tbuckley/cabot-search huggingface dataset:
Abstract 5697: Cellular iron depletion weakens isothiocyanate-induced HO-1 upregulation
Authors: George Loo
Journal: Cancer Research (2010)

Abstract Heme oxygenase-1 (HO-1) is an important cytoprotective gene, whose expression is known to be elevated in various carcinomas. Also, overexpression of HO-1 is known to inhibit apoptosis particularly in cancer cells. Interestingly, exposing cancer cells to certain chemopreventive agents such as isothiocyanates causes induction of HO-1, perhaps as an attempt by the cells to help them survive the stressful situation. However, it is not completely known what nutritive factors or related components in cancer cells influence HO-1 induction as caused by isothiocyanates. Thus, the aim was to test the hypothesis that adequate iron is needed to enable cancer cells to optimally express HO-1 when induced by isothiocyanates. In HCT-116 human colon adenocarcinoma cells, phenethylisothiocyanate and sulforaphane increased expression of HO-1 and also heme oxygenase activity. However, cells made iron-deficient with the iron chelator, desferrioxamine (DFO), and then exposed to isothiocyanates had much lower heme oxygenase activity. This suppressive effect of DFO on isothiocyanate-mediated induction of heme oxygenase activity was in association with repression of HO-1 protein and mRNA expression. The suppression by DFO of isothiocyanate-induced HO-1 upregulation was reversed upon replenishing the iron-deficient cells with the missing iron. Additionally, it was found that thiol antioxidants (glutathione and N-acetylcysteine) inhibited isothiocyanate-induced HO-1 upregulation, implying that the HO-1 upregulation involved an oxidant signaling pathway. Indeed, NADPH oxidase (NOX) inhibitors, namely, diphenyleneiodonium (DPI) and apocynin, and a superoxide scavenger (Tiron) inhibited isothiocyanate-induced upregulation of HO-1 as well. DPI was the most potent and also inhibited nuclear translocation of redox-sensitive Nrf-2, which is known to activate the HO-1 gene. These findings suggest the possibility that adequate amounts of iron, which at the atomic level can serve as the pivotal element of heme in NOX, must be present in the cells to permit what appears to be NOX-dependent upregulation of HO-1 by isothiocyanates. It is concluded that iron-deficient HCT-116 cells are less able to increase expression of cytoprotective HO-1 when exposed to isothiocyanates, which may make the cancer cells more susceptible to killing. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5697.
Case 1-2011
Authors: Adolf W. Karchmer, Thomas E. MacGillivray, Terrance T. Healey, James R. Stone
Journal: New England Journal of Medicine (2011)

A 35-year-old man was admitted to the hospital because of fever, bacteremia, and a mass in the left atrium. Two weeks before admission, fever and shaking chills developed. A transesophageal echocardiogram showed a mass that was attached to the nonseptal side of the left atrium.
Homozygous Methylenetetrahydrofolate Reductase C677T Mutation and Male Infertility
Authors: Guntram Bezold, Monika Lange, Ralf Uwe Peter
Journal: New England Journal of Medicine (2001)

To the Editor: Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. The C677T in the gene that encodes MTHFR decreases the activity of the enzyme by 35 percent in persons who are heterozygous for the mutation and by 70 percent in those who are homozygous.1 The prevalence of the homozygous form is estimated to be between 5 percent and 10 percent. One study showed an increase in sperm count and motility after three months of treatment with folinic acid.2 By determining the frequency of the MTHFR C677T mutation, it may be possible to identify patients who have a . . .
P424Short-term ACE Inhibition upregulates cardiac expression of SERCA2a and protects against ventricular arrhythmias in healthy rats:
Authors: P Kruzliak, M Matus, D Kucerova, K Turcekova, J Kyselovic, P Krenek, U Kirchhefer, FU Muller, P Boknik, J Klimas
Journal: Cardiovascular Research (2014)

Introduction: Chronic angiotensin converting enzyme inhibitor (ACEIs) treatment can suppress arrhythmogenesis. To examine whether the effect is more immediate and independent of suppression of pathological remodelling, we tested the antiarrhythmic effect of short-term ACE inhibition in healthy normotensive rats.
Abstract LB-518: Amplification and activation of EGFR wild-type mediates invasion of human glioblastoma in vivo
Authors: Krishna M. Talasila, Anke Soentgerath, Philipp Euskirchen, Gro V. Rosland, Jian Wang, Peter C. Huszthy, Lars Prestegarden, Kai Ove Skaftnesmo, Per Øystein Sakariassen, Eskil Eskilsson, Olivier Keunen, Narve Brekka, Ingrid Moen, Janice Nigro, Olav Vintermyr, Morten Lund-Johansen, Sverrre J. Mørk, Per Øyvind Enger, Rolf Bjerkvig, Hrvoje Miletic
Journal: Cancer Research (2012)

Abstract Glioblastoma (GBM) is the most aggressive form of primary brain tumors with a median survival of 15 months. Although angiogenesis is one of the main features of GBMs, non-angiogenic tumor infiltration into brain parenchyma still is the major challenge for therapy. Tumor cells can migrate very far from the main tumor mass and the invasive pattern of tumor subpopulations has not been characterized properly. Epidermal growth factor receptor (EGFR) gene amplification is one of the major mutations of primary GBMs, where multiple copies of the wild-type EGFR gene are present as double minutes. Although studies have proposed a role for EGFR gene amplification in tumor development, the function of EGFR in vivo is not characterized properly mainly due to inefficient tumor models. Here, we report a key role for EGFR wild-type in tumor invasion. In a human GBM xenograft model, we show that tumor cells with EGFR amplification and expression are highly invasive and non-angiogenic. By blocking EGFR activation using Cetuximab and a dominant-negative approach, we show that maintenance of the non-angiogenic, invasive growth pattern is dependent on EGFR function and that downregulation of its activity leads to angiogenic tumor growth. As EGFR amplification and expression is present in 40-60% of GBMs, our results might implicate that activation of EGFR wild-type is one of the major mechanisms of glioblastoma invasion in vivo. 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-518. doi:1538-7445.AM2012-LB-518
SAT0081 Clinical predictors of response to methotrexate treatment in DMARD naÏve patients with early rheumatoid arthritis: Results from a longitudinal observational study:
Authors: A.-B. Aga, E. Lie, T. Uhlig, T.K. Kvien, E. Haavardsholm
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Methotrexate (MTX) is the most widely prescribed DMARD and at present the first line treatment for rheumatoid arthritis (RA). Knowledge about predictors of response to MTX is of potential clinical use as it is important to know which patients who are less likely to respond, so that these patients could receive more potent treatment earlier. <h3>Objectives</h3> To identify clinical predictors of EULAR good response to MTX treatment. <h3>Methods</h3> Data was extracted from the NOR-DMARD register where adult patients with inflammatory arthropathies starting a new DMARD treatment have been consecutively included since 2000 and followed longitudinally. For this analysis RA patients satisfying the following criteria were included: disease duration &lt;1 year, no prior DMARD and DAS28 ≥3.2 (moderate or high disease activity) at baseline were included [N=588, 67% females, mean (SD) age 56.3 (13.5) years, 62% rheumatoid factor (RF) positive, DAS28 5.29 (1.15), MHAQ score 0.74 (0.51)]. The following covariates were tested in univariate logistic regression with 3-month EULAR good response as the dependent variable: gender, age, disease duration (&gt;1 month vs. ≤1 month), cigarette smoking habits, level of education, RF status, swollen and tender joint counts (28 joints), physician and patient global assessments, fatigue, ESR, MHAQ score, and concurrent prednisolone and NSAID use. CRP and pain VAS were excluded due to co-linearity with ESR and patient global, respectively. Variables yielding a p-value &lt;0.25 were included in a subsequent multivariate regression analysis, and non-significant variables were removed from the model one at the time (starting with the least significant variable), checking for confounding. Appropriate tests for linearity and goodness of fit were performed. <h3>Results</h3> EULAR good response was achieved by 33.2% of patients at 3 months. Disease duration, baseline prednisolone use and lower baseline ESR and fatigue came out as independent predictors, and university/college education was significant vs. the lowest level of education (Table). The fit of the model was satisfactory (Hosmer-Lemeshow goodness of fit test: p=0.53). <h3>Conclusions</h3> Shorter disease duration, baseline prednisolone use, lower baseline SR, lower baseline fatigue level, and university/college education were independent predictors of achieving EULAR good response in patients with new-onset RA starting MTX in a real life setting. <h3>Disclosure of Interest</h3> None Declared
SAT0189 Muscle T2 Mapping: A Tool in the Diagnostic Imaging of Neuromuscular Disorders
Authors: J.-P. Mattei, Y. Le Fur, N. Cuge, S. Guis, P. Cozzone, M. Bernard, D. Bendahan
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Although Magnetic Resonance Imaging has been widely used as a diagnostic tool in neuromuscular disorders, the analysis of images has remained essentially qualitative. <h3>Objectives</h3> Even if visual scores of deterioration have been proposed and achieve a good sensitivity their specificity remain low. The calculation and mapping of T2 relaxation time, a quantitative index of fat and muscle physical characteristics, can provide reliable information regarding fatty infiltration and inflammatory signs in neuromuscular disorders. <h3>Methods</h3> In addition to routine images acquired using T1 and STIR sequences, T2 mapping has been obtained from the dominant thigh of 55 patients with various muscle diseases (myositis, myopathies, rhabdomyolysis) and 36 control subjects. Based on the T2 values, we have developed an automatic segmentation method in order to distinguish muscle from fat. Two variables have been defined <i>i.e</i>. the most frequent T2 values (T2mf) and the numbers of T2 values ranging from 60 ms (the upper limit of normal muscle) to 75 ms (the lower limit of fat) expressed as a surface (NT2 60-75ms). <h3>Results</h3> We observed large T2 variations in patients and controls with a clear positive effect of age (0.23 p&lt;0.001) and no relation to sex. T2<sub>mf</sub> and NT2<sub>60–75ms</sub> values reduced this variation and were significantly affected by muscle diseases (Table 1). They increased from rabdomyolysis, myositis, to myopathies (Table 2). A diagnostic strategy obtained from a CHAID analysis shows that if STIR images analyses were not convincing to conclude, T2<sub>mf</sub> and NT2<sub>60–75ms</sub> variable allowed to distinguish patients from controls. <h3>Conclusions</h3> T2 mapping is a quantitative approach more robust than the sole visual inspection to characterize changes in the muscles of patients with neuromuscular diseases. Additional indices such as T2<sub>mf</sub> and NT2<sub>60–75ms</sub> provide alternative measures of disease activity which could be used for diagnosis, investigation of the natural history of muscle diseases and the effects of therapeutic strategies. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.1602
Prophylaxis of Gonococcal and Chlamydial Ophthalmia Neonatorum
Authors: M Laga, F A Plummer, P Piot, P Datta, W Namaara, J O Ndinya-Achola, H Nzanze, G Maitha, A R Ronald, H O Pamba
Journal: New England Journal of Medicine (1988)

We evaluated the use of silver nitrate drops and tetracycline ointment for the prophylaxis of ophthalmia neonatorum in a controlled trial involving 2732 newborns in Nairobi, Kenya. The overall rates of prevalence of intrapartum maternal gonococcal and chlamydial infection were 6.4 and 8.9 percent, respectively. After prophylaxis with silver nitrate, the incidence rates of gonococcal, chlamydial, and nongonococcal, nonchlamydial ophthalmia neonatorum were 0.4, 0.7, and 6.2 percent, respectively, whereas after prophylaxis with tetracycline, the rates were 0.1, 0.5, and 4.5 percent. The attack rates of gonococcal ophthalmia neonatorum in newborns exposed to Neisseria gonorrhoeae at birth were 7.0 percent in those receiving silver nitrate and 3.0 percent in those receiving tetracycline (95 percent confidence interval for the difference in rates, -3.4 to 11.4 percent). As compared with historical controls, the incidence of gonococcal ophthalmia neonatorum decreased 83 percent among infants treated with silver nitrate and 93 percent among those treated with tetracycline. Failure of prophylaxis was associated with postpartum maternal endometritis (P = 0.05). Among newborns exposed to maternal infection with Chlamydia trachomatis, chlamydial conjunctivitis developed in 10.1 percent given silver nitrate and in 7.2 percent given tetracycline (95 percent confidence interval for the difference in rates, -4.7 to 10.5 percent), yielding reductions in the incidence of chlamydial ophthalmia of 68 and 77 percent, respectively, as compared with the historical controls. We conclude that tetracycline is as effective as silver nitrate in preventing gonococcal ophthalmia neonatorum.
Benzene and Leukemia
Authors: Enrico C. Vigliani, Giulio Saita
Journal: New England Journal of Medicine (1964)

HYPOREGENERATIVE and aplastic types of hemopathy brought about by exposure to benzene were described in the nineteenth century, and the question of leukemic myelosis from the same cause has been debated since the first description of a case of leukemia referred to the action of benzene.1 A paper by Cronkite2 (1961) summarizes the natural history of "benzene leukemia." From this and other American papers on benzene poisoning it seems that the European and especially the Italian literature on benzene leukemias is poorly known. Therefore, we thought that it would be of some interest to give a short account of the . . .
TCT-608 A New Thin-Strut, Low-Dose, Sirolimus-Eluting Stent With Abluminal-Only Biodegradable Polymeric Coating: Safety and Efficacy Clinical Performance of the Inspiron™ Stent in High-Risk Patients
Authors: Guy F.A. Prado, Pedro Henrique Craveiro Melo, Celso Takimura, Gustavo M. Alves, Welingson V. Guimarães, Jose Mariani, Luiz J. Kajita, Carlos M. Campos, Breno A. Falcão, Marcus N. Gama, Gilberto Marchiori, Antonio Esteves-Filho, Pedro E. Horta, Micheli Z. Galon, Andre G. Spadaro, Silvio Zalc, Paulo R. Soares, Marco A. Perin, Expedito Ribeiro, Roberto Kalil-Filho, Pedro A. Lemos
Journal: Journal of the American College of Cardiology (2014)
SAT0170 Ultrasound Composite Score for the Assessment of Inflammatory and Structural Pathologies in Psoriatic Arthritis
Authors: A. Ficjan, R. Husic, J. Gretler, A. Lackner, C. Duftner, W. Graninger, J. Hermann, C. Dejaco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> In clinical trials and routine practice of Psoriatic arthritis (PsA), disease activity is still monitored by RA specific clinical composites even if these measures are of questionable value for the assessment of PsA because of the heterogeneous nature of the disease affecting articular and extraarticular sites. (1) <h3>Objectives</h3> To develop ultrasound composite score(s) for the assessment of joint, peri-articular and enthesal pathologies in Psoriatic Arthritis (PsA). <h3>Methods</h3> Prospective study on 83 PsA patients with two study visits scheduled 6 months apart. B-mode and Power Doppler (PD-) findings were semiquantitatively scored at 68 joints (evaluating synovia, peritendinous tissue, tendons and bony changes) and 14 entheses. We used a hierarchical approach to construct a bilateral and a unilateral (focusing the dominant site) ultrasound composite scores. Discriminatory, internal and external validity, sensitivity, reliability and feasibility of the scores were tested. <h3>Results</h3> The bilateral score includes wrists, 2nd, 3rd, 5th metacarpophalangeal (MCP) joints, 2nd, 3rd proximal (PIP) and distal (DIP) interphalangeal joints, knees, 1st metatarsophaangal (MTP) and 3rd DIP joints of feet (F-DIP), lateral epicondyles and distal patellar tendons. The unilateral score compromises wrist, 2nd, 5th MCPs, 1st, 2nd, 3rd PIPs, 2nd DIP, knee, 1st,5th MTP, 1st F-PIP, 2nd, 3rd F-DIP, lateral epicondyle and distal patellar tendon of the dominant site. Both scores revealed a moderate to high sensitivity (bilateral composite 42-100%, unilateral 36-100%) to detect inflammatory and structural lesions. Data correlated with results from 68-joint/14-entheses score (corr<sub>coeffs</sub> 0.39-1.0) and with clinical parameters (corr<sub>coeffs</sub> 0-0.41). Patients achieving remission yielded greater reductions of ultrasound verified inflammation than patients did with stable clinical activity. <h3>Conclusions</h3> We propose two new ultrasound composite scores for assessment of inflammatory and structural lesions in PsA. Both scores revealed discriminatory, internal and external validity, reliability and feasibility. <h3>References</h3> Smolen JS, Braun J, Dougados M et al. Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to target: recommendations of an international task force. Ann Rheum Dis. 2014 Jan;73(1):6-16. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5188
Abstract 3038: Epithelial Membrane Protein-2 (EMP2) promotes glioblastoma growth via upregulating invasion and angiogenesis.
Authors: Yu Qin
Journal: Cancer Research (2013)

Abstract Recent data suggests that EMP2 is a novel oncogene in a number of tumors including breast, ovarian, endometrial and primary central nervous system malignancies. Its expression correlates with poor survival and can serve as a prognostic indicator in many tumors. Glioblastoma multiforme (GBM) is an aggressive brain tumor with a medium survival of 18 months, and we have found that EMP2 is expressed in the majority of GBM tumors but not in healthy brains. In order to therapeutically exploit the expression of EMP2 on these tumors, we have developed recombinant antibodies to this oncogene. In experimental models, use of the anti-EMP2 antibodies showed profound efficacy in reducing GBM tumor load. We further dissected the underlying molecular mechanisms and found that EMP2 accelerated GBM tumor growth through increasing αvβ3 integrin surface expression in GBM cells, activating downstream FAK and Src kinases and promoting cell migration and invasion. Furthermore, EMP2 upregulated vascular endothelial growth factor (VEGF) in several GBM cell lines. This increase appeared to be functionally relevant as conditioned medium from GBM cells with forced overexpression of EMP2 increased human umbilical vein endothelial cell (HUVEC) migration and capillary tube formation, suggesting a role for EMP2 in the regulation of tumor angiogenesis. Our results suggest the importance of this oncogene in the control of the tumor microenvironment and that targeting EMP2 expression may be a novel therapy for GBM. Citation Format: Yu Qin. Epithelial Membrane Protein-2 (EMP2) promotes glioblastoma growth via upregulating invasion and angiogenesis. [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 3038. doi:10.1158/1538-7445.AM2013-3038
Abstract 4320: Overexpression of Homeobox A5 decreases the invasive and migration capabilities of lung cancer cells
Authors: Ya-Jung Liu, Sung-Liang Yu, Jeremy J. W. Chen, Chi-Chung Wang
Journal: Cancer Research (2012)

Abstract Homeobox genes are a family of regulatory genes containing a common homeobox and act as transcription factors. Many cancers exhibit unusual alteration and expression in homeobox genes, including leukemia, colon, skin, prostate, breast, and ovary cancers. Recent studies indicated that homeobox A5 (HOXA5) may behave as a tumor suppressor gene in breast cells. However, the real roles of HOXA5 in lung cancer remains to be further clarified. In this study, we investigated the effect of HOXA5 on the invasive ability of more invasive CL1-5 cells transfected with HOXA5 constitutively expressed system. The results revealed that the excessive expression of HOXA5 can inhibit tumor cell invasion and migration capabilities. In addition, the HOXA5 specific siRNA could restore these effects. The results of metastatic analysis in SCID mice also demonstrated that HOXA5-overexpressed transfectants could decrease in vivo tumor nodule numbers. Furthermore, the HOXA5 mRNA expression was measured by real time RT-PCR in NSCLC surgical specimens and correlated with the patients’ clinical outcome. The HOXA5 downstream genes and HOXA5-regulated pathways were identified by using Affymetrix microarray and CRSD bioinformatics platform built in-house. Our studies herein provide a new insight into how HOXA5 may contribute to tumor metastasis inhibition in lung cancer. 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 4320. doi:1538-7445.AM2012-4320
Abstract 3085: The IFN inducible p53 target gene TRIM22 binds to the translation initation factor eIF4E and represses translation through disturbing the assembly of the eIF4F complex
Authors: Jessica Petersson, Malin Ageberg, Tor Olofsson, Urban Gullberg, Kristina Drott
Journal: Cancer Research (2011)

Abstract TRIM22 (Staf50) is an interferon (IFN)-inducible protein as well as a p53 target gene. It belongs to the TRIM (TRIpartite Motif) family proteins, characterized of a conserved tripartite motif consisting of a RING finger, B-box and a coiled-coil domain. The TRIM family includes more than 70 proteins, involved in various biological processes; e.g. apoptosis and cell proliferation. Consistently, several TRIM family members are involved in cancer. TRIM22 has been suggested to be an antiviral protein, capable of restricting HIV-, hepatitis B- and encephalomyocarditis replication. The molecular mechanisms for TRIM22 are unclear, but the antiviral activity may be dependent on the ubiquitylation capacity of TRIM22. We have previously shown it to suppress the clonogenic growth of leukemic U-937 cells, suggesting anti-proliferative or cell death-inducing effects. Now, we demonstrate that TRIM22 binds to the translation initiation factor eIF4E, and inhibits the binding of eIF4E to eIF4G, thus disturbing the assembly of the eIF4F complex, vital for cap dependent translation of mRNA. As a consequence, TRIM22 represses translation, as shown by decreased reporter protein levels, as well as global protein synthesis. Pulse-chase and cycloheximide experiments reveal that the repressive effects on the reporter protein is not due to increased protein degradation. Taken together, our data show TRIM22 to repress the binding of eIF4E to eIF4G, suggesting a novel translation regulating mechanism, possibly mediated in response to p53 and/or IFN signaling. 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 3085. doi:10.1158/1538-7445.AM2011-3085