tbuckley/cabot-search huggingface dataset:
IκB Kinase α Is Required for Development and Progression of <i>KRAS</i>-Mutant Lung Adenocarcinoma
Authors: Malamati Vreka, Ioannis Lilis, Maria Papageorgopoulou, Georgia A. Giotopoulou, Marina Lianou, Ioanna Giopanou, Nikolaos I. Kanellakis, Magda Spella, Theodora Agalioti, Vasileios Armenis, Torsten Goldmann, Sebastian Marwitz, Fiona E. Yull, Timothy S. Blackwell, Manolis Pasparakis, Antonia Marazioti, Georgios T. Stathopoulos
Journal: Cancer Research (2018)

Although oncogenic activation of NFκB has been identified in various tumors, the NFκB-activating kinases (inhibitor of NFκB kinases, IKK) responsible for this are elusive. In this study, we determined the role of IKKα and IKKβ in KRAS-mutant lung adenocarcinomas induced by the carcinogen urethane and by respiratory epithelial expression of oncogenic KRASG12D Using NFκB reporter mice and conditional deletions of IKKα and IKKβ, we identified two distinct early and late activation phases of NFκB during chemical and genetic lung adenocarcinoma development, which were characterized by nuclear translocation of RelB, IκBβ, and IKKα in tumor-initiated cells. IKKα was a cardinal tumor promoter in chemical and genetic KRAS-mutant lung adenocarcinoma, and respiratory epithelial IKKα-deficient mice were markedly protected from the disease. IKKα specifically cooperated with mutant KRAS for tumor induction in a cell-autonomous fashion, providing mutant cells with a survival advantage in vitro and in vivo IKKα was highly expressed in human lung adenocarcinoma, and a heat shock protein 90 inhibitor that blocks IKK function delivered superior effects against KRAS-mutant lung adenocarcinoma compared with a specific IKKβ inhibitor. These results demonstrate an actionable requirement for IKKα in KRAS-mutant lung adenocarcinoma, marking the kinase as a therapeutic target against this disease.Significance: These findings report a novel requirement for IKKα in mutant KRAS lung tumor formation, with potential therapeutic applications. Cancer Res; 78(11); 2939-51. ©2018 AACR.
Comparaison des performances de la coloscopie virtuelle et de la coloscopie conventionnelle dans la détection des néoplasies rectocoliques
Authors: L Golli, F Hamila, A Ben Slama, H Turki, S Hamila, H Jemni, S Hmissa, A Jmaa, S Ajmi
Journal: Endoscopy (2009)

Introduction: Le but de notre étude était de comparer les performances de la coloscopie virtuelle à celle de la coloscopie conventionnelle (CC) dans la détection des lésions néoplasiques colo rectales et de rapporter les résultats d'une première experience tunisienne.
CORRELATION BETWEEN ENDOSCOPIC AND HISTOLOGICAL DIAGNOSES OF DUODENAL ATROPHY
Authors: S Ben Amor, A Khsiba, O Gharbi, L Hamzaoui, M Medhioub, MM Azouz
Journal: Endoscopy (2018)

Duodenal atrophy (DA) is a mandatory condition for the diagnosis of celiac disease. This study aimed to evaluate the correlation between endoscopic and histological findings of DA.
ENDOSCOPIC ALLPICATION OF NEW HEMOSTATIC POWDER (UI-EWD®) IN GASTROINTESTINAL BLEEDING
Authors: YW Shin, BW Bang, K Kwon, HK Kim, DH Lee
Journal: Endoscopy (2018)

This was a prospective study investigating the efficacy of UI-EWD® in patients with various gastrointestinal bleeding. The UI-EWD powder was applied to post-ESD/EMR ulcer or to the bleeding sites undergoing insufficient hemostasis.
ADVANCED ENDOSCOPIC RESECTION IS SUFFICIENT TO TREAT SMALL DUODENAL CARCINOIDS
Authors: A Martínez-Alcalá García, S Sarker, KR Kyanam Kabir Baig, AM Ahmed, K Mönkemüller
Journal: Endoscopy (2018)

This is an observational, open-label, retrospective, single-arm, consecutive case series patients who underwent endoscopic resection of primary duodenal carcinoid neoplasms confirmed by histopathological and immunohistochemical tests during a 12-months period. Neuroendocrine markers including chromogranin A and 5-HIAA were measured. Ki-67 and synaptophysin stains were analysed from the tissue samples. The resections werre performed using injection chromoendoscopy and cap or ligation devices.
TYPICAL EUS FINDINGS IN LARGE DUODENAL BRUNNER'S GLAND HAMARTOMA
Authors: H Kim, KJ Lee, JS Choi
Journal: Endoscopy (2018)

Brunner's gland hamartoma or adenoma is a benign proliferative disorder of the duodenum. A large tumor (over 1 cm in diameter) is rare and difficult for endoscopic diagnosis. In this study, the feasibility of EUS on diagnosis of this tumor was investigated.
Place de la ponction guidée sous échoendoscopie pour le diagnostic des tumeurs endocrines du pancréas
Authors: M Giovannini, G Monges, E Bories, C Pesenti, F Caillol, JR Delpero
Journal: Endoscopy (2009)

But: Le but de cette étude rétrospective a été d'évaluer l'impact de la ponction guidée par échoendoscopie (PGEE) dans la prise en charge des tumeurs endocrines du pancréas (TEP). Peu d'études dans la littérature ont évalué le rendement de la PGEE pour les TEP. Nous rapportons notre expérience chez 86 patients.
Alleviation of Murine Osteoarthritis by Cartilage‐Specific Deletion of IκBζ
Authors: Moon‐Chang Choi, Takashi MaruYama, Churl‐Hong Chun, Yoonkyung Park
Journal: Arthritis & Rheumatology (2018)

Objective IκBζ, an atypical IκB family member, regulates gene expression in the nucleus as a transcriptional cofactor. Although IκBζ has been extensively studied in the immune system, its specific roles in osteoarthritis (OA) are currently unknown. The objective of this study was to investigate the potential role of IκBζ in chondrocyte catabolism and OA pathogenesis. We also determined the molecular mechanism underlying its relationship to the transcription factor NF‐κB. Methods We determined expression levels of IκBζ in mouse chondrocytes treated with interleukin‐1β (IL‐1β), in human OA cartilage, and in mouse experimental OA cartilage. Adenovirus‐mediated overexpression and small interfering RNA knockdown of IκBζ were performed to determine the impact of IκBζ on catabolic gene expression in vitro. Cartilage‐specific IκBζ‐transgenic and ‐knockout mice were generated and used for in vivo studies. Experimental and spontaneous OA were induced by surgical destabilization of the medial meniscus and by aging, respectively. Coimmunoprecipitation assay was used to examine the association between IκBζ and NF‐κB subunits. Results IκBζ was highly up‐regulated in chondrocytes in response to IL‐1β and in OA cartilage of human and mouse knee joints. Overexpression of IκBζ in chondrocytes promoted spontaneous OA development by activating chondrocyte catabolism. Genetic ablation of IκBζ in chondrocytes abolished catabolic gene induction by IL‐1β and protected against the development of experimental OA. IκBζ formed complexes with NF‐κB members to regulate catabolic factor expression. Conclusion These findings demonstrate a critical role for IκBζ in OA pathogenesis. Inhibition of IκBζ function might be an effective therapeutic approach for OA treatment.
SBCE IN IRON-DEFICIENT ANEMIA FOR PREMENOPAUSAL WOMEN – NOT ALWAYS A MATTER OF GENDER
Authors: C Arieira, P Boal Carvalho, F Dias de Castro, B Rosa, M João Moreira, J Cotter
Journal: Endoscopy (2018)

Small bowel capsule endoscopy (SBCE) is the gold standard in the investigation of iron deficiency anemia (IDA) after negative esophagogastroduodenoscopy (EGD) and colonoscopy. IDA occurs in 2 – 5% of adult men and postmenopausal women (PsM) and is a common cause of referral to gastroenterologists. IDA in premenopausal women (PrM) is often presumed to be due gynecological causes, and investigation is generally deferred in favor of iron replacement therapy.
Liposome-supported peritoneal dialysis in the treatment of severe hyperammonemia: An investigation on potential interactions
Authors: Giovanna Giacalone, Simon Matoori, Valentina Agostoni, Vincent Forster, Meriam Kabbaj, Sarah Eggenschwiler, Martin Lussi, Andrea De Gottardi, Nicola Zamboni, Jean-Christophe Leroux
Journal: Journal of Controlled Release (2018)
Efficacité, complications et suivi à long terme de 234 mucosectomies coliques réalisées dans un centre hospitalier général
Authors: C Barrault, D Gillot, B Pellat, I Rosa Hezode, A Chryssostalis, T Lons, AC Lesage, M Chousterman, H Hagège
Journal: Endoscopy (2009)

Introduction: La mucosectomie permet l'exérèse de polypes coliques sessiles de grande taille, mais comporte un risque de complications non négligeable. Cette étude avait pour but d'évaluer la faisabilité et la morbi-mortalité de cette technique ainsi que les résultats à long terme chez des patients suivis dans un centre hospitalier général.
The microbiome in precision medicine: the way forward
Authors: Joseph F. Petrosino
Journal: Genome Medicine (2018)

Novel associations between the human microbiome and health and disease are routinely emerging, and important host–microbiome interactions are targets for new diagnostics and therapeutics. Understanding how broadly host–microbe associations are maintained across populations is revealing individualized host–microbiome phenotypes that can be integrated with other 'omics' data sets to enhance precision medicine.
Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study
Authors: Roope Männikkö, Leonie Wong, David J Tester, Michael G Thor, Richa Sud, Dimitri M Kullmann, Mary G Sweeney, Costin Leu, Sanjay M Sisodiya, David R FitzPatrick, Margaret J Evans, Iona J M Jeffrey, Jacob Tfelt-Hansen, Marta C Cohen, Peter J Fleming, Amie Jaye, Michael A Simpson, Michael J Ackerman, Michael G Hanna, Elijah R Behr, Emma Matthews
Journal: The Lancet (2018)

BackgroundSudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. Variants in NaV1.4 that directly alter skeletal muscle excitability can cause myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome. SCN4A variants have also been found in infants with life-threatening apnoea and laryngospasm. We therefore hypothesised that rare, functionally disruptive SCN4A variants might be over-represented in infants who died from SIDS.MethodsWe did a case-control study, including two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched controls without a history of cardiovascular, respiratory, or neurological disease. We compared the frequency of rare variants in SCN4A between groups (minor allele frequency <0·00005 in the Exome Aggregation Consortium). We assessed biophysical characterisation of the variant channels using a heterologous expression system.FindingsFour (1·4%) of the 278 infants in the SIDS cohort had a rare functionally disruptive SCN4A variant compared with none (0%) of 729 ethnically matched controls (p=0·0057).InterpretationRare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. These findings indicate that dysfunction of muscle sodium channels is a potentially modifiable risk factor in a subset of infant sudden deaths.FundingUK Medical Research Council, the Wellcome Trust, National Institute for Health Research, the British Heart Foundation, Biotronik, Cardiac Risk in the Young, Higher Education Funding Council for England, Dravet Syndrome UK, the Epilepsy Society, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program.
THE NOVEL SWIPE CRYOBALLOON ABLATION DEVICE FOR TREATING LARGER AREAS OF BARRETT'S ESOPHAGUS: A MULTICENTER STUDY TO EVALUATE SAFETY AND DOSE-RESPONSE
Authors: S van Munster, A Overwater, G Raicu, C Seldenrijk, W Nagengast, E Schoon, J Bergman, B Weusten
Journal: Endoscopy (2018)

Cryoballoon ablation (CBA) has been gaining attention as therapy for Barrett's esophagus (BE). CBA preserves the extracellular matrix and might therefore result in improved tolerability and lower stricture-rates when compared to other therapies. It comprises a through-the-scope system with a conformable balloon, that is simultaneously inflated and cooled using nitrous-oxide. Focal CBA has shown promising results, but is only suitable for limited BE. The 90 °-Swipe system (90 °-SCBA) has been developed to ablate 25% of the circumference over 3 cm in a single-step process.
ENDOSCOPIC MUCOSAL RESECTION IN DYSPLASTIC BARRETT'S OESOPHAGUS WITH UNDERLYING OESOPHAGEAL VARICES USING BAND LIGATION
Authors: H Uchima, I Serra, L Torrealba, C Huertas, M Figa, M Hombrados, X Aldeguer
Journal: Endoscopy (2018)

Dysplastic Barrett's oesophagus (BE) is usually treated by techniques such as endoscopic mucosal resection (EMR) and radiofrequency ablation.
Evaluation de la qualité de l'information délivrée au patient hospitalisé pour une coloscopie programmée
Authors: A Chryssostalis, M Soulier, I Rosa Hezode, C Barrault, AC Lesage, T Lons, P Cattan, D Gillot, C Grateau, B Pellat, H Hagège
Journal: Endoscopy (2009)

Introduction: La coloscopie, examen couramment pratiqué dans nos services, comporte un risque de complications potentiellement graves. La loi du 4 mars 2002 donne obligation au médecin de fournir une information sur les bénéfices et les risques de ce type d'examen et le recueil du consentement éclairé doit être formalisé. Le but de ce travail a été d'évaluer la qualité de l'information délivrée et également la compréhension de celle-ci par le patient.
ENDOSCOPIC RESECTIONS IN CIRRHOTIC PATIENTS: OUTCOMES AND ADVERSE EVENTS OF 269 PROCEDURES
Authors: C Miaglia, J Rivory, O Guillaud, V Lépilliez, C Chambon-Augoyard, J Dumortier, T Ponchon, M Pioche
Journal: Endoscopy (2018)

Endoscopic resection (ER) is a safe method for treatment of superficial digestive neoplasia. However, results in cirrhotic patients have not been fully evaluated. On the contrary, abdominal surgery is at high risk of hepatic decompensations, infections and bleedings. ER could be an interesting alternative.
Abstract B64: The role of deubiquitinating enzyme USP17, hyaluronan synthase 2, and hyaluronan in non-small-cell lung cancer oncogenic transformation
Authors: Merima Mehic, Vanessa Karen de Sá, Sandra Hebestreit, Paraskevi Heldin, Carl Henrik Heldin
Journal: Clinical Cancer Research (2018)

Abstract Introduction: Lung cancer is the result of a multistep accumulation of genetic and/or epigenetic alterations; therefore, a better understanding of the molecular mechanism by which these alterations affect lung cancer pathogenesis would provide new diagnostic procedures and prognostic factors for early detection of recurrence. The remarkable qualitative and quantitative modifications of extracellular matrix components as the deubiquitinating enzyme (USP17), hyaluronan (HA), and hyaluronan synthases 2 (HAS 2) may favor invasion, cellular motility, and proliferation in several cancers including lung. Results: The silencing of USP17 led to decreased hyaluronan production, whereas the suppression of USP4 increased hyaluronan synthesis. Importantly, high levels of USP17 and HAS2 were detected in a panel of cancer cell lines compared to normal cells, and immunohistochemical stainings revealed higher expression of USP17 and HAS2 in tissues of lung cancer patients compared to normal tissue. Numerous epithelial cells expressed USP17 and HAS2 in dysplasia compared to squamous cell carcinoma (SqCC) (p=0.001). USP17 and HAS2 were prominently expressed in adenocarcinoma (ADC) (p≤0.005). HA immunostaining indexes were increased in ADC and SqCC compared to normal and dysplasia cells (p=0.05). Consistent with the immunohistochemical analyses, low amounts of hyaluronan and USP17 were observed in SqCC by confocal analysis, coincident with less colocalization as determined by confocal microscopy. In contrast, a high expression of hyaluronan (48% of positive index) and high USP17 expression (78% of positive index) in ADC was consistent with a higher degree of colocalization. Conclusions: HAS2, hyaluronan and USP17 were expressed at higher levels in particular in preneoplastic lesions and ADC, suggesting a role in NSCLC oncogenic transformation, possibly by promoting cellular division by USP17-mediated. Elucidation of the mechanism of how USP17 and HAS2 cooperate in the regulation of the cell cycle might be of therapeutic importance. Citation Format: Merima Mehic, Sr., Vanessa Karen de Sá, Sr., Sandra Hebestreit, Sr., Paraskevi Heldin, Sr., Carl Henrik Heldin, Sr.. The role of deubiquitinating enzyme USP17, hyaluronan synthase 2, and hyaluronan in non-small-cell lung cancer oncogenic transformation [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr B64.
Assessment of Tumor Sequencing as a Replacement for Lynch Syndrome Screening and Current Molecular Tests for Patients With Colorectal Cancer
Authors: Heather Hampel, Rachel Pearlman, Mallory Beightol, Weiqiang Zhao, Daniel Jones, Wendy L. Frankel, Paul J. Goodfellow, Ahmet Yilmaz, Kristin Miller, Jason Bacher, Angela Jacobson, Electra Paskett, Peter G. Shields, Richard M. Goldberg, Albert de la Chapelle, Brian H. Shirts, Colin C. Pritchard
Journal: JAMA Oncology (2018)

Universal tumor screening for Lynch syndrome (LS) in colorectal cancer (CRC) is recommended and involves up to 6 sequential tests. Somatic gene testing is performed on stage IV CRCs for treatment determination. The diagnostic workup for patients with CRC could be simplified and improved using a single up-front tumor next-generation sequencing test if it has higher sensitivity and specificity than the current screening protocol.To determine whether up-front tumor sequencing (TS) could replace the current multiple sequential test approach for universal tumor screening for LS.Tumor DNA from 419 consecutive CRC cases undergoing standard universal tumor screening and germline genetic testing when indicated as part of the multicenter, population-based Ohio Colorectal Cancer Prevention Initiative from October 2015 through February 2016 (the prospective cohort) and 46 patients with CRC known to have LS due to a germline mutation in a mismatch repair gene from January 2013 through September 2015 (the validation cohort) underwent blinded TS.Sensitivity of TS compared with microsatellite instability (MSI) testing and immunohistochemical (IHC) staining for the detection of LS.In the 465 patients, mean age at diagnosis was 59.9 years (range, 20-96 years), and 241 (51.8%) were female. Tumor sequencing identified all 46 known LS cases from the validation cohort and an additional 12 LS cases from the 419-member prospective cohort. Testing with MSI or IHC, followed by BRAF p.V600E testing missed 5 and 6 cases of LS, respectively. Tumor sequencing alone had better sensitivity (100%; 95% CI, 93.8%-100%) than IHC plus BRAF (89.7%; 95% CI, 78.8%-96.1%; P = .04) and MSI plus BRAF (91.4%; 95% CI, 81.0%-97.1%; P = .07). Tumor sequencing had equal specificity (95.3%; 95% CI, 92.6%-97.2%) to IHC plus BRAF (94.6%; 95% CI, 91.9%-96.6%; P > .99) and MSI plus BRAF (94.8%; 95% CI, 92.2%-96.8%; P = .88). Tumor sequencing identified 284 cases with KRAS, NRAS, or BRAF mutations that could affect therapy for stage IV CRC, avoiding another test. Finally, TS identified 8 patients with germline DPYD mutations that confer toxicity to fluorouracil chemotherapy, which could also be useful for treatment selection.Up-front TS in CRC is simpler and has superior sensitivity to current multitest approaches to LS screening, while simultaneously providing critical information for treatment selection.
Health-Related Quality-of-Life Analysis From KEYNOTE-045: A Phase III Study of Pembrolizumab Versus Chemotherapy for Previously Treated Advanced Urothelial Cancer
Authors: David J. Vaughn, Joaquim Bellmunt, Yves Fradet, Jae Lyun Lee, Lawrence Fong, Nicholas J. Vogelzang, Miguel A. Climent, Daniel P. Petrylak, Toni K. Choueiri, Andrea Necchi, Winald Gerritsen, Howard Gurney, David I. Quinn, Stephane Culine, Cora N. Sternberg, Yabing Mai, Haojie Li, Rodolfo F. Perini, Dean F. Bajorin, Ronald de Wit
Journal: Journal of Clinical Oncology (2018)

Purpose In the phase III KEYNOTE-045 study ( ClinicalTrials.gov identifier: NCT02256436), pembrolizumab significantly prolonged overall survival compared with investigator's choice of chemotherapy in patients with previously treated advanced urothelial cancer. Here, we report the results of health-related quality-of-life (HRQoL) analyses from the KEYNOTE-045 trial. Patients and Methods Patients were randomly assigned 1:1 to pembrolizumab 200 mg or investigator's choice of docetaxel 75 mg/m2, paclitaxel 175 mg/m2, or vinflunine 320 mg/m2 administered intravenously every 3 weeks. Key prespecified HRQoL analyses were time to deterioration (TTD) and mean change from baseline to week 15 in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire C30 global health status/quality-of-life score. Results Of 542 patients who were randomly assigned, 519 were included in HRQoL analyses (pembrolizumab, n = 266; chemotherapy, n = 253). HRQoL compliance was > 95% at baseline and approximately 88% at week 15 for both groups. Pembrolizumab prolonged TTD in global health status/quality-of-life score compared with chemotherapy (median, 3.5 months v 2.3 months; hazard ratio, 0.72; nominal one-sided P = .004). Mean (95% CI) change from baseline to week 15 in global health status/quality-of-life score was 0.69 (-2.40 to 3.77) with pembrolizumab and -8.36 (-11.84 to -4.89) with chemotherapy (mean difference, 9.05 points; 95% CI, 4.61 to 13.50; nominal two-sided P < .001). Conclusion Pembrolizumab prolonged TTD in HRQoL compared with chemotherapy. Patients who were treated with pembrolizumab had stable or improved global health status/quality of life, whereas those who were treated with investigator's choice of chemotherapy experienced declines in global health status/quality of life. Combined with efficacy and safety outcomes, these data support pembrolizumab as standard of care for patients with platinum-refractory advanced urothelial cancer.
Intérêt de l'étude endoscopique et immunohistochimique dans le diagnostic du segment court d'endobrachyoesophage: étude prospective de 111 cas
Authors: MH Ezzine
Journal: Endoscopy (2009)

Introduction: Le diagnostic de segment court d'Endobrachyoesophage (SCEBO), nécessite une confirmation anatomopathologique qui repose sur la mise en évidence d'une métaplasie intestinale (MI) dite spécialisée. Cependant, la distinction histologique entre un SCEBO et une cardite avec MI en rapport avec une infection à hélicobacter pylori (Hp) est souvent difficile mais capitale car l'évolution de ces deux lésions est différente. Le but de notre travail était d'évaluer l'apport de l'endoscopie et la contribution de l' immunohistochimie utilisant les anticorps anticytokératines (CK) 7 et CK 20 dans la MI au niveau de la jonction oesogastrique pour différentier un SCEBO d'une cardite à Hp.
EUS FNA Diagnostic Yield of Malignancy in Solid Pancreatic Masses: A Benchmark for Quality Performance Measurement
Authors: T Savides, G Hunt, M Donohue, C Behling
Journal: Endoscopy (2006)

Introduction: No benchmarking exists to assess EUS/FNA quality performance. Diagnostic yield of EUS/FNA of solid pancreatic masses (SPM) is a potential benchmark because the pre-test probability that a SPM is malignant is high (80–90%) and the EUS/FNA sensitivity for diagnosing malignancy is good (80–90%).