tbuckley/cabot-search huggingface dataset:
AB0860 A New Safety Meta-Analysis of Ketoprofen VS Ibuprofen and Diclofenac: Risk and Benefit of NON Steroidal Anti-Inflammatory Drugs beyond Efficacy Meta-Analysis
Authors: P. Sarzi-Puttini, F. Atzeni, L. Lanata, A. Monguzzi, M. Bagnasco
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Over the last decades, ketoprofen, ibuprofen and diclofenac have been the most often prescribed drugs in the management of mild-to-moderate pain, chronic inflammatory and degenerative joint diseases. <h3>Objectives</h3> The aim of this study was to perform a new meta-analysis of randomised controlled trials (RCTs) in order to compare the safety of oral ketoprofen with that of ibuprofen and/or diclofenac therefore obtaining complete risk/benefit profiles of these drugs. <h3>Methods</h3> A systematic literature search was performed on main databases (Medline, Cochrane Central and Embase) until July 2013 to identify RCTs comparing directly therapeutic doses of oral ketoprofen (50-200 mg/day) vs ibuprofen (600-1800 mg/day) or diclofenac (75-150 mg/day). in accordance with the Cochrane Collaboration guideline, two rheumatologists carried out independently study selection. <h3>Results</h3> A total of 10 RCTs involving 843 patients met the inclusion criteria: six comparing ketoprofen vs ibuprofen and four comparing ketoprofen vs diclofenac. 6 of the 10 RCTs included 493 patients with systemic rheumatic diseases such as RA, OA, ankylosing spondylitis (AS), low back pain or painful shoulder. Treatments based on oral administration of ketoprofen showed a RR (Risk Ratio) of 1.02 of developing an adverse event (AE) vs treatments based on diclofenac or ibuprofen, even though there was no statistical significance in this result (P=0.91, 95% CI 0.78, 1.33). The difference between rates of AEs (Risk difference) with the three molecules was equal to 0 (P=0.91, 95% CI -0.05, 0.05), and no serious AE was observed. Moreover, there was no difference across the studies in the heterogeneity test for the safety outcome (χ<sup>2</sup>=9.07 - df=9 - P=0.43, I<sup>2</sup> =1%), demonstrating homogeneity of trials and reliability of meta-analysis results. <h3>Conclusions</h3> Taken together, the results of this meta-analysis show that ketoprofen is well tolerated and its safety profile is comparable to ibuprofen and diclofenac, with no serious AE observed. Therefore, these data on oral ketoprofen support its recommendation in clinical practice. <h3>References</h3> Sarzi-Puttini P, et al. Efficacy of ketoprofen vs ibuprofen and diclofenac: a systematic review of the literature and meta-analysis. Clin Exp Rheumatol. 2013;31:731-8 <h3>Disclosure of Interest</h3> P. Sarzi-Puttini Grant/research support: He received a restritcted grant for study, F. Atzeni: None declared, L. Lanata Employee of: Dompe9SpA, A. Monguzzi Employee of: Dompe9 SpA, M. Bagnasco Employee of: Dompe9 SpA <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.3690
Abstract 4080: Metformin and rapamycin inhibit proliferation and alter glucose metabolism in endometrial and ovarian cancer cell lines
Authors: Chunxiao Zhou, Hallum Dickens, Jada Robinson, Paola A. Gehrig, Victoria L. Bae-Jump
Journal: Cancer Research (2011)

Abstract Objectives: A well-established phenomenon of tumor cells is a shift in glucose metabolism from oxidative phosphorylation to aerobic glycolysis, termed the “Warburg” effect. Glycolysis is a much less efficient mechanism of producing ATP, suggesting that cancer cells may have an inherently high need for rapidly metabolized glucose. Glucose metabolism and growth control are tightly linked in proliferating cells and involve signaling pathways such as the PI3K/Akt/mTOR pathway. Metformin and rapamycin both exert their anti-tumorigenic effects through inhibition of the PI3K/Akt/mTOR pathway. Thus, our goal was to investigate the mechanism of action of metformin and rapamycin on proliferation and glucose metabolism in vitro using both endometrial and ovarian cancer cell lines Methods: The endometrial cancer cell lines, ECC-1 and Ishikawa, and the ovarian cancer cell lines, CAOV-3 and SKOV-3, were used in these studies. Cell proliferation was assessed after exposure to metformin and rapamycin, and viable cell densities were determined by measuring conversion of the metabolic dye, MTT. Western immunoblotting was performed to determine the expression of the glucose transporters, GLUT1 and GLUT4, and phosphorylated glycogen synthase kinase-3 alpha and beta (GSK-α and GSK-β). Expression of phosphorylated S6, a downstream target of the mTOR pathway, was also evaluated by Western immunoblotting. Results: Metformin and rapamycin both potently inhibited growth in a dose-dependent manner in the endometrial and ovarian cancer cell lines (IC50 of 1-10 mM for metformin and IC50 of 5-18 nM for rapamycin). Metformin and rapamycin also stimulated expression of the glucose transporters, GLUT1 and GLUT4, and increased phosphorylation of GSK-α and GSK-β among the endometrial and ovarian cancer cell lines. In parallel, S6 phosphorylation was decreased after treatment with metformin and rapamycin. Conclusions: Metformin and rapamycin are both potent inhibitors of cell proliferation and potentially alter glucose metabolism in endometrial and ovarian cancer cells. These findings suggest that metformin and rapamycin may have two interrelated anti-tumorigenic benefits – inhibition of the PI3K/Akt/mTOR pathway and disruption of glucose uptake and utilization by tumor 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 4080. doi:10.1158/1538-7445.AM2011-4080
Abstract LB-340: Inhibition of autophagy enhances the anticancer activity of the retinoic acid derivative VN/12-1 in endocrine resistant human breast cancer cell lines
Authors: Abhijit M. Godbole, Puranik Purushottamachar, Lalji K. Gediya, Vincent C. O. Njar
Journal: Cancer Research (2010)

Abstract Breast cancer is the most common cancer and the second leading cause of cancer related deaths among women in the United States. Although endocrine therapies such as anti-estrogens and aromatase inhibitors have improved the overall survival, resistance to this therapy remains a major concern. Autophagy is a unique, regulated mechanism of cell survival by catabolism of proteins under nutrient deprivation or chemotherapeutic stress. It is an important cause of resistance to chemotherapeutic agents. VN/12-1, a novel 4-imidazolyl methyl ester of retinoic acid synthesized in our laboratory, showed excellent anti-proliferative activity (as shown by MTT assay) in endocrine resistant human breast cancer cell lines SK-BR-3 and MDA-MB-231. Its IC50 in SK-BR-3 cells was 5.2 μM compared to 15.2 μM (all-trans retinoic acid-ATRA) and 45.6 μM (letrozole). For MDA-MB-231 cells, IC50 of VN/12-1 was 7.3 μM compared to 53.7 μM (ATRA) and 74.3 μM (letrozole). At low micromolar concentrations of VN/12-1 treatment on these cells, western blot analysis and imaging studies confirmed the presence of autophagosomes. This was associated with up-regulation of proteins involved in endoplasmic reticulum (ER) stress, markers for DNA damage and downregulation of cyclin D1 and phosphorylated Akt. Co-treatment with chloroquine (an autophagy inhibitor) resulted in increased sensitivity of cells to VN/12-1 as indicated by decrease in cell viability from 71.22% for VN/12-1 (3 μM) alone, 90.18% chloroquine (3 μM) alone to 34.31% for the combination of VN/12-1 (3 μM) and chloroquine (3 μM) in SK-BR-3 cells. It also resulted in induction of apoptosis which was caspase mediated. In summary, ER stress and DNA damage induced by VN/12-1 resulted in cell cycle arrest and induction of autophagy. Inhibition of autophagy by chloroquine overwhelmed this cellular stress and resulted in apoptotic cell death in endocrine resistant breast cancer cell lines. Significance: VN/12-1 and its combination with autophagy inhibitor chloroquine is a novel therapeutic alternative to treat endocrine resistant breast cancer and hence warrants further pre-clinical and clinical development. This is the first in vitro study which showed an enhancement of anti-cancer activity of a retinoic acid derivative by an autophagy inhibitor in endocrine resistant human breast cancer cell lines. 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-340.
A7.10 Results of abatacept treatment in patients with different duration of rheumatoid arthritis
Authors: MA Kanonirova, GV Lukina, YA Sigidin, ES Aronova, SI Glukhova, EL Luchihina, DE Karateev, EL Nasonov
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Efficacy and tolerability of abatacept (ABA) is confirmed in randomised clinical trials. There isn’t enough data about results of ABA treatment in patients (pts) with different duration of rheumatoid arthritis (RA). <h3>Objectives</h3> To analyse efficacy and safety of ABA treatment in pts with early (ERA) and long-standing (LS) RA. <h3>Materials and methods</h3> Eighty patients with active RA were divided in two groups, the first one, less than three years duration (ERA - 51%) and the second one, more than three years duration (LS RA – 49%). Most of them were women, age 49 ± 13.5 years, with a high disease activity (DAS28=5.25 ± 1.15), RF-positive (75,7%) and ACPA-positive (75%). Disease activity was measured by DAS28, functional status – by HAQ-DI. Results were assessed every 12 weeks by EULAR criteria. <h3>Results</h3> Pts had high disease activity by DAS28 (ERA DAS28–5.1 ± 0.9, LS RA - 5,3) and mild disability by HAQ-DI (ERA - 1.3 ± 0.6, LS RA - 1.6 ± 0.9) before treatment. Good and moderate response by EULAR criteria was achieved in 80% in the group of ERA and in 67% of pts with LS RA (p &lt; 0.05) after 3 months of therapy. There was no significant difference in achieving good EULAR response between two groups after 6 months of therapy (43.75% - ERA; 38.4% - LS RA). The number of non-responders was similar after 3 months (ERA – 20%, LS RA – 31.4%) and 6 months (ERA – 18.7%, LS RA – 19.2%). After 3 months and 6 months the improvement of HAQ-DI in ERA group was significantly higher, than in LS RA group (p &lt; 0.05). 28 adverse events (AE) in 17 (20%) pts were registered. One pt has herpes zoster and one, abscess of the right thumb. <h3>Conclusion</h3> ABA has shown significant improvement in reduction of disease activity in pts with an inadequate response to previous therapy. There was no significant difference in achieving good EULAR response between pts with early and LS RA. However, pts in ERA group had significant improvement of HAQ-DI comparing with LS RA group. ABA has good safety profile, adverse events were registered only in 20% of pts.
P651 CIRRHOSIS AND LIVER TRANSPLANTATION ARE ASSOCIATED WITH A HIGHER PREVALENCE OF HEPATITIS E VIRUS INFECTION
Authors: M. Riveiro-Barciela, F. Rodríguez-Frías, L. Castells, I. Campos-Varela, M. Homs, C. Cantarell, M. Crespo, R. Esteban, M. Buti
Journal: Journal of Hepatology (2014)
Chromosome Ends Produce a Potential Means of Treatment
Authors: J. McCann
Journal: JNCI Journal of the National Cancer Institute (1995)

Journal Article Chromosome Ends Produce a Potential Means of Treatment Get access Jean McCann Jean McCann Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 87, Issue 9, 3 May 1995, Pages 638–639, https://doi.org/10.1093/jnci/87.9.638 Published: 03 May 1995
FRI0234 Cardiac- Specific Troponin-I and Interleukin-6 PREDICT Coronary Atherosclerosis Burden in Rheumatoid Arthritis: Table 1
Authors: G.A. Karpouzas, P. Rezaeian, J. Estis, J. Todd, M.J. Budoff
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is associated with accelerated coronary atherogenesis<sup>1</sup>, myocardial infarction, and mortality. This risk transcends classic cardiac risk factors and may reflect the high inflammatory burden present in this condition. <h3>Objectives</h3> We explored whether various plasma inflammatory biomarkers, or their combinations, predict coronary plaque presence and burden in patients with RA and no symptoms or prior diagnosis of coronary artery disease. <h3>Methods</h3> One hundred and fifty RA patients underwent 64-slice computed tomography angiography (CTA); plaque was evaluated using a standardized AHA 15-segment model. Segment involvement score (SIS- n of segments with plaque), stenosis severity score (sum of individual segmental stenoses- SSS) and plaque burden score (sum of segmental plaque burden- PBS) were computed. High sensitivity cardiac Troponin-I (cTnI), tumor necrosis factor alpha (TNFα), vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), interleukin-17A and F (IL-17A, IL-17F), were quantified in plasma collected at the time of CTA, using the Erenna immunoassay System (Singulex, Alameda, CA). Linear regression models examined associations of individual biomarkers with all plaque outcomes. The ability of individual or combinations of binarized biomarkers to predict plaque outcomes was explored in logistic regression models adjusted for age and gender (model 1), or additionally for hypertension, diabetes, smoking, dyslipidemia, body mass index, and prednisone use (model 2). <h3>Results</h3> Higher tertiles of cTnI correlated with plaque prevalence, as well as increasing CAC, SIS, SSS, and PBS (p-values 0.006, 0.005, 0.01, and 0.009 respectively – not shown). IL-6 and cTnI individually and independently predicted various plaque parameters after age and gender adjustments (model 1, table 1). The combination of elevated cTnI with elevated IL-6 predicted plaque burden after adjustments both for age and gender, as well as additional cardiac risk factors (model 2, table 1). <h3>Conclusions</h3> In RA, biomarkers of cardiac dysfunction (cTnI) and inflammation (IL-6) can predict the presence and burden of coronary plaque as evaluated by CTA. Their associations and prognostic implications for atherosclerosis deserve further evaluation. <h3>References</h3> Karpouzas GA et al. Ann Rheum Dis. 2013 Jul 25. doi: 10.1136/annrheumdis-2013-203617. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2077
Post-Partum Hematoma
Authors: Arthur W. Lyons
Journal: New England Journal of Medicine (1949)

IN REVIEWING discussions on intra-partum and post-partum complications in the obstetric textbooks one finds little space allotted to hematomas. A survey of the literature discloses 188 cases of paravaginal hematoma reported from 1554 to 1948. The incidence varies from 1:1951 deliveries reported by Moschkow1 to 1:7000 by De Lee.2 The immediate vulvar type is the most common. In a review of 1250 deliveries 3 cases of hematoma were found: the first was vulvar, requiring removal of episiotomy sutures, evacuation of the clot and resuturing two hours after delivery; the second was vulvar, requiring removal of sutures, evacuation of the clot . . .
Isolated Uvular Angioedema
Authors: Ana Viana-Tejedor, Ivan Javier Nunez-Gil
Journal: New England Journal of Medicine (2014)

A 59-year-old man was admitted to the coronary care unit with an inferior ST-segment elevation MI. Physical examination uvular angioedema, which resolved within 24 hours after treatment with antihistamines and glucocorticoids. Videos show the angioedema and its resolution.
A3.19 The miR-148a is Induced by TWIST1 and TBET and Promotes the Survival of Effector Memory T Helper 1 Lymphocytes by Regulating the Proapoptotic Gene<i>BIM</i>
Authors: Claudia Haftmann, Anna-Barbara Stittrich, Kristyna Hradlikova, Zhuo Fang, Markus Bardua, Kerstin Westendorf, Gitta Anne Heinz, Thomas Häupl, Joachim Sieper, Hyun-Dong Chang, Nikolaus Rajewsky, Hans-Martin Jäck, Andreas Radbruch, Mir-Farzin Mashreghi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Repeatedly activated effector memory (EM) T helper 1 (Th1) cells in the context of autoimmunity and chronic inflammation exhibit a varity of differences in their cellular programme compared to regular EM Th1 cells. They function independently of activation signals and therefore escape physiological and therapeutical regulation. The acquirement of these properties is probably mediated by reduced expression of the pro-apoptotic protein <i>Bim</i>. Recent results suggest that microRNA (miRNA) mediated regulation of <i>Bim</i> may play an important role for the persistence of EM Th1 cells in autoimmune disease. Therefore, we aimed to identify miRNAs with the ability to suppress the expression of <i>Bim</i> in EM Th1 cells. <h3>Material and Methods</h3> Assuming that Th1 cells involved in autoimmune inflammation have a history of repeated restimulation by persistent (auto-) antigens, we use in vitro generated acutely (once) and chronically (four times) activated murine EM Th1 cells. By using high-throughput sequencing of miRNA expression libraries, we have identified miRNAs being differentially expressed between once and repeatedly reactivated Th1 cells. By performing gain or loss of function experiments we examined the functional impact of miR-148a in chronically activated EM Th1 cells. <h3>Results</h3> We found that among Th subsets chronically activated EM Th1 cells uniquely express microRNA-148a. MiR-148a regulates expression of the proapoptotic gene <i>Bim</i> leading to a decreased <i>Bim/Bcl2</i> ratio. When inhibiting miR-148a using antagomirs in Th1 cells Bim expression increases, leading to enhanced apoptosis and reduced expansion of repeatedly reactivated EM Th1 cells. Knockdown of <i>Bim</i> expression by siRNA in miR-148a antagomir treated cells restored viability of the Th1 cells. This clearly proofs that miR-148a controls viability exclusively by regulating Bim expression. T cells isolated from the synovium of arthritic patients exhibit elevated miR-148a expression. Interestingly, Tbet (Th1 master transcription factor) and Twist1 (marker for chronically activated EM Th1 cells) induce expression of miR-148a. <h3>Conclusions</h3> Taken together the data imply that Tbet and Twist1, besides controlling pathogenicity of Th1 cells, also regulate the longevity in chronic inflammation via the miR-148a-Bim-axis. MiR-148 plays an important role for the survival of EM Th1 cells in autoimmunity and chronic inflammation, thus, represents a highly potent molecular target for therapeutical treatment.
Abstract 4982: Comparison of T cell responses to a melanoma-related antigen in elderly and young melanoma patients.
Authors: Nitya G. Chakraborty, Prashant Singh, Soheil S. Dadras, Bijay Mukherji, Upendra P. Hegde
Journal: Cancer Research (2013)

Abstract It is widely believed that a hypo-and/or dysfunctional state in T cells in the elderly is a negative factor in immune defense against cancer. Accordingly, cancer patients are often excluded from immune-based clinical trials and therapies. The incidence of melanoma is rapidly rising in the elderly. To our knowledge, a critical assessment of the immune responsiveness by the elderly against a relevant melanoma associated antigen has not been carried out. Using the MART-127-35 (M27) epitope as a melanoma-associated target epitope and M27 specific T cell receptor (TCR)-engineered T cells from the elderly (over 70) and young (below 45) as common elements in the comparison, we examined the T cell responses in both cohorts to the M27 epitope and to the Influenza matrix peptide MP58-66 (Flu58) as a control, ex vivo. We also compared the expressions of a number of genes associated with immune response by real-time reverse transcription polymerase chain reaction (qPCR) in formalin fixed primary melanomas from both cohorts, in situ. While we detected a compromised CD8+ T cell response to Flu58 in the elderly, T cells from both cohorts proliferated and synthesized Th1 type cytokines in comparable levels when stimulated by the M27 epitope. qPCR analyses of primary melanomas from elderly patients showed lower levels of Fox-P3 expression but revealed comparable levels of expression of IL-2, IFNγ, TNF α, IL-4, IL-10, IDO, and TGFβ. These findings indicate that elderly patients are quite capable of responding to tumor antigens and need not be excluded from immune-based therapies or clinical trials. Citation Format: Nitya G. Chakraborty, Prashant Singh, Soheil S. Dadras, Bijay Mukherji, Upendra P. Hegde. Comparison of T cell responses to a melanoma-related antigen in elderly and young melanoma patients. [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 4982. doi:10.1158/1538-7445.AM2013-4982
F-18 FDG PET/CT Contributes to More Accurate Detection of Lymph Nodal Metastasis From Actively Proliferating Esophageal Squamous Cell Carcinoma
Authors: Shunsuke Tanabe, Yoshio Naomoto, Yasuhiro Shirakawa, Yasuhiro Fujiwara, Kazufumi Sakurama, Kazuhiro Noma, Munenori Takaoka, Tomoki Yamatsuji, Takao Hiraki, Yoshihiro Okumura, Masahiko Mitani, Mitsumasa Kaji, Susumu Kanazawa, Toshiyoshi Fujiwara
Journal: Clinical Nuclear Medicine (2011)

Evaluating the status of disease progression is critical for planning a therapeutic strategy for esophageal cancer. In this regard, F-18 fluorodeoxyglucose-labeled positron emission tomography (PET) is one of the most useful diagnostic modalities. However, there is room to improve its diagnostic performance, such as distinguishing lymph nodal metastases from false positives. In this study, we examined the diagnostic accuracy of fluorodeoxyglucose PET accompanied by computed tomography imaging (PET/CT) to detect regional lymph nodal metastasis from esophageal squamous cell carcinoma (ESCC).A total of 102 patients diagnosed as ESCC were subjected to this study. These patients had a preoperative PET/CT examination to evaluate the existence of metastasis. The values of maximum standardized uptake value (SUVmax) in primary tumors and in metastasized lymph nodes were measured to analyze their relationship with various clinicopathologic characteristics including the status of tumor cell proliferation, which was assessed by immunohistochemistry for Ki-67.The SUVmax of the primary tumor was positively correlated with tumor size and vessel invasion, and was positively related with the SUVmax of lymph nodal metastasis, especially in cases of poorly differentiated ESCC. The SUVmax of metastasized lymph nodes was higher in larger-sized metastasized lymph nodes, whereas the Ki-labeling index of lymph nodal metastasis was positively related with the SUVmax per unit area (SUVmax/mm). The diagnostic accuracy of PET/CT (87.3%) was higher than that of conventional CT scans (78.4%).The improved diagnostic accuracy of PET/CT can be explained by its ability to detect actively progressive metastasis at an early phase regardless of size.