tbuckley/cabot-search huggingface dataset:
Mammography Surveillance and Mortality in Older Breast Cancer Survivors
Authors: Timothy L. Lash, Matthew P. Fox, Diana S.M. Buist, Feifei Wei, Terry S. Field, Floyd J. Frost, Ann M. Geiger, Virginia P. Quinn, Marianne Ulcickas Yood, Rebecca A. Silliman
Journal: Journal of Clinical Oncology (2007)

There are more than 2,000,000 breast cancer survivors in the United States today. While surveillance for asymptomatic recurrence and second primary is included in consensus recommendations, the effectiveness of this surveillance has not been well characterized. Our purpose is to estimate the effectiveness of surveillance mammography in a cohort of breast cancer survivors with complete ascertainment of surveillance mammograms and negligible losses to follow-up.We enrolled 1,846 stage I and II breast cancer patients who were at least 65 years old at six integrated health care delivery systems. We used medical record review and existing databases to ascertain patient, tumor, and therapy characteristics, as well as receipt of surveillance mammograms. We linked personal identifiers to the National Death Index to ascertain date and cause of death. We matched four controls to each breast cancer decedent to estimate the association between receipt of surveillance mammogram and breast cancer mortality.One hundred seventy-eight women died of breast cancer during 5 years of follow-up. Each additional surveillance mammogram was associated with a 0.69-fold decrease in the odds of breast cancer mortality (95% CI, 0.52 to 0.92). The protective association was strongest among women with stage I disease, those who received mastectomy, and those in the oldest age group.Given existing recommendations for post-therapy surveillance, trials to compare surveillance with no surveillance are unlikely. This large observational study provides support for the recommendations, suggesting that receipt of surveillance mammograms reduces the rate of breast cancer mortality in older patients diagnosed with early-stage disease.
Phase I Trial of a Bivalent Gangliosides Vaccine in Combination with β-Glucan for High-Risk Neuroblastoma in Second or Later Remission
Authors: Brian H. Kushner, Irene Y. Cheung, Shakeel Modak, Kim Kramer, Govind Ragupathi, Nai-Kong V. Cheung
Journal: Clinical Cancer Research (2014)

Abstract Purpose: To report on a phase I trial designed to find the maximally tolerated dose in children of the immunologic adjuvant OPT-821 in a vaccine containing neuroblastoma-associated antigens (GD2 and GD3; Clinicaltrials.gov NCT00911560). Secondary objectives were to obtain preliminary data on immune response and activity against minimal residual disease (MRD). Treatment also included the immunostimulant β-glucan. Experimental Design: Patients with neuroblastoma in ≥2nd complete/very good partial remission received vaccine subcutaneously (weeks 1–2–3–8–20–32–52). Vaccine contained 30 μg each of GD2 and GD3 stabilized as lactones and conjugated to the immunologic carrier protein keyhole limpet hemocyanin; and OPT-821, which was dose escalated as 50, 75, 100, and 150 μg/m2 per injection. Oral β-glucan (40 mg/kg/day, 14 days on/14 days off) started week 6. Results: The study was completed with 15 patients because there was no dose-limiting toxicity at 150 μg/m2 of OPT-821 (the dosing used in adults). Thirteen of fifteen patients received the entire protocol treatment, including 12 who remain relapse-free at 24+ to 39+ (median 32+) months and 1 who relapsed (single node) at 21 months. Relapse-free survival was 80% ± 10% at 24 months. Vaccine and β-glucan were well tolerated. Twelve of fifteen patients had antibody responses against GD2 and/or GD3. Disappearance of MRD was documented in 6 of 10 patients assessable for response. Conclusions: This immunotherapy program lacks major toxicity and is transportable to any outpatient clinic. Patient outcome is encouraging but the efficacy is uncertain because of the complexity and heterogeneity of prior therapies. A larger phase II trial is underway. Clin Cancer Res; 20(5); 1375–82. ©2014 AACR.
Basic Mechanisms Responsible for Osteolytic and Osteoblastic Bone Metastases
Authors: Theresa A. Guise, Khalid S. Mohammad, Gregory Clines, Elizabeth G. Stebbins, Darren H. Wong, Linda S. Higgins, Robert Vessella, Eva Corey, Susan Padalecki, Larry Suva, John M. Chirgwin
Journal: Clinical Cancer Research (2006)

Abstract Certain solid tumors metastasize to bone and cause osteolysis and abnormal new bone formation. The respective phenotypes of dysregulated bone destruction and bone formation represent two ends of a spectrum, and most patients will have evidence of both. The mechanisms responsible for tumor growth in bone are complex and involve tumor stimulation of the osteoclast and the osteoblast as well as the response of the bone microenvironment. Furthermore, factors that increase bone resorption, independent of tumor, such as sex steroid deficiency, may contribute to this vicious cycle of tumor growth in bone. This article discusses mechanisms and therapeutic implications of osteolytic and osteoblastic bone metastases.
Acting on incidental findings in research imaging
Authors: J. M. Wardlaw, H. Davies, T. C. Booth, G. Laurie, A. Compston, C. Freeman, M. O. Leach, A. D. Waldman, D. J. Lomas, K. Kessler, F. Crabbe, A. Jackson
Journal: BMJ (2015)

Incidental findings of imaging research studies can turn healthy individuals into anxious patients, while putting an extra burden on primary care. <b>J M Wardlaw and colleagues</b> argue that doctors should ensure that the personal, ethical, healthcare, and cost implications of these common findings are managed proportionately, sensitively, and economically
Narrative Review: The Emerging Clinical Implications of the Role of Aldosterone in the Metabolic Syndrome and Resistant Hypertension
Authors: James R. Sowers
Journal: Annals of Internal Medicine (2009)

The prevalence of obesity, diabetes, hypertension, and cardiovascular and chronic kidney disease is increasing in developed countries. Obesity, insulin resistance, and hypertension commonly cluster with other risk factors for cardiovascular and chronic kidney disease to form the metabolic syndrome. Emerging evidence supports a paradigm shift in our understanding of the renin–angiotensin–aldosterone system and in aldosterone's ability to promote insulin resistance and participate in the pathogenesis of the metabolic syndrome and resistant hypertension. Recent data suggest that excess circulating aldosterone promotes the development of both disorders by impairing insulin metabolic signaling and endothelial function, which in turn leads to insulin resistance and cardiovascular and renal structural and functional abnormalities. Indeed, hyperaldosteronism is associated with impaired pancreatic β-cell function, skeletal muscle insulin sensitivity, and elevated production of proinflammatory adipokines from adipose tissue, which results in systemic inflammation and impaired glucose tolerance. Accumulating evidence indicates that the cardiovascular and renal abnormalities associated with insulin resistance are mediated in part by aldosterone acting on the mineralocorticoid receptor. Although we have known that mineralocorticoid receptor blockade attenuates cardiovascular and renal injury, only recently have we learned that mineralocorticoid receptor blockade improves pancreatic insulin release, insulin-mediated glucose utilization, and endothelium-dependent vasorelaxation. In summary, aldosterone excess has detrimental metabolic effects that contribute to the metabolic syndrome and endothelial dysfunction, which in turn contribute to the development of resistant hypertension as well as cardiovascular disease and chronic kidney disease.
Genome-wide analyses of Shavenbaby target genes reveals distinct features of enhancer organization
Authors: Delphine Menoret, Marc Santolini, Isabelle Fernandes, Rebecca Spokony, Jennifer Zanet, Ignacio Gonzalez, Yvan Latapie, Pierre Ferrer, Hervé Rouault, Kevin P White, Philippe Besse, Vincent Hakim, Stein Aerts, Francois Payre, Serge Plaza
Journal: Genome biology (2013)

Abstract Background Developmental programs are implemented by regulatory interactions between Transcription Factors (TFs) and their target genes, which remain poorly understood. While recent studies have focused on regulatory cascades of TFs that govern early development, little is known about how the ultimate effectors of cell differentiation are selected and controlled. We addressed this question during late Drosophila embryogenesis, when the finely tuned expression of the TF Ovo/Shavenbaby (Svb) triggers the morphological differentiation of epidermal trichomes. Results We defined a sizeable set of genes downstream of Svb and used in vivo assays to delineate 14 enhancers driving their specific expression in trichome cells. Coupling computational modeling to functional dissection, we investigated the regulatory logic of these enhancers. Extending the repertoire of epidermal effectors using genome-wide approaches showed that the regulatory models learned from this first sample are representative of the whole set of trichome enhancers. These enhancers harbor remarkable features with respect to their functional architectures, including a weak or non-existent clustering of Svb binding sites. The in vivo function of each site relies on its intimate context, notably the flanking nucleotides. Two additional cis -regulatory motifs, present in a broad diversity of composition and positioning among trichome enhancers, critically contribute to enhancer activity. Conclusions Our results show that Svb directly regulates a large set of terminal effectors of the remodeling of epidermal cells. Further, these data reveal that trichome formation is underpinned by unexpectedly diverse modes of regulation, providing fresh insights into the functional architecture of enhancers governing a terminal differentiation program.
Relation between metabolic syndrome and acute exacerbation of COPD
Authors: Hajer ben Abdelghaffar, Eya Tangour, Soraya Fenniche, Leila El Fekih, Dorra Greb, Ines Akrout, Hela Hassene, Wided Ben hamad, Hela Kammoun, Dalinda Belhabib, Mohamed Lamine Megdiche
Journal: European Respiratory Journal (2012)

The concept of COPD as a systemic disease has been widely accepted in the past several years. However, to date, rare studies have analyzed correlation between exacerbations of COPD (ECOPD) and Metabolic Sndrome (MetS).  The aim of this study was to examine if presence of MetS increases the frequency, duration and severity of ECOPD.  Methods: Patients with COPD were prospectively enrolled and followed between January 2008 and December 2011. Medical records, pulmonary function tests, chest X-rays; laboratory test results were gathered to establish the presence of COPD and MetS. Patients were divided in two groups; with and without MetS. The ECOPD was defined as worsening of symptoms requiring increased use of rescue medications and/or need for either systemic steroids or antibiotics or that led to emergency room visit or hospitalizations during 36 months follow-up. A total of 100 patients were recruited, 60 with MetS and 40 without. The mean exacerbation of COPD frequency was 2 in MetS group versus 0.7 in the control group during the follow-up period (P
Phase III trial of adjuvant 5-fluorouracil and adriamycin versus 5-fluorouracil, adriamycin, and polyadenylic–polyuridylic acid (poly A:U) for locally advanced gastric cancer after curative surgery: final results of 15-year follow-up
Authors: H.-C. Jeung, Y.W. Moon, S.Y. Rha, N.C. Yoo, J.K. Roh, S.H. Noh, J.S. Min, B.S. Kim, H.C. Chung
Journal: Annals of Oncology (2007)
Methacholine responsiveness in infants assessed with low frequency forced oscillation and forced expiration techniques
Authors: G L Hall
Journal: Thorax (2001)

<h3>BACKGROUND</h3> The contribution of the pulmonary tissues to the mechanical behaviour of the respiratory system is well recognised. This study was undertaken to detect airway and lung tissue responses to inhaled methacholine (Mch) using the low frequency forced oscillation technique (LFOT). <h3>METHODS</h3> The respiratory system impedance (Zrs, 0.5–20 Hz) was determined in 17 asymptomatic infants. A model containing airway resistance (Raw) and inertance (Iaw) and a constant phase tissue damping (G) and elastance (H) was fitted to Zrs data. Tissue hysteresivity (η) was calculated as η=G/H. The raised volume rapid thoracic compression technique (RVRTC) was used to generate forced expiratory volume in 0.5 seconds (FEV<sub>0.5</sub>). Lung function was determined at baseline and following inhaled Mch in doubling doses (0.25–16 mg/ml) until the maximal dose was reached or a fall of 15% in FEV<sub>0.5</sub> was achieved (PC<sub>15</sub>FEV<sub>0.5</sub>). The response to Mch was defined in terms of the concentration of Mch provoking a change in lung function parameters of more than two standard deviation units (threshold concentration). <h3>RESULTS</h3> At PC<sub>15</sub>FEV<sub>0.5</sub> a response in Raw, Iaw, G, and η, but not H, was detected (mean (SE) 61.28 (12.22)%, 95.43 (34.31)%, 46.28 (22.36)%, 44.26 (25.83)%, and –6.48 (4.94)%, respectively). No significant differences were found between threshold concentrations of LFOT parameters and FEV<sub>0.5</sub>. <h3>CONCLUSIONS</h3> Inhaled Mch alters both airway and respiratory tissue mechanics in infants.
Poor air quality in classrooms related to asthma and rhinitis in primary schoolchildren of the French 6 Cities Study
Authors: Isabella Annesi-Maesano, Marion Hulin, François Lavaud, Chantal Raherison, Christine Kopferschmitt, Frederic de Blay, Denis André Charpin, Caillaud Denis
Journal: Thorax (2012)

Relationships between indoor air quality (IAQ) found in schools and the allergic and respiratory health of schoolchildren have been insufficiently explored. A survey was conducted in a large sample of classrooms of primary schools in France to provide objective assessments of IAQ to which young schoolchildren are exposed in classrooms, and to relate exposure to major air pollutants found in classrooms to asthma and allergies of schoolchildren.Concentrations of fine particles with aerodynamic diameter ≤2.5 μm (PM(2.5)), nitrogen dioxide (NO(2)) and three aldehydes were objectively assessed in 401 randomly chosen classrooms in 108 primary schools attended by 6590 children (mean age 10.4 years, SD ±0.7) in the French 6 Cities Study. The survey incorporated a medical visit including skin prick testing (SPT) for common allergens, a test for screening exercise-induced asthma (EIA) and a standardised health questionnaire completed by parents.Children were differently exposed to poor air quality in classrooms, with almost 30% being highly exposed according to available standards. After adjusting for confounders, past year rhinoconjunctivitis was significantly associated with high levels of formaldehyde in classrooms (OR 1.19; 95% CI 1.04 to 1.36). Additionally, an increased prevalence of past year asthma was found in the classrooms with high levels of PM(2.5) (OR 1.21; 95% CI 1.05 to 1.39), acrolein (OR 1.22; 95% CI 1.09 to 1.38) and NO(2) (OR 1.16; 95% CI 0.95 to 1.41) compared with others. The relationship was observed mostly for allergic asthma as defined using SPT. A significant positive correlation was found between EIA and the levels of PM(2.5) and acrolein in the same week.In this random sample, air quality in classrooms was poor, varied significantly among schools and cities, and was related to an increased prevalence of clinical manifestations of asthma and rhinitis in schoolchildren. Children with a background of allergies seemed at increased risk.
Oesophageal lichen planus: a missed diagnosis
Authors: A. R Mohammed
Journal: Journal of the Royal Society of Medicine (2006)

Lichen planus is a chronic inflammatory mucocutaneous disease of unknown aetiology with no racial predisposition, although there is a considerable variation in its incidence. Involvement of oesophagus is considered to be extremely rare; the diagnosis is often not made until complications occur. An epidemiological study of 584 patients with oral lichen planus showed oesophageal involvement in only six patients, clearly showing a rare prevalence. The incidence of this disease in dermatology clinics is 1.4%, compared to 3% in oral medicine clinics. We describe a 69-year-old woman who presented with a 2-year history of odynophagia due to oesophageal lichen planus. This case is very unusual in that she had skin involvement 28 years before and had no recurrence.
Gastro-oesophageal reflux symptoms and the risks of oesophageal cancer: are the effects modified by smoking, NSAIDs or acid suppressants?
Authors: N Pandeya, P M Webb, S Sadeghi, A C Green, D C Whiteman
Journal: Gut (2009)

<h3>Objective:</h3> To measure the extent to which risks of oesophageal cancers associated with gastro-oesophageal reflux (GOR) are modified by common factors including smoking, non-steroidal anti-inflammatory drugs (NSAIDs) and acid suppressant medications. <h3>Design and setting:</h3> Population-based case–control study. <h3>Participants:</h3> Cases were patients with oesophageal (OAC; n = 365) or gastro-oesophageal junction (GOJAC; n = 426) adenocarcinomas, or squamous cell carcinomas (OSCC; n = 303). Controls were sampled from a population register (n = 1580). <h3>Main outcome measure:</h3> Odds ratio and 95% confidence interval. <h3>Results:</h3> Frequent (at least weekly) symptoms of GOR were associated with significant 6.4-fold, 4.6-fold and 2.2-fold increased risks of OAC, GOJAC and OSCC, respectively. Under models examining effects of combined exposure, patients with frequent GOR symptoms who were also heavy smokers had markedly higher OAC risks (OR = 12.3, 95% CI 6.3 to 24.0) than those with frequent GOR who did not smoke (OR = 6.8, 95% CI 3.6 to 12.9). Similar patterns were observed for GOJAC and OSCC. Among people with frequent GOR symptoms, regular use of aspirin/NSAIDs was associated with almost two-thirds lower OAC risks (OR = 4.8, 95% CI 2.5 to 9.2) than non-users (13.9, 95% CI 6.5 to 30.0). In contrast, among those with frequent GOR symptoms, users of acid suppressants had similar OAC risks (OR 7.8, 95% CI 5.2 to 11.8) to non-users (OR 5.3, 95% CI 3.2 to 9.0). <h3>Conclusions:</h3> People experiencing frequent GOR symptoms have markedly increased risks of OAC and GOJAC, and this effect may be greater amongst smokers. Use of aspirin and NSAIDs, but not acid suppressants, significantly reduced the risks of oesophageal cancers associated with GOR.
Potential therapeutic role of antagomiR17 for the treatment of chronic lymphocytic leukemia
Authors: Sara Dereani, Paolo Macor, Tiziana D’Agaro, Nelly Mezzaroba, Michele Dal-Bo, Sara Capolla, Antonella Zucchetto, Erika Tissino, Giovanni Del Poeta, Sonia Zorzet, Valter Gattei, Riccardo Bomben
Journal: Journal of Hematology & Oncology (2014)

Recently it was reported that microRNA from the miR-17 ~ 92 family may have a key role in chronic lymphocytic leukemia (CLL). Here, we designed specific oligonucleotides to target endogenous miR-17 (antagomiR17). In-vitro administration of antagomiR17 effectively reduced miR-17 expression and the proliferation of CLL-like MEC-1 cells. When injected in-vivo in tumor generated by the MEC-1 cells in SCID mice, antagomiR17 dramatically reduced tumor growth and significantly increase survival. Altogether, our results provide the rationale for the use of antagomiR17 as a novel potential therapeutic tool in CLL and in other lymphoproliferative disorders where miR-17 has a driver role in tumor progression.
Histamine Induces Expression of Cycloxygenase-2 and Regulates the Production of Prostacyclin(PGI2) and Thromboxane-A2(TXA2) in Human Coronary Artery Endothelial Cells(HCAEC)
Authors: S. Essengue, J. Talreja, D.J. Stechschulte, K.N. Dileepan
Journal: Journal of Allergy and Clinical Immunology (2006)
Improved treatment response to dornase alfa in cystic fibrosis patients using controlled inhalation
Authors: E.M. Bakker, S. Volpi, E. Salonini, E.C. van der Wiel-Kooij, C.J.J.C.M. Sintnicolaas, W.C.J. Hop, B.M. Assael, P.J.F.M. Merkus, H.A.W.M. Tiddens
Journal: European Respiratory Journal (2011)

Better treatment of obstructed small airways is needed in cystic fibrosis. This study investigated whether efficient deposition of dornase alfa in the small airways improves small airway obstruction. In a multicentre, double-blind, randomised controlled clinical trial, cystic fibrosis patients on maintenance treatment with 2.5 mL dornase alfa once daily were switched to a smart nebuliser and randomised to small airway deposition (n=24) or large airway deposition (n=25) for 4 weeks. The primary outcome parameter was forced expiratory flow at 75% of forced vital capacity (FEF 75% ). FEF 75% increased significantly by 0.7 sd (5.2% predicted) in the large airways group and 1.2 sd (8.8% pred) in the small airways group. Intention-to-treat analysis did not show a significant difference in treatment effect between groups. Per-protocol analysis, excluding patients not completing the trial or with adherence &lt;70%, showed a trend (p=0.06) in FEF 75% Z-score and a significant difference (p=0.04) between groups in absolute FEF 75% (L·s −1 ) favouring small airway deposition. Improved delivery of dornase alfa using a smart nebuliser that aids patients in correct inhalation technique resulted in significant improvement of FEF 75% in children with stable cystic fibrosis. Adherent children showed a larger treatment response for small airway deposition.
Expression of Carbonic Anhydrase IX in Astrocytic Tumors Predicts Poor Prognosis
Authors: Joonas A. Haapasalo, Kristiina M. Nordfors, Mika Hilvo, Immo J. Rantala, Ylermi Soini, Anna-Kaisa Parkkila, Silvia Pastoreková, Jaromir Pastorek, Seppo M. Parkkila, Hannu K. Haapasalo
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Carbonic anhydrase IX (CA IX) is a hypoxia-inducible enzyme, which is associated with neoplastic growth. Ectopic CA IX expression has been observed in several tumors, whose normal counterparts do not express this enzyme. Normal human brain tissue shows only slight or no expression of CA IX. Experimental Design: We describe CA IX expression in human diffusely infiltrating astrocytomas. The association of CA IX is evaluated with clinicopathologic and molecular factors including cell proliferation and apoptosis as well as the expression of p53 and epidermal growth factor receptor. Results: CA IX immunopositivity was observed in 284 cases of 362 (78%) tumors. The positive areas were often located in close proximity to necrotic regions (P &amp;lt; 0.001). The CA IX immunoreactivity showed strong association with tumor malignancy grades (P &amp;lt; 0.0001). CA IX showed no association with p53 expression nor did it correlate with epidermal growth factor receptor–amplification, apoptosis, or cell proliferation. CA IX intensity had significant prognostic value in univariate (P=0.0011, log-rank test) and multivariate survival analysis (P = 0.038, Cox analysis). Conclusions: CA IX expression is common in diffusely infiltrating high-grade astrocytomas. Our results suggest that CA IX is a useful biomarker for predicting poor prognosis of astrocytic tumors. It may also be a promising target molecule for the improvement of therapeutic interventions in astrocytomas.