tbuckley/cabot-search huggingface dataset:
A2.32 Macroautophagy proteins control dendritic cell activation and shape the TH1/TH17 response during antigen induced arthritis
Authors: J Niven, G Palmer-Lourenco, P Sattonnet-Roche, D Talabot-Ayer, C Gabay, M Gannagé
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Macroautophagy is a major catabolic pathway that plays a key role in cellular homeostasis. Macroautophagy has been recently implicated in shaping the innate and adaptive immune responses via cytokine secretion and antigen presentation in various diseases. However the contribution of the pathway to autoimmune arthritis is still not established. Our aim was to address the role of macroautophagy in the adaptive immune response during antigen induced arthritis (AIA), using mice that are deficient in macroautophagy in their dendritic cells. <h3>Materials and methods</h3> CD11c-Cre mice (C57BL/6), were crossed with Atg5<sup>flox/flox </sup>mice (C57BL/6) resulting in the complete abolishment of a functional autophagy pathway in dendritic cells (DC/ATG5<sup>-/-</sup>). For AIA, mice were immunised with methylated BSA (mBSA) and CFA. Monoarthritis was induced at day 21. At day 28 animals were sacrificed. For histological scoring knees sections were stained with hematoxylin and eosin and toluidine blue. T cell function was monitored by cytokine production and CFSE staining. For <i><i>in vitro</i></i> analysis, bone marrow derived dendritic cells (BMDC) were treated with TLR ligands. Cytokines production was quantified by ELISA, and co-stimulatory molecule expression analysed by flow cytometry. <h3>Results</h3> Our results identified autophagy as a negative regulator of the inflammatory response during AIA. Indeed we found that in the absence of autophagy in dendritic cells AIA was more severe correlating with an enhanced Th1/Th17 response. Histological analysis showed an enhanced inflammatory score, due to enhanced cartilage destruction and bone erosion in (DC/ATG5<sup>-/-</sup>) mice. Interestingly, the Th1/Th17 response in DC/ATG5<sup>-/-</sup> mice was significantly increased. Indeed lymph node cell cultures showed enhanced CD4 T cell proliferation with increased INF-gamma and IL-17 production. This was observed both in an antigen specific manner from <i><i>ex vivo</i></i> treatment with mBSA or with CD3/CD28 treatment. <i><i>In vitro</i></i> analysis showed that in response to TLR activation DC/ATG5<sup>-/-</sup> has enhanced IL-1B production, and higher expression of co-stimulatory molecules. <h3>Conclusions</h3> Autophagy deficiency in dendritic cells exacerbates the Th1/Th17 inflammatory response in the AIA model, resulting in increased cartilage destruction and bone erosion. The precise <i>in vivo</i> mechanism behind this regulation is under investigation; however this might be in part due to enhanced IL-1β production and increased co-stimulatory molecule expression on antigen presenting cells.
Organizations, Government Are Scrambling to Ensure Quality Mammography
Authors: F. S. Antoine
Journal: JNCI Journal of the National Cancer Institute (1991)

Journal Article Organizations, Government Are Scrambling to Ensure Quality Mammography Get access Florence S. Antoine Florence S. Antoine Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 83, Issue 6, 20 March 1991, Pages 395–396, https://doi.org/10.1093/jnci/83.6.395 Published: 20 March 1991
NIH Building Renamed to Honor Pepper
Authors: K. Smigel
Journal: JNCI Journal of the National Cancer Institute (1989)

NIH Building Renamed to Honor Pepper Get access Kara Smigel Kara Smigel Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 81, Issue 12, 21 June 1989, Page 899, https://doi.org/10.1093/jnci/81.12.899 Published: 21 June 1989
STENT PLASTICO VERSUS METALICO EN EL PREOPERATORIO DE PACIENTES CON OBSTRUCCION BILIAR MALIGNA POR TUMOR PERIAMPULAR RESECABLE: ESTUDIO PROSPECTIVO ALEATORIZADO
Authors: F González-Huix Llado, M Figa Francesch, M Alburquerque Miranda, S Lopez Ben, MT Albiol Quer, J Figueras Felip
Journal: Endoscopy (2013)

Introducción: Los stents metálicos cubiertos (SMC) podrian ser una alternativa costo-eficaz a los plásticos (SP) para drenaje endoscópico preoperatorio de tumores periampulares resecables. Objetivo: Comparar la eficacia de SP versus SMC en el drenaje endoscópico preoperatorio de la obstrucción biliar maligna periampular primaria subsidiaria de resección curativa. Material y Método: Diseño prospectivo, comparativo aleatorizado. Pacientes consecutivos con obstrucción maligna por tumores primarios periampulares resecables por edad/comorbilidad y evaluación clinicoradiológica. Inclusión: Bilirrubina > 15 y/o imposibilidad quirúrgica en< 10 días, paso estenosis con guía en CPRE. Aleatorización: SP 10 F (Flexima®) versus SMC (Wallflex®). Datos demográficos, complicaciones CPRE-cirugía, intra/postoperatorias, coste. Objetivo primario: complicaciones intervalo CPRE-cirugía por el stent. Resultados: 63 pacientes, edad: 68,03 ± 8,5; 42 varones, 35 Ca. páncreas, 11 ColangioCa y 17 Ampulomas. SP: 28 y SMC 35 SMC. Trece pacientes se descartan finalmente para cirugía. Complicaciones preoperatorias: 9/28 (32,1%) grupo SP vs. 2/35 (5,7%) grupo SMC (p = 0,008) según intención tratamiento, y 8/24 (33,3%) grupo SP y 1/26 (3,8%) grupo SMC (p = 0,009) según protocolo. Intervalo medio de tiempo CPRE-cirugía: SP = 37,0 días; SMC = 37,5 días; p = 0,9. Hospitalización post-CPRE por complicacion: Grupo SP: 4,8 ± 4,7 días (coste medio: 3556 €); grupo SMC: 2,5 ± 3,5 días (coste medio de 1334 €). Reintervenciones: 6 (5 CPRE grupo SP y 1 grupo SMC). Se hace cirugía resectiva en 38, en 12 solo derivativa. En 25% grupo SP y 42,3% grupo SMC (p = ns) hubo trastornos hilio hepático relacionados con stent que no dificultan la cirugía. Hubieron 5 pacientes con complicaciones intraoperatorias (10%), y 20 (31,7%) postquirúrgicas. Fue necesario 3,32 ± 0,4 días de UCI y 3,12 ± 7,1 días de ingreso postoperatorio. Sin diferencias estadisticas entre grupos en estas variables. Conclusiones: Los SMC se acompañan de menor número de complicaciones, tienen mejor relación coste-efectividad y deberían indicarse como primera opción en el drenaje preoperatorio de la obstrucción biliar maligna por tumores periampulares primarios subsidiarios de cirugía resectiva.
P85 Human mesenchymal stem cells bind preferentially to injured liver in a 1-integrin and CD44 dependent manner
Authors: V. Aldridge, N. Davies, J. Youster, D. Kavanagh, N. Kalia, P. Lalor, J. Frampton, P. Newsome
Journal: Gut (2011)

<h3>Introduction</h3> Human bone-marrow mesenchymal stem cells (hMSCs) are multipotent cells which have been considered in liver repair due to their immunomodulatory properties. However, they have also been implicated in liver fibrogenesis. These differing actions may reflect the existence of different functional sub-sets of hMSCs or differing environmental cues. Understanding the mechanisms governing the entry and retention of hMSCs into liver would allow this to be modified for clinical benefit in disease settings. <h3>Aim</h3> To determine the mechanisms underpinning the adhesion and engraftment of human MSCs into injured liver. <h3>Method</h3> Flow cytometric analysis of hMSCs was performed to determine the expression of adhesion molecules corresponding to up-regulated ligands in injured liver. Adhesion of hMSCs to normal and injured liver tissue, human hepatic sinusoidal endothelium (HSEC) and extracellular matrices (VCAM-1, fibronectin and hyaluronan) was undertaken in vitro using static and physiologically relevant modified-flow assays. Fluorescently-labelled hMSCs were infused via the portal vein into mice injured with chronic CCl<sub>4</sub> to determine engraftment. To define the molecular mechanisms underpinning hMSC interactions neutralising antibodies were utilised in these assays. <h3>Results</h3> hMSCs expressed high levels of β<sub>1</sub>-integrin and CD44. Adhesion of hMSCs was greatest on diseased human liver compared to normal liver. Neutralising antibodies against β<sub>1</sub>-integrin, CD44 and VCAM-1 reduced binding of hMSCs to diseased liver by 34%, 35% and 40% respectively (p&lt;0.05). hMSCs were seen to fast-roll at 500 μm/s, firmly adhere and transmigrate across HSEC. Rolling was completely abolished by β<sub>1</sub>-integrin blockade on both HSEC and VCAM-1. Firm adhesion to HSEC was reduced by blockade of β<sub>1</sub>-integrin (55%, p=0.02) and CD44 (51%, p=0.04). To determine which ligands on HSEC mediate hMSC binding we studied the ligands in isolation. HSEC express VCAM-1, fibronectin and hyaluronan, all of which supported firm adhesion of hMSCs under modified flow. β<sub>1</sub>-integrin blockade reduced adhesion to VCAM-1 (66%, p=0.001) and Fibronectin (29%, p=0.007), while CD44 blockade reduced adhesion to fibronectin (18%, p=0.02) and hyaluronan (43%, p=0.04). Neutralising antibodies to the β<sub>1</sub>-integrin subunit and CD44 reduced hepatic engraftment of hMSCs in chronically injured mice, confirming the data obtained in vitro. <h3>Conclusion</h3> hMSCs bind preferentially to injured liver and undergo rolling and firm adhesion, which is differentially regulated. β<sub>1</sub>-integrin/VCAM-1 interactions regulate rolling while β<sub>1</sub>-integrin/CD44 interactions with fibronectin and hyaluronan regulate adhesion.
Abstract LB-161: A complete regression and therapeutic vaccination against aggressive malignant rat mesenchymal tumors with “stemness” characteristics obtained by intratumoral injection of LTX-315 (Oncopore®)
Authors: Øystein Rekdal, MengYu Wang, Ketil Camilio, Baldur Sveinbjornsson, Bent Rolstad, Gunnar Kvalheim
Journal: Cancer Research (2011)

Abstract Background: In order to develop more effective anticancer agents there is a shift from not only treating the bulk of cells in a tumor but also to target the self renewing cancer stem cells (CSCs). Standard treatment with chemotherapy and radiotherapy is unable to eradicate CSCs and therefore other treatment modalites against CSCs are needed. LTX-315 (Oncopore®) is a chemically modified cytolytic peptide which is equally active against drug-sensitive and drug-resistant cancer cells. Earlier animal studies have demonstrated that treatment of syngenic murine A20 B-lymphomas and CT26WT carcinomas with intratumoral (i.t.) injection with LTX-315 resulted in complete tumor regression. The present study was undertaken to investigate whether LTX-315 induced an antitumor response in vivo in a novel malignant rat mesenchymal tumor model with “stemness” properties. Methods: Following long-term culturing of bone marrow-derived rat mesenchymal cells, a transformed mesenchymal cell line (rTMSC) has been been developed. rTMSC has, as the non-malignant rMSC, maintained osteogenic and adipose differentation properties and side population cells from rTMSC are highly clonogenic both in vitro and in vivo. Previously we have shown that s.c. as well as i.v. or i.p. injection of rTMSCs form immature solid sarcomas both in nude rats as well as in PVG rats. In this study the rTMSCs were marked with a dual reporter gene GFP and Luciferase and a CCD camera was used for dynamic living imaging. rTMSCs (5×105 cells) were subcutaneously inoculated into PVG rats and established tumors treated i.t. with LTX-315. Results: Intratumoral treatment with LTX-315 resulted in a complete regression in the majority of the treated animals. Successfully treated mice were protected against s.c. or i.p. re-challenge with rTMSCs. Conclusions: Taken together, our results suggest that LTX-315 treatment induced complete regression and long-term, specific cellular immunity against malignant rat mesenchymal tumor cells with “stemness” properties”. Thus, intratumoral administration of a cytolytic peptide might, in addition to providing local tumor control, confer a novel strategy for therapeutic vaccination against established cancers containing CSCs 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-161. doi:10.1158/1538-7445.AM2011-LB-161
OC-045 Reduced Risk Of Emergency Admission For Colorectal Cancer Associated With Introduction Of Bowel Cancer Screening Across England: Retrospective National Cohort Study
Authors: J Geraghty, M Shawihdi, E Thompson, S Sarkar, M Pearson, K Bodger
Journal: Gut (2014)

<h3>Introduction</h3> We examined whether roll out of the bowel cancer screening programme (BCSP) across England was associated with a reduced risk of emergency hospital admission for people presenting with colorectal cancer (CRC) during this period. <h3>Methods</h3> Design: Retrospective cohort study of 27,763 incident cases of CRC over a 1-year period during the roll-out of screening across parts of England. Primary outcome: Emergency (unplanned) hospital admission during diagnostic pathway. Primary exposure: Living in an area where BCSP was active at the time of diagnosis. Patients were categorised into three exposure groups: BCSP not active (reference group), active &lt;6 months or active ≥6 months. To explore confounding we studied risk of emergency admission for cases of oesophagogastric cancer using the same design. <h3>Results</h3> Risk of emergency admission for CRC in England was associated with increasing age, female gender, co-morbidity and social deprivation. After adjusting for these factors in logistic regression, the odds ratio for emergency admission in patients diagnosed ≥6 months after start-up of local screening was 0.83 (CI: 0.76–0.90). The magnitude of risk reduction was greatest for cases of screening age (OR 0.75; CI: 0.63–0.90) but this effect was apparent also for cases outside the 60–69 year age-group (OR 0.85; CI: 0.77–0.94). Living in an area with active BCSP conferred no reduction in risk of emergency admission for people diagnosed with oesophagogastric cancer during the same period. <h3>Conclusion</h3> The start-up of bowel cancer screening in England was associated with a substantial reduction in risk of emergency admission for CRC in people of all ages. This suggests that the roll-out of the programme had early and indirect benefits beyond those related directly to participation in screening. <h3>Disclosure of Interest</h3> J. Geraghty Grant/research support from: Cook Medical, M. Shawihdi: None Declared, E. Thompson: None Declared, S. Sarkar: None Declared, M. Pearson: None Declared, K. Bodger: None Declared.
Comprehensive change is needed to realise potential of community services, says UK think tank
Authors: Z. Kmietowicz
Journal: BMJ (2014)

Radical changes must be made to how community health services are organised if the government is to achieve its ambition of moving more care out of hospitals and closer to people’s homes, says a new report.1

The report, from the healthcare think tank the King’s Fund, said that community services were unnecessarily complex, fragmented, and often poorly coordinated—making them difficult to understand, even for health professionals.

The report said that “patients receive multiple visits from different professionals, incurring high costs of coordination, and leading to frustration for the referring clinicians, their patients and carers. Not only is this not necessarily cheaper, but it may also mean that important opportunities to notice changes in the patient’s condition are missed.”

The fund convened a …
P145 Evaluation of a quadriceps muscle endurance leg lift test in patients with chronic obstructive pulmonary disease
Authors: S. Hattle, C. Hayton, J. Elia, A. M. Wilson
Journal: Thorax (2010)

<h3>Introduction and objectives</h3> Quadriceps muscle strength is commonly used to assess patients with chronic obstructive pulmonary disease (COPD). However a simple endurance test is not routinely available. We wished to evaluate a simple test of muscle endurance. <h3>Methods</h3> We developed a quadriceps muscle leg lift test whereby seated patients extended their dominant leg from 90° flexion to 0° flexion for 5 s with a weight (2 kg for Men and 1 kg for women) strapped to their ankle. They repeated cycles of flexion and extension (with 5 s hold at each extension) until exhaustion. The duration of this test and number of lifts was compared to the duration and distance walked during an endurance shuttle walk test (at the speed equivalent to 85% of maximum oxygen uptake as determined from an incremental shuttle walk test), muscle strength (using an dynometer) and the dyspnoea and fatigue domains of the Chronic Respiratory Questionnaire (CRQ). <h3>Results</h3> 43 (30 Males) patients with COPD with mean (standard deviation) of 68.9 (9.3) years and forced expiratory volume in 1 s (FEV<sub>1</sub>) of 42.5 (13.8) percent of predicted normal completed the tests. The mean (standard deviation) quadriceps strength was 16.1 (5.0) kg, number of lifts was 12.5 (7.1) in 85.2 (48.3) s, endurance shuttle-walk test (ESWT) distance was 177.3 (89.8) m in 184.7 (88.8) s and dyspnoea and fatigue domains of the CRQ were 2.4 (1.1) and 3.3 (1.2) respectively. The correlation coefficients comparing the measures are shown in Abstract P145 Table 1. <h3>Conclusion</h3> The endurance leg lift test was closely associated with the fatigue domain of the Chronic Respiratory Questionnaire but poorly associated with the dyspnoea domain. This new test may have some clinical utility given that it more closely relates to fatigue than either muscle strength or the endurance shuttle-walk test.
DETERMINANTS OF RECURRENT HEPATOCELLULAR CARCINOMA AFTER LIVER TRANSPLANTATION
Authors: A Abu Shanab, N Starr, Z Hutchinson, J Hegarty, A McCormick, R Merriman
Journal: Gut (2013)

<h3>Introduction</h3> The outcome of orthotopic liver transplantation (OLT) for hepatocellular carcinoma (HCC) depends significantly on pre-OLT radiologic stage. Other putative factors such as Lymphovascular invasion (LVI), peak pre-OLT AFP level, the need for down-staging and short waiting times on OLT list are less well-defined. <h3>Aims/Background</h3> To characterize the factors associated with recurrent HCC in patients after OLT with short waiting times. <h3>Method</h3> Retrospective cohort data analysis of patients with HCC who had OLT in a single centre from 2002–2011. Pre- and post-OLT variables were studied that included clinical characteristics, pre-OLT radiologic staging, explant pathological stage, tumour markers, use of ablative therapy and waiting times. <h3>Results</h3> Sixty-eight patients with HCC had OLT for HCC from 2002–2011. Recurrent HCC occurred in 8/68 patients (11.7%), male (6), mean age 60. For these with recurrent HCC, the median waiting time was 2.5 months. Pre-OLT locoregional therapy occurred in 50%. All patients had stage T2 HCC pre-OLT (without downstaging). Three of 8 patients had an elevated AFP &gt;500 pre-OLT. Pathological staging was pT2 in 62.5%, (two pT3, one pT1) that were moderately differentiated in 56% and with LVI in 25%. All 3 patients with high AFP and two without high AFPs pre-OLT developed high AFPs with recurrent HCC. No significant differences in waiting times and a pre-OLT AFP &gt;500. <h3>Conclusion</h3> Recurrent HCC is uncommon for patients transplanted within Milan criteria. We were unable to demonstrate an effect of short waiting time or high AFP level pre-OLT on the likelihood of recurrent HCC.
NETWORK META-ANALYSIS OF RELATIVE EFFICACY AND SAFETY OF EDOXABAN VERSUS OTHER NOVEL ORAL ANTICOAGULANTS (NOACS) AMONG ATRIAL FIBRILLATION PATIENTS WITH CHADS2 SCORE ≥ 2
Authors: Beth Sherrill, Maria Fernandez, Jianmin Wang, Xin Ye, Winghan Kwong, Bintu Sherif, Susan Hogue
Journal: Journal of the American College of Cardiology (2015)
Abstract 395: Rapid engraftment of human primary acute leukemic cells in NOD/SCID mice by intrasplenic inoculation: a robust human primary leukemia (Hukemia) model for preclinical evaluation of new therapies
Authors: Huang Liang, Amy Zhang, Na Wang, Shuyan Ma, Jingping Liu, Xiaoxu Qi, Xiaoming Song, Taiping Chen, Michelle Xia, Jean-Pierre Wery, Xingjun Chen, Yiyou Chen, Jianfeng Zhou, Pengfei Zhou
Journal: Cancer Research (2010)

Abstract The ability to engraft human leukemia cells directly from patient samples into immunodeficient rodents such as NOD/SCID mice would be uniquely valuable in preclinical prioritization of novel therapies for future clinical trial. The aim of this study was to develop an animal model for human acute leukemia in which the kinetics, characteristics and chemosensitivity of leukemia can be sequentially monitored in individual immunodeficient mouse model. Continuous xenografts from 28 acute myeloid leukemia (AML) patients and 18 acute lymphoblastic leukemia (ALL) patients with AML-ETO, CBFβ/MYH11, TAL/SIL1, MLL/AF4 fusion genes were established in NOD/SCID mice by intrasplenic inoculation of human leukemic cells from born marrow. Progression of leukemia was monitored throughout the development of disease by determination of immunophenotyping and karyotyping of the engraftment tumor cells. Chemosensitivity and in vivo efficacy to standard of care therapies were screened in xenografts from both AML and ALL patients. Genetic lesions and special surface markers in different passages of cells in recipient mice were also examined by gene array and FACS analysis. Intrasplenic inoculation of leukemia cells significantly enhanced the engraftment rate and expedited disease development when compared with I.V. route. Relative to engrafted human primary cells, negligible changes in growth rates, chromosomal aberrations and immunophenotype were observed at second, third and fourth passages. The in vivo sensitivity of xenografts to standard of care correlated significantly with clinical course and patient outcome. We have also uncovered key molecular events and serum immunoassay biomarkers which correlate with the efficacy and potency of the drugs for AML and ALL models. The biologic and genetic characteristics and patterns of chemosensitivity of xenografts from acute leukemia patients accurately reflect the clinical disease. The efficient engraftment and rapid expansion of the leukemia within NOD/SCID mice affords a robust model for the preclinical evaluation of new therapies. 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 395.