tbuckley/cabot-search huggingface dataset:
FRI0114 The effect of combination therapy and prednisolone on haemostatic markers in rheumatoid arthritis: The cobra-light study:
Authors: I.A. van den Oever, D.J. Stuijver, D. den Uyl, B. van Zaane, M.M. Terwee, W.F. Lems, J.C. Meijers, V.E. Gerdes, M.T. Nurmohamed
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> There is accumulating evidence that rheumatoid arthritis (RA) should be considered as prothrombotic state, explaining the increased risk of thromboembolic events. Suppressing inflammation could reduce this hypercoagulability. COBRA, the combination of step-down prednisolone, methotrexate and sulfasalazine (SSZ) is an effective antirheumatic therapy. Whether glucocorticoids induce a procoagulant state is controversial and depends on the population, thus the effect of prednisolone in RA is unknown. <h3>Objectives</h3> To evaluate the course of haemostatic markers in RA patients during anti-inflammatory therapy and the dose-dependent effect of prednisolone on coagulation and fibrinolysis. <h3>Methods</h3> 22 patients diagnosed with early RA, were randomised to either COBRA therapy or an attenuated form (COBRA-light) with halved initial prednisolone dose and without SSZ. At baseline and after 1, 4 and 26 weeks of treatment, 10 ml of citrated blood was collected for measurement of prothrombin time (PT), activated partial thromboplastin time (aPTT) and five haemostatic markers: prothrombin fragment 1+2 (F1+2), factor VIII (FVIII), von Willebrand factor (vWF), plasminogen activator inhibitor (PAI-1) and D-dimer. For statistical analyses t-tests and linear regression were used. <h3>Results</h3> Baseline characteristics were not significantly different between the 2 groups (each 11 patients). DAS44, CRP, ESR, aPTT, D-dimer and F1+2 decreased during treatment in all patients (table). There was a significant positive association between decrease in CRP and BSE with D-dimer and decrease in CRP, BSE and DAS44 with F1+2 at all time points. There was no difference in the markers between the two groups, except for a stronger decrease in aPTT after 2 weeks (p=0.03) in the COBRA group. This difference was no longer seen at 4 weeks. <h3>Conclusions</h3> Overall, both COBRA and COBRA-light therapy induced an improvement of inflammatory and procoagulant factors in RA. There were no remarkable differences in the haemostatic markers between the two groups, indicating that doses higher than 30 mg of prednisolone have no attributable effect on the procoagulant state in RA. <h3>Disclosure of Interest</h3> None Declared
P1104 IMPACT OF NITAZOXANIDE IN COMBINATION WITH PEGYLATED INTERFERON AND RIBAVIRIN ON END-OF-TREATMENT RESPONSE (ETR) IN PATIENTS WITH CHRONIC HEPATITIS: A DOUBLE BLIND PLACEBO-CONTROLLED TRIAL
Authors: M. Kohla, H. El-Said, A. El-Fert, N. Ehsan, S. Ezzat, H. Taha
Journal: Journal of Hepatology (2014)
Intrauterine growth pattern and risk of childhood onset insulin dependent (type I) diabetes: population based case-control study
Authors: G. Dahlquist, S. S. Bennich, B. Kallen
Journal: BMJ (1996)

To investigate whether prenatal growth affects the risk of development of childhood onset insulin dependent (type I) diabetes mellitus.Population based case-control study.Data from a nationwide childhood diabetes case register were linked with data from the nationwide Swedish Medical Birth Registry.Data from a total of 4584 diabetic children born after 1973 and diagnosed with diabetes from 1978 to 1992 were studied. For each child with insulin dependent diabetes three control children were randomly selected from among all infants born in the same year and at the same hospital as the proband.Birth weight, gestation, maternal age and parity, number of previous spontaneous abortions, and sex specific birth weight by gestational week expressed as multiples of the standard deviation (SD).There was a clear trend in the odds ratio for childhood onset diabetes according to SD of birth weight. The odds ratio (95% confidence interval) for small for gestational age after stratification for maternal age, parity, smoking habits, and maternal diabetes was 0.81 (0.65 to 0.99) and for large for gestational age after similar stratification was 1.20 (1.02 to 1.42).Intrauterine conditions that affect prenatal growth seem also to affect the risk of development of childhood diabetes in the way previously described for postnatal growth: a poor growth decreases and an excess growth increases the risk. The mechanism for this association is unclear.
Abstract P1-08-02: Gene expression changes in methylnitrosourea (MNU)-induced ER+ mammary cancers following short-term treatment of rats with SERMs (Tamoxifen and Arzoxifene)
Authors: R Lubet, P Vedell, C Grubbs, P Bernard, M You
Journal: Cancer Research (2012)

Abstract SERMs have proven to be highly effective in both therapy and prevention of ER+ breast cancers. Tamoxifen has been the most commonly used SERM, but arzoxifene (another high- affinity competitive SERM agonist) showed strong activity in early clinical trials against ER+ breast cancer; although further development was discontinued. Both SERMs have shown a dose dependent effect on prevention and therapy of rat mammary tumors in the ER+ MNU model of cancer. Of interest, the doses required for prevention was significantly lower than the doses required for therapy. In the present study, rats bearing mammary cancers induced by MNU were treated with tamoxifen (0.66, 3.3, 20 and 100 ppm in diet) or arzoxifene (3.0 ppm in diet) for 5 days. Global gene expression analysis showed that more than 100 genes were down-regulated and more than 100 genes were up-regulated (p &amp;lt; 0.05 and fold change &amp;gt;1.5) in cancers treated with tamoxifen doses &amp;gt; 3 ppm; and that many of these gene changes were dose dependent. The genes modulated by tamoxifen and arzoxifene were enriched in the cell cycle pathway that were related to chromosome condensation in prometaphase [including Aurora-A, Aurora-B, Bub1B, non-SMC condensing I complex, subunit H (BRRN1), Condensin, CAP-G, CAP-G/G2, CAP-H/H2, CAP-D2/D3, CAP-E, TOP2, Cyclin A, Cyclin B, CDK1, Histone H1 and inter-centromere protein (INCENP]. Employing a different set of tamoxifen treated samples, we were able to confirm that many of the same genes were modulated employing a quantitative RT-PCR assay. Finally, we will compare certain of the gene changes obtained in the animal model with gene changes observed in human neoadjuvant trials. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-08-02.
Abstract 100A: Prognostic significance of the expression levels of target genes of retinoic acid in hepatocellular carcinoma.
Authors: Goshi Shiota, Keita Kanki
Journal: Cancer Research (2013)

Abstract Hepatocellular carcinoma (HCC), a common and fatal malignancy, is increasing in incidence in developed countries. HCC generally arises in cirrhotic livers and has a poor prognosis because of the high incidence of disease recurrence after curative treatment. To improve patient prognosis, identification of new targets for early detection, chemoprevention, and treatment is urgently required. In the pathogenesis of chronic liver disease, activation of hepatic stellate cells accompanied by decreasing vitamin A storage has been observed, leading to development of the hypothesis that the loss of retinoid content is closely associated with the progression of chronic liver diseases including HCC. In a previous study, we observed steatohepatitis and HCC development in transgenic mice that express a dominant-negative form of RAR in a liver-specific manner. These findings indicate that identifying genes regulated by retinoid signaling is important for understanding the molecular mechanisms of liver disease leading to hepatocarcinogenesis. To identify novel retinoic acid (RA)-responsive genes facilitating the antitumor activity of RA in hepatocellular carcinoma (HCC), we performed a gene screening based on in silico analysis of retinoic acid response elements (RAREs), chromatin immunoprecipitation analysis of the retinoic acid receptor (RAR), and gene expression analysis. We identified 201 candidate genes with promoter regions containing consensus RAREs using in silico analysis. We identified 126 candidate genes with functional RAREs which are occupied by RAR and finally selected 26 RA-responsive genes in 2 human HCC and 1 human breast cancer cell lines. Among these genes, we identified OTU domain-containing 7B (OTUD7B) and frizzled family receptor 4 (FZD4) as potential inducers of RA-mediated antitumor activity. OTUD7B and FZD4 were involved in the regulation of nuclear factor κB and Wnt/β-catenin signaling, respectively, and affected the viability of HCC cell lines. To evaluate the clinical significance of RA-responsive genes in HCC, gene expression analysis was performed using tumor and nontumor tissues from 171 patients. In univariate and multivariate analyses, low OTUD7B mRNA expression in tumor tissue was associated with a poor prognosis forHCC patients. Conclusion: We identified RA-responsive genes that exhibit antitumor activity against HCC cells. These findings provide useful information to understand the molecular mechanisms underlying the chemopreventive effects of RA against liver diseases, including HCC. Citation Format: Goshi Shiota, Keita Kanki. Prognostic significance of the expression levels of target genes of retinoic acid in hepatocellular carcinoma. [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 100A. doi:10.1158/1538-7445.AM2013-100A
Abstract 1498: Breast adipose mesenchymal stem cells and mammary fibrosis
Authors: Molly L. Bristol, Patrick Sachs, Xu Wang, Min Zhao, Lynn Elmore
Journal: Cancer Research (2012)

Abstract Introduction: At a biochemical level, the most common symptom of aging and its related pathologies (i.e. cancer) is the accumulation of altered or abnormal proteins. Aberrant proteins can induce oxygen free radical generation and inflammation; additionally an abnormal inflammatory response can lead to over-production and deposition of extracellular matrix (ECM) components, leading to fibrosis. The linkage between fibrosis and cancer is well established in the lung; alternatively breast fibrosis is a less understood phenomenon. Fibrosis is characterized by the excess production and altered composition and crosslinking of the ECM. Myofibroblasts are the principal mediators of fibrosis, producing abundant ECM as well as inflammatory and angiogenic factors; chronic tissue fibrosis is associated with tumor development. Likewise, stromal cells within the breast tumor microenvironment can provide tumor-promoting effects. Yet, very little is known regarding the role of local-adipose mesenchymal stem cells (MSCs) in the development of cancer. Objectives: If breast density and fibrosis are both associated with less fat and more connective tissue, we reason that resident breast MSCs (b-MSCs) are chemoattracted toward mammary glandular elements where they trigger a desmoplastic response characterized by their transdifferentiation into myofibroblasts, rather than differentiating along an adipocytic lineage; thus proposing that b-MSCs, an understudied yet abundant stromal constituent, contribute early in the development of breast cancer. Moreover, if b-MSCs contribute to fibrosis, it is critical to understand and deter this early fibrotic initiation factor. Preliminary Data, Methodology, and Future Directions: Affymetrix data, qRT-PCR, and western blotting results reveal that undifferentiated b-MSCs constitutively express multiple matrix metalloproteinases and chemokine receptors, which could guide these stromal cells from local fat stores into the parenchyma, activating a cascade of events leading to fibrosis. qRT-PCR reveals b-MSCs express multiple members of the epidermal growth factor (EGF) receptor family, most notably HER1. Soluble heparin binding epidermal growth factor (HB-EGF) and EGF modestly effects b-MSC growth, but markedly enhances migration. Moreover, HB-EGF and EGF interfere with adipogenic differentiation. Future studies will analyze the fibrogenic response initiated by b-MSCs in co-culture with normal, pre-malignant and malignant breast epithelial cells and evaluate the effectiveness of the dipeptide, carnosine, on reducing fibrogenesis. Support: This work was supported by a DOD Breast Cancer Research Program Idea Award (BC094734) to L.E. 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 1498. doi:1538-7445.AM2012-1498
Dual Origin of Intimal Cells in Cardiac-Allograft Arteriosclerosis
Authors: L. James Kennedy, Irving L. Weissman
Journal: New England Journal of Medicine (1971)

The origin of the cells present in the arterial intimal thickening in a human cardiac allograft surviving for two years was determined by fluorescent antiserums directed against the donor and host HL-A antigens. The majority of the cells in the thickened intima were of donor tissue type, but in one vessel an appreciable number of cells from the host were identified in the thickened arterial intima.
P779Constructing a new myocardial bioprosthesis for cardiac repair
Authors: C Prat-Vidal, C Galvez-Monton, I Perea-Gil, S Roura, A Llucia-Valldeperas, C Soler-Botija, A Bayes-Genis
Journal: Cardiovascular Research (2014)

Purpose: Currently, progenitor cells and tissue engineering are being proposed as an addition to conventional therapies of myocardial infarction. Engineered tissue grafts and myocardial bioprostheses aim to improve cellular engraftment and viability, combining cellular components with supporting materials. Here, we proposed a new bioprosthesis composed by human pericardial-derived scaffold and adipose tissue progenitor cells (ATPCs) for human cardiac repair. Methods: Surgical samples of human pericardium were obtained from 39 patients (27 males, 12 females; mean age 68±11 years; range 50 to 84 years) undergoing cardiothoracic surgery, with apparently healthy pericardia. For decellularization, a protocol combining detergents, enzymatic digestion and agitation was used and remaining DNA was quantified by spectrophotometry. Decellularized pericardia were lyophilized by drying under vacuum, sterilized by gamma irradiation and analyzed by scanning electron microscopy. To assess in vitro degradation, lyophilized scaffolds were incubated with 0.1% collagenase I. Recellularization was carried out by mixing equal volume of cell suspension (GFP+-ATPCs in 10% sucrose) with hydrogel (RAD16-I 0.3% in 10% sucrose). In vitro biocompatibility was tested by loading hydrogel (with or without GFP+-ATPCs) in the pericardial scaffolds and then cultured 1 week under standard conditions. Masson's trichrome staining was performed to verify recellularization and cell viability was analyzed with a commercial kit. Results: After decellularization, human pericardia were pale collagen scaffolds free of cellular debris and rich in filaments. Total DNA content within the acellular scaffold was significantly lower (P=0.012) than that obtained for native pericardium (66±24 ng DNA/mg scaffold vs. 214±79 ng DNA/mg pericardium, respectively). Nuclei staining with Hoechst 33342 confirmed no residual nucleic acids in decellularized pericardium. Furthermore, biodegradability experiments showed that scaffolds lost ~70% of their original weight after collagenase I treatment (P<0.001). After 1 week of recellularization, the majority of GFP+-ATPCs remained viable inside the bioprosthesis. Conclusions: Decellularization protocol efficiently removed all cellular and nuclear material of human pericardial tissue. In addition, evidences of biocompatibility and biodegradation of the resulting bioprosthesis were further provided in vitro. This pericardial-based bioprosthesis could be deliverable via currently used, minimally invasive methods, to promote cell homing into damaged myocardium.
GENO-34UNBIASED BIOINFORMATIC CLUSTERING ANALYSIS REVEALS HIGH RISK PATIENT POPULATION OF GRADE 2 GLIOMAS
Authors: Shan He, Yunpeng Liu, Desire Ngoga, Kate Hollinshead, Weiqi Chen, Marina Vabistsevits, Daniel Swan, Jean-Baptiste Cazier, Katrin Lamszus, Garth Cruickshank, Daniel Tennant
Journal: Neuro-Oncology (2015)

Gliomas are the most common type of brain tumour, yet their biology is still poorly understood. Despite recent advances in our understanding of low grade gliomas through the discovery of mutations in isocitrate dehydrogenase (IDH) enzymes 1&2 in the majority of patients, this has only provided us with a single line of sight to new therapies to treat these devastating tumours. To further unpick the biology of grade 2 gliomas, we used an unbiased consensus clustering approach to identify biologically similar groups of tumours based on their gene expression profiles. Through this, we identified three clusters of tumours with significantly differing survival rates, which did not always correlate with IDH status. Importantly, this method of tumour stratification identified a population of patients with an overall survival of  6 years. We therefore report three novel biological groups of grade 2 tumours, and in doing so identified a high risk subgroup of patients who would likely benefit from aggressive early intervention.
THU0447 Calculation of the smallest detectable change (SDC) of radiographic progression in clinical trials with multiple time points: The mean SDC is a valid approximation of the overall SDC:
Authors: V. Navarro-Compán, D. van der Heijde, H. Ahmad, C. Miller, R. Landewé
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> SDC is an important statistic in evaluating radiographic progression in clinical trials in Rheumatoid Arthritis (RA). Two methods to estimate the SDC are available: one is based on the standard deviation (SD) of the difference between change-scores obtained by two readers (according to Bland&amp;Altman (B&amp;A)) and the other is based on generalisability analysis (using ANOVA). ANOVA is required in the case of multiple time points and multiple readers, but is more complicated and time consuming. <h3>Objectives</h3> To evaluate if the average SDC of all available time intervals using the B&amp;A method is a valid surrogate for the ANOVA method to estimate the SDC of radiological progression in RA studies including multiple time points. <h3>Methods</h3> Fifteen datasets from radiographic trials in RA comprised of 20,098 radiographic time points from 7,643 patients were scored by 13 readers as pairs. Scoring was performed by each reader independently according to the modified Sharp van der Heijde method (SHS)<sup>1</sup> with the reader blinded to chronological sequence. The number of time points per study was 2 in 2 trials, 3 in 10 trials, and 4 in 3 trials. According to the B&amp;A method, the datasets were evaluated to calculate the 95% limits of agreement SDC [(± 1.96*SD<sub>Δ (changescore)</sub>)/($√ $2*$√ $K)], where K represents the number of readers, for all intervals between different time points per study and its average. Using the ANOVA method, calculations of the SDC per study were performed considering all time points. Statistical analysis was performed using SPSS software version 18.0. <h3>Results</h3> Median (range) baseline- and progression score was 32 (18-48) and 0.9 (0.5-1.8) units, respectively. Table 1 shows the results for all SDCs using both methods. The average SDC of all intervals calculated with the B&amp;A method was very similar to SDC obtained by ANOVA. The mean difference between both methods was -0.13 (SD 0.28, range -0.48-0.25) units. <h3>Conclusions</h3> We propose to report the mean interval SDC as a good surrogate for the true SDC in trials with multiple time points. <h3>References</h3> van der Heijde DM. Lancet. 1989 May 13;1(8646):1036-8. <h3>Disclosure of Interest</h3> None Declared
Unique findings on endoscopy with narrow-band imaging in colonic lesions of Henoch-Schönlein purpura
Authors: K. Endo, R. Moroi, H. Shiga, S. Takahashi, Y. Kakuta, Y. Kinouchi, T. Shimosegawa
Journal: Endoscopy (2013)

A 61-year-old woman presented with acute lower abdominal pain, bloody diarrhea, and purpura on the right thigh ([Fig. 1]). Urgent sigmoidoscopy revealed edema and multiple hyperemic ecchymotic lesions in the sigmoid colon and rectum ([Fig. 2]), which appeared reddish on viewing with conventional white light and cyan on narrow-band imaging (NBI) ([Fig. 3]). These lesions were indicative of bleeding in the subepithelial layer, which was confirmed on histopathologic examination ([Fig. 4]). On the basis of the endoscopic findings and purpura on the thigh, the patient was clinically diagnosed as having Henoch–Schönlein purpura (HSP). This diagnosis was confirmed following histopathological examination of a skin biopsy specimen. Intravenous administration of prednisolone resulted in rapid improvement of the abdominal symptoms and the purpura of the thigh. Sigmoidoscopy carried out 6 days after the onset of the patient's symptoms, showed complete resolution of the edema and of the multiple hyperemic ecchymotic lesions ([Fig. 5]).
TUMOR UPTAKE OF TRACERS AS A FUNCTION OF TUMOR MASS.
Authors: L. E. Williams, R. B. Duda, R. T. Proffitt, B. G. Beatty, J. D. Beatty, J. Y.C. Wong, J. E. Shively, R. J. Paxton
Journal: Clinical Nuclear Medicine (1987)

Williams, L. E.; Duda, R. B.; Proffitt, R. T.; Beatty, B. G.; Beatty, J. D.; Wong, J. Y.C.; Shively, J. E.; Paxton, R. J. Author Information