tbuckley/cabot-search huggingface dataset:
Cólera en la region mediterránea: epidemia en Albania
Authors: D Greco, I Luizzi, A Sallabanda, A Dibra, E Kacarricy, L Shapo
Journal: Eurosurveillance (1995)

En los anos 1990, la epidemia de colera causada por Vibrio cholerae 01El Tor se expandio desde el Norte de Pakistan al Mediterraneo. Casosesporadicos de colera y focos epidemicos fueron declaradosen 1993 en varios paises del Sur de Europa y del Este. Igualmente senotificaron casos en Crimea y Turquia; en Grecia, solo seregistro un caso importado (1).
P3.07-008 Development of Immunomonitoring Assays for Dendritic Cell-Based Lung Cancer Immunotherapy
Authors: O. Palata, L. Sadílková, N. Hradilova, I. Vančurová, D. Myšíková, H. Mrazkova, R. Lischke, R. Špíšek, I. Adkins
Journal: Journal of Thoracic Oncology (2017)
La sorveglianza della tubercolosi è migliorata
Authors: J M Watson
Journal: Eurosurveillance (2000)

Nel 1996, e stato raggiunto un accordo (consensus statement) sulla sorveglianza della tubercolosi in Europa, che ha stabilito che la raccolta dei dati su tutti i casi di tubercolosi venga effettuata a livello locale (1). Tale accordo, sostenuto dall'International Union Against Tuberculosis and Lung Disease, dall'Organizzazione Mondiale della Sanita e dai rappresentanti dei paesi europei, ha raccomandato l'impiego di un set comune di dati e che i dati individuali vengano confrontati e analizzati a livello locale e regionale/nazionale (1). Al tempo stesso, e stato organizzato un programma (Euro TB), finanziato dell'Unione Europea, per la collazione e l'analisi di questi dati standardizzati. I risultati di questa collaborazione sono gia stati pubblicati (2,3).
Hyper-endémie prolongée d’infections à méningocoque B en Seine Maritime, France, janvier 2003 à juin 2005
Authors: Pascale Rouaud, A Perrocheau, M K Taha, C Sesboué, A M Forgues, I Parent du Châtelet, D Lévy-Bruhl
Journal: Eurosurveillance (2006)

Entre janvier 2003 et juin 2005, une hyper-endemie d’infections a meningocoques est survenue dans le departement de la Seine-Maritime en France. Quatre-vingt-six cas ont ete declares, representant une incidence moyenne annuelle de 2,7 cas pour 100 000 habitants, compare a une incidence annuelle nationale de 1,6. Une zone plus particulierement touchee a ete identifiee, incluant la ville de Dieppe et ses environs (26 cas, soit une incidence annuelle de 12 cas pour 100 000). Cette epidemie etait due a N. meningitidis phenotype B:14:P1.7,16 appartenant au complexe clonal ST-32/ET-5. Trente-et-un cas de B14:P1.7,16 ont ete confirmes par phenotypage au Centre National de Reference des meningocoques (CNR) associes a un taux de mortalite (19%) et une proportion de purpura fulminans (42%) particulierement eleves. Les groupes d’âge les plus touches etaient les jeunes de 15 a 19 ans et les enfants entre un an et neuf ans. En 2003, les autorites sanitaires ont mis en place une surveillance epidemiologique renforcee. Parallelement, elles ont lance des campagnes d’information sur la maladie aupres des medecins et du public. En 2004, le comite national des vaccinations a evalue l’interet d’un vaccin a base de vesicules de membranes externes de N. meningitis B developpe sans licence en Norvege, qui confererait une protection contre la souche B14:P1.7,16. En 2006, le Ministere de la Sante decide de proposer une vaccination avec ce vaccin chez les sujets âges de un a 19 ans en Seine Maritime.
GENE-28. CLINICAL AND MOLECULAR ANALYSES OF LONG-TERM SURVIVORS OF GLIOBLASTOMA
Authors: Danielle Burgenske, Jeanette Eckel-Passow, Paul Decker, Matthew Kosel, Ryan Youland, Dioval Remonde, Thomas Kollmeyer, Hugues Sicotte, Alissa Caron, Caterina Giannini, Daniel Lachance, Robert Jenkins, Jann Sarkaria
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is a uniformly fatal disease with standard treatments conferring a median overall survival of only 14.6 months. Because of limited local control with these frontline therapies, less than 10% of patients will survive five years. The molecular mechanisms that promote improved therapeutic responses in this long-term survivor group remain unknown. Therefore, we strove to identify features that render these typically refractory tumors highly sensitive to radiation and/or temozolomide (TMZ). We identified GBM patients who survived more than five years (long-term survivors; LTS) and who had tissue available for molecular analysis. These patients were frequency matched to patients who survived less than two years (short-term survivors; STS) by IDH mutation, TERT promoter mutation and 1p/19q codeletion. We focused our analyses on patients who were TERT-mutation only (IDH wild-type and non-codeleted), triple-negative and IDH-mutation only (TERT wild-type and non-codeleted). We molecularly characterized patients using the following technology: Illumina EPIC methylation array, RNA sequencing, Oncoscan copy number array, and DNA mutation sequencing. The Cancer Genome Atlas (TCGA) data were used to classify patients into methylation and RNA expression subtypes. We analyzed 22 LTS (9 TERT-mutation only, 3 triple-negative, 8 IDH-mutation only, and 2 triple positive) and 43 STS (35 TERT-mutation only, 5 triple-negative and 3 IDH-mutation only). Generally, LTS were younger at diagnosis (45 vs. 59 years), experienced longer median survival (6.9 years vs. 1.2 years) and median progression-free survival (5.2 years vs. 0.7 years). LTS were also more likely to have gross total resection (68% vs. 56%; p=0.16). Moreover, STS experienced recurrence at a higher rate than LTS (84% vs 59%; p=0.03). All IDH-mutation only patients were classified into LGm1-LGm2 methylation subtypes, regardless of outcome. Similarly, all TERT-mutation only and triple-negative patients were classified as LGm4-LGm6 methylation subtypes, regardless of outcome. Our results suggest differences exist between LTS and STS.
MA 18.09 Enrollment of Minorities, the Elderly, and Women in Lung Cancer Clinical Trials
Authors: N. Duma, C. Yu, J. Paludo, J. Vera Aguilera, M.Gonzalez Velez, C. Haddox, A. Mansfield, R. Go, A. Adjei
Journal: Journal of Thoracic Oncology (2017)
Quantitation of N-acetyl-S-(9,10-dihydro-9-hydroxy-10-phenanthry)-L-cysteine (Phe-epoxide-NAC) in human urine: comparison with glutathione-S-transferase genotypes.
Authors: Stephen S. Hecht, Priyanka A. Rao, Pramod Upadhyaya, Peter W. Villalta, J. Bradley Hochalter
Journal: Cancer Research (2006)

5666   Polycyclic aromatic hydrocarbons (PAH) are likely to play a major role in cancer induction in smokers and certain occupationally exposed groups. Humans vary widely in their abilities to metabolically activate or detoxify PAH, and these variations may be related to cancer risk. Many studies have examined the possible relationship between variants in genotypes of carcinogen metabolizing enzymes such as glutathione- S -transferases and cancer risk. Phenotyping may be a better way to determine inter-individual differences in PAH metabolism. Our laboratory has developed methods for analysis of phenanthrene metabolites in urine, as an approach to PAH metabolite phenotyping. Methods to measure metabolic activation by the diol epoxide pathway and detoxification by phenol formation have already been published. In this study, we developed a method to quantify Phe-epoxide-NAC, the urinary meracapturic acid end-product of glutathione conjugation of phenanthrene-9,10-epoxide, and compared levels of this metabolite to variants in glutathione- S -transferase genotypes. [D 10 ]Phe-epoxide-NAC was used as internal standard. Urine samples were purified by passage through cation exchange, anion exchange, and reverse phase solid phase extraction cartridges. Analysis and quantitation was achieved using liquid chromatography-electrospray ionization-tandem mass spectrometry with selected reaction monitoring, in the negative ion chemical ionization mode. The transition  m/z  356 (M − 1) −  →  m/z  209 [M − (H 2 O+ CH 2 CH(COOH)NHCOCH 3 )] was monitored. Clean peaks corresponding to two diastereomers of Phe-epoxide-NAC were observed in 15 urine samples while none were detected in another 17. Levels of this metabolite varied from not detected ( GSTM1  present than in  GSTM1  null individuals (15.8 ± 30.1, N = 22). Levels of this metabolite were also higher in individuals with both  GSTM1  and  GSTT1  present than in those with both  GSTM1  and  GSTT1  null. These results suggest that  GSTM1  and  GSTT1  presence or absence do affect levels of PAH detoxification through the mercapturic acid pathway. This is the first report of quantitation of a PAH mercapturic acid in human urine thus allowing a phenotype-genotype comparison for this important carcinogen detoxification pathway.
ANGI-08. PREDICTING IN VIVO TUMOR GROWTH AND ANGIOGENESIS WITH AN MRI CALIBRATED BIOPHYSICAL MODEL
Authors: David Hormuth, Angela Jarrett, Xinzeng Feng, Thomas Yankeelov
Journal: Neuro-Oncology (2017)

Tumor induced angiogenesis is a critical element of supporting tumor growth and invasion. The variation in intratumoral vascularity and perfusion inevitably alters tumor cell proliferation and death, as well as the efficacy of chemo- and radiotherapies. Accurate characterization of tumor growth, the recruitment of new vessels, and the death (or collapse) of existing vessels may provide a valuable tool for optimizing therapy for an individual patient. To this end, we have developed a predictive biophysical model of tumor growth and angiogenesis that is calibrated on an individual basis using diffusion-weighted MRI (DW-MRI) and dynamic contrast enhanced MRI (DCE-MRI). The spatial-temporal evolution of tumor cells and blood volume were described using two coupled, partial differential equations consisting of proliferation, diffusion, and death terms. To evaluate this model, rats (n = 4) with C6 gliomas were imaged seven times over 10 days with DW-MRI and DCE-MRI. DCE-MRI was used to identify tumor boundaries and quantify blood volume, while DW-MRI was used to estimate cellularity within the tumor. The first three imaging time points were used for model calibration, while the remaining four time points were used for validation of model predictions. The predicted tumor growth had less than 12.1% error in tumor volume at all prediction time points compared to the data. At the voxel-level, a strong level of agreement was observed for both tumor cell number (concordance correlation coefficient (CCC) = 0.49) and blood volume (CCC = 0.65). These preliminary results indicate the potential predictive accuracy of calibrating subject-specific biophysical models with clinically relevant imaging measurements.
STEM-30. CDK5 INHIBITION RESOLVES PKA/cAMP-INDEPENDENT ACTIVATION OF CREB1 SIGNALING IN GLIOMA STEM CELLS
Authors: Subhas Mukherjee, Carol Tucker-Burden, Emily Kaissi, Austin Newsam, Monica Chau, Changming Zhang, Bhakti Diwedi, Manali Rupji, Sandra Seby, Jeanne Kowalski, Jun Kong, Renee Read, Daniel Brat
Journal: Neuro-Oncology (2017)

Glioma stem cells (GSCs) represent only a small subset of the intratumoral cell population but greatly influence the growth of the high-grade glioblastoma. GSCs favor neoplastic growth in part through deregulated asymmetric cell division, which enhances self-renewing populations and disturbs the balance between self-renewal and multipotent differentiation. To delineate/discover mechanisms and potential therapeutic targets relevant to self-renewal of GSCs, we performed a genetic screen for kinases that reverse the tumor phenotype of our novel adult Drosophila brain tumor model and found that knock down of the brain specific dCdk5 was highly effective. Unlike other cyclin dependent kinase members, dCdk5 and its human ortholog CDK5 (79% identity) do not regulate the cell cycle in normal cells, but do so in cancer cells through over activation of the CDK5 pathway. We demonstrate that GBMs highly express CDK5 mRNA and protein, likely related to copy number gains of chromosome 7, with a strong positive correlation with stem cell markers and marked effects on tumor-propagating properties in limiting dilution assays. Using patient-derived GBM stem cells grown in vivo as orthotopic xenografts, we show that pharmaceutical suppression of CDK5 inhibits self-renewal of GSCs, at least partially by suppressing CREB1 activation independently of PKA/cAMP. Analysis of TCGA GBM data indicates that the gene expression of CDK5 and asymmetric cell division markers segregate non-mesenchymal patient samples from mesenchymal clusters. This may indicate a preferential dependence of non-mesenchymal tumors on the CDK5 signaling axis and sensitivity to its inhibition. Together, our results demonstrate that direct CDK5-CREB1 regulation is required for GSC self-renewal and that CDK5 antagonism could be an effective therapeutic approach for GBM.
SCDT-15. DRUG-LOADED AND EGFR-TARGETED NANO-CONSTRUCTS SUCCESSFULLY TREAT INTRACRANIAL GLIOMA IN MOUSE MODELS
Authors: Martyn Sharpe, David Baskin
Journal: Neuro-Oncology (2017)

We have developed a peptidyl-targeted nanovector system, the nanosyringe, capable of transferring large amounts of hydrophobic dyes/drugs into cells bearing a targeted surface epitope, in vitro and in vivo. The nanovector is made from a hydrophobic, oxidized graphene core, with polyethylene glycol (PEG) tendrils attached via amide bonds. This untargeted nanovector is both water soluble and has a large internal volume that can be filled with hydrophobic drugs/dyes. Targeting the nanovectors toward specific epitopes is achieved by covalently linking targeting peptides to the PEG terminals, using peptides selected from phage-display libraries. The nanosyringe interior is readily loaded with hydrophobic drugs/dyes and when the GE11 peptide is attached, these nanosyringes are taken up by EGFR-expressing cells along with the nanosyringe payload. In our in vitro and in vivo studies we demonstrate that binding of nanosyringe activates EGFR, which in turn initiates binding/internalization and transfer of payload into the cells. Nanosyringe binding to EGFR causes activation of the clathrin coated-pit endosomal pathway, internalizing the nanosyringes within endosomes. When drugs such as doxorubicin are loaded into nanosyringes, we observe initial transfer into cellular plasma/endosomal membranes, followed by diffusion into the cytosol, then into DNA. In intracranial mouse models of glioma, when drugs are loaded into EGFR-targeted nanosyringes, we observe both enhanced efficacy of chemotherapeutics and lower off-target toxicity. In GBM, highly effective chemotherapeutics such as Vinblastine and Doxorubicin are seldom used clinically because of their off-target toxicity. When comparing native and nanosyringe-loaded chemotherapy in an aggressive intracranial glioma mouse model we observe a huge enhancement (>7-fold) in animal survival, and far lower off-target toxicity. 38% of vinblastine and 50% of doxorubicin treated animals out survived the empty vector controls by more than a year.
Salmonella enteritidis y S. typhimurium en Europa occidental en 1993-1995: informe de vigilancia a cargo de Salm-Net
Authors: I. S.T. Fisher
Journal: Eurosurveillance (1997)

La vigilancia ha sido definida como “la recogida continua de datos, su analisis y la distribucion regular y rapida de informacion resultante a quienes tienen necesidad de su conocimiento para emprender una accion” (1). Esto se consigue de dos maneras. En primer lugar, a corto plazo, mediante la identificacion e investigacion de epidemias y, en segundo lugar, mediante el estudio de tendencias a de la incidencia y prevalencia de enfermedades para evaluar necesidades e intervenciones. Los datos historicos son importantes para conocer incidencias esperadas de las infecciones: con frecuencia, las epidemias se identifican cuando la incidencia observada de una enfermedad supera la incidencia prevista. Uno de los objetivos de la red europea de vigilancia de salmonellas, Salm-Net, es crear una base de datos de salmonellas aisladas de personas en Europa (2). Se esta creando un grupo basico de datos por cada aislamiento, para que posteriormente pueda utilizarse en la identificacion de tendencias en la incidencia de salmonelosis de Europa occidental. Este informe analiza datos sobre los serotipos de salmonella notificados con mayor frecuencia entre 1993 y 1995.
RARE-23. INFRATENTORIAL GLIOBLASTOMA: INCIDENCE AND ASSOCIATED PROGNOSTIC FACTORS AMONGST OVER 1000 CONSECUTIVE GLIOBLASTOMAS
Authors: Fara Dayani, Edward F Chang, Philip V Theodosopoulos, Michael W McDermott, Mitchel S Berger, Manish Aghi
Journal: Neuro-Oncology (2017)

Infratentorial glioblastoma is rare in adults. We analyzed glioblastomas resected at our institution 2004-2014 to determine any distinguishing characteristics of infratentorial glioblastomas. Glioblastomas cases involving cerebellar parenchyma were reviewed. 58 newly diagnosed glioblastomas with cerebellar involvement fell into 3 cohorts: (1) purely cerebellar glioblastomas (n=11=19.0%); (2) glioblastomas that began supratentorial and developed infratentorial tumor in continuity with supratentorial tumor (n=28=48.3%); (3) glioblastomas that began supratentorial and developed infratentorial tumor at a distant site from supratentorial tumor (n=19=32.7%). Mean ages at cerebellar glioblastoma diagnosis, gender distribution, and diameter of the cerebellar glioblastoma were 49.4,57.21,53.2 years(P=0.19), 55%,57%,53% Males (P=0.4), 3.5,2.6,1.5 cm (P=0.002) for cohorts 1,2,3 respectively. The most common preoperative symptoms were: ataxia (n=9) and headache (n=8). Surgical procedures were: biopsy (9%), STR (73%), and GTR (18%). 18% of patients developed hydrocephalus needing shunt placement a mean of 4.5 months after diagnosis. Median OS from GBM diagnosis for the 3 cohorts was 10.6,12.4,16.5 months, compared to 15.8 months for purely supratentorial GBMs(P= 0.04, 0.6, 0.4 respectively). We performed focal analyses of patients with supratentorial GBMs who developed cerebellar foci (cohorts 2/3). Median time from diagnosis of supratentorial GBM to developing infratentorial GBM was 4.5,10 months (P=0.4).16.8%,25.0% (P=0.02) patients received bevacizumab, and 28.6%,31.8% (P=0.04) received GTR in cohort 2,3. The most common sites of supratentorial tumor were temporal (45%), frontal (62%). Median OS from identification of infratentorial GBM was 6,7 months. Purely cerebellar glioblastomas at diagnosis conferred a better prognosis than supratentorial GBMs. Local or distant spread of supratentorial GBMs to the cerebellum did not worsen prognosis, with the latter occurring earlier in the disease course. Purely cerebellar glioblastomas should be treated aggressively given their good prognosis.
ANGI-19. THE AXON GUIDANCE RECEPTOR PLEXIN-B2 PROMOTES TUMORIGENICITY OF GLIOBLASTOMA
Authors: Yong Huang, Rut Tejero-Villalba, Santosh Kesari, Hongyan Zou, Roland Friedel
Journal: Neuro-Oncology (2017)

Invasive growth is a major determinant of the high lethality of malignant gliomas. Plexin-B2, an axon guidance receptor regulating migration and proliferation of neural progenitors during development, is upregulated in gliomas, but its function therein remains poorly understood. Combining bioinformatic analyses, immunoblotting and immunohistochemistry of patient samples, we have demonstrated previously that Plexin-B2 is consistently upregulated in all types of human gliomas and that its expression levels correlate with glioma grade and poor survival. Activation of Plexin-B2 by Sema4C ligand in glioblastoma cells induced actin-based cytoskeletal dynamics and invasive migration in vitro. We have now conducted CRISPR/Cas9 mediated knockout of the Plexin-B2 gene in human glioma stem cell lines (GSC), and we are studying the function of Plexin-B2 in glioma tumorigenicity with PDX intracranial transplant models. Our preliminary data suggests an important role of Plexin-B2 in promoting tumor cell invasion and lethality. Similarly, in vitro experiments with 3D glioma organoid cultures suggest that Plexin-B2 promotes the self-renewal characteristics of GSC. Lentiviral overexpression of Plexin and Semaphorin molecules in GSC allows us to conduct structure-function studies to elucidate molecular mechanisms of Plexin-B2 action. Our results indicate that Plexin-B2 promotes glioma invasion and stem cell features of glioma stem cells, and they identify Plexin-B2 as a potential novel player in glioma malignancy. Targeting the Plexin-B2 pathway may represent a novel therapeutic approach to curtail invasive growth of glioblastoma.
NIMG-94. FEASIBILITY OF PROTON MRS FOR ASSESSING CEREBRAL METABOLIC ACTIVITY OF AN ATKINS-BASED DIET IN PATIENTS WITH GLIOMA
Authors: Karisa C Schreck, Adam Berrington, Bobbie M Barron, Lindsay Blair, Adam Hartman, Eric Kossoff, Linda Easter, Chris Whitlow, Fang-Chi Hsu, Mackenzie C Cervenka, Jaishri O Blakeley, Peter B Barker, Roy E Strowd
Journal: Neuro-Oncology (2017)

There is renewed interest in exploring treatment strategies which target metabolic pathways involved in gliomagenesis, including ketogenic diets. The purpose of this pilot study was to evaluate the feasibility of proton MR spectroscopy (MRS) to detect the cerebral metabolic activity of an 8-week GLioma Atkins-based Diet (GLAD) in patients with glioma. Patients with grade 3-4 astrocytoma were enrolled after completing adjuvant chemotherapy, before first recurrence. GLAD consisted of 20gm carbohydrate restriction (modified Atkins diet) along with 2 days per week of intermittent fasting (caloric restriction to 20% recommended daily allowance). MRS was performed in both the lesion and a mirror voxel in the contralateral hemisphere at baseline and week 8. Data were analyzed using the ‘LCModel’ program using a basis set of three ketone bodies (acetone (Ace), beta-hydroxybutyrate (BHB), acetoacetate (AcAc)), 2-hydroxyglutarate (2-HG), citrate (Cit), and some standard metabolites. Interim analysis is reported after 12 patients enrolled; mean age 49 ± 11 years; 8 male; 5 grade IV astrocytomas. Two patients did not complete the study; two were excluded for incomplete data. As expected, concentrations of tNAA (p<0.028) and Lac (p<0.023) were different between lesion and normal brain at baseline. Ketone body concentrations were nearly undetectable at baseline; however by week 8, Ace and BHB were reliably detected in both lesion ([Ace]=0.08->0.32 ± 0.19, p=0.005; [BHB]=0.07->0.6 ± 0.68, p=0.05) and contralateral brain ([Ace]=0.01->0.16 ± 0.14, p=0.015; [BHB]=0->0.23 ± 0.25, p=0.021). In the lesion, BHB rose by 1.0mM from baseline to Week 8 in IDH1 mutant as compared to a decrease by -0.13mM in wild-type astrocytomas (p<0.002). The increase in BHB but not Ace was also significantly greater in patients with higher dietary compliance as measured by urine ketones (p<0.03). These preliminary results demonstrate the ability of brain MRS to monitor the metabolic consequences of a ketogenic diet in patients with high-grade glioma.