tbuckley/cabot-search huggingface dataset:
Abstract LB-378: The outlier approach discriminates drivers from passengers among genes methylated in cancers
Authors: Mizuho Kikuyama, Hideyuki Takeshima, Takayuki Kinoshita, Eriko Okochi-Takada, Mika Wakabayashi, Sadako Akashi-Tanaka, Toshihisa Ogawa, Yasuyuki Seto, Toshikazu Ushijima
Journal: Cancer Research (2012)

Abstract A large number of genes are methylated in cancers, and most of them are methylated as passengers of carcinogenesis, and this fact hampers identification of drivers, tumor-suppressor genes (TSGs), silenced by aberrant methylation of promoter CpG islands (CGIs). To overcome this issue, we focused on the rule that the vast majority of genes methylated in cancers lack, in normal cells, RNA polymerase II (Pol II) and have trimethylation of histone H3 lysine 27 (H3K27me3) in their promoter CGIs. However, approximately 5% of the genes methylated in cancers are against this general rule, constituting a group of “outliers”. It is expected that TSGs belong to this group of outliers since they are expressed or ready to be expressed in normal cells. Here, we aimed to demonstrate that TSGs belong to the group of outliers, and that searching for outliers enables us to identify TSGs. First, we demonstrated that some of known TSGs in breast and colon cancers had Pol II and lacked H3K27me3 in normal cells, being outliers of the rule. We then made a genome-wide search for outlier genes in breast cancers. Based on Pol II binding and H3K27me3 statuses in normal cells and DNA methylation statuses in five breast cancer cell lines, 14 outlier genes were identified from 280 methylated genes. Among these genes, four genes were confirmed to be methylated in primary breast cancer samples, and two (HOXA5 and FBN2) of these were known TSGs. Among the remaining two genes, DZIP1 was shown to suppress growth of breast cancer cells, suggesting it to be a novel TSG. These results showed that some of known TSGs are the outlier genes and that TSGs can be efficiently identified by searching for outliers against the rule, the outlier approach. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-378. doi:1538-7445.AM2012-LB-378
PREVALENCE OF ELECTROCARDIOGRAPHIC PATTERNS ASSOCIATED WITH SUDDEN CARDIAC DEATH IN GENERAL POPULATION OLDER THAN FORTY YEARS
Authors: Paula Awamleh, Catherine Graupner, Pedro Talavera, Jose Maria Serrano Antolin, Juan Gomez-Doblas, Javier Muñiz, Joaquin Alonso, Eulalia Roig, Rosa Jimenez, Carmen Cristóbal
Journal: Journal of the American College of Cardiology (2015)
FRI0363 Do serum biomarkers of bone and OF cartilage degradation reflect structural damage in juvenile idiopathic arthritis (JIA)?
Authors: S. Pederzoli, C. Malattia, G. Cangemi, S. Barco, A. Pistorio, M. Mazzoni, A. Madeo, A. Beltramo, S. Lanni, D. Beleva, A. Consolaro, A. Martini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Serum biomarkers of bone and of cartilage degradation have been found to predict structural damage progression in Rheumatoid Arthritis (RA). Their potential value in JIA has never been explored. <h3>Objectives</h3> To examine correlations between a panel of soluble biomarkers of bone and of cartilage degradation (C1-2C, CTX1) and joint damage as assessed by Conventional Radiography (CR) and Magnetic Resonance Imaging (MRI) in JIA <h3>Methods</h3> The clinically more affected wrist of 62 JIA patients (female: 49, male:13, median age: 11.3 years, median disease duration: 4.1 years) was studied with CR (adapted Sharp-van der Heijde method and Poznanski score) and MRI (paediatric targeted and RA MRIs scores), coupled with standard clinical assessment. Forty-one patients had one-year imaging follow-up.Serum C1-2C, CTX1 were measured by ELISA assays in all JIA patients (N=62) and in gender- and age-matched healthy controls (N=140). <h3>Results</h3> C1-2C and CTX1 levels did not significantly differ between JIA patients and healthy controls. Furthermore, C1-2C and CTX1 values in patients without radiological detected damage progression were comparable to those of the patients with radiographic progressive damage. Unexpectedly, as cross-sectional analysis, biomarkers of bone and of cartilage degradation did not significantly correlate with radiological structural damage. C1-2C was moderately correlated with physician's global assessment of disease activity (r<sub>s</sub>=0.42) and with CHAQ (r<sub>s</sub>=0.42). CTX1 was fairly correlated only with disease duration (r<sub>s</sub> =0.46).Baseline values of bone and of cartilage degradation did not predict structural damage progression at 1 year follow-up. <h3>Conclusions</h3> Unlike adults with RA, C1-2C, and CTX1 do not seem to correlate with structural damage progression in JIA. The overlap in levels not only between patients and healthy controls but also between patients with progression and without progression significantly limits the clinical utility of these biomarkers. <h3>References</h3> Syversen SW. Biomarkers in early rheumatoid arthritis: longitudinal associations with inflammation and joint destruction measured by magnetic resonance inaging and conventional radiographs. Ann Rheum Dis 2010, 69: 845-850 <h3>Disclosure of Interest</h3> None Declared
Ice Cream as a Source of Riboflavin, Carotene and Ascorbic Acid
Authors: Arthur D. Holmes, John W. Kuzmeski, Carleton P. Jones, Frank T. Canavan
Journal: New England Journal of Medicine (1946)

MANY people consider ice cream as a luxury food, a dessert or an attractive adjunct to teas and other social occasions where light refreshments are served. Consequently, this food does not ordinarily receive proper recognition as a valuable source of protein, fat, carbohydrate, minerals and vitamins, all of which are essential dietary constituents. In fact, most people fail to realize the extent to which ice cream is consumed in this country. It is reported that 412,144,000 gallons were used during 1943,1 or over 3 gallons for every man, woman and child. It is difficult to estimate accurately the retail value . . .
THU0389 Erythema over the joint may help to distinguish familial mediterranean fever from other rheumatologic conditions:
Authors: S. Ugurlu, F. Mehmedali, F. Nalci, A. Gurbuz, B. Canbay, Y. Sengul, G. Hatemi, H. Ozdogan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Familial Mediterranean fever (FMF) is a clinical diagnosis and depends mainly on disease history of recurrent attacks of serositis. A history of recurrent arthritis with erythema over the involved joint (red arthritis) is considered an important feature of FMF and used as a tool in the clinic to distinguish it from other rheumatologic conditions. <h3>Objectives</h3> The aim of this study is to determine whether history of erythema over the joint would predict FMF compared to diseased controls. <h3>Methods</h3> We surveyed patients with FMF (n=100; M, F), gout (n=16), ankylosing spondylitis (AS) (n=55), inflammatory bowel disease (IBD), (n=51) rheumatoid arthritis (RA) (n=70), Behçet’s syndrome (BS) (n=50) and systemic lupus erythematosus (SLE) (n=50) followed in our rheumatology outpatient clinics. Only those who had joint involvement were analyzed. We used a 20-item questionnaire that sought details of joint involvement. All patients were shown a picture of erythema over the joint to confirm if they had experienced a similar condition. <h3>Results</h3> Demographic features and the number of patients with a history of erythema over the joint in each group are given in the Table. Erythema over the joint predicted a diagnosis of FMF compared to overall controls which included BS, SLE, RA, AS,IBD and gout with an odds ratio of 2.5 (95% CI 1.3-4.7) (p=0.002). When the odds ratio was calculated for each control group, erythema over the joint discriminated FMF from AS OR=3.2 (95% CI 1.2-9.0) (p=0.04) and RA OR=4.9 (95% CI 2.3-10.8) (p=0.001). If history of red arthritis with an onset before the age of 20 is considered, an OR of 22.8 (95% CI 8.8-61) is obtained, giving a sensitivity of 79.4% and a specificity of 85.4% for the diagnosis of FMF <h3>Conclusions</h3> History of erythema over the joint (red arthritis) may discriminate FMF arthritis from certain arthritidies. The sensitivity and specificity improves significantly if age of onset of red arthritis is taken into consideration. This observation should be improved by including a control group consisting of other periodic fever syndromes. <h3>Disclosure of Interest</h3> None Declared
P12 The Usefulness Of Heartburn As A Marker Of The Success Of Acid Suppression Therapy In Chronic Cough
Authors: H. Badri, I. Satia, A. Woodcock, J. Smith
Journal: Thorax (2014)

<h3>Background</h3> A recent retrospective analysis of randomised controlled trials has suggested that patients with chronic cough reporting heartburn are more likely to benefit from acid suppressive treatment than those without heartburn.<sup>1</sup> Therefore we set out to investigate the response rate to acid suppression treatment (PPI and or H2 antagonists) in patients attending our specialist cough clinic. <h3>Objective</h3> To determine the relationship between reported responses to acid suppression treatment and the presence or absence of heartburn. <h3>Methods</h3> We performed a retrospective review of 59 consecutive new referrals to the clinic. The presence or absence of heartburn is collected routinely in our standard clinic proforma. Patients who were treated with acid suppression either at our clinic or previously at another centre were included, together with their reported response to treatment. A Fisher’s exact test was used to assess whether those with heartburn were more likely to report a response of their cough to acid suppression treatment than those without heartburn. <h3>Results</h3> Of 59 new referrals (median age 58 (range 26–76), 44 female), 21 (35.6%) reported heartburn, whereas 38 (64.4%) did not. Forty-four subjects had completed a trial of acid suppression therapy; 7 (15.9%) reported either a partial or complete resolution of their cough, but 37 (84.0%) reported no response. Of those reporting heartburn, 5/21 (23.8%) also reported a response to acid suppression. Of those not reporting heartburn, 2/23 (8.7%) reported a response to acid suppression. Although a greater proportion of those with heartburn reported improvement of cough with acid suppression, this did not reach statistical significance (p = 0.23). <h3>Conclusion</h3> This data suggests that in the setting of a specialist cough clinic few patients report a response of their cough to acid suppression therapy, even in the context of heartburn. However, a larger dataset is required to understand whether those with heartburn might be more likely to respond. <h3>References</h3> Karhilas PJ. Response of chronic cough to acid-suppressive therapy in patients with gastroesophageal reflux disease. <i>Chest</i> 2013
Bone and Lymph Node Metastases From Neuroblastoma Detected by 18F-DOPA-PET/CT and Confirmed by Posttherapy 131I-MIBG but Negative on Diagnostic 123I-MIBG Scan
Authors: Ugur Demirsoy, Hakan Demir, Funda Corapcoğlu
Journal: Clinical Nuclear Medicine (2014)

Department of Pediatric Hematology/Oncology, Kocaeli University School of Medicine, Kocaeli, Turkey, E-mail: [email protected] Department of Nuclear Medicine, Kocaeli University School of Medicine, Kocaeli, Turkey Department of Pediatric Hematology/Oncology, Kocaeli University School of Medicine, Kocaeli, Turkey Conflicts of interest and sources of funding: none declared.
SAT0138 Prediction of Response to Tocilizumab Using Biomarkers (Interleukin-1 Beta, D-Dimer and Fibrinogen) in Patients with Rheumatoid Arthritis
Authors: T. Okano, T. Koike, M. Tada, Y. Sugioka, K. Mamoto, K. Inui, H. Nakamura
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Better objective measures are needed to evaluate the responses to biologics in rheumatoid arthritis (RA) patients because such responses are not predictable and useful indicators remain unclear. Furthermore, to predict the early effect of tocilizumab (TCZ) is difficult because inflammatory markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) become negative regardless of clinical effect. <h3>Objectives</h3> We aimed to identify factors that could predict the early effects of TCZ therapy in patients with RA in the clinical Predictors of Effectiveness in Tocilizumab Therapy (PETITE) trial (Registration number, UMIN000002246). <h3>Methods</h3> We treated 60 patients with RA (male, n = 5; female, n = 55) with TCZ for 52 weeks between September 2009 and December 2011 at Osaka City University Hospital and related hospitals. Serum interleukin-1 beta (IL-1β), D-dimer and fibrinogen were measured before and after 4 weeks of TCZ therapy. The effect of TCZ and clinical changes were assessed as changes in the disease activity score (DAS) 28-ESR and clinical disease activity index (CDAI) between baseline and 52 weeks. The last observation carried forward (LOCF) and linear imputation were used in the analysis of clinical efficacy when data were missing. <h3>Results</h3> Mean age and disease duration were 60.4 ± 14.9 (22 – 85) and 11.2 ± 10.2 (0 – 45) years, respectively. The DAS28-ESR and the ratio of the CDAI decrease were significantly decreased in the group below, than within the upper detection limits of serum IL-1β after 4 weeks (-2.36 vs. -1.66; p &lt; 0.01). The increase in IL-1β after 4 weeks predicted less of a decrease in the DAS28-ESR at 52 weeks. Baseline levels and changes in D-dimer and fibrinogen between baseline and after 4 weeks did not predict changes in the DAS28-ESR and CDAI at 52 weeks. <h3>Image/graph</h3> <h3>Conclusions</h3> The decreases in the DAS28-ESR and in the ratio of the CDAI decrease at 52 weeks was larger in the group below, than in the upper detection limit of serum IL-1β at 4 weeks. Thus, serum IL-1 β levels after 4 weeks of TCZ administration are potent tools for identifying new candidate biomarkers with which to predict responses to TCZ at 52 weeks. <h3>References</h3> Gibbons LJ, Hyrich KL. Biologic therapy for rheumatoid arthritis: clinical efficacy and predictors of response. BioDrugs. 2009;23:111-24. <h3>Disclosure of Interest</h3> T. Okano: None Declared, T. Koike Speakers bureau: Takeda Pharmaceutical, Mitsubishi Tanabe Pharma Corporation, Chugai Pharmaceutical, Eisai, Abbott Japan, Teijin Pharma, Banyu Pharmaceutical and Ono Pharmaceutical, M. Tada Grant/research support from: Japan Osteoporosis Foundation grant 2013, Y. Sugioka: None Declared, K. Mamoto: None Declared, K. Inui: None Declared, H. Nakamura: None Declared
Milk and Membranous Nephropathy
Authors: Agnes B. Fogo
Journal: New England Journal of Medicine (2011)

Membranous nephropathy is a common cause of the nephrotic syndrome in adults, but it is rare in children, and the prognosis is highly variable.13 The diagnosis is based on renal-biopsy findings, including characteristic immune-complex deposits along the glomerular basement membranes and thickened capillary walls with projections of basement membrane, and matrix (“spikes”) formed in response to the subepithelial deposits.4 Substantial progress has been made recently in understanding the heterogeneous pathogenesis of membranous nephropathy. Numerous causes involving both endogenous and exogenous antigens have been implicated. In this issue of the Journal, Debiec et al. add another mechanism — namely, that . . .
EPA Finds Passive Smoking Causes Lung Cancer
Authors: T. Reynolds
Journal: JNCI Journal of the National Cancer Institute (1993)

Journal Article EPA Finds Passive Smoking Causes Lung Cancer Get access Tom Reynolds Tom Reynolds Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 85, Issue 3, 3 February 1993, Pages 179–180, https://doi.org/10.1093/jnci/85.3.179 Published: 03 February 1993
Impact diagnostique d'une stratégie de surveillance prospective de l'intestin grêle chez les patients ayant un syndrome de Lynch
Authors: E Samaha, G Rahmi, G Malamut, J Edery, B Landi, N Siauve, CA Cuenod, P Laurent-Puig, C Cellier
Journal: Endoscopy (2012)

Le risque cumulé de cancer de l'intestin grêle chez les patients ayant un syndrome de Lynch varie entre 1 et 8% selon la littérature. Les modalités de surveillance de ce cancer ne sont pas encore codifiées.
Abstract 5379: Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung.
Authors: Ester Bonastre, Ilse Zondervan, Federica Facchinetti, Enric Condom, Suvi Savola, Julian Carretero, David Sidransky, Luca Roz, Elisabeth Brambilla, Montse Sanchez-Cespedes
Journal: Cancer Research (2013)

Abstract In spite of the recent advances in cancer genomics, the genetics underlying the development of lung squamous cell carcinomas (SCC) is still poorly understood. Here, we investigated the contribution of the cell polarity-related gene, PARD3, to lung SCC carcinogenesis. First, we tested for PARD3 alterations in lung cancer cell lines from various histopathological types. The analysis confirmed an intragenic deletion at the H157 cells and unveiled biallelic mutations in another cell line. Both cell lines are SCCs, which circumscribed PARD3 alterations to this lung cancer type. Next, we extended the genetic screening, which included the determination of mutations and of intragenic deletions by multiplex ligation-dependent probe amplification (MLPA) assay, to lung primary SCCs. Overall, our analysis found that eight per cent of the 125 lung SCCs tested, endured biallelic and tumor-specific alterations at PARD3. The absence of PAR3 protein was evident in those tumors carrying frameshift-type mutations or intragenic deletions, while abnormally high immunostaining of PAR3 was observed in some PARD3 wild type tumors, suggesting positive feedback mechanisms. Further, we demonstrate that, as compared to the wild type, PAR3 mutant proteins were not able to significantly reduce cell growth, restore the appropriate formation of tight junctions or regulate downstream targets, evidencing the lack of function of these mutations. In conclusion, here we report, for the first time, the presence of recurrent and deleterious mutations at PARD3 in lung primary SCCs, which attest to its relevance in the development of lung SSCs. Citation Format: Ester Bonastre, Ilse Zondervan, Federica Facchinetti, Enric Condom, Suvi Savola, Julian Carretero, David Sidransky, Luca Roz, Elisabeth Brambilla, Montse Sanchez-Cespedes. Recurrent inactivation of PARD3, a polarity-related gene, in squamous cell carcinomas of the lung. [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 5379. doi:10.1158/1538-7445.AM2013-5379
Abstract SY29-03: Following single mRNAs from birth to death in living cells and tissues.
Authors: Robert Singer
Journal: Cancer Research (2013)

Abstract Imaging has been an essential tool to analyze the dynamic properties of RNA. New technologies in optical microscopy and tagging methods have allowed us to detect and track individual mRNA molecules in single living cells, yielding insights that could not have been obtained through any ensemble measurement: for instance in measuring the time for transcription elongation or nuclear pore transport. We have been dedicated to developing and implementing these technologies to further the understanding of dynamics of mRNA regulation in cells. We have utilized various microscopic approaches to analyze the components of real-time transcription of endogenous genes in living tissues of a transgenic mouse where the mRNAs are labeled by a fluorescent RNA binding protein. These approaches employ a plethora of imaging techniques, ranging from confocal and multiphoton microscopy, long-term cell imaging, high-speed real-time widefield microscopy, single molecule tracking, super-registration microscopy and fluorescence fluctuation analysis. The kinetics of the key elements of RNA metabolism: initiation, elongation, termination, as well as nuclear pore export, cytoplasmic trafficking, localization, translation and decay are now tractable at the single molecule level in vivo. By using mathematical modeling to extract the quantitative parameters of these kinetics, we can describe these processes precisely in living cells, leading to an understanding of the regulatory events governing gene expression-fundamental to the mechanism of disease. Supported by NIH GMS Grants to RH Singer. Citation Format: Robert Singer. Following single mRNAs from birth to death in living cells and 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 SY29-03. doi:10.1158/1538-7445.AM2013-SY29-03
Retention of Chromosome 3 in Extrapulmonary Small Cell Cancer Shown by Molecular and Cytogenetic Studies
Authors: B. E. Johnson, J. Whang-Peng, S. L. Naylor, B. Zbar, H. Brauch, E. Lee, A. Simmons, E. Russell, M. H. Nam, A. F. Gazdar
Journal: JNCI Journal of the National Cancer Institute (1989)

In small cell lung carcinoma, one of the short arms of chromosome 3 is typically lost. To investigate chromosome 3 in extrapulmonary small cell carcinoma, we used DNA probes that detect restriction-fragment-length polymorphisms at loci on 3p. These probes were used to study DNA extracted from tumors and normal tissues and/or tumor cell lines from five patients with extrapulmonary small cell cancer. Tumor DNA from four of the five patients with extrapulmonary small cell cancer retained heterozygosity at loci on 3p. Cytogenetic studies of the tumor cell lines established from these four patients showed retention of both short arms of chromosome 3. We conclude that the loss of genetic material from 3p observed in small cell lung cancer is not typical in extrapulmonary small cell cancer. [J Natl Cancer Inst 81:1223–1228, 1989]