tbuckley/cabot-search huggingface dataset:
Abstract 1296: Identification of human nuclear factor 1 (NF-1) as a potential transcription factor which regulates the gene expression of Sulfotransferase isoform 1A1 (SULT1A1) in human breast cancer
Authors: Aiwei Yao-Borengasser, Xinfeng Yu, Ishwori B. Dhakal, Vineetha K. Edavana, Suzanne Williams, Susan A. Kadlubar
Journal: Cancer Research (2012)

Abstract Sulfotransferase isoform 1A1 (SULT1A1) plays a central role in drug metabolism. SULT1A1 expression is tissue specific, with little to no expression in normal breast epithelia but plentiful protein expression in most breast tumors. Revelation of the regulators of SULT1A1 expression in breast tissues is important in predicting breast tissue response to therapeutic agents that are substrates of SULT1A1, particularly tamoxifen which can be used for both breast cancer treatment and chemoprevention. In order to identify the appropriate transcription factors that regulate the gene expression of SULT1A1, we performed transcription factor (TF) Activation Profiling Plate Array assay (Signosis, Sunnyvale, CA) in normal breast MCF10A cells and breast cancer ZR-75 cells. TF activation profile differences in MCF10A cells and ZR-75 cells were quantitatively analyzed and compared. Out of 48 TFs DNA-binding activities allowed per plate, 18 TFs’ activities were at least 1.5 fold higher in ZR75 cells compared to that of in MCF10A cells. Matching of the 18 TFs to the possible TF binding consensus sequences in SULT1A1, which were predicted by software Alibaba 2.0, was performed and we found that nuclear factor 1 (NF-1) and GATA transcription factor 1 (GATA-1) were putative transcription factors involved in the regulation of SULT1A1 expression. To further study the relationship between NF-1 and GATA-1 and SULT1A1, we measured mRNA levels of NF-1, GATA-1, and SULT1A1 using total RNA isolated from 97 human liver samples. The liver samples were obtained from 43 female and 54 male health subjects (age range 26-102 year, mean 59.0 years). The real-time RT-PCR results showed that only NF-1, not GATA-1, mRNA level showed significant correlation with SULT1A1 mRNA level (r=0.64, p&amp;lt;0.0001). Therefore, we have identified that NF-1 as a new strong candidate for SULT1A1 gene expression regulation. The finding has laid foundation for the study on the effect of NF-1 on SULT1A1 gene expression, which could provide a mechanistic explanation for the differential expression of SULT1A1 between normal breast tissue and breast tumors. 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 1296. doi:1538-7445.AM2012-1296
Low Levels of High-Affinity Growth Hormone-Binding Protein in African Pygmies
Authors: Gerhard Baumann, Melissa A. Shaw, Thomas J. Merimee
Journal: New England Journal of Medicine (1989)

The cause of growth hormone resistance and short stature in African Pygmies is unknown. Low levels of insulin-like growth factor I that fail to respond to growth hormone suggest a possible deficiency of growth hormone receptors. The high-affinity growth hormone-binding protein is a fragment of the growth hormone receptor and may be an indicator of the number of receptors in tissues. We measured growth hormone-binding activity in plasma from 20 pygmies and 12 control subjects (7 white Americans and 5 non-Pygmy black Africans of normal stature). Growth hormone binding to the high-affinity binding protein was significantly reduced in the Pygmies as compared with the controls (mean ±SD, 6.50±2.33 percent vs. 12.95±3.95 percent bound per 160 μl of plasma; P<0.001); however, there was substantial overlap between the values for Pygmies and controls. Growth hormone binding to the low-affinity binding protein was similar in Pygmies and control subjects. We conclude that Pygmies have low levels of high-affinity growth hormone-binding protein in their plasma, which may indicate a reduced number of growth hormone receptors in their tissues. This finding may help explain the resistance to growth hormone in Pygmies, but there may be additional reasons, related to the receptors or not, for their short stature. (N Engl J Med 1989; 320:1705–9.)
AB0067 IL-17F Gene Polymorphism Correlated with Longer Disease Duration of Rheumatoid Arthritis Patients
Authors: K. Demircan, Z.S. Yasar, S. Yüksel, R. Hasgul, H. Cakirbay, O. Cemeroglu, B. Yanik, E.U. Aslan, K. Senel
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is an autoimmune disease that results in chronic systemic inflammatory disorder that may affect many tissues and organs but principally attacks synovial joints. Interleukin-17F (IL-17) is a proinflammatory cytokine and IL17 F gene is an excellent candidate for chronic inflammatory cytokine. <h3>Objectives</h3> To investigate the potential association between rheumatoid arthritis and IL17 F gene polymorphism. <h3>Methods</h3> We investigated the potential association between rheumatoid arthritis and IL17 F gene polymorphism. 185 RA patients and 50 healthy control subjects were used. We compare IL17 F gene polymorphism with disease activity score, DAS28, Tender joints, Swollen joints, CRP. <h3>Results</h3> The polymorphisms of the IL-17F gene were not correlated with susceptibility to RA patients. However, the IL-17F variant was associated with parameters of disease activity, such as number of tender joints, DAS-28-CRP. Moreover, our findings have shown that IL-17F gene polymorphism may be correlated with longer disease duration in patients with RA. <h3>Conclusions</h3> Our results showed the relationship between IL-17F gene polymorphisms and severity of RA. <h3>References</h3> Seiderer J, Elben I, Diegelmann J et al. Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in activated Crohn9s disease and analysis of the IL-17F p.His161Arg polymorphism in IBD. Inflamm Bowel Dis 2008;14:437–45. Ramsey CD, Lazarus R, Camargo CA Jr, Weiss ST, Celedo9n JC. Polymorphisms in the interleukin 17F gene (IL17F) and asthma. Genes Immun 2005;6:236–41 Paradowska A, Maśliński W, Grzybowska-Kowalczyk A, Łacki J. The function of interleukin 17 in the pathogenesis of rheumatoid arthritis. Arch Immunol Ther Exp 2007;55:1–6. Moseley TA, Haudenschild DR, Rose L, Reddi AH. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev 2003;14:155–74. A. Paradowska-Gorycka, E. Wojtecka-Lukasik, J. Trefler, B. Wojciechowska, J.K. Lacki, S. Maslinski. Association between IL-17F Gene Polymorphisms and Susceptibility to and Severity of Rheumatoid Arthritis (RA). <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5482
Abstract 2983: Nkx3.1 and c-Myc co-regulate shared target genes involved in prostate cancer
Authors: Philip D. Anderson, Sydika A. McKissic, Monica Logan, Meejeon Roh, Omar Franco, Jie Wang, Irina Doubinskaia, Riet van der Meer, Simon Hayward, Christine Eischen, Isam-Eldin A. Eltoum, Sarki A. Abdulkadir
Journal: Cancer Research (2012)

Abstract Cooperativity between oncogenic mutations is recognized as a fundamental feature of malignant transformation, and may be mediated by synergistic regulation of the expression of pro- and anti-tumorigenic target genes. However, the mechanisms by which oncogenic mutations cooperatively regulate downstream target gene expression remain largely unknown. Here we used chromatin immunoprecipitation coupled with massively parallel sequencing (ChIP-seq) and gene expression analyses to identify direct targets of the prostate tumor suppressor Nkx3.1 in the mouse prostate. Our analysis showed that a significant fraction of Nkx3.1 targets are also targets of the oncoprotein c-Myc, suggesting that these two proteins may cooperate in prostate tumorigenesis by directly co-regulating a common set of target genes. Using ChIP, we confirmed binding of Nkx3.1 and c-Myc to the regulatory regions of shared target genes in mouse and human prostate epithelial cells. In conditional mutant mice, loss of Nkx3.1 cooperates with concurrent overexpression of c-MYC to promote prostate tumorigenesis. Furthermore, dysregulation of the shared NKX3.1/c-MYC target gene set was associated with relapse in human prostate tumors. We propose that co-regulation of target gene expression by oncogenic/tumor suppressor transcription factors may represent a general mechanism for the cooperativity of oncogenic mutations during tumorigenesis. 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 2983. doi:1538-7445.AM2012-2983
Abstract 335: Human neuroblastoma cells undergo TGF-beta mediated mesenchymal change in the transition to drug resistance
Authors: Jessica A. Naiditch, Sandra Clark, Timothy B. Lautz, Chunfa Jie, Mary Beth Madonna, Fei Chu
Journal: Cancer Research (2012)

Abstract Background: Hypoxia inducible factor 1-alpha (HIF1-alpha) is overexpressed in doxorubicin-resistant neuroblastoma cell lines relative to drug sensitive parental cells lines, and has been implicated in inducing epithelial to mesenchymal transition (EMT). We hypothesized that the transition of human neuroblastoma cells from a drug-sensitive to drug-resistant phenotype involves mesenchymal change. Methods: A doxorubicin resistant (DoxR) human neuroblastoma cell line was generated by incubating parental wild type (WT) SK-N-Be(2)C cells in stepwise concentrations of doxorubicin. Cells were deemed resistant after surviving in a concentration of drug approximately 2 Log above the wild type IC50, confirmed by MTT colorimetric survival assay. Cell migration and capacity for invasion were assayed using the scratch test and Matrigel invasion culture system. EMT pathway related genes differentially expressed in the DoxR cells relative to the parental (WT) lines were analyzed using the Ilumina Human HT-12 v4 Expression Beadchip. Genes of interest with a fold change in expression &amp;gt;1.5 and an adjusted p &amp;lt; 0.1 are reported. Quantitative RT-PCR and western blot analysis were used to confirm the results. Results: Western blot confirmed that HIF1-alpha was up-regulated in BE(2)C/DoxR cells relative to WT. DoxR cells also demonstrated increased migration and invasion typical of mesenchymal cells. Up-regulation of TGF-beta dependent induction pathways of EMT via RhoA, PI3K, and ILK and via SMADs was seen on microarray pathway analysis in BE(2)C DoxR cells when compared to WT cells. Genes involved in these EMT pathways that were up-regulated in DoxR cells included TGFBRII, the gene encoding TGF beta-receptor II, TGFB3, the gene for TGF beta 3, as well as other genes implicated in TGF-beta signaling, including PAK1, LEF1, SMAD3, ZEB2, and NET1. EMT markers including vimentin (VIM), and slug (SNAI2) were also up-regulated. Interestingly, CDH2, the gene for N-cadherin, and TWIST1 were down regulated in DoxR cells. CDH1, the gene for E-cadherin, and SNAI1, the gene for Snail-1, were not differentially expressed. Conclusions: As SK-BE(2)C human neuroblastoma cell lines acquire drug-resistance, they undergo mesenchymal change via TGF-beta mediated pathways, displaying increased invasion and migration. 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 335. doi:1538-7445.AM2012-335
Are Paranoid Schizophrenics Biologically Different from Other Schizophrenics?
Authors: Steven G. Potkin, H. Eleanor Cannon, Dennis L. Murphy, Richard Jed Wyatt
Journal: New England Journal of Medicine (1978)

Two studies were undertaken to verify the presence of lowered platelet monoamine oxidase activity in chronic schizophrenia. In the first study, a retrospective chart analysis, the mean platelet activity of patients with chronic schizophrenia (7.73+/-0.64 nmol of benzylaldehyde product per 10(8) platelets per hour [S.E.M.]) differed significantly from that of normal controls (12.13+/-0.2, P less than 0.001). Chronic paranoid schizophrenics (4.81+/-0.46) differed significantly from chronic nonparanoid schizophrenics (8.6+/-0.75, P less than 0.03). A separate prospective study confirmed significantly lower values for monoamine oxidase activity in chronic schizophrenic patients diagnosed as paranoid (5.97+/-1.17) or as having secondary paranoid features (6.28+/-0.71) as compared to chronic nonparanoid schizophrenics (9.81+/-0.87, P less than 0.001). Chronic paranoid schizophrenia may be a separate disorder from the other chronic forms of schizophrenia, and this difference may be related, at least in part, to biochemical characteristics.
733 THE APPARENT DIFFUSION COEFFICIENT MAP OF DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING CAN BE USED TO PREDICT RECURRENCE AND SURVIVAL AFTER RADIOFREQUENCY ABLATION FOR HEPATOCELLULAR CARCINOMA
Authors: Y. Mori, H. Tamai, N. Shingaki, K. Moribata, H. Deguchi, K. Ueda, I. Inoue, T. Maekita, M. Iguchi, J. Kato, M. Ichinose
Journal: Journal of Hepatology (2012)
Cobalamin and Osteoblast-Specific Proteins
Authors: Ralph Carmel, K.-H. William Lau, David J. Baylink, Sunita Saxena, Frederick R. Singer
Journal: New England Journal of Medicine (1988)

Cobalamin deficiency has well-known hematologic and neurologic effects, but little is known about its other effects. We therefore studied the effect of cobalamin on osteoblast-related proteins. We found that mean (+/- 1 SD) levels of skeletal alkaline phosphatase in the blood were lower in 12 cobalamin-deficient patients (3.89 +/- 2.19 units per liter) than in 5 nondeficient and 5 iron-deficient control subjects (7.55 +/- 3.99 units per liter). The degree of the megaloblastic anemia correlated with the reduction in skeletal alkaline phosphatase levels (r = 0.67, P less than 0.01). With cobalamin therapy, levels of skeletal alkaline phosphatase rose in 11 of the 12 cobalamin-deficient subjects but not in the controls. The cobalamin-deficient patients also had significantly lower osteocalcin levels than the control subjects (1.11 +/- 0.77 vs. 1.84 +/- 0.49 nmol per liter). During cobalamin therapy, these levels rose in the cobalamin-deficient patients but not in the controls. In contrast to the levels of osteoblast-related proteins, hepatic alkaline phosphatase levels were similar in the patients and controls and were usually unaffected by cobalamin therapy. In vitro studies of calvarial cells from chicken embryos showed that their alkaline phosphatase content was cobalamin-dependent, thus supporting our in vivo observations in humans. Our findings suggest that osteoblast activity depends on cobalamin and that bone metabolism is affected by cobalamin deficiency, but we do not yet know whether cobalamin deficiency produces clinically important bone disease.
Abstract 3065: Is cytology a suitable source of NSCLC tumor material for EGFR mutation testing
Authors: Gillian L. Dalgliesh, Emma Donald, Rashmita Sahoo, Geeta Patil, Meena Augustus, Rose McCormack, Gillian Ellison
Journal: Cancer Research (2011)

Abstract Somatic mutations in the epidermal growth factor receptor (EGFR) affect non small cell lung cancer (NSCLC) sensitivity to the EGFR tyrosine kinase inhibitor gefitinib. In many countries, prospective testing of NSCLC patients for EGFR mutations is required to determine patient suitability for gefitinib. Mutation profiling is usually performed on DNA extracted from tumour biopsy samples, however the acquisition of biopsy material from NSCLC patients is often difficult and, in some cases is not available, as diagnosis is routinely made by other means. Diagnostic cytology samples, obtained by fine needle aspiration (FNA), may provide an additional source of tumour material for molecular analysis. The aims of this project were to assess the suitability of FNA for EGFR mutation testing and optimisation of DNA extraction and mutation detection methods suitable for analysis of FNA material. FNA smears of 3 human cell lines, obtained from mouse xenografts, were used to optimise DNA extraction methods. DNA was extracted from diagnostic FNA smears or paraffin embedded FNA derived cells, from 25 NSCLC patients of Indian origin, using the optimised protocols. Following successful DNA extraction from all patient samples, EGFR mutation status was determined by both DNA sequencing and using the therascreen EGFR Mutation Test Kit (L858R and exon 19 deletion mutations only). Twelve of the 25 patients harboured an EGFR mutation. For this sample type, the therascreen EGFR Mutation Test Kit was more effective at identifying mutation positive patients with only 4 of 12 detected mutations also evident by DNA sequencing. DNA extracted using a spin column based kit and quantified by real time PCR prior to performing molecular analysis gave the most robust, reproducible results. In conclusion, these data suggest that diagnostic FNA smears or cell blocks are suitable for assessing EGFR mutation status of NSCLC patients and may prove a useful source of tumour material when biopsies are unavailable. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3065. doi:10.1158/1538-7445.AM2011-3065
Unraveling Obamacare — Can Congress and the Supreme Court Undo Health Care Reform?
Authors: Jonathan Oberlander
Journal: New England Journal of Medicine (2014)

Interview with Prof. Jonathan Oberlander on what the midterm election results mean for the future of the Affordable Care Act. (08:23)Download As long as Obamacare's namesake is in the Oval Office, congressional repeal of the Affordable Care Act remains a fantasy. Could Republicans overturn Obamacare after Obama's presidency ends in 2017, or could a Supreme Court decision seriously damage the law?
Absence of Dystrophin and Utrophin in a Boy with Severe Muscular Dystrophy
Authors: Marie-Pierre Chevron, Bernard Echenne, Jacques Demaille
Journal: New England Journal of Medicine (1994)

To the Editor: Utrophin is an autosomally inherited protein encoded by chromosome 6 that is homologous to dystrophin and localized in normal adult muscle exclusively at neuromuscular junctions.1 No clinical disorder is recognized that relates to altered utrophin expression. Rather, utrophin levels have always been reported to increase in the absence of dystrophin in Duchenne's muscular dystrophy1–4 (and unpublished data) or of adhalin (50-kd dystrophin-associated glycoprotein) in severe autosomal recessive muscular dystrophy of childhood2 (and unpublished data). We describe a patient with defects of both dystrophin and utrophin in muscle fibers. Clinically, the patient had early-onset Duchenne's muscular dystrophy. . . .
FRI0185 Tofacitinib versus biologic treatments with and without methotrexate in patients with active rheumatoid arthritis who have had an inadequate response to traditional disease modifying anti-rheumatic drugs - a network meta-analysis
Authors: M.C. Vieira, G.V. Wallenstein, J.D. Bradley, D. Gruben, T. Koncz, S.H. Zwillich, J.P. Jansen
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Tofacitinib (CP-690,550) is a novel, oral Janus kinase inhibitor that is being investigated as a targeted immunomodulator and disease-modifying therapy in rheumatoid arthritis (RA). <h3>Objectives</h3> A network meta-analysis to evaluate the efficacy and safety of tofacitinib 5 and 10 mg BID relative to biologic disease-modifying anti-rheumatic drugs (DMARDs) in the treatment of RA patients who have shown an inadequate response to DMARDs (DMARD-IR), based on available randomised controlled trials (RCTs). <h3>Methods</h3> Thirty-three RCTs evaluating tofacitinib and various biologic DMARDs, dosed as monotherapy or in combination with methotrexate (MTX) or another DMARD, were identified through a systematic literature search. Individual study efficacy data, based on American College of Rheumatology (ACR) responses at Mo 3 and 6, were combined with network meta-analyses. Comparisons of safety were based on rates of treatment withdrawal due to adverse events (AEs). <h3>Results</h3> Both as monotherapy and in combination with MTX, tofacitinib 5 and 10 mg BID showed ACR responses comparable to currently available tumour necrosis factor inhibitors and tocilizumab at Mo 3 (see Table) and 6. Furthermore, in this analysis tofacitinib is at least as efficacious as abatacept, anakinra, and rituximab. Withdrawal rates from trials due to AEs were comparable. <h3>Conclusions</h3> Based on analyses of available RCTs, tofacitinib has similar efficacy in improving signs and symptoms as biologic DMARDs for DMARD-IR patients. Further analyses are needed to explore the impact of factors that may impact the magnitude of the placebo response and confound comparative treatment effects in treatment of RA. Impact of factors that confound comparative treatment effects in treatment of RA needs to be explored (e.g. starting MTX dose, duration and number of prior DMARDs). <h3>Disclosure of Interest</h3> M. Vieira Consultant for: Pfizer Inc, G. Wallenstein Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Bradley Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, D. Gruben Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, T. Koncz Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, S. Zwillich Shareholder of: Pfizer Inc, Employee of: Pfizer Inc, J. Jansen Consultant for: Pfizer Inc
Dietary Intake of Marine n-3 Fatty Acids, Fish Intake, and the Risk of Coronary Disease among Men
Authors: Alberto Ascherio, Eric B. Rimm, Meir J. Stampfer, Edward L. Giovannucci, Walter C. Willett
Journal: New England Journal of Medicine (1995)

It has been hypothesized that a diet containing n-3 fatty acids from fish reduces the risk of coronary heart disease, but few large epidemiologic studies have examined this question.
GENDER DIFFERENCES IN RISK OF STROKE IN PATIENTS WITH RESTLESS LEGS SYNDROME
Authors: Zoe Heis, Beneet Pandey, Susan Olet, Samian Sulaiman, Saagar Pamulapati, Mary Meyer, Lynda Daley Barsch, Michael N. Katzoff, A. Jamil Tajik, Arshad Jahangir
Journal: Journal of the American College of Cardiology (2016)