tbuckley/cabot-search huggingface dataset:
The potential role of IGF1r in young adult patients with gastroinetstinal stromal tumor (GIST)
Authors: M. Pantaleo, A. Astolfi, M. Di Battista, P. Paterini, D. Santini, F. Catena, M. Nannini, M. Saponara, C. Lolli, A. Maleddu, G. Biasco
Journal: Journal of Clinical Oncology (2009)

10562 Background: The insulin-like growth factor 1 receptor (IGF1r) is a tyrosine kinase receptor that plays a key role in the growth of normal tissues. The aberration of IGF system has been found in many cancers. Some interesting results about IGF1r were published on GISTs. However, until now the real role on the pathogenesis of this disease and its clinical implications still needs to be defined. Methods: We studied IGF1r in 8 patients affected by gastric GIST. Seven patients underwent surgery at diagnosis, whereas one patient was operated after imatinib and sunitinib treatment. Two patients were young (&lt; 30 years old), and other patients ranged between 54 and 85 years. IGF1r was studied as gene expression profiling performed with Affymetrix GeneChip HG-U133 Plus 2.0 arrays, as genomic copy number with SNP array analysis Affymetrix Genome Wide Human SNP 6.0 arrays, and with western blotting (WB) usinganti-IGF-IRβ (Santa Cruz Biotechnology). Results: The unsupervised analysis of gene expression profiling of our patients merged with a data set from a gastric GIST identified two groups with different regulation of IGF1r (FDR threshold to 0.2%). In particular, IGF1r was up-regulated in the two youngest patients (28 and 30 years-old). The SNPs array analysis gene copy number showed that none of the patients bore IGF1r amplification. The quantitative analysis of protein level by WB again showed that only the two youngest patients had an over-expression of IGF1r. In all the other patients the WB analysis was negative. Conclusions: These results suggest that IGF1r seems to be a novel signalling pathway other than KIT and PDGFRA in a subset of GISTs. The young adult patients had a strongly different molecular background in comparison to the other older ones. The correlation between IGF1r and mutational status of KIT and PDGFRA, clinical outcome, treatments responsiveness as well as its role as potential target deserves to be further investigated. No significant financial relationships to disclose.
PTH-039 Prevalence of sessile serrated adenomas/polyps in distal colon during screening colonoscopy/flexible sigmoidoscopy: a single bowel cancer screening experience from uk
Authors: R Rameshshanker, F Purchiaroni, W Ana, S Thomas-Gibson, A Rajendran, BP Saunders, Z Tsiamoulos
Journal: Endoscopy (2017)

<h3>Introduction</h3> Sessile Serrated Adenomas/Polyps (SSA/P) are responsible for nearly 20% of colo rectal cancer (CRC). Despite the utility of novel image enhancing techniques including narrow band imaging it is difficult to differentiate hyperplastic (HP) polyps from SSA/Ps. Vast proportion of endoscopists leave the diminutive and possibly small HP polyps <i>in situ</i> in the recto sigmoid area (diagnose and disregard approach). Hence there is a possibility of leaving SSA/P in the recto sigmoid region which could potentially lead to CRC later in life. <h3>Aim</h3> To estimate the prevalence of SSA/P in recto sigmoid colon at screening colonoscopy and flexible sigmoidoscopy (FS). <h3>Method</h3> Patients aged &gt;55 years underwent a screening colonoscopy (n=500) or a flexible sigmoidoscopy (n=500) at our institution between August 2014 and April 2015 were included. Data collected from 500 consecutive patients who underwent a colonoscopy or a FS. Demographic, procedural and polyp data were retrieved from our endoscopy database. <h3>Results</h3> 99.6% of (498/500) colonoscopy and 97.6% of flexible sigmoidoscopy procedures were completed. Screening colonoscopy detected 1006 polyps and FS detected 249 polyps. Polyp size ranged between 1–80 mm (colonoscopy mean size 6 mm, SD 7.2 mm; FS mean 3.4 mm, SD 3.9 mm). While colonoscopy detected 43 SSA/Ps (4.3%), FS detected only 6 SSA/Ps (2.4%) which equates to an overall prevalence of 3.9% (49/1255). Image 1 summarises the SSA/Ps prevalence by colonic segment. In recto sigmoid there were 21 SSA/Ps detected and resected which equals to a 3.9% of all recto sigmoid polyps. All SSA/Ps detected in this segment were less than 10 mm in size (range 2–10 mm). Only one of the SSA/P had dysplasia (4.7%). Prevalence of SSA/Ps in proximal colon was 4.8%. <h3>Conclusion</h3> Our cohort showed a slightly higher prevalence of SSA/Ps in rectum and sigmoid colon. Therefore, it becomes clinically relevant to differentiate SSA/Ps from HP polyps in recto sigmoid before adapting a diagnose and disregard approach for small (&lt;9 mm) hyperplastic looking polyps in this location. <h3>Disclosure of Interest</h3> None Declared
Pericardial Fat Thickness Increases with Greater Burden of Adverse Metabolic Factors Among Adults with Normal-Range Body Mass Index: The Framingham Heart Study
Authors: Philimon N. Gona, Jane J. Lee, Noriko Oyama-Manabe, Carol J. Salton, Warren J. Manning, Michael L. Chuang, Christopher J. O'Donnell
Journal: Circulation (2017)

Introduction: Greater burden of pericardial fat is associated with increased body mass index (BMI). Obesity is associated with unfavorable metabolic characteristics such as hypertension, dyslipidem...
The Possible Tumorigenicity of Nitrite: Reply
Authors: Sidney S. Mirvish, Ph.D.
Journal: JNCI Journal of the National Cancer Institute (1981)

The Possible Tumorigenicity of Nitrite: Reply Get access Sidney S. Mirvish, Ph.D. Sidney S. Mirvish, Ph.D. Eppley Institute for Research in Cancer University of Nebraska Medical Center, Omaha, Nebraska 68105 Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 66, Issue 2, February 1981, Page 216, https://doi.org/10.1093/jnci/66.2.216 Published: 01 February 1981
L’exploration des anémies d’origine digestive: exploration parla vidéocapsule endoscopique et impact de la prise de médicaments anticoagulants
Authors: CH Boustiere, G Lambot, O Lebars, P Castellani, V Oules, L Lecomte, M Bourliere
Journal: Endoscopy (2004)

Introduction: L’intérêt d’une exploration par vidéocapsule (ViCap) a été souligné par plusieurs équipes pour le diagnostic des anémies par saignement digestif occulte (ASD). Cette étude rétrospective vise à déterminer quel a été le rendement diagnostique de la ViCap dans le diagnostic des ASD et surtout d’essayer d’évaluer le rôle des anticoagulants (ATCG) dans l’apparition du saignement et la stratégie thérapeutique qui en découle. Patients et Méthodes: Sur une période de 18 mois (mars 2002 à septembre 2003), nous avons exploré 68 patients par ViCap (âge moyen = 56,2 ans, 33H/35F) dont 55 patients (82%) dans le cadre d’une ASD avec nécessité d’une transfusion dans 33 cas et traitement par ATCG dans 15 cas. Tous ont eu un bilan endoscopique préalable complet comprenant gastroscopie et iléocoloscopie, un transit baryté du grêle et pour certains un scanner abdomino pelvien. Une origine hématologique était exclue et les femmes avaient eu au minimum un examen gynécologique. Le matériel utilisé est la vidéocapsule M2A de Given Imaging avec station de travail dédiée utilisant le logiciel Rapid reader 2. Les enregistrements étaient lus indépendamment par 2 gastroentérologues endoscopistes expérimentés avec une conclusion concertée. Les lésions étaient classées en fonction de leur pertinence en 3 catégories selon la classification de Saurin modifiée: P1: lésion non responsable de saignement, P2: lésion potentiellement hémorragique et P3: si saignement actif. Nous avons étudié la fréquence et la localisation des lésions, les relations avec la prise d’anticoagulants, et les conséquences thérapeutiques. Résultats: Sur les 55 patients explorés pour anémie, l’examen était considéré comme strictement normal dans 24 cas (43%). Parmi les 31 examens pathologiques, nous avons retrouvé 11 lésions P1, 12 lésions P2 et 8 lésions P3. Quinze patients prenaient des ATCG avec une relation entre la prise d’ATCG et la pertinence des lésions chez 10 des 20 patients P2/P3 et surtout chez 5 des 8 patients P3, contre 1 seul chez les 11 patients avec lésions P1. La majorité de ces lésions P2/P3 se trouvait au niveau du duodénum distal ou jéjunum proximal (14/20) avec des angiomes ou angiodysplasies dans 16 cas. Un simple arrêt des ATCG a été proposé chez les 10 patients P2 et P3 avec une amélioration nette de l’anémie dans 8 cas. Les 10 autres patients P2/P3 ont été traités par coagulation Argon sous entéroscopie dans 7 caset opérés dans 3 cas (2 angiomes du grêle distal et 1 lésion tumorale). Conclusion: L‘exploration des saignements digestifs par ViCap présente dans notre expérience un impact diagnostique dans 2 cas sur 5. La prise d’ATCG est retrouvée dans la moitié des cas positifs et leur simple arrêt suffit le plus souvent à corriger l’anémie. L’entéroscopie à visée thérapeutique sera proposée aux autres patients P2 et P3 en fonction du type de lésion et de leur localisation.
Abstract 15675: Increased Osteoprotogerin and Osteopontin Serum Levels are Associated with Multivessel Coronary Artery Disease
Authors: Konstantinos Maniatis, Gerasimos Siasos, Dimitris Tousoulis, Evangelos Oikonomou, Marina Zaromitidou, Stamatios Kioufis, Christina Kollia, Antigoni Miliou, Dimitrios Athanasiou, Efstathios Dimitropoulos, Konstantinos Toutouzas, Konstantinos Tsioufis, Athanasios G Papavassiliou, Christodoulos Stefanadis
Journal: Circulation (2012)

Background: Coronary artery disease (CAD) is one of the most important manifestations of atherosclerosis. Osteoprotogerin (OPG) and osteopontin (OPN) has recently emerged as key factor in both vascular remodeling and development of atherosclerosis. The study was designed to evaluate the association of serum concentration of OPG and OPN with multivessel CAD. Methods: The study population consisted of 409 subjects undergoing diagnostic coronary angiography for suspected CAD. Angiography categorized subjects in: 280 patients with single-vessel (1VD) or multivessel (2VD, or 3VD) CAD (mean aged 61±11years), and in: 129 healthy subjects, as control group (CL), (mean aged 60±12 years). Serum OPG and OPN levels were measured, using ELISA. Results: CAD patients had significantly higher levels of OPG (3.91±1.87 pmol/l vs. 2.88± 2.17 pmol/l, p<0.001) and logOPN (1.81±0.18 ng/ml vs. 1.71±0.24 ng/ml, p<0.001). Analysis of variance revealed that OPG (CL:2.87±2.17 vs.1VD:3.75±1.76 vs. 2VD:3.41±1.68 vs. 3VD:4.48±2.15 pmo...
Impact diagnostique et thérapeutique de la ponction guidée par échoendoscopie. Résultats d’une base de données chez 1544 patients
Authors: M Giovannini, G Monges, E Bories, CH Pesenti, C Danisi, V Moutardier, B Lelong, JR Delpero
Journal: Endoscopy (2004)

But: Le but de cette étude rétrospective a été d’évaluer l’impact diagnostique et thérapeutique de la ponction guidée par échoendoscopie (PGEE) chez un collectif de 1544 patients. Patients et Méthodes: De novembre 1991 à septembre 2002:1544 patients (904 H, 640 F) d’âge moyen (67,2 ans extrêmes 17–88 ans) ont eu une ou plusieurs PGEE. L’indication de la PGEE a été une lésion solide du pancréas dans 534 cas, une masse ou des ganglions du médiastin dans 363 cas, des adénopathies coeliaques dans 245 cas, une masse ou des ganglions péri rectaux dans 121 cas, une lésion du foie gauche dans 104 cas, des gros plis gastriques avec macro biopsies endoscopiques négatives dans 63 cas, un épanchement pleural ou péritonéal dans 68 cas, une tumeur sous muqueuse dans 32 cas, une tumeur de la surrénale gauche dans 11 cas et une lésion de la vésicule biliaire dans 3 cas. Quatre vingt deux pour cents des PGEE ont été réalisées en ambulatoire. Les résultats de la PGEE ont été répertoriés dans une base de données prospectives (Fox-pro) corrélant le résultat de la PGEE avec les caractéristiques cliniques, biologiques, radiologiques et le suivi du patient. Le croisement de ces bases de données a permis d’étudier le réel impact du résultat de la PGEE sur le diagnostic de malignité et sur la décision thérapeutique prise. Résultats: Quinze patients ont présenté une complication (0,97%), il s’agissait de 9 bactériémies, 5 épisodes de pancréatite aiguë et 1 hémorragie. Toutes ces complications ont été résolues médicalement. Pour le diagnostic global de malignité, la sensibilité, la spécificité, la valeur prédictive positive, la valeur prédictive négative et la fiabilité de la PGEE ont été respectivement de 84,6%, 98,4%, 99,6%, 54,7% et 86,9% pour les 1544 patients. Pour le diagnostic sans avoir recours à une technique invasive (médiastinoscopie, laparotomie), la PGEE a eu un impact chez 678/1544 patients soit 43,9%. La décision thérapeutique a été directement influencée par le résultat de la PGEE chez 242/534 masses solides du pancréas (45,3%). Il s’agissait de 91 adénocarcinomes non diagnostiqués par la tomodensitométrie, et 151 lésions »non adénocarcinomateuses«. Enfin, le traitement a été également modifié par la PGEE chez 161 patients présentant une tumeur maligne de l’ésophage, de l’estomac, du pancréas ou du rectum par la mise en évidence »histologique« de ganglions métastatiques dans des sites dits »distants« dans la classification TNM ou par le diagnostic de petites métastases hépatiques non vues par la tomodensitométrie. Conclusion: La PGEE a influencé directement le diagnostic et le traitement chez 1081/1544 patients (70,1%). Ces résultats sont à interpréter en fonction de la prise en charge de ces patients dans un CLCC et l’inclusion de 25% d’entre eux dans des protocoles de traitements néo-adjuvants.
Identification of a Non-Growth Factor Role for GM-CSF in Advanced Atherosclerosis
Authors: Manikandan Subramanian, Edward Thorp, Ira Tabas
Journal: Circulation Research (2014)

Granulocyte macrophage colony-stimulating factor (GM-CSF, Csf2) is a growth factor for myeloid-lineage cells that has been implicated in the pathogenesis of atherosclerosis and other chronic inflammatory diseases. However, the role of GM-CSF in advanced atherosclerotic plaque progression, the process that gives rise to clinically dangerous plaques, is unknown.To understand the role of GM-CSF in advanced atherosclerotic plaque progression.Ldlr(-/-) mice and Csf2(-/-)Ldlr(-/-) mice were fed a Western-type diet for 12 weeks, and then parameters of advanced plaque progression in the aortic root were quantified. Lesions from the GM-CSF-deficient mice showed a substantial decrease in 2 key hallmarks of advanced atherosclerosis, lesional macrophage apoptosis and plaque necrosis, which indicates that GM-CSF promotes plaque progression. Based on a combination of in vitro and in vivo studies, we show that the mechanism involves GM-CSF-mediated production of interleukin-23, which increases apoptosis susceptibility in macrophages by promoting proteasomal degradation of the cell survival protein Bcl-2 (B-cell lymphoma 2) and by increasing oxidative stress.In low-density lipoprotein-driven atherosclerosis in mice, GM-CSF promotes advanced plaque progression by increasing macrophage apoptosis susceptibility. This action of GM-CSF is mediated by its interleukin-23-inducing activity rather than its role as a growth factor.
PTH-008 “real-world”, single-centre experience with over-the-scope clip placement
Authors: H Smart, N Haslam, A Young
Journal: Endoscopy (2017)

<h3>Introduction</h3> Over-the-scope clip (OTSC) application is indicated for the management of perforations, leaks, fistulas and gastrointestinal bleeding. We present our "real world" experience of the outcome of this technique in a variety of indications. <h3>Method</h3> Procedures were performed under moderate sedation or propofol using either a diagnostic (Olympus H260 or HQ290) or therapeutic (Olympus 1 T240 or 2 T240) gastroscope. The OTSC clip (Ovesco Endoscopy) or the Padlock clip (Diagmed Healthcare) was employed. Depending upon indication, tissue was acquired by either suction alone or the use of various accessories (OTSC Tissue Anchor or OTSC Twin Grasper, Ovesco Endoscopy) to enable OTSC deployment. <h3>Results</h3> All patients undergoing an OTSC procedure were recorded prospectively in an Excel spreadsheet and their outcomes analysed retrospectively after interrogation the hospital clinical, laboratory and endoscopy systems. A total of 16 patients (11 female) mean age 63.2 (range 24–78) years underwent 19 OTSC applications from June 2013 until September 2016. The median follow up was 192 (range 12–1294) days. The site, indication and outcomes are shown in the table. There were 6 deaths; median survival 47.5 (range 12–99) days. Deaths were in patients with aero-digestive (4) or post PEG (1) fistulae and spontaneous oesophageal perforation (1) despite adequate treatment. <h3>Conclusion</h3> In our centre the commonest indication for OTSC was fistula management. Although initial success in closure was high, recurrence was common (40%). All patients with an aero-digestive fistula had successful closure; however, all but 1 succumbed to their underlying disease, stressing the difficult management challenge of such cases. <h3>Disclosure of Interest</h3> None Declared
抗骨肉腫ドラッグデリバリーと骨形成分化のためのリン酸カルシウムりん酸化アデノシンハイブリッドミクロスフェア【Powered by NICT】
Authors: Zhou Zi-Fei, Sun Tuan-Wei, Chen Feng, Zuo Dong-Qing, Wang Hong-Sheng, Hua Ying-Qi, Cai Zheng-Dong, Tan Jun
Journal: Biomaterials (2017)
PTH-001 Results from the first uk virtual complex polyp mdm
Authors: A Chattree, M Rutter
Journal: Endoscopy (2017)

<h3>Introduction</h3> Data from the UK Bowel Cancer Screening Programme (BCSP) has established that the assessment and management of large non pedunculated colorectal polyps (LNPCPs) varies markedly, leading to variable and often suboptimal outcomes, especially for the most complex lesions<sup>1</sup>. A multicentre complex polyp multidisciplinary team meeting was created within the North East of England BCSP with the aim of ensuring more robust decision making and management of complex LNPCPs. <h3>Method</h3> A virtual multicentre MDM was conducted via audioteleconferencing within the North East of England between 2014–6 to discuss complex LNPCPs (LNPCPs with increased risk of malignancy or complexity associated with endotherapy, as defined in BSG/ACPGBI guidelines<sup>2</sup>). Non-complex LNPCPs were not discussed. Patient data was distributed securely via NHSmail. Outcomes were assessed prospectively using key performance indicators (KPIs) from the BSG/ACPGBI guidelines<sup>2</sup> <h3>Results</h3> 61 complex LNPCP cases were managed via the MDM with 8 excluded from analysis (7: managed prior to MDM referral, 1: MDM advice not followed), 27 lesions were managed with primary endotherapy, 23 with primary surgery and 3 cases conservatively. Of the endoscopic cases, 2 required surgery due to failed endotherapy and 2 due to a finding of malignancy. 12 month recurrence was 8.7% with no reported complications. The rate of surgical management using the BSG/ACPGBI KPI (including only surgically managed benign lesions or lesions subject to failed endotherapy) was 39.5%. The en-bloc resection rate of complex LNPCPs with features suggestive of increased malignancy risk was 71.4%. <h3>Conclusion</h3> Despite our series focusing on complex LNPCPs only, endoscopic 12 month outcomes remained within accepted BSG/ACPGBI standards (&lt;10% recurrence) <sup>1</sup>. Whilst the use of surgery was considerable (39.5%), this likely reflects the complex nature of this series with all except 2 lesions (appendiceal orifice lesions unsuitable for endotherapy) managed surgically classified as SMSA level 4, and all subject to detailed discussion beforehand<sup>1</sup>. We propose that dividing the KPI assessing surgical management of LNPCPs into SMSA 4, SMSA 3 and high malignancy risk may enable more optimal assessment of the quality of decision-making processes in this area. The findings from the complex polyp MDM support its continuation to develop a larger dataset and obtain detailed statistical analysis. <h3>References</h3> . Chattree A, Nylander D, Silcock J, et al. UEG15-ABS-1622. Marked Variation in Endoscopic Mucosal Resection Outcomes Within the UK Bowel Cancer Screening Programme. United European Gastroenterology Journal 2015; 2015: (Suppl 1). 2. Rutter MD, Chattree A, Barbour JA, et al. British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland Guidelines for the Management of Large Non-Pedunculated Colorectal Polyps. Gut 2015; 0:1–27. <h3>Disclosure of Interest</h3> None Declared
Co-stimulatory function in primary germinal center responses: CD40 and B7 are required on distinct antigen-presenting cells
Authors: Masashi Watanabe, Chiharu Fujihara, Andrea J. Radtke, Y. Jeffrey Chiang, Sumeena Bhatia, Ronald N. Germain, Richard J. Hodes
Journal: The Journal of Experimental Medicine (2017)

T cell-dependent germinal center (GC) responses require coordinated interactions of T cells with two antigen-presenting cell (APC) populations, B cells and dendritic cells (DCs), in the presence of B7- and CD40-dependent co-stimulatory pathways. Contrary to the prevailing paradigm, we found unique cellular requirements for B7 and CD40 expression in primary GC responses to vaccine immunization with protein antigen and adjuvant: B7 was required on DCs but was not required on B cells, whereas CD40 was required on B cells but not on DCs in the generation of antigen-specific follicular helper T cells, antigen-specific GC B cells, and high-affinity class-switched antibody production. There was, in fact, no requirement for coexpression of B7 and CD40 on the same cell in these responses. Our findings support a substantially revised model for co-stimulatory function in the primary GC response, with crucial and distinct contributions of B7- and CD40-dependent pathways expressed by different APC populations and with important implications for understanding how to optimize vaccine responses or limit autoimmunity.