tbuckley/cabot-search huggingface dataset:
El nuevo calendario de vacunación de Italia reduce la cobertura vacunal contra la poliomielitis en Nápoles
Authors: M. G. Panico, N M Trinchese, B Serpieri, F Attena
Journal: Eurosurveillance (2000)

El 7 de abril de 1999, el Ministerio de Sanidad italiano modifico los programas de inmunizacion infantil, incluida la vacunacion contra la poliomielitis. Los cambios incluyeron la sustitucion de las dos primeras dosis infantiles de poliovacuna oral (VPO) por la vacuna contra la polio inactivada inyectable (VPI). Esta medida fue introducida una vez comparado el riesgo de contraer poliomielitis salvaje con el riesgo de desarrollar poliomielitis paralitica asociada a la vacuna (riesgo relativo 0/10). El ultimo caso indigena de poliomielitis surgido en Italia tuvo lugar en 1983 y el ultimo caso importado se registro en 1988 (1). Este articulo describe la repercusion de la nueva ley en la tasa de vacunacion antipoliomielitica en una zona de Napoles, perteneciente a la autoridad sanitaria local (ASL NA4) y compuesta por 11 distritos sanitarios en los que, en 1998, nacieron 7.500 bebes.
ATIM-08. IMMUNOMARKERS IN THE DNX-2401 (DELTA-24-RGD) ONCOLYTIC VIRUS PHASE I CLINICAL TRIAL
Authors: Juan Fueyo, Candelaria Gomez-Manzano, Paloma Villalobos, Jaime Rodriguez-Canales, Ignacio Wistuba, Kenneth R Hess, Marta M Alonso, Sonia Tejada, Ricardo Diez Valle, Brett Ewald, Frank Tufaro, Fred Lang
Journal: Neuro-Oncology (2017)

As part of a phase 1, dose-escalation, biological-endpoint clinical study (NCT00805376) of DNX-2401 (Delta-24-RGD), a Rb-targeted, tumor-selective, replication-competent oncolytic adenovirus, conducted in 37 patients with recurrent malignant glioma, 12 patients received an intratumoral injection through an implanted catheter, followed 14-days later by en bloc resection and DNX-2401 injections into the post-resection tumor bed. 10 surgical post-treatment specimens and 5 pre-treated tumors were examined for markers of immune response. From all selected cases, formalin fixed, paraffin embedded tissue blocks were selected. IHC was performed using a Leica Bond Max automated stainer as previously described. The slides were scanned in an Aperio AT2 scanner (Leica Biosystems). The IHC scores for CD3, CD4, CD8, CD45Ro, FOXP3, TIM3, LAG-3, VISTA, CD20, CD57, CD68, and OX40 were expressed as cell density in the inflammatory cell population (number of positive cells per mm square of tumor area), except PD-L1, PD-L2, B7-H3, B7-H4, IDO-1, which were expressed using percentage of positive tumor cells, and also as H-Score of the tumor cells. Correlations between immunostaining marker values and survival and dose level were assessed using Spearman rank correlation analysis. Differences in immunostaining marker values before and after treatment were assessed. These analyses demonstrated that all the target proteins are expressed in gliomas in different patterns and tumor regions. Although, we did not observe significant treatment-related changes in the expression of PD-1 in lymphocytes and PD-L1 in glioma cells, TIM3, a marker for T cell exhaustion, was downregulated after DNX-2401 treatment. In addition, expression of B7-H3, a marker of poor prognosis in other tumors, correlated with poorer survival. Because PD-1 and TIM3 cooperate to maintain T-cell exhaustion our data provide a rationale for the combination of DNX-2401 and anti-PD-1 antibodies for the treatment of malignant gliomas. A multicenter clinical trial (NCT02798406) to test this strategy is ongoing.
TMIC-39. CROSSTALK WITH VASCULAR ENDOTHELIAL CELLS DRIVES PRONEURAL GLIOMA STEM CELL PROLIFERATION THROUGH THE UPREGULATED NTF3/TrkB PATHWAY
Authors: Suojun Zhang, Hai Yu, Soniya Bastola, Mutsuko Minata, Heba Allah Alsheikh, Kyung-Don Kang, Ichiro Nakano
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is a highly heterogeneous solid tumor characterized by an extensive vasculature network that contributes to its heterogeneity and malignant progression. Previously, we and others have identified that the perivascular niches maintain glioma stem cells with proneural subtype, but the detailed mechanism remains unclear. In this study, we aimed to identify effective small molecule compounds that attenuate the intercellular signals from endothelial cells to proneural glioma stem cells. To this end, we used 3 patient-derived glioma sphere cells (glioma stem-like cells, GSCs) for the screening of the tyrosine kinase inhibitor library. Out of the 168 compounds, we identified several compounds which potentially inhibit the promotive GSC growth. Among them, the neurotrophic tyrosine receptor kinase (Trk) inhibitors displayed a prominent inhibitory effect. Screening was further validated in vitro using varying doses on 5 patient-derived primary glioma cell lines. Detailed in vitro and in vivo functional data, as well as the mechanism of action, will be described.
OA 11.04 Effect of Early Palliative Care on Aggressiveness of Cancer Care near End of Life in Lung Cancer Patient
Authors: W. Chanprasertpinyo, S. Semsarn, V. Tangsujaritvijit, N. Ngamphaiboon, T. Reungwetwattana, S. Chaiviboontham, J. Konmun, V. Sachdev, P. Chansriwong
Journal: Journal of Thoracic Oncology (2017)
Prognostic role of disease extent and lymphocyte-monocyte ratio in advanced melanoma
Authors: D. Iacono, D. Basile, L. Gerratana, M.G. Vitale, G. Pelizzari, M. Cinausero, E. Poletto, F. Puglisi, G. Fasola, A.M. Minisini
Journal: Annals of Oncology (2017)
Increased frequency of acute reactions to iodinated contrast media after anti-CTLA-4 immunomodulating antibodies in cancer patients
Authors: L. Ridolfi, P. Elisabetta, D. Francesco, R. Alice, C. Carla, G. Nicola, G. Giorgia, N. Oriana, F. Alberto, G. Massimo
Journal: Annals of Oncology (2017)
Multigenic and dietary analysis of bladder cancer risk on special reference on nucleotide excision repair and folate intake
Authors: Hua Zhao, Margaret R. Spitz, Matthew B. Schabath, Aditi Hazra, H. Barton Grossman, Xifeng Wu
Journal: Cancer Research (2004)

2898   Deficiencies in both DNA repair capacity and dietary folate intake may synergistically lead to elevated cancer risk. The nucleotide excision repair (NER) pathway removes the majority of helix distorting lesions, but NER-related polymorphisms may alter protein function and individual capacity to repair damaged DNA, conferring a predisposition to cancer. To explore the association between NER gene polymorphisms and bladder cancer (BC) risk, we examined five polymorphisms in four core NER genes in 459 Caucasian BC patients and 430 Caucasian healthy controls. The polymorphisms were studied for gene-gene and gene-nutrient associations for BC risk. The specific polymorphic loci examined include:  XPA  (A/G at 5’ untranslated region),  XPC  (polyAT),  XPD  exon 23 (Lys751Gln) and exon 10 (Asp312Asn) and  XPG  (His1104Asp). The presence of one or two copies of the  XPA  G-allele variant was associated with increased BC risk (OR = 1.58, 95% CI = 1.09 - 2.29). The risk was further modified for younger individuals ( P  for trend = 0.001). The  XPD  exon 10 variant genotypes and  XPG  variant genotypes were also associated with an increased BC risk in various subgroups of individuals. A gene-smoking interaction was evident as well. There was a significant trend for an increased risk of BC in individuals possessing a higher number of putative high-risk alleles ( P  for trend = 0.004). The highest risk group with more than 5 putative high-risk alleles, had a two-fold increased risk (OR = 2.02, 95% CI = 1.31 - 3.14) compared to the lowest risk group with less than 2 putative high-risk alleles. Since dietary folate is essential for efficient DNA repair and synthesis, we also studied the joint effects between these polymorphisms and dietary folate equivalents (μg DFE/kcal/day) as assessed from a food frequency questionnaire. We have previously shown that BC cases have a lower intake of DFE compared to healthy controls, and that low DFE is associated with a statistically significant increased risk for BC. In the present study, the risk for individuals with the  XPA  variant allele was 1.23 (95% CI = 0.70 - 2.14), while the risk for low DFE was 1.25 (95% CI = 0.62 - 2.53), and individuals with both low intake of DFE and  XPA  variant alleles had an OR of 2.06 (95% CI = 1.20 - 3.53). Similar findings were observed for  XPC ,  XPD  and  XPG  polymorphisms with intake of DFE. This large study offers a simultaneous analysis of multiple polymorphic genes and new insights for the role of NER polymorphisms in risk for BC. These data suggest that individuals with low intake of dietary folate and deficient DNA repair are at a greater risk for BC.  Supported by the NCI grants CA 91846, CA 74880, and CA 86390.
P1.05-019 Effects of Tumor Stroma and Inflammation on Survival of Stage I-IIp Lung Cancer
Authors: L. Millares, J. Alcaraz, A. Martinez, I. Benchea, J. Carrasco, J. Sanchez De Cos, M.A. Gonzalez-Castro, A. Blanco, R. Sanchez-Gil, M. Serra, R. Rami-Porta, J. Sauleda, E. Fernandez, R. Melchor, L. Seijo, L. De Esteban Julvez, E. Barreiro, E. Monsó
Journal: Journal of Thoracic Oncology (2017)
P3.01-022 Prognostic Value of Clinical, Immune and Biochemical Markers in EGFR-Mutant NSCLC Patients Treated with First-Line EGFR TKIs
Authors: I. Ng, N. Kumarakulasinghe, N. Syn, R. Teng, R. Soo
Journal: Journal of Thoracic Oncology (2017)
RARE-16. CASE REPORT: DELAYED DEVELOPMENT OF PSEUDOPROGRESSION IN 2 GLIOBLASTOMA PATIENTS TREATED WITH TTFIELDS
Authors: Sarah Hurrell, Elizabeth Cochran, Wade M Mueller, Sean McGarry, Christopher J Schultz, Malika Siker, Scott Rand, Peter S LaViolette, Kathleen M Schmainda, Jennifer M Connelly
Journal: Neuro-Oncology (2017)

Pseudoprogression in response to chemoradiation is a recognized problem in treating glioblastoma (GBM) patients. Imaging can show increased T1+C enhancement or FLAIR hyperintensity not associated with histopathological progression. Two indicators for pseudoprogression are positive MGMT methylation status and length of time after initial chemoradiation treatment. Pseudoprogression most commonly occurs 3 months after radiation therapy and can occur up to 6 months later. Tumor treatment fields (TTFields) have been shown to improve progression free and overall survival but has not yet been investigated for its effects on pseudoprogression. We present here the first 2 cases of TTField delayed pseudoprogression. CASE REPORT: Two GBM patients being treated with TTFields showed signs of radiographic progression 5+ months after completing radiation. Patient 1 is a 66-year-old female with a history of breast cancer who presented with new onset seizure. Imaging revealed a right frontal ring-enhancing lesion with diffusely infiltrating FLAIR. Patient 2 is a 47-year-old male with a history of neurofibromatosis and HIV related anal lymphoma. He presented with left sided parasthesia. Imaging found a heterogeneously enhancing right parietal mass. Both patients were diagnosed pathologically with MGMT un-methylated GBM. Chemoradiation treatment was completed followed by temodar (TMZ) plus TTFields. Five and 7 months after radiation treatment, respectively, radiographic progression was noted. A second surgical resection was pathologically evaluated and both cases were discovered to be treatment effect. These are the first 2 known cases of delayed pseudoprogression in patients on adjuvant TMZ with TTFields. Both patients developed new enhancement outside the typical pseudoprogression window and were unlikely candidates given their methylation status. Both patients resumed adjuvant TMZ with TTFields. New contrast enhancement in patients on adjuvant TMZ with TTFields should be interpreted cautiously as it may represent pseudoprogression. Pathologic confirmation of tumor progression should be considered prior to changing treatment.
PL 02.02 Patient-Reported Outcomes with Durvalumab after Chemoradiation in Locally Advanced, Unresectable NSCLC: Data from PACIFIC
Authors: R. Hui, M. Özgüroğlu, D. Daniel, D. Baz, S. Murakami, T. Yokoi, A. Chiappori, K.H. Lee, M. De Wit, B. Chul Cho, J. Gray, A. Rydén, L. Viviers, L. Poole, P. Dennis, S. Antonia
Journal: Journal of Thoracic Oncology (2017)
P3.02-006 Monitoring Genetic Alterations in Plasma during Anti-Cancer Treatment in Advanced NSCLC (MAGIC1-Validation Cohort: Preliminary Results)
Authors: L. Bonanno, I. Attili, E. Zulato, G. Nardo, M. Verza, A. Pavan, P. Del Bianco, G. Pasello, G. Zago, V. Polo, S. Frega, N. Milite, M. Carlucci, F. Calabrese, G.L. De Salvo, P. Conte, S. Indraccolo
Journal: Journal of Thoracic Oncology (2017)
TMIC-25. TUMOR MIGRATION AND ROLE OF MICROENVIRONMENT IN DIFFUSE INTRINSIC PONTINE GLIOMA
Authors: Madhuri Kambhampati, Eshini Panditharatna, Sridevi Yadavilli, Cheng-Ying Ho, Lindsay Kilburn, Eugene Hwang, Brian Rood, Miriam Bornhorst, Suresh Magge, Jamila Gittens, Madeline Clark, Roger Packer, Javad Nazarian
Journal: Neuro-Oncology (2017)

Diffuse intrinsic pontine glioma (DIPG) is a fatal pediatric brain cancer which presents an immense therapeutic challenge. Our previous work has shown that histone mutations (H3K27M) arise in the pontine tumor but in most cases necessitates an obligate partner mutation for tumorigenesis and spread. Our established standard operating procedure for performing autopsy has allowed us to collect 20 whole brains from DIPG patients. Sagittal sections from whole brains (n=8) were processed for histological analyses to identify the tumor migratory path (pontine to extra-pontine). Histological examination of all neuroanatomical locations indicated: i) Tumor cell infiltration to extra-pontine regions in 7/8 brains as indicated by histology, ii) In 4/7 brains, tumor cells migrated to extra-pontine regions but failed to form tumors. These regions were histologically “normal” according to the World Health Organization grading criteria, but harbored tumor cells as indicated by H3K27M stains and digital PCR. Given the age of disease onset, and neuroanatomical location, it is plausible that tumor microenvironment plays a critical role in tumor spread. To test the role of pontine microenvironment in tumorigenesis, we performed a pilot study by injecting human pontine tumor cells (n= 4 patients) into 3-4 week old murine cerebral cortex, which represents the age of DIPG disease onset. Necropsy specimens were examined for tumor presence by histological analyses for H&E and H3K27M stains. We identified tumor in both cortex (injection site) and brainstem. Tumor cells migrated to populate brainstem in all four, and cerebellum in 2/4 xenograft models. Furthermore these tumors were positive for human mitochondrial protein (MAB1273) and were authenticated by STR to demonstrate their human cell of origin. These observations strongly show the presence of: i) anatomically suitable migration paths (e.g. axonal guidance, leptomeningeal), and ii) tissue-specific microenvironment and molecular events, governing susceptibility and sensitivity of particular neuroanatomical locations to tumor formation.
MA 08.07 Can the Early Intervention of the Lung Cancer CNS Reduce the Length of Stay for Patients Admitted via the Emergency Route on First Presentation?
Authors: J. Draffen, K. Clayton, P. Shepherd, S. Bolton, V. Beattie, P. Rees, J. Roberts, J. Mcphelim, S. Kefyalew, Y. Jeffs, D. Denby
Journal: Journal of Thoracic Oncology (2017)
GENE-32. ACTIVE CHROMATIN REGULATORY MAPS IDENTIFY CORE CELL STATE DRIVERS OF GLIOBLASTOMA
Authors: Stephen Mack, Xiuxing Wang, Jeremy Rich
Journal: Neuro-Oncology (2017)

The genomic, transcriptomic, and epigenomic heterogeneity of glioblastoma (GBM) underlies its aggressive nature, resistance to therapy, and high mortality rate. Compounding the molecular differences between GBM patients is a diverse cellular hierarchy of tumor cells, capable of microenvironmental adaptation and therapeutic resistance. We hypothesized that defining the ‘active’ chromatin maps of GBM tumors and GBM primary cultures would uncover molecular patterns that dissect both its tumor diversity, and identify novel cellular dependencies as future targets for therapy. Histone lysine 27 acetylation (H3K27ac) is a chromatin modification that marks ‘active’ regions of the epigenome. We performed a genome-wide and integrated analysis of 100 GBM samples by chromatin immunoprecipitation of H3K27ac (H3K27ac ChIP-seq) combined with transcriptional profiling by RNA-seq. Our findings uncover the landscape of recurrent transcriptional enhancer lesions that define GBM, its molecular subtypes, and associated patient-derived GBM models. We pinpoint distal enhancer regions that specify subsets of GBM tumors, which converge on distinct oncogenic and lineage programs such as the YAP1/Hippo pathway and OLIG1/2 signaling. Further, broad transcriptional enhancers (i.e super enhancers, SEs) reveal core cell state drivers of GBM and its subtypes, such as MSI2, CDK6, SOX2, EGFR, CDK9 and MYC, which represent novel candidates for targeted therapy. SE regions are leveraged to reconstruct and define the transcriptional regulatory circuitries of GBM, and provide insight into the principal components of GBM tumor cell maintenance. In conclusion, our study reveals the ‘active’ chromatin signatures of GBM to identify novel cell state drivers as potential targets for therapy, and broadly, provides a resource for decoding the epigenomic landscapes of glioblastoma.
Epidémie de shigellose dans une institution pour enfants à Queluz - Portugal - 1995
Authors: A Suspiro, L Menezes
Journal: Eurosurveillance (1996)

L' introduction de shigella dans un centre d'accueil pour enfants entraine un risque eleve de contamination secondaire interhumaine dans le centre (1). Nous rapportons une epidemie de shigellose, survenue au debut de 1995 dans une creche-garderie accueillant des enfants de moins de 10 ans, qui a touche 99 enfants, 17 membres de leurs familles et 7 membres du personnel. Pour controler l'epidemie, le ministere de la sante a ferme le centre durant cinq jours ; de plus, toutes les familles a risque ont ete contactees afin de donner aux personnes affectees un traitement antimicrobien approprie.
MA 16.04 Phase II Trial of S-1 Treatment as Palliative-Intent Chemotherapy for Previously Treated Advanced Thymic Carcinoma
Authors: F. Ohyanagi, Y. Okuma, Y. Goto, K. Sunami, Y. Nakahara, S. Kitazono, Y. Tambo, N. Yanagitani, S. Kanda, A. Horiike, H. Horinouchi, Y. Fujiwara, H. Nokihara, N. Yamamoto, M. Nishio, Y. Ohe, Y. Hosomi
Journal: Journal of Thoracic Oncology (2017)
Nuevas características epidemiológicas de la enfermedad meningocócica en Bélgica
Authors: F Carion, M van Looveren, H Goossens
Journal: Eurosurveillance (1997)

En Belgica, tras la epidemia ocurrida a principios de la decada de los setenta causada por Neisseria meningitidis B:2b:P1.2 (maximas incidencias en 1.971 y 1.972 con 5 casos por 100.000 habitantes por ano), la incidencia de la enfermedad meningococica disminuyo a unas proporciones interepidemicas normales de 1/100.000 por ano. Sin embargo, desde principios de los anos noventa, la incidencia anual de la enfermedad ha aumentado gradualmente a 2/100.000. El numero total de aislamientos recibidos en el laboratorio de referencia nacional subio de 96 en 1.991 a 210 en 1.996. Casi todos los casos ocurrieron en la region norte de Belgica: en 1.993 se observo un aumento constante de enfermedad meningococica en la provincia de Amberes y en 1.995 en Flandes Occidental.
MA 02.09 A Ph I/II Study of BGB324, a Selective AXL Inhibitor as Monotherapy and in Combination with Erlotinib in Advanced NSCLC
Authors: D. Gibbons, L. Byers, D. Gerber, J. Peguero, D. Micklem, M. Yule, J. Lorens
Journal: Journal of Thoracic Oncology (2017)
Caso de tuberculosis en un vuelo de larga distancia: dificultades de la investigación
Authors: A Vassiloyanakopoulos, G Spala, E Mavrou, C Hadjichristodoulou
Journal: Eurosurveillance (1999)

En 1996, se notifico la transmision de Mycobacterium tuberculosis entre pasajeros a bordo de un vuelo de larga distancia (1). Anteriormente se habian publicado otros casos, especialmente desde los Centers for Disease Control (CDC) que, en su dia, propusieron unos criterios para la investigacion epidemiologica de tales casos (2). Mas recientemente, en 1998, la Organizacion Mundial de la Salud (OMS) ha publicado unas pautas en relacion con dichas investigaciones, resaltando la duracion del vuelo (mas de ocho horas), la capacidad de contagiar del paciente indice y la proximidad de los expuestos (3).
TMOD-29. DEVELOPMENT OF PRECLINICAL GLIOMA MOUSE MODELS FOR GENE FUSIONS
Authors: Barbara Oldrini, Carolina Marques, Massimo Squatrito
Journal: Neuro-Oncology (2017)

The occurrence and importance of gene fusions in glioma has been appreciated only recently, largely due to high throughput technologies, and gene fusions have been indicated as one of the major genomic abnormalities in GBM. The functional role of the vast majority of these alterations is completely unexplored. Although these events are rare, not exceeding 1% to 2% per rearrangement. Some of them will be instantly translatable given the accessibility of existing tyrosine kinase inhibitors (TKI) that either have been FDA- approved or are under investigation in other indications. The Trk receptor family comprises three transmembrane proteins indicated as TrkA, TrkB and TrkC receptors, and are encoded by the NTRK1, NTRK2 and NTRK3 genes, respectively. These receptor tyrosine kinases are expressed in human neuronal tissue, and play a critical function in the nervous system through activation by neurotrophins. Recurrent gene fusions involving NTRK1, 2 and 3 genes have been recently identified in both low and high-grade gliomas. Through the use of CRISPR/Cas9 technology we are developing preclinical mouse models of the gene fusions involving the family of the Trk receptor family. We have identified eighteen different fusions involving NTRK genes in gliomas. Our preliminary data on one of those fusions, Bcan-Ntrk1, indicate that we are able to generate gene rearrangements in neuronal stem cells and that this fusion is able to generate tumors in combination with p53 loss in vivo. Cells isolated from these tumors are sensitive to the pan-Trk inhibitor Entrectinib. This approach will be particularly useful to conduct preclinical trials using Trk inhibitors and study possible mechanism of resistance to such inhibitors.
Synchronous immune alterations mirror clinical response during allergen immunotherapy
Authors: Amedee Renand, Mohamed H. Shamji, Kristina M. Harris, Tielin Qin, Erik Wambre, Guy W. Scadding, Peter A. Wurtzen, Stephen J. Till, Alkis Togias, Gerald T. Nepom, William W. Kwok, Stephen R. Durham
Journal: Journal of Allergy and Clinical Immunology (2017)