tbuckley/cabot-search huggingface dataset:
Abstract 1478: Role of Stat3 Ser727 phosphorylation in mouse hepatocarcinogenesis
Authors: Katsuhiro Ogawa, Masaaki Miyakoshi, Masahiro Yamamoto, Hiroki Tanaka, Yuji Yaginuma
Journal: Cancer Research (2010)

Abstract Inappropriate activation of signal transducer and activator of transcription 3 (Stat3) occurs with extreme frequency in a wide variety of cancers including HCC, and constitutive Stat3 activation in hepatocytes was demonstrated to accelerate hepatocarcinogenesis, while repression of Stat3 activation suppresses hepatocarcinogenesis. Diverse factors such as cytokines, growth factors and oncoproteins can activate Stat3, where phosphorylation of the conserved tyrosine residue at the C-terminus (Y705) results in the Stat3 homodimer or the heterodimer with Stat1, and phosphorylation of the serine residue on the transactivation domain (S727) contributes to its maximal transcriptional activity. The activated Stat dimers bind to specific DNA-response elements in the promoter of target genes and thereby induce unique gene expression programs cooperating with other transcription factors and cofactors. We investigated Stat3 activation in mouse hepatocarcinogenesis induced by neonatal treatment with diethylnitrosamine (DEN) and found that Stat3 phosphorylation occurred by two steps, where S727 phosphorylation was seen in the preneoplastic stage, whereas Y705 phosphorylation was further associated with malignant progression. In mouse HCC cells, serum treatment induced Ser727 phosphorylation via MAPK activation, associating with cell proliferation and Stat3 nuclear translocation, whereas IL-6 induced Tyr705 phosphorylation via JAK activation without stimulating cell proliferation and the Stat3 nuclear translation. On the other hand, the Ser727 phosphorylation dead Stat3 (S727A), in which the serine residue was replaced by alanine, reduced the cell proliferation and Stat3 nuclear translocation, while the Ser727-phosphorylation mimic Stat3 (S727D), in which the serine residue was replaced by aspartic acid, enhanced the cell proliferation and Stat3 nuclear translocation. To further investigate the role of Stat3 Ser727 phosphorylation, the Stat3 knockdown HCC cell lines were established by introducing the Stat3 siRNA into the mouse HCC cells. These cell lines showed retarded growth and less attachment to the substrate forming spheroidal aggregates, whereas the parent cells showed rapid proliferation and attached to the substrate with extended morphology. cDNA array analysis revealed that the Stat3 knockdown cells showed variety of gene expression changes relating to cell survival and growth, and RT-PCR demonstrated that the expression of EGFR, FGFR and E-cadherin was markedly reduced in the Stat3 knockdown cells. Our findings indicate that the Ser727-phosphorylated Stat3 plays an important role from the early stage in mouse hepatocarcinogenesis, presumably by controlling cellular growth and survival. 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 1478.
AB0505 Case report of allogeneic unrelated-donor mesenchymal stem cells (msc) infusion in systemic sclerosis (ssc)
Authors: R. Chakr, T. Pavan, I. Siqueira, D. Zanchet, N. Calegaro, N. Andrade, G. Neto, M. Neves, M. Bredemeier, P. Palominos, C. Kohem, B. Amorin, V. Valim, A. Alegretti, L. Silla, O. Monticielo, C. Brenol, R. Xavier, J. Brenol
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Intravenous MSC infusion has been reported occasionally in SSc treatment. To our knowledge this is the first case report of allogeneic unrelated-donor intravenous MSC infusion in SSc without immunosuppresive induction of MSC transplantation. <h3>Objectives</h3> To report the case of a cutaneous diffuse SSc patient with severe lung and skin manifestations treated with MSC infusion. To review the current literature on intravenous MSC infusion for SSc. <h3>Methods</h3> Literature review and multidisciplinary discussion were thoroughly performed before treatment protocol was approved by institutional ethics committee and patient and family signed informed consent form. <h3>Results</h3> A 36 year-old white female with a 10-year history of diffuse SSc manifested by severe scleroderma (Rodnan score 47/51), skin ulcers and extensive lung fibrosis refractory to methotrexate, azathioprine and cyclophosphamide received two infusions of allogeneic unrelated-donor 2x10<sup>6</sup>/Kg MSC. No immediate reactions occurred. Despite treatment, patient died of refractory shock and respiratory failure. No infections or tomographic changes had been detected. In other reports, fatality was not attributed to MSC infusion (Table). <h3>Conclusions</h3> Intravenous MSC infusion has been reported in few cases of SSc. In previous allogeneic related-donor or autologous MSC infusions and in the present allogeneic unrelated-donor MSC infusion reports, patients were heterogeneous and treatment protocols differed significantly. Larger studies are needed to validate clinical efficacy and safety and to standardize treatment protocol of MSC infusion in SSc. <h3>References</h3> Christopeit M, Schendel M, Foll J, <i>et al</i>. Marked improvement of severe progressive systemic sclerosis after transplantation of mesenchymal stem cells from an allogeneic haploidentical-related donor mediated by ligation of CD137L. Leukemia. 2008 May;22(5):1062-4. Guiducci S, Porta F, Saccardi R, <i>et al</i>. Autologous mesenchymal stem cells foster revascularization of ischemic limbs in systemic sclerosis: a case report. Ann Intern Med. 2010 Nov 16;153(10):650-4. Keyszer G, Christopeit M, Fick S, <i>et al</i>. Treatment of severe progressive systemic sclerosis with transplantation of mesenchymal stromal cells from allogeneic related donors: report of five cases. Arthritis Rheum. 2011 Aug;63(8):2540-2. <h3>Disclosure of Interest</h3> None Declared
AB1307 Intra- and interreader reliability of the omeract joint space narrowing score on magnetic resonance imaging and computed tomography in rheumatoid arthritis wrist and metacarpophalangeal joints
Authors: U. Møller Døhn, P.G. Conaghan, I. Eshed, A. Boonen, P. Bøyesen, F. Gandjbakhch, S. Lillegraven, P. Bird, V. Foltz, C.G. Peterfy, H.K. Genant, E.A. Haavardsholm, F.M. Mcqueen, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> The OMERACT RA MRI scoring system (RAMRIS) evaluates bone erosions, bone edema, and synovitis. The system is validated and increasingly used as an outcome measure in RA clinical trials. However, joint space narrowing (JSN), reflecting cartilage damage, is an important aspect of the joint damage in RA, and reliable assessment of this could constitute a useful additional outcome measure in RA clinical trials. <h3>Objectives</h3> The aim of the present OMERACT initiative was to validate the newly proposed MRI scoring system for JSN [1]. <h3>Methods</h3> Fourteen RA patients’ and one healthy control’s 2nd-5th metacarpophalangeal joints (MCP2-5) and wrist on one hand were assessed for JSN on MRI and CT by three experienced readers. Images were read twice with different identification numbers for blinding. <h3>Results</h3> Patient demographics: 71% female, age median 61 years (range 31-78), disease duration 5 (1-20), 71% IgM rheumatoid factor positive, Sharp/van der Heijde X-ray scores: Total 75 (3-106), joint space narrowing 40 (1-70), erosion 27 (2-44)). On both MRI and CT, high intrareader (ICCs ≥0.91) and interreader (ICCs ≥0.89) reliability were found for total assessment of JSN (see table). The agreement was generally lower for MCP joints than the wrist, particularly for CT. <h3>Conclusions</h3> High intra- and interreader reliabilty was obtained by three readers assessing JSN on MRI and CT using the OMERACT JSN MRI scoring system. The score may be a useful outcome measure in RA clinical trials. <h3>References</h3> Østergaard M, et al.: Development and preliminary validation of a magnetic resonance imaging joint space narrowing score for use in rheumatoid arthritis: potential adjunct to the OMERACT RA MRI scoring system. J.Rheumatol. 2011;38:2045-50. <h3>Disclosure of Interest</h3> None Declared
Immune Responses and Reactions to Diphtheria and Tetanus Toxoids, with Pertussis Vaccine, Aluminum Phosphate Precipitated
Authors: James A. McComb, Marion Z. Trafton
Journal: New England Journal of Medicine (1950)

IMMUNIZATIONS combining diphtheria and tetanus toxoids with pertussis vaccine, using alum or aluminum hydroxide as an adjuvant, have been reported in studies by di Sant' Agnese,1 Volk,2 Fleming3 and others. Holt4 has described the preparation of a purified diphtheria toxoid with aluminum phosphate as the mineral carrier. Clinical trials of this material have been extensive.5 We agree with Holt4 "that aluminum phosphate is an extremely suitable vehicle for adsorbing diphtheria toxoid when used for human prophylaxis, in that local or general reactions were absent or trifling."This study presents the use of a new product in the sense that aluminum . . .
A10.18 Correlation of RANKL, OPG and OPG antibodies in rheumatic diseases
Authors: B Hauser, PL Riches, T Gilchrist, M Rios, SH Ralston
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Introduction</h3> Receptor Activator of NfκB-Ligand (RANKL)&nbsp;and Osteoprotegerin (OPG)&nbsp;play a key role in the pathogenesis of osteoporosis in rheumatic diseases. We have recently shown that autoantibodies against OPG (OPG ab) are detectable in patients with rheumatic diseases and are associated with increased bone resorption in RA and reduced bone mineral density (BMD) in AS patients. Our aim was to examine the relation between OPG ab concentration and RANKL and OPG levels andto investigate if OPG abs interfere with free RANKL ELISA, which uses recombinant OPG as capture antigen. <h3>Methods</h3> Circulating free soluble RANKL (Biomedica), total soluble RANKL (BioVendor) and OPG (BioVendor)were measured in sera from 26 RA, 15 Spondyloarthropathy and 14 SLE patients, using commercial available ELISA kits. OPG ab concentrations were measured by an in-house made ELISA, using recombinant human OPG as the capture antigen with detection of antigen-antibody complex through HRP conjugated anti-human IgG antibodies. In order to investigate the effect of OPG antibodies on free RANKL detection, purified IgG from 6 patients serawas added to different RANKL concentrations (200 and 800pg/ml) and&nbsp;analysed by free RANKL ELISA. <h3>Results</h3> Free RANKL concentrations were undetectably low in 23 (41.8%) patients however this was not associated with the presence of OPG ab. In contrastthere was a significant positive&nbsp;correlation between free RANKL and OPG Ab concentrations (r = 0.273, p = 0.001) found. Mean OPG concentrations were significantly higher in patients above 67 years (6.31 ± 2.50 pmol/L) than in patients under 67 years of age (4.75 ± 1.70pmol/L) (p = 0.022). There was no association between OPG ab concentrations and OPG or total RANKL measurements. The addition of purified IgG reduced free RANKL detection through ELISA significantly (p &lt; 0.001) however there was no difference on RANKL suppression between IgG addition with high and low OPG ab levels. In conclusion there is no correlation between circulating OPG and OPG ab concentrations. The presence of circulating OPG ab may increase free RANKL concentrations by stopping OPG binding to RANKL. Purified Immunoglobulins interfere with the measurement of free soluble RANKL independent of OPG ab presence.
BI-27 * ANALYSIS OF THE BIOCHEMICAL PROFILE OF LOW GRADE GLIOMA WITH DIFFERENT IDH1 MUTATION STATUS USING VIBRATIONAL SPECTROSCOPY
Authors: O. Uckermann, T. Juratli, M. Conde, R. Galli, D. Krex, K. Geiger, G. Schackert, A. Temme, G. Steiner, M. Kirsch
Journal: Neuro-Oncology (2014)

Mutations in human cytosolic isocitrate dehydrogenases 1 (IDH1) are a common feature of low grade gliomas (LGG) and cause profound changes of the metabolites of the Krebs cycle. Vibrational spectroscopy comprises label-free techniques that probe a sample's molecular composition. Therefore, we investigated the ability of fourier-transform infrared (FT-IR) spectroscopy to analyze the IDH1-mutation status in cell culture systems and human brain tumor samples. Cell lines (U87-MG, SVG p12 and the primary glioblastoma cell lines HT7606, HT12346 and HT12347) were transduced with either IDH1 wild-type or mutated IDH1. Clusteranalysis and principal-component-analysis were able to detect differences in the respective FT-IR spectral datasets in regions assigned to saccharides (1050 and 1120 cm−1) and proteins (1236, 1545 and 1651 cm−1). Brain tumor samples of human LGG were obtained during routine surgery and the IDH1 mutation status was determined by DNA sequencing (n = 17). Difference spectra (IDH1-mut vs. IDH1-wt) showed changes in the region around 1100 cm−1 which is attributed to saccharides. Additionally, amide I and amide II spectral bands (around 1550 and 1650 cm−1, respectively) were reduced in the IDH1-mut dataset whereas the band at 1740 cm−1 assigned to C = O stretching vibrations was more pronounced. Principal-component-analysis confirmed differences between the two groups based on spectral regions assigned to saccharides, proteins and to C = O stretching vibrations, as identified previously in the difference spectra. Supervised classification recognized relevant spectral regions at 974, 1005, 1038-1044, 1078-1082, 1267-1275, 1342, 1417-1421, 1479 cm−1 and was able to assign 16 of the 17 tumor samples to the correct group. On the basis of FT-IR spectroscopy samples of LGG carrying IDH1 mutations can be discerned from IDH1 wildtype tumors. Relevant spectral regions assigned to saccharides and C = O stretching vibrations can be explained by changes in the Krebs cycle and in particular by the accumulation of 2-hydroxyglutarate (rich in C = O bonds).
Abstract LB-366: Patient-derived EBV-immortalized B-lymphocytes are a dominant contaminant of in vitro cultured human neuroblastoma tumor-initiating cells isolated from bone marrow
Authors: Sven Påhlman, Sofie A. Johnsson, Alexander Pietras, Caroline Wigerup, Ingrid Øra, Michael Andäng, Kenneth Nilsson, Tor Olofsson, David Gisselsson
Journal: Cancer Research (2011)

Abstract Neuroblastoma is one of the most common solid tumors of infancy and is believed to originate from immature sympathetic nervous system progenitor cells. Tumor stem cells from different cancer forms have during the last decade been isolated and propagated in vitro in stem cell-promoting medium. These cells have given the opportunity to study the population within the tumor that is believed to be responsible for relapse and metastatic disease. Three years ago, putative neuroblastoma tumor-initiating cells (TICs) were isolated from bone marrow of patients with high stage disease. Several findings concerning these cells have been difficult to explain in a neuroblastoma context, i.e. that initially only cells from MYCN non-amplified tumors could be established as proliferating cultures in vitro, that they have a B-cell phenotype with VDJ rearrangement as presented at the 2010 Advances in Neuroblastoma Research (ANR) meeting, and as presented here, that they lack genomic imbalances and fail to recapitulate neuroblastoma morphology when xenografted. We show that these widely studied patient-derived TIC cultures (NB12, NB88 and NB122R), also at low passages, are highly contaminated by proliferating cells of a B-lymphocyte phenotype, with the absolute majority of cells expressing multiple B-cell antigens while lacking expression of neuroblastoma-associated markers. We further show that these lymphoblastoid cells are Epstein-Barr virus (EBV)-infected with robust expression of the two EBV nuclear antigens EBNA2 and EBNA3A. In addition, orthotopic and subcutaneous TIC-derived xenograft tumors all have EBNA2 and B-cell marker CD19 positive cells at a high frequency. Published and unpublished results based on the use of the proposed TIC lines as a model for neuroblastoma development should be considered with caution, as these lines, at least with time in culture, mainly consist of EBV-transformed B-lymphoblastoid cells. 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-366. doi:10.1158/1538-7445.AM2011-LB-366
AB1464-HPR Development of a musculoskeletal ultrasound evaluation and reporting tool
Authors: C. Dobrica, F. Lovegrove, S. Cullinane, J. McLaren, H. Harris, J. Gibson
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> MSUS is used in our Department by all Consultant Rheumatologists at early RA and review Rheumatology Clinics but is not used by the Rheumatology Nurse Practitioner (RNP) who sees RA review patients. In order to provide MSUS during the RNP review clinic, a Rheumatology Specialist Physiotherapist/Sonographer (RSPS) was allocated to scan all patients immediately prior to attendance with the RNP. To ensure that the findings of the MSUS were accurately documented and interpreted, an evaluation tool needed to be developed. <h3>Objectives</h3> 1) To determine the rate of inter-reader reliability of the tool. 2) To determine whether use of the new tool is time-efficient <h3>Methods</h3> A series of graphical forms reflecting MSUS standard examination were designed and subsequently trialled by all MSUS practitioners, resulting in the final format. Scoring was graded 0 to 3 according to EULAR, OMERACT scoring for synovitis, and synovial hypertrophy. The erosions were recorded for presence and position. Each joint was graphically represented as a box containing the appropriate MSUS image with a tick-box system for grading synovial hypertrophy, synovitis, and presence of erosions (see Image 1). The RNP was trained to interpret the new form and inter-observer variability was reviewed in clinics between September 2011 and January 2012 for 100 consecutive patients. <h3>Results</h3> The Inter-reader reliability for the form was 100%. The time required to document and report the MSUS findings was 1 minute. Previous handwritten reports took 5 minutes. For a clinic with 10 patients, using the new form can save up to 40 minutes. <h3>Conclusions</h3> The use of our MSUS graphical tick-box tool ensured 100% inter-reader reliability between the RNP and the RSPS. Provision of one-stop reports of the MSUS findings allows the RNP to base clinical decisions on presence or absence of US detected synovitis and erosions.It is fast to complete and read, thus saving time in clinic. <h3>Disclosure of Interest</h3> None Declared
First-Trimester Urine Concentrations of Phthalate Metabolites and Phenols and Placenta miRNA Expression in a Cohort of U.S. Women
Authors: Jessica LaRocca, Alexandra M. Binder, Thomas F. McElrath, Karin B. Michels
Journal: Environmental Health Perspectives (2015)

There is increasing concern that early-life exposure to endocrine-disrupting chemicals (EDCs) can influence the risk of disease development. Phthalates and phenols are two classes of suspected EDCs that are used in a variety of everyday consumer products, including plastics, epoxy resins, and cosmetics. In utero exposure to EDCs may affect disease propensity through epigenetic mechanisms.The objective of this study was to determine whether prenatal exposure to multiple EDCs is associated with changes in miRNA expression of human placenta, and whether miRNA alterations are associated with birth outcomes.Our study was restricted to a total of 179 women co-enrolled in the Harvard Epigenetic Birth Cohort and the Predictors of Preeclampsia Study. We analyzed associations between first-trimester urine concentrations of 8 phenols and 11 phthalate metabolites and expression of 29 candidate miRNAs in placenta by qRT-PCR.For three miRNAs--miR-142-3p, miR15a-5p, and miR-185--we detected associations between Σphthalates or Σphenols on expression levels (p < 0.05). By assessing gene ontology enrichment, we determined the potential mRNA targets of these microRNAs predicted in silico were associated with several biological pathways, including the regulation of protein serine/threonine kinase activity. Four gene ontology biological processes were enriched among genes significantly correlated with the expression of miRNAs associated with EDC burden.Overall, these results suggest that prenatal phenol and phthalate exposure is associated with altered miRNA expression in placenta, suggesting a potential mechanism of EDC toxicity in humans.
Abstract LB-248: Towards a global picture of breast cancer: transcriptional networks, pathways, regulators, and validation
Authors: Bin Zhang, Linh Tran, Derry Jonathan, Jun Zhu, Stephen Friend
Journal: Cancer Research (2010)

Abstract The unprecedented volumes of large-scale genomic and genetic data being generated today, combined with the poor understanding of the genetics underlying complex biological systems, demand a systems biology approach to identify a global landscape of interactomes that contribute to a variety of clinical endpoints such as tumor progression. Along this direction, two kinds of gene network analyses, association (gene coexpression network) and causality inference (Bayesian network), have been almost independently developed in the past decade. In spite of the significant success of the methods, it is still far away from generating a clear picture for even a single pathway involved in complex human disease like cancer due to insufficient information and various limitations of the methods. Here we present a framework to combine the two types of network analyses with an aim of integrating many high-throughput gene expression datasets on multiple platforms. By applying the integrative network approach to four large scale microarray datasets in breast cancer, we first systematically uncover gene modules/pathways involved in breast cancer progression through a weighted gene coexpression network analysis, then use these gene modules to partition a complex Bayesian network constructed from the same datasets, and finally identify key regulators of the modules predictive of outcomes. A significant portion of the predicted novel gene targets are validated through a large number of siRNA experiments in breast cancer cell lines. This allows us to globally validate breast cancer gene networks. The integrative approach and the findings will have a significant impact on breast cancer research and drug development. 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 LB-248.