tbuckley/cabot-search huggingface dataset:
PTU-061 Human Intestinal Transcriptome Analysis in Inflammatory Bowel Disease
Authors: L Demandt, A Onoufriadis, F Gracio, A Amar, E de Rinaldis, CG Mathew, P Irving, NJ Prescott
Journal: Gut (2016)

<h3>Introduction</h3> Inflammatory Bowel Disease (IBD) is a complex genetic disease characterised by chronic inflammation of the gastro-intestinal tract. Genome-wide association study (GWAS) meta-analysis and replication has identified over 200 genomic regions involved in IBD susceptibility although only a few of the associated single nucleotide polymorphisms (SNPs) directly alter the coding sequence of a gene. In addition, &gt;92 of the IBD-susceptibility loci are known to co-localise with active regulatory elements, suggesting the majority of IBD associated SNPs alter gene expression in some way. Here we employ whole transcriptome sequencing to investigate the role of altered gene expression in intestinal tissue. <h3>Methods</h3> Patients and non-IBD control individuals were recruited after informed consent through endoscopy clinics at Guy’s and St Thomas’ Hospital, London. Whole RNA was extracted from 2–4 colonic biopsies from 104 IBD patients (76 CD, 28 UC) and 24 non-IBD controls and ribo-depleted (Ribo-zero, Illumina). We performed whole RNA sequencing using Illumina TruSeq and HiSeq2500 on pools of 4 indexed RNA libraries across 1–2 lanes. Quality control of sequence reads was performed via FastQC. Subsequent alignment and assembly, quantification and differential expression (DE) analysis of each transcript was performed using Tophat2, Cufflinks, Cuffmerge and EdgeR. <h3>Results</h3> So far a detailed bioinformatics analysis has been carried out on the first 32 whole RNA-seq libraries. We have observed expression above background (FPKM &gt; 1) for approximately 46% of all known transcripts located within known IBD susceptibility loci. DE analysis identified 249 transcripts with significant difference in expression (q &lt; 0.06) between IBD cases and controls, 23 of which were located within 500 Kbp of a known IBD susceptibility locus including <i>HLA-DRB5</i>, <i>MUC19</i>, <i>LRRC7</i> and 4 long non-coding RNAs (lncRNAs). Gene set enrichment analysis (GSEA) on the differentially expressed genes identified 19 functional sets with significant enrichment (FDR &lt; 0.25), of which, 13 were immune response related. Most notably, enrichment was seen in gene sets related to Th1, Th2 immune response pathways, known to be relevant in IBD. <h3>Conclusion</h3> We have generated high coverage whole RNAseq data on intestinal biopsy samples from 128 individuals. We have shown &lt;50% of genes mapping to IBD-associated loci are expressed in these intestinal samples and DE analysis have identified genes of potential interest in IBD pathogenesis. Further bioinformatics analysis of the remaining 96 colonic RNA libraries is ongoing. <h3>Disclosure of Interest</h3> None Declared
Comparison of Steady-State Imatinib (IM) Trough Levels, Clinical Response, and Safety Between Caucasian and Asian Patients with Chronic Lyeloid Leukemia in Chronic Phase (CML-CP) Treated with 400mg and 800mg Daily Doses of IM in the Tyrosine Kinase Inhibitor Optimization and Selectivity (TOPS) Study.
Authors: Dong-Wook Kim, Camille Granvil, Eren Demirhan, John Reynolds, Yu Jin, Yanfeng Wang, Michele Baccarani, Jorge Cortes-Franco, Brian J. Druker, Timothy P. Hughes, François Guilhot
Journal: Blood (2009)
A Phase-II-Study To Evaluate Efficacy and Safety of Imatinib in Eosinophilia-Associated Myeloproliferative Disorders and Idiopathic Hypereosinophilic Syndrome.
Authors: Georgia Metzgeroth, Helena Popp, Christoph Walz, Philipp Erben, Jürgen Mix, Martin C. Müller, Rüdiger Hehlmann, Andreas Hochhaus, Andreas Reiter
Journal: Blood (2006)
SAT0095 Leucine-Rich Alpha2-Glycoprotein Is A Useful Biomarker To Evaluate The Clinical Disease Activities of Rheumatoid Arthritis under Treatments
Authors: Y. Hosono, M. Hashimoto, M. Fujimoto, S. Serada, M. Furu, H. Ito, C. Terao, W. Yamamoto, T. Fujii, T. Mimori, T. Naka
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Acute phase biomarkers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are usually used for the evaluation of the disease activity of rheumatoid arthritis (RA). However, these biomarkers are sometimes not useful in evaluating the disease activity of RA patients in daily clinical practice, because they often become within normal range after the initiation of treatments. Thus, new biomarker which reflects the disease activity of RA under the treatment is required. Leucine-rich-α2-glycoprotein (LRG) is a newly identified biomarker that reflects inflammation and is correlated with the 28-joint Disease Activity Score even in patients treated with IL-6 receptor antagonist. <h3>Objectives</h3> To assess whether serum LRG levels could be a biomarker to evaluate the disease activity of RA under treatments in daily clinical practice. <h3>Methods</h3> Serum LRG levels were measured by enzyme-linked immunoabsorbant assay in 370 consecutive RA patients who were under treatments in our facility in 2012. Disease activity was evaluated by Clinical Disease Activity Index (CDAI) that does not include ESR or CRP as components. Radiological joint destruction was evaluated by modified Total Sharp Score (mTSS). Multivaiate analysis of covariance (MANOVA) was used to assess the association between CDAI and LRG, ESR, CRP levels and the association between mTSS and LRG, ESR, CRP, disease duration, and anti-CCP antibody level. <h3>Results</h3> Among 370 patients, 71% were treated by methotrexate and 29% by biological DMARDs and average CDAI was 7.8±6.2 (low disease activity). After MANOVA analysis, LRG but not ESR or CRP showed the significant correlation with CDAI (LRG; effect size 0.034, p=0.0007, CRP; effect size 0.010, p=0.055, ESR; effect size 0.0053, p=0.18). LRG significantly correlated with the disease activities in RA patients, even when ESR or CRP levels were within normal range. In addition, LRG showed the significant correlation with mTSS as well as disease duration and anti-CCP antibody level (LRG; effect size 0.019, p=0.017, disease duration; effect size 0.769, p&lt;0.001, and anti-CCP antibody; effect size 0.036, p=0.0011), while ESR and CRP did not (ESR; effect size 0.0038, p=0.28, CRP; effect size 0.00073, p=0.64). <h3>Conclusions</h3> LRG is useful marker to evaluate the disease activity and to estimate the joint damage of RA patients under treatments in daily clinical practice independent of CRP and ESR levels. <h3>Disclosure of Interest</h3> None declared
Bortezomib-Based Induction Therapy Induces Better Responses and Outcomes of Autologous Stem Cell Transplantation in Newly Diagnosed Patients with Multiple Myeloma: The Results of Korean Multiple Myeloma Working Party Retrospective Study, KMM84
Authors: Seok Jin Kim, Kihyun Kim, Jae Hoon Lee, Min Kyoung Kim, Jae-Yong Kwak, Hun-Mo Ryoo, Cheolwon Suh, Sung-Soo Yoon, Moon-Hee Lee, Yeung-Chul Mun, Hyo-Jin Lee, Chang-Ki Min, Jin Seok Kim, Hwi-Joong Yoon
Journal: Blood (2008)
AB0732 Persistence on Treatment and Optimization among Anti-TNFα Agents in Psoriatic Arthritis Patients in Clinical Practice
Authors: J. Pinto-Tasende, E. Alonso, C. Bejerano, J. Gromaz, B. Acasuso, C. Fernandez-Lopez, N. Oreiro, M. Acasuso, J. De Toro, F. Blanco
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> As in rheumatoid arthritis some patients with psoriatic arthritis (PsA) can be refractory to anti-TNF-α therapy, may lose responsiveness, or develop drug intolerance over time and a switch to another TNFα antagonist can often restore therapeutic response. <h3>Objectives</h3> The study aim was to determine treatment persistence and to identify causes of discontinuation in PsA patients in clinical practice. <h3>Methods</h3> Patients with PsA (classified on the basis of CASPAR criteria) and treated with blockers of the TNF-α (following EULAR recommendations) adalimumab (ADA), etanercept (ETA), golimumab (GOL), infliximab (INF) or certolizumab (CTZ), between 2011–2015, were retrospectively included. Treatment persistence was analyzed and differences between therapies were assessed by means of an analysis of variance model (ANOVA), while a chi-square test was used to evaluate relationships between therapies and causes of treatment discontinuation and the administration of concomitant disease-modifying antirheumatic drugs (DMARDs) among therapies and types of disease. <h3>Results</h3> One hundred and ninety-six patients received: 98 ETA, 63 ADA, 22 GOL, 10 INF and 3 CTZ, with an age mean of 51.7±12.4 years old without differences among groups of therapies (p 0.993), and 111 were men (56.6%). Combination treatment with DMARDs was in 126 patients (64.3%) and no differences were observed among five anti-TNF therapies. One hundred and forty-three patients (73.0%) had persistence in first anti-TNF, mean 61.2 (12.8) months, and by groups was: 84.7% ETA, 60.3% ADA, 59.1% GOL, 70% INF and 66.7% CTZ, p 0.007, without differences among clinical subtypes (p 0.978). Combination therapy with DMARDs was associated with a higher persistence in first anti-TNF, 67.8% vs 55.9%, but without statistical significance (p 0.108). Change of first anti-TNF occurred in 53 patients: failure to treatment was in 33 patients (62.3%) and discontinuation by adverse event was in 20 patients (37.7%) without differences among groups (p 0.535). Discontinuation by failure to treatment has happen with a mean of 66.1 (43.1) months and by adverse event in 53.4 (30.2) months (p0.235). In 68 (34.7%) patients without clinical activity dosing interval of treatment was increased and we have not observed differences among the groups (p 0.265). <h3>Conclusions</h3> In this cohort, anti-TNFα therapy was associated with high persistence at first anti-TNF therapy, mainly etanercept. Switching to another anti-TNF-α agent occurred in a quarter of patients, when treatment was suspended because of failure to response or an adverse event. Furthermore, treatment was optimized in one third of patients. <h3>Disclosure of Interest</h3> None declared
ThaDD Regimen for Patients with Multiple Myeloma Aged ≥ 65 Years: An Update of the First 50 Patients Enrolled
Authors: Massimo Offidani, Laura Corvatta, Claudia Polloni, Maria-Novella Piersantelli, Silvia Gentili, Piero Galieni, Giuseppe Visani, Francesco Alesiani, Massimo Catarini, Marino Brunori, Arduino Samori, Maurizio Burattini, Riccardo Centurioni, Mario Ferranti, Luciano Giuliodori, Marco Candela, Anna Mele, Monica Marconi, Attilio Olivieri, Pietro Leoni
Journal: Blood (2008)
C1q-TNF-Related Protein-9 Promotes Cardiac Hypertrophy and Failure
Authors: Mahesh Appari, Astrid Breitbart, Florian Brandes, Malgorzata Szaroszyk, Natali Froese, Mortimer Korf-Klingebiel, Mona Malek Mohammadi, Andrea Grund, Gesine M. Scharf, Honghui Wang, Carolin Zwadlo, Daniela Fraccarollo, Ulrike Schrameck, Mona Nemer, G. William Wong, Hugo A. Katus, Kai C. Wollert, Oliver J. Müller, Johann Bauersachs, Joerg Heineke
Journal: Circulation Research (2016)

Rationale: Myocardial endothelial cells promote cardiomyocyte hypertrophy, possibly through the release of growth factors. The identity of these factors, however, remains largely unknown, and we hypothesized here that the secreted CTRP9 (C1q-tumor necrosis factor–related protein-9) might act as endothelial-derived protein to modulate heart remodeling in response to pressure overload. Objective: To examine the source of cardiac CTRP9 and its function during pressure overload. Methods and Results: CTRP9 was mainly derived from myocardial capillary endothelial cells. CTRP9 mRNA expression was enhanced in hypertrophic human hearts and in mouse hearts after transverse aortic constriction (TAC). CTRP9 protein was more abundant in the serum of patients with severe aortic stenosis and in murine hearts after TAC. Interestingly, heterozygous and especially homozygous knock-out C1qtnf9 (CTRP9) gene-deleted mice were protected from the development of cardiac hypertrophy, left ventricular dilatation, and dysfunction during TAC. CTRP9 overexpression, in turn, promoted hypertrophic cardiac remodeling and dysfunction after TAC in mice and induced hypertrophy in isolated adult cardiomyocytes. Mechanistically, CTRP9 knock-out mice showed strongly reduced levels of activated prohypertrophic ERK5 (extracellular signal-regulated kinase 5) during TAC compared with wild-type mice, while CTRP9 overexpression entailed increased ERK5 activation in response to pressure overload. Inhibition of ERK5 by a dominant negative MEK5 mutant or by the ERK5/MEK5 inhibitor BIX02189 blunted CTRP9 triggered hypertrophy in isolated adult cardiomyocytes in vitro and attenuated mouse cardiomyocyte hypertrophy and cardiac dysfunction in vivo, respectively. Downstream of ERK5, we identified the prohypertrophic transcription factor GATA4, which was directly activated through ERK5-dependent phosphorylation. Conclusions: The upregulation of CTRP9 during hypertrophic heart disease facilitates maladaptive cardiac remodeling and left ventricular dysfunction and might constitute a therapeutic target in the future.
Hippo signaling interactions with Wnt/β-catenin and Notch signaling repress liver tumorigenesis
Authors: Wantae Kim, Sanjoy Kumar Khan, Jelena Gvozdenovic-Jeremic, Youngeun Kim, Jason Dahlman, Hanjun Kim, Ogyi Park, Tohru Ishitani, Eek-hoon Jho, Bin Gao, Yingzi Yang
Journal: Journal of Clinical Investigation (2016)

Malignant tumors develop through multiple steps of initiation and progression, and tumor initiation is of singular importance in tumor prevention, diagnosis, and treatment. However, the molecular mechanism whereby a signaling network of interacting pathways restrains proliferation in normal cells and prevents tumor initiation is still poorly understood. Here, we have reported that the Hippo, Wnt/β-catenin, and Notch pathways form an interacting network to maintain liver size and suppress hepatocellular carcinoma (HCC). Ablation of the mammalian Hippo kinases Mst1 and Mst2 in liver led to rapid HCC formation and activated Yes-associated protein/WW domain containing transcription regulator 1 (YAP/TAZ), STAT3, Wnt/β-catenin, and Notch signaling. Previous work has shown that abnormal activation of these downstream pathways can lead to HCC. Rigorous genetic experiments revealed that Notch signaling forms a positive feedback loop with the Hippo signaling effector YAP/TAZ to promote severe hepatomegaly and rapid HCC initiation and progression. Surprisingly, we found that Wnt/β-catenin signaling activation suppressed HCC formation by inhibiting the positive feedback loop between YAP/TAZ and Notch signaling. Furthermore, we found that STAT3 in hepatocytes is dispensable for HCC formation when mammalian sterile 20–like kinase 1 and 2 (Mst1 and Mst2) were removed. The molecular network we have identified provides insights into HCC molecular classifications and therapeutic developments for the treatment of liver tumors caused by distinct genetic mutations.
Concordance of Assays Designed for the Quantitation of JAK2 1849G&amp;gt;T (V617F): A Multi-Centre Study.
Authors: Eric Lippert, François Girodon, Emma Hammond, Serge Carillo, Céline Richard, Boris Fehse, Mirjam Hermans, Ian James, Jaroslav Jelinek, Christophe Marzac, Marina Migeon, Daniela Pietra, Josef T. Prchal, N. Scott Reading, Marta Sobas, Valérie Ugo, Radek C. Skoda, Sylvie Hermouet
Journal: Blood (2007)
US adults are more likely to have poor health than those in 10 similar countries, survey finds
Authors: Michael McCarthy
Journal: BMJ (2016)

US adults are more likely to skip care because of cost, to struggle to afford basic necessities, and to have poorer health than adults living in 10 other high income countries, a survey has found.1

The Commonwealth Fund conducted the survey, which was based on interviews with nearly 27 000 adults in Australia, Canada, France, Germany, the Netherlands, New Zealand, Norway, Sweden, Switzerland, the United Kingdom, and the United States. The results were published on 16 November in the journal Health Affairs .1

The survey is the latest of a series of international surveys conducted …
Induction of Cyclooxygenase-2 by chemotherapy in non-small cell lung cancer cells involves p53
Authors: Emanuela Pinto, Mariana Duarte, Luciene Schluckebier, Elizangela Pontes, Joyce Moraes, Carlos Ferreira
Journal: Cancer Research (2007)

1255  Introduction: Lung cancer is the leading cause of cancer death. NSCLC accounts for over 80% of newly diagnosed cases. NSCLC is extremely resistant to chemotherapeutic agents, such as cisplatin and paclitaxel. High expression of the inflammatory enzyme Cyclooxygenase-2 (Cox-2) has been shown to inhibit chemotherapy-induced apoptosis, but little is known about Cox-2 regulation after drug treatment. Recent literature indicates the tumor suppressor protein p53 as an important regulator of Cox-2. Therefore, TP53 status could change tumor sensitivity to chemotherapy through induction of the anti-apoptotic protein Cox-2. It has also been proposed that specific inhibition of Cox-2 may increase the citotoxic effect of chemotherapeutic agents. Objectives: The main objective of this work is to analyze the effect of chemotherapy on the expression of Cox-2, according to TP53 status. Methods: We used NSCLC cell lines with different TP53 mutational status: wild type (H460 and A549), mutant (ACC-LC-94) and null (ACC-LC-319 and Calu-1). Cells were treated with cisplatin or paclitaxel and/or Cox-2 selective inhibitor (celecoxib) for 48h and 72h. MTT assay was used to determine drug effect on cell proliferation, with determination of IC50 for each cell line. Cox-2 mRNA expression was analyzed by semi-quantitative RT-PCR in parallel with quantitative real-time RT-PCR. Protein expression of COX-2, p53 and p21 (p53-target gene) was investigated by western blotting, using β-actin as an endogenous control. To detect Cox-2 activity, amounts of PGE2 released by cells were measured in the culture medium by enzyme immunoassay. RNA interference was used to silence p53 expression and evaluate its impact on Cox-2 mRNA and protein expression after drug treatment. Results: Rapid accumulation of p53 protein was observed after cisplatin treatment of A549 and H460 cells, followed by induction of p21 and Cox-2 proteins after 12hs and 24hs, respectively. p21 and Cox-2 expressions were not detected or changed after chemotherapy treatment of cells containing an inactive form of p53. RT-PCR analysis has shown a 10-fold increase in COX-2 mRNA after cisplatin treatment of A549 and H460. For paclitaxel treatment, a 4- and 7-fold increase in COX-2 expression was observed in H460 and A549, respectively. PGE2 production was also enhanced in A549 and H460 cells after cisplatin treatment. For paclitaxel treatment, this effect was seen only in the A549 cell line. After silencing of wild-type p53 expressed in A549 cells, chemotherapy was no longer able to induce Cox-2 mRNA and protein expression. Conclusions: Overall, the results showed that chemotherapy clearly induced Cox-2 expression, but only in cells containing an active p53. Silencing of p53 has confirmed its involvement in chemotherapy induction of Cox-2. These data may have therapeutic implications in the selection of patients and strategy for future Cox-2 inhibition trials.
Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification
Authors: E.J. Giamarellos-Bourboulis, T. Tsaganos, I. Tsangaris, M. Lada, C. Routsi, D. Sinapidis, M. Koupetori, M. Bristianou, G. Adamis, K. Mandragos, G.N. Dalekos, I. Kritselis, G. Giannikopoulos, I. Koutelidakis, M. Pavlaki, E. Antoniadou, G. Vlachogiannis, V. Koulouras, A. Prekates, G. Dimopoulos, A. Koutsoukou, I. Pnevmatikos, A. Ioakeimidou, A. Kotanidou, S.E. Orfanos, A. Armaganidis, C. Gogos
Journal: Clinical Microbiology and Infection (2016)
Is R-CODOX-M/IVAC Inferior to Other Regimens in Burkitt’s Lymphoma: A Single Center Experience
Authors: Erden Atilla, Ugur Sahin, Pinar Ataca, Atilla Uslu, Ekin Kircali, Berna Atesagaoglu, Gultekin Pekcan, Mustafa Merter, Mehmet Gunduz, Mehmet Ozen, Sinem Civriz Bozdag, Selami Kocak Toprak, Pervin Topcuoglu, Onder Arslan, Taner Demirer, Hamdi Akan, Gunhan Gurman, Meral Beksac, Osman Ilhan, Nahide Konuk, Muhit Ozcan
Journal: Blood (2014)
Serum Amyloid A (SAA) as a Molecular Marker for Pre-Engraftment Immune Reactions (PIR) after Cord Blood Transplantation.
Authors: Yuriko Morita-Hoshi, Yuji Heike, Yuka Ohsaki, Mieko Shiwa, Kazuhiro Masuoka, Atsushi Wake, Shuichi Taniguchi, Kensei Tobinai, Yoichi Takaue
Journal: Blood (2006)
Dynamics of Molecular Response in Patients (pts) with Acute Myeloid Leukemia (AML) Withy Core Binding Factor (CBF) Abnormalities Treated with High-Dose Cytarabine Regimen
Authors: Elias J. Jabbour, Hagop M. Kantarjian, Yin Cameron, Farhad Ravandi, Jorge E. Cortes, Guillermo Garcia-Manero, Hady Ghanem, Tapan M. Kadia, Stefan Faderl, Susan O'Brien, Michael S Mathisen, Mark Brandt, Naveen Pemmaraju, Deborah A. Thomas, Joyce Bass, Gautam Borthakur
Journal: Blood (2012)
Roles of CD19 Molecules That Suppress Proliferation and Induce Apoptosis in Human Myeloma Cells.
Authors: Xu Zheng, Hideaki Ishikawa, Naohiro Tsuyama, Saeid Abroun, Shangqin Liu, Fu-Jun Li, Ken-ichiro Otsuyama, Zi Ma, Yasuko Maki, Msanori Obata, Michio M. Kawano
Journal: Blood (2004)
Deletions of Chromosomes 6q and 13q, and Trisomy 4 Are the Most Common Cytogenetic Abnormalities in Waldenstrom Macroglobulinemia. Preliminary Results of a Multicentric Study.
Authors: Florence Nguyen-Khac, Elise Chapiro, Sarah Mould, Carole Barin, Agnes Daudignon, Nathalie Gachard, Stéphanie Struski, Catherine Henry, Dominique Penther, Hossein Mossafa, Joris Andrieux, Bernard Perissel, Virginie Eclache, Chrystele Bilhou-Nabera, Isabelle Luquet, Christine Terre, Laurence Baranger, Francine Mugneret, Marie-Jose Gregoire, Jean Chiesa, Sylvie Ramond, Marie-Joelle Mozziconacci, Evelyne Callet-Bauchu, Helene Merle-Beral, Veronique Leblond
Journal: Blood (2008)
P07.22 Kinetic modeling and graphical analysis of 18F-fluoromethylcholine (FCho), 18F-fluoroethyltyrosine (FET) and 18F-fluorodeoxyglucose (FDG) PET for the discrimination between high-grade glioma and radiation necrosis in rats
Authors: J. Bolcaen, K. Lybaert, L. Moerman, B. Descamps, K. Deblaere, T. Boterberg, J. Kalala, F. De Vos, C. Vanhove, I. Goethals
Journal: Neuro-Oncology (2016)
Should healthy people take a vitamin D supplement in winter months?
Authors: Tim D Spector, Louis Levy
Journal: BMJ (2016)

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