tbuckley/cabot-search huggingface dataset:
P3.09-009 Fourteen Cases Study of 5 Year Survivors of Malignant Pleural Mesothelioma Following Extrapleural Pneumonectomy
Authors: A. Kuroda, N. Kondo, A. Fukuda, T. Nakamichi, A. Nakamura, M. Hashimoto, T. Takuwa, S. Matsumoto, T. Tsujimura, K. Takashi, S. Hasegawa
Journal: Journal of Thoracic Oncology (2017)
PDTM-23. THE ACTIVE REGULATORY LANDSCAPE OF EPENDYMAL TUMORS
Authors: Stephen Mack, Kristian W Pajtler, Lukas Chavez, Stefan M Pfister, Marcel Kool, Michael Taylor, Jeremy Rich
Journal: Neuro-Oncology (2017)

Genomic sequencing has driven precision-based oncology therapy; however, genetic drivers remain unknown or non-targetable for many malignancies, demanding alternative approaches to identify therapeutic leads. Ependymomas comprise histologically similar tumour entities driven by distinct molecular mechanisms, such as fusion oncoproteins, genome-wide chromosomal instability, or disruption of DNA methylation patterns. Despite these differences, ependymomas commonly resist chemotherapy and lack available targeted agents for clinical trial development. In the case of genomically balanced ependymomas, and those driven by fusion oncoproteins, we hypothesized that the chromatin landscapes could uncover oncogenes that would inform actionable targets for therapy and reveal specific transcriptional circuitries to identify the molecular origins of the disease. To this end, we mapped active chromatin landscapes in 42 primary ependymomas in discovery and validation cohorts using H3K27 acetylation ChIP-seq. Enhancer regions revealed novel oncogenes, molecular targets, and pathways, which when subjected to small molecule inhibitor or shRNA treatment, increased survival and halted proliferation in mouse and neurosphere patient-derived models of ependymomas. Reconstruction of enhancer networks permitted the identification of core transcription factors (TFs) that establish ependymoma cell state, and lineage-specifying TFs that dictate molecular subgroup identity. Lineage-associated TFs point to distinct spatio-temporal origins of ependymoma subgroups such as FOXJ1 TF activity and expression observed preferentially in subsets of hindbrain ependymomas. To translate our results into a potential clinical paradigm, we demonstrate cancer dependencies on super enhancer associated genes and lineage TFs, and establish the utility of chromatin landscape analysis to predict novel targets for cancer therapy.
Un enfoque múltiple para comprender la resurgencia y la evolución de la sífilis en Europa occidental
Authors: K Fenton
Journal: Eurosurveillance (2004)

Casi ocho anos despues del brote de sifilis ocurrido en Bristol, Inglaterra [1], brotes sucesivos afectaron a la mayor parte de los paises del Europa occidental [2]. Este numero de Eurosurveillance trata de la resurgencia reciente y de la evolucion de la sifilis en siete paises europeos, con el objetivo de hacer un analisis critico de nuestra comprension de su epidemiologia, y de proponer soluciones para reorientar las intervenciones en el futuro [3-9]. Estos articulos tambien permiten profundizar en las causas multifactoriales de los brotes de sifilis [10], y en las medidas preventivas que pueden hacer cambiar esta situacion.
MA 08.09 Postoperative Mobilization and Rehabilitation Requirements for Lung Cancer Patients Undergoing Minimally Invasive Surgery
Authors: P. Agostini, S. Lugg, K. Adams, T. Smith, M. Kalkat, P. Rajesh, R. Steyn, B. Naidu, A. Rushton, E. Bishay
Journal: Journal of Thoracic Oncology (2017)
Informe del Sexto Congreso Internacional del Grupo de Trabajo del Laboratorio Europeo sobre la Difteria, Bruselas, Bélgica
Authors: S Lai, A Efstratiou
Journal: Eurosurveillance (2002)

Paralelamente a la aparicion de la difteria en Europa del este en los diez ultimos anos, tambien se ha podido constatar la aparicion de infecciones provocadas por Corynebacterium diphtheriae no toxigenica y por C. diphtheriae no toxigenica, pero portadora del gen de la toxina. Dado que estas cepas se pueden manifestar como infecciones sintomaticas de distintos grados de gravedad, es preciso evaluar su importancia clinica y epidemiologica. La presencia persistente de cepas toxigenicas y no toxigenicas de C. diphtheriae asociada a la variabilidad de genotipos y biotipos, implica que es necesaria una innovacion en las medidas de vacunacion de poblaciones. Hoy por hoy, el metodo de proteccion de mayor eficacia para el grupo de poblacion mas vulnerable (los adultos) es administrar una dosis de recuerdo de la vacuna. Ademas de combinar un buen sistema de vigilancia con una profilaxis antibiotica eficaz y un programa de vacunacion actualizado, tambien se deben realizar estudios serologicos que permitan vigilar el estado inmunitario de la poblacion. Las comunicaciones presentadas en el Sexto Congreso Internacional
Control de la rubéola en Italia
Authors: M L Ciofi Degli Atti, A Filia, M G Revello, W Buffolano, S Salmaso
Journal: Eurosurveillance (2004)

En Italia, la vacunacion contra la rubeola en ninas preadolescentes se recomienda desde 1972 y, desde 1990, para todos los ninos de dos anos. No obstante, la cobertura de ninos de 12 a 24 meses es inferior a la optima (56% en 1998, 78% en 2003), con grandes variaciones entre regiones.
Como consecuencia, la rubeola sigue circulando por todo el pais y, en 1996, el porcentaje de mujeres de 15 a 39 anos susceptibles a la rubeola fue g 5%. 
De 1987 a 1991, el sindrome de rubeola congenita (SRC) estaba sujeto a declaracion, con un rango de casos declarados anualmente de 8-76. Desde 1992, ya no se dispone de datos de incidencia nacional pero los informes locales indican que aun se producen casos de SRC. 
Hacen falta acciones de ambito nacional, coordinadas y uniformes que controlen el SRC de forma eficaz. Por ello, se acaba de lanzar el Plan Nacional de Eliminacion del Sarampion y de la Rubeola Congenita. Este plan incluye estrategias destinadas a incrementar la cobertura vacunal en ninos y medidas de control especificas para la rubeola congenita, es decir, mejorar la vacunacion de mujeres susceptibles en edad fertil, y volver a introducir la vigilancia nacional del SRC.
P1.01-032 Detection of EGFR, ALK and Other Driver Oncogenes from Plasma cfDNA by Single Molecule Amplification and Re-sequencing Technology (cSMART)
Authors: T. Mok, S. Lu, Y. Cheng, J. Wang, Y. Wang, T. Wang, T. Yung, X. Su, F. Sun, L.T. Wang, Y. Wu
Journal: Journal of Thoracic Oncology (2017)
P2.02-072 Reliability of Small Biopsy Samples for Tumor PD-L1 Expression in Non-Small-Cell Lung Cancer
Authors: A. Tsunoda, K. Morikawa, M. Okamoto, T. Inoue, H. Kida, N. Furuya, H. Handa, H. Nishine, T. Inoue, T. Miyazawa, M. Mineshita
Journal: Journal of Thoracic Oncology (2017)
STEM-12. TARGETING GLIOMA STEM CELL MIRNA NETWORKS
Authors: Deobrat Dixit, Lisa C Wallace, Christine Lee, Tyler E Miller, Briana Prager, Jeremy Rich
Journal: Neuro-Oncology (2017)

Glioma stem cells (GSCs) are self-renewing, highly tumorigenic cells that often display therapeutic resistance, supporting a need for discovery of novel molecular targeting strategies. Using a whole genome miRNA screen, we identified novel miRNAs that regulate GSC stemness and survival. Leveraging three patient-derived GSC models, we performed a primary miRNA screen using 2051 miRNA-mimics. The top 5% miRNAs (18 miRNAs) that increased or decreased cell viability were selected for further validation, with 10 passing validation in a secondary screen in six patient-derived GSCs. In vitro limiting dilution assays confirmed that these miRNAs significantly modulate stemness of GSCs. IPA analysis predicted these miRNAs as regulators in key biological processes important for cancer, cell cycle, cell death and survival. Ongoing experiments are dissecting the molecular mechanisms regulated by selected miRNAs and optimizing in vivo targeting. Collectively, this novel miRNA screening may inform novel glioblastoma therapies and provide global gene regulatory networks integral to GSC biology.
Abstract SY18-01: Targeting the p53-MDM2 interaction for cancer therapy
Authors: Lyubomir T. Vassilev
Journal: Cancer Research (2010)

Abstract The p53 tumor suppressor is tightly controlled by MDM2 which binds p53 and negatively modulates its transcriptional activity and stability. Many tumors overproduce MDM2 to impair p53 function. Restoration of p53 activity by inhibiting the p53-MDM2 interaction may offer a novel approach to cancer therapy. Recently developed potent and selective small-molecule MDM2 antagonists, the nutlins, interact specifically with the p53-binding pocket of MDM2 and release p53 from negative control. Treatment of cancer cells expressing wild-type p53 with nutlins stabilized p53 and activated the p53 pathway. Although half of human tumors retain wild-type p53, the function of the tumor suppressor could be compromised by defective signaling in the pathway. Using nutlin-3a to probe downstream p53 signaling we find that the cell cycle arrest function of p53 is preserved in all tested cancer cell lines expressing wild-type p53 but many have compromised ability to undergo p53-dependent apoptosis. The p53 transcription target and potent CDK inhibitor, p21, has been shown to inhibit the apoptotic response to genotoxic p53 activation. Although it is strongly upregulated by MDM2 antagonists in all tested cancer cell lines, p21 does not affect the apoptotic outcome of nutlin treatment, suggesting that it does not play anti-apoptotic role during non-genotoxic p53 activation. MDM2 controls p53 stability and activity through a feedback mechanism by which both proteins mutually regulate their cellular levels. Nutlins disrupt this regulatory circuit leading to upregulation of both p53 and MDM2. They selectively block the p53-MDM2 interaction but do not affect MDM2 E3 ligase activity that is elevated in the presence of the drug. MDMX, a known p53 inhibitor and MDM2 ubiqutination target decreased with the increase of MDM2, suggesting that MDM2 contributes to antitumor activity of nutlins at least in part by facilitating MDMX degradation. Elevated MDM2 contributes to the apoptotic outcome of nutlin treatment also by interfering with the maturation of subsets of microRNAs. Nutlin-3a doses that shrink xenograft tumors activated p53 signaling in mouse tissues but caused only mild changes in bone marrow, thymus and spleen. These results suggest that p53 activation by MDM2 antagonists may provide an acceptable safety window for cancer therapy. A member of the nutlin family of MDM2 antagonists is currently undergoing Ph I clinical testing in patients with solid and hematological malignancies. Citation Format: Lyubomir T. Vassilev. Targeting the p53-MDM2 interaction for cancer therapy [abstract]. In: Proceedings of the AACR 101st Annual Meeting 2010; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr SY18-01
CBIO-22. PATIENT-DERIVED GLIOBLASTOMA CELLS RELEASE CILIARY VESICLES THAT STIMULATE TUMOR CELL PROLIFERATION
Authors: Lan Hoang-Minh, Joshua Breunig, Matthew Sarkisian
Journal: Neuro-Oncology (2017)

The mechanisms by which glioblastoma (GBM) cell primary cilia influence tumor pathogenesis are unclear. The common view that primary cilia are exclusively sensory organelles has recently been challenged. In non-glioma cells, primary cilia release vesicles from their tips, vesicles which can contain matrix metalloproteinases, G protein-coupled receptors, signaling mediators (e.g., Arl13b), and transcription factors that promote cell proliferation. The goals of this study were to track GBM cell cilia formation, behavior, and potential vesicle release and assess the effects of conditioned media derived from ciliated and non-ciliated GBM cell cultures on cell proliferation. We used piggybac technology to generate GBM patient-derived cell lines that stably express Arl13b:GFP, which labels GBM cilia. First, live imaging of Arl13b:GFP-positive GBM cilia revealed the release of ciliary vesicles into the extracellular milieu across several GBM cell clones. The excised buds were characterized by the presence of Arl13b but the absence of acetylated alpha-tubulin, for both human and mouse glioma cells. Recent studies reported this phenomenon occurs during G0, prior to ciliary resorption and cell cycle re-entry, and requires recruitment of F-actin and actin regulators into the cilium. Analysis of patient biopsies, tumors of human GBM-bearing mice, and GBM cell lines revealed scattered cilia expressing F-actin, indicating that GBM cilia may use a similar actin network-based mechanism to release vesicles into the tumor microenvironment. Importantly, GBM cell proliferation was significantly decreased when cells were grown in media derived from cilia-depleted GBM cells when compared with media from ciliated GBM cells, suggesting GBM cilia release factors that affect tumor cell growth. While the content and functional significance of GBM cilia vesicles warrant further investigation, our data raise the possibility that the release of ciliary material represents a novel mode of intercellular communication that might contribute to GBM pathogenesis.
TMIC-20. INHIBITION OF SLC7A11 REDUCES EXCITATORY SYNAPTIC INPUT OF PERITUMORAL NEURONS IN GLIOMA PATIENTS
Authors: Thomas Sauvigny, Lasse Dührsen, Dietmar Kuhl, Manfred Westphal, Ora Ohana, Tobias Martens
Journal: Neuro-Oncology (2017)

Malignant glioma is frequently associated with drug-resistant epilepsy which limits quality-of-life. Expression of SLC7A11, a cysteine-glutamate antiporter, in gliomas has been shown to be associated with poor survival and an increased rate of glioma induced epilepsy. However, the mediators of the effect of glioma cells on neurons in the glioma infiltrated cortex are not well known and new therapeutic targets for seizure treatment are needed. Therefore, in this study, we examined synaptic events in the human peritumoral brain during inhibition of SLC7A11. We recorded intracellular neuronal activity in acute brain slices of tumor infiltrated cortex of patients who underwent a neurosurgical glioma resection. Postsynaptic currents were recorded in whole-cell voltage-clamp configuration in an artificial cerebrospinal fluid. SLC7A11 was inhibited using sulfasalazine (SAS). The data was analyzed using either a one-way ANOVA or a paired t-test in SPSS®v23.0. In total, we analyzed 12355 excitatory postsynaptic events in 12 neurons in the peritumoral cortex of seven patients with an astrocytic glioma. Five patients (71%) suffered from glioma induced epilepsy. After administration of SAS we observed a significantly lower rate of excitatory synaptic events compared to the baseline condition (2.7Hz; vs. 3.9Hz, p=0.03). Moreover, we found a reduction of the events’ peak-amplitude and area under the curve (22.95pA vs. 29.93pA; p<0.001 and 58.49pA*ms vs. 109.9pA*ms; p<0.001). The interevent interval was prolonged under SAS-conditions (264.3ms vs. 214.5ms; p<0.001). Inhibition of SLC7A11 leads to a significant reduction of excitatory synaptic input in neurons in the glioma infiltrated human cortex. Our data suggest that specific inhibition of glutamate driven neuronal hyperexcitability may be a putative target for treatment of glioma associated epilepsy.
P3.14-001 Impact of PCI on Prognosis of LD-SCLC Through Pattern of Brain Metastases as a First Recurrence Site
Authors: M. Nakamura, M. Onozawa, A. Motegi, H. Hojo, S. Zenda, N. Nakamura, H. Udagawa, K. Kirita, S. Matsumoto, S. Umemura, K. Yoh, S. Niho, K. Goto, T. Akimoto
Journal: Journal of Thoracic Oncology (2017)
Cisplatin in addition to single-agent first-line chemotherapy in elderly patients with advanced non-small-cell lung cancer (NSCLC): efficacy results of a joint analysis of the multicentre, randomized phase 3 MILES-3 and MILES-4 studies
Authors: A. Morabito, L. Cavanna, A. Luciani, P. Maione, L. Bonanno, E. Piazza, S. Leo, S. Cinieri, F. Morgillo, M.A. Burgio, D. Ferrara, D. Cortinovis, F. Rosetti, R. Costanzo, C. Sandomenico, G. Daniele, S. Signoriello, M.C. Piccirillo, C. Gallo, F. Perrone, C. Gridelli
Journal: Annals of Oncology (2017)
P1.09-011 LUME-Meso Phase II/III Study: Nintedanib + Pemetrexed/Cisplatin in Chemo-Naïve Patients with Malignant Pleural Mesothelioma
Authors: A. Tsao, N. Vogelzang, A. Nowak, S. Popat, R. Gaafar, J. Van Meerbeeck, T. Nakano, J. Barrueco, N. Morsli, G. Scagliotti
Journal: Journal of Thoracic Oncology (2017)
SCDT-24. SYNERGISTIC EFFECTS OF VALPROIC ACID AND TRAIL-SECRETING hMSCs IN GLIOMA THERAPY
Authors: Jung-hoon Kim, Young Joo Kim, Sin-soo Jeun
Journal: Neuro-Oncology (2017)

Histone deacetylase inhibitors have been shown to enhance the sensitivity of tumor cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced cytotoxicity. Valproic acid (VPA), a histone deacetylase inhibitor (HDACi), is approved for the treatment of epilepsia, bipolar disorders and clinically used for schizophrenia. Currently, VPA is also examined in numerous clinical trials for different leukaemias and solid tumor entities. In our previous experiments, we demonstrated that TRAIL secreting hBM-MSCs (hMSCs-TRAIL) inhibits tumor growth after intratumaral injection in glioma bearing mice. However, incomplete tumor regression for hMSCs-TRAIL treatment has also been described. To overcome this problem, combination of hMSCs-TRAIL and VPA, has been attempted as a strategy to sensitise glioma cell sensitivity to TRAIL-induced apoptosis. The anticancer effect of VPA, TRAIL, and a combination of the two drugs were evaluated in U87 glioma cell. VPA and TRAIL induced a dose-dependent cell death of U87 glioma cell and the synergistic effect was confirmed by using DR5/Fc, DR5-specific blocking chimera antibody. A synergistic cell growth inhibitory effect was observed at a combination treatment with VPA and TRAIL. The FACS analysis also indicated that synergistic effects by VPA enhanced DR5 expression in U87 glioma cell. Furthermore, in vivo efficacy experiments showed that combination treatments of hMSCs-TRAIL and VPA significantly inhibited tumor growth and prolonged the survival of glioma-bearing mice compared with control groups. Our results provide a rationale for the development of hMSCs-TRAIL and VPA combination treatment as a novel therapeutic regimen for glioma therapy.
Prevalence and incidence of chronic spontaneous urticaria in the entire Korean adult population
Authors: Y.S. Kim, S.H. Park, K. Han, C.H. Bang, J.H. Lee, Y.M. Park
Journal: British Journal of Dermatology (2017)

Background: Ethnic differences and temporal trends in the epidemiology of chronic spontaneous urticaria (CSU) are not well understood.
Objectives: The aim of our study was to investigate recent trends in the prevalence and incidence of CSU among adult Korean subjects from 2006 to 2014.
Methods: This study used the national health claims database of Korea, which covers nearly the entire Korean population. Data from all Koreans aged ≥20 years were included in this study. We defined a diagnosis of CSU when one of the following two criteria and a prescription criterion were met: either (1) two outpatient diagnoses of L50.1, L50.8, or L50.9; or (2) one outpatient diagnosis of L50.1, L50.8, or L50.9 plus one diagnosis of T78.3 at least 6 weeks apart within one year, and 42 days or longer prescription of an antihistamine under the diagnosis of L50.1, L50.8, or L50.9 within one year of the initial diagnosis. Age-adjusted prevalence and incidence of each year from 2006 to 2014 were calculated.
Results: The annual age-adjusted prevalence and incidence of CSU were in the range of 0.16-0.45%, and 1.02-2.43 per 1,000 person-years, respectively. Women had a higher prevalence and incidence than men throughout tye years from 2006 to 2014. The prevalence and incidence of CSU consistently increased annually from 2006 to 2014.
Conclusion: We presented the longitudinal prevalence and incidence of CSU in the entire adult Korean population and found recent increasing trends.
MA 05.06 Comparison Study of PD-L1 Immunohistochemistry Assays with 22C3 and 28-8: Analysis on Surgical Specimens of NSCLC
Authors: T. Saito, K. Tsuta, M. Ishida, H. Ryota, Y. Takeyasu, K. Fukumoto, H. Matsui, Y. Taniguchi, H. Yanagimoto, T. Yokoi, T. Kurata, T. Murakawa
Journal: Journal of Thoracic Oncology (2017)
Esplosione di infezioni da Salmonella nel 2003 in Olanda: estate torrida o effetti collaterali dell'epidemia dell'influenza aviaria?
Authors: W van Pelt, D. J Mevius, H G Stoelhorst, S Kovats, A. W van de Giessen, W J B Wannet, Y T H P Duynhoven
Journal: Eurosurveillance (2004)

A giugno del 2003, il Dutch national Salmonella centre ha evidenziato un numero significativo di isolati di Salmonella Enteritidis, rispetto ai dati relativi agli anni precedenti e forniti dai principali laboratori regionali di salute pubblica. Alla fine del 2003 si aggiunsero altri 540 casi confermati dal laboratorio e registrati nell'intera Olanda; nella popolazione generale si giunse a circa 7.500 casi di gastroenterite causati dalla S. Enteritidis, che corrisponde a un aumento del 50% rispetto agli anni precedenti. La causa di questo incremento non e imputabile alle temperature elevate, che hanno caratterizzato l'estate del 2003, quanto piuttosto all'aumentata importazione di uova contaminate da Salmonella, in seguito all'epidemia di influenza aviaria.
EPID-09. INCREASED OVERALL SURVIVAL IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA OVER THE PAST 40 YEARS, EXCEPT IN THE ELDERLY
Authors: Joe Mendez, Quinn Ostrom, Haley Gittleman, Carol Kruchko, Jill Barnholtz-Sloan, Lisa DeAngelis, Christian Grommes
Journal: Neuro-Oncology (2017)

There has been significant improvement in treatment outcomes of Primary Central Nervous System Lymphoma (PCNSL) at specialized centers over the past several decades. However, it is unclear if these changes have translated to benefits in the general population. In this study, we utilized two national databases to examine incidence and survival trends over time for PCNSL (Central Brain Tumor Registry of the United States (CBTRUS, 2000 – 2013) and 18 Surveillance, Epidemiology and End Results (SEER, 1973 – 2013) registries). The annual incidence of PCNSL in 2013 was 0.4 per 100,000 population (CBTRUS/SEER). Incidence increased from 0.1 per 100,000 in the 1970s to 0.4 per 100,000 in the 1980s, correlating with an increase in the diagnosis of patients ≥70 years (1973:0.2 vs 2013:2.1 – SEER). Incidence rates differed greatly between young and elderly patients (age 20–29 years: 0.08 vs 70–79: 4.32 – CBTRUS). Even though the median overall survival of all patients doubled from 12.5 months in the 1970s to 26 months in the 2010s, this survival benefit was limited to patients <70 years. Survival in the elderly population, ≥70 years, did not change over the last 40 years (6 months in the 1970s vs 7 months in the 2010s, p-value = 0.1). The poor outcome seen in this vulnerable patient population highlights the need for clinical trials targeting the elderly in hopes of improving treatment strategies and survival.