tbuckley/cabot-search huggingface dataset:
NIMG-36. DELINEATION OF IMMUNE RESPONSES AFTER IMMUNOTHERAPY IN GLIOBLASTOMA USING PET AND MRI
Authors: Horacio Soto, Joseph Antonios, Richard Everson, Diana Moughon, Anthony Wang, Joey Orpilla, Caius Radu, Benjamin Ellingson, Jason Lee, Timothy Cloughesy, Michael Phelps, Johannes Czernin, Linda Liau, Robert Prins
Journal: Neuro-Oncology (2017)

Contrast-enhanced MRI is typically used to follow treatment response and progression in glioblastoma (GBM) patients. However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by advancements in imaging techniques. Non-invasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that novel PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI. Orthotopic malignant gliomas were established in syngeneic immunocompetent mice, and subsequently treated with dendritic cell (DC) vaccination and/or PD-1 mAb blockade. Mice were then imaged with [18F]d-FAC PET/CT and MRI with intravenous contrast. Pre-contrast T1 was subtracted from T1+C to generate a contrast subtraction map. Co-registration of PET and MRI voxel data further co-localized areas of contrast enhancement with areas of PET-denoted inflammatory response, which was only visualized within the groups that were treated with immunotherapy. The ratio of contrast enhancement on MRI to normalized PET probe uptake, which we termed the Immunotherapeutic Response Index (ITRI), delineated specific regions of immune inflammatory activity. On post-mortem examination, FACS-based enumeration of intracranial tumor-infiltrating lymphocytes directly correlated with quantitative [18F]d-FAC PET probe uptake. Three GBM patients undergoing treatment with tumor lysate-pulsed dendritic cell vaccination and PD-1 mAb blockade were also imaged using MRI and a clinical PET probe for dCK before and after therapy. [18F]-FAC is not clinically relevant due to rapid catabolism in humans, thus enhanced [18F]-Clofarabine ([18F] CFA) PET probe accumulation was identified in tumor and secondary lymphoid organs after immunotherapy. Our findings identify a non-invasive modality capable of imaging the host anti-tumor immune response against intracranial tumors.
P2.14-001 Mid-Treatment Perfusion PET/CT Is More Effective Than Ventilation PET/CT in Functionally-Adapted Radiotherapy for NSCLC
Authors: R. Thomas, G. Turgeon, M. Hofman, J. Callahan, N. Anderson, N. Hardcastle, T. Kron, M. Bressel, D. Steinfort, M. Shaw, N. Plumridge, M. Macmanus, R. Hicks, D. Ball, S. Siva
Journal: Journal of Thoracic Oncology (2017)
TMOD-19. SOMATIC GENOME EDITING WITH THE RCAS-CRISPR/Cas9 SYSTEM FOR PRECISION GLIOMA MODELING
Authors: Álvaro Curiel García, Barbara Oldrini, Carolina Marques, Veronica Matia, Massimo Squatrito
Journal: Neuro-Oncology (2017)

It has been gradually established that the vast majority of human tumors are extraordinarily heterogeneous at a genetic level. To accurately recapitulate this complexity, it is now evident that in vivo animal models of cancers will require to recreate not just a handful of simple genetic alterations, but possibly dozens and increasingly intricate. Here we have combined the RCAS/tv-a system with the CIRSPR/Cas9 genome editing tools to somatically target neural stem cells (NSCs) for precise modeling of human glioma. We show that deletion, both in pups and adult mice, of a variety of known tumor suppressor genes (Trp53, Cdkn2a and Pten), in combination with the expression of an oncogene driver, leads to high-grade glioma formation. Moreover, by simultaneously delivery into NSCs of pairs of gRNAs we show for the first time that the Bcan-Ntrk1 gene fusions, is able to induce high-grade gliomas. We further established that cells derived from Bcan-Ntrk1 tumors are remarkably sensitive to a Pan-Ntrk inhibitor. Lastly, using homology directed repair (HDR), we generated the Braf V600E mutation into NSCs and we demonstrated that it’s sufficient to induce glioma tumor formation. In summary, we have developed an extremely powerful and versatile mouse model for in vivo somatic genome editing. Our system will elicit the generation of more accurate glioma models, particularly suitable for preclinical testing.
Controles de calidad para el diagnóstico de enfermedades virales para mejorar la respuesta a las alertas en Europa
Authors: O Donoso-Mantke, H Schmitz, H Zeller, P Heyman, A Papa, M Niedrig
Journal: Eurosurveillance (2005)

La amenaza representada por las enfermedades emergentes y reemergentes, y desde menos tiempo, la emision deliberada de agentes infecciosos en una poblacion susceptible, se considera muy seriamente tanto al nivel nacional como internacional. Se han intensificado los esfuerzos en salud publica para reforzar la deteccion, la vigilancia y el control de esas enfermedades. Sin embargo, los medicos clinicos y los laboratorios clinicos desempenan un papel importante en la deteccion precoz de las enfermedades, la identificacion del agente implicado, y la notificacion a las autoridades competentes. Para ser eficaces en este papel, los laboratorios deben estar especialmente preparados para manipular los agentes virales con seguridad y son necesarias, entre otras cosas, pruebas de diagnostico sensibles y rapidas. La Red Europea para el diagnostico de enfermedades viricas importadas (European Network for Diagnostics of “Imported” Viral Diseases, ENIVD), establecida en 1998, incluye actualmente entre sus miembros permanentes 44 laboratorios con experiencia en 21 Estados Miembros de la Union Europea (UE) y cuatro paises fuera de la UE. ENIVD forma parte de las redes sobre enfermedades transmisibles financiadas por la Comision Europea. La red ENIVD esta a cargo de varias tareas esenciales para la vigilancia y el control de las infecciones virales importadas, raras y emergentes, como el intercambio de expertos y la organizacion de programas de control de calidad externa, necesarios para mejorar los diagnosticos. El articulo que aqui se presenta hace una sintesis de los datos procedentes de las actividades recientes de control de calidad, especialmente sobre los diagnosticos de infecciones por hantavirus, virus del Dengue, filovirus, Fiebre de Lassa, orthopox virus y el coronavirus del SRAS. Estos analisis se hicieron entre 1999 y 2004 e incluian 93 laboratorios de 41 paises, incluso laboratorios de paises fuera de Europa. En un futuro proximo, los paises candidatos a la UE, y los paises vecinos del este seran invitados a unirse a la red. Existe una pagina web disponible para el publico, con la direccion http://www.enivd.de.
P2.03-019 Sizing Capillary Electrophoresis with PCR to Detect Various EGFR Exon 19 Deletions in Non-Small Cell Lung Cancer
Authors: E. Nakajima, M. Sugita, K. Furukawa, H. Takahashi, Y. Kawaguchi, T. Ohira, N. Ikeda, F.R. Hirsch, W. Franklin
Journal: Journal of Thoracic Oncology (2017)
PATH-03. “DEDIFFERENTIATED” GLIOBLASTOMA: A CLINICOPATHOLOGICAL AND MOLECULAR STUDY
Authors: Malak Abedalthagafi, Soma Sengupta, Ray Huang, Keith Ligon
Journal: Neuro-Oncology (2017)

Some glioblastoma can lack robust evidence of classic glioma markers like OLIG2 or GFAP. Such tumors seem to frequently be poorly differentiated morphology and are often referred to as glioblastoma with PNET like area or “dedifferentiated” GBM in common practice and may not be identified as gliomas or GBM at all. The incidence and clinical features of “dedifferentiated” GBM is not known. Therefore, we undertook this retrospective study to evaluate a large series of patients with glioblastomas at Brigham and Women’s hospital and Dana-Farber Cancer Institute from 2010-2014. The goal of this study was to estimate the incidence of dedifferentiated glioblastomas and to examine their genomic profile and the clinical characterization. A total of 23 patients out of the 733 patients (3.13%) were identified to have the “dedifferentiated” phenotypes. have examined the clinical, histological, staining patterns, and the genomic print of a cohort of challenging cases of “dedifferentiated” glioblastomas. Our study shows considerable heterogeneity at the molecular level. This phenotype can be a diagnostic challenge for the pathologists because of its rarity and lack of the expression of classic glial immunohistochemical markers, we found that these glioblastoma lacked OLIG2 expression and variable histological features. They have more aggressive clinical course with tendency to leptomeningial spread. Recognizing this phenotype is important for patient’s managements.
JCES 01.16 Altered Expression of Programmed Death-1 Receptor（PD-1）and Its Ligand PD-L1, PD-L2 after Neo-Adjuvant Chemotherapy in Lung Cancer
Authors: W. Sun, K. Ma, X. Wang, Y. Liu, H. He, Y. Guo
Journal: Journal of Thoracic Oncology (2017)
MA 10.11 Hyperprogressive Disease (HPD) Is Frequent in Non-Small Cell Lung Cancer (NSCLC) Patients (Pts) Treated with Anti PD1/PD-L1 Agents (IO)
Authors: R. Ferrara, C. Caramella, M. Texier, C. Audigier-Valette, L. Tessonnier, L. Mezquita, J. Lahmar, J. Mazieres, G. Zalcman, S. Brosseau, V. Westeel, S. Le Moulec, L. Leroy, B. Duchemann, C. Lefebvre, R. Veillon, S. Champiat, C. Fertè, D. Planchard, M. Boucher, G. Martinez-Bernal, E. Bria, G. Tortora, J. Soria, B. Besse
Journal: Journal of Thoracic Oncology (2017)
Recent advances in transarterial embolotherapies in the treatment of hepatocellular carcinoma
Authors: Edward Wolfgang Lee, Sarah Khan
Journal: Clinical and Molecular Hepatology (2017)

Management of hepatocellular carcinoma (HCC) can be maximized with the utilization of multiple treatment modalities including transplant, surgical resection and locoregional therapies including ablative therapies and transarterial embolotherapies. Although transplant and surgical resection offer the best clinical outcomes, a limited number of patients are amenable to these surgical treatment options due to the advanced disease at presentation. Transarterial embolotherapies including conventional transarterial chemoembolization (cTACE), bland transarterial embolization (TAE), drug-eluting beads transarterial chemoembolization (DEB-TACE) and selective internal radiation therapy (SIRT) with Yttrium 90 (90Y) have played an increasingly important role for these patients with unresectable HCC. With a better understanding of different transarterial embolotherapies, more personalized and precise treatment should be implemented for these patients with unresectable HCC. In this review, the updated evidence on the current role of each embolotherapy in the treatment of HCC is summarized.
Situation actuelle de la bothriocéphalose en Europe
Authors: J Dupouy-Camet, R Peduzzi
Journal: Eurosurveillance (2004)

La bothriocephalose, parasitose due au grand ver plat Diphyllobothrium latum, se contracte par la consommation de chair crue ou mal cuite de poisson d'eau douce. L'objectif de l'etude a ete d'evaluer la situation de cette parasitose au cours de 20 dernieres annees en Europe, par l'analyse de bases de donnees et l'utilisation de moteurs de recherche (Medline, Cabi Helminthological abstracts,Yahoo, Google) et par un questionnaire envoye a un reseau de parasitologues europeens et a des laboratoires d'analyse medicales situes sur les bords des grands lacs alpins. Cette etude a montre que plusieurs dizaines de cas etaient signales chaque annee en Finlande et en Suede, que les cas etaient nombreux dans les zones francophones ou italophones des lacs subalpins et que seuls, des cas sporadiques etaient observes en Autriche, en Espagne, en Grece, en Roumanie, en Pologne, et en Norvege. Depuis 1990, plus d'une trentaine de cas ont ete identifies sur les rives suisses du lac Majeur et 70 cas entre 1993 et 2002 sur les rives suisses et francaises du lac Leman. Huit a 12% des filets de perche du lac Leman et 7,8% des perches du lac Majeur contiennent des larves infestantes. Les sources de contamination sont les filets marines de poisson dans le nord de l'Europe, le  carpaccio di persico en Italie du Nord ainsi que la perche et l'omble chevalier consommes crus ou peu cuits autour du lac Leman. La persistance d'un rejet d'eaux usees dans les lacs, la pratique de la peche touristique ainsi qu'un possible reservoir animal sont autant de facteurs permettant d'entretenir le cycle parasitaire.
IMMU-11. TARGETING THE CD200 CHECKPOINT BLOCKADE: A NEW DIRECTION FOR IMMUNOTHERAPY
Authors: Michael Olin, Elisabet Ampudia-Mesias, Zhengming Xiong, Elizabeth Pluhar, Christopher Moertel
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme is an incurable primary brain tumor. The standard of care consists of resection followed by radiation and chemotherapy is associated with a median overall survival of 14.6 months. To address this dismal outcome, aggressive interventions need to be pursued. Recently, the FDA approved immune checkpoint inhibitor therapy for solid tumors that are otherwise refractory to standard therapy heralding a new era for effectively treating cancer. Yet, immune checkpoint inhibitors yield poor responses for patients with glioblastoma, calling into question whether cancer immunotherapy can be applied to glioblastoma. We have recently reported that inhibiting an alternative immune checkpoint, CD200, inhibits tumor-induced immunosuppression without toxic side effects. CD200 protein suppresses immune activation after engaging the CD200 inhibitory receptor, which is restricted to immune cells. We have previously shown that C200 is expressed in malignant brain tumors and is an important barrier to effective immunotherapy. By exploring peptide fragments resulting from protease cleavage of the CD200 protein, we observed that CD200 actually functions through paired receptors and that certain peptide ligands (CD200 inhibitor) actually surmount the immunosuppressive effects of CD200 to stimulate immune response. This was validated in glioma murine models. We recently developed humanized CD200 inhibitors, which was verified in vitro measuring the immune response of human cells to CMV antigen (pp65495–503). We conducted a clinical trial in companion dogs with primary gliomas and showed that canine-specific CD200 inhibitor. In this ongoing clinical trial using dogs diagnosed with high-grade glioma, receiving a canine specific CD200 inhibitor in combination with the autologous tumor lysate vaccine had enhanced survival up to 615 days, relative to 214 days with lysate alone, without any observed toxicity or signs of reoccurrence. As a result of these findings, we believe that is important to move forward with phase I human clinical trials utilizing inhibitor peptidomimetics.
Faltering growth in children: improving early detection of cleft palate
Authors: Sophie Butterworth, David Sainsbury, Peter Hodgkinson
Journal: BMJ (2017)

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Primary and Acquired Resistance to Immune Checkpoint Inhibitors in Metastatic Melanoma
Authors: Tuba N. Gide, James S. Wilmott, Richard A. Scolyer, Georgina V. Long
Journal: Clinical Cancer Research (2017)

Immune checkpoint inhibitors have revolutionized the treatment of patients with advanced-stage metastatic melanoma, as well as patients with many other solid cancers, yielding long-lasting responses and improved survival. However, a subset of patients who initially respond to immunotherapy, later relapse and develop therapy resistance (termed "acquired resistance"), whereas others do not respond at all (termed "primary resistance"). Primary and acquired resistance are key clinical barriers to further improving outcomes of patients with metastatic melanoma, and the known mechanisms underlying each involves various components of the cancer immune cycle, and interactions between multiple signaling molecules and pathways. Due to this complexity, current knowledge on resistance mechanisms is still incomplete. Overcoming therapy resistance requires a thorough understanding of the mechanisms underlying immune evasion by tumors. In this review, we explore the mechanisms of primary and acquired resistance to immunotherapy in melanoma and detail potential therapeutic strategies to prevent and overcome them. Clin Cancer Res; 24(6); 1260-70. ©2017 AACR.
P3.02b-044 Afatinib versus Gefitinib as First-Line Treatment for EGFR Mutation-Positive NSCLC Patients Aged ≥75 Years: Subgroup Analysis of LUX-Lung 7
Authors: Keunchil Park, Eng Huat Tan, Li Zhang, Vera Hirsh, Ken O'Byrne, Michael Boyer, James Chih-Hsin Yang, Tony Mok, Barbara Peil, Angela Märten, Luis Paz-Ares
Journal: Journal of Thoracic Oncology (2017)
Tendencias en el riesgo de transmisión de infecciones virales (VIH, VHC, VHB) a través de transfusiones sanguíneas en Francia (1992-2003) e impacto de la prueba de ácidos nucleicos (NAT)
Authors: J Pillonel, S Laperche
Journal: Eurosurveillance (2005)

La vigilancia de las tendencias del riesgo residual de transmision de infecciones virales por transfusion sanguinea es importante para evaluar las mejoras en la seguridad de la sangre y productos sanguineos y para adaptar las politicas de reduccion de riesgo. Se estudiaron estas tendencias en Francia sobre cuatro periodos de tres anos (1992-1994, 1995-1997, 1998-2000 y 2001-2003). Las estimaciones para 2001-2003 se compararon con los resultados del NAT (nucleic acid testing, prueba de los acidos nucleicos) para el VIH-1 y el virus de la hepatitis C (VHC) realizados en Julio de 2001 en todas las donaciones sanguineas. Gracias a la mejora del reclutamiento y de la seleccion de los donantes, progresos en tecnicas de cribado y medidas de prevencion para el control de las infecciones, los riesgos residuales para el VIH, y los virus de la hepatitis C y B (VHB) bajaron de modo significativo entre 1992 y 2003. Actualmente, el riesgo residual es muy bajo; entre 2001 y 2003 se estimaba en 1 por 3,15 millones de donaciones para el VIH, 1 por 10 millones para el VHC y 1 por cada 640.000 para el VHB. En los 6,14 Millones de donaciones sanguineas analizadas por NAT entre Julio de 2001 y Diciembre de 2003, se eliminaron dos donaciones positivas para el VIH y tres para el VHC, representando un rendimiento de 1 por 3,07 millones para el HIV y de 1 por 2,05 millones para el VHC. Estos resultados ponen de manifiesto la ventaja limitada del NAT asi como su escasa relacion coste-eficacia.
Epidémies d'origine alimentaire au nord du Portugal, 2002
Authors: A M Correia, G Gonçalves, Margarida Saraiva
Journal: Eurosurveillance (2004)

En octobre 2001, les epidemies d'origine alimentaire ont ete inclues dans le systeme de surveillance portugais d'alerte et de reponse. Les autorites sanitaires de la region nord (Delegado Regional de Saude do Norte - DRSN) ont alors debute un programme de surveillance des epidemies d'origine alimentaire. Cet article decrit brievement les donnees de l'annee 2002 obtenues par ce systeme. Chaque epidemie a fait l'objet d'un rapport des autorites sanitaires locales (Delegado de Saude Concelhio - DSC). Cinquante neuf pour cent des 27 epidemies etudiees par les DSC en 2002 ont ete rapportees dans les 72 heures suivant la date du debut de la maladie. Sur les 577 patients identifies, 9,6% ont ete hospitalises, et aucun deces n'a ete declare. L'agent etiologique a ete identifie chez les patients dans 63,0% des epidemies, et dans les aliments dans 18,5% des situations. Salmonella enterica etait responsable de 73,7% des epidemies pour lesquelles la presence de l'agent avait ete confirmee en laboratoire. Les repas incrimines dans les epidemies etaient principalement prepares dans des restaurants ou a la maison (75.0% des epidemies). Les facteurs contribuants les plus souvent rapportes par les DSC etaient une conservation, une preparation ou une manipulation des aliments inadaptees. La surveillance et le controle epidemiologiques des epidemies d'origine alimentaire doivent etre renforces au Portugal dans le cadre d'une strategie plus large pour promouvoir la securite alimentaire.
Brote de infección por Salmonella enteritidis fagotipo 1 en turistas británicos visitantes de Mallorca en junio de 1996
Authors: P Wall, L Ward, S Crespi, C Furtado
Journal: Eurosurveillance (1997)

Tres turistas britanicos enfermaron durante su estancia en el mismo hotel de Alcudia, Mallorca, del 11 al 25 de junio de 1996; a su regreso a Inglaterra se les diagnostico la infeccion por Salmonella enteritidis. El 10 de julio de 1996, un inspector sanitario de medio ambiente asi lo informo a la Seccion de Enfermedades Gastrointestinales del 'PHLS Communicable Disease Surveillance Centre' (CDSC). El CDSC contacto con un microbiologo de Alcudia, quien informo que ya habia investigado un brote de gastroenteritis en el hotel cuando alli se hospedaron los tres huespedes ingleses. Se trata de un gran hotel que trabaja exclusivamente con turistas britanicos y el precio de la habitacion suele incluir desayuno y cena. Los turistas que contraen gastroenteritis durante su estancia en el hotel son atendidos por el medico general de la zona que suele utilizar el hotel. La mayoria de los casos reciben tratamiento sintomatico y la toma de muestras de heces no es sistematica. Solo se ingresan en el hospital los casos muy graves.
P2.01-016 Prognostic Impact of a New Score Using Neutrophil-To-Lymphocyte Ratios in the Serum and Malignant Pleural Effusion in Lung Cancer Patients
Authors: H. Nam, C. Kim, D. Kim, J.H. Lim, S. Jeon, J.S. Kim, Y.S. Lee, J.H. Cho, J. Ryu
Journal: Journal of Thoracic Oncology (2017)