tbuckley/cabot-search huggingface dataset:
Abstract PD09-06: Obesity Promotes Breast Cancer Progression and Tamoxifen Resistance Via Cross-Talk between Growth Factor and Estrogen Signaling Pathways
Authors: LW Bowers, DA Cavazos, RE De Angel, RS Price, SD Hursting, AJ Brenner, LA. deGraffenried
Journal: Cancer Research (2010)

Abstract Epidemiological studies indicate that obesity increases the risk of breast cancer by approximately 50% in postmenopausal women. This population most commonly develops estrogen receptor (ER) alpha positive breast cancer, suggesting that elevated estrogen synthesis by the adipose tissue and local mammary epithelia is the primary mediator of breast tumorigenesis in obese postmenopausal women. However, the specific mechanisms by which obesity promotes the development of postmenopausal breast cancer remain unclear. In vitro and animal studies have indicated that obesity-associated growth factor and cytokine signaling also play a role in breast tumorigenesis. Specifically, obesity is accompanied by elevated levels of insulin, insulin-like growth factor 1 (IGF-1), and leptin, and these all have significant tumorigenic effects in the breast. In the current study, we utilize an in vitro model of obesity to examine the effects of elevated circulating hormones and growth factors on breast cancer cells. C57BL/6 mice were randomized at six weeks of age to either a 60% fat diet to induce obesity or a 10% fat diet to produce a lean comparison and maintained on these diets for 12 weeks prior to sacrifice. Sera was obtained from the mice at the time of euthanasia and used to treat ER alpha positive MCF-7 breast cancer cells at a concentration of 2% in serum-free media. Preliminary data indicates that sera from the obese mice induces 31% greater proliferation of MCF-7 cells in comparison to sera from lean animals (p=0.0025). This proliferation is mediated primarily via a phosphoinositide 3-kinase (PI3K) pathway, as evidenced by the ability of LY294002, a PI3K inhibitor, to neutralize the proliferative effect of the obese sera. The addition of LY294002 to MCF-7 cells treated with 2% obese sera decreased proliferation by 43% (p=0.0083). Intriguingly, tamoxifen did not significantly affect proliferation in the cells treated with obese sera (p=0.2425), suggesting that obesity may induce tamoxifen resistance. Consequently, we hypothesize that obesity promotes breast cancer progression and tamoxifen resistance via cross-talk between growth factor and ER alpha signaling pathways. Further studies will be conducted to examine the pathways through which circulating factors mediate obesity-induced breast cancer progression. These will include measurement of the expression and activation of ER alpha, Akt, Erk1/2, IGF-1 receptor, and other proteins in MCF-7 cells in response to treatment with sera from obese and lean mice. By improving our understanding of the mechanisms linking obesity and post-menopausal breast cancer risk, we ultimately hope to develop a rational and effective chemopreventive regimen for this population. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr PD09-06.
AB1111 Selection of Patients for Cardiovascular Risk Assessment in Rheumatological Care
Authors: T. Eidner, G. Wolf, P. Oelzner
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In patients with rheumatoid arthritis (RA) or spondyloarthritis (SpA), but without manifest cardiovascular disease (CVD) or diabetes mellitus (DM), individual cardiovascular risk (CVR) should be estimated according to the SCORE-algorithm [1,2] and the EULAR recommendations for CVR-management [3]. A 10-year risk of fatal cardiovascular disease of &gt;10% (“high 10yCVR”) is often used as threshold for special therapeutic interventions such as statin therapy. <h3>Objectives</h3> To evaluate CVR in patients with RA or SpA in a rheumatological outpatient department, and to define groups of patients with high probability for a high 10yCVR, on which CVR-assessment can be focused in routine rheumatological care. <h3>Methods</h3> In 352 consecutive patients &gt;40 years of age with RA (274) or SpA (78), but without manifest CVD or DM, CVR was estimated according to the SCORE-algorithm based on age, gender, smoking status, lipid status, blood pressure, duration of disease and RF/CCP-antibody-status. On the basis of the distribution of these probabilities in domains characterized by gender, age and smoking status, subgroups of patients with preferably high sensitivity to cover the patients with high 10yCVR were defined. <h3>Results</h3> From 99 patients in the age between 40 and 55 years nobody had a 10yCVR&gt;10%. The prevalence of a high 10yCVR in patients older than 55 y. was 18,6% (47/253). Most of these high-risk patients were older than 65 years. Limiting CVR-assessment to the age-group older than 65 years showed a sensitivity of 87,2% (41/47) for the identification of patients with high 10yCVR (together with a specificity of 51,0% in the group of patients older than 55 y.). A higher sensitivity could be reached with a more differentiated strategy only using the basic criteria gender, age and smoking status by the restriction of detailed CVR-assessment to women &gt;65 y. and to men &gt;60 y. (male smoker &gt;55 y.). This strategy had a sensitivity of 100% and a specificity of 41,7% for the identification of rheumatic patients with high 10yCVR in the group older than 55 y. <h3>Conclusions</h3> In routine rheumatological care detailed CVR-assessment by SCORE algorithm can be limited to a predefined group of RA and SpA patients. Easy to implement preselection strategies are: A) to assess10yCVR only in patients older than 65 years B) to assess 10yCVR only in women &gt;65 years and men &gt;60 years (male smoker &gt;55 years) In our study group both strategies had a high sensitivity (A 87%, B 100%) for the identification of patients with a 10yCVR of at least 10%. <h3>References</h3> Conroy et al.; Eur Heart J 2003;24:987–1003. Keil et al.; Dt Ärzteblatt 2005; 102: A1808-12. [3] Peters et al.; Ann Rheum Dis 2010 69: 325-331. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4698
Modification of Risk Factors for Coronary Heart Disease
Authors: H J Walter, A Hofman, R D Vaughan, E L Wynder
Journal: New England Journal of Medicine (1988)

We conducted a study of the effectiveness of an educational intervention designed to modify risk factors associated with coronary heart disease among 3388 children in 37 schools in two demographically dissimilar areas (the Bronx and Westchester County) in and around New York City. Schools within each area were randomly assigned to either intervention or nonintervention groups. In schools targeted for intervention, children in the fourth through eighth grades were taught a teacher-delivered curriculum focusing on diet, physical activity, and cigarette smoking. Risk-factor levels were measured in all schools at base line and at four follow-up points. A total of 1769 of the children qualified for analysis of the intervention effect. After five years, the net mean change in plasma levels of total cholesterol was -1.7 mg per deciliter per year (-0.04 mmol per liter) (95 percent confidence interval, -2.7 to -0.7 mg per deciliter [-0.07 to -0.02 mmol per liter]) in the Westchester County schools, or -8.5 mg per deciliter (-0.22 mmol per liter) (5.1 percent) over a period of five years. In the schools in the Bronx, the net mean change was -1.0 mg per deciliter per year (-0.03 mmol per liter) (95 percent confidence interval, -2.3 to +0.3 mg per deciliter [-0.06 to +0.01 mmol per -2.3 to +0.3 mg per deciliter [-0.06 to +0.01 mmol per liter]), or -5.0 mg per deciliter (-0.13 mmol per liter) (2.9 percent) over a period of five years. Favorable trends in dietary intake and health knowledge were also observed, whereas the other targeted risk factors were not significantly altered. If these findings can be replicated, this will suggest that educational programs to modify coronary risk factors are feasible and may have a favorable (albeit small) effect on blood levels of cholesterol in children.
Abstract 1577: Subtype dependent carcinoma initiation by Rb tumor suppressor inactivation in multiple epithelial tissues.
Authors: Yurong Song, Chunyu Yang, Wenqi Pan, Alisan Fathalizadeh, Lucy Lu, Debra Gilbert, T. Norene O'Sullivan, Diana C. Haines, Philip L. Martin, Terry Van Dyke
Journal: Cancer Research (2013)

Abstract Carcinomas arise in a complex microenvironment consisting of multiple distinct epithelial lineages surrounded by mesenchymal cells. Of major importance is to understand the relationship among cell types, initiation event, and ultimate cancer outcome. Mouse models facilitate the prospective examination of early oncogenic events, which is not feasible in humans, permitting an analysis of epithelial subtype susceptibility. Since most solid tumors harbor aberrations in the pRb network, we assessed the susceptibility of epithelial subtypes expressing cytokeratin (K) 18 or K19 to the disruption of Rb tumor suppression (Rb-TS) in vivo. Tumorigenesis could be initiated in either K18- or K19-expressing cells. However, the susceptibility of epithelial tissues was subtype-dependent. K19 cells were more prone to hyperplasia and neoplasia than K18 targeted cells. Given that a single genetic event was engineered, a small percentage of animals developed carcinoma/adenocarcinoma, providing the opportunity to define progression events via engineering or spontaneous evolution. To extend our analysis to a specific tissue, we employed a prostate-specific Cre line to target either K18- or K19-expressing prostate epithelial cells. Differential responses observed in the frequency and extent of premalignant hyperplastic lesions strongly supported the notion of cell type-dependent susceptibility to Rb-TS inactivation. Our data suggest that the tumorigenic consequences of a single initiation event are dictated by cellular subtype distinctiveness, underscoring the importance of the tumor cell of origin. Citation Format: Yurong Song, Chunyu Yang, Wenqi Pan, Alisan Fathalizadeh, Lucy Lu, Debra Gilbert, T. Norene O'Sullivan, Diana C. Haines, Philip L. Martin, Terry Van Dyke. Subtype dependent carcinoma initiation by Rb tumor suppressor inactivation in multiple epithelial tissues. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1577. doi:10.1158/1538-7445.AM2013-1577
Weighing the Benefits and Costs of HPV Vaccination of Young Men
Authors: Jane J. Kim
Journal: New England Journal of Medicine (2011)

New data suggest that a human papillomavirus (HPV) vaccine prevents anal intraepithelial neoplasia in men, particularly in men who have sex with men. As the FDA reviews this new evidence, the debate over routine HPV vaccination of boys and men is likely to be reignited.
Scintigraphic Evolution of a Breast Cancer with Tc-99m MIBI Scintimammography
Authors: J J Mateos, S Vidal, M Muñoz, D Fuster, F Martin, M Ortega, F Pons
Journal: Clinical Nuclear Medicine (2000)

Early detection and prompt treatment of breast cancer are the main tools to decrease mortality rates. Several diagnostic techniques such as mammography, magnetic resonance imaging, and ultrasound are used, but none of these are conclusive. The authors describe a 56-year-old woman who was suspected of having breast cancer on mammography. Tc-99m MIBI scintimammography showed a small mass with elevated radiotracer uptake located near the pectoral muscle of the patient's left breast. The possible tumor was confirmed with fine-needle aspiration biopsy. After the diagnosis was established, the patient did not allow any treatment. Eighteen months later, a second scintimammography was performed, showing a large mammary tumor with a high radiotracer uptake, a new small lesion located in the left upper quadrant, and axillary lymph node involvement. Chemotherapy treatment was instituted and after treatment, Tc-99m MIBI scintimammography was normal. This case report provides further evidence for Tc-99m MIBI scintimammography for the detection of breast cancer as well as to evaluate the response to chemotherapy.
Abstract 3009: Evaluating the role of cell cycle inhibition in celecoxib toxicity through microRNA analysis
Authors: Andrew C. Heaford, Christy B. Erbe, Jonathan M. Bock
Journal: Cancer Research (2010)

Abstract Squamous cell carcinoma of the head and neck (SCCHN) is a major health problem worldwide, with over 45,000 new cases predicted to occur in the United States in 2009. Adjuvant therapies that can augment established treatments for SCCHN without causing significant additional morbidity are needed for this disease. Cyclooxygenase-2 (COX-2) inhibition has emerged as a potential adjuvant to established treatment regimens for SCCHN with this concept in mind, as COX-2 is known to be overexpressed in SCCHN. Celecoxib is a COX-2 specific NSAID with known antineoplastic activity against many human tumors, and is currently being used in clinical trials as a chemopreventive agent and adjuvant to established chemotherapy and radiation therapy protocols. The underlying mechanism of celecoxib toxicity remains poorly understood. Previous work from our laboratory has demonstrated marked inhibition of cell cycle progression through the G1 phase and induction of apoptosis following treatment with celecoxib in SCCHN, leading to cell cycle phase-specific toxicity to S and G2 phase cells and induction of p21waf1/cip1 with downstream inhibition of nuclear E2F activity. We therefore hypothesize that decreasing the observed cell cycle inhibition induced by celecoxib treatment may augment celecoxib toxicity by inducing cells to progress through more highly toxic cell cycle phases during celecoxib exposure. Further understanding of the mechanism of G1 arrest following celecoxib administration is therefore needed to effectively exploit this potential toxicity. MicroRNAs have been implicated in the control of cell cycle transition in several recent publications in stem cells and human cancers, and we believe that they may be involved in the cell cycle arrest seen after celecoxib treatment in SCCHN. To evaluate this hypothesis, SCCHN cells were exposed to celecoxib for 24 hours and G1 arrest was confirmed via flow cytometry. RNA and protein were extracted from celecoxib-treated and control cells and microRNA expression profiles were established by quantitative real-time PCR microarray analysis. Alterations in cell cycle gene expression across the cell cycle were assessed by similar microarray, and targets were confirmed by further western blotting and PCR analysis. Correlations between microRNA alterations in celecoxib-treated cells and cell cycle control genes were observed and extrapolated. These data provide a microRNA and cell cycle gene expression signature for celecoxib treatment in SCCHN, and further illustrate the potential role that microRNA expression plays in control of G1 cell cycle checkpoint kinetics and subsequent celecoxib toxicity. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3009.
Impact of treatment on the outcome of acute myeloid leukemia with inversion 16: a single institution's experience
Authors: BI Razzouk, SC Raimondi, DK Srivastava, M Pritchard, FG Behm, X Tong, JT Sandlund, JE Rubnitz, C-H Pui, RC Ribeiro
Journal: Leukemia (2001)
Right-to-Left Shunt on a Lung Scan
Authors: C A Moses, F S Mishkin
Journal: New England Journal of Medicine (1999)

Figure 1. A 45-year-old woman with pulmonary hypertension and polycythemia presented with increasing cyanosis, edema of the legs, and dyspnea on exertion. She had a partial pressure of arterial oxygen of 35 mm Hg (pH, 7.35). The chest radiograph (lower left panel) showed an enlarged pulmonary artery, small peripheral vessels, and global cardiomegaly. Right posterior oblique (RPO) and left posterior oblique (LPO) perfusion scans showed medium-sized segmental defects in the posterior segment of the right upper lobe and the superior segments of both the right and left lower lobes (arrows in upper left and middle panels). These defects were normally . . .
EXPERIENCE WITH A NOVEL IRRIGATED MULTIPOLAR IRRIGATED ABLATION CATHETER (NMARQ) FOR ATRIAL FIBRILLATION ABLATION: ACUTE SAFETY, EFFICACY AND FOLLOW-UP DATA
Authors: Thomas Deneke, Patrick Müller, Anja Schade, Joachim Krug, Rainer Schmitt, Markus Roos, Atilla Szöllözi, Karin Nentwich
Journal: Journal of the American College of Cardiology (2015)
P104 Nebulised hypertonic saline improves quality of life in adult patients with non-cystic fibrosis bronchiectasis: Abstract P104 Table 1.
Authors: K Bentley, ZL Borrill
Journal: Thorax (2013)

<h3>Background</h3> Nebulised hypertonic saline (HTS) improved lung function, quality of life and exacerbation frequency in a study of patients with non-cystic fibrosis (CF) bronchiectasis<sup>1</sup>. It may improve chest clearance by increasing water content of airway surface liquid, enhancing mucociliary clearance. A protocol was developed for the use of HTS in a district hospital setting. Safety, tolerability, lung function and quality of life data are presented. <h3>Methods</h3> Patients with non-CF bronchiectasis were assessed on a locally developed chest clearance pathway consisting of active cycle breathing technique, postural drainage, flutter device and mucolytic. Patients with ongoing symptoms were given a trial dose of 4 mls HTS 7% with spirometry measured pre and post. Patients continued on 4 mls HTS od/bd for 12 months if tolerated. Adverse effects, quality of life and spirometry was collected at 4 weeks and 6 months. Data were compared using paired t tests. <h3>Results</h3> 34 patients (mean age 62, 25 female, mean FEV<sub>1</sub> 66% predicted) were assessed. 2 (6%) patients did not proceed with treatment due to (a. FEV<sub>1</sub> decline &gt;15% and b. severe nausea). 9 (26%) patients experienced mild side effects. FEV<sub>1</sub> improved significantly at 4 weeks (1.53 vs 1.41 p = 0.01). Leicester Cough Questionnaire improved significantly at 4 weeks (mean total score 13.7 vs 11.8 p = 0.0003) with a mean difference in LCQ of 1.9 (minimum clinically important difference MCID &gt; 1.3<sup>2</sup>). St Georges Respiratory Questionnaire improved significantly at 6 months (mean total score 56.1 vs 67.8 p = 0.01) with a mean difference of 11% (MCID &gt; 4%<sup>3</sup>). <h3>Conclusions</h3> In this uncontrolled study, HTS was well tolerated and resulted in improved lung function and quality of life in patients with non-CF bronchiectasis. <h3>References</h3> Kellett F Niven RM. Nebulised 7% hypertonic saline improves lung function and quality of life in bronchiectasis. <i>Respiratory Medicine</i> 2011; 105: 1831–1835. Raj AA <i>et al</i>. Clinical cough IV: what is the minimally important difference for the Leicester Cough Questionnaire? <i>Handb Exp Pharmacol</i> 2009; 187: 311–320. Jones PW. Interpreting thresholds for a clinically significant change in health status in asthma and COPD. <i>Eur Respir J</i>. 2002; 19: 398–404.
MESENCHYMAL STEM CELLS COMBINED WITH HEPATOCYTE GROWTH FACTOR THERAPY FOR ATTENUATING ISCHEMIC MYOCARDIAL FIBROSIS: ASSESSMENT WITH MULTIMODAL MOLECULAR IMAGING
Authors: Huizhu Chen, Rui Xia, Zhenlin Li, Lizhi Zhang, Chunchao Xia, Zhigang Yang, Hua Ai, Yingkun Guo
Journal: Journal of the American College of Cardiology (2016)
SAT0163 Defective autophagy in T lymphocytes from patients with systemic lupus erythematosus: Potential role of anti-lymphocyte autoantibodies
Authors: C. Alessandri, M. Pierdominici, F. Conti, S. Truglia, C. Barbati, M. Pendolino, D. Vacirca, P. Piscopo, A. Maselli, T. Colasanti, A. Perl, E. Ortona, W. Malorni, G. Valesini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Autophagy, the cytoprotection mechanism that takes place in cells under metabolic impairment, has been implicated in the pathogenesis of autoimmune diseases (1-5). Evidence also supports a role for sera obtained from patients with systemic lupus erythematosus (SLE) in inducing autophagy, thus suggesting the hypothesis that autophagy could play a pathogenetic role in autoimmunity. <h3>Objectives</h3> We investigated the autophagic behaviour of peripheral T lymphocytes obtained from patients with SLE and healthy donors. We also tested the hypothesis that humoral autoimmune factors may contribute to the dysregulation of lymphocyte homeostasis in SLE via a pathway involving autophagy modulation. <h3>Methods</h3> Thirty-four consecutive patients with SLE (32 women, 2 men) and an equal number of age-and sex-matched healthy donors were enrolled in the study. Current SLE disease activity was measured using the SLE Disease Activity Index (SLEDAI). Disease modyfing antirheumatic drugs were discontinued at least 24 hours before venipuncture. The experimental methods included combined cellular and molecular approaches (cell culture techniques, flow cytometry, Western blot, RT-PCR). <h3>Results</h3> In order to reveal differences in the autophagy level between T cells from SLE patients and healthy donors, <i>ex vivo</i> analysis of these cells for the presence of the autophagosomal marker microtubule-associated protein-1 light chain 3 (LC3)-II was performed by Western blot. A great inter-individual variability for LC3-II levels was present both in SLE patients and in healthy donors. However, there were no significant differences in the quantity of LC3-II in SLE compared with normal T cells. Further experiments were performed <i>in vitro</i> challenging lymphocytes with sera collected from SLE patients. We found that SLE sera increased autophagy in T lymphocytes from healthy donors via a mechanism involving anti-lymphocyte antibodies, while they were ineffective in inducing autophagy in T lymphocytes from SLE patients. Accordingly, genes negatively regulating autophagy were upregulated in lymphocytes from SLE patients. <h3>Conclusions</h3> Our data clearly suggest that a defective autophagy can occur in T cells from SLE patients. This could open new perspectives in molecularly targeted therapeutic strategies aimed at the modulation of the T cells autophagic propensity in SLE. <h3>References</h3> Levine, B., and Kroemer, G. (2008) Cell 132, 27-42 Harley, J.B. et al. (2008) Nat Genet 40, 204-210 Perl, A. (2010) Autoimmunity 43, 32-47 Zhou, X.J. et al. (2011) Ann Rheum Dis 70, 1330-1337 Towns, R. et al. (2005) Autophagy 1, 163-170 <h3>Disclosure of Interest</h3> None Declared
A Comparison of Osteopathic Spinal Manipulation with Standard Care for Patients with Low Back Pain
Authors: Gunnar B.J. Andersson, Tracy Lucente, Andrew M. Davis, Robert E. Kappler, James A. Lipton, Sue Leurgans
Journal: New England Journal of Medicine (1999)

The effect of osteopathic manual therapy (i.e., spinal manipulation) in patients with chronic and subchronic back pain is largely unknown, and its use in such patients is controversial. Nevertheless, manual therapy is a frequently used method of treatment in this group of patients.
Predicting cross-cultural patterns in sex-biased parental investment and attachment
Authors: Robert J. Quinlan
Journal: Behavioral and Brain Sciences (2009)

Abstract If parenting behavior influences attachment, then parental investment (PI) theory can predict sex differences and distributions of attachment styles across cultures. Trivers-Willard, local resource competition, and local resource enhancement models make distinct predictions for sex-biased parental responsiveness relevant to attachment. Parental investment and attachment probably vary across cultures in relation to “local fitness currencies” for status, wealth, and well-being.