tbuckley/cabot-search huggingface dataset:
Anchoring of self-expanding metal stents using the over-the-scope clip, and a technique for subsequent removal
Authors: Sandhya Mudumbi, Jacobo Velazquez-Aviña, Helmut Neumann, K. Kyanam Kabir Baig, Klaus Mönkemüller
Journal: Endoscopy (2014)

<b>Background and study aims:</b> Standard clips do not consistently prevent the migration of covered self-expanding metal stents (SEMS). The aims of this study were to assess the efficacy and safety of the over-the-scope clip (OTSC) system for anchoring SEMS to the esophagus, and to evaluate a novel OTSC removal technique. <b>Methods:</b> This was a single-center, retrospective, cohort study of consecutive patients undergoing SEMS anchoring with OTSC. Removal of the OTSC was accomplished using an inject-and-resect technique. <b>Results:</b> A total of 12 patients were included. The indications for endoscopic stenting were: tracheo-esophageal fistula (n = 7), postoperative leak or fistula (n = 4), perforation (n = 1). Successful application of the OTSC system was accomplished in all patients (100 %). Stent migration during follow-up (mean 3 weeks, range 2 – 4 weeks) occurred in two patients (16.7 %). After healing of the underlying condition, the stent was removed in six patients (50.0 %). In four patients (33.3 %), the anchored stent was left indefinitely in order to treat the underlying condition. There were no complications associated with deployment of the OTSC or SEMS removal. <b>Conclusions:</b> Although endoscopic anchoring of fully covered SEMS with the OTSC was feasible, easy to accomplish, safe, and prevented stent migration in most cases, larger studies are needed to confirm these encouraging early findings. The inject-and-resect technique was safe and efficient for OTSC and stent removal in all cases in which it was attempted.
A Severe Outbreak of<i>Escherichia coli</i>O157:H7–Associated Hemorrhagic Colitis in a Nursing Home
Authors: A O Carter, A A Borczyk, J A Carlson, B Harvey, J C Hockin, M A Karmali, C Krishnan, D A Korn, H Lior
Journal: New England Journal of Medicine (1987)

In September 1985, an outbreak of Escherichia coli O157:H7 enteritis affected 55 of 169 residents and 18 of 137 staff members at a nursing home. The outbreak was characterized by two phases: a primary wave whose source was probably a contaminated sandwich meal and a secondary wave compatible with person-to-person transmission of infection. Among the elderly residents, the incubation period was 4 to 9 days (mean, 5.7 +/- 1.2). Older age and previous gastrectomy increased the risk of acquiring the infection (P = 0.01 and 0.03, respectively). Antibiotic therapy during exposure was associated with acquiring a secondary infection (P = 0.001). Hemolytic uremic syndrome developed in 12 affected residents (22 percent), 11 of whom died. Overall, 19 (35 percent) of the affected residents died, 17 (31 percent) from causes attributable to their infection. Antibiotic therapy after the onset of symptoms was associated with a higher case fatality rate in the more severe cases, possibly because patients with more severe disease tended to be treated with antibiotics. There were no complications or deaths among the affected members of the staff. Evidence of infection by verotoxin-producing E. coli O157:H7 was detected in 30 of 70 cases on the basis of isolation of this organism or demonstration of free verotoxin in stools. All isolates belonged to the same phage type. The high morbidity and mortality associated with this condition emphasize the need for proper food hygiene, rapid identification of outbreaks of disease, and prompt institution of infection-control techniques among the institutionalized elderly.
Abstract 2795: An onco-protein axis linking polycomb repressive complex 2 and polycomb repressive complex 1 through miRNAs in cancer
Authors: Qi Cao, Ram Mani, Bushra Ateeq, Saravana M. Dhanasekaren, Irfan Asangani, Jindan Yu, John Prensner, Jung J. Kim, J. Chad Brenner, Xuhong Cao, Xiaojun Jing, Rui Wang, Yong Li, Arun Dahiya, Lei Wang, Robert Lonigro, Scott Tomlins, Nallasivam Palanisamy, Christopher Maher, Sooryanarayana Varambally, Arul M. Chinnaiyan
Journal: Cancer Research (2011)

Abstract Enhancer of Zeste Homolog 2 (EZH2) is the catalytic histone methyltransferase subunit of the Polycomb Repressive Complex 2 (PRC2), that trimethylates histone H3 at lysine 27 (H3K27me3) resulting in the silencing of target genes. PRC2 plays a critical role in many basic cellular processes including cell proliferation, differentiation, early embryogenesis, and X chromosome inactivation. In cancer, EZH2 upregulation is implicated in metastasis and tumor aggressiveness of prostate and breast cancer and several other solid tumors. Recently our lab reported the genomic loss of miR-101 microRNA accompanying EZH2 overexpression in tumor cells. Here we identified several microRNAs that were downregulated by EZH2 and their levels were restored upon EZH2 depletion in cancer cell lines, and expression levels of these microRNAs were negatively correlated with EZH2 in human prostate tumors. Additionally, H3K27me3 modification was observed in the upstream regions of the miRNAs, suggesting a direct role for EZH2 in their regulation. Ectopic overexpression of the miRNAs suppressed cell proliferation, invasion, anchorage-independent growth, sphere formation and xenograft tumor growth of aggressive prostate and breast cancer cell lines. Finally, our investigations showed that the miRNAs also repress the expression of Polycomb Repressive Complex 1 (PRC1) members BMI1 and RING2, leading to a global decrease in the epigenetic marker, ubiquityl-H2A-K119 (uH2A) in cells, a key step in PRC1-mediated silencing. Our findings provide compelling argument for a regulatory axis joining PRC2 and PRC1 through miRNAs. This novel link between PRC2 and PRC1 indicates a coordinated mechanism by polycomb group proteins to promote an aggressive cancer phenotype. 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 2795. doi:10.1158/1538-7445.AM2011-2795
EVALUATION OF LUNG GLUCOSE UPTAKE WITH FLUORINE-18 FLUORODEOXYGLUCOSE POSITRON EMISSION TOMOGRAPHY/CT IN PATIENTS WITH PULMONARY ARTERY HYPERTENSION AND PULMONARY HYPERTENSION DUE TO LEFT HEART DISEASE
Authors: Hiroshi Ohira, Rob Beanlands, Brian McArdle, Robert deKemp, Jennifer Renaud, Ran Klein, Ross Davies, Tayebeh Hadizad, George Chandy, Vladamir Contreras Dominguez, Duncan Stewart, Carolyn Pugliese, Rosemary Dunn, Lisa Mielniczuk
Journal: Journal of the American College of Cardiology (2015)
Abstract LB-233: IGF activation in a molecular subclass of hepatocellular carcinoma and preclinical efficacy of IGF-1R blockage
Authors: Victoria Tovar, Clara Alsinet, Augusto Villanueva, Yujin Hoshida, Derek Y. Chiang, Manel Solé, Swan Thung, Susana Moyano, Sara Toffanin, Beatriz Minguez, Laia Cabellos, Judit Peix, Myron Schwartz, Vincenzo Mazzaferro, Jordi Bruix, Josep M. Llovet
Journal: Cancer Research (2010)

Abstract Background: IGF signaling contributes to proliferation and cell survival through PI3K/AKT and MAPK pathways. It has a relevant role in a variety of human malignancies. Aims: (1) To analyze the role of IGF signaling in early hepatocellular carcinoma (HCC; BCLC class 0 or A) and (2) To asses the antitumoral activity of IGF pathway targeted therapies. Methods: An integrative molecular dissection of the axis was performed in a cohort of 104 HCCs, including gene (quantitative PCR and Affymetrix U133 2.0® microarray) and miRNA expression (ligation-mediated amplification method), structural aberrations (Affymetrix STY Mapping Array®) and protein activation (immunohistochemistry). The therapeutic potential of a selective IGF-1R inhibitor, the monoclonal antibody A12, was assessed in vitro through viability and proliferation assays. A xenograft model of HCC was used to evaluate A12 activity in vivo. Results: Activation of the IGF axis was observed in 21% of early HCCs. Several molecular aberrations were identified, such as overexpression of IGF2 -resulting from reactivation of fetal promoters-, IGFBP3 downregulation and allelic losses of IGF2R (25% of cases). A gene signature defining IGF-1R activation was developed. Overall, activation of IGF signaling in HCC was significantly associated with IGF2 overexpression (p=0.03), mTOR signaling (p=0.035) and was enriched in a molecularly distinct HCC subclass defined through unsupervised hierarchical clustering of the same cohort of samples (Proliferation subclass) (p=0.001). We also found an inverse correlation between IGF activation and miR-100/miR-216 levels (FDR&amp;lt;0.05). In vitro studies showed that A12-induced abrogation of IGF-1R activation and downstream signaling significantly decreased cell viability and proliferation. In vivo, A12 treated mice exhibited delayed tumor growth and prolonged survival in comparison to control mice, a reduction in proliferation rates and induction of apoptosis was observed in treated mice tumoral samples. Conclusions: Integrative genomic analysis showed enrichment of activation of IGF signaling in the Proliferation subclass of HCC. Effective blockage of IGF signaling with A12 provides the rationale for testing this therapy in clinical trials. 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-233.
Slow and Deliberate: NCCS Moves Into 1992
Authors: Julie A. Steele
Journal: JNCI Journal of the National Cancer Institute (1992)

Slow and Deliberate: NCCS Moves Into 1992 Get access Julie A. Steele Julie A. Steele Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 84, Issue 1, 1 January 1992, Pages 15–16, https://doi.org/10.1093/jnci/84.1.15 Published: 01 January 1992
A1.5 Rheumatoid arthritis alters the preservative role of IL-15 on bone-marrow-resident TREG cells towards a pro-inflammatory phenotype
Authors: M Massalska, E Kuca-Warnawin, A Radzikowska, U Musialowicz, U Skalska, M Plebanczyk, T Burakowski, P Maldyk, E Kontny, W Maslinski
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background and objectives</h3> Inflammatory process observed in bone-marrow (BM) of RA patients (called bone marrow oedema) together with autoantibodies production was shown to precede joint destruction in RA. Natural producers of IL-15 in bone marrow are mesenchymal stromal cells and locally overproduced IL-15 was proved to elevate recently activated T cells number. In the present work we show increased production of main pro-inflammatory cytokine TNF by otherwise suppressive Treg cells (Tregs) isolated from bone marrow of RA patients. <h3>Materials and methods</h3> Bone marrow samples were obtained from RA and OA patients as a standard procedure during hip bone replacement surgery. Isolated bone marrow mononuclear cells (BMMC) were stimulated by IL-15 in 72 h <i>in vitro</i> culture before isolation of CD4<sup>+</sup>CD25<sup>+</sup><sup>++</sup> Tregs and CD4<sup>+</sup>CD25<sup>-</sup> responder T cells (Tresp) by cells sorter for functional activity measurement. TNF and IFN-gamma were estimated by specific ELISA in the supernatants removed before addition of [<sup>3</sup>H] thymidine in proliferation assays. Data are shown as mean ± SEM. <h3>Results</h3> Concentration of TNF produced by Tregs isolated from RA BM was comparable with TNF produced by responder T cells (14.2 ± 2.7 pg/ml in Tregs vs. 12.7 ± 1.8 pg/ml in Tresp) and higher then TNF produced by Tregs isolated from OA BM (8.5 ± 3.1 pg/ml) or healthy volunteers blood (7.7 ± 1.9 pg/ml). However, despite high TNF production, Tregs from RA BM remain functionally active and suppress proliferation, TNF and IFN-gamma production in coculture with Tresp. In RA number of Tregs as well as Foxp3 MFI was increased by IL-15 stimulation but TNF production stayed at the same level (11.6 ± 4.7 after IL-15 treatment vs. 14.2 ± 2.7 without IL-15 treatment). However, when the cells were additionally stimulated by anti-CD3/CD28, TNF production by Tregs significantly increased (42.6 ± 7.4 vs. 15.2 ± 4.8; p = 0.043) after IL-15 stimulation. <h3>Conclusions</h3> IL-15 overproduced in bone marrow of RA patients may exert opposite effects on Tregs – increase number and Foxp3 expression from one side and increase TNF production from the other. Thus Treg present in RA BM share suppressive capacities with pro-inflammatory feature, that may contribute to RA pathogenesis.
Abstract 5599: A novel treatment strategy targeting shugoshin 1 in hematological malignancies.
Authors: Takayuki Ikezoe, Jing Yang, Chie Nishioka, Akihito Yokoyama
Journal: Cancer Research (2013)

Abstract The shugoshin 1(SGOL1), a member of centromeric proteins, plays an important role in mitosis. The present study explored the levels of SGOL1 in hematological malignancies and found that SGOL1 was aberrantly expressed in various types of human leukemia cell lines (n=10, e.g., HL60, U937, MOLM-13, K562, EOL-1, etc.) and freshly isolated leukemia cells from individuals with acute myelogenous leukemia (AML, n=43, p&amp;lt;0.001) compared with bone marrow mononuclear cells isolated from healthy volunteers (n=9), as measured by real-time RT-PCR. Forced-expression of SGOL1 in hematopoietic stem/progenitor cells (HSPCs) significantly increased colony numbers for CFU-M and CFU-GM compared with control vector transduced infected HSPCs, suggesting that SGOL1 might act as an oncogene in hematopoietic cells. In addition, we found that repression of SGOL1 by a small interfering RNA (siRNA) slowed the proliferation of NB4, EOL-1 and U937 cells compared to the control siRNA transfected cells, in parallel with appearance of precocious dissociation of centromeric cohesion and separation of sister chromatids in these cells. Furthermore, we found that repression of SGOL1 by an siRNA accumulated EOL-1 and U937 cells in the G2/M phase of the cell cycle, in conjunction with up-regulation of spindle checkpoint protein BubR1, followed by apoptosis via caspase pathways. Taken together, SGOL1 may be a promising molecular target for individuals with AML. Citation Format: Takayuki Ikezoe, Jing Yang, Chie Nishioka, Akihito Yokoyama. A novel treatment strategy targeting shugoshin 1 in hematological malignancies. [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 5599. doi:10.1158/1538-7445.AM2013-5599 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.
Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA
Authors: Kazuya Masuda, Barry Ripley, Kishan Kumar Nyati, Praveen Kumar Dubey, Mohammad Mahabub-Uz Zaman, Hamza Hanieh, Mitsuru Higa, Kazuo Yamashita, Daron M. Standley, Tsukasa Mashima, Masato Katahira, Toru Okamoto, Yoshiharu Matsuura, Osamu Takeuchi, Tadamitsu Kishimoto
Journal: The Journal of Experimental Medicine (2016)

Balance in signal transducer and activator of transcription (STAT) activation is a key factor in regulating the fate of naive CD4+ T cells. Here, we demonstrate that AT-rich interactive domain-containing protein 5a (Arid5a) in T cells directs naive CD4+ T cells to differentiate into inflammatory CD4+ T cells, especially Th17 cells, through selective stabilization of Stat3 (but not Stat1 and Stat5) mRNA in an IL-6–dependent manner. Loss of Arid5a in T cells led to reduction of STAT3 level under Th17-polarizing conditions, whereas STAT1 and STAT5 in Arid5a-deficient T cells were highly activated compared with those of WT T cells under the same conditions. These cells displayed the feature of antiinflammatory (Il10-expressing) CD4+ T cells. Thus, we show a T cell–intrinsic role of Arid5a on fate decisions of naive CD4+ T cells through selective stabilization of Stat3 mRNA.
AB0295 Relationship between ADMA and Endothelial Dysfunction in Patients with Rheumatoid Arthritis
Authors: T. Senturk, N.C. Yilmaz, K. Koseoglu, C. Yenisey
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic, inflammatory disease of the joints with multisystemic involvement. Endothelial dysfunction caused by inflammatory process increases the risk of cardiovascular disease (CVD). As a consequence the morbidity and mortality in these patients is increasing. Flow mediated dilatation (FMD) is a radiological method that demonstrate endothelial dysfunction. At earlier studies ADMA correlated with FMD, in showing endothelial dysfunction, can be used as a simple and a cheaper method. <h3>Objectives</h3> At earlier studies asymmetric dimethylarginine (ADMA) correlated with FMD, in showing endothelial dysfunction, can be used as a simple and a cheaper method. In this study we assessed the availability of ADMA as a marker shoving endothelial dysfunction in RA patients. <h3>Methods</h3> We have studied 40 patients below age of 65, which were diagnosed as RA by 1987 ARA classification criteria and have taken 29, age matched and healthy, non-smoking controls. Exclusion criterias were the diagnosis of coronary and peripheral artery disease, hypertension, diabetes mellitus, smoking and renal failure. FMD and ADMA levels were measured in all patients and controls. We also assessed the affect of disease activity and severity on vascular functions in this study. Therefore DAS28, CRP, ESR and anti-CCP and RF levels were measured, and the relationship between these markers and endothelial dysfunction were evaluated. <h3>Results</h3> In our study, ADMA levels were significantly higher in RA patients and were inversely correlated with FMD. Disease duration and age of the patients affected ADMA levels. Relationship between impairment in vascular function and disease activity parameters was not detected. Significant association with anti-CCP positivity was not seen either. <h3>Conclusions</h3> The result obtained in our study, supports the hypothesis that ADMA can be used in the assessment of endothelial dysfunction in patients with RA. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.2107
Abstract 5348: Transduction of tumors <i>in vivo</i> with choline kinase shRNA downregulates breast cancer stem cell markers
Authors: Balaji Krishnamachary, Marie-France Penet, Mayur M. Gadiya, Noriko Mori, Yelena Mironchik, Kristine Glunde, Zaver M. Bhujwalla
Journal: Cancer Research (2012)

Abstract Increased phosphocholine is one of the metabolic signatures of cancer, and is closely associated with malignant transformation, invasion and metastasis. Increased phosphocholine is primarily due to increased expression of choline kinaseα, the enzyme that converts choline to the membrane precursor phosphocholine. Stem-like breast cancer cells (SBCCs) are drug resistant, invasive, and likely to lead to recurrence and repopulation. High CD44 adhesion molecule expression and high expression of the drug transporter ABCG2 are two markers associated with populations enriched with SBCCs [1]. Here we have examined the relationship between choline kinase and these two markers of SBCCs. We have determined the relationship between choline kinase downregulation and two markers of SBCCs, CD44 and ABCG2 in MDA-MB-231 breast cells in vitro and tumors in vivo upon lentiviral transduction of shRNA targeting choline kinase [2]. CD44 and its variant isoforms CD44v6 and CD44v8, together with ABCG2 showed a significant reduction in mRNA (30% for CD44 total; 80% for CDv6 and v8, and 45% for ABCG2) and protein expression levels following transduction of MDA-MB-231 cells with lentivirus expressing shRNA against choline kinase. Similar decreases were also observed following systemic intravenous injections of lentivirus expressing choline kinase shRNA delivered over four weeks. These studies provide insight into potential metabolic targeting of SBCCs. 1. Al-Hajj, M et al., Proc Natl Acad Sci U S A, 2003. 2. Krishnamachary, B et al., Cancer Research, 2009. This work was supported by NIH R01CA136576 and P50 CA103175. 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 5348. doi:1538-7445.AM2012-5348
Rolofylline, an Adenosine A<sub>1</sub>−Receptor Antagonist, in Acute Heart Failure
Authors: Barry M. Massie, Christopher M. O'Connor, Marco Metra, Piotr Ponikowski, John R. Teerlink, Gad Cotter, Beth Davison Weatherley, John G.F. Cleland, Michael M. Givertz, Adriaan Voors, Paul DeLucca, George A. Mansoor, Christina M. Salerno, Daniel M. Bloomfield, Howard C. Dittrich
Journal: New England Journal of Medicine (2010)

Worsening renal function, which is associated with adverse outcomes, often develops in patients with acute heart failure. Experimental and clinical studies suggest that counterregulatory responses mediated by adenosine may be involved. We tested the hypothesis that the use of rolofylline, an adenosine A1-receptor antagonist, would improve dyspnea, reduce the risk of worsening renal function, and lead to a more favorable clinical course in patients with acute heart failure.We conducted a multicenter, double-blind, placebo-controlled trial involving patients hospitalized for acute heart failure with impaired renal function. Within 24 hours after presentation, 2033 patients were randomly assigned, in a 2:1 ratio, to receive daily intravenous rolofylline (30 mg) or placebo for up to 3 days. The primary end point was treatment success, treatment failure, or no change in the patient's clinical condition; this end point was defined according to survival, heart-failure status, and changes in renal function. Secondary end points were the post-treatment development of persistent renal impairment and the 60-day rate of death or readmission for cardiovascular or renal causes.Rolofylline, as compared with placebo, did not provide a benefit with respect to the primary end point (odds ratio, 0.92; 95% confidence interval, 0.78 to 1.09; P=0.35). Persistent renal impairment developed in 15.0% of patients in the rolofylline group and in 13.7% of patients in the placebo group (P=0.44). By 60 days, death or readmission for cardiovascular or renal causes had occurred in similar proportions of patients assigned to rolofylline and placebo (30.7% and 31.9%, respectively; P=0.86). Adverse-event rates were similar overall; however, only patients in the rolofylline group had seizures, a known potential adverse effect of A1-receptor antagonists.Rolofylline did not have a favorable effect with respect to the primary clinical composite end point, nor did it improve renal function or 60-day outcomes. It does not show promise in the treatment of acute heart failure with renal dysfunction. (Funded by NovaCardia, a subsidiary of Merck; ClinicalTrials.gov numbers, NCT00328692 and NCT00354458.).
Case 21-1985
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, Betty U. McNeely
Journal: New England Journal of Medicine (1985)

Presentation of Case A 21-year-old man was admitted to the hospital because of lower-extremity weakness and urinary retention. Three months earlier he traveled to Kenya to study and used malarial prophylactic medication in the form of chloroquine and pyrimethamine–sulfadoxine (Fansidar) weekly. One month later he swam in a slow-moving stream in the Machakos district of Kenya with five fellow students and noted no subsequent rash or pruritus. All six were subsequently treated at a hospital in Nairobi because of diarrhea and fever. A diagnosis of malaria was considered likely but was not proved. Nearly four weeks later the patient experienced . . .