tbuckley/cabot-search huggingface dataset:
PWE-052 Bowelscope Screening – The South Of Tyne And Wear Experience: Abstract PWE-052 Table 1
Authors: R Bevan, H Miller, D Thapa, M Ritchie, J Painter, C Rees
Journal: Gut (2014)

<h3>Introduction</h3> The National Bowel Cancer Screening Programme has been extended to include a one-off flexible sigmoidoscopy (FSIG) to all aged 55, after a large UK study demonstrated reduction in colorectal cancer incidence and death rates when FSIG is performed and adenomas removed. BowelScope screening is being piloted in 6 centres – South of Tyne and Wear (SOTW), Norwich, St Mark’s, Surrey, Kent and Medway, and Wolverhampton. SOTW was the first centre to offer screening. <h3>Methods</h3> We describe delivery of BowelScope at SOTW. The Bowel Cancer Screening System (BCSS) database was interrogated for procedural data. A study was performed recording timings of lists. Patients complete a satisfaction survey the morning after the procedure; anonymised results are provided to the centre. <h3>Results</h3> 2 endoscopists were accredited in March 2013– 1 medical research fellow, and 1 staff grade surgeon. 2 existing BCSP colonoscopists also support the BowelScope lists as required. First invitations were sent from the Northern Hub on 21.03.13, and first screening list held on 07.05.13. Lists are held on Tuesday and Thursday evenings, recently increasing to include Saturday lists. Lists initially had 12 slots available, but were reduced to 10 in light of over-running lists. Average list length 229 min (11/12 points) vs 199 min (≤10 points). 248 FSIGs were completed in ≤110 min, 172 in 11–15 min, and 88 in &gt; 115 min (data missing in 7). Comfort was recorded by SSPs as none/minimal/mild discomfort in 484 cases, and moderate/severe in 35. Entonox was used by 94 screenees. Patient surveys showed patient reported moderate/severe pain in 44%. Failure to attend– 52 (9%). As of 20.12.2013: <h3>Conclusion</h3> We demonstrate that BowelScope screening can be adequately delivered by existing screening centres. Adjustments may need to be made to list templates in order to ensure minimal waiting for patients. Uptake is less than for the FOB programme but is higher than in early pilots. Some slots are wasted with the 9% FTA rate; a new text messaging reminder service has been developed to address this. Patient reported pain levels are higher than those recorded by the SSPs, highlighting a need for accurate assessment of patient experience. <h3>Disclosure of Interest</h3> None Declared.
A3.23 Vitamin D Antagonises the Suppressive Effect of Inflammatory Cytokines upon CTLA-4 Expression and Regulatory Function
Authors: LE Jeffery, K Raza, DM Sansom
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background and Objectives</h3> The suppressive protein, cytotoxic T lymphocyte antigen–4 (CTLA-4), is constitutively expressed by TRegs and induced in effector T cells upon activation. Its crucial role in adaptive immunity is apparent from the fatal autoimmune pathology of CTLA-4 knockout mice and the association of CTLA-4 genetic variants with autoimmunity. We have recently shown that CTLA-4 functions by depleting antigen-presenting cells of their co-stimulatory ligands, CD80 and CD86 (Qureshi <i>et al</i>, Science 2011). However, little is known about the factors that regulate CTLA-4 expression and function. Since low vitamin D status and elevated Th17 frequencies are evident in many autoimmune conditions, we have investigated the effect of vitamin D and Th17 polarising cytokines upon CTLA-4 expression and function. <h3>Methods</h3> Peripheral blood CD4<sup>+</sup>CD25<sup>–</sup> T cells were stimulated under Th17 polarising conditions (TGFbeta, IL-1beta, IL-6 and IL-23) with or without active vitamin D (1.25(OH)<sub>2</sub>D<sub>3</sub>). FoxP3 and CTLA-4 were measured by flow cytometry and the vitamin D receptor (VDR) by qPCR. To assess CTLA-4 function, T cells were cultured with anti-CD3 and cells expressing GFP-tagged CD86. CD86-GFP acquisition by T cells with or without CTLA-4 blockade was then monitored by flow cytometry. For suppression assays, separately labelled activated T cells and CD4<sup>+</sup>CD25<sup>−</sup> responder T cells were co-cultured with dendritic cells in the presence of anti-CD3 and T cell proliferation assessed at five days by flow cytometry. <h3>Results</h3> Vitamin D increased CTLA-4 expression and the frequency of FoxP3+CTLA-4+ T cells. By contrast, Th17 polarising cytokines suppressed CTLA-4. Interestingly, when supplied together, Th17 polarising cytokines synergised with vitamin D resulting in significantly higher CTLA-4 expression than with vitamin D alone. This synergy corresponded with increased VDR expression under Th17 conditions. Using a novel assay to test CTLA-4 function, we further confirmed that these changes in CTLA-4 expression correlated with ligand removal. Moreover, in dendritic cell driven stimulations vitamin D-treated T cell blasts showed enhanced CTLA-4-mediated suppression. <h3>Conclusions</h3> Vitamin D overrides the inhibitory effect of pro-inflammatory Th17 polarising cytokines upon CTLA-4 expression and function. Given the importance of CTLA-4-mediated suppression in the control of autoimmune diseases, including RA, these data highlight the importance of vitamin D in immune regulation and its potential as a therapeutic agent.
Abstract 2541: Effect of carcinogen acrolein on DNA repair and mutagenic susceptibility.
Authors: Hsiang-Tsui Wang
Journal: Cancer Research (2012)

Abstract Lung cancer death is the number one cause of cancer death in the United States. Cigarette smoking is the major cause of lung cancer. Cigarette smoke (CS) contains more than 60 human carcinogens. Our early work has demonstrated that acrolein (Acr), one of the most abundant aldehydes in CS, reacts with DNA to form α- and α-hydroxy-1, N2-cyclic propano-dG adducts (α-Acr-dG and α-Acr-dG). The distribution of Acr-dG in the p53 gene coincides with lung cancer p53 mutational spectrum. Acr-dG adducts induce mainly G to T and G to A mutations that are similar to the mutation signature found in the p53 gene in lung cancer. We have also found that Acr inhibits DNA repair. Therefore, we concluded that Acr is a major etiological agent for CS related lung cancer. In this study, we found that Acr-dG adducts are poorly repaired in Acr treated normal human bronchial epithelial (NHBE) cells. Intriguingly, NHBE cell lysates are competent in carrying out in vitro repair synthesis assay using Acr-modified as well as UV-irradiated DNA as substrates. These results indicate that Acr treatment impairs DNA repair function. We found that Acr not only inhibits nucleotide excision repair (NER), it also inhibits base excision repair (BER) and mismatch repair (MMR). Acr does not change the expression of XPA, XPC, hOGG1, PMS2 or MLH1 genes. However, Acr causes a reduction of XPA, XPC, hOGG1, PMS2 and MLH1 proteins and that this effect can be neutralized by the proteosome inhibitor, MG132. We further found that Acr treatment enhances both bulky and oxidative DNA damage-induced mutagenesis. These results indicate that Acr not only damages DNA, but can also modify DNA repair proteins and further cause degradation of these modified repair proteins. We propose that these two detrimental effects contribute to Acr mutagenicity and carcinogenicity. 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 2541. doi:1538-7445.AM2012-2541
The Prevalence of Ulcerated Plaques in the Aortic Arch in Patients with Stroke
Authors: Pierre Amarengo, Charles Duyckaerts, Christophe Tzourio, Dominique Hénin, Marie-Germaine Bousser, Jean-Jacques Hauw
Journal: New England Journal of Medicine (1992)

The cause of cerebral infarction is obscure in up to 40 percent of patients with this disorder who are studied prospectively. In this investigation, we determined the frequency of ulcerated plaques in the aortic arch and explored the part they may play in the formation of cerebral emboli. Using an autopsy data bank, we studied the prevalence of ulcerated plaques in the aortic arch in 500 consecutive patients with cerebrovascular and other neurologic diseases who were studied at autopsy.
394 THE NOVEL ENDOCANNABINOID NOLADIN ETHER SELECTIVELY INDUCES CELL DEATH IN HEPATIC STELLATE CELLS VIA AN ROS-DEPENDENT MECHANISM
Authors: A. Wojtalla, M. Schlosser, M.V. Singer, T. Sauerbruch, A. Zimmer, S. Siegmund
Journal: Journal of Hepatology (2012)
Abstract 19211: Myocardial Connective Tissue Growth Factor (CCN2/CTGF) Improves Infarct Healing and Attenuates Left Ventricular Remodeling after Myocardial Infarction
Authors: Jørgen Gravning, Stein rn, Thor Edvardsen, Vladimir N Martinov, Cord Manhenke, Kenneth Dickstein, Havard Attramadal, Mohammed S Ahmed
Journal: Circulation (2010)

Purpose:  Myocardial CCN2/CTGF is induced in both experimental and human heart failure. However, its pathophysiological role in ischemic heart failure remains unresolved.   Methods:  Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were compared with nontransgenic littermate control mice (NLC). Myocardial infarction (MI) was induced by ligation of the left coronary artery in Tg-CTGF (n=22) and NLC mice (n=21). Left ventricular (LV) remodeling and cardiac function was assessed after 4 weeks. Area at risk was estimated in separate groups of animals after perfusion with Evans blue dye, and was similar among Tg-CTGF and NLC mice. In addition, serum levels of CTGF (s-CTGF) were measured in 42 patients admitted to hospital for ST-elevation MI, 2 days, 1 week, 2 months and 1 year after percutaneous coronary intervention (PCI). Cardiac MRI was performed at the same time points to determine infarct size and LV ejection fraction (EF).   Results:  During the 4 weeks follow-up, survival was significantly higher in Tg-CTGF than in NLC mice; 64% vs. 38%, p   Conclusion:  CTGF prevents development of ischemic heart failure in mice, and increase in s-CTGF levels in patients after MI is associated with attenuated LV remodeling and improved cardiac function. These results indicate cardioprotective effects of CTGF in ischemic heart failure.
Ingrowth and device disintegration in an intralobar abscess cavity during endosponge therapy for esophageal anastomotic leakage
Authors: B. Schniewind, C. Schafmayer, M. Both, A. Arlt, A. Fritscher-Ravens, J. Hampe
Journal: Endoscopy (2011)

A 53-year-old man underwent esophageal resection for esophageal adenocarcinoma that extended from 29 cm to 33 cm from the incisors. The pathology specimen was staged as a T2N0 adenocarcinoma with an R0 resection. At 7 days post resection, the patient developed signs of systemic inflammation, which progressed within 12 hours to a septic condition requiring artificial ventilation and vasopressor support.
Through-the-skin ERCP and endoscopic ultrasound-guided cystogastrostomy in a patient with a Roux-en-Y gastric bypass
Authors: Joshua Max, William Cooney, James Scheiman, Matthew Dimagno, Badih Elmunzer
Journal: Endoscopy (2014)

A 40-year-old woman with a history of Roux-en-Y gastric bypass (RYGB) 10 years previously was transferred to our institution with acute pancreatitis complicated by acute pancreatic fluid collections (APFCs). The patient complained of severe epigastric abdominal pain and tenderness. Her amylase and lipase, which had peaked at around 5000 U/L several days before, were noted to be 116 IU/L (normal 30 – 100) and 305 U/L (normal 5 – 50), respectively. Her remaining laboratory results were unremarkable. Computed tomography (CT) and subsequent magnetic resonance imaging (MRI) scans revealed extensive pancreatic stranding and multiple APFCs, including an 8-cm collection that was compressing the duodenum and resulting in distension of the excluded stomach.
Abstract 2360: Dimethyl sulfoxide induces upregulation of tumor suppressor HLJ1 through activator protein-1 activation in human lung adenocarcinoma CL1-5 cells
Authors: Chi-Chung Wang, Ai-Me Lin, Yi-Hua Lai, Sheng-Yi Lin, Pan-Chyr Yang, Jeremy J. W. Chen
Journal: Cancer Research (2011)

Abstract Dimethyl sulfoxide (DMSO) is an amphipathic molecule and has a diversity of antitumor activities. Previous studies demonstrated that DMSO could modulate AP-1 activity and lead to cell cycle arrest at G1 phase. HLJ1 is a newly identified tumor and invasion suppressor that inhibits tumorigenesis and cancer metastasis. Its transcriptional activity is also regulated by transcription factor AP-1. However, the effect of DMSO on HLJ1 is still unknown. In this study, low-HLJ1 expressing highly invasive CL1-5 lung adenocarcinoma cells were subjected to DMSO treatment. We found that DMSO can significantly inhibit cancer cell invasion and migration capabilities through up-regulation of HLJ1 in a concentration-dependent manner. In addition, knockdown of HLJ1 expression by siRNA was able to block the effects of DMSO-induction. The HLJ1 promoter and enhancer reporter assay revealed that DMSO transcriptionally upregulates HLJ1 expression through an AP-1 site within the HLJ1 enhancer. Furthermore, AP-1 subfamily members, JunD and JunB, were significantly upregulated by DMSO in a concentration-dependent manner. In conclusion, our results suggest that DMSO could be an important stimulator of the tumor suppressor protein, HLJ1, through AP-1 activation in highly invasive lung adenocarcinoma CL1-5 cells. Our findings provide some important information for further investigations to develop new drugs such as DMSO-derived analogues which may inhibit cancer invasion and progression by targeting HLJ1. 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 2360. doi:10.1158/1538-7445.AM2011-2360
Abstract 4857: The role of autophagy in taxane resistant breast cancer models
Authors: Nesrin S. Rechache, Rebecca B. Riggins, Ayesha N. Shajahan, Alan Zwart, Robert Clarke
Journal: Cancer Research (2010)

Abstract Treatment with the taxanes (Paclitaxel or Docetaxel) is often the therapy of choice for women with advanced breast cancer. In most cases, the taxanes can arrest cell proliferation at the G2/M phase and cause cell death. However, some tumors develop resistance during the course of treatment, which is a major concern for both patients and physicians. Several mechanisms have been proposed to explain how resistance to the taxanes occurs, but this phenomenon remains incompletely understood. We hypothesize that changes in cell death signaling, through apoptotic and non-apoptotic pathways, are responsible for taxane resistance in breast cancer. Using the MDA-MB-231 breast cancer cell line model, we selected cells that are resistant to either Docetaxel (DocR) or Paclitaxel (PacR). Subsequently we studied levels of cell death and the response to IC50 concentrations of these drugs. Given the molecular crosstalk that can occur between cells dying by apoptosis and the autophagy process, Western blots for prosurvival Bcl-2 and NFκB were performed, and these showed reduced expression in the taxane resistant cells compared to the sensitive cell lines. In conjunction with changes in apoptotic markers in the resistant cell lines, there were also changes in autophagy protein markers such as increased expression of cleaved LC3 and a decrease in p62/SQSTM1 expression, particularly in the PacR cells. Beclin-1 and XBP-1 expression, however, were not differentially expressed between the sensitive and both resistant cell lines. Beclin-1 and p62 have been implicated in the regulation of both Bcl-2 and NFκB expression. In order to determine whether the changes in autophagy marker protein expression was an indication of an alternative cell death process or cell survival, proliferation assays were performed with sensitive and resistant cells. Cells were counted after exposure for 7 days with and without 3-Methyladenine, an inhibitor of autophagosome formation. The addition of 3-MA significantly decreased cell number suggesting that autophagy may be a mechanism of cell survival in both taxane resistant models. Given our preliminary data, we propose to further investigate the role of autophagy and other alternative cell death evasion pathways seen in MDA-MB-231 taxane resistant and sensitive breast cancer cells. Our studies aim to improve the understanding of how different mechanisms of cell death evasion contribute to the resistance phenotype. Ultimately our studies may not only improve our understanding of taxane resistance at the bench, but may also provide the framework for formulation of novel therapies that may improve the success of taxane therapy in women with breast cancer in the clinic. 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 4857.
P13.02 * PROTON THERAPY FOR BRAIN AND SKULL BASE TUMORS AT THE NEW OPENING TRENTO FACILITY
Authors: D. Amelio, M. Cianchetti, B. Rombi, S. Vennarini, F. Dionisi, L. Vinante, M. Amichetti
Journal: Neuro-Oncology (2014)

BACKGROUND: Thanks to their distinct physical properties proton therapy (PT) offers a superior dose distribution than photon radiation therapy. For brain and skull base (SB) tumors such dose sparing can be harnessed: a) in benign tumors, to achieve long-term better quality of life and reduced risk of neurocognitive deficits as well as radiation-related malignancies by delivering standard dose level; b) in malignant tumors or malignancies with local aggressiveness, to improve local control by safe delivery of tumor dose escalation. In the following we report an overview on our facility and the neuro-oncology program. METHODS/RESULTS: The Trento facility is built on over an area that will host the new Trento Hospital so that it will be a hospital-based PT center. As opposed to most centers using PT in the past, our facility is equipped with active beam delivery employing the spot scanning technique. A cyclotron provides a library of pencil beams of variable energy (70 - 226 MeV) and spot size (σ, 3 - 7 mm). Within the center, radiation therapy is offered in two treatment rooms. To allow for 360° rotation of the beamline these rooms are equipped with two gantries. In the treatment rooms, patients are placed on a robotic treatment table offering maximal variability and flexibility for patient positioning. The rooms are also equipped with devices enabling X-ray for treatment position verification. In a second step, the rooms will be equipped with cone-beam CT (room 1) and CT on-rails (room 2). Additionally there is one room equipped with horizontal beamline and equivalent beam scanning technology dedicated to quality assurance and preclinical research. For treatment planning imaging, the center is equipped with a dedicated CT and 1.5T MR. The staff is composed by professionals that experienced in leading particle centers in Villigen (CH), Heidelberg (GER), Boston (USA), Jacksonville (USA), Philadelphia (USA). Dedicated protocols for tumors of the brain and SB, for both adults and pediatric patients will be conducted based on the previous conducted trials on PT and potential expected benefit. As mentioned above, according to different clinical aims we are going to treat both benign and malignant tumors. The former group includes pituitary adenomas, schwannoma, benign meningioma, chondrosarcoma, craniopharyngioma, ependymoma, low-grade gliomas, medulloblastoma. In a second step, a PT radiosurgery program will be implemented for some of them. The latter group includes chordoma, high-grade gliomas, and atypical-malignant meningiomas. Regardless of the tumor type patients can be accepted also for re-irradiation. CONCLUSIONS: After a dedicated planning, construction and commissioning phase, patient treatment at Trento PT center is expected for summer 2014. Based on the already demonstrated as well as further potential clinical benefit neuro-oncology represents one of the most important field of interest.
Candy-like sign during endoscopic ultrasound-guided choledochoduodenostomy as an indication of the long distance between the bile duct and duodenal wall
Authors: Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Taiki Kudo, Yoko Abe, Kimitoshi Kubo, Yoshimasa Kubota, Naoya Sakamoto
Journal: Endoscopy (2014)

Endoscopic ultrasound-guided choledocoduodenostomy (EUS-CDS) using a covered self-expandable metallic stent (SEMS) is an established alternative drainage technique for patients in whom endoscopic retrograde cholangiopancreatography has failed [1] [2]. This report describes the case of a patient who underwent successful EUS-CDS with a partially covered SEMS placed far from the duodenal wall.
A memorable patient: Truth drug
Authors: I. D Conacher
Journal: BMJ (1998)

It was Remembrance Day poppies that brought him to mind and made me seek out his picture. He was my last first world war veteran patient and he had kindly allowed me to record his wound for posterity. 

I found the photos and looked on a dignified elderly man with a ramrod back and military moustache and a foreshortened upper limb that hung strangely and limply by his side. I remember his whole persona exuded a rigid, traditional, regimental career and yet it was founded on just six months of soldiering. As old as the century he had, as was typical, lied about his age and volunteered. After some square bashing and rudimentary combat training he had been landed in France, picked his regiment on site from the lists of the decimated, and, as he had chosen a Scottish regiment, was put in a kilt and sent to the front. There, a German shell had bisected his arm at the elbow. Even though he was slipping in and out of consciousness, he was ordered to make his own way back, unaided, through the lines and mud, under fire. At some point he was picked up by a horse drawn ambulance and taken to a casualty clearing station run by the French. The military doctor felt that the limb was salvageable because the injury was bone and soft tissue, and the hand was neurologically intact. 

Many operations and months later he did indeed come out with a limb which, as I had discovered when I shook his hand, he could make perfectly functional with some tricks of movement and positioning, and it had served him well for 70 years. He discoursed the fate of his comrades of the day while I conducted the anaesthetic preliminaries for his prostatectomy. As he felt the influence of the thiopentone sapping his consciousness, he began to overemphasise his words, but clearly, coherently, and very determinedly, he expressed a last thought: “That bastard Haig should have been hung.”