tbuckley/cabot-search huggingface dataset:
Epoxyeicosanoids stimulate multiorgan metastasis and tumor dormancy escape in mice
Authors: Dipak Panigrahy, Matthew L. Edin, Craig R. Lee, Sui Huang, Diane R. Bielenberg, Catherine E. Butterfield, Carmen M. Barnés, Akiko Mammoto, Tadanori Mammoto, Ayala Luria, Ofra Benny, Deviney M. Chaponis, Andrew C. Dudley, Emily R. Greene, Jo-Anne Vergilio, Giorgio Pietramaggiori, Sandra S. Scherer-Pietramaggiori, Sarah M. Short, Meetu Seth, Fred B. Lih, Kenneth B. Tomer, Jun Yang, Reto A. Schwendener, Bruce D. Hammock, John R. Falck, Vijaya L. Manthati, Donald E. Ingber, Arja Kaipainen, Patricia A. D’Amore, Mark W. Kieran, Darryl C. Zeldin
Journal: Journal of Clinical Investigation (2011)

Epoxyeicosatrienoic acids (EETs) are small molecules produced by cytochrome P450 epoxygenases. They are lipid mediators that act as autocrine or paracrine factors to regulate inflammation and vascular tone. As a result, drugs that raise EET levels are in clinical trials for the treatment of hypertension and many other diseases. However, despite their pleiotropic effects on cells, little is known about the role of these epoxyeicosanoids in cancer. Here, using genetic and pharmacological manipulation of endogenous EET levels, we demonstrate that EETs are critical for primary tumor growth and metastasis in a variety of mouse models of cancer. Remarkably, we found that EETs stimulated extensive multiorgan metastasis and escape from tumor dormancy in several tumor models. This systemic metastasis was not caused by excessive primary tumor growth but depended on endothelium-derived EETs at the site of metastasis. Administration of synthetic EETs recapitulated these results, while EET antagonists suppressed tumor growth and metastasis, demonstrating in vivo that pharmacological modulation of EETs can affect cancer growth. Furthermore, inhibitors of soluble epoxide hydrolase (sEH), the enzyme that metabolizes EETs, elevated endogenous EET levels and promoted primary tumor growth and metastasis. Thus, our data indicate a central role for EETs in tumorigenesis, offering a mechanistic link between lipid signaling and cancer and emphasizing the critical importance of considering possible effects of EET-modulating drugs on cancer.
Amino Acid Signaling to mTOR Mediated by Inositol Polyphosphate Multikinase
Authors: Seyun Kim, Sangwon F. Kim, David Maag, Micah J. Maxwell, Adam C. Resnick, Krishna R. Juluri, Anutosh Chakraborty, Michael A. Koldobskiy, Seung Hun Cha, Roxanne Barrow, Adele M. Snowman, Solomon H. Snyder
Journal: Cell Metabolism (2011)
Reply to L. Gianni et al
Authors: Dawn L. Hershman, Joseph M. Unger
Journal: Journal of Clinical Oncology (2015)

Randomized Multicenter Placebo-Controlled Trial of Omega-3 Fatty Acids for the Control of Aromatase Inhibitor-Induced Musculoskeletal Pain: SWOG S0927." 2 Many of the points raised were addressed in the discussion section of our article.In all trials, difficult choices must be made with regard to the design of the study that may influence the results, such as the choice of outcome measure, the duration of therapy, the dose of drug, the formulation of the drug, the inclusion criteria, and the choice of placebo.In addition, overall negative findings do not preclude the fact that some subsets may achieve more of a benefit than others.In our trial, ongoing analyses will explore factors that may differentiate patients who did and did not achieve an improvement in symptoms over time, both in the active arm as well as the placebo arm, which may inform future studies.But importantly, the patients in the randomized arms of this large multicenter trial were well balanced across multiple domains of potential confounding factors, and overall, the trial did not find a benefit of omega-3 fatty acids compared with placebo.Although it is possible that another rigorous trial could observe a benefit, we do not feel there is sufficient evidence to suggest there is a role for omega-3 fatty acids for treating aromatase inhibitor-induced arthralgias.
Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies
Authors: Q. Qi, A. Y. Chu, J. H. Kang, J. Huang, L. M. Rose, M. K. Jensen, L. Liang, G. C. Curhan, L. R. Pasquale, J. L. Wiggs, I. De Vivo, A. T. Chan, H. K. Choi, R. M. Tamimi, P. M. Ridker, D. J. Hunter, W. C. Willett, E. B. Rimm, D. I. Chasman, F. B. Hu, L. Qi
Journal: BMJ (2014)

<b>Objective</b> To examine the interactions between genetic predisposition and consumption of fried food in relation to body mass index (BMI) and obesity. <b>Design</b> Prospective cohort study. <b>Setting</b> Health professionals in the United States. <b>Participants</b> 9623 women from the Nurses’ Health Study, 6379 men from the Health Professionals Follow-up Study, and a replication cohort of 21 421 women from the Women’s Genome Health Study. <b>Main outcome measure</b> Repeated measurement of BMI over follow-up. <b>Results</b> There was an interaction between fried food consumption and a genetic risk score based on 32 BMI-associated variants on BMI in both the Nurses’ Health Study and Health Professionals Follow-up Study (P≤0.001 for interaction). Among participants in the highest third of the genetic risk score, the differences in BMI between individuals who consumed fried foods four or more times a week and those who consumed fried foods less than once a week amounted to 1.0 (SE 0.2) in women and 0.7 (SE 0.2) in men, whereas the corresponding differences were 0.5 (SE 0.2) and 0.4 (SE 0.2) in the lowest third of the genetic risk score. The gene-diet interaction was replicated in the Women’s Genome Health Study (P&lt;0.001 for interaction). Viewed differently, the genetic association with adiposity was strengthened with higher consumption of fried foods. In the combined three cohorts, the differences in BMI per 10 risk alleles were 1.1 (SE 0.2), 1.6 (SE 0.3), and 2.2 (SE 0.6) for fried food consumption less than once, one to three times, and four or more times a week (P&lt;0.001 for interaction); and the odds ratios (95% confidence intervals) for obesity per 10 risk alleles were 1.61 (1.40 to 1.87), 2.12 (1.73 to 2.59), and 2.72 (2.12 to 3.48) across the three categories of consumption (P=0.002 for interaction). In addition, the variants in or near genes highly expressed or known to act in the central nervous system showed significant interactions with fried food consumption, with the FTO (fat mass and obesity associated) variant showing the strongest result (P&lt;0.001 for interaction). <b>Conclusion</b> Our findings suggest that consumption of fried food could interact with genetic background in relation to obesity, highlighting the particular importance of reducing fried food consumption in individuals genetically predisposed to obesity.
A randomized phase III trial on maintenance treatment with bevacizumab alone or in combination with erlotinib after chemotherapy and bevacizumab in metastatic colorectal cancer: the Nordic ACT Trial
Authors: A. Johnsson, H. Hagman, J.-E. Frödin, Å. Berglund, N. Keldsen, E. Fernebro, J. Sundberg, R. De Pont Christensen, K.-L. Garm Spindler, D. Bergström, A. Jakobsen
Journal: Annals of Oncology (2013)
Clinical parameters model for predicting pathologic complete response following preoperative chemoradiation in patients with esophageal cancer
Authors: J.A. Ajani, A.M. Correa, W.L. Hofstetter, D.C. Rice, M.A. Blum, A. Suzuki, T. Taketa, J. Welsh, S.H. Lin, J.H. Lee, M.S. Bhutani, W.A. Ross, D.M. Maru, H.A. Macapinlac, J. Erasmus, R. Komaki, R.J. Mehran, A.A. Vaporciyan, S.G. Swisher
Journal: Annals of Oncology (2012)
Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes
Authors: Kaixin Zhou, Celine Bellenguez, Chris C A Spencer, Amanda J Bennett, Ruth L Coleman, Roger Tavendale, Simon A Hawley, Louise A Donnelly, Chris Schofield, Christopher J Groves, Lindsay Burch, Fiona Carr, Amy Strange, Colin Freeman, Jenefer M Blackwell, Elvira Bramon, Matthew A Brown, Juan P Casas, Aiden Corvin, Nicholas Craddock, Panos Deloukas, Serge Dronov, Audrey Duncanson, Sarah Edkins, Emma Gray, Sarah Hunt, Janusz Jankowski, Cordelia Langford, Hugh S Markus, Christopher G Mathew, Robert Plomin, Anna Rautanen, Stephen J Sawcer, Nilesh J Samani, Richard Trembath, Ananth C Viswanathan, Nicholas W Wood, Lorna W Harries, Andrew T Hattersley, Alex S F Doney, Helen Colhoun, Andrew D Morris, Calum Sutherland, D Grahame Hardie, Leena Peltonen, Mark I McCarthy, Rury R Holman, Colin N A Palmer, Peter Donnelly, Ewan R Pearson
Journal: Nature Genetics (2010)
Treating Diastolic Heart Failure With Statins
Authors: Michael R. Zile
Journal: Circulation (2005)

iastolic heart failure (DHF) is a significant healthcare problem. 1,2Nearly 50% of all patients with chronic heart failure have DHF.Once hospitalized for heart failure, patients with DHF have a 50% chance of rehospitalization within 6 months.Patients with DHF have a 5% to 6% yearly mortality rate.It is estimated that treating patients with DHF costs in excess of $3.5 billion/year.Despite the significant impact that DHF has on heart failure incidence, prognosis, and cost, only 1 large randomized clinical trial has been completed that examined the treatment of patients with DHF, Candesartan cilexitil (Atacand) in Heart failure Assessment of Reduction Mortality and morbidity-Preserved (CHARM-Preserved).
CARD15/NOD2 single nucleotide polymorphisms do not confer susceptibility to type I psoriasis
Authors: D. Plant, J. Lear, A. Marsland, J. Worthington, C.E.M. Griffiths
Journal: British Journal of Dermatology (2004)

Background A psoriasis susceptibility locus on chromosome 16q was identified recently. This region coincides with a locus predisposing to Crohn's disease. Patients with Crohn's disease have a fivefold greater relative risk for development of psoriasis. In Crohn's disease mutation of the caspase recruitment domain family, member 15 (CARD15) gene (chromosome 16q12.1) confers susceptibility. In light of the overlap in linkage data, and the observation of comorbidity between Crohn's disease and psoriasis, it is plausible that both diseases share a common genetic factor. Objectives To assess the genetic contribution of CARD15 single nucleotide polymorphisms (SNPs) in the pathogenesis of type I psoriasis. Methods Eight SNPs in CARD15 were genotyped in 148 patients with type I psoriasis and 192 unrelated controls, following a test for population stratification. Genotype and allele frequencies were compared along with estimated SNP haplotype frequencies. Results No differences were observed in genotype allele or haplotype frequencies between the case and control cohorts. Conclusions The most complete assessment of CARD15 SNPs in type I psoriasis to date reveals no evidence of association to type I psoriasis.
Smoking and Incidence of Diabetes Among U.S. Adults
Authors: Capri Gabrielle Foy, Ronny A. Bell, Deborah F. Farmer, David C. Goff, Lynne E. Wagenknecht
Journal: Diabetes Care (2005)

OBJECTIVE—The objective of this study was to determine the association between smoking and incident diabetes among U.S. adults. RESEARCH DESIGN AND METHODS—The Insulin Resistance Atherosclerosis Study (IRAS) was a prospective study of the associations of insulin sensitivity and cardiovascular risk factors. We examined the relationship between smoking status categories (never, former, and current) and incident 5-year type 2 diabetes among 906 participants free of diabetes at baseline. We also considered the effect of pack-year categories (never, former &amp;lt;20 pack-years, former ≥20 pack-years, current &amp;lt;20 pack-years, and current ≥20 pack-years) upon diabetes incidence. RESULTS—Of current smokers, 96 (25%) developed diabetes at 5 years, compared with 60 (14%) never smokers. After multivariable adjustment, current smokers exhibited increased incidence of diabetes compared with never smokers (odds ratio [OR] 2.66, P = 0.001). Similar results were found among current smokers with ≥20 pack-years with normal glucose tolerance (5.66, P = 0.001). CONCLUSIONS—Smoking shares a robust association with incident diabetes, supporting the current Surgeon General’s warnings against cigarette smoking.
Combination of everolimus with trastuzumab plus paclitaxel as first-line treatment for patients with HER2-positive advanced breast cancer (BOLERO-1): a phase 3, randomised, double-blind, multicentre trial
Authors: Sara A Hurvitz, Fabrice Andre, Zefei Jiang, Zhimin Shao, Max S Mano, Silvia P Neciosup, Ling-Min Tseng, Qingyuan Zhang, Kunwei Shen, Donggeng Liu, Lydia M Dreosti, Howard A Burris, Masakazu Toi, Marc E Buyse, David Cabaribere, Mary-Ann Lindsay, Shantha Rao, Lida Bubuteishvili Pacaud, Tetiana Taran, Dennis Slamon
Journal: The Lancet Oncology (2015)
An independent validation of the mortality score for the short-term prognostic prediction in patients with chronic HCV infection and advanced liver disease
Authors: Edoardo G Giannini, Vincenzo Savarino
Journal: Gut (2015)

<b>Aim:</b> To assess whether intraocular pressure (IOP) is associated with refractive error or axial length in children. <b>Methods:</b> Of subjects from the Singapore Cohort Study of the Risk Factors for Myopia (SCORM), 636 Chinese children aged 9–11 years from two elementary schools underwent non-contact tonometry, cycloplegic autorefraction, and A-scan biometry during 2001. For analyses, refractive error was categorised into four groups; hypermetropia (spherical equivalent refraction (SE) ⩾+1.0D), emmetropia (−0.5D&lt;SE&lt;+1.0D), low myopia (−3.0D&lt;SE⩽−0.5D) and high myopia (SE⩽−3.0D). <b>Results:</b> Of the 636 children examined, 50.6% were male. The mean IOP was 16.6 (SD 2.7) mm Hg. There were no significant IOP differences between low (mean IOP = 16.4 (2.8) mm Hg) or high myopes (16.7 (2.5) mm Hg) and emmetropes (16.7 (2.9) mm Hg), p = 0.57. IOP was not correlated with spherical equivalent refraction (Spearman correlation, <i>r</i> = 0.009) or axial length (<i>r</i> = 0.030). In regression analyses adjusting for diastolic blood pressure, neither spherical equivalent (regression coefficient = 0.014) nor axial length (regression coefficient = 0.027) were significantly associated with IOP. <b>Conclusion:</b> These findings do not support an association between IOP and refractive error or axial length in children. This questions postulated roles of IOP in the pathogenesis of myopia.
Cystic pneumatosis in coeliac disease.
Authors: J M Sackier, E J Smith, C B Wood
Journal: Gut (1988)

This report presents a patient with proximal small bowel cystic pneumatosis associated with poorly controlled coeliac disease and pseudo-obstruction. Cystic pneumatosis is rare in the proximal small bowel and we can find no report of its occurrence in association with coeliac disease.
Demonstration of supernumerary tracheal bronchus by computed tomographic scanning and magnetic resonance imaging.
Authors: S J Freeman, J E Harvey, P R Goddard
Journal: Thorax (1995)

A bronchus arising directly from the trachea is an infrequent congenital anomaly which usually represents the displaced origin of a normal bronchus. Rarely, a true supernumerary tracheal bronchus occurs supplying an associated tracheal lobe. The case is described of a patient in whom a supernumerary tracheal bronchus and tracheal lobe was demonstrated by computed tomographic scanning and magnetic resonance imaging.
N<scp>UTRITION IN THE</scp> P<scp>ERIOPERATIVE</scp> P<scp>ATIENT</scp>
Authors: Lyn Howard, Christopher Ashley
Journal: Annual Review of Nutrition (2003)

The association of malnutrition with surgical morbidity and mortality is well recognized. The question of whether this relationship is causal or simply an association in sick patients has been hotly debated. The field of nutrition support has grown out of the belief that correcting malnutrition will modify associated risks for poor outcome. It has been easier to substantiate this belief in some clinical situations than in others. The evidence for nutrition support during the perioperative period is reviewed and recommendations are made about where nutrition support is most useful and where it may be counterproductive. Some of the important unanswered questions about perioperative nutrition support are raised.
Remodeling of ventricular conduction pathways in healed canine infarct border zones.
Authors: R A Luke, J E Saffitz
Journal: Journal of Clinical Investigation (1991)

Remodeling of myocyte interconnections may be an important determinant of ventricular tachycardia in regions bordering healed infarcts. We used quantitative electron microscopy to characterize the distribution of gap junctions in 10 canine left ventricles 3-10 wk after coronary occlusion. In three normal canine left ventricles analyzed ultrastructurally, myocardial gap junctions were distributed anisotropically; gap junction profile length was significantly greater in the transverse than in longitudinal planes of section. In infarct border zone tissues, the normal anisotropic distribution was completely abolished and fewer gap junctions per unit intercalated disk length were observed. Analysis of individual gap junction profile length distributions revealed selective disruption of the largest gap junctions that collectively comprised only 9.6% of total junction profiles, but encompassed nearly 40% of aggregate gap junction length in the transverse plane of section. Three-dimensional reconstructions of myocyte interconnections by high resolution quantitative light microscopy of serial sections demonstrated a reduction in the number of cells connected by intercalated disks to a single myocyte from 11.2 +/- 1.0 in normal myocardium to 6.5 +/- 1.3 in border zone tissues (P less than 0.001). Connections of cells in primarily side-to-side apposition were reduced by 75%, whereas primarily end-to-end connections were reduced by only 22% (P less than 0.05). These alterations would disproportionately enhance axial resistivity in the transverse direction, potentially contributing to development of reentrant arrhythmias.
Prevalence and Characteristics of Painful Diabetic Neuropathy in a Large Community-Based Diabetic Population in the U.K.
Authors: Caroline A. Abbott, Rayaz A. Malik, Ernest R.E. van Ross, Jai Kulkarni, Andrew J.M. Boulton
Journal: Diabetes Care (2011)

OBJECTIVE To assess, in the general diabetic population, 1) the prevalence of painful neuropathic symptoms; 2) the relationship between symptoms and clinical severity of neuropathy; and 3) the role of diabetes type, sex, and ethnicity in painful neuropathy. RESEARCH DESIGN AND METHODS Observational study of a large cohort of diabetic patients receiving community-based health care in northwest England (n = 15,692). Painful diabetic neuropathy (PDN) was assessed using neuropathy symptom score (NSS) and neuropathy disability score (NDS). RESULTS Prevalence of painful symptoms (NSS ≥5) and PDN (NSS ≥5 and NDS ≥3) was 34 and 21%, respectively. Painful symptoms occurred in 26% of patients without neuropathy (NDS ≤2) and 60% of patients with severe neuropathy (NDS &amp;gt;8). Adjusted risk of painful neuropathic symptoms in type 2 diabetes was double that of type 1 diabetes (odds ratio [OR] = 2.1 [95% CI 1.7–2.4], P &amp;lt; 0.001) and not affected by severity of neuropathy, insulin use, foot deformities, smoking, or alcohol. Women had 50% increased adjusted risk of painful symptoms compared with men (OR = 1.5 [1.4–1.6], P &amp;lt; 0.0001). Despite less neuropathy in South Asians (14%) than Europeans (22%) and African Caribbeans (21%) (P &amp;lt; 0.0001), painful symptoms were greater in South Asians (38 vs. 34 vs. 32%, P &amp;lt; 0.0001). South Asians without neuropathy maintained a 50% increased risk of painful neuropathy symptoms compared with other ethnic groups (P &amp;lt; 0.0001). CONCLUSIONS One-third of all community-based diabetic patients have painful neuropathy symptoms, regardless of their neuropathic deficit. PDN was more prevalent in patients with type 2 diabetes, women, and people of South Asian origin. This highlights a significant morbidity due to painful neuropathy and identifies key groups who warrant screening for PDN.
Reduced pH in the airways alters bacterial killing in CFTR−/− porcine lungs
Authors: Elspeth Potton
Journal: Thorax (2012)

Reduced pH in the airways alters bacterial killing in CFTR-/-porcine lungsMolecular defects in the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene are well understood.Despite this, how defects in the CFTR lead to CF is not clear.This paper addresses the mechanism of impaired bacterial killing in a CF model of disease developed in pigs (CFTR-/-), which mirrors human disease.Viability of bacteria within the airways of newborn pigs was assessed using bacteria bound to gold grids.In 6-hour-old pigs, there was a significant reduction in killing of bacteria when grids were applied to the tracheal surface of CFTR-/-pigs compared with wild-type pigs.This finding was reproduced in cultured epithelial cells suggesting that the defect was not due to dysfunctional innate immune cells.Airway Surface Liquid (ASL) was harvested from the CFTR-/-and wildtype pigs and the ability of ASL to modulate bacterial killing in epithelial cultures was assessed.There was no difference in the ability of ASL to kill bacteria and no difference in levels of known antimicrobials within ASL.However, a reduction of pH levels to that seen within CFTR-/-ASL in vivo decreased bacterial killing.Moreover, correcting the ASL pH to normal levels corrected this deficit.This paper demonstrates that an early reduction of pH of ASL in CFTR-/-pigs may alter early bacterial killing within the airways.It is unclear whether treating this would have an effect on lung inflammation.Modulation of abnormal ASL pH improves killing and therefore this finding may have wider implications for treating respiratory diseases where ASL pH is altered.
Analysis of Fcγ Receptor IIIa and IIa Polymorphisms: Lack of Correlation with Outcome in Trastuzumab-Treated Breast Cancer Patients
Authors: Sara A. Hurvitz, David J. Betting, Howard M. Stern, Emmanuel Quinaux, Jeremy Stinson, Somasekar Seshagiri, Ying Zhao, Marc Buyse, John Mackey, Adrian Driga, Sambasivarao Damaraju, Mark X. Sliwkowski, Nicholas J. Robert, Vicente Valero, John Crown, Carla Falkson, Adam Brufsky, Tadeusz Pienkowski, Wolfgang Eiermann, Miguel Martin, Valerie Bee, Omkar Marathe, Dennis J. Slamon, John M. Timmerman
Journal: Clinical Cancer Research (2012)

Abstract Purpose: The mechanisms by which trastuzumab imparts clinical benefit remain incompletely understood. Antibody-dependent cellular cytotoxicity via interactions with Fcγ receptors (FcγR) on leukocytes may contribute to its antitumor effects. Single-nucleotide polymorphisms (SNP) in FCGR3A and FCGR2A genes lead to amino acid substitutions at positions 158 and 131, respectively, and affect binding of antibodies to FcγR such that 158V/V and 131H/H bind with highest affinity. This study aimed to determine whether high-affinity SNPs are associated with disease-free survival (DFS) among patients with HER2-positive nonmetastatic breast cancer. Experimental Design: Genomic DNA was isolated from 1,286 patients enrolled in a trial of adjuvant trastuzumab-based chemotherapy. Genotyping was conducted using Sanger sequencing and Sequenom mass spectrometry. Results: Patient samples (N = 1,189) were successfully genotyped for FCGR3A and 1,218 for FCGR2A. Compared with the overall results of the BCIRG006 study, in the subset of patients genotyped in this analysis, a less robust improvement in DFS was observed for the trastuzumab arms than control arm (HR, 0.842; P = 0.1925). When stratified for prognostic features, the HR in favor of trastuzumab was consistent with that of the overall study (HR, 0.74; P = 0.036). No correlation between DFS and FCGR3A/2A genotypes was seen for trastuzumab-treated patients (158V/V vs. V/F vs. F/F, P = 0.98; 131H/H vs. H/R vs. R/R, P = 0.76; 158V/V and/or 131H/H vs. others, P = 0.67). Conclusion: This analysis evaluating the association between FCGR3A/2A genotypes and trastuzumab efficacy in HER2-positive breast cancer did not show a correlation between FCGR3A-V/F and FCGR2A-H/R SNPs and DFS in patients treated with trastuzumab. Clin Cancer Res; 18(12); 3478–86. ©2012 AACR.