tbuckley/cabot-search huggingface dataset:
Contributions of inflammation and tumor microenvironment to neurofibroma tumorigenesis
Authors: Chung-Ping Liao, Reid C. Booker, Jean-Philippe Brosseau, Zhiguo Chen, Juan Mo, Edem Tchegnon, Yong Wang, D. Wade Clapp, Lu Q. Le
Journal: Journal of Clinical Investigation (2018)

Neurofibromatosis type 1 associates with multiple neoplasms, and the Schwann cell tumor neurofibroma is the most prevalent. A hallmark feature of neurofibroma is mast cell infiltration, which is recruited by chemoattractant stem cell factor (SCF) and has been suggested to sustain neurofibroma tumorigenesis. In the present study, we use new, genetically engineered Scf mice to decipher the contributions of tumor-derived SCF and mast cells to neurofibroma development. We demonstrate that mast cell infiltration is dependent on SCF from tumor Schwann cells. However, removal of mast cells by depleting the main SCF source only slightly affects neurofibroma progression. Other inflammation signatures show that all neurofibromas are associated with high levels of macrophages regardless of Scf status. These findings suggest an active inflammation in neurofibromas and partly explain why mast cell removal alone is not sufficient to relieve tumor burden in this experimental neurofibroma model. Furthermore, we show that plexiform neurofibromas are highly associated with injury-prone spinal nerves that are close to flexible vertebras. In summary, our study details the role of inflammation in neurofibromagenesis. Our data indicate that prevention of inflammation and possibly also nerve injury at the observed tumor locations are therapeutic approaches for neurofibroma prophylaxis and that such treatment should be explored.
MORPHEUS: A phase Ib/II multi-trial platform evaluating the efficacy and safety of cancer immunotherapy (CIT)-based combinations in patients (pts) with gastric or pancreatic cancer.
Authors: Gulam Abbas Manji, Johanna C. Bendell, Do-Youn Oh, Kyu-Pyo Kim, Teresa Macarulla, Mariano Ponz-Sarvisé, Jaffer A. Ajani, Paul Oberstein, Yelena Yuriy Janjigian, Ian Chau, Heba Abdullah, Xian He, Xiaosong Zhang, Jun Wang, Hila Barak, Edward Cha, William Grossman, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2018)

TPS530 Background: CIT has demonstrated significant survival benefits across multiple cancers. Despite remarkable success, only subsets of pts derive clinical benefit from CIT monotherapy. Thus, CIT combinations may be needed to address the mechanisms that allow cancers to escape antitumor immunity. However, a large number of potential combinations would have to be tested to identify an effective CIT combination regimen. The MORPHEUS platform consists of multiple, global, open-label, randomized Phase Ib/II trials designed to assess the impact of CIT combination therapies in pts with different tumor types. The randomized trial designs allow comparison of a single control arm vs multiple CIT combination arms. The trials will aid development of CIT combinations by identifying early signals and have the flexibility to open arms with new CIT combinations and close arms that show minimal clinical activity or unacceptable toxicity. Various CIT combinations that simultaneously enhance immune cell priming and activation, tumor infiltration and/or recognition of tumor cells for elimination will be evaluated. Here, we will describe Phase Ib/II trials in pts with gastric or gastroesophageal junction cancer (GC) and metastatic pancreatic ductal adenocarcinoma (mPDAC), both of which represent populations with high unmet medical need. Methods: MORPHEUS-GC (NCT03281369) will enroll 2 cohorts including pts with advanced unresectable or metastatic GC who have not received prior chemotherapy (chemo) or have progressed on platinum- or fluoropyrimidine-based chemo. MORPHEUS-PDAC (NCT03193190) will enroll pts with mPDAC who have progressed on prior chemo. Further eligibility criteria details will be provided. Pts will be randomized to one of the CIT combination arms or a control arm (up to 8 arms across 2 cohorts in GC; 4 arms in PDAC). Pts experiencing loss of clinical benefit or unacceptable toxicity may be eligible to continue on a different CIT combination arm. Primary endpoints are investigator-assessed ORR per RECIST v1.1 and safety. Secondary endpoints include PFS, OS, DCR and DOR. Multiple exploratory biomarkers will also be examined. Clinical trial information: NCT03281369, NCT03193190.
A new multi-tasking platform for advanced intraluminal and NOTES procedures: learning curve assessment and accuracy in an endoscopic mucosal resection model
Authors: G Fernández-Esparrach, SN Shaikh, NJ Soper, ES Hungness, RI Rothstein, LL Swanstrom, CC Thompson
Journal: Endoscopy (2008)

Introduction: Multi-tasking platforms for advanced intraluminal and NOTES procedures may surmount the technical challenges seen with standard flexible endoscopes. One such platform is the Direct Drive Endoscopic System (DDES) (Boston Scientifc Corporation). As such platforms are developed, the challenge moves to training and skill independent assessments of utility. We aim to develop training aids for evaluating multi-tasking platforms and to assess the learning curve and accuracy of DDES.
An <i>APOO</i> Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels
Authors: May E. Montasser, Elizabeth A. O’Hare, Xiaochun Wang, Alicia D. Howard, Rebecca McFarland, James A. Perry, Kathleen A. Ryan, Kenneth Rice, Cashell E. Jaquish, Alan R. Shuldiner, Michael Miller, Braxton D. Mitchell, Norann A. Zaghloul, Yen-Pei C. Chang
Journal: Circulation (2018)

Elevated levels of low-density lipoprotein cholesterol (LDL-C) are a major risk factor for cardiovascular disease via its contribution to the development and progression of atherosclerotic lesions. Although the genetic basis of LDL-C has been studied extensively, currently known genetic variants account for only ≈20% of the variation in LDL-C levels.
Flexible Endoscopic Treatment of Zenker's Diverticulum: a New Approach
Authors: C J Mulder, G den Hartog, R J Robijn, J E Thies
Journal: Endoscopy (1995)

In the past, a number of treatment modalities have been used for the management of a Zenker's diverticulum. These include transcervical diverticulectomy, myotomy, or laser or diathermy treatment via rigid endoscopes. Up to the present, no reports of the treatment of a Zenker's diverticulum with a flexible endoscope have been published.In this study, we present the results of our first 20 patients (13 male; mean age 82 years) prospectively treated with a flexible endoscope applied through diathermy. All patients had significant symptoms such as dysphagia, recurrent aspiration pneumonia and/or weight loss.Treatment using a mean of three sessions per patient was successful, with a good symptomatic response in all subjects. There were no severe complications associated with the therapy. Four patients complained about a sore throat for a few days. During follow-up (mean 6-7 months), three patients died due to unrelated causes, and 17 remained asymptomatic.An important advantage is that it is possible to perform the treatment without general anesthesia, and therefore also in patients whose general health is poor. The technique can easily be performed in an interventional endoscopy unit. Our first experiences show that flexible endoscopic treatment is an effective and relatively safe method.
Rôle de l'autofluorescence et du Narrow-Band Imaging dans la détection de la dysplasie de l'eosophage de Barrett
Authors: A Geagea, JF Rey
Journal: Endoscopy (2009)

Introduction: La recherche de dysplasie reste un élément majeur dans le suivi des œsophages de Barrett (OB). Le NBI a montré son utilité dans cette indication. L'index d'Autofluorescence (AFI) basé sur l'augmentation du réseau vasculaire secondaire à l'inflammation muqueuse semble être prometteur pour la recherche de dysplasie. Le but de cette étude est de rechercher l'utilité du NBI et de l'AFI dans le dépistage de dysplasie.
Barrett's esophagus, reflux esophagitis, and eosinophilic esophagitis
Authors: F. Vleggaar, P. Siersema
Journal: Endoscopy (2012)

Many new and exciting endoscopy-related studies on Barrett’s esophagus, reflux esophagitis, and eosinophilic esophagitis were presented during the 2012 Digestive Disease Week (DDW; 19 – 22 May, San Diego, California, USA). Endoscopic research in Barrett’s esophagus mainly focused on surveillance, detection, and ablation therapy, while clinical studies in eosinophilic esophagitis concerned budesonide treatment and dietary measures, and those on reflux esophagitis covered various issues related to anti-reflux surgery. In this review, we discuss our top 20 DDW 2012 abstracts on these three topics.
ADVERSE EVENTS IN PERFORMING SINGLE-OPERATOR PERORAL CHOLANGIOSCOPY: A COMPARISON OF SPYGLASS SYSTEM AND DIRECT POC UNDER CARBON DIOXIDE INSUFFLATION
Authors: KH Kim, JH Moon, YN Lee, HW Lee, HJ Choi, TH Lee, MH Choi, SW Cha, YD Cho, SH Park
Journal: Endoscopy (2018)

Recently, single-operator peroral cholangioscopy (SOC) systems were introduced and its various clinical implications were reported. Although it has been reported to be safe procedure, data on adverse events related to the procedure is limited. The aim of this study was to evaluate the incidence of adverse events in performing SOC in comparison of SpyGlass Direct Visualization System (SDVS) and direct peroral cholangioscopy (DPOC) by using an ultra-slim endoscope.
Intracellular Chloride and Scaffold Protein Mo25 Cooperatively Regulate Transepithelial Ion Transport through WNK Signaling in the Malpighian Tubule
Authors: Qifei Sun, Yipin Wu, Sima Jonusaite, John M. Pleinis, John M. Humphreys, Haixia He, Jeffrey N. Schellinger, Radha Akella, Drew Stenesen, Helmut Krämer, Elizabeth J. Goldsmith, Aylin R. Rodan
Journal: Journal of the American Society of Nephrology (2018)

Background With No Lysine kinase (WNK) signaling regulates mammalian renal epithelial ion transport to maintain electrolyte and BP homeostasis. Our previous studies showed a conserved role for WNK in the regulation of transepithelial ion transport in the Drosophila Malpighian tubule. Methods Using in vitro assays and transgenic Drosophila lines, we examined two potential WNK regulators, chloride ion and the scaffold protein mouse protein 25 (Mo25), in the stimulation of transepithelial ion flux. Results In vitro , autophosphorylation of purified Drosophila WNK decreased as chloride concentration increased. In conditions in which tubule intracellular chloride concentration decreased from 30 to 15 mM as measured using a transgenic sensor, Drosophila WNK activity acutely increased. Drosophila WNK activity in tubules also increased or decreased when bath potassium concentration decreased or increased, respectively. However, a mutation that reduces chloride sensitivity of Drosophila WNK failed to alter transepithelial ion transport in 30 mM chloride. We, therefore, examined a role for Mo25. In in vitro kinase assays, Drosophila Mo25 enhanced the activity of the Drosophila WNK downstream kinase Fray, the fly homolog of mammalian Ste20-related proline/alanine-rich kinase (SPAK), and oxidative stress-responsive 1 protein (OSR1). Knockdown of Drosophila Mo25 in the Malpighian tubule decreased transepithelial ion flux under stimulated but not basal conditions. Finally, whereas overexpression of wild-type Drosophila WNK , with or without Drosophila Mo25 , did not affect transepithelial ion transport, Drosophila Mo25 overexpressed with chloride-insensitive Drosophila WNK increased ion flux. Conclusions Cooperative interactions between chloride and Mo25 regulate WNK signaling in a transporting renal epithelium.
Effect and safety of proton beam therapy for locally recurrent rectal cancer.
Authors: Yusuke Ogi, Tomohiro Yamaguchi, Yusuke Kinugasa, Akio Shiomi, Hiroyasu Kagawa, Yushi Yamakawa, Akinobu Furutani, Yusuke Yamaoka, Shoichi Manabe, Hitoshi Hino, Yoshinobu Nagasawa, Takuya Suzuki, Kakeru Torii, Shunichiro Kato, Kohei Koido, Shigeyuki Murayama
Journal: Journal of Clinical Oncology (2018)

743 Background: The first choice of treatment for locally recurrent rectal cancer is surgical resection. However, the operation is often difficult with high perioperative risk. For surgically unfit cases, proton beam therapy (PBT) is proposed as the treatment option. However, its efficacy for locally recurrent rectal cancer remains unclear. Therefore, this study aimed to evaluate the efficacy and safety of PBT for locally recurrent rectal cancer. Methods: A total of 23 patients with locally recurrent rectal cancer who received PBT were retrospectively evaluated, from November 2005 to July 2014. Patients with single lesion, who refuse the radical surgical therapy, or who were considered unfit for the operation were included in this study. All patients were treated with 2.8Gy relative biological effectiveness (RBE)/fraction. Twenty-five irradiations were performed, with a total irradiation of 70Gy RBE. Unfit for operation criteria include invasion to the vertebra higher than the third sacrum or lateral lymph node recurrence after a lateral lymph node dissection. To assess the safety of PBT, adverse events were evaluated by using the Common Terminology Criteria for Adverse Effects (CTCAE version4.0). To assess the efficacy, the overall and relapse-free survival rates and local control rate were evaluated. Results: Sixteen patients were unfit for operation, and seven refused surgery. Three patients experienced Grade 3 late adverse events in the CTCAE (two ileum fistula and one urinary tract obstruction). The median follow-up time was 28.9 months. The 5-year overall and relapse-free survival rates were 47.6% and 20.2%, respectively. Fifteen patients (65.2%) showed distant metastasis or regrowth at the locally recurrent site. The 5-year local control rate was 39.0%. Ten patients (43.4%) showed regrowth at the proton beam irradiation site. Conclusions: PBT was relatively effective for locally recurrent rectal cancer with manageable adverse effects. Therefore, PBT may be considered as the therapeutic option for selected locally recurrent rectal cancer patients.
PREDICTIVE FACTORS FOR REBLEEDING IN VARICEAL UPPER GASTROINTESTINAL BLEEDING IN PATIENTS WITH LIVER CIRRHOSIS
Authors: I Groza, M Acalovschi, S Pasca, B Procopet, H Stefanescu, M Tantau, D Matei
Journal: Endoscopy (2018)

Upper gastrointestinal bleeding (UGIB) is one of the most frequent and severe gastroenterological emergencies. Rebleeding occurs in 50 – 80% of these patients, more than half of them occuring, during the first 6 weeks. The higher risk of rebleeding is known to be between 5 days and 6 weeks.
Why Do some Patients Die Following Therapeutic ERCP? – Results of the United Kingdom National Confidential Enquiry into Patient Outcome and Death
Authors: A Murdock, TCK Tham, CMK Hargraves
Journal: Endoscopy (2006)

Aims: The aim is to critically appraise the clinical process of those who died during or following ERCP. NCEPOD is an independent organisation intended to improve clinical outcomes from interventional medical procedures.
EUS-Guided Ethanol Injection for Treatment of Pancreatic Cancer
Authors: Yang Xiujiang, Xiong Wujun, Gao Yong, Zhong Lan, Ye Jing, Shen Jianwei
Journal: Endoscopy (2011)

Objective: To evaluate the safety and efficacy of performing endosonography-guided cancer mass direct injection (EUS CPN) in patients with pancreatic cancer.
Phase III non-inferiority study of cabazitaxel (C) 20 mg/m<sup>2</sup> (C20) versus 25 mg/m<sup>2</sup> (C25) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel (D).
Authors: Johann S. De Bono, Anne-Claire Hardy-Bessard, Choung-Soo Kim, Lajos Geczi, Daniel Ford, Loic Mourey, Joan Carles, Phillip Parente, Albert Font, Gabriel Kacso, Mustapha Chadjaa, Wenping Zhang, François Ravez, Mario A. Eisenberger
Journal: Journal of Clinical Oncology (2016)

5008 Background: The Phase III TROPIC study (NCT00417079) reported a significant improvement in overall survival (OS) for C plus prednisone (P) (25 mg/m2once every 3 weeks plus 10 mg orally once daily) versus mitoxantrone plus P (Hazard Ratio [HR] 0.70; P < 0.0001) in pts with mCRPC previously treated with D. This PROSELICA study (NCT01308580) was designed to determine the relative efficacy and safety profile of C20 plus P compared with C25 plus P. Methods: In this randomized, open-label, multinational phase III study, pts with mCRPC and ECOG performance status 0–2, who progressed after treatment with D, were stratified (ECOG, RECIST, region) and randomized 1:1 to C20 or C25. To show that C20 could preserve ≥ 50% of the efficacy benefit showed by C25 in TROPIC, the HR of C20 vs C25 for the primary endpoint OS could not exceed 1.214 under 1-sided 98.89% confidence level adjusted after interim analyses. Secondary endpoints included progression free survival (PFS), safety, PSA, pain and tumor responses and quality of life. Results: From April 2011 to December 2013, 1200 pts were randomized (C20 n = 598; C25 n = 602). Patient characteristics were similar for C20 and C25. Median number of C cycles was 6 for C20 and 7 for C25. The median survival of C20 and C25 did not differ significantly and the HR boundaries (99% confidence level) were within the non-inferiority margins assumptions, therefore meeting the study's non-inferiority endpoint. PSA and RECIST response rates were higher in C25 (see Table). Grade 3–4 adverse events: 39.7% C20; 54.5% C25. Grade 4 laboratory neutropenia: 21.3% C20; 48.6% C25. Neutropenic sepsis/infection: 2.2% C20; 6.1% C25. Conclusions: In pts with mCRPC progressing after treatment with D, C20 demonstrates non-inferiority for OS compared with C25 and an improved overall safety profile. Clinical trial information: NCT01308580.Outcome (HR) C20 N = 598 C25 N = 602 C20 vs C25 Median OS, mos 13.4 (12.19 to 14.88) 14.5 (13.47 to 15.28) Upper Limit of 98.89% Confidence Interval (CI): 1.184 Median PFS, mos 2.9 (2.79 to 3.45) 3.5 (3.12 to 3.94) HR (95% CI): 1.099 (0.974 to 1.24) PSA response, % 29.5 (25.6 to 33.3) 42.9 (38.8 to 47.1) P < 0.0001 ORR, n/N 50/271 18.5% 60/256 23.4%
Electronic Health Record Usability Issues and Potential Contribution to Patient Harm
Authors: Jessica L. Howe, Katharine T. Adams, A. Zachary Hettinger, Raj M. Ratwani
Journal: JAMA (2018)

This study analyzed patient safety reports in and near Pennsylvania from 2013 through 2016 to identify those that contained explicit language associating possible patient harm with an electronic health record usability issue.
Long intergenic non-coding RNAs have an independent impact on survival in multiple myeloma
Authors: Mehmet Kemal Samur, Stephane Minvielle, Annamaria Gulla, Mariateresa Fulciniti, Alice Cleynen, Anil Aktas Samur, Raphael Szalat, Masood Shammas, Florence Magrangeas, Yu-Tzu Tai, Daniel Auclair, Jonathan Keats, Paul Richardson, Michel Attal, Philippe Moreau, Kenneth C. Anderson, Giovanni Parmigiani, Hervé Avet-Loiseau, Nikhil C. Munshi
Journal: Leukemia (2018)
Endomicroscopie confocale intraductale (EMID): Résultats d'une étude de phase I chez des patients présentant une sténose de la voie biliaire principale (VBP)
Authors: M Giovannini, E Bories, C Pesenti, F Caillol, G Monges, JR Delpero
Journal: Endoscopy (2009)

But: L'endomicroscopie confocale est une technique émergeante permettant la réalisation de véritables biopsies optiques au niveau du tube digestif. Le but de cette étude a été d'évaluer un nouveau microscope confocal miniaturisé pouvant être introduit dans les voies biliaires lors d'un cathétérisme rétrograde endoscopique de la papille (CPRE). Le principal objectif était la faisabilité de la technique et l'objectif secondaire de décrire les aspects normaux et pathologiques de la muqueuse des voies biliaires en microscopie confocale.
Abstract 14722: Preoperative Left Ventricular End-diastolic volume is a Single Predictive Factor of Functional Recovery After Coronary Artery Bypass Grafting for Ischaemic Cardiomyopathy
Authors: Shin Yajima, Koichi Toda, Teruya Nakamura, Shigeru Miyagawa, Yasushi Yoshikawa, Satsuki Fukushima, Shunsuke Saito, Keitaro Domae, Takayoshi Ueno, Toru Kuratani, Yoshiki Sawa
Journal: Circulation (2016)

Introduction:  It has been indicated that prognostic effects of coronary artery bypass grafting (CABG) for patients having low left ventricular ejection fraction (LVEF) preoperatively depend upon the stage of the LV remodeling at the time of the surgery. Magnitude of functional recovery post-CABG in association with the prognostic effects is however not fully understood. We therefore investigated long-term outcomes post-CABG for low LVEF patients in association with postoperative LV function and the predictive factors of functional recovery post-CABG.   Methods:  A consecutive series of 60 patients who had LVEF less than 40% preoperatively and underwent isolated CABG in our institution between 2002 and 2013 was enrolled in this study. Ischaemic territories were successfully grafted as assessed by early postoperative coronary angiography in all patients, who were echocardiographically followed-up for more than 30 days.   Results:  Since 40 patients (67%) showed improvement in LVEF by more than 5% during 3.7±2.9 years postoperatively, the cohorts were divided into the following two groups for further analysis; ΔEF >5% group (n=40) and ΔEF ≤5% group (n=20). Although survival at 1, 5 and 10 years were not significantly different between the two groups (ΔEF >5%: 100%, 93%, and 93%; ΔEF ≤5%: 85%, 85%, and 85%, respectively), freedom from major adverse cardiac everts at 1, 5 and 10 years was significantly greater in the ΔEF >5% group (95%, 89% and 44%, respectively) than the ΔEF ≤5% group (79%, 53% and 40%, respectively), as assessed by Kaplan-Meier analysis. LV end-diastolic volume index was a single independent predictive factor for the improvement LVEF (>5%), as assessed by multivariate logistic regression analysis, while its cut-off value was set in 92 ml/m 2 , as assessed by the ROC curve analysis.   Conclusions:  Greater than 60% of patients having LVEF ≤40% preoperatively showed a substantial improvement in LVEF after CABG, warranting prognostic effects of isolated CABG for ischemic cardiomyopathy. However, those having advanced stage of the LV remodelling preoperatively are unlikely to show functional recovery post-CABG, associated with adverse cardiac events.
Abstract 11427: Activation of Invariant Natural Killer T Cells Ameliorates the Development of Angiotensin II-Mediated Abdominal Aortic Aneurysm Formation in Obese ob/ob Mice
Authors: Akimichi Saito, Naoki Ishimori, Satoshi Tokuhara, Atsushi Nozawa, Mikito Nishikawa, Hiroyuki Tsutsui
Journal: Circulation (2013)

Objective: The infiltration and activation of macrophages and lymphocytes within the vascular wall contribute to the pathogenesis of abdominal aortic aneurysm (AAA). We have demonstrated that invar...
Dissection sous muqueuse endoscopique de l'estomac à l'aide d'un bistouri électrique: Expérience préliminaire de 11 cas
Authors: S Farhat, R Coriat, U Chaput, M Gaudric, B Terris, M Bensoussan, F Prat, S Chaussade
Journal: Endoscopy (2009)

Introduction: La dissection sous muqueuse endoscopique (ESD) est une nouvelle technique d'exérèse des lésions pré néoplasiques, des cancers superficiels ou des tumeurs sous muqueuses de l'estomac [1]. Son intérêt réside dans la réalisation d'une exérèse monobloc des lésions permettant un examen histologique de qualité ce qui est particulierement important dans la stratégie therapeutiques des cancers superficiels de l'estomac.
CSF1Rシグナル伝達の阻害は,前立腺癌における腫瘍浸潤骨髄性細胞を抑え,放射線治療の有効性を向上させる
Authors: XU Jingying, Escamilla Jemima, Mok Stephen, David John, Priceman Saul, West Brian, Bollag Gideon, Mcbride William, WU Lily
Journal: Cancer Research (2013)