tbuckley/cabot-search huggingface dataset:
AB0855 Bone mineral density in patients with ankylosing spondylitis before and after one year treatment with or without bisphosphonate
Authors: M. Soroush, S. Soroush, M. Mirtalebi, B. Nadimi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Ankylosing Spondylitis (AS) is a chronic inflammatory disease characterized by inflammation at the enthesis in the spine and peripheral skeleton, which may lead to a local bony erosion or juxta insertionally osteoporosis in the early stages. Osteoporosis has long been recognized as a common finding in patients with AS. In different reports, the osteopenia or osteoporosis frequency ranged from 50 to 92 percent. Osteoporosis arising from AS is caused by: genetic disposition, Calcium and Vitamin D absorption disorder, which relates to chronic inflammatory bowel damages and some taken medications in this group of diseased such as Glucocorticoids which effects are depending on the taken dose and treatment period. <h3>Objectives</h3> To determine the frequency of osteoporosis in AS and to compare changes of bone densitometry (BMD) after one year treatment with or without Bisphosphonate. <h3>Methods</h3> We checked two BMD with one year interval, early in our management and after one year treatment of disease with or without the use of Bisphosphonate. Total patients over whom we did our survey were 57, eight of which were women and 49 were men. 28 of patients, received standard treatment of AS and 29 other ones not only treated normally but also received Alendronate as well. <h3>Results</h3> Before treatment, T-score average of lumbar vertebrae in the group which used Alendronate was -2.26 (± 1.69) and this amount in the other group was -1.14 (± 1.12) (p-value 0.00). After passing one year of treatment this amount changed to -1.67 (± 1.74) in the group which have taken Alendronate and -0.96 (± 1.48) (p-value 0.04) in the other group. In addition the average of T-score deference of lumbar vertebrae, before and after passing one year of treatment in that group received Alendronate was -0.59 (± 0.38) and 0.18 (± 1.17) in the other group (p-value 0.04). Before treatment, T-score average of the femoral neck in the group which used Alendronate was -1.6 (± 1.23) and this amount in the other group was 0.69 (± 0.9) (p-value 0.00). After passing one year of treatment this amount changed to -0.97 (± 1.29) in the group which have taken Alendronate and -0.77 (± 0.95) (p-value 0.02) in the other group. In addition the average of T-score deference of the femoral neck, before and after passing one year of treatment in the group that received Alendronate was -0.62 (± 0.68) and 0.08 (± 0.69) in the other group (p-value 0.00). <h3>Conclusions</h3> Altogether, densitometry survey done over these two groups showed that T-score of diseased in both groups has been improved after treatment in comparison with the period they passed before treating, of course this amount of enhancement was more notable it the first group which received Alendronate. <h3>Disclosure of Interest</h3> None Declared
Effects of Thyroxine as Compared with Thyroxine plus Triiodothyronine in Patients with Hypothyroidism
Authors: Robertas Bunevičius, Gintautas Kažanavičius, Rimas Žalinkevičius, Arthur J. Prange
Journal: New England Journal of Medicine (1999)

Patients with hypothyroidism are usually treated with thyroxine (levothyroxine) only, although both thyroxine and triiodothyronine are secreted by the normal thyroid gland. Whether thyroid secretion of triiodothyronine is physiologically important is unknown.
Abstract 5683: The dietary anti-estrogenic agent 3,3′-diindolylmethane inhibits metastatic propensity in thyroid cancer cells
Authors: Shilpi Rajoria, Andrea George, Arulkumaran Shanmugam, Uchechukwu Megwalu, Stimson P. Schantz, Jan Geliebter, Raj K. Tiwari, Robert Suriano
Journal: Cancer Research (2010)

Abstract The incidences of thyroid proliferative diseases (TPD) including thyroid cancer and goiter are ever increasing with thyroid cancer being the most common among endocrine cancers. Recent statistics reveal 37,000 new cases diagnosed in US alone in 2008 and worldwide almost 27 million patients are affected. Diet has always been of prime importance in its association with cancer development and prevention. Several studies have found inverse association of cancer risk with consumption of dietary products, such as tomatoes, soy and cruciferous vegetables. We have been studying the effect of DIM (3,3′-diindolylmethane), a chemopreventive agent against hormone responsive cancers. In this study we show that thyroid cells express functional estrogen receptor (ER) -α and ER-β and DIM has anti-cancer effects on estrogen responsive thyroid cancer cells. Interestingly, we found that DIM does not affect the levels of ER but it does target metastatic phenotype of thyroid cells as evidenced by decreased adhesion, invasion and migration in vitro. In an attempt to define the cellular target of this inhibition, we observed that DIM mediates down-regulation of matrix metalloproteinases (MMPs) and cell adhesion proteins, integrins. This correlates with decreased thyroid cell proliferation and inhibition of metastatic propensity by DIM in thyroid cancer cells. These preclinical studies are being extended to the clinic where the anti-estrogenic property of DIM is being examined in goiter patients. 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 5683.
Repair of a gastrocolic fistula using a wire-guided, simultaneous dual scope approach
Authors: A. Nici, S. Hussain, M. Rubin, S. Kim
Journal: Endoscopy (2013)

A 72-year-old man with a history of diverticulitis 1 year previously, requiring a partial colectomy, presented to our hospital complaining of fever and weight loss over the preceding 3 weeks. Blood cultures revealed Gram-negative bacteremia. Antibiotics were initiated and a complete workup for infectious diseases was done without any success. Barium imaging and computed tomography (CT) of his abdomen revealed a 14-cm long fistulous tract extending from the greater curvature of the stomach to the area of the sigmoid colon ([Fig. 1]). It was felt that the bacteremia was most likely due to the gastrocolic fistula and endoscopic closure was planned. At upper endoscopy, the gastric fistula opening was visualized on the greater curvature of the gastric body ([Fig. 2]). After injection of contrast into the tract, a 0.025-cm Jag wire (Boston Scientific, Natick, Massachusetts, USA) was threaded into the fistula under fluoroscopic guidance ([Fig. 3]). Colonoscopy was carried out simultaneously to visualize the guide wire's exit point, which was emerging out of a field of diverticula in the sigmoid colon. The fistula was then flushed with sterile water and a cytobrush (Cytomax II Double Lumen Cytology Brush, Wilson-Cook Medical, Winston-Salem, North Carolina, USA) was passed over the guide wire to denude the mucosa and promote closure. Lastly, both the proximal and distal ends of the fistula were closed with Resolution clips (Boston Scientific). The patient tolerated the procedure well. A repeat upper gastrointestinal series performed 4 days later failed to show the fistula and the patient was discharged. At 3 months, a lower gastrointestinal series confirmed successful long-term closure ([Fig. 4]). To our knowledge this is the first reported case of a long gastrocolic fistula being repaired via this novel method of dual endoscopic closure with use of Resolution clips.
c-Met–mediated endothelial plasticity drives aberrant vascularization and chemoresistance in glioblastoma
Authors: Menggui Huang, Tianrun Liu, Peihong Ma, R. Alan Mitteer, Zhenting Zhang, Hyun Jun Kim, Eujin Yeo, Duo Zhang, Peiqiang Cai, Chunsheng Li, Lin Zhang, Botao Zhao, Laura Roccograndi, Donald M. O’Rourke, Nadia Dahmane, Yanqing Gong, Constantinos Koumenis, Yi Fan
Journal: Journal of Clinical Investigation (2016)

Aberrant vascularization is a hallmark of cancer progression and treatment resistance. Here, we have shown that endothelial cell (EC) plasticity drives aberrant vascularization and chemoresistance in glioblastoma multiforme (GBM). By utilizing human patient specimens, as well as allograft and genetic murine GBM models, we revealed that a robust endothelial plasticity in GBM allows acquisition of fibroblast transformation (also known as endothelial mesenchymal transition [Endo-MT]), which is characterized by EC expression of fibroblast markers, and determined that a prominent population of GBM-associated fibroblast-like cells have EC origin. Tumor ECs acquired the mesenchymal gene signature without the loss of EC functions, leading to enhanced cell proliferation and migration, as well as vessel permeability. Furthermore, we identified a c-Met/ETS-1/matrix metalloproteinase-14 (MMP-14) axis that controls VE-cadherin degradation, Endo-MT, and vascular abnormality. Pharmacological c-Met inhibition induced vessel normalization in patient tumor-derived ECs. Finally, EC-specific KO of Met inhibited vascular transformation, normalized blood vessels, and reduced intratumoral hypoxia, culminating in suppressed tumor growth and prolonged survival in GBM-bearing mice after temozolomide treatment. Together, these findings illustrate a mechanism that controls aberrant tumor vascularization and suggest that targeting Endo-MT may offer selective and efficient strategies for antivascular and vessel normalization therapies in GBM, and possibly other malignant tumors.
NI-53 * PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY MIMICKING HIGH GRADE GLIOMA IN AN IMMUNOCOMPETENT PATIENT: A CASE REPORT
Authors: M. Lee, K. Walsh, R. Rey-Dios, M. Anderson
Journal: Neuro-Oncology (2014)

Progressive multifocal leukoencephalopathy is an uncommon and fatal demyelinating disease of the central nervous system that is due to reactivation of the JC virus. It is most often seen in immunocompromised patients, such as those with HIV/AIDS or those on chronic immunosuppressive therapy. We present a case of biopsy-proven idiopathic PML in a presumed immunocompetent patient, with imaging characteristics suggestive of glioma. A 66-year-old white male with a history of cirrhosis presented with subacute onset of progressive deterioration of mental status, aphasia, and right hemiparesis. Laboratory and cerebrospinal fluid studies were unremarkable for any infection, autoimmune disease, and malignancy. MRI brain revealed a non-contrast enhancing lesion involving the left frontal, parietal, and temporal lobes with marked sparing of overlying cortex, characterized by increased T2/FLAIR hyperintensity, T1 hypointensity, and facilitated diffusion. MR spectroscopy of the lesion demonstrated elevated choline, with lactate peaks and decreased NAA. A high grade glioma was suspected and patient underwent a brain biopsy. Histological analysis revealed enlarged oligodendrocytes with myelin loss consistent with active demyelination. The enlarged oligodendrocytes had smudged nuclear chromatin, were positive for JC virus by in situ hydridization, and also showed strong staining for p53. A diagnosis of progressive multifocal leukoencephalopathy (PML) was made. Although rare in immunocompetent individuals, this unusual presentation suggests that PML be considered in the approach to the diagnosis and management of such lesions.
OP0142 Masking CD94/NKG2A using a novel therapeutic MAB results in significant suppression of IL-6 levels and reduced osteoclast formation in rheumatoid arthritis ex vivo cultures
Authors: K. Söderström, Y. Sundström, L. Berg, D. Schepis, E.D. Galsgaard, L. Klareskog, N. Wagtmann
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Natural killer (NK) cells expressing CD94/NKG2A, an inhibitory receptor binding HLA-E, accumulate in the inflamed joints of Rheumatoid Arthritis (RA) patients [1]. At this site they frequently interact with multiple inflammatory cell subsets. Recent data indicate that NK cells may play a role in RA disease pathology by their capacity to trigger the differentiation of monocytes into osteoclasts [2]. <h3>Objectives</h3> The aim of this study was to determine whether blocking the CD94/NKG2A interactions with HLA-E using a novel therapeutic mAb affects osteoclastogenesis in <i>ex vivo</i> RA synovial fluid mononuclear cell (SFMC) cultures. <h3>Methods</h3> To study osteoclastogenesis and <i>in vitro</i> bone mineral erosion, SFMCs were cultured in the absence or presence of IL-15. These cultures were treated with and without the antagonistic humanized anti-NKG2A mAb (NNC141-0100) followed by analysis of the formation of TRAP+ multinucleated osteoclasts and functional bone mineral erosion. To measure cytokine release, supernatants were harvested at various time points followed by detection using a Bioplex array. <h3>Results</h3> Blocking CD94/NKG2A in SFMC cultures resulted in a significantly reduced formation of TRAP+ multinucleated cells (p&lt;0.01, n=14), reduced bone mineral erosion (p&lt;0.03, n=5), and reduced IL-6 levels (p&lt;0.01, n=11). <h3>Conclusions</h3> This study shows that blocking CD94/NKG2A with anti-NKG2A mAb NNC141-0100 that is currently being developed for the treatment of RA, leads to suppression of osteoclast formation and subsequent bone erosion, as well as a reduction in IL-6 levels <i>in vitro</i>. Based on these findings, we propose that anti-NKG2A therapy may have a beneficial effect <i>in vivo</i> in RA patients. <h3>References</h3> Teixeira de Matos C et al. Activating and inhibitory receptors on synovial fluid natural killer cells of arthritis patients: role of CD94/NKG2A in control of cytokine secretion. Immunology. 2007 Oct;122(2):291-301. Söderström K et al. Natural killer cells trigger osteoclastogenesis and bone destruction in arthritis. Proc Natl Acad Sci U S A. 2010 Jul 20;107(29):13028-33. <h3>Disclosure of Interest</h3> K. Söderström Employee of: novo nordisk, Y. Sundström Grant/Research support from: novo nordisk, L. Berg Grant/Research support from: novo nordisk, D. Schepis Grant/Research support from: novo nordisk, E. Galsgaard Shareholder of: novo nordisk, Employee of: novo nordisk, L. Klareskog Grant/Research support from: novo nordisk, N. Wagtmann Shareholder of: novo nordisk, Employee of: novo nordisk
P60 HUMAN HEPATOCELLULAR CARCINOMA DENDRITIC CELL INTERACTIONS INDUCE A NOVEL SUBSET OF CD8+REGULATORY T-CELLS WHICH MEDIATE IMMUNOSUPPRESSION THROUGH CD39
Authors: K.-K. Li, Y.J. Resheq, S.M. Curbishley, S.T. Ward, T. Bruns, H.W. Zimmermann, P.J. Trivedi, C.J. Weston, D.H. Adams
Journal: Journal of Hepatology (2014)
THE ACUTE RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY IS NOT RELATED TO LEFT VENTRICULAR LEAD POSITION OR ELECTRICAL SEPARATION TIME
Authors: Stian Ross, Erik Kongsgaard, Thor Edvardsen, Trine Haland, Rita Skaardal, Gammelsrud Lars Ove, Trent Fischer, Richard Cornelussen, Hans Henrik Odland
Journal: Journal of the American College of Cardiology (2015)
Abstract 3210: Proteomic study of 5-fluorouracil resistance in colon cancer cell lines.
Authors: Marta Guerrero-Valero, Consuelo Marin-Vicente, Roman A. Zubarev, Neus Visa
Journal: Cancer Research (2013)

Abstract The anticancer drug 5-fluorouracil (5-FU) is a chemotherapy agent that has been in use against colon cancer for about 40 years. However, inherent and acquired drug resistance phenomena often limit the effectiveness of 5-FU chemotherapy, which makes it necessary to explore the underlying resistance mechanisms. In addition, it is important to identify useful markers to predict the sensitivities of different tumors to 5-FU therapy. In order to study the mechanism of 5-FU resistance, we used three 5-FU-resistant cell lines (HCT116/5-FU, H630/5-FU and RKO/5-FU) and their parental cell lines (HCT116, H630 and RKO). The proteomes of the untreated cells and of cells treated with 5-FU for 24 h were analyzed by label-free mass spectrometry using a nano-LC-ESI-LTQ Orbitrap Velos. When we compared the untreated proteomes, we could detect significant differences among resistant and parental cell lines, and we identified 21 proteins overexpressed and 12 underexpressed in the three resistant cell lines. Many of these proteins were associated with the mitochondria or were involved in carboxylic acid metabolism, in response to chemical stimuli, in regulation of programmed cell death, in oxidoreductase ativity or in DNA repair/cell cycle control pathways. The observed differences among the 5-FU resistant and the parental proteomes were even more pronounced in cells treated with 5-FU for 24 h. The numbers of proteins overexpressed and underexpressed in the resistant cell lines rose to 25 and 17, respectively. Moreover, many of the differentially expressed proteins were associated to the ribosome and were involved in translation and RNA metabolism. The mass spectrometric results were validated by semi-quantitative Western blotting and complemented with cell proliferation assays and with pathway analysis. Altogether, our results not only led to the identification of potential protein markers of 5-FU resistance, but also provided information about the underlying resistance mechanisms. Citation Format: Marta Guerrero-Valero, Consuelo Marin-Vicente, Roman A. Zubarev, Neus Visa. Proteomic study of 5-fluorouracil resistance in colon cancer cell lines. [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 3210. doi:10.1158/1538-7445.AM2013-3210
Carditis during Second Attacks of Rheumatic Fever
Authors: Ann G. Kuttner, Florence E. Mayer
Journal: New England Journal of Medicine (1963)

A NUMBER of studies have reported that patients without clinical evidence of carditis in their first attack of rheumatic fever or chorea usually do not acquire carditis in subsequent attacks and often escape residual rheumatic heart disease. The reports, however, differ in the percentage of such patients with normal cardiac findings on follow-up examinations.In 1937 Roth and his co-workers1 reported data on the second attack in 149 children who had had polyarthritis without clinical signs of carditis. During their second attack 51 of these 149 children (34 per cent) had carditis. In 1938 Boone and Levine2 presented 225 cases . . .
Abstract 1746: Modulation of ABCG2 mediated multidrug resistance by xanthine derivatives
Authors: Rui Ding, Jia Shi, Kathleen W. Scotto
Journal: Cancer Research (2011)

Abstract ABCG2 is an ATP-binding-cassette (ABC) transporter that confers multidrug resistance (MDR) in tumor cells by extruding a broad variety of chemotherapeutic agents, ultimately leading to failure of cancer therapy. Accordingly, the downregulation of ABCG2 expression and/or function has been proposed as part of a regimen to improve cancer therapeutic efficacy. Adenosine receptors (ARs), belong to the G-protein coupled receptor superfamily, and play important roles in stimulating neuronal cells, regulating cell proliferation and controlling immune responses. Adenosine receptor antagonists, a large collection of small molecules mainly composed of methylxanthines and other xanthine derivatives, have been used or implicated in many therapeutic applications, such as treatment of asthma, chronic bronchitis, emphysema and neural degenerative diseases. Previously, we have shown that the non-selective AR antagonist 1,3,7-methyxanthine (caffeine) can dramatically downregulate ABCG2 expression levels in cancer cell lines, increasing the intracellular retention of the ABCG2 specific substrate Mitoxantrone (MX) and markedly sensitizing cells to this chemotherapeutic agent. In order to find more potent and specific modulators of ABCG2 expression, we recently tested other ARs antagonists. Among the compounds we have examined, the non-selective antagonists theophylline, theobromine, paraxanthine, and the A2R selective antagonists 8-(3-chlorostyryl), caffeine (CSC) and 3,7-dimethyl-1-propargylxanthine (DMPX), were capable of downregulating ABCG2 protein levels to varying degrees. An A1R selective antagonist, 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX), currently in clinical trials, also decreased the expression of ABCG2 significantly at physiologically- relevant concentrations. In addition, the natural ligand of the ARs, adenosine, completely blocked the downregulation of ABCG2 by caffeine, suggesting that adenosine receptors and their downstream signaling pathways are involved in the regulation of ABCG2 gene expression. These findings suggest that xanthine adenosine receptor antagonists could be developed as combination therapy to improve the efficacy of drugs that are ABCG2 substrates. 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 1746. doi:10.1158/1538-7445.AM2011-1746
Abstract LB-242: Dissecting Cell Signaling Mediated by Multi-spanning Transmembrane Domain Association
Authors: Hang Yin
Journal: Cancer Research (2011)

Abstract The association of protein transmembrane domains regulates many pivotal signal transduction pathways. Molecular recognition by polytopic membrane proteins is especially poorly understood due to their difficult preparation, characterization and analysis. Herein, we demonstrate a modular approach designed to study multi-spanning transmembrane domain association, using hydrophobic peptides representing individual transmembrane helices. Transmembrane helices have a high level of intrinsic stability due to the energetic requirement to sequester the polar backbone from the hydrophobic environment of the membrane causing them to adopt native-like structures in membrane-mimetic environments. Biophysical and biochemical experiments on individual transmembrane helices identified a novel protein-oligomerization hotspot for a representative membrane protein, latent membrane protein 1, and the key residue was confirmed as biologically relevant in the full-length protein. This generally applicable approach provides a novel strategy to study multi-spanning transmembrane proteins. 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 LB-242. doi:10.1158/1538-7445.AM2011-LB-242