tbuckley/cabot-search huggingface dataset:
Abstract LB-23: Ras signaling interrupts TGF-beta-induced KLF5 acetylation to alter the KLF5-Smads transcriptional assembly in epithelial cells
Authors: Peng Guo, Changsheng Xing, Xue-Yuan Dong, Jin-Tang Dong
Journal: Cancer Research (2012)

Abstract β (TGF-β) suppresses early stage tumorigenesis but promotes late stage tumor progression. While also presenting dual roles in tumorigenesis, KLF5 in the acetylated form is essential for TGF-β to properly regulate gene transcription in the inhibition of cell proliferation. The Ras oncogenic signaling not only converts TGF-β from a tumor suppressor to a tumor promoter but also uses KLF5 as a functional effector. One intriguing question is whether and how Ras signaling uses the KLF5 transcription factor to modulate TGF-β function. In this study, we addressed this question by examining whether and how Ras signaling alters TGF-β-induced KLF5 acetylation and the assembly of the p300-KLF5-Smads transcriptional complex in gene regulation. We found that Ras inhibited TGF-β-induced KLF5 acetylation and interfered with TGF-β in p15 induction and Myc repression. In addition, TGF-β-induced Smad3 phosphorylation at the C-terminal region was necessary for TGF-β to induce KLF5 acetylation, and Ras interrupted this phosphorylation. Ras signaling further interrupted the interactions among p300, KLF5 and Smad4, as well as the binding of the p300-KLF5-Smads complex onto the TGF-β-responsive promoter elements for both p15 and Myc. Without TGF-β, however, Ras signaling increased KLF5 acetylation, enhanced the p300-KLF5 interaction, and promoted the binding of the KLF5 transcriptional complex onto the TGF-β-responsive promoter elements. These findings suggest that KLF5 mediates the crosstalk between TGF-β and Ras signaling, and that suppression of TGF-β-induced KLF5 acetylation by Ras signaling alters TGF-β-induced assembly of p300-KLF5-Smads complex onto gene promoters, thus switching the function of TGF-β in gene regulation. 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-23. doi:1538-7445.AM2012-LB-23
THU0252 Higher Anti-Citrullinated Peptide Antibody (ACPA) Titers and Persistence of Inflammatory Indices in Ethnic Minorities with Rheumatoid Arthritis (RA)
Authors: G. Kerr, C. Swearingen, Y. Yazici
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Ethnic minorities with RA suffer greater disability than Caucasians, but prospective data on disease burden is absent. <h3>Objectives</h3> To assess RA disease burden in ethnic minorities over time. <h3>Methods</h3> EMRAC participants with any recorded followup clinical data were analyzed. RA inflammatory and clinical indices as well as drug usage were evaluated by racial/ethnic group. Repeated measure linear regression models were used to estimate association of inflammatory indices with clinical indices adjusting for race, disease duration and drug use. <h3>Results</h3> 392 EMRAC participants with a total 1207 visits were available for analysis. At baseline, African-American (AA) had significantly higher ACPA titers (mean 181±89) compared to Caucasian (CA) (mean 91±108) and Other races (mean 125±113) (P=0.005). Both ESR and CRP were also elevated in AA compared to the other races (P&lt;0.001 for both) at baseline. Racial differences persisted throughout followup as AA laboratory measures remained significantly higher than CA and Other. However, baseline and followup composite disease activity scores (RAPID3, DAS28 and CDAI) did not differ between AA, CA and Other when evaluated in unadjusted analysis. Repeated measures analysis estimated significant positive association between ESR and CRP with RAPID3, DAS28, and CDAI (P≤0.001 for all), but not ACPA, adjusting for race, duration and concurrent drug use. <h3>Conclusions</h3> ACPA is not a significant predictor of RA disease burden and regardless of serology and race all patients should be treated aggressively. The implications of higher inflammatory indices in AA with RA, such as smoking and cardiovascular disease, needs to be examined further. <h3>References</h3> Shidara, K. Rheumatol Int, 2012. Tok Iren, U. J. Rheumatol, 2005. Mikuls, T. Arthritis Rheumatol, 2010. <h3>Acknowledgements</h3> EMRAC (L. Espinoza, E. Treadwell, S. Dowell, M. Quinones, R. Perez Alamino, I. Garcia Valladares, Y. Sherrer, A. Mosley-Williams, T. Lawrence Ford, C. Flowers, A. Ince, H. Tian, A. Godoy, J. Amatruda, C. Stephens) <h3>Disclosure of Interest</h3> : G. Kerr Grant/research support: Genentech, Pfizer, Bristol Myers Squibb, C. Swearingen Grant/research support: Genentech, Pfizer, Bristol Myers Squibb, Y. Yazici Grant/research support: Genentech, Pfizer, Bristol Myers Squibb <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5571
THU0475 Identification of A Transcriptome-Wide Gene Expression Signature on Peripheral Blood from Patients with Systemic Lupus Erythematosus and Rheumatoid Arthritis by High-Throughput DNA Sequencing
Authors: K. Suzuki, K. Yoshimoto, M. Takeshita, T. Kurasawa, T. Takeuchi
Journal: Annals of the Rheumatic Diseases (2014)

Novel methods of detecting and quantitating cooperative interactions between an agent and both a tritiated (muscarinic) antagonist and the endogenous agonist (acetylcholine), acting at a common (muscarinic) receptor, have been devised. In a semiquantitative protocol, binding data are transformed into affinity ratios (the ratios of the apparent affinity of the ligand in the presence of the agent to the affinity of the ligand alone), which allow estimates to be made of the potency of the agent and its cooperativity with the tritiated antagonist and with the unlabeled ligand. These parameters have been quantitated by detailed binding assays or guanosine-59-O-(3-[35S]thio)triphosphate functional assays. The kinetic phenomena associated with the allosteric interactions have been exploited in two non-equilibrium binding assays, from which the affinity constants describing the allosteric interactions can be extracted. The different assay methods give quantitatively similar and internally consistent estimates of the parameters describing the cooperative interactions. Using these assays, strychnine has been found to act allosterically at muscarinic receptors. Strychnine has an affinity of approximately 10(5) M-1 at the unliganded m1, m2, and m4 receptors but is 5-10-fold weaker at m3 receptors. It is positively cooperative with N-methylscopolamine at m2 and m4 receptors and exhibits neutral and negative cooperativity with m1 and m3 receptors, respectively. With acetylcholine, it is negatively cooperative but the degree of cooperativity is relatively low (2-7-fold), particularly at m1 and m4 receptors. The methods and equations described should be useful in detecting and quantitating allosteric interactions of agents with the endogenous neurotransmitter at G protein-coupled receptors.
Case 6-2001
Authors: Maureen M. Jonas, Fiona M. Graeme-Cook
Journal: New England Journal of Medicine (2001)

Presentation of CaseA 17-year-old girl was admitted to the hospital because of progressive jaundice and weight loss.The patient had been well until four months earlier, when she experienced the onset of malaise, anorexia, a sore throat, and tender cervical lymph nodes. Two months later, she ate “hallucinogenic mushrooms.” Five weeks before admission, she observed blood clots in her stool twice on a single day. Three weeks later, she ate more mushrooms. Progressive jaundice subsequently developed, with vomiting, dark urine, and light stools.Ten days before admission, laboratory tests were ordered by the patient's physician (Table 1 and Table 2). Tests . . .
CN-09 * POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME AND PRIMARY BRAIN TUMORS
Authors: C. Kamiya-Matsuoka, D. Cachia, T. Armstrong, M. Gilbert
Journal: Neuro-Oncology (2014)

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a neurotoxic encephalopathic state associated with reversible cerebral vasogenic edema. It is an increasingly recognized occurrence in the oncology population. However, it is very uncommon in patients with primary brain tumors (PBT). The aim of this study is to analyze the clinical manifestations, radiological features and report clinical outcomes of PRES in PBT patients. METHODS: In this retrospective review, we identified 4 patients with PBTs who developed PRES at MDACC between 2012 and 2014. Clinical and radiographic data were abstracted from their records. In addition, we also solicited 2 cases from the literature. RESULTS: The median age at diagnosis of PRES was 47 years (range 5-62), the male:female ratio was 1:5 and occurred in patients with glioblastoma (N = 3), diffuse intrinsic pontine glioma (N = 1), anaplastic ependymoma (N = 1) and atypical meningioma (N = 1). The two cases from literature review had received bevacizumab, and only one case received chemotherapy (cisplatin/etoposide/temozolomide) before the symptoms onset. Clinical presentation included seizures (N = 3), altered mental status (N = 3), headache (N = 2) and focal neurologic deficits (N = 2). All of the patients presented with elevated blood pressure. Three patients had atypical imaging findings, one of them also developed infarctions in those areas. Three of our MDACC patients recovered completely in 3 to 4 weeks after the symptoms onset. One patient died due to active cancer and several comorbidities including PRES. CONCLUSIONS: HTN seems to be the most important co-existent risk factor for development of PRES. The clinical and radiological course of PRES in PBT patients did not vary from the classical descriptions of PRES found in other causes. Resolution of PRES was an independent process even to that of tumor progression. PRES distribution did not correlate with the brain tumor location. Delay in diagnosis can result in permanent residual deficits.
Abstract P2-01-12: Circulating tumor cells and Epithelial Mesenchymal Transition in primary breast cancer patients.
Authors: M Mego, M Karaba, G Minarik, J Benca, T Sedlackova, D Manasova, G Sieberova, P Gronesova, J Pechan, J Mardiak, JM Reuben
Journal: Cancer Research (2012)

Abstract Background: Circulating tumor cells (CTCs) are prognostic in breast cancer (BC) patients. CTCs represent a heterogeneous population of cells with different phenotypes and biological value. Epithelial-mesenchymal transition (EMT) gives rise to cells with stem cell-like properties with increased chemotherapy resistance and may be responsible for undetection of CTC by conventional methods in a fraction of patients with early or advanced breast cancer. The aim of this study was to characterize CTCs based on the expression of epithelial and mesenchymal markers in non-metastatic breast cancer patients before surgery. Methods: This prospective ongoing translational study consists of 36 patients with non-metastatic breast cancer. CTCs were detected before surgery, before 1st cycle and before 2nd cycle of adjuvant therapy. Herein, we present preliminary data related to CTCs detection before surgery. Isolated peripheral blood mononuclear cells (PBMC) were depleted of cells of hematopoietic origin (CD45+) using RossetteSep kit (StemCell Technologies) negative selection with anti-CD45 antibody. RNA extracted from CD45-depleted (CD45−) PBMC was interrogated for expression of EMT-inducing transcription factors (TWIST1, SNAIL1, SLUG, FOXC2) and epithelial (CK19, EpCAM) gene transcripts by quantitative reverse transcription-PCR. Expressions of gene transcripts in CD45- PBMC from patients were compared to those of CD45- PBMC of 30 healthy donors (HD). Results: Median age was 62 year (range: 40–80 years). TWIST1, SNAIL1, SLUG, FOXC2, CK19 and EpCAM were overexpressed in CD45- PBMC in 2.8%, 2.8%, 11.1%, 13.9%, 19.4% and 2.8% respectively. Totally, CTCs were detected in 36.2% of patients. CTCs with only epithelial markers were present in peripheral blood of 5.6% patients; CTC with EMT phenotype were present in 13.9% of patients, while in 16.7% of patients CTCs exhibited both epithelial and mesenchymal markers. Overexpression of different EMT-related transcription factors in peripheral blood samples were mutually exclusive. There was no association between the presence of CTCs and analyzed clinico-pathological variables. Conclusions: CTCs with EMT phenotypes are more prevalent compared to CTCs with epithelial phenotype in early breast cancer patients before surgery, and EMT genes may be involved in the dissemination of CTCs. These data support the concept of CTCs heterogeneity in breast cancer patients. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-01-12.
AB0413 Hepatitis B Serologic Profile and Reactivation in Rheumatic Patients Treated with Biological Therapies – Single Centre Experience
Authors: V. Romao, M. Saavedra, M. Costa, C. Macieira, E. Vieira-Sousa, F. Ramos, C. Resende, S. Capela, R. Barros, J. Polido-Pereira, A. Rodrigues, J. Madruga-Dias, R. Campanilho-Marques, C. Ponte, A. Castro, C. Furtado, S. Fernandes, M. Gonçalves, J. Pereira da Silva, H. Canhao, J. Fonseca
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biologic therapy for rheumatic diseases has been associated with increased risk of latent infections reactivation such as tuberculosis or hepatitis B (HB), due to severe immunosuppression. However, the actual risk of HB reactivation is still unclear regarding the several biologics available, especially in low-incidence countries such as Portugal. <h3>Objectives</h3> To evaluate the serologic HB profile of biologic-treated rheumatic patients in a single centre and assess the incidence of HB reactivation. <h3>Methods</h3> We retrospectively collected electronically available HB serology of rheumatic patients that ever started biological therapy at our department and we reviewed the clinical course to identify reactivation cases, defined as raising viral load and transaminases. <h3>Results</h3> We included 288 patients with available electronic data on HB serologies. Mean age was 43.9±15.7 years (3.1 to 82.3 years), disease duration was 10.9±9.5 years, 63.9% of patients were female and the most common rheumatic disease was rheumatoid arthritis (112, 38.9%), followed by ankylosing spondylitis (76, 26.4%) and psoriatic arthritis (54, 18.8%). As first biologic, 254 patients (88.2%) started anti-TNF agents, 14 (4.9%) rituximab, 11 (3.8%) tocilizumab and 9 patients (3.1%) another biologic. 30 patients (10.4%) eventually stopped biologic treatment. 185 patients (64.2%) were treated with concomitant methotrexate (mean dosage 15.7±5.4mg), 81 (28.1%) with other DMARDs and 169 (58.7%) were treated with corticosteroids (58.7%). All of the 288 patients were HBsAg negative and 23 were anti-HBc positive (9%). The 23 anti-HBc positive patients did not differ significantly from the overall population in terms of age, gender distribution, disease duration, follow-up time, biologic discontinuation or biologic started. No patient received prophylactic antiviral therapy and there were no cases of reactivation or isolated rise in viral load during a cumulative biologic exposure of 1005.6 patient-years (Fig. 1). <h3>Conclusions</h3> In our cohort, there were no cases of HB reactivation on the 288 patients treated with biologic therapy. Anti-HBc positivity was infrequent, viral load was undetectable in all cases and no chronic HB cases were detected. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.4716
Hemodynamic and Electrocardiographic Effects of Selective Coronary Angiography in Man
Authors: Alberto Benchimol, Edward M. McNally
Journal: New England Journal of Medicine (1966)

SELECTIVE coronary angiography has become an invaluable means of distinguishing syndromes due to coronary-artery disease from those arising from other causes. Though much speculation has been made regarding the hemodynamic effects of injecting contrast mediums into the human coronary circulation, little in the way of objective data has been reported. The present report describes the hemodynamic changes that occur during and for a short interval after injection of diatrizoate sodium§ into coronary arteries.Materials and MethodsTwenty-nine patients, 20 men and 9 women, ranging from twenty-eight to sixty-four years of age, were studied. Angiography revealed a normal or negligibly diseased . . .
S25 IL 17 production in primary and secondary Respiratory Syncytial Virus (RSV) infection and neutrophil transmigration
Authors: K. B. Ugonna, K. Plant, M. L. Everard
Journal: Thorax (2010)

<h3>Introduction and Objectives</h3> RSV causes winter epidemics of respiratory disease particularly in infants and the immunocompromised. Infected ciliated airway epithelial cells, local macrophages and dendritic cells secrete cytokines including interleukins (IL) 6 and 8, promoting a strong neutrophilic response that is important in disease clearance and airway inflammation. The IL 17 inflammatory pathway, which is important in surface immunity, has been little studied in RSV infection to date. The following hypothesis was explored: <i>The IL17 pathway is important in neutrophil chemotaxis and restriction of RSV replication</i>. <h3>Methods</h3> A transwell model of the airway was devised, co-culturing A549s (an immortalised bronchial epithelial cell line) and neutrophils to study the effect of RSV and IL17 on the transmigration of neutrophils. Neutrophil transmigration was assessed using light microscopic immunocytochemistry. Nasal swabs were taken from infants with RSV positive Bronchiolitis (n=49), RSV negative Bronchiolitis (n=12), the symptomatic older siblings of RSV positive infants (n=15) and uninfected, asymptomatic children (n=20). Cytokines released (IL6/IL8/IL17a/IL21/TNF) were analysed by cytokine bead array. <h3>Results</h3> IL 17 and RSV caused significantly increased number of neutrophils to transmigrate compared to either IL 17 or RSV alone. Primary RSV infections which caused hospitalisation, are characterised by high levels of nasal epithelial derived cytokines (IL 6, IL 8). Less severe secondary RSV infections are characterised by relatively low levels of IL 6 and IL 8 and relatively high levels of IL 17. <h3>Conclusions</h3> There is evidence that IL 17 is synergistic with RSV induced IL 8 in promoting neutrophil transmigration <i>in vitro</i>. There is evidence to support IL 17 as an important cytokine restricting RSV production in secondary infection <i>in vivo</i>. This study suggests that the IL 17 pathway is important in the pathogenesis of RSV bronchiolitis and could be potentially important in the development of novel therapies for this ubiquitous and important cause of respiratory disease.
Abstract 1796: Analysis of TCGA RNASeq data using SpliceSeq provides a survey of alternative splicing in cancer.
Authors: Michael C. Ryan, John N. Weinstein
Journal: Cancer Research (2013)

Abstract The vast majority of human genes express more than one transcript isoform, and aberrant splicing patterns or changes in isoform expression ratios can lead to disease, notably cancer. Next generation sequencing platforms deliver the finest resolution yet of the transcriptome, and the wealth of sequencing data produced by TCGA provides an excellent basis for a broad study of alternative splicing in cancer. We have developed an interactive, exceptionally user-friendly tool, SpliceSeq, for investigation of alternative splicing in RNASeq data. The program is a follow-up to our SpliceCenter package (http://projects.insilico.us/SpliceCenter/SpliceOverview.jsp), which provides tools for use by the bench biologist in assessing experimental observations that may result from splice variation. Our results from SpliceSeq for TCGA RNASeq data from several cancer types will be presented. We identify pervasive changes in splicing patterns across different cancer types by comparing tumor vs. normal and clinical subgroups (e.g. tumor stage, hyper-mutator status, and MSI designation). Interesting observations include striking splice variations in APP, the amyloid beta precursor protein, and in PKM, which is centrally involved in the balance between oxidative and glycolytic metabolism in tumors. SpliceSeq is freely available at http://bioinformatics.mdanderson.org/main/SpliceSeq:Overview. 1. Ryan MC, Cleland J, Kim R, Wong WC, Weinstein JN. SpliceSeq: A Resource for Analysis and Visualization of RNA-Seq Data on Alternative Splicing and Its Functional Impacts. Bioinformatics, 10.1093, 2012. 2. Ryan MC, Zeeberg BR, Caplen NJ, Cleland JA, Kahn AB, Liu H, and Weinstein JN. SpliceCenter: a suite of web-based bioinformatic applications for evaluating the impact of alternative splicing on RT-PCR, RNAi, microarray, and peptide-based studies. BMC Bioinformatics 9:313, 2008. 3. Kahn AB, Ryan MC, Liu H, Zeeberg BR, Jamison DC, Weinstein JN. SpliceMiner: a high-throughput database implementation of the NCBI Evidence Viewer for microarray splice variant analysis. BMC Bioinformatics 8:752, 2006. Supported by NCI Grant No. U24CA143883. The content is solely the responsibility of the authors and does not necessarily represent official views of NCI or NIH. Also supported in part by a gift from the Mary K. Chapman Foundation and a grant from the Michael and Susan Dell Foundation honoring Lorraine Dell. Citation Format: Michael C. Ryan, John N. Weinstein. Analysis of TCGA RNASeq data using SpliceSeq provides a survey of alternative splicing in cancer. [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 1796. doi:10.1158/1538-7445.AM2013-1796
Abstract SY21-01: Chromatin remodeling proteins in transcription and development
Authors: Trevor K. Archer, Kevin W. Trotter, Ajeet Singh
Journal: Cancer Research (2012)

Abstract The assembly of DNA with histones into chromatin provides a mechanism to regulate gene expression in time and space. The precise architecture of various DNA regulatory elements within the hierarchy of chromatin structures controls the access and activity of transacting factors, both protein and RNA. Epigenetic marks within DNA and histones allow regulatory information to act during development and across generations. The enzymes that mediate these processes are diverse and multifunctional, capable of posttranslationally modifying DNA and histones as well as remodeling the chromatin architecture. Among these enzymes the human SWI/SNF or BRG1 remodeling complex is particularly important with clear roles in signal transduction, development and cancer. In the presentation I will describe our recent work on the detailed mechanism of action of the BRG1 complex in gene expression and during early development in the mouse. We focus on the contribution that sub-domains in the BRG1 N terminus makes if protein partners outside the normal BRG1 associated Factors (BAFs) to initiate steroid receptor mediated transcription. Studies of the complex during development highlight the roles of individual BAF proteins and their contribution to organogenesis. These findings highlight the intimate connections between chromatin remodeling and epigenetics for normal healthy development. 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 SY21-01. doi:1538-7445.AM2012-SY21-01