tbuckley/cabot-search huggingface dataset:
Abstract 108: Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status.
Authors: Maria Simonsson, Viktoria Söderlind, Maria Henningson, Maria Hietala, Carsten Rose, Christian Ingvar, Helena C. Jernström
Journal: Cancer Research (2013)

Abstract Whether coffee modulates response to endocrine therapy in breast cancer patients is currently unknown. The CYP1A2 and CYP2C8 enzymes contribute to tamoxifen and caffeine metabolism. The aim was to investigate the impact of coffee consumption on tumor characteristics and disease-free survival in relation to breast cancer treatment and CYP1A2 and CYP2C8 genotypes. Questionnaires regarding lifestyle were completed preoperatively by 592 patients in Southern Sweden. CYP1A2*1F and CYP2C8*3 were genotyped. Clinical data and tumor characteristics were obtained from patients’ charts, population registries, and pathology reports. Coffee consumption was categorized as low (0-1 cups/day), moderate (2-4 cups/day), or high (5+cups/day). The proportion of estrogen receptor negative (ER-) tumors increased with increasing coffee consumption (Ptrend=0.042). Low consumption was associated with higher frequency of discordant receptor status (ER+PgR-) OR 2.61 (1.59-4.29) compared to higher consumption. Median follow-up time was 4.92 years. Tamoxifen-treated patients with low consumption had significantly increased risk for early events compared to patients who consumed two or more cups/day, adjusted HR 2.50 (1.20-5.26). Low coffee consumption was also associated with higher risk for distant metastases in tamoxifen-treated patients with ER+ tumors, adjusted HR 2.43 (1.00-5.88). Low consumption combined with at least one CYP1A2*1F C-allele or CYP2C8*3 was associated with a high risk for early events in tamoxifen-treated patients, adjusted HRs 3.49 (1.54-7.90) and 6.14 (2.46-15.34), respectively. In conclusion, a moderate to high coffee consumption of caffeinated coffee was associated with significantly lower risk for early breast cancer events in tamoxifen-treated patients. This may be due to modification of the hormone receptor status or altered CYP enzyme activity. If confirmed, new recommendations regarding coffee consumption during tamoxifen-treatment may be warranted. Citation Format: Maria Simonsson, Viktoria Söderlind, Maria Henningson, Maria Hietala, Carsten Rose, Christian Ingvar, Helena C. Jernström. Coffee prevents early events in tamoxifen-treated breast cancer patients and modulates hormone receptor status. [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 108. doi:10.1158/1538-7445.AM2013-108
Screening Inpatients for MRSA — Case Closed
Authors: Michael B. Edmond, Richard P. Wenzel
Journal: New England Journal of Medicine (2013)

One of the most controversial concepts in health care epidemiology during the past decade has been the active detection and isolation of patients with methicillin-resistant Staphylococcus aureus (MRSA) colonization. The basic strategy is to screen inpatients for MRSA, typically with a polymerase-chain-reaction–based technology, in order to rapidly identify patients colonized with the organism and then initiate contact precautions (place them in a private room and require gowns and gloves on room entry). This approach has been used for decades to control outbreaks caused by epidemiologically important pathogens. As MRSA became endemic in hospitals, studies began to appear suggesting that active . . .
P1239 HIGH SVR24 RATES WITH MERICITABINE (MCB), TELAPREVIR (TVR) PLUS PEGIFN ALFA-2a/RIBAVIRIN (P/R) IN HCV G1-INFECTED PRIOR NULL RESPONDERS: RESULTS FROM DYNAMO 2
Authors: K.E. Sherman, X. Forns, A. Scalori, S. Zhao, A. Voulgari, J. Thommes
Journal: Journal of Hepatology (2014)
SAT0271 Predictors of physical function and mobility in nonradiographic axial spondyloarthritis and ankylosing spondylitis
Authors: J. Sieper, S.A. Rao, N. Chen, M.A. Cifaldi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The definition of axial spondyloarthritis is evolving with a new ASAS classification. Maintenance of physical function and patient mobility are primary goals in the treatment of ankylosing spondylitis (AS) and nonradiographic axial SpA (nr-axSpA). Bath AS Functional Index (BASFI) and Bath AS Mobility Index (BASMI) were developed to measure physical function and mobility in AS patients. HAQ-S is a measure of physical function for Spondyloarthropathies. Predictors for these outcomes may be different for nr-axSpA. <h3>Objectives</h3> To identify physical function and mobility predictors in nr-axSpA and AS patients. <h3>Methods</h3> Baseline data from ABILITY-1 (N=185) and ATLAS (N=315) clinical trials were analyzed. Separate stepwise regression analyses were conducted for AS and nr-axSpA groups. For physical function, the dependent variables were BASFI for (AS) and HAQ-S for (nr-axSpA). Model selection included age, sex, disease duration, Bath AS Disease Activity Index (BASDAI), CRP level, SF-36 Mental Component Summary (MCS), nocturnal pain, total back pain, Patient's Global Assessment (PGA), Physician's Global Assessment (PhGA), and BASMI. For mobility the dependent variable was BASMI for both diseases. Model selection included the same variables plus other measures of physical function; BASFI, SF-36 Physical Component Summary (PCS), and SF-36 Physical Function (PF). <h3>Results</h3> <i>Physical Function:</i> Based on the stepwise regression, disease activity, age and mobility were predictors in both AS and nr-axSpA. For nr-axSpA, these were the only predictors for physical function. For AS patients, PGA of disease activity explained most of the variance in the model. CRP levels were also significant predictors of physical function in AS (Table 1). <i>Mobility:</i> Based on the stepwise regression, age and physical function were predictors of mobility in AS (BASFI) and nr-axSpA patients (HAQ-S) (Table 2). For AS patients, disease activity, PhGA of disease activity, and disease duration were also predictors of BASMI. <h3>Conclusions</h3> In AS and nr-axSpA, age, disease severity, and mobility predict physical functioning at baseline, while physical function and age are consistent predictors for mobility. Both emphasize the importance of early treatment. Self-assessment of disease activity is a key predictor of physical function in AS, suggesting that these patients judge disease activity based on ability to function. For mobility, physician's assessment of disease activity is a key predictor. <h3>Disclosure of Interest</h3> J. Sieper Grant/Research support from: Abbott, Consultant for: Abbott, Speakers Bureau: Abbott, S. Rao Shareholder of: Abbott, Employee of: Abbott, N. Chen Shareholder of: Abbott, Employee of: Abbott, M. Cifaldi Shareholder of: Abbott, Employee of: Abbott
OP0095 Customized CNV microarray identified UGT2B17 as a novel susceptibility gene associated with familial ankylosing spondylitis
Authors: M. Uddin, D.D. O'Reilly, R.D. Inman, W.P. Maksymowych, D.D. Gladman, S. Hamilton, R. Yazdani, P. Rahman
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing spondylitis (AS) exhibits a strong genetic predisposition which is only partially accounted for with SNP-based genome-wide associations. To date no structural variations such as copy number variations (CNVs) have been reported to be associated with AS. <h3>Objectives</h3> To identify highly penetrant, novel CNVs associated with familial AS by employing a custom genome-wide microarray. <h3>Methods</h3> Our custom microarray which was comprised of 2 X 1 million probes targeting the rearrangement hotspots (mean spacing of 280 bp) was applied on a large multiplex three generational Caucasian AS family of North European ancestry. This multiplex family was consisted of five (5) individuals affected with AS, two (2) members with Systemic lupus erythematosus (SLE) and three (3) unaffected individuals. An ethnically-matched control was used for hybridization. A minimum of five (5) probes were required to call an aberration with an average intensity &gt;0.25 and &lt;-0.25 for a duplication and deletion, respectively. Independent validation was performed for CNV’s identified by the custom microarray using taqman-based quantitative polymerase chain reaction (qPCR). <h3>Results</h3> Microarray analysis revealed complex rearrangements within AS patients in multiple regions not present within the unaffected family members. The most compelling evidence for structural variation was excessive genomic gains observed for the <i>UGT2B17</i> gene. Duplication of the <i>UGT2B17</i> gene was present in all five (5) patients with AS (i.e., two males and three females) and in a patient with SLE. No genomic gain was detected in unaffected family members. Validation using qPCR demonstrated complete concordance with the microarray results with all five (5) AS individuals contained ≥2 copies of the <i>UGT2B17</i> gene, whereas unaffected individuals had only a single copy. The population frequency of the <i>UGT2B17</i> CNV among Caucasians is 0.15 for a deletion, 0.45 for one copy, and 0.25 for two or more copies. The <i>UGT2B17</i> gene encodes a key enzyme responsible for glucuronidation of androgens which stimulate bone formation. Interestingly, deletion of the <i>UGT2B17</i> gene has been associated with osteoporosis (Yang TL <i>et al</i>., 2008); however, this association was not replicated in an independent study (Chew S <i>et al</i>., 2011). <h3>Conclusions</h3> This is the first report of structural variants (i.e., CNVs) being associated with familial AS. Given the proposed function of this gene in stimulating bone formation, it should be considered a high priority susceptibility gene in familial AS. Replication studies and further functional studies are warranted. <h3>Disclosure of Interest</h3> None Declared
SP0186 Modelling Longitudinal Data
Authors: S. Ramiro
Journal: Annals of the Rheumatic Diseases (2014)

<h3></h3> Longitudinal studies are increasingly used in rheumatology, especially in long-term cohorts, and are a source of important information that helps us drawing meaningful conclusions. Longitudinal studies are defined as studies in which the same outcome variable is repeatedly measured over time in the same patient. They can be applied in any field and be used to address different types of research questions. Examples of longitudinal studies are the registries that have been created during the last decade (several of them based on patients using biologicals, others broader) that aim at investigating disease and/or treatment outcomes over time. Questions like: 9Does disease activity lead to structural damage?9 or 9Does functional disability result from high disease activity?9 can be appropriately addressed with a longitudinal study. Longitudinal studies allow us to investigate the development or the course of a variable over time if analyzed appropriately, and may provide insight into the longitudinal relationship between several variables over time. Appropriate analysis means that adjustment for correlated data takes place in order to avoid spurious relationships. Correlated data are data collected within the same patient. Furthermore, in longitudinal analysis, all data collected for a given patient over time are used. Due to this efficient data usage, this type of analysis has more analytical power. Longitudinal analysis is nowadays increasingly frequent and widespread, and it is important that researchers and clinicians learn about the principles of longitudinal data analysis in order to be able to interpret articles appropriately. In this presentation, longitudinal analysis will be discussed, its advantages as well as its challenges. Several examples of longitudinal data analysis will be presented, and the strengths of longitudinal analysis will be discussed. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.6157
Abstract 1064: Sloan-Kettering Institute (Ski) protein plays distant roles in activation of Smad proteins in response to nodal and TGF-β in prostate cancer cells
Authors: BaoHan T. Vo, Bianca Cody, Yang Cao, Shafiq A. Khan, Center for Cancer Research and Therapeutic Development
Journal: Cancer Research (2012)

Abstract Transforming growth factor-β (TGF-β) acts as a tumor suppressor in the early stages of epithelial cancers by inhibiting proliferation and inducing apoptosis. However, in the later stages of the disease, TGF-β acts as a tumor promoter and is associated with aggressive forms of cancer due to its effects on angiogenesis, immune suppression, and metastasis. Previously, we have demonstrated that Nodal, another member of the TGF-β superfamily and its receptors are expressed in prostate cancer cell lines. Nodal and TGF-β exerted differential effects on prostate cancer cells; both inhibited proliferation in WPE, RWPE1, and DU145 cells while neither had effect on the proliferation of LNCaP and PC3 cells. On the other hand, Nodal and TGF-β induced migration in PC3 cells, but had no effect on cell migration in DU145 cells. Nodal primarily employs Smad2 for intracellular signaling while TGF-β is essential for both Smad2/3 phosphorylations. In the present study, we have determined the expression and role of Ski in Nodal and TGF-β signaling in prostate cancer cells. Ski is a co-repressor of the Smad-mediated TGF-β signaling. Ski was originally classified as an oncogene based on its ability to transform chicken and quail fibroblasts. RT-PCR analysis showed comparable mRNA levels of Ski in several established prostate cell lines; however, high levels of Ski protein were only detected in prostate cancer cell lines and Ski protein levels were very low or absent in normal cells. Ski protein levels were also high in prostate cancer tissue samples compared to normal prostate tissues. Treatment with Nodal and TGF-β had no effects on Ski mRNA levels; however, Nodal had no effect on Ski protein levels while TGF-β induced degradation of Ski protein levels mediated by the proteasome pathway. Reduced Ski levels correlated with increased basal and TGF-β-induced Smad2/3 phosphorylation. Knockdown of endogenous of Ski reduced proliferation in DU145 prostate cancer cells and enhanced migration of PC3 cells. We conclude that high level of Ski expression in prostate cancer cells may be responsible for repression of TGF-β and Smad2/3 signaling, but Ski protein levels do not influence Nodal effects. 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 1064. doi:1538-7445.AM2012-1064
PULMONARY HYPERTENSION AND CHRONIC KIDNEY DISEASE: INVASIVE HEMODYNAMIC ETIOLOGY AND OUTCOMES IN A LARGE ELECTRONIC MEDICAL RECORD-BASED COHORT
Authors: Jared Martin O’Leary, Tufik Assad, Anna Hemnes, Meng Xu, Quinn Wells, Eric Farber-Eger, Kelly A. Birdwell, Evan Brittain
Journal: Journal of the American College of Cardiology (2016)
AB0429 Regime of Use of Rituximab in Patients with Rheumatoid Arthritis in Daily Clinical Practice:
Authors: L. Merino-Meléndez, I. Llorente-Cubas, T. Velasco, S. Castañeda, J. Άlvaro-Gracia, I. González-Άlvaro
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> The recommended therapeutic regime for Rituximab (RTX) in Rheumatoid Arthritis (RA), according to prescribing information, includes two 1000-milligram infusions given two weeks apart, every 6 months. However, this is often not the case in clinical practice, since both consensus documents and information from clinical trials consider other alternatives. <h3>Objectives</h3> Our objective in this study was to analyze the regime of use of RTX in RA in daily clinical practice. <h3>Methods</h3> This is a retrospective study that includes patients treated with RTX between 1998 and 2013 in a single university hospital. We reviewed medical records and collected demographic data, number of cycles, doses and intervals of RTX administered to the patients, response duration, as well as frequency and reasons of treatment discontinuation. Descriptive analysis was performed using the statistical package Stata v. 12. <h3>Results</h3> Ninety-three patients were studied, of which 83% were women. Median age at disease onset was 51 years with an interquartile range (IQR) of 39 to 60 years. Median age at the start of treatment with RTX was 60 [IQR: 51-70] years. Out of the 93 patients, 11 had negative rheumatoid factor. The number of cycles of RTX administered to each patient ranged from one to nine. Treatment was discontinued in 33% of the patients. The reasons for discontinuation were inefficacy (16%), adverse effects (7%) and others (10%). RTX was most commonly withdrawn during the first two cycles. The main data related to use of RTX in our study are summarized in the following table. Response duration in males tended to be longer [12 months; IQR: 8-13] than in females [10 months; IQR: 7-12], but this didn9t reach statistical significance (p=0911, Mann-Whitney9s test). Longer response duration was observed in patients with a longer RA history (r =0.24, P=0.001, Pearson9s test). RTX dose per cycle did not modify the response duration (1 vs 2 grams, 9.5 and 10 months respectively). <h3>Conclusions</h3> Our data show that, in daily clinical practice, RTX is more frequently used on demand, tending to abandon the fixed regime of 2 grams every six months. In addition, we observe a tendency to an increased use of 1 gram cycles with time. This results in cost savings without apparent decrease in healthcare quality. <h3>References</h3> Martín Mola et al. Grupo de Expertos en Rituximab. Reumatol Clin. 2011;7:30-44 <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4562
Overexpression of LMW cyclin E results in faster M phase progression via Cdc25C interaction leading to chromosome missegragation in breast cancer cells.
Authors: R Bagheri-Yarmand, K Keyomarsi
Journal: Cancer Research (2009)

Abstract Abstract #5032 Cyclin E is a G (1) cyclin essential for S-phase entry and has a profound role in oncogenesis. Cyclin E is overexpressed and present in low-molecular-weight (LMW) isoforms in breast cancer cells and tumor tissues compared to normal cells and tissues. Such alteration of cyclin E is linked to poor patient outcome. We have previously shown that ectopic expression of low molecular weight of Cyclin E (LMW-E) in breast cancer cell lines induces genomic instability by promoting aneuploidy and the formation of structural chromosomal lesion. To determine the mechanism of induction of genomic instability by ectopic expression of LMW-E, we generated the MCF-7 cells inducibly expressing either the full length (EL) or low molecular weight (LMW-E) form of cyclin E. We observed 5.5 fold higher number of cells with centrosome defects in LMW-E induced versus EL induced cells. Notably, elevated levels of LMW-E led to a significant increase in fragmented nuclei and multinucleated cells. Immunofluorescence analysis also showed a 4-5 fold increase in the number of cells containing lagging chromosomes and anaphase bridges. Karyotype analysis for gross chromosomal aberrations metaphase preparation of the uninduced and EL and LMW induced cells showed a significantly higher percentage of chromosomal defects including dicentric chromosome and chromosomal breaks associated with LMW-E overexpression. We also show that while overexpression of EL leads to accumulation of cells in S and G2/M phases of the cell cycle, the overexpression of LMW of cyclin E causes a faster M phase progression. As a consequence, LMW-cyclin E overexpressing cells are resistant to nocodazole-induced M phase arrest. Using biochemical assays, we show that EL and LMW-E interact with the phosphatase Cdc25C and when either EL or LMW are in complex with CDK2 that they phosphorylate Cdc25C. Such association of LMW-E with Cdc25C results premature inactivation of cyclin B/CDK1 upon treatment of these cells with nocodazole. Additionally, continued induction of LMW-E results in premature inactivation of PLK1 in mitotic cells and deregulated localization of PLK1 such that it is no longer associated to central spindles during anaphase and telophase. Collectively, these results suggest that overexpression of LMW-E interferes with the activation of CDK1 during mitosis. The relatively low activity of CDK1 during the passage through prophase, prometaphase, and metaphase interferes with the regulation of the spindle checkpoint and facilitates the premature transition of dividing cells from metaphase to anaphase resulting in chromosomal instability and aneuploidy. This is the first observation of how mechanistically the overexpression of a proto-oncogene can lead to genomic instability in breast cancer. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5032.
AB0319 Treatment with tocilizumab improved rheumatoid arthritis patients clinically and structurally regardless of the prior use of anti-tnf biologics in daily clinical practice
Authors: K. Izumi, Y. Kaneko, H. Yasuoka, N. Seta, H. Kameda, M. Kuwana, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> To explore the radiographic efficacy of tocilizumab (TCZ) in rheumatoid arthritis (RA) patients with or without the prior use of anti-tumor necrosis factor (TNF) agents in daily clinical practice. <h3>Methods</h3> Of a total of consecutive 115 RA patients initiating TCZ treatment in Keio university hospital from July 2008 to March 2011, 46 patients who had x-rays of the both hands and feet were assessed stratified by the use of prior biologics (BIO+) and no use of them (BIO-). They received 8 mg/kg of TCZ every 4 weeks, and were observed for 52 weeks to evaluate the clinical and structural outcomes. <h3>Results</h3> Baseline patient characteristics (BIO+, BIO-) were as follows: mean age of 54.8±11.2 years, 52.5±12.5 years; mean disease duration of RA of 6.8±6.5 years, 4.0±3.4 years; concomitant use of methotrexate in 76.9%, 48.5% and use of concomitant glucocorticoid was in 46.2%, 36.4%. Baseline patients' characteristics were comparable between BIO+ and BIO- groups except for ESR (65.9±32.3 in BIO+ vs 42.4±35.3 in BIO-). In BIO+ and BIO- patients, DAS28 remission (DAS28-ESR &lt; 2.6) was achieved in 61.5% and 81.8%, SDAI remission in 38.5% and 54.5%, CDAI remission 38.5% and 51.5%, respectively. Radiographic remission (Δmodified Total Sharp Score ≦0.5) was 46.2% (6/13) in BIO+ patients and 66.7% (22/33) in BIO- patients. There were no significant differences in clinical and structural remission rates between the two groups. <h3>Conclusions</h3> The treatment with TCZ improved RA patients clinically and structurally regardless of the prior use of anti-TNF biologicsin daily clinical practice. <h3>Disclosure of Interest</h3> None Declared
THE RATIO OF SERUM EICOSAPENTAENOIC ACID TO ARACHIDONIC ACID AS A PREDICTOR OF HIGH RISK PLAQUE CHARACTERISTICS ON CORONARY COMPUTED TOMOGRAPHY ANGIOGRAPHY
Authors: Yasuomi Nagahara, Sadako Motoyama, Masayoshi Sarai, Hajime Ito, Hideki Kawai, Kayoko Takada, Yoko Takakuwa, Meiko Miyagi, Junichi Ishii, Yukio Ozaki
Journal: Journal of the American College of Cardiology (2015)
Book: Breast Cancer
Authors: J M. Dixon
Journal: BMJ (1999)

Eds J J Kavanagh, S E Singletary, N Einhorn, A D DePetrillo Blackwell Science, £66, pp 208 ISBN 0 632 04431 4 Rating: ![Graphic][1]</img> When I am asked to be involved in a new book on breast cancer or when I simply read one, I ask the same question: “Do we need any more textbooks on this subject?” Evidently people buy and read them, otherwise publishers would not continue to produce them. They are usually written or edited by experienced clinicians working in centres treating large numbers of breast cancer patients. This may explain their popularity because for no other cancer is there such good evidence that patients treated by doctors who manage large numbers of cases have a … [1]: /embed/inline-graphic-1.gif