction, thereby restoring protective autophagy and attenuating cardiomyocyte apoptosis and pathologic remodeling. This beneficial effects on the early toxicity of DOXO is associated with enhanced CSCs survival and regenerative potential. Overall these data point to a potential clinical role by diet supplementation with polyphenol-rich fraction of citrus bergamot in counteracting antracycline-induced cardiomyopathy. Copyright © 2018. Published by Elsevier Ltd.
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Increasing frequency of extremely severe cyclonic storms over the Arabian Sea
NASA Astrophysics Data System (ADS)
Murakami, Hiroyuki; Vecchi, Gabriel A.; Underwood, Seth
2017-12-01
In 2014 and 2015, post-monsoon extremely severe cyclonic storms (ESCS)—defined by the WMO as tropical storms with lifetime maximum winds greater than 46 m s-1—were first observed over the Arabian Sea (ARB), causing widespread damage. However, it is unknown to what extent this abrupt increase in post-monsoon ESCSs can be linked to anthropogenic warming, natural variability, or stochastic behaviour. Here, using a suite of high-resolution global coupled model experiments that accurately simulate the climatological distribution of ESCSs, we show that anthropogenic forcing has likely increased the probability of late-season ECSCs occurring in the ARB since the preindustrial era. However, the specific timing of observed late-season ESCSs in 2014 and 2015 was likely due to stochastic processes. It is further shown that natural variability played a minimal role in the observed increase of ESCSs. Thus, continued anthropogenic forcing will further amplify the risk of cyclones in the ARB, with corresponding socio-economic implications.
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Reference values for pulmonary diffusing capacity for adult native Finns.
Kainu, Annette; Toikka, Jyri; Vanninen, Esko; Timonen, Kirsi L
2017-04-01
Measurement standards for pulmonary diffusing capacity were updated in 2005 by the ATS/ERS Task Force. However, in Finland reference values published in 1982 by Viljanen et al. have been used to date. The main aim of this study was to produce updated reference models for single-breath diffusing capacity for carbon monoxide for Finnish adults. Single-breath diffusing capacity for carbon monoxide was measured in 631 healthy non-smoking volunteers (41.5% male). Reference values for diffusing capacity (DLCO), alveolar volume (VA), diffusing capacity per unit of lung volume (DLCO/VA), and lung volumes were calculated using a linear regression model. Previously used Finnish reference values were found to produce too low predicted values, with mean predicted DLCO 111.0 and 104.4%, and DLCO/VA of 103.5 and 102.7% in males and females, respectively. With the European Coalition for Steel and Coal (ECSC) reference values there was a significant sex difference in DLCO/VA with mean predicted 105.4% in males and 92.8% in females (p < .001). New reference values for DLCO, DLCO/VA, VA, vital capacity (VC), inspiratory vital capacity (IVC), and inspiratory capacity (IC) are suggested for clinical use to replace technically outdated reference values for clinical applications.
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Weathering resistance of thin plasma polymer films on pre-coated steel =
NASA Astrophysics Data System (ADS)
Serra, Ricardo Gil Henriques
O trabalho apresentado teve origem no projecto de investigacao “Tailored Thin Plasma Polymers Films for Surface Engineering of Coil Coated Steel”, financiado pelo Programa Europeu ECSC Steel Research. Sistemas de aco galvanizado pre-pintado em banda a base de poliester e poliuretano foram submetidos a um processo de polimerizacao por plasma onde um filme fino foi depositado de modo a modificar as propriedades de superficie. Foram usados reactores de catodo oco, microondas e radio frequencia para a deposicao do polimero fino. Os sistemas preparados foram analisados de modo a verificar a influencia do processo de polimerizacao por plasma na alteracao das propriedades barreira dos sistemas pre-pintados em banda. Foi estudado o efeito dos diferentes passos do processo de polimerizacao por plasma, bem como o efeito de diferentes variaveis operatorias. A mistura precursora foi variada de modo a modificar as propriedades da superficie de modo a poder vir a obter maior hidrofobicidade, maior resistencia a marcas digitais, bem como maior facilidade de limpeza. Os testes foram conduzidos em solucao de NaCl 0,5 M. Para o trabalho foram usadas tecnicas de analise da morfologia da superficie como Microscopia de Forca Atomica e Microscopia Electronica de Varrimento. As propriedades electroquimicas dos sistemas foram estudadas por Espectroscopia de Impedancia Electroquimica. A estrutura dos filmes gerados no processo de polimerizacao por plasma foi caracterizada por Microscopia de Transmissao Electronica. A modificacao das propriedades opticas devido ao processo de polimerizacao por plasma foi tambem obtida.
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Rossi, Esther Diana; Bizzarro, Tommaso; Monterossi, Giorgia; Inzani, Frediano; Fanfani, Francesco; Scambia, Giovanni; Zannoni, Gian Franco
2017-04-01
Mixed endometrial carcinomas (MECs) refer to tumors characterized by 2 or more distinct histotypes mostly that comprised endometrioid (EC) and serous/clear cell carcinomas (SC/CC). The specific quantification of these distinct components represents a challenging and critical point for both prognosis and management. Herein, we analyze a large series of MEC and compare them with EC and SC/CC. We evaluated a series of 69 MECs between January 2002 and December 2015. We compared the MEC series with 186 ECs (including 117 endometrioid G3), 31 SCs, and 38 CCs. The prognostic implication of the percentage of each component was analyzed. Among the 69 MECs, those patients older than 45 years represent the significant population, with 52.2% of them with stage III-IV disease. A similar result was found among pure SC. The comparative analysis of some prognostic parameters (multifocality, vascular invasion, and lymph node metastasis) underlined that MECs with a type II component larger than 5% represent a more aggressive entity. However, relapse, disease-free survival, mortality, and overall survival are statistically significant (P<.05) in EC-SC (SC<5%or >5%) and in EC-CC (CC<5%or >5%), whereas they are not significant (P>.05) in SC-CC (SC/CC<%or >5%). MECs, including also cases with less than 5% of SC/CC, show features as aggressive as those of pure SC/CC. In this perspective, MEC should be followed by personalized and tailored managements. The presence of different components suggests different pathogenic and metastatic processes when compared with pure carcinomas. Copyright © 2016. Published by Elsevier Inc.
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Boros, P; Martusewicz-Boros, M; Doboszyńska, A; Kowalski, J; Droszcz, W
1998-01-01
Work place environment plays an important role in development diseases because of the time spend in and different toxic factors placed in it. The aim of study was to assess the ventilatory efficiency in individuals employed in Generating Plant (GP) in relation to the pollution of the work place and the tobacco smoking habit during 3 years. The study covered a group of 144 male individuals employed at GP. (age 39.3 +/- 8.7 yrs, period of employment 20.3 +/- 8.6 yrs, smokers 53.5%. Lung function tests consisted of VC, FVC, FEV1, FEV1%VC, PEF, FEF50 counted from flow-volume curve and TGV, Rt measured using pletysmographic method. All tests were performed using pletysmograph (Masterlab) "Jaeger" placed on the ambulance near to the work place. The measurements were taken in May 1993 and 1996. Results were compared to with normal values (acc. ECSC). The anamnesis was obtained from all workers in the form of questionnaire projected for this study. All measurements were done during work time (9.00 a.m. to 2.00 p.m.). Mean values of the ventilation indices remained within the normal range but comparing results in smokers and non-smokers group significant differences in FEV1 and TGV were found. The symptoms of chronic bronchitis were present in 20.8% of persons. Spirometric criteria for the COPD diagnosis were found in 16 persons (11%). Only 5 persons (31%) were symptomatic. The mean decrease of FEV1 was 16.2 ml/yr, in the COPD group it was 82.5 ml/yr. The greater annual loss of FEV1 was found in the smokers and symptoms groups.
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Molecular Analysis of Mixed Endometrial Carcinomas Shows Clonality in Most Cases.
Köbel, Martin; Meng, Bo; Hoang, Lien N; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C Blake; Lee, Cheng-Han
2016-02-01
Mixed endometrial carcinoma refers to a tumor that comprises 2 or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas-11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade ECs (CCC/EC), and 2 mixed CCC and SCs (CCC/SC), using targeted next-generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC, and 1 SC/CCC) showed an SC molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch-repair protein deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and 1 EC/CCC case showed both shared and unique molecular features in the 2 histotype components, suggesting early molecular divergence from a common clonal origin. In 2 cases, there were no shared molecular features, and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphologic mimicry, whereby tumors with serous-type molecular profile show morphologic features of EC or CCC, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors).
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Molecular analysis of mixed endometrial carcinomas shows clonality in most cases
Hoang, Lien N.; Almadani, Noorah; Li, Xiaodong; Soslow, Robert A; Gilks, C. Blake; Lee, Cheng-Han
2016-01-01
Mixed endometrial carcinoma refers to a tumor that is comprised of two or more distinct histotypes. We studied 18 mixed-type endometrial carcinomas - 11 mixed serous and low-grade endometrioid carcinomas (SC/EC), 5 mixed clear cell and low-grade endometrioid carcinomas (CCC/EC), and 2 mixed clear cell and serous carcinoma (CCC/SC), using targeted next generation sequencing and immunohistochemistry to compare the molecular profiles of the different histotypes present in each case. In 16 of 18 cases there was molecular evidence that both components shared a clonal origin. Eight cases (6 EC/SC, 1 EC/CCC and 1 SC/CCC) showed a serous carcinoma molecular profile that was the same in both components. Five cases (3 CCC/EC and 2 SC/EC) showed a shared endometrioid molecular profile and identical mismatch repair protein (MMR) deficiency in both components. A single SC/EC case harbored the same POLE exonuclease domain mutation in both components. One SC/CCC and one EC/CCC case showed both shared and unique molecular features in the two histotype components, suggesting early molecular divergence from a common clonal origin. In two cases, there were no shared molecular features and these appear to be biologically unrelated synchronous tumors. Overall, these results show that the different histologic components in mixed endometrial carcinomas typically share the same molecular aberrations. Mixed endometrial carcinomas most commonly occur through morphological mimicry, whereby tumors with serous-type molecular profile show morphological features of endometrioid or clear cell carcinoma, or through underlying deficiency in DNA nucleotide repair, with resulting rapid accrual of mutations and intratumoral phenotypic heterogeneity. Less commonly, mixed endometrial carcinomas are the result of early molecular divergence from a common progenitor clone or are synchronous biologically unrelated tumors (collision tumors). PMID:26492180