tbuckley/cabot-search huggingface dataset:
SP0020 Adam17 as a masterswitch in the regulation of inflammation and cancer
Authors: S. Rose-John, A. Chalaris
Journal: Annals of the Rheumatic Diseases (2013)

Cytokine receptors exist in membrane bound and soluble form. While most soluble receptors are antagonists, some soluble receptors are agonists like soluble receptors of the gp130 cytokine family. <i>In vivo</i>, the IL-6/soluble IL-6R complex stimulates several types of target cells not stimulated by IL-6 alone, since they do not express the membrane bound IL-6R. This process has been named trans-signaling [1]. We have shown that soluble gp130 is the natural inhibitor of IL-6/soluble IL-6R complex responses. The recombinant soluble gp130 protein is a molecular tool to discriminate between gp130 responses via membrane bound and soluble IL-6R responses. We have constructed a fusion of soluble gp130 and the Fc portion of human IgG1. This sgp130Fc protein proved to be efficient in blocking responses via the IL-6/soluble IL-6R complex without affecting IL-6 responses, which are mediated via the membrane bound IL-6R [1]. The soluble IL-6R is mostly generated by proteolysis of the IL-6R transmembrane protein. Shedding of the IL-6R is mediated by the metalloprotease ADAM17, which is also responsible for the cleavage of TNF-α and ligands of the EGF-R. Consequently, activation of ADAM17 has different effects on the activation of the immune response as well as on induction of regenerative responses [2,3]. We have generated hypomorphic ADAM17 mice which express undetectable levels of ADAM17 in all tissues [2]. These mice have been used to address the role of ADAM17 in animal models of inflammation and cancer. Addressing the role of IL-6, we show that the extent of IL-6 trans-signaling in chronic inflammatory diseases and cancer is controlled by the soluble IL-6R. Using the sgp130Fc protein or sgp130Fc transgenic mice we demonstrate that in several chronic inflammatory diseases and cancers including inflammatory bowel disease, peritonitis, rheumatoid arthritis, colon cancer, ovarian cancer and pancreatic cancer, that IL-6 trans-signaling via the soluble IL-6R is a crucial step in the development and the progression of the disease. Therefore, sgp130Fc is a novel therapeutic agent for the treatment of chronic inflammatory diseases and cancer [1, 4-9]. <h3>References</h3> Jones et al (2011) J Clin Invest 121: 3375-3383 Chalaris et al (2010) J Exp Med 207: 1617-1624 Scheller et al (2011) Trends Immunol 32: 380-387 Barkhausen et al Crit Care Med 39: 1407-1413 Greenhill et al (2011) J Immunol, 186: 1199-208 Lesina et al (2011) Cancer Cell 19: 456-469 Schiechl et al (2011) J Clin Invest 121: 1692-1708 Lo et al (2011) Cancer Res 71: 424-34 Schuett et al (2012) Arterioscler Thromb Vasc Biol32: 281-290 <h3>Disclosure of Interest</h3> S. Rose-John Shareholder of: Conaris Research Institute, A. Chalaris: None Declared
One Woman Begins Fight to Eliminate China's Massive Smoking Problem
Authors: F. X. Mahaney
Journal: JNCI Journal of the National Cancer Institute (1989)

Journal Article One Woman Begins Fight to Eliminate China's Massive Smoking Problem Get access Francis X. Mahaney, Jr. Francis X. Mahaney, Jr. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 6, 15 March 1989, Pages 392–394, https://doi.org/10.1093/jnci/81.6.392 Published: 15 March 1989
AB0166 Up-regulation of SOCS3 by calcineurin inhibitor, tacrolimus, suppresses IL-6/SIL-6R-mediated rankl expression in fibroblast-like synoviocytes
Authors: W.-T. Chung, H. Lee, J.H. Kim, S.-H. Park, J.-Y. Choe, S.-K. Kim
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objectives</h3> Interactions between interleukin-6 (IL-6)/gp130/Janus activated kinase (JAK)/signal transducer and activator of transcription-3 (STAT3) and suppressor of cytokine signaling (SOCS) are responsible for the expression of receptor activator of NF-kB ligand (RANKL), essential factor for osteoclastogenesis. We investigated whether calcineurin inhibitor, tacrolimus, suppresses RANKL expression in fibroblast-like synoviocytes through regulation of IL-6-mediated signaling. <h3>Methods</h3> RANKL/JAK/STAT/SOCS expressions from IL-6-stimulated fibroblast-like synoviocytes (FLS), cultured from synovium of rheumatoid arthritis (RA) patients, were assessed by western blotting. RANKL levels after tacrolimus were measured by real-time polymerase chain reaction (PCR) and Ensyme-linked immunosorbent assay (ELISA). SOCS3 knockdown FLS using siRNA transfection for SOCS was used to evaluate the effect of tacrolimus on SOCS3. Immunofluorescent staining was also performed to identify the effect of tacrolimus on RANKL and SOCS. <h3>Results</h3> We identify that RANKL expression in RA FLS is regulated through IL-6/sIL-6R/JAK2/STAT3/SOCS3 pathway. Tacrolimus inhibits the RANKL expression in IL-6/sIL-6R-stimulated FLS through STAT3 suppression by up-regulation of SOCS3. Tacrolimus more potently suppresses the RANKL expression in FLS, compared to dexamethasone and methotrexate. Among negative regulators of JAK/STAT pathway such as CIS1, SOCS1, and SOCS3, only SOCS3 is regulated by tacrolimus. <h3>Conclusions</h3> Tacrolimus might be a potent regulator for osteoclastogenesis through down-regulation of RANKL production of RA FLS. <h3>Disclosure of Interest</h3> None Declared
Reply to Chun et al. (2)
Authors: W. Gong, F. Zhi, B. Jiang
Journal: Endoscopy (2012)

We read the letter of Chun et al. with great attention. They raised several pertinent questions about endoscopic submucosal tunnel dissection (ESTD) for the treatment of upper gastrointestinal submucosal tumors (SMTs), concerning the indications, advantages, and disadvantages. We do agree with some of the opinions they put forward. However, regarding some other questions, we would like to give some further explanation.
Targeting Agents Alone to Cure Acute Promyelocytic Leukemia
Authors: Sai-Juan Chen, Zhu Chen
Journal: New England Journal of Medicine (2013)

Acute promyelocytic leukemia (APL) is a distinct subtype of acute myeloid leukemia (AML) that is characterized by abnormal promyelocytes, a life-threatening bleeding syndrome, and t(15;17) chromosomal translocation. APL used to be the worst form of leukemia.1,2 The introduction of anthracycline-based chemotherapy in the 1970s yielded a complete remission rate of 70% and a long-term survival rate of 35 to 45%.1 The use of all-trans retinoic acid (ATRA) in the 1980s represented a revolution in APL treatment because of a high complete-remission rate (>90%) and an essential clue to the leukemogenicity of the chimeric gene product PML-RARA resulting from . . .
Treatment of Malignant Pelvic Tumors by Extracorporeal Perfusion with Chemotherapeutic Agents
Authors: W. Gerald Austen, Antony P. Monaco, George S. Richardson, William H. Baker, Robert S. Shaw, John W. Raker
Journal: New England Journal of Medicine (1959)

AN important limitation to intravenous systemic use of nitrogen mustard and allied compounds has been the toxicity of the drugs to the normal tissues of the gastrointestinal tract and hematopoietic system.1 Doses within the limits of systemic tolerance are often without tumorocidal effect, and larger doses may cause systemic toxicity hazardous to life. Direct intra-arterial administration of nitrogen mustard produces high local tumorocidal levels but does not entirely eliminate systemic toxicity2 and is frequently associated with severe local reaction and vascular thrombosis.3 , 4 By isolating the circulation of a region bearing a tumor and perfusing it by a method utilizing an . . .
Treatment of a 6-Year-Old Girl with Vesicoureteral Reflux — Polling Results
Authors: Daniela J. Lamas, Julie R. Ingelfinger, Lisa S. Rosenbaum
Journal: New England Journal of Medicine (2011)

In late July, we presented the case of a 6-year-old girl with persistent bilateral vesicoureteral reflux. Readers' votes in favor of watchful waiting, antibiotic prophylaxis, or surgical repair are shown by country.
DONOR-RECIPIENT RACE MISMATCH INCREASES GRAFT FAILURE AND MORTALITY AFTER ADULT HEART TRANSPLANTATION: A PROPENSITY-MATCHED STUDY OF THE UNITED NETWORK FOR ORGAN SHARING DATABASE
Authors: Marjan Mujib, Nabila K. Mazumder, Dhaval Kolte, Sahil Khera, Wilbert Aronow, Prakash Harikrishnan, Chandrasekar Palaniswamy, Sachin Sule, Ali Ahmed, Diwakar Jain, Gregg Lanier, Alan Gass, Howard A. Cooper, Gregg Fonarow, Julio Panza
Journal: Journal of the American College of Cardiology (2015)
LEFT VENTRICULAR REGIONAL TIME CORRELATION BY ECHOCARDIOGRAPHIC STRAIN ANALYSIS IS PREDICTIVE OF SURVIVAL FREE FROM ARRHYTHMIAS IN NON-LEFT BUNDLE BRANCH PATIENTS AFTER CARDIAC RESYNCHRONIZATION THERAPY
Authors: Stephanie C. Holt, Bhupendar Tayal, Antonia Delgado-Montero, Sanjeev Shroff, David Schwartzman, Samir Saba, John Gorcsan
Journal: Journal of the American College of Cardiology (2015)
P136 DEFICIENCY OF IL-33 SENSITIZES TO SEVERE LIVER INJURY INDUCED BY ConA BUT NOT BY CCl4 IN MICE
Authors: M.I. Arshad, A. Filliol, V. Genet, C. Lucas-Clerc, J.-P. Girard, C. Piquet-Pellorce, M. Samson
Journal: Journal of Hepatology (2014)
Abnormal Schilling Test Corrected by Intestinal Juice
Authors: Robert H. Resnick, Robert Colman, Abram London, Howard Richter
Journal: New England Journal of Medicine (1963)

A NUMBER of pathologic processes may impair the intestinal absorption of vitamin B12. These conditions include pernicious anemia,1 sprue and other malabsorptive syndromes,2 blind loops,3 , 4 massive intestinal resection,5 iron deficiency6 and postgastrectomy states.7 , 8 Reversal of this abnormality may depend upon intrinsic factor9 (as in pernicious anemia), ACTH10 (as in sprue), surgical correction of blind intestinal loops11 or suppression of bacterial flora with antibiotics.3 , 12 Recently, Colle et al.13 described improvement in absorption of radioactively labeled vitamin B12 after oral administration of intestinal secretions. Nevertheless, the data presented indicate failure to reproduce the effect on one occasion as well . . .
Effect in Man of Large Doses of Pyridoxine on Serum Cholesterol
Authors: ROBERT B. FAILEY
Journal: Circulation Research (1958)

Pyridoxine (400 mg./day) was given to 21 individuals for periods up to a maximum of 36 days. A slight but significant fall in serum cholesterol levels was observed, the effect being more marked in diabetic than in nondiabetic subjects.
Indwelling Arterial Catheters as a Source of Nosocomial Bacteremia
Authors: Walter E. Stamm, Joseph J. Colella, Roger L. Anderson, Richard E. Dixon
Journal: New England Journal of Medicine (1975)

Between mid-May and mid-October, 1973, 49 blood cultures from 14 patients in an intensive care unit were positive for flavobacterium species, Group II-b. We conducted an investigation to determine how patients were being infected with this unusual organism. Comparison of the 14 infected patients with 37 controls associated indwelling arterial catheters with subsequent flavobacterium bacteremia (p = 0.005). Risk of infection was greatest during the period in which blood gas determinations were done most frequently (the first three days of catheterization) and in which infected patients had more blood gas determinations than control patients with arterial catheters (p less than 0.05). Flavobacterium species was cultured from in-use arterial catheters, from stopcocks, and from ice in the intensive-care unit's ice machine; the catheters were probably contaminated by syringes that were cooled in ice before being used to obtain arterial specimens for blood gas determination. This outbreak calls attention to arterial monitoring systems as a potential source of nosocomial infection.
SAT0304 Comparison of sacroiliac MRI evaluation versus sacroiliac X-rays in peripheral psoriatic arthritis: Evidence of silent disease
Authors: J.L. Fernandez-Sueiro, J. Pinto Tasende, S. Pertega Diaz, E. González, F. Blanco
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Although there are no consensus on how to define spinal involvement in axial psoriatic artritis (axPsA), our data suggest that the presence of spinal symptoms (defined as a combination of inflammatory back pain plus back stiffness) can be sufficient. However x-ray evaluation of sacroiliac joints may be normal at the first stage of the disease. <h3>Objectives</h3> To evaluate the negative predictive value of sacroiliac x-rays versus MRI to rule out the diagnosis of sacroiliitis in peripheral PsA. <h3>Methods</h3> Cross sectional descriptive and observational study of PsA patients classified according to CASPAR criteria. All patients had peripheral arthritis not spinal back pain and normal or grade I sacroiliac involvement determined by x-rays. All patients were evaluated according to current standard care. HLA-B27 was determined in all patients. Sacroiliac MRI was performed with either a Tesla 1.5 Gyroscan Intera (Philips MS) or Tesla 1.5 Signa-Excite with the following coronal sequences T1-TSE, T2-TGE and STIR with slices of 4mm of thickness, criteria for lesions were as ASAS proposal. The negative predictive value of x-rays versus MRI was determined as well as the 95% CI. Patients’ characteristics were compared according to MRI results, by means of Mann-Whitney U test, chi-squared test and Fisher’s exact test. <h3>Results</h3> Sacroiliac MRI was performed in 59 patients from a total of 97 PsA patients with peripheral arthritis. There were not significant differences in both groups of patients. MRI patients had a medium age of 49,2±12,9 years, a time of evolution of the disease of 9,4±7,6 years. 96,4% patients had a normal sacroiliac x-rays, 2 had grade I unilateral and bilateral sacroiliitis respectively. HLA-B27 was negative in 93,2% (n=55) patients. 20,3% (n=12) showed active inflammatory lesions (1 with x-rays grade I bilateral). All patients were HLA-B27 negative. There were not significant clinical differences between MRI positive/negative patients, the exception was the occiput to wall distance (p=0,032). The negative predictive value of sacroiliac x-rays versus sacroiliac MRI was of 79,7% (95%IC: 68,5%–90,8%) <h3>Conclusions</h3> Conventional x-rays versus MRI for the evaluation of sacroiliitis had a negative predictive value of 79,7%. In this study the sacroiliac involvement in PsA does not depend on the presence of spinal pain, HLA-B27 or radiological sacroiliitis. Funded with a grant from: Instituto de Salud Carlos III, FIS PI080789 <h3>Disclosure of Interest</h3> None Declared
THU0081 STAT3 Blockade Suppresses Autoimmune Arthritis in Mice Via the Reciprocal Regulation of Treg and Th17 Cells
Authors: J. Lee, J.-H. Lee, S.-M. Jung, S.-K. Kwok, K.-S. Park, S.-H. Park, H.-Y. Kim, Y.-G. Jeong
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> IL-6-mediated STAT3 signaling which is essential to Th17 differentiation plays the central role in the pathogenesis of rheumatoid arthritis. <h3>Objectives</h3> To investigate the molecular mechanism underlying the anti-rheumatic effects and the T cell regulatory effects of STAT3 inhibition, we studied the effects of JAK2 inhibitor, AG490, on Th17/Treg balance and osteoclastogenesis. <h3>Methods</h3> AG490, inhibitor of Jak2, was administered via intraperitoneal injection in collagen-induced arthritis (CIA) model and the <i>in vivo</i> effects of AG490 were determined. The differential expressions of proinflammatory cytokines including IL-17, IL-1β and IL-6 were analyzed by immunohistochemistry. The levels of phosphorylated STAT3 and STAT5, the differentiation of Th17 and Treg after the treatment of AG490 in CIA model were analyzed by immunostaining. In vitro development of Th17 and Treg was analyzed by flowcytometry and real-time polymerase chain reaction. <h3>Results</h3> AG490 administration ameliorated the arthritic phenotype of CIA and increased the proportion of Foxp3-positive Treg cells. In contrast, the proportion of IL-17-producing T cells and the levels of inflammatory markers were reduced in AG490-treated group. The pSTAT3-positive CD4 T cells were reduced, whereas pSTAT5-positve CD4 T cells were elevated with treatment of AG490. Further, AG490 markedly enhanced the expression of molecules associated with Treg development (ICOS, PD-1, ICAM-1 and CD103) as well as Foxp3. The development and the function of osteoclast were also suppressed with AG490 treatment. <h3>Conclusions</h3> Our results suggest that AG490 which specifically regulates JAK2/STAT3 pathway may be the promising treatment strategy for rheumatoid arthritis. <h3>Disclosure of Interest</h3> None Declared
18F-FDG PET/CT Findings of a Recurrent Adenocarcinoma Arising From Malignant Transformation of Abdominal Wall Endometriosis
Authors: Maoqing Jiang, Ping Chen, Long Sun, Qiuli Huang, Hua Wu
Journal: Clinical Nuclear Medicine (2014)

Abdominal wall endometriosis (AWE) is defined as endometrial tissue located superficial to the peritoneum, which usually develops in a surgical scar of cesarean delivery. Malignant transformation of AWE is a very rare disease. The most frequent histotype of malignancy developing from AWE is endometrioid adenocarcinoma. We present F-FDG PET/CT findings in a 37-year-old woman with a recurrent adenocarcinoma arising from malignant transformation of AWE, who underwent a repeat PET/CT scan because of a recurrent mass at the upper right side of the surgical incision after a previous cesarean delivery.
PHYSICIAN ADHERENCE TO PUBLISHED GUIDELINES IN PRESCRIBING ANTI-ARRHYTHMIC MEDICATIONS IN THE MANAGEMENT OF ATRIAL FIBRILLATION
Authors: George Leef, Dingxin Qin, Mian Bilal Alam, Rohit Rattan, Muhammad Bilal Munir, Divyang Patel, Furqan Habib Khattak, Nishit Vaghasia, Sandeep Jain, Samir Saba
Journal: Journal of the American College of Cardiology (2015)
Cooperation of innate and acquired immune system derived signals induces stromal cell activation in chronic inflammation and ectopic lymphoneogenesis
Authors: S Nayar, T Cloake, M Bombardieri, C Pitzalis, P J Lane, M Coles, C D Buckley, F Barone
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Background</h3> Acquisition of lymphoid-like features is a hallmark of ectopic lymphoneogenesis. In lymph nodes, gp8+ fibroblastic reticular cells (FRC) are responsible for lymphoid chemokines/cytokine production and lymphocyte compartmentalisation. gp38 up-regulation on stromal cells has been observed in in cancer and inflammation, suggesting that stroma can acquire lymphoid like features in these conditions. IL-22 and IL-4 are produced by a novel population of innate lymphoid cells (ILCs), similar to lymphoid tissue inducer cells, which have been shown to be critical regulators of stromal cell activation in lymphoneogenesis. The role of ILCs as well as other innate immune cells, in the context of stromal cell activation in inflammation is unknown. The authors designed a novel inducible model of ectopic lymphoneogenesis, in adenoviral infected murine salivary glands to evaluate the dynamics of gp38 expression and the signals regulating stromal cell activation in different phases of inflammation. <h3>Materials and methods</h3> Flow cytometry on disaggregated tissue, qRT-PCR and immunofluorescence was performed at different time points post cannulation (pc) in WT and knockout mice (IL-4R-/-, IL-22-/-, Rag-/-, Ltα-/-, LTβR-/-) in order to investigate the role of these molecules in stromal cell activation. <h3>Results</h3> FACS analysis showed that in WT mice stromal cell activation occurs with significant increase in the percentage of FRC (CD45-GP38+CD31- cells) at day 2 pc. with peak of activation between day 5–8 pc. The full acquisition of lymphoid stromal features with high levels of lymphoid chemokine and cytokine expression was attained by day15 pc. This correlates with acquisition of lymphoid features by the inflammatory aggregates. In absence of innate immune system signals (IL-22, IL-4) lack of gp38 up-regulation at day 2 pc, 5 pc and 8 pc was observed suggesting their role in the initial stromal cell activation. Interestingly, RAG, LTβR, LTα KO mice did not show this defect instead there was a normal degree of stromal cell activation in the early phases (2–8 days pc) but a dramatic decrease in the number of FRCs by day 15 pc. This decrease associated with a significant decrease in lymphoid chemokine/cytokine expression and disorganisation of the inflammatory aggregates. <h3>Conclusions</h3> Overall, these data suggest that stromal cell activation in ectopic sites results from the coordinated actions of signals derived by both the innate and acquired immune system. While innate immune cell signals are likely to be responsible for early activation of local stroma and gp38 acquisition, but maturation into lymphoid stromal requires lymphocyte derived signals and is dependent on LTβR signalling.
1971-1991: Diagnosis and Treatment Advances Improve Survival
Authors: H. Mclntosh
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article 1971−1991: Diagnosis and Treatment Advances Improve Survival Get access Hugh Mclntosh Hugh Mclntosh Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 4, 20 February 1991, Pages 234–236, https://doi.org/10.1093/jnci/83.4.234 Published: 20 February 1991
PROGNOSTIC VALUE OF HEMOCONCENTRATION IN ACUTE DECOMPENSATED HEART FAILURE WITH PRESERVED AND REDUCED EJECTION FRACTION: DATA FROM THE KOREAN HEART FAILURE (KORHF) REGISTRY
Authors: Jaewon Oh, Seok-Min Kang, Namki Hong, Jong-Chan Youn, Sungha Park, Sang-Hak Lee, Donghoon Choi
Journal: Journal of the American College of Cardiology (2015)