tbuckley/cabot-search huggingface dataset:
Abstract 3914: Androgen receptor (AR) degradation is controlled by the co-operation of PMEPA1 and the E3 ubiquitin ligase NEDD4-1
Authors: Hua Li, Albert Dobi, Shiv Srivastava
Journal: Cancer Research (2012)

Abstract Introduction and Objective: Androgen receptor (AR) plays critical roles in prostate growth and differentiation and prostate tumorigenesis. Our recent investigations have discovered a novel mechanism of AR degradation in CaP cells involving PMEPA1 and NEDD4-1 which is independent of MDM2. Previously we have shown that PMEPA1 is a highly androgen-inducible gene in CaP cells that recruits the NEDD4-1, an E3 ubiquitin ligase, to degrade AR. In an independent study NEDD4-1 has been identified as an E3 ligase controlling the levels of PTEN. We hypothesize that decreased or loss of PMPEA1 expression that is frequently observed in human prostate tumor cells may lead to enhanced AR functions. Elevated AR levels may increase NEDD4-1 and in turn destabilize PTEN in prostate cancer cells. Here, we further investigate the co-operation between PMEPA1 and NEDD4-1 to alter AR and PTEN protein levels. Methods: PMEPA1 and NEDD4-1 were ectopically expressed in androgen responsive LNCaP and VCaP cells by pCMV-XL4 and pcDNA3.1 vectors, respectively. AR, PMEPA1, NEDD4-1, MDM2 and PTEN were silenced by using specific siRNAs. Cell growth was monitored in response modulation of PMEPA1, NEDD4 and AR. Protein levels of AR, PMEPA1, NEDD4-1, PTEN and PSA were assessed by immunoblot assays. Results: Decreases in AR protein levels, inhibited AR signaling and cell growth in response to heterologous expression of NEDD4-1. Consistent with this observation, inhibition of NEDD4-1 by siRNA resulted in elevated AR protein levels, AR signaling and increased cell growth. Reduced cell growth by AR knock-down or by heterologous expression of NEDD4-, were rescued by the knockdown of PMEPA1. It was also shown that AR up-regulates the expression of NEDD4-1 in hormone responsive CaP cells. In VCaP cells, overexpression of NEDD4-1 resulted in decreased PTEN protein levels. Remarkably, PMEPA1 knockdown resulted in elevated AR and NEDD4-1 levels and the downregulation of PTEN protein. Conclusions: NEDD4-1 mediated AR degradation in hormone responsive CaP cells requires PMEPA1. The frequently observed decreased expression of PMEPA1 results in elevated AR protein levels and may facilitate NEDD4-1 mediated degradation of PTEN in CaP. Our findings revealed a complex interplay of the AR, PMEPA1, NEDD4 and PTEN underscoring the impact of the loss of PMEPA1 to increased AR and decreased PTEN, both proteins critical in prostate tumorigenesis. This study is supported by the NIH grant (R01CA106653) to SS. 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 3914. doi:1538-7445.AM2012-3914
Painting the global picture of HER2-testing for breast cancer. The ONCOLLEGE-001 survey study
Authors: S.C. Altuna, C. Lengyel, D. Trapani, E.M. Elfaham, S. Hussain, A. Petrillo, K. El Bairi, S.A. Mazher, B.S. Habeeb, S.Z. Khan
Journal: Annals of Oncology (2019)

Background: Breast cancer (BC) is the most common cancer in women and the leading cause of cancer-related death. HER2 is overexpressed in approximately 15-20% of BCs. HER2 expression is not only a prognostic biomarker but a predictive biomarker of response to HER2 targeted therapies. The ONCOLLEGE-001 project addresses the distribution & disparities of HER2-testing (H2T) methods (IHC or in situ hybridization (ISH), which may use either fluorescent (FISH), chromogenic (CISH) or silver (SISH) detection method) in breast cancer, with the aim of painting the global picture (GP). Methods: A simple, internet-based survey was developed by the international ONCOLLEGE (ONC) working group and the questionnaire was sent to 227 oncology providers by email, was shared on medical social networks (using snowballing as a multiplier effect of promotion and diffusion). Data were analysed per country-income (World Bank groupings) and WHO Regions. Responders authorized for the use of the data. Results: 210 providers responded, across 45 countries (27% from high-income HIC; 35% upper-middle UMIC; 38% lower-middle and low, LMICs; 50% in the Eastern Mediterranean Region), mostly medical and clinical oncologist (58%; 20%) from research hospitals (52%) and public non-teaching (17%) or private institutions (17%). H2T was available only in private setting or abroad in 5%, 42% and 34% of HIC, UMIC and LMICs responders' institutions. Only IHC (no ISH) may be performed as H2T in 7% & 9.4% of UMIC & LMICs. FISH (54%) and CISH+FISH (14%) were the most common ISH H2T. IHC and ISH were available within 14 days (55%; 29%) and 28 days (38%; 44%) with no dramatic income-restricted patterns of delay. 30% of the responders from LMICs reported affordability issues related to H2T, more for ISH, related to out of pocket expenses and exposure to catastrophic health expenditure, compared to 12% of UMIC and none for HIC (full reimbursement). Conclusions: The GP of H2T provided by the ONC networking painted a heterogeneous picture, with disparities related to the availability of appropriate cancer testing and affordability with high risk of financial toxicity in the diagnostic phase. An ongoing further analysis addresses also the prioritization and access to HER2 medicines in our ONCOLLEGE-001 project. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
EUS-GUIDED TANS-RECTAL TREATMENT FOR SYMPTOMATIC PELVIC COLLECTIONS: PUNCTURE/ASPIRATION OR DRAINAGE? RESULTS FROM A LARGE MONOCENTRIC STUDY
Authors: JM Gonzalez, M Guingand, M Gasmi, M Barthet
Journal: Endoscopy (2019)

Abdomino-pelvic symptomatic collections have recently been managed endoscopically by EUS-guideed transrectal drainage (EUS-TRD). We pesent the result of our experience. The main objective was to elucidate the acute efficacy of EUS-TRD (symptoms resolution). The secondary objectives were to document the morbidity, the recurrence (after one month), and to identify predictive factors for failure (persisting of symptomatic collection despite drainage +/- need for surgery).
ERCP PERFORMED IN A PATIENT WITH TOTAL SITUS INVERSUS VISCERUM
Authors: M Rocha, T Capela, R Loureiro, MJ Silva, G Ramos, R Pato, T Baptista, AM Dias, J Canena, J Coimbra
Journal: Endoscopy (2019)

Situs inversus viscerum is a rare congenital condition characterized by complete transposition of all viscera. Endoscopic exams are often challenging in these patients, namely ERCP.
THE UAB RAPTOR METHOD FACILITATES DIRECT PERCUTANEOUS ENDOSCOPIC GASTROSTOMY WITH JEJUNAL EXTENSION TUBE PLACEMENT (WITH VIDEO)
Authors: A Martinez-Alcala, PT Kroener, S Peter, C Diaz-Tobar, K Mönkemüller
Journal: Endoscopy (2019)

Direct percutaneous endoscopic gastrostomy with jejunal extension tube (PEG-J) is a useful method to provide nutrition to patients with a variety of gastrointestinal (GI) problems. The present study describes a novel and simple method of direct percutaneous endoscopic gastrostomy with jejunal extension tube placement.
Rheumatoid arthritis: glucocorticoids are associated with nearly double infection risk post-surgery
Authors: Elisabeth Mahase
Journal: BMJ (2019)

Patients with rheumatoid arthritis (RA) who are taking a glucocorticoid, in dosages above 10 mg per day, have almost double the risk of developing an infection after joint replacement surgery compared with those who do not take a steroid, a study has found.1

Researchers from the US set out to compare the risk for postoperative infection among patients taking biologic drugs and those on glucocorticoids and reported their findings in the Annals of Internal Medicine .

Biologic disease modifying antirheumatic drugs are increasingly used in the treatment of RA …
An international outbreak of Salmonella enterica serotype Enteritidis linked to eggs from Poland: a microbiological and epidemiological study
Authors: Roan Pijnacker, Timothy J Dallman, Aloys S L Tijsma, Gillian Hawkins, Lesley Larkin, Saara M Kotila, Giusi Amore, Ettore Amato, Pamina M Suzuki, Sarah Denayer, Sofieke Klamer, Judit Pászti, Jacquelyn McCormick, Hassan Hartman, Gareth J Hughes, Lin C T Brandal, Derek Brown, Joël Mossong, Cecilia Jernberg, Luise Müller, Daniel Palm, Ettore Severi, Joannna Gołębiowska, Blaženka Hunjak, Slawomir Owczarek, Simon Le Hello, Patricia Garvey, Kirsten Mooijman, Ingrid H M Friesema, Coen van der Weijden, Menno van der Voort, Valentina Rizzi, Eelco Franz, Sophie Bertrand, Martine Brennan, Lynda Browning, Ryan Bruce, Vera Cantaert, Marie Chattaway, John Coia, Sarah Couper, Tjaša Žohar Čretnik, Ondřej Daniel, Anna Maria Dionisi, Laetitia Fabre, Ife Fitz-James, Karolina Florek, Martina Florianová, Eithne Fox, Tatjana Frelih, Eva Grilc, Vera Katalinic Jankovic, Nathalie Jourdan, Renata Karpíšková, Hans van den Kerkhof, Sjoerd Kuiling, Sanja Kurečić Filipović, Valeska Laisnez, Heidi Lange, Niall deLappes, Judith Leblanc, Ida Luzzi, Georgia Mandilara, Henry Mather, Wesley Mattheus, Kassiani Mellou, Deborah Morgan, Judit Pászti, Elizabeth de Pinna, Catherine Ragimbeau, Margrethe Hovda Røed, Saara Salmenlinna, Robert Smith, Alison Smith-Palmer, Michaela Špačková, Mia Torpdahl, Marija Trkov, Linda Trönnberg, Myrsini Tzani, Lara Utsi, Dariusz Wasyl, Pierre Weicherding
Journal: The Lancet Infectious Diseases (2019)
Inhibition of Pyruvate Dehydrogenase Kinase Enhances the Antitumor Efficacy of Oncolytic Reovirus
Authors: Barry E. Kennedy, John Patrick Murphy, Derek R. Clements, Prathyusha Konda, Namit Holay, Youra Kim, Gopal P. Pathak, Michael A. Giacomantonio, Yassine El Hiani, Shashi Gujar
Journal: Cancer Research (2019)

Abstract Oncolytic viruses (OV) such as reovirus preferentially infect and kill cancer cells. Thus, the mechanisms that dictate the susceptibility of cancer cells to OV-induced cytotoxicity hold the key to their success in clinics. Here, we investigated whether cancer cell metabolism defines its susceptibility to OV and if OV-induced metabolic perturbations can be therapeutically targeted. Using mass spectrometry–based metabolomics and extracellular flux analysis on a panel of cancer cell lines with varying degrees of susceptibility to reovirus, we found that OV-induced changes in central energy metabolism, pyruvate metabolism, and oxidative stress correlate with their susceptibility to reovirus. In particular, reovirus infection accentuated Warburg-like metabolic perturbations in cell lines relatively resistant to oncolysis. These metabolic changes were facilitated by oxidative stress–induced inhibitory phosphorylation of pyruvate dehydrogenase (PDH) that impaired the routing of pyruvate into the tricarboxylic acid cycle and established a metabolic state unsupportive of OV replication. From the therapeutic perspective, reactivation of PDH in cancer cells that were weakly sensitive for reovirus, either through PDH kinase (PDK) inhibitors dichloroacetate and AZD7545 or short hairpin RNA–specific depletion of PDK1, enhanced the efficacy of reovirus-induced oncolysis in vitro and in vivo. These findings identify targeted metabolic reprogramming as a possible combination strategy to enhance the antitumor effects of OV in clinics. Significance: This study proposes targeted metabolic reprogramming as a valid combinatorial strategy to enhance the translational efficacy of oncolytic virus–based cancer therapies.
EDUCATIONAL TELEPHONE INTERVENTION BY ENDOSCOPY NURSE. IMPACT ON THE ADHERENCE OF OUTPATIENT COLONOSCOPY
Authors: A Seoane Urgorri, X Font Lagarriga, R Pérez Berbegal, C Pérez Carregal, M Parrilla Carrasco, J Romero Xandre, MA Álvarez González, M Pantaleón Sánchez, CF Enriquez, F Riu Pons, JM Dedeu Cusco, LE Barranco Priego, X Bessa Caserras, I Ibañez Zafón
Journal: Endoscopy (2019)

The growing complexity of colonoscopy in endoscopy units has increased the need for good patient preparation and the endoscopy nurse role is crucial for it. This study was directed to determine the impact of an educational telephone intervention on colonoscopy adherence. The compliance with colonoscopy preparation protocols and patient satisfaction were also assessed.
SGLT Inhibitors for Type 1 Diabetes: Proceed With Extreme Caution
Authors: Joseph I. Wolfsdorf, Robert E. Ratner
Journal: Diabetes Care (2019)

Intensive insulin management is currently the only option for effective treatment of type 1 diabetes. Recent data from the T1D Exchange (T1DX) registry (1), which comprises leading U.S. diabetes treatment centers, show that despite the widespread availability of insulin analogs and increasing use of insulin pumps and continuous glucose monitoring systems, only about 20% of adult patients achieve the A1C target of <7% (53 mmol/mol) recommended by the American Diabetes Association (2). It is reasonable to assume that glycemic control of patients receiving care outside of major centers might be even worse. The T1DX registry has also shown that nearly 5% of adult participants experienced one or more episodes of diabetic ketoacidosis (DKA) within the past 12 months (3), and the Centers for Disease Control and Prevention recently reported a 6.3% annual increase in hospitalization rates for DKA from 2009 to 2014, with highest rates in persons aged <45 years (4). Moreover, the majority of patients are either overweight or obese, potentially increasing their risk of cardiovascular disease (1). There is clearly an unmet need for noninsulin adjunctive therapies that improve glycemic control without increasing the risk of hypoglycemia or contributing to weight gain, and it is noteworthy that among nearly 50,000 pediatric and adult participants in the T1DX registry in the U.S. and the Prospective Diabetes Follow-up (DPV) registry in Germany and Austria, two large consortia of diabetes centers, adjuvant medications are being used off-label by 5.4% of participants in T1DX and 1.6% in DPV (5).

Sodium–glucose cotransporter 2 (SGLT2) inhibitors block the SGLT2 transporter in the proximal renal tubule resulting in glucosuria and natriuresis and are approved and indicated for type 2 diabetes. Dual SGLT1+2 inhibitors have the additional effect of inhibiting SGLT1 in the gastrointestinal tract, thereby delaying intestinal absorption of glucose and galactose. Owing to …
SMALL BOWEL ANGIOECTASIAS REBLEEDING AND THE IDENTIFICATION OF HIGHER RISK PATIENTS
Authors: C Arieira, R Magalhães, FD de Castro, PB Carvalho, B Rosa, MJ Moreira, J Cotter
Journal: Endoscopy (2019)

Small Bowel Capsule Endoscopy (SBCE) is the gold standard in Mid-gastrointestinal bleeding (MGIB). Angioectasias are the most common vascular anomalies in the GI tract and considering their frequency, their usual intermittent bleeding nature and their risk of rebleeding, the aim of this study was to identify some characteristics and possible predictors of rebleeding in the presence of these lesions.
Patterns of survival in patients with recurrent mantle cell lymphoma in the modern era: progressive shortening in response duration and survival after each relapse
Authors: Anita Kumar, Fushen Sha, Ahmed Toure, Ahmet Dogan, Andy Ni, Connie L. Batlevi, Maria Lia M. Palomba, Carol Portlock, David J. Straus, Ariela Noy, Steven M. Horwitz, Alison Moskowitz, Paul Hamlin, Craig H. Moskowitz, Matthew J. Matasar, Andrew D. Zelenetz, Anas Younes
Journal: Blood Cancer Journal (2019)

As the survival of patients with mantle cell lymphoma (MCL) continues to improve, patients are increasingly being treated with multiple regimens. However, outcome after each line remains poorly characterized in the modern era. To address this knowledge gap, we retrospectively studied 404 consecutive MCL patients who were managed between 2000 and 2014 at Memorial Sloan Kettering Cancer Center. Histologic diagnosis was centrally confirmed, and patients were followed longitudinally from diagnosis throughout their disease course. Progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier method. The median OS and PFS after first-line treatment were 9.7 and 4.0 years, respectively. After second-line therapy, the median OS and PFS were 41.1 and 14.0 months, third line were 25.2 and 6.5 months, and fourth line were 14.4 and 5.0 months. In patients less than 65 years, stem cell transplant (SCT)-based frontline regimens were associated with improved PFS compared with non-SCT regimens (median PFS: 86.2 versus 40.0 months; P < 0.01), with a trend toward longer OS (median OS: 165.0 versus 120.0 months; P = 0.06). Early treatment failure after first-line regimens was associated with worse OS (5.9 versus 2.5 years; P < 0.01). Our study should facilitate establishing proper endpoints for future clinical trials using novel treatment approaches.
Bullous pemphigoid autoantibody‐mediated complement fixation is abolished by the low‐molecular‐weight heparin tinzaparin sodium
Authors: A. Gutjahr, F. Heck, S. Emtenani, A.‐K. Hammers, J.E. Hundt, P. Muck, D.L. Siegel, E. Schmidt, J.R. Stanley, D. Zillikens, C.M. Hammers
Journal: British Journal of Dermatology (2019)

Linked Comment: Hashimoto, Kanazawa and Inoue. Br J Dermatol 2019; 181:448–449.
UPPER GASTROINTESTINAL BLEEDING (UGIB)- TRANSFUSION POLICIES AND TIMING OF ENDOSCOPY. ARE GUIDELINE RECOMMENDATIONS INCORPORATED IN "REAL WORLD" CLINICAL PRACTICE? A NORTHERN GREECE, SINGLE-CENTRE, 1 YEAR EXPERIENCE
Authors: E Stournaras, A Protopapas, G Neokosmidis, D Stogiannou, G Panagiotou, N Gerothanassi, E Triantafyllou, N Pimenidou, A Protopapas
Journal: Endoscopy (2019)

Aim of the study is to assess whether guidelines are incorporated in our clinical practice and to recommend performance improvement strategies.
DFMO and 5-Azacytidine Increase M1 Macrophages in the Tumor Microenvironment of Murine Ovarian Cancer
Authors: Meghan Travers, Stephen M. Brown, Matthew Dunworth, Cassandra E. Holbert, Karla R. Wiehagen, Kurtis E. Bachman, Jackson R. Foley, Meredith L. Stone, Stephen B. Baylin, Robert A. Casero, Cynthia A. Zahnow
Journal: Cancer Research (2019)

Although ovarian cancer has a low incidence rate, it remains the most deadly gynecologic malignancy. Previous work has demonstrated that the DNMTi 5-Azacytidine (5AZA-C) activates type I interferon signaling to increase IFNγ+ T cells and natural killer (NK) cells and reduce the percentage of macrophages in the tumor microenvironment. To improve the efficacy of epigenetic therapy, we hypothesized that the addition of α-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor, may further decrease immunosuppressive cell populations improving outcome. We tested this hypothesis in an immunocompetent mouse model for ovarian cancer and found that in vivo, 5AZA-C and DFMO, either alone or in combination, significantly increased survival, decreased tumor burden, and caused recruitment of activated (IFNγ+) CD4+ T cells, CD8+ T cells, and NK cells. The combination therapy had a striking increase in survival when compared with single-agent treatment, despite a smaller difference in recruited lymphocytes. Instead, combination therapy led to a significant decrease in immunosuppressive cells such as M2 polarized macrophages and an increase in tumor-killing M1 macrophages. In this model, depletion of macrophages with a CSF1R-blocking antibody reduced the efficacy of 5AZA-C + DFMO treatment and resulted in fewer M1 macrophages in the tumor microenvironment. These observations suggest our novel combination therapy modifies macrophage polarization in the tumor microenvironment, recruiting M1 macrophages and prolonging survival. SIGNIFICANCE: Combined epigenetic and polyamine-reducing therapy stimulates M1 macrophage polarization in the tumor microenvironment of an ovarian cancer mouse model, resulting in decreased tumor burden and prolonged survival.
COMPARING THE REVISED EUROPEAN, AGA AND IAP GUIDELINES ON PANCREATIC CYSTIC NEOPLASMS: ACCURACY IN IDENTIFYING ADVANCED NEOPLASIA IN IPMN
Authors: N van Huijgevoort, S ten Bokkel-Huinink, SJ Lekkerkerker, I Somers, M Del Chiaro, P Fockens, MG Besselink, JE van Hooft
Journal: Endoscopy (2019)

Accurate detection of advanced neoplasia (AN; high-grade dysplasia/cancer) in pancreatic cystic neoplasms (PCN) will improve outcome while minimizing unnecessary surgery. The European, American Gastroenterological Association (AGA) and International Association of Pancreatology (IAP) guidelines provide recommendations on surveillance and surgical intervention for PCN based on symptoms and risk of malignancy. We aimed to identify which guideline is the most accurate in predicting AN in IPMN.
Abstract 17918: Platelet Depletion Exacerbates Myocardial Injury Through Decreasing Stem Cell Mobilization and S1P Concentration Following Myocardial Infarction
Authors: Amr Idris, Shaojing Ye, Himi Tripathi, Ahmed Abdel-Latif
Journal: Circulation (2016)

Introduction: Myocardial infarction (MI) and its associated complications are the leading cause of morbidity and mortality in the United States. Platelets play a major role in homeostasis and wound...
Blockade of CCL24 with a monoclonal antibody ameliorates experimental dermal and pulmonary fibrosis
Authors: Adi Mor, Michal Segal Salto, Avi Katav, Neta Barashi, Victoria Edelshtein, Mirko Manetti, Yair Levi, Jacob George, Marco Matucci-Cerinic
Journal: Annals of the Rheumatic Diseases (2019)

We aimed to assess the expression of the CCL24 chemokine in systemic sclerosis (SSc) and to evaluate the possible pathogenic implications of the CCL24/CCR3 axis using both in vitro and in vivo models. We further investigated the efficacy of an anti-CCL24 monoclonal antibody (mAb), CM-101, in inhibiting cell activation as well as dermal and pulmonary inflammation and fibrosis in experimental animal models.We used ELISA and fluorescence immunohistochemistry to determine CCL24 levels in serum and CCL24/CCR3 expression in skin biopsies of SSc patients. Skin fibroblasts and endothelial cells treated with CCL24 or SSc serum with or without CM-101 were used to follow cell activation and differentiation. Prevention and treatment in vivo bleomycin (BLM)-induced models were used to evaluate experimental dermal and pulmonary fibrosis progression following treatment with the CM-101 mAb.CCL24 circulating levels were significantly elevated in SSc patients. CCL24/CCR3 expression was strongly increased in SSc skin. Blockade of CCL24 with CM-101 significantly reduced the activation of dermal fibroblasts and their transition to myofibroblasts induced by SSc serum. CM-101 was also able to significantly inhibit endothelial cell activation induced by CCL24. In BLM-induced experimental animal models, CM-101 profoundly inhibited both dermal and pulmonary fibrosis and inflammation.CCL24 plays an important role in pathological processes of skin and lung inflammation and fibrosis. Inhibition of CCL24 by CM-101 mAb can be potentially beneficial for therapeutic use in SSc patients.
<i>Mycobacterium tuberculosis</i> infection prevents asthma and abrogates eosinophilopoiesis in an experimental model
Authors: Raquel Tarancón, Santiago Uranga, Carlos Martín, Nacho Aguiló
Journal: Allergy (2019)

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Lésions endoscopiques après ingestion d'eau de javel
Authors: B Hasnaoui, M Mahmoudi, A Ouni, A Khsiba, M Medhioub, L Hamzaoui, MM Azouz
Journal: Endoscopy (2019)

L'ingestion de produits caustiques est un motif de plus en plus fréquent d'exploration endoscopique digestive en urgence. L'hypochlorite de sodium (eau de Javel) qui est un oxydant utilisé pour le nettoyage domestique souvent après dilution, figure au premier rang parmi les produits caustiques ingérés. Le but de notre travail est d'étudier les lésions endoscopiques secondaires à l'ingestion de l'eau de Javel.