tbuckley/cabot-search huggingface dataset:
Activation of KIF4A as a Prognostic Biomarker and Therapeutic Target for Lung Cancer
Authors: Masaya Taniwaki, Atsushi Takano, Nobuhisa Ishikawa, Wataru Yasui, Kouki Inai, Hitoshi Nishimura, Eiju Tsuchiya, Nobuoki Kohno, Yusuke Nakamura, Yataro Daigo
Journal: Clinical Cancer Research (2007)

Abstract Purpose and Experimental Design: To identify molecules that might be useful as diagnostic/prognostic biomarkers and as targets for the development of new molecular therapies, we screened genes that were highly transactivated in a large proportion of 101 lung cancers by means of a cDNA microarray representing 27,648 genes. We found a gene encoding KIF4A, a kinesin family member 4A, as one of such candidates. Tumor tissue microarray was applied to examine the expression of KIF4A protein and its clinicopathologic significance in archival non–small cell lung cancer (NSCLC) samples from 357 patients. A role of KIF4A in cancer cell growth and/or survival was examined by small interfering RNA experiments. Cellular invasive activity of KIF4A on mammalian cells was examined using Matrigel assays. Results: Immunohistochemical staining detected positive KIF4A staining in 127 (36%) of 357 NSCLCs and 19 (66%) of 29 small-cell lung cancers examined. Positive immunostaining of KIF4A protein was associated with male gender (P = 0.0287), nonadenocarcinoma histology (P = 0.0097), and shorter survival for patients with NSCLC (P = 0.0005), and multivariate analysis confirmed its independent prognostic value (P = 0.0012). Treatment of lung cancer cells with small interfering RNAs for KIF4A suppressed growth of the cancer cells. Furthermore, we found that induction of exogenous expression of KIF4A conferred cellular invasive activity on mammalian cells. Conclusions: These data strongly implied that targeting the KIF4A molecule might hold a promise for the development of anticancer drugs and cancer vaccines as well as a prognostic biomarker in clinic.
Abstract #LB-157: Exploratory analysis of gender and age aspects in a finished placebo-controlled randomized trial with the cancer vaccine IGN101 in 762 NSCLC patients in the adjuvant setting
Authors: Hans Loibner, Franz Groiss, Erich Stoelben
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

IGN101 is a cancer vaccine acting via the Epithelial Cell Adhesion Molecule (EpCAM) frequently expressed on epithelial cancers. It consists of 0.5 mg alum-adsorbed murine Mab 17-1A that bears EpCAM mimotopes to trigger an anti-EpCAM immune response by repeated s.c. injections (AACR 2007). In a randomized, placebo-controlled double-blind trial 762 NSCLC pts stage Ib, II and IIIa following R0 resection were repeatedly vaccinated with placebo or IGN101, primary endpoint was relapse-free survival (RFS), no other treatment was permitted. The study analysis revealed no difference in RFS between treatment groups. However, as result of a prospectively defined subgroup analysis, patients with neutrophil and lymphocyte counts at baseline below 5x10E9/L and 1,6x10E9/L resp. had significantly improved RFS when treated with IGN101. Vaccinations were very well tolerated, no systemic side effects were observed (ASCO 2008). Here we report recent exploratory analyses of this randomized NSCLC study regarding gender and age. 604 male and 158 female patients were enrolled into this study. For the whole study population (regardless of treatment with IGN101 or placebo), there was no difference in RFS between males and females, however, a significantly improved overall survival of female patients was observed (HR 0,735; p=0,03). When comparing IGN101 and placebo, there was no difference in RFS for male patients, however, interestingly in female patients treated with IGN101 a trend to improved RFS was seen (HR 0,758; p=0,23). For the whole study population, there was no difference in RFS between different age groups (33-56, 57-67, > 67). When comparing IGN101 and placebo, there was no difference in RFS in age groups 33-56 and 57-67. However, patients with an age > 67 (n=169) showed a trend to improved RFS when treated with IGN101 (HR 0,734; p=0,16). In summary, repeated vaccination of adjuvant NSCLC patients with the cancer vaccine IGN101 may have a positive impact on RFS in female patients and in older patients. IGN101 therefore may become a very well tolerated alternative to toxic chemotherapy regimens for patients who do not tolerate such a treatment. Additional properly designed studies to assess age and gender parameters are required to substantiate these results.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-157.
Game theory and the evolution of behaviour
Authors: J. Maynard Smith
Journal: Behavioral and Brain Sciences (1984)

Abstract Evolutionary game theory is a method of analysing the evolution of phenotypes (including types of behaviour) when the fitness of a particular phenotype depends onits frequency in the population. It was first applied to pairwise contests between animals. Such contests usually have some associated asymmetry, in size, prior residence, or age or sex status; the theory predicts that the asymmetry will be used as a cue to settlethe contest, and this is found to be the case. The theory can also be applied when individuals are competing against the population as a whole, or some part of it. In such cases, the evolution of variable behaviour - so-called mixed strategies - is predicted; actual examples of this are given. Game theory can be applied to the evolution of cooperative as well as of antagonistic behaviour. An analysis of the evolution of learning leads to testable predictions about learning behaviour.
Unusual Problems in Breast Cancer and a Rare Lung Cancer Case
Authors: Giuseppe Tonini, Bruno Vincenzi, Daniele Santini, Giuseppe Avvisati, Annalisa La Cesa, Alfonso Baldi
Journal: Journal of Clinical Oncology (2003)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2003.04.195 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12775749 Unusual Problems in Breast Cancer and a Rare Lung Cancer Case Case 1. Clinical Complete Response of Breast Cancer Metastases After Trastuzumab-Based Immunotherapy Giuseppe ToninixGiuseppe ToniniSearch for articles by this author , Bruno VincenzixBruno VincenziSearch for articles by this author , Daniele SantinixDaniele SantiniSearch for articles by this author , Giuseppe AvvisatixGiuseppe AvvisatiSearch for articles by this author , Annalisa La CesaxAnnalisa La CesaSearch for articles by this author , Alfonso BaldixAlfonso BaldiSearch for articles by this author Show More Università Campus Bio-Medico, Rome, Italy; and Regina Elena Cancer Institute, Rome, Italy https://doi.org/10.1200/JCO.2003.04.195 First Page Full Text PDF Figures and Tables © 2003 by American Society of Clinical Oncology
Implications of the Changing Use of Hospitalization to Treat Anorexia Nervosa
Authors: Molly G. Willer, Paul Thuras, Scott J. Crow
Journal: American Journal of Psychiatry (2005)

This study sought to compare inpatient hospitalization practices for treating anorexia nervosa at two time periods and to assess whether differences in practices affected treatment outcome.Hospital charts were examined for all patients with a diagnosis of anorexia nervosa and a body mass index < or = 17.5 kg/m2 at admission who were admitted to a university hospital during 1975-1980 (early) or 1990-1995 (later).The "later cohort" had significantly higher admission and discharge body mass indexes, shorter lengths of stay, higher rates of weight gain, and more readmissions. Predictors of rehospitalization for the later cohort were increased length of stay, prior hospitalizations, and more rapid weight gain.This study suggests that the use of hospitalization to treat anorexia nervosa has changed over time and is associated with increased rates of readmission.
Development of disability in chronic obstructive pulmonary disease: beyond lung function
Authors: M. D. Eisner, C. Iribarren, P. D. Blanc, E. H. Yelin, L. Ackerson, N. Byl, T. A. Omachi, S. Sidney, P. P. Katz
Journal: Thorax (2010)

<h3>Background</h3> COPD is a major cause of disability, but little is known about how disability develops in this condition. <h3>Methods</h3> The authors analysed data from the Function, Living, Outcomes and Work (FLOW) Study which enrolled 1202 Kaiser Permanente Northern California members with COPD at baseline and re-evaluated 1051 subjects at 2-year follow-up. The authors tested the specific hypothesis that the development of specific non-respiratory impairments (abnormal body composition and muscle strength) and functional limitations (decreased lower extremity function, poor balance, mobility-related dyspnoea, reduced exercise performance and decreased cognitive function) will determine the risk of disability in COPD, after controlling for respiratory impairment (FEV<sub>1</sub> and oxygen saturation). The Valued Life Activities Scale was used to assess disability in terms of a broad range of daily activities. The primary disability outcome measure was defined as an increase in the proportion of activities that cannot be performed of 3.3% or greater from baseline to 2-year follow-up (the estimated minimal important difference). Multivariable logistic regression was used for analysis. <h3>Results</h3> Respiratory impairment measures were related to an increased prospective risk of disability (multivariate OR 1.75; 95% CI 1.26 to 2.44 for 1 litre decrement of FEV<sub>1</sub> and OR 1.57 per 5% decrement in oxygen saturation; 95% CI 1.13 to 2.18). Non-respiratory impairment (body composition and lower extremity muscle strength) and functional limitations (lower extremity function, exercise performance, and mobility-related dyspnoea) were all associated with an increased longitudinal risk of disability after controlling for respiratory impairment (p&lt;0.05 in all cases). Non-respiratory impairment and functional limitations were predictive of prospective disability, above-and-beyond sociodemographic characteristics, smoking status and respiratory impairment (area under the receiver operating characteristic curve increased from 0.65 to 0.75; p&lt;0.001). <h3>Conclusions</h3> Development of non-respiratory impairment and functional limitations, which reflect the systemic nature of COPD, appear to be critical determinants of disablement. Prevention and treatment of disability require a comprehensive approach to the COPD patient.
<scp>d</scp>-Cycloserine as an Augmentation Strategy With Cognitive-Behavioral Therapy for Social Anxiety Disorder
Authors: Stefan G. Hofmann, Jasper A.J. Smits, David Rosenfield, Naomi Simon, Michael W. Otto, Alicia E. Meuret, Luana Marques, Angela Fang, Candyce Tart, Mark H. Pollack
Journal: American Journal of Psychiatry (2013)

d-Cycloserine does not enhance the effectiveness of CBT for social anxiety disorder but could temporarily accelerate the speed of treatment response, reducing patient distress and limiting the avoidance tendencies of patients with anxiety disorders during exposure treatments.
Oxidation of a specific methionine in thrombomodulin by activated neutrophil products blocks cofactor activity. A potential rapid mechanism for modulation of coagulation.
Authors: C B Glaser, J Morser, J H Clarke, E Blasko, K McLean, I Kuhn, R J Chang, J H Lin, L Vilander, W H Andrews
Journal: Journal of Clinical Investigation (1992)

Endothelial thrombomodulin (TM) plays a critical role in hemostasis as a cofactor for thrombin-dependent formation of activated protein C, a potent anticoagulant. Chloramine T, H2O2, or hypochlorous acid generated from H2O2 by myeloperoxidase rapidly destroy 75-90% of TM cofactor activity. Activated PMN, the primary in vivo source of biological oxidants, also rapidly inactivate TM. Oxidation of TM by PMN is inhibited by diphenylene iodonium, an inhibitor of NADPH oxidase. Both Met291 and Met388 in the six epidermal growth factor-like repeat domain are oxidized; however, only substitutions of Met388 lead to TM analogues that resist oxidative inactivation. We suggest that in inflamed tissues activated PMN may inactivate TM and demonstrate further evidence of the interaction between the inflammatory process and induction of thrombotic potential.
The Yorkton Psychiatric Centre: A Five-Year Review
Authors: COLIN F. LIPSCOMB
Journal: American Journal of Psychiatry (1970)

In recent years doubt has been cast upon the effectiveness of community mental health programs. The author reviews one program, that of the Yorkton Psychiatric Centre in Saskatchewan, that seems to have succeeded. He pays particular attention to problem areas of the service and makes suggestions about what factors might control the success or failure of such programs.
Dose-response study of sodium cromoglycate in exercise-induced asthma.
Authors: K R Patel, K E Berkin, J W Kerr
Journal: Thorax (1982)

Ten patients with exercise-induced asthma participated in a single-blind dose-response study comparing the protective effect of inhaled sodium cromoglycate in increasing concentrations from 2 to 40 mg/ml. Saline was used as a control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after the patients had run on a treadmill for eight minutes. There was slight bronchodilation evident from the increase in baseline FEV1 after inhalation of sodium cromoglycate, the difference reaching statistical significance with the highest concentration (5.7%, p less than 0.05). After exercise the maximal percentage falls in FEV1 (means and SEM) after saline and after sodium cromoglycate at 2, 10, 20, and 40 mg/ml were 37.3 +/- 4.7, 17.3 +/- 4.1, 10 +/- 3.3, 7.6 +/- 2.4, and 12 +/- 2.9. Sodium cromoglycate inhibited the exercise-induced fall in FEV1 at all the concentrations used in the study (p less than 0.001) and its inhibitory effect increased from 2 to 20 mg/ml. The mean FEV1 returned to baseline values within 15 minutes at higher concentrations of sodium cromoglycate (20 and 40 mg/ml) and a small bronchodilator effect was noted at 30 minutes. The findings suggest that the protective effect of sodium cromoglycate in exercise asthma is dose related. At higher concentration the drug suppresses chemical mediator release from the lung mast cells and may also modify the bronchial reactivity to release mediators.
Echocardiographic Features of Congestive Cardiomyopathy Compared with Normal Subjects and Patients with Coronary Artery Disease
Authors: BETTY C. CORYA, HARVEY FEIGENBAUM, SUSAN RASMUSSEN, MARY J. BLACK
Journal: Circulation (1974)

Echocardiograms of ten patients with congestive cardiomyopathy were compared to those of three groups of patients: (1) 17 with no catheterization or angiographic evidence of cardiac disease; (2) 19 with 75% or greater obstruction of one or more coronary arteries (CAD); and (3) 8 with previous myocardial infarction and congestive heart failure (CAD-CHF). Echocardiographic values of interest included the left ventricular internal dimension at end-diastole/body surface area (LVIDd index), the amplitudes of the left septal echo (LSa) and posterior endocardial echo (ENa), LSa + ENa, and the maximum rate of rise of the posterior endocardial echo ([See Equation in PDF File]). Septal and posterior wall thicknesses were measured and the presence or absence of pericardial effusion and abnormal mitral valve closure were observed. All of the left ventricular measurements were significantly different when comparing the cardiomyopathy group with the normal and CAD groups. Differentiating cardiomyopathy from the CAD-CHF group was far more difficult with the only highly significant difference being the LSa + ENa ( P &lt; 0.001). Only one cardiomyopathy patient and one CAD-CHF patient had a sum of LSa + ENa overlapping the other group. These results are consistent with the diffuse disease usually seen in congestive cardiomyopathy and the segmental nature of coronary artery disease in which some area of the left ventricle moves well even in the presence of congestive heart failure.
Trefoil factor 2 rapidly induces interleukin 33 to promote type 2 immunity during allergic asthma and hookworm infection
Authors: Marsha Wills-Karp, Reena Rani, Krista Dienger, Ian Lewkowich, James G. Fox, Charles Perkins, Lauren Lewis, Fred D. Finkelman, Dirk E. Smith, Paul J. Bryce, Evelyn A. Kurt-Jones, Timothy C. Wang, Umasundari Sivaprasad, Gurjit K. Hershey, De’Broski R. Herbert
Journal: The Journal of Experimental Medicine (2012)

The molecular mechanisms that drive mucosal T helper type 2 (T(H)2) responses against parasitic helminths and allergens remain unclear. In this study, we demonstrate in mice that TFF2 (trefoil factor 2), an epithelial cell-derived repair molecule, is needed for the control of lung injury caused by the hookworm parasite Nippostrongylus brasiliensis and for type 2 immunity after infection. TFF2 is also necessary for the rapid production of IL-33, a T(H)2-promoting cytokine, by lung epithelia, alveolar macrophages, and inflammatory dendritic cells in infected mice. TFF2 also increases the severity of allergic lung disease caused by house dust mite antigens or IL-13. Moreover, TFF2 messenger RNA expression is significantly increased in nasal mucosal brushings during asthma exacerbations in children. These experiments extend the biological functions of TFF2 from tissue repair to the initiation and maintenance of mucosal T(H)2 responses.
RECQL1 and WRN Proteins Are Potential Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
Authors: Akihito Arai, Tokuhiro Chano, Kazunobu Futami, Yasuhiro Furuichi, Kaichiro Ikebuchi, Takuma Inui, Hitosuke Tameno, Yasuko Ochi, Taketoshi Shimada, Yasuo Hisa, Hidetoshi Okabe
Journal: Cancer Research (2011)

Abstract RECQL1 and WRN proteins are RecQ DNA helicases that participate in suppression of DNA hyper-recombination and repair. In this study, we report evidence supporting their candidacy as cancer therapeutic targets. In hypopharyngeal carcinomas, which have the worst prognosis among head and neck squamous cell carcinomas (HNSCC) that are rapidly rising in incidence, we found that RECQL1 and WRN proteins are highly expressed and that siRNA-mediated silencing of either gene suppressed carcinoma cell growth in vitro. Similarly, siRNA administration in a murine xenograft model of hypopharyngeal carcinoma markedly inhibited tumor growth. Moreover, combining either siRNA with cis-platinum (II) diammine dichloride significantly augmented the in vivo anticancer effects of this drug that is used commonly in HNSCC treatment. Notably, we observed no recurrence of some tumors following siRNA treatment in this model. Our findings offer a preclinical proof of concept for RECQL1 and WRN proteins as novel therapeutic targets to treat aggressive HNSCC and perhaps other cancers. Cancer Res; 71(13); 4598–607. ©2011 AACR.
Alpha-adrenoceptor stimulation with exogenous norepinephrine or release of endogenous catecholamines mimics ischemic preconditioning.
Authors: Z Bankwala, S L Hale, R A Kloner
Journal: Circulation (1994)

BACKGROUND Brief episodes of ischemia induced by proximal coronary artery occlusion can precondition the myocardium. Whether other stressful stimuli have the potential to protect the myocardium from subsequent ischemia remains controversial. METHODS AND RESULTS To study the hypothesis that transient alpha-adrenoceptor stimulation mimics preconditioning, for 5 minutes we administered 0.25 micrograms.kg-1.min-1 norepinephrine or saline 10 minutes before a 30-minute coronary occlusion and 4 hours of reperfusion in an in vivo rabbit model. The area of necrosis (AN) and area of risk (AR) were measured. We found that norepinephrine pretreatment caused a reduction in infarct size when compared with controls (AN/AR, 0.17 +/- 0.04 versus 0.31 +/- 0.04; P &lt; .02). Ischemic preconditioning also reduced infarct size (AN/AR, 0.22 +/- 0.03). The protection observed with norepinephrine treatment was entirely eliminated by pretreatment with alpha-adrenergic blockade using prazosin (AN/AR, 0.42 +/- 0.06). Tyramine, an agent that causes release of endogenous catecholamines, was administered (1.5 mg/kg i.v.) 10 minutes before coronary occlusion in another group of rabbits. Tyramine pretreatment resulted in a smaller infarct size than in untreated controls (AN/AR, 0.16 +/- 0.04 versus 0.41 +/- 0.07; P &lt; .01). Both norepinephrine and tyramine caused an increase in systemic arterial pressure during infusion; tyramine also increased heart rate. In rabbits pretreated with prazosin, heart rate and systemic pressure during the norepinephrine infusion were similar to baseline values. During coronary occlusion, the degree of ischemia was similar in all groups. CONCLUSIONS Exposure of the heart to either transient exogenous norepinephrine or endogenous release of norepinephrine and/or other catecholamines by tyramine can mimic the effects of ischemic preconditioning in rabbits.
Evidence for an Endothelium-Derived Hyperpolarizing Factor in the Superior Mesenteric Artery From Rats With Cirrhosis
Authors: Eric Barriere, Khalid A. Tazi, Jean-Pierre Rona, Fabienne Pessione, Jörg Heller, Didier Lebrec, Richard Moreau
Journal: Hepatology (2000)

In cirrhosis, in splanchnic arteries, endothelium–dependent relaxation may persist even if overactive nitric oxide synthase (NOS) and cyclooxygenase (COX) are inhibited. In normal arteries, a significant endothelium–dependent relaxation to acetylcholine persists after NOS/COX inhibition. This relaxation is caused by smooth muscle cell (SMC) membrane hyperpolarization, which is sensitive to a combination of the potassium channel blockers apamin and charybdotoxin, and is mediated by an endothelium–derived hyperpolarizing factor (EDHF). The aim of this study was to detect EDHF and evaluate its pathophysiologic role in isolated superior mesenteric arteries from cirrhotic rats. Arterial rings were obtained and exposed to N w –nitro–L–arginine (L–NNA, a NOS inhibitor) and indomethacin (a COX inhibitor). Acetylcholine–induced membrane potential responses and concentration–response curves to the relaxant of acetylcholine were obtained with and without apamin plus charybdotoxin. Acetylcholine–induced responses were measured in certain rings from endothelium–denuded arteries. Contractions caused by the α 1 –adrenoceptor agonist phenylephrine were obtained in cirrhotic and normal rings with and without apamin and charybdotoxin. Significant acetylcholine–induced, endothelium–dependent, apamin– and charybdotoxin–sensitive, SMC membrane hyperpolarization and relaxation were found. An apamin– and charybdotoxin–sensitive hyporesponsiveness to the contractile action of phenylephrine was found in cirrhotic rings. In conclusion, in cirrhotic rats, in the superior mesenteric artery exposed to NOS/COX–inhibitors, an EDHF exists that may replace NOS/COX products to induce endothelium–dependent arterial relaxation.