tbuckley/cabot-search huggingface dataset:
AB0104 Serum adipokine (adiponectin, leptin, visfatin, and resistin) levels in patients with rheumatoid arthritis are differentially modulated by disease activity but may not contribute to treatment resistance
Authors: S.-J. Hong, R. Song, S.-H. Lee, Y.-A. Lee, H.-I. Yang, J.-W. Hur, K.-S. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Even though it is well known that adipokines play important roles in the pathogenesis of RA, the in vivo role of adipokines and their association with disease activity is poorly understood. In particular, the modulation of serum adipokines (adiponectin, leptin, resistin, and visfatin) by RA disease activity or type of therapy including disease-modifying antirheumatic drugs (DMARDs) and tumor necrosis factor (TNF)-α blockers should be more elucidated. <h3>Objectives</h3> This study aimed to determine if disease activity and type of therapy in patients with rheumatoid arthritis (RA) differentially modulates serum adipokine levels and if pre-therapy adipokine levels contribute to treatment resistance. <h3>Methods</h3> Fasting blood samples from 40 patients with RA were collected at baseline and six months after therapeutic treatment with disease-modifying antirheumatic drugs (DMARDs) and/or tumor necrosis factor (TNF)-α blockers. Serum levels of adiponectin, leptin, visfatin, and resistin were measured by ELISA. <h3>Results</h3> Baseline adipokine levels were not significantly different between patients with moderate and high disease activity based on Disease Activity Score (DAS) 28. Among adipokines, only adiponectin was significantly increased in patients who responded to DMARD and/or TNF-α blocker therapy based on ACR20 at six months (from 2,964±1,237 to 3,683±1,511, <i>P</i>&lt;0.01).However, adiponectin levels in non-responders were not significantly increased (3,192±2,090 to 3,222±1,150). In vitro adipokine expression patterns of human adipocytes in response to inflammatory stimuli were different from those seen in the serum of patients with RA. <h3>Conclusions</h3> Adipokine levels (adiponectin, leptin, visfatin, and resistin) are differentially modulated by disease activity and type of therapeutic treatment in patients with RA. Adipokine level may not contribute to therapeutic resistance to DMARD and/or TNF-α blocking agents. <h3>References</h3> Trayhurn P, Wood IS: Adipokines: inflammation and the pleiotropic role of white adipose tissue. Br J Nutr 2004, 92(3):347-355. Cansu B, Cansu DU, Kasifoglu T, Gulbas Z, Korkmaz C: Disease-modifying antirheumatic drugs increase serum adiponectin levels in patients with rheumatoid arthritis. J Clin Rheumatol 2011, 17(1):14-17. <h3>Disclosure of Interest</h3> None Declared
P1067 RESPONSE-GUIDED PEGINTERFERON ALFA-2a (PegIFN alfa-2a) THERAPY IN PATIENTS WITH HBeAg-POSITIVE CHRONIC HEPATITIS B (CHB)
Authors: J. Hou, H. Ma, J. Sun, Q. Xie, Y. Xie, Y. Sun, H. Wang, G. Shi, M. Wan, J. Niu, Q. Ning, Y. Yu, Y. Xie
Journal: Journal of Hepatology (2014)
841 THE EFFECT OF MILD TO MODERATE HEPATIC IMPAIRMENT ON THE PHARMACOKINETICS OF ALISPORIVIR (ALV)
Authors: S.J. Kovacs, J. Ke, J. Praestgaard, A. Barve, J. Zhang, R. Maietta, G. Sunkara, D.S. Stein
Journal: Journal of Hepatology (2013)
STEM-12FATE OF BEVACIZUMAB IN GLIOBLASTOMA
Authors: Gaelle Muller-Greven, Cathleen Carlin, Steven Toms, Manmeet Ahluwalia, Markus Bredel, Justin Lathia, Jeremy Rich, Petra Hamerlik, Candece L. Gladson
Journal: Neuro-Oncology (2015)
Abstract 2614: Inhibition of class I histone deacetylases attenuates anthracycline induced activation of the ATM pathway
Authors: Kenneth (Ted) Thurn, Scott Thomas, Paromita Raha, Ian Qureshi, Pamela N. Munster
Journal: Cancer Research (2011)

Abstract Breast cancer is one of the most common cancers to afflict women in the world. Anthracycline-based regimens, including doxorubicin and epirubicin (epidoxorubicin), are common therapies for patients with breast cancer. Doxorubicin and epirubicin are inhibitors of topoisomerase II, which cause double strand DNA breaks. Following anthracycline-induced damage, DNA damage response pathways are activated in order to initiate cell cycle arrest, DNA repair, and/or cell death. The recent introduction of PARP inhibitors highlights the clinical relevance of targeting DNA repair pathways in treating this disease. Recently, two histone deacetylase (HDAC) inhibitors have been approved by the Federal Drug Administration for the treatment of cutaneous T-cell lymphoma: vorinostat and romidepsin. HDAC inhibitors reduce the repair of DNA, and are being used in combination with DNA damaging chemotherapeutic agents. The mechanisms regulating the HDAC inhibitor-mediated reduction of DNA repair in breast cancer cells are not well established. Understanding these mechanisms will identify key therapeutic targets for reducing DNA repair, define the role of HDACs in DNA repair, and allow for the enrichment of patients most susceptible to HDAC inhibitor-chemotherapy combined treatment. Previously, our group has demonstrated an increase in DNA decondensation which permits greater access of anthracyclines to DNA after therapeutic inhibition of HDACs. New results demonstrate that phosphorylation of p53 at Serine 15 is decreased in the presence of epirubicin after pre-treatment with vorinostat in a time- and concentration-dependent manner. Total p53 protein levels are also decreased, while mRNA levels remain unchanged after combined treatment. Treatment of breast cancer cells with valproic acid or entinostat also attenuates phosphorylation of p53 after epirubicin treatment, suggesting the involvement of Class I HDACs in the activation of p53. Phosphorylation of DNA repair kinase ATM is also decreased following DNA damage in the presence of clinically relevant concentrations of vorinostat, and corresponds with a decrease in activation of downstream factors including CHK1, CHK2, and BRCA1. These results demonstrate that inhibition of Class I HDACs in breast cancer cells delays DNA damaging response signaling through p53 modification after anthracycline administration; suggesting a possible mechanism for synergy between HDAC inhibitors and DNA damaging agents. 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 2614. doi:10.1158/1538-7445.AM2011-2614
Abstract 214: High expression of CKS1B antagonizes MLN4924, a nedd8-activating enzyme inhibitor, that induces myeloma cell growth inhibition through decreased neddylation of SCF complex
Authors: Fenghuang Zhan, He Wang, Maurizio Zangari, Guido Tricot
Journal: Cancer Research (2012)

Abstract Background: MLN4924 binds to the NEDD8-activating enzyme (NAE), and promotes neddylation of SCF (Skp1-Cul1 / Cdc53-F-box protein) complex resulting in inhibition of proteasomal degradation of several substrates. CKS1B acts as an adaptor of SCF complexes involved in cell cycle progression and DNA damage repair in many cancers, including multiple myeloma (MM). In this study, we investigate the functional role of CKS1B expression on MLN4924 in myeloma and determine whether CKS1B can be used as a potential biomarker for sensitivity to MLN4924 treatment in MM. Methods: Three myeloma cell lines, KMS12, KMS28PE, and OCI-MY5 in which CKS1B was artificially over-expressed (CKS1B-OE) as well as their empty vector (EV) controls were treated with MLN4924 at different concentrations. The IC50 and growth inhibition of cells were analyzed via a fluorencent screeing assay. APC-labeled annexinV and PI were assessed by flow cytometry to detect apoptosis and cell cycle changes. The expression of Cullin-NEDD8 and a series of ubiquitined SCF substrates were analyzed by non-reducing western blot. Results: MLN4924 effectively inhibited cell growth and induced cell apoptosis in both CKS1B-OE and EV MM cells. However, MM cells transfected with EV were more sensitive than those transfected with CKS1B-OE as evidenced by the IC50 values (KMS28PE OE vs. EV 99: 65 nM; KMS12 OE vs. EV 125: 72 nM; and OCI-MY5 OE vs. EV 106:89 nM). The cell viabilities at 100 nM were 49.6% vs. 26.7%, 54.5% vs. 34.2%, and 53.6% vs. 36.8% in CKS1B-OE versus EV KMS28PE, KMS12, and OCI-MY5 cells (P&amp;lt;0.05). Western blots showed that over-expression of CKS1B significantly decreased expression of cullin1, nedd8, and the conjugated complex of cullin-nedd8 in MLN4924 treated cells (100 nM, 24h) compared with EV in all tested three cell lines. We also found that high expression of CKS1B was negatively correlated with SCF substrates including p21, CDT-1, p27 and CDT-1. MLN4924 induced a dose-dependent accumulation of these substrates in all three MM cell lines. Conclusion: High expression of CKS1B induces SCF substrate ubiquitination and degradation in MM cells. The NAE inhibitor MLN4924 induces cell apoptosis through decreased neddylation of SCF complex resulting in increase of p27, p21, CDT-1 and p130. CKS1B can be used as a marker of drug resistance to MLN4924, suggesting that a combination of MLN4924 with other drugs will be necessary to treat myeloma patients with high endogenous expression of CKS1B. 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 214. doi:1538-7445.AM2012-214
Carrier Detection in Duchenne Muscular Dystrophy
Authors: A. D. Roses, M. J. Roses, S. E. Miller, K. L. Hull, S. H. Appel
Journal: New England Journal of Medicine (1976)

We measured endogenous phosphorylation of peak II (apparent molecular weight of 220,000 daltons) of the erythrocyte membrane in 21 mothers of patients with Duchenne muscular dystrophy. The mean values of mothers with affected sons were significantly increased over those of matched controls (77.0 and 55.8 pmoles per milligram of 15-minute incubation; P less than 0.01). Detailed testing of mothers of affected sons revealed proximal muscle weakness. Seven mothers of isolated patients who had normal levels of creatine phosphokinase and no daughters with elevated levels were identified as carriers, because their mean value of peak II phosphorylation was increased (75.9 pmoles per milligram per 15 minutes) and equivalent to the level demonstrated in the 14 acknowledged carriers. Our results suggest that cases of Duchenne muscular dystrophy previously considered to be new mutations are much less common than estimated.
New players for cerebellar long-term depression
Authors: Masanobu Kano
Journal: Behavioral and Brain Sciences (1996)

In 1994 and 1995, several new reports appeared regarding cellular mechanisms of LTD. These concern (1) involvement of mGluRl, (2) involvement of glutamate receptor δ2 subunit (GluRδ2), (3) involvement of Ca2+ release from intracellular stores, and (4) origin of nitric oxide (NO). I would like to add these new results to the review article by Crépel et al. [CRÉPEL et al.]
Transnasal endoscopy for direct visual control of esophageal stent placement without fluoroscopy
Authors: M. Borgulya, C. Ell, J. Pohl
Journal: Endoscopy (2012)

Placement of self-expanding metal stents (SEMSs) is a well-established treatment for esophageal stenosis and postoperative anastomotic leaks. Conventional endoscopic procedures for SEMS placement require fluoroscopic guidance, but transnasal endoscopy (TNE) with ultraslim endoscopes may allow precise stent release under direct visual control without the need for fluoroscopy. This prospectively collected data investigated the feasibility and safety of TNE-guided SEMS placement without fluoroscopy. Between March 2009 and February 2011, 20 consecutive patients underwent TNE-guided SEMS placement without fluoroscopy. The technical success rate was 100 % and no fluoroscopy was required during the procedures. Five patients underwent SEMS placement as a bedside procedure in the intensive care unit. The mean intervention time was 13.4 minutes (range 6 – 26) and there were no early complications. In summary, TNE-guided SEMS placement allows precise stent placement without fluoroscopic control and can therefore be performed as a simple bedside procedure.
Significance of Early Tubular Extraction in the First Minute of Tc-99m MAG3 Renal Transplant Scintigraphy
Authors: EUGENE LIN, ABASS ALAVI
Journal: Clinical Nuclear Medicine (1998)

Renal transplant perfusion curves obtained using Tc-99m MAG3 differ from those with Tc-99m DTPA. The perfusion curve can be divided into a first phase (up to the first-pass peak) and a second phase (the curve after the initial peak). The second phase of the MAG3 perfusion curve is usually ascending in contrast to the descending Tc-99m DTPA curve. This ascending MAG3 curve reflects early tubular extraction of MAG3. However, the second phase of the MAG3 curve is sometimes flat or descending. We hypothesized that a flat or descending curve reflects poor early tubular extraction and therefore graft dysfunction. Ninety-two studies of 59' renal transplant patients were retrospectively reviewed. The second phase of the perfusion curve was visually classified as ascending, flat, or descending. 77.2% of studies had ascending curves, 16.3% flat curves, and 6.5% descending curves. A descending curve had a positive predictive value (PPV) of 100% for medical graft dysfunction, while a flat curve had a PPV of 93.3%. A nonascending second phase curve was specific (96.4%) but not sensitive (33.9%) for graft dysfunction. Patients with acute tubular necrosis were not significantly more likely to have a nonascending curve than those with acute rejection. There was no significant difference in creatinine level between patients with medical graft dysfunction and ascending vs. nonascending curves. A nonascending second phase Tc-99m MAG3 perfusion curve is predictive for graft dysfunction. An ascending curve is nonspecific and can be seen in both normally and poorly functioning grafts.
Amebic Hepatitis Presenting as Fever of Unknown Origin
Authors: Paul Heller, Roy J. Korn, Hyman J. Zimmerman
Journal: New England Journal of Medicine (1953)

THE protean nature of amebiasis has been amply discussed,1 2 3 4 5 6 7 and because of increased alertness to the various clinical syndromes that it may produce, the frequency of its diagnosis has increased during the past ten years.8 9 10 Thorough analyses by Klatskin,3 DeBakey and Ochsner,4 Sodeman5 , 6 and others have clearly outlined the clinical features of amebic dysentery, hepatitis, involvement of other organs and the "asymptomatic carrier state." Amebic hepatitis, however, presenting as obscure fever has been insufficiently described. In uncomplicated intestinal amebiasis, fever is relatively rare; Browne and his co-workers11 cited the presence of low-grade fever in only 6.5 per cent of 790 . . .
Abstract 3401: Amplification of the <i>STOML3, FREM2</i>, and <i>LHFP</i> genes is associated with mesenchymal differentiation in gliosarcoma
Authors: Masaya Nagaishi, Young-Ho Kim, Michel Mittelbronn, Felice Giangaspero, Werner Paulus, Anne Vital, Yoichi Nakazato, Joël Lachuer, Hiroko Ohgaki
Journal: Cancer Research (2012)

Abstract Gliosarcoma is a rare glioblastoma variant characterized by a biphasic tissue pattern with alternating areas displaying glial (GFAP-positive) or mesenchymal (reticulin-positive) differentiation. Previous analyses showed identical genetic alterations in both glial and mesenchymal tumor areas, suggesting that gliosarcomas are genetically monoclonal, and mesenchymal differentiation was considered to reflect the elevated genomic instability of glioblastomas. In the present study, we compared genome-wide chromosomal imbalances using array CGH (105K) in glial and mesenchymal tumor areas of 13 gliosarcomas. Patterns of gain and loss were similar, except for gain at 13q13.3-q14.1 (log2 ratio ≤ 3), containing the STOML3, FREM2, and LHFP genes, which was restricted to the mesenchymal tumor area of a gliosarcoma. Further analyses of 64 cases of gliosarcoma using quantitative PCR showed amplification of the STOML3, FREM2 and LHFP genes in 14 (21%), 10 (15%), and 7 (11%) of mesenchymal tumor areas but not in glial tumor areas. Immunohistochemistry confirmed that STOML3 and FREM2 overexpression was more extensive in mesenchymal than in glial tumor areas. These results suggest that mesenchymal components in a small fraction of gliosarcomas may be derived from glial cells with additional genetic alterations. 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 3401. doi:1538-7445.AM2012-3401
Abstract LB-291: Role of exosomes in tumor cell adhesion and survival
Authors: Rainelli B. Koumangoye
Journal: Cancer Research (2012)

Abstract Exosomes are nanovesicles secreted by all living cells. These vesicles are abundant in serum and other extracellular fluids and contain a large repertoire of proteins, mRNA and microRNA. Exosomes have been implicated in cell to cell communication, the transfer of infectious agents, neurodegenerative diseases as well as tumor progression. However, the precise mechanisms by which they are internalized and/or secreted remain poorly understood. In order to follow their release and uptake in breast tumor cells in real time, cell-derived exosomes were tagged with green fluorescent protein (GFP)-CD63. Shown here for the first time is the demonstration that detachment of adherent cells from substratum induces a rapid and substantial secretion of exosomes which then concentrate on the cell surfaces and are re-internalized to mediate adhesion to various extracellular matrix molecules (ECM). In contrast, ECM-immobilized exosomes inhibited cell adhesion and spreading. Disruption of lipid rafts with methyl-beta-cyclodextrin (MβCD) inhibits the internalization of exosomes. Moreover, when short hairpin RNA techniques are used to knockdown lipid raft-interacting proteins AnxA2 and AnxA6, the resultant Anx-depleted breast carcinoma cell lines exhibited decreased exosomes uptake and decreased cellular adhesion. Non-transformed primary breast epithelial cells treated with exosomes induced rapid cell cycle progression, disorganized cellular masses and anoikis resistance in three-dimensional cell culture systems. These data indicate that exosomes contribute to both cancer cell adhesion and survival mechanisms. 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-291. doi:1538-7445.AM2012-LB-291
Case 2-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Barry W. Levine, Eugene J. Mark
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 59-year-old woman was admitted to the hospital because of multiple pulmonary nodules.There was a history of asthma in childhood, but all symptoms subsided after several years. A questionable myocardial infarction occurred 14 years before admission; a treadmill stress test was reported to show evidence of myocardial ischemia, and a coronary angiographic examination revealed single-vessel disease that was not considered critical. Deep venous thrombosis occurred in the left leg six years before entry and was complicated by pulmonary embolism. During the three years before admission the patient was treated for "bronchitis" on six occasions. Two years . . .
OP0297 Calprotectin (S100A8/9) as Serum Biomarker for Clinical Response in Proof-Of-Concept Trials in Axial and Peripheral Spondyloarthritis
Authors: M.C. Turina, N. Yeremenko, J.E. Paramarta, L. De Rycke, D. Baeten
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Biomarkers complementing clinical evaluations may help to reduce the length and size of proof-of-concept (PoC) trials aimed to obtain quick "go/no go" decisions in the clinical development of new treatments. <h3>Objectives</h3> We aimed to identify and validate serum biomarkers to predict clinical response in spondyloarthritis (SpA) PoC trials. <h3>Methods</h3> The candidate biomarkers high sensitive-C-reactive protein (hs-CRP), interleukin-6 (IL-6), pentraxin-3 (PTX-3), alpha-2-macroglobulin (alpha-2-MG), matrix metalloproteinase-3 (MMP-3), calprotectin, and Vascular Endothelial Growth Factor (VEGF) were determined by ELISA in healthy controls (n=20) and SpA patients before and after 2 weeks of infliximab (n=18) or placebo (n=19) treatment. Clinical outcome was evaluated at week 12. Results were validated in ankylosing spondylitis (AS) with infliximab and peripheral SpA with etanercept. <h3>Results</h3> Serum levels of calprotectin, hs-CRP, PTX-3, VEGF (all <i>P</i>&lt;0.001) and MMP-3 (<i>P</i>=0.062), but not IL-6 and alpha-2-MG, were increased in SpA versus healthy controls. Treatment with infliximab, but not placebo, significantly decreased calprotectin (<i>P</i>&lt;0.001) and hs-CRP (<i>P</i>&lt;0.001<i>)</i> levels, with a similar trend for MMP-3 (<i>P=</i>0.063). The Standardized Response Mean (SRM), which reflects the ability to detect changes over time, was high for calprotectin (1.26), good for hs-CRP (0.96) and moderate for MMP-3 (0.52). Calprotectin and hs-CRP, but not MMP-3, were good biomarkers of treatment response in axial SpA as evaluated in 2 separate cohorts. All 3 markers reflected response to etanercept treatment in peripheral SpA with SRMs above 0.5. <h3>Conclusions</h3> Calprotectin and hs-CRP are good serum biomarkers to predict clinical response at the group level in small-scale, short term PoC trials in SpA. <h3>Disclosure of Interest</h3> M. Turina: None declared, N. Yeremenko: None declared, J. Paramarta: None declared, L. De Rycke: None declared, D. Baeten Grant/research support: AbbVie, Centocor, Janssen-Cilag, MSD, Novartis, and Pfizer, Consultant for: AbbVie, BMS, Boehringer Ingelheim, Centocor, Janssen, MSD, Novartis, Pfizer, and UCB <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2837