tbuckley/cabot-search huggingface dataset:
Comparison of Increased Aromatase versus ERα in the Generation of Mammary Hyperplasia and Cancer
Authors: Edgar S. Díaz-Cruz, Yasuro Sugimoto, G. Ian Gallicano, Robert W. Brueggemeier, Priscilla A. Furth
Journal: Cancer Research (2011)

Factors associated with increased estrogen synthesis increase breast cancer risk. Increased aromatase and estrogen receptor α (ERα) in both normal epithelium and ductal carcinoma in situ lesions are found in conjunction with breast cancer, leading to the idea that altered estrogen signaling pathways predispose the mammary gland to cancer development. Here, we developed a transgenic mouse that conditionally expresses aromatase in the mammary gland, and used it along with a deregulated ERα expression model to investigate the molecular pathways involved in the development of mammary gland preneoplasia and carcinoma. Both increased ERα and aromatase expression led to the development of preneoplasia, but increased preneoplasia, in addition to carcinoma, was found in aromatase overexpressing mice. Increased prevalence of mammary pathologic changes in mice expressing aromatase correlated with increased cyclin E and cyclin-dependent kinase 2 expression. Gain of both ERα and aromatase increased expression of ERα and progesterone receptor, but aromatase produced a higher increase than ERα, accompanied by higher levels of downstream target genes Ccnd1, Myc, and Tnfsf11. In summary, whereas gain of both ERα and aromatase activate abnormal growth pathways in the mammary gland, aromatase induced a wider range of abnormalities that was associated with a higher prevalence of mammary preneoplasia and cancer progression.
Integrin signalling: The tug-of-war in heart hypertrophy
Authors: M BRANCACCIO, E HIRSCH, A NOTTE, G SELVETELLA, G LEMBO, G TARONE
Journal: Cardiovascular Research (2006)

The mechanical stress imposed by hemodynamic overload on heart walls is a primary event in triggering the cardiac hypertrophic response. Integrins, a class of membrane receptors, are major players in transmitting the mechanical force across the plasma membrane and sensing the mechanical load in cardiomyocytes. In fact, integrins, together with a number of associated cytoskeletal proteins, connect the sarcomeric contractile apparatus to the extracellular matrix across the plasma membrane and trigger intracellular signaling pathways activating the cardiomyocyte hypertrophy program.
Contribution of modifiable risk factors to social inequalities in type 2 diabetes: prospective Whitehall II cohort study
Authors: S. Stringhini, A. G. Tabak, T. N. Akbaraly, S. Sabia, M. J. Shipley, M. G. Marmot, E. J. Brunner, G. D. Batty, P. Bovet, M. Kivimaki
Journal: BMJ (2012)

<b>Objective</b> To assess the contribution of modifiable risk factors to social inequalities in the incidence of type 2 diabetes when these factors are measured at study baseline or repeatedly over follow-up and when long term exposure is accounted for. <b>Design</b> Prospective cohort study with risk factors (health behaviours (smoking, alcohol consumption, diet, and physical activity), body mass index, and biological risk markers (systolic blood pressure, triglycerides and high density lipoprotein cholesterol)) measured four times and diabetes status assessed seven times between 1991-93 and 2007-09. <b>Setting</b> Civil service departments in London (Whitehall II study). <b>Participants</b> 7237 adults without diabetes (mean age 49.4 years; 2196 women). <b>Main outcome measures</b> Incidence of type 2 diabetes and contribution of risk factors to its association with socioeconomic status. <b>Results</b> Over a mean follow-up of 14.2 years, 818 incident cases of diabetes were identified. Participants in the lowest occupational category had a 1.86-fold (hazard ratio 1.86, 95% confidence interval 1.48 to 2.32) greater risk of developing diabetes relative to those in the highest occupational category. Health behaviours and body mass index explained 33% (−1% to 78%) of this socioeconomic differential when risk factors were assessed at study baseline (attenuation of hazard ratio from 1.86 to 1.51), 36% (22% to 66%) when they were assessed repeatedly over the follow-up (attenuated hazard ratio 1.48), and 45% (28% to 75%) when long term exposure over the follow-up was accounted for (attenuated hazard ratio 1.41). With additional adjustment for biological risk markers, a total of 53% (29% to 88%) of the socioeconomic differential was explained (attenuated hazard ratio 1.35, 1.05 to 1.72). <b>Conclusions</b> Modifiable risk factors such as health behaviours and obesity, when measured repeatedly over time, explain almost half of the social inequalities in incidence of type 2 diabetes. This is more than was seen in previous studies based on single measurement of risk factors.
Proteomics and screening of lung cancer: Biomarkers selection by mass spectrometry and ELISA in the exhaled breath condensate (EBC)
Authors: Laura Núñez-Naveira, Luis Antonio Mariñas-Pardo, Carmen Montero-Martínez
Journal: European Respiratory Journal (2013)

Background: EBC is a non-invasive sample attractive for screening the non-small cell lung cancer (NSCLC).  Aims: To characterize the EBC protein profile in 4 groups: NSCLC, chronic obstructive pulmonary disease (COPD), healthy non-smokers and smokers, to find out disease-specific biomarkers.  Method: EBC was collected twice, from 10 subjects in each group. Half of the samples were concentrated by using the POROS R2 resin (Applied Biosystems) and protein profile was determined by mass spectrometry analysis (Maldi Tof-Tof). The remaining samples were analyzed by ELISA.  Results: 19 proteins were identified by mass spectrometry. Those suspected to be contaminations (amylases or keratins) were discarded. Three candidates were selected for further analysis based on their role on the defense against the development of NSCLC, the lack of previous publications relating the protein with lung cancer and the availability of commercial ELISA kits. Dermcidin, S100-A9 and Cathepsin G were quantified. Cathepsine G was almost undetectable on control groups and there were no differences between NSCLC and COPD groups (0.32±0.48 vs 0.22±0.24 ng/mL). Dermcidin and S100-A9 concentrations were higher in NSCLC and COPD groups, being the differences statistically significant (Dermcidin, 0.24±0.15 vs 0.32±0.07; S100-A9, 2.68±1.17 vs 4.41±0.76, ng/mL).  Conclusions: Cathepsine G seems to be a biomarker specific for NSCLC and COPD but it does not allow the discrimination between the two conditions. Nevertheless, the concentration of Dermcidin and S100-A9 was found to be disease-specific which makes them a very attractive target for the research on these conditions.
Use of home sleep studies for diagnosis of the sleep apnoea/hypopnoea syndrome
Authors: A. T. Whittle, S. P. Finch, I. L. Mortimore, T. W. MacKay, N. J. Douglas
Journal: Thorax (1997)

BACKGROUND: A study was undertaken to test the hypothesis that unsupervised domiciliary limited sleep studies do not impair the accuracy of diagnosis when used to investigate the sleep apnoea/hypopnoea syndrome (SAHS) and can be cheaper than laboratory polysomnography. METHODS: For validation, 23 subjects with suspected SAHS underwent laboratory polysomnography and a home study (EdenTec 3711) on successive nights. All subjects with &gt; 15 apnoeas + hypopnoeas (A + H)/hour on polysomnography showed &gt; 30 A + H/hour on their home study. Thereafter, in a prospective trial 150 subjects had a home study as the initial investigation and studies showing &gt; 30 events/hour were regarded as diagnostic of SAHS. Those showing fewer events were investigated with polysomnography if necessary. Time to treatment, outcome, and costs of this protocol were compared with those of 75 patients investigated initially with polysomnography. RESULTS: Of the prospective trial subjects, 29% had &gt; 30 A + H/hour and proceeded directly from home study to treatment; 15% without daytime sleepiness were not investigated further. Polysomnography was undertaken to establish a diagnosis in 56% of cases, including 18% whose home studies were unsuccessful. Compared with the 75 control patients, this protocol gave a diagnosis faster (median 18 (range 0-221) versus 47 (0-227) days, p &lt; 0.001) and more cheaply (mean (SD) 164 pounds (104) versus 210 pounds (0), p &lt; 0.001). The proportions offered CPAP (61% versus 67%) and subsequent objective CPAP usage (mean 4.7 (2.4) versus 5.0 (2.4) hours/night) were not different. CONCLUSIONS: Use of home sleep studies has benefits in time and cost. For diagnostic reliability a further sleep study was required in 56% of cases.
Corticotropin Releasing Factor promotes breast cancer cell motility and invasiveness
Authors: Ariadne Androulidaki, Erini Dermitzaki, Maria Venihaki, Effie Karagianni, Olga Rassouli, Erini Andreakou, Christos Stournaras, Andrew N Margioris, Christos Tsatsanis
Journal: Molecular Cancer (2009)

Cancer cells secrete bioactive peptides that act in an autocrine or paracrine fashion affecting tumor growth and metastasis. Corticotropin-releasing factor (CRF), a hypothalamic neuropeptide that controls the response to stress, has been detected in breast cancer tissues and cell lines. CRF can affect breast cancer cells in an autocrine or paracrine manner via its production from innervating sympathetic neurons or immune cells.In the present study we report our findings regarding the impact of CRF on breast cancer cell motility and invasiveness. For this purpose we used the MCF7 breast cancer cell line and evaluated the effect of CRF on motility and invasiveness using the wound-healing and boyden-chamber assays. In addition, we measured the effect of CRF on molecules that mediate motility by western blot, immunofluorescence, ELISA and RT-PCR.Our findings show that: 1. CRF transiently inhibited the apoptosis of MCF7 cells. 2. CRF enhanced MCF7 cell motility in a wound healing assay and their invasiveness through extracellular matrix. 3. CRF increased actin polymerization, phosphorylation of Focal Adhesion Kinase (FAK), providing a potential mechanism for the observed induction of MCF7 motility. 4. CRF induced the expression of Cox-1 but not Cox-2 in MCF7 cells as well as the production of prostaglandins, factors known to promote invasiveness and metastasis.Overall, our data suggest that CRF stimulates cell motility and invasiveness of MCF7 cells most probably via induction of FAK phosphorylation and actin filament reorganization and production of prostaglandins via Cox1. Based on these findings we postulate that the stress neuropeptide CRF present in the vicinity of tumors (either produced locally by the tumor cells themselves or by nearby normal cells or secreted from the innervations of surrounding tissues) may play an important role on breast tumor growth and metastatic capacity, providing a potential link between stress and tumor progression.
Evaluation of Venous Bypass Grafts from Aorta to Coronary Artery by Inert Gas Desaturation and Direct Flowmeter Techniques
Authors: David G. Greene, Francis J. Klocke, George L. Schimert, Ivan L. Bunnell, Stephen M. Wittenberg, Thomas Lajos
Journal: Journal of Clinical Investigation (1972)

Blood flow through aorta-to-coronary artery bypass grafts has been measured selectively in 16 patients at or within 6 wk after operation. Inert gas desaturation curves were obtained from coronary venous blood samples after a 7-15 min infusion of dissolved H(2) directly into the graft. Samples were analyzed chromatographically and curves resolved to 1-3% of initial H(2) concentrations. Average flow per unit volume (F/V) was 67+/-21 (sd) ml/min per 100 g. Semilogarithmic plots showed F/V to be distributed heterogeneously in every case. In nine studies at operation, H(2) measurements of average F/V were combined with electromagnetic measurements of total flow to estimate revascularized tissue mass. Electromagnetic flows ranged from 25 to 170 ml/min and averaged 69 ml/min. Tissue mass ranged from 46 to 155 g and averaged 88 g. We conclude that bypass grafts provide nutritive flow to significant amounts of myocardium at and shortly after operation. However, nutritive flow is not distributed evenly throughout the revascularized segment. The majority of the segment has a F/V within the accepted range of normal but there remain areas in which F/V is reduced significantly. The combination of inert gas and electromagnetic techniques allows a revascularized area to be characterized in terms of total flow, F/V, and tissue mass.
Distinct clinical phenotypes of airways disease: a primary-care clinician perspective
Authors: D. Hahn
Journal: European Respiratory Journal (2010)

To the Editors: 

As a clinician involved in the diagnosis, treatment and aetiological research of obstructive airways disease in primary care practice-based networks, I read with interest the description by Weatherall et al. 1 of four or five distinct clinical types of airways disease. Their results appear to confirm and extend observations from an earlier population-based study that distinguished asthma and chronic airway obstruction, which was termed AS-CAO (analogous to their Cluster 1), from smoking-associated emphysematous chronic obstructive pulmonary …
S123 Mononuclear inflammation and disruption of normal alveolar structure following deletion of G q/11, but not G 12/13, in type II alveolar epithelial cells
Authors: A. E. John, J. Porte, L. Jolly, A. L. Tatler, R. G. Jenkins
Journal: Thorax (2010)

Activation of latent TGFβ by the epithelially restricted αvβ6 integrin is induced by activators of the RhoA signalling pathway and is critical in the pathogenesis of lung injury and fibrosis. The G-proteins, Gα12 and Gα13 are known to activate RhoA and we have previously shown that the αvβ6 integrin can mediate TGFβ activation via Gαq and RhoA. To establish the role of these G-proteins in both normal lung development and following lung injury, we generated mice with a targeted deletion of Gαq/11 or Gα12/13 in SpC-positive Type II alveolar epithelial cells. SpC-Cre mice were crossed with either Gαq(flox-flox)/11(-/-) or Gα12(-/-)/13(flox-flox) mice and the lungs analysed histologically at 6 and 8 weeks after birth. At 6 weeks, lungs from mice with a homozygous deficiency in SpC-Gαq/11 contained focal inflammatory infiltrates consisting primarily of mononuclear leukocytes. Inflammation was associated with the localised disruption of normal alveolar architecture and the appearance of abnormal Type I and Type II alveolar epithelial cells, identified by SpC and T1α immunohistochemistry, within in the alveolar airspaces. Furthermore, immunohistochemical analysis of phosho-Smad2 levels in these lungs detected increased staining in the inflammatory foci within the homozygous SpC-Gαq/11 knockout lungs. At 8 weeks, the inflammatory foci were more numerous and lung architecture was severely disrupted with multiple abnormally large alveolar airspaces detected. In contrast, mice with at least one floxed Gαq or null Gα11 allele showed no abnormalities at either 6 or 8 weeks. We also detected no abnormal lung phenotype in 6- and 8-week old mice with a homozygous or heterozygous deficiency in SpC-Gα12/13. These data suggest that Gα11/q signalling is required to prevent pulmonary inflammation and our findings would be consistent with impaired epithelial TGFβ activation in the lungs of these mice. Further studies are required to determine the origin of the cells activating TGFβ in these lungs.
Splenic irradiation as primary therapy for prolymphocytic leukemia
Authors: A. Kiss, A. Haubenstock, H. Bognar, R. Scheiderbauer, M. Ai‐Mobarak, W. Base
Journal: American Journal of Hematology (1989)

Abstract A patient with prolymphocytic leukemia (PLL), a lymphoproliferative disorder that carries a poor prognosis, is presented. The disease was diagnosed at an early stage and treatment could be delayed for four years. When massive, painful splenomegaly developed, splenic irradiation (SI) was chosen as the primary form of therapy and an excellent systemic response could be achieved. Our observation is in agreement with preliminary studies, which advocate SI as the primary form of therapy in PLL. Furthermore, it is emphasized that an early diagnosis of PLL is necessary to establish its true course and that the prognosis may be better than originally thought.
Analysis of Continuous Glucose Monitoring in Pregnant Women With Diabetes: Distinct Temporal Patterns of Glucose Associated With Large-for-Gestational-Age Infants
Authors: Graham R. Law, George T.H. Ellison, Anna L. Secher, Peter Damm, Elisabeth R. Mathiesen, Rosemary Temple, Helen R. Murphy, Eleanor M. Scott
Journal: Diabetes Care (2015)

OBJECTIVE Continuous glucose monitoring (CGM) is increasingly used to assess glucose control in diabetes. The objective was to examine how analysis of glucose data might improve our understanding of the role temporal glucose variation has on large-for-gestational-age (LGA) infants born to women with diabetes. RESEARCH DESIGN AND METHODS Functional data analysis (FDA) was applied to 1.68 million glucose measurements from 759 measurement episodes, obtained from two previously published randomized controlled trials of CGM in pregnant women with diabetes. A total of 117 women with type 1 diabetes (n = 89) and type 2 diabetes (n = 28) who used repeated CGM during pregnancy were recruited from secondary care multidisciplinary obstetric clinics for diabetes in the U.K. and Denmark. LGA was defined as birth weight ≥90th percentile adjusted for sex and gestational age. RESULTS A total of 54 of 117 (46%) women developed LGA. LGA was associated with lower mean glucose (7.0 vs. 7.1 mmol/L; P &amp;lt; 0.01) in trimester 1, with higher mean glucose in trimester 2 (7.0 vs. 6.7 mmol/L; P &amp;lt; 0.001) and trimester 3 (6.5 vs. 6.4 mmol/L; P &amp;lt; 0.01). FDA showed that glucose was significantly lower midmorning (0900–1100 h) and early evening (1900–2130 h) in trimester 1, significantly higher early morning (0330–0630 h) and throughout the afternoon (1130–1700 h) in trimester 2, and significantly higher during the evening (2030–2330 h) in trimester 3 in women whose infants were LGA. CONCLUSIONS FDA of CGM data identified specific times of day that maternal glucose excursions were associated with LGA. It highlights trimester-specific differences, allowing treatment to be targeted to gestational glucose patterns.
Phase II Study of Accelerated Hypofractionated Three-Dimensional Conformal Radiotherapy for Stage T1-3 N0 M0 Non-Small Cell Lung Cancer: NCIC CTG BR.25
Authors: Patrick Cheung, Sergio Faria, Shahida Ahmed, Pierre Chabot, Jonathan Greenland, Elizabeth Kurien, Islam Mohamed, James R Wright, Helmut Hollenhorst, Catherine de Metz, Holly Campbell, Thi Toni Vu, Anand Karvat, Elaine S Wai, Yee C Ung, Glenwood Goss, Frances A Shepherd, Patti O'Brien, Keyue Ding, Chris O'Callaghan
Journal: JNCI Journal of the National Cancer Institute (2014)

BackgroundA multi-institutional phase II trial was performed to assess a hypofractionated accelerated radiotherapy regimen for early stage non–small cell lung cancer (NSCLC) in an era when stereotactic body radiotherapy was not widely available.
24-h ambulatory blood pressure is linked to chromosome 18q21–22 and genetic variation of NEDD4L associates with cross-sectional and longitudinal blood pressure in Swedes
Authors: C. Fava, F. von Wowern, G. Berglund, J. Carlson, B. Hedblad, L. Rosberg, P. Burri, P. Almgren, O. Melander
Journal: Kidney International (2006)
Prognostic and Therapeutic Relevance of Molecular Subtypes in High-Grade Serous Ovarian Cancer
Authors: Gottfried E. Konecny, Chen Wang, Habib Hamidi, Boris Winterhoff, Kimberly R. Kalli, Judy Dering, Charles Ginther, Hsiao-Wang Chen, Sean Dowdy, William Cliby, Bobbie Gostout, Karl C. Podratz, Gary Keeney, He-Jing Wang, Lynn C. Hartmann, Dennis J. Slamon, Ellen L. Goode
Journal: JNCI Journal of the National Cancer Institute (2014)

Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.
Clinical presentation of exclusive cystic fibrosis lung disease
Authors: I. Bronsveld, J. Bijman, F. Mekus, M. Ballmann, H. J Veeze, B. Tummler
Journal: Thorax (1999)

The diagnosis of cystic fibrosis (CF) is based on the occurrence of two mutations in the cystic fibrosis transmembrane conductance regulator (<i>CFTR</i>) gene and on assays that measure the basic defect of abnormal chloride transport in the affected organs. However, in cases of atypical CF not all diagnostic tests may be positive. We present a patient with an atypical CF phenotype in whom the only presenting symptom was severe CF-like lung disease substantiated by an abnormal nasal potential difference. Genetic analysis showed that the patient was a symptomatic heterozygote, which suggests that one lesion in the<i>CFTR</i> gene may be sufficient to cause CF-like lung disease.
Hypoxia-derived oxidative stress mediates epigenetic repression of PKCɛ gene in foetal rat hearts
Authors: Andrew J. Patterson, Daliao Xiao, Fuxia Xiong, Brandon Dixon, Lubo Zhang
Journal: Cardiovascular Research (2011)

Hypoxia causes protein kinase C epsilon (PKCε) gene repression in foetal hearts, resulting in heightened cardiac susceptibility to ischaemic injury in offspring. We tested the hypothesis that hypoxia inducible factor 1 (HIF-1) and/or reactive oxygen species (ROS) mediate hypoxia-induced PKCε gene repression.Hypoxia induced in vivo to pregnant rats, ex vivo to isolated foetal rat hearts, and in vitro in the rat embryonic ventricular myocyte cell line H9c2 resulted in a comparable decrease in PKCε protein and mRNA abundance in foetal hearts and H9c2 cells, which was associated with a significant increase in CpG methylation of the SP1-binding sites at the PKCε promoter. In H9c2 cells and foetal hearts, hypoxia caused nuclear accumulation of HIF-1α, which was inhibited by 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole and 2-methoxy estradiol. The HIF-1α inhibitors had no significant effect on hypoxia-induced PKCε mRNA repression. Hypoxia produced a time-dependent increase in ROS production in H9c2 cells and foetal hearts that was blocked by ROS scavengers N-acetyl-cysteine or tempol. In accordance, N-acetyl-cysteine and tempol, but not apocynin, inhibited the hypoxic effect and restored PKCε protein and mRNA expression to the control values in foetal hearts and H9c2 cells. The ROS scavengers blocked hypoxia-induced CpG methylation of the SP1-binding sites, restored SP1 binding to the PKCε promoter, and abrogated the hypoxia-induced increase in the susceptibility of the heart to ischaemic injury in offspring.The results demonstrate that hypoxia induces epigenetic repression of the PKCε gene through a NADPH oxidase-independent ROS-mediated pathway in the foetal heart, leading to heightened heart vulnerability to ischaemic injury in offspring.
Inducible FGFR-1 Activation Leads to Irreversible Prostate Adenocarcinoma and an Epithelial-to-Mesenchymal Transition
Authors: Victor D. Acevedo, Rama D. Gangula, Kevin W. Freeman, Rile Li, Youngyou Zhang, Fen Wang, Gustavo E. Ayala, Leif E. Peterson, Michael Ittmann, David M. Spencer
Journal: Cancer Cell (2007)