tbuckley/cabot-search huggingface dataset:
STEM-14. RSAD1 IS A NOVEL TARGET IMPLICATED IN THE GLIOBLASTOMA STEM CELL STRESS RESPONSE
Authors: Briana Prager, Qi Xie, Jeremy Rich
Journal: Neuro-Oncology (2017)

Glioblastoma is highly resistant to chemo- and radiotherapy. Despite treatment, median survival is only 12-15 months. Tumor cells rely upon elevated stress response pathways to survive and maintain a rapid proliferative rate in the harsh tumor microenvironment. Glioblastoma stem cells (GSCs) are particularly enriched in their ability to survive in the context of nutrient deprivation, high reactive oxygen species, DNA damage and radiation. Upregulation of heat shock proteins (HSPs) and the unfolded proteins response (UPR) promote cell survival during stress. These pathways are elevated in glioblastoma and knockdown induces chemosensitivity and cell death. We performed an in silico analysis using The Cancer Genome Atlas database to identify genes that were upregulated in glioblastoma vs. normal brain, and genes for which higher expression was associated with worse survival. We intersected these gene sets to identify genes that may contribute to worse outcome in glioblastoma. In vitro validation of our tops hits revealed that RSAD1 (Radical S-Adenosyl Methionine Domain Containing 1) is critical for GSC survival and proliferation. We have further identified RSAD1 as a novel dependency in GSCs and a putative mediator of the UPR in glioblastoma stem cells. RSAD1 expression is increased in GSCs versus their differentiated counterparts and GSCs have a stem cell-specific transcriptional peak at the RSAD1 promoter as determined by histone 3 lysine 27 acetyl chromatin immunoprecipitation followed by deep sequencing (H3K27ac ChIP-seq). RSAD1 knockdown significantly impairs proliferation in GSCs in vitro. Preliminary evidence suggests that RSAD1 binding partners enrich for UPR regulators and HSPs. Future work will determine whether RSAD1 promotes survival in GSCs through activation of the UPR, and therefore represents a potential chemo- or radiosensitizer of GSCs with the potential to serve as a novel target for synergistic therapy in glioblastoma.
Does bevacizumab plus chemotherapy matter in metastatic colorectal cancer patients with mucinous histology? A multicenter, retrospective analysis on 685 patients
Authors: V. Catalano, F. Bergamo, C. Cremolini, B. Vincenzi, F. Negri, F. Graziano, P. Giordani, P. Alessandroni, R. Intini, L. Rumanò, D. Rossini, B. Borelli, D. Santini, D. Sarti, M.B. Rocchi, S. Lonardi, A. Falcone, V. Zagonel, R. Mattioli
Journal: Annals of Oncology (2017)
Les infections à Hantavirus en Finlande
Authors: O Vapalahti, A Vaheri, H Henttonen
Journal: Eurosurveillance (1995)

Les hantavirus, responsables de la fievre hemorragique avec syndrome renal (FHSR) et de pneumonies, sont tres repandus dans le monde entier (1). Le virus est transmis a l'homme par l'inhalation d'excretats provenant de rongeurs. Pres de 200 000 personnes presentent une FHSR chaque annee, principalement en Eurasie
Relevance of immunohistochemical (IHC) surrogate reclassification of pT1 breast cancer in luminal-like subtypes: a 15-years long-term observational retrospective study
Authors: A. Emiliani, A. Iannace, G. Manna, T. Losanno, I. Speranza, F.S. Di Lisa, L. Filomeno, S. Pecorari, J.R. Giron Berios, P. Seminara
Journal: Annals of Oncology (2017)
P3.02-078 Establishing Malignant Pleural Mesothelioma Primary Cell Lines Using the 3D Spheroid Method Produces a Model with Better Tumor Architecture
Authors: Y.Y. Cheng, K. Sarun, K. Lee, C. Clark, N.C. Cheng, N. Van Zandwijk, S. Klebe, G. Reid
Journal: Journal of Thoracic Oncology (2017)
MA 07.09 ALK/ROS1/TRK Inhibitor TPX-0005 Effectively Overcomes Clinical Resistance Solvent Front Mutations
Authors: J.J. Cui, D. Zhai, W. Deng, E. Rogers, J. Ung, X. Zhang, H. Zhang, Z. Huang, J. Whitten, J. Lim, Y. Li
Journal: Journal of Thoracic Oncology (2017)
EXTH-67. TG02, A BRAIN-PENETRANT MULTI-CDK INHIBITOR, POTENTLY SUPPRESSES MYC-DRIVEN GLIOBLASTOMA
Authors: Jonathan Tsang, Sarah Sung, Laura Gosa, Kristan Meetze, Timothy Cloughesy, David Nathanson
Journal: Neuro-Oncology (2017)

MYC is a central driver of tumorigenesis in many malignancies, including the universally lethal glioblastoma (GBM). However, developing direct inhibitors of MYC have proven challenging. One appealing alternative strategy to target MYC-driven cancers is to interfere with the signaling program necessary to facilitate MYC-dependent transcription. Cyclin-dependent kinase 9 (CDK9) has emerged as an attractive candidate through its function as a critical regulator in the transcriptional elongation of MYC and its target genes. Using a panel of patient-derived GBM cells, here we demonstrate that CDK9 inhibition with the brain-penetrant multi-CDK inhibitor, TG02, potently suppresses GBM cell growth. Importantly, the anti-GBM efficacy of TG02 strongly correlates with MYC expression and appears to be independent of methylation status, suggesting a critical role for CDK9 in MYC-driven GBMs. These preliminary results indicate that CDK9 may be an actionable therapeutic target in GBM with aberrant MYC signaling and, importantly, the clinical stage oral small molecule, TG02, is an appealing drug candidate for GBM with elevated MYC activity. Ongoing in vivo efficacy studies are evaluating TG02 in clinically relevant MYC-driven GBM mouse models.
Surtos de origem alimentar no Norte de Portugal, 2002
Authors: A M Correia, G Gonçalves, Margarida Saraiva
Journal: Eurosurveillance (2004)

Em Portugal, em Outubro de 2001, as toxinfeccoes alimentares colectivas (TAC) foram incluidas num sistema de alerta e resposta. Indo de encontro a essa orientacao, o Centro Regional de Saude Publica do Norte criou um programa de vigilância epidemiologica das TAC. Com este relatorio pretende-se fazer uma descricao sumaria dos dados gerados por esse programa durante o ano de 2002. Cinquenta e nove por cento dos 27 surtos de TAC estudados pelos Delegados de Saude Concelhios durante 2002 foram conhecidos nas 72 horas a seguir a sua ocorrencia. Foram identificados 577 casos de doenca, tendo ocorrido internamento hospitalar em 9,6% dos doentes. Nao se registou qualquer obito. O agente etiologico foi isolado em produtos biologicos dos doentes em 63,0% dos surtos de TAC, e nos alimentos em 18,5% das situacoes. A Salmonella enterica foi responsavel por 73,7% dos surtos nos quais houve confirmacao laboratorial do agente etiologico. A maioria das refeicoes que estiveram na origem dos surtos foi confeccionada em estabelecimentos de restauracao ou em casa particulares (75,0% dos surtos). Os factores contributivos mais vezes identificados foram o processamento, preparacao e manipulacao inadequados dos alimentos. Pensamos que a vigilância epidemiologica das TAC, enquanto elemento fundamental duma estrategia mais alargada de promocao da seguranca alimentar, deve ser reforcada em Portugal.
TMIC-38. MODULATION OF CANCER CELL METABOLISM AND IMMUNE PHENOTYPE BY TTFIELDS
Authors: Eric Wong, Johnson Fong, Oliver Xu, Kenneth Swanson
Journal: Neuro-Oncology (2017)

Therapeutic low dose alternating electric fields (TTFields) have been demonstrated to disrupt cells during mitosis leading to aberrant mitotic exit. Cells exposed to TTFields exhibit evidence of endoplasmic reticulum stress, surface expression of immune stimulatory stress marker proteins calreticulin, and the secretion of the Alarmin/DAMP protein, HMGB1. Co-culture of bone marrow derived macrophages with TTFields-treated CT26 cells resulted in the up-regulation of cell surface activation markers that was reversed by the addition of anti-HMGB1 antibodies. Macrophages co-cultured with TTFields-exposed cells also produced increased levels of pro-inflammatory chemokines and the reduction of anti-inflammatory cytokines, further supporting the hypothesis that TTFields induce anti-tumor immunity as part of their mechanism of action. In addition, cells exposed to TTFields exhibited reductions in levels of culture media acidification. Analysis of intracellular metabolites showed evidence for an increase in mitochondrial respiration products, including increased ATP, GTP and phosphocreatine as well as increases in early intermediates from the glycolysis and glutaminolysis pathways. These metabolic changes are consistent with a decreased requirement for lactate production. Exposure to both increased levels of lactate and low pH have been demonstrated to influence the differentiation and stabilization of immunosuppressive subsets of both myeloid and lymphoid cells that promote immune tolerance needed for tumor immune evasion. Thus, low pH within the tumor likely contributes to tumor aggressiveness and has been correlated with poor clinical outcome in glioma patients. Analysis of urine from TTFields-treated patient revealed a correlation between low pH and poor clinical outcome in TTFields-treated patients. Together, these data suggests a novel mechanism by which TTFields increase tumor cell immunogenicity and alter cancer cell metabolism which perturbs immune suppressive functions within the tumor microenvironment facilitating immune recognition and rejection. This model of TTFields action may provide an additional basis to improve treatment efficacy.
Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation
Authors: Yubin Lei, Lingling Liu, Shujing Zhang, Shicheng Guo, Xiaoqing Li, Jiucun Wang, Bo Su, Yuchao Fang, Xiaofeng Chen, Hengning Ke, Wufan Tao
Journal: Molecular Cancer (2017)

Lung cancer is the leading cause of cancer death worldwide. However, the molecular mechanisms underlying lung cancer development have not been fully understood. The functions of histone deacetylases (HDACs), a class of total eighteen proteins (HDAC1-11 and SIRT1-7 in mammals) that deacetylate histones and non-histone proteins, in cancers are largely unknown.Hdac7 +/-/K-Ras mice and HDAC7-depleted human lung cancer cell lines were used as models for studying the function of Hdac7 gene in lung cancer. Kaplan-Meier survival analysis was performed to explore the relationship between HDAC7 expression and prognosis of human lung cancers. Recombinant lentivirus-mediated in vivo gene expression or knockdown, Western blotting, and pull-down assay were applied to investigate the underlying molecular mechanism by which Hdac7 promotes lung tumorigenesis.The number and burden of lung tumor were dramatically reduced in Hdac7 +/-/K-Ras mice compared to control K-Ras mice. Also, in Hdac7 +/-/K-Ras mice, cell proliferation was significantly inhibited and apoptosis in lung tumors was greatly enhanced. Similarly, cell proliferation and anchorage-independent growth of human lung cancer cell lines expressing shHDAC7 were also significantly suppressed and apoptosis was dramatically elevated respectively. Mechanistic study revealed that Hdac7 mutation in mouse lung tumors or HDAC7 depletion in human tumor cell lines resulted in significantly enhanced acetylation and tyrosine-phosphorylation of Stat3 and HDAC7 protein directly interacted with and deacetylateed STAT3. The Hdac7 mutant-mediated inhibitory effects on lung tumorigenesis in mice and cell proliferation/soft agar colony formation of human lung cancer cell lines were respectively reversed by expressing dnStat3. Finally, the high HDAC7 mRNA level was found to be correlated with poor prognosis of human lung cancer patients.Our study suggests that Hdac7 promotes lung tumorigenesis by inhibiting Stat3 activation via deacetylating Stat3 and may shed a light on the design of new therapeutic strategies for human lung cancer.
P1.03-038 A Phase I Trial of Afatinib and Bevacizumab in Untreated Patients with Advanced NSCLC Harboring EGFR-Mutations: OLCSG1404
Authors: S. Kuyama, K. Kudo, T. Tamura, T. Nishi, D. Harada, A. Bessho, N. Fujimoto, D. Minami, K. Aoe, T. Ninomiya, K. Kiura
Journal: Journal of Thoracic Oncology (2017)
PUB026 PD-L1 Expression, Using SP142 and 22C3 Antibody Clones, in NSCLC Patients with Known Status of EGFR and ALK Genes
Authors: T. Kucharczyk, P. Krawczyk, B. Jarosz, A. Grenda, K. Reszka, J. Pankowski, K. Wojas-Krawczyk, M. Nicoś, J. Szumiło, T. Trojanowski, J. Milanowski
Journal: Journal of Thoracic Oncology (2017)
NIMG-76. SURFACE-ENHANCED RAMAN SPECTROSCOPY (SERS) FOR INTRAOPERATIVE BRAIN TUMOR IMAGING AND PHOTOTHERMAL THERAPY
Authors: Hamed Arami, Edwin Chang, Chirag B Patel, Steven James Madsen, Ryan Miller Davis, Robert Sinclair, Sanjiv S Gambhir
Journal: Neuro-Oncology (2017)

Developing intraoperative methods to better delineate brain tumor margins could maximize the extent of tumor resection while minimizing post-operative sequelae. Raman spectroscopy has recently been used for intraoperative brain tumor detection in humans. However, that tumor delineation was based on minor differences between Raman scattering of different endogenous biomolecules in tumor versus normal brain tissue. In contrast, cancer imaging using surface-enhanced Raman spectroscopy (SERS) offers significantly higher sensitivity and signal specificity. Gold nanoparticles (GNPs) have been extensively used as SERS nanoprobes, due to their surface plasmon characteristics and biocompatibility. In addition, surface plasmon resonance in GNPs results in photothermal effects, which can be used for tumor ablation. Therefore, successful delivery of GNPs to brain tumors could aid in SERS-assisted detection and ablation of the tumors. Here, we present results of the application of this highly sensitive approach for brain tumor imaging and photothermal therapy, using an orthotopic human glioblastoma xenograft model (U87-MG modified to express eGFP and luciferease) in mice. The Raman GNPs consist of a gold core coated with silica and a monolayer of active Raman molecules. We labelled the GNPs for near-infrared fluorescent (NIRF) imaging. Then, GNPs were injected into tumors intracranially at 3mm depth, and brains were analyzed by Raman and NIRF imaging, scanning electronic microscopy (SEM) and histology. Raman and NIRF imaging of the brains (n=3) at 1 and 24h post-injection times, showed that GNPs diffused only within the tumor, enabling delineation of brain tumor margins 24h after their injection. SEM analysis confirmed GNP diffusion into the tumor tissues and showed ablation marks in the tumor areas resulting from local high temperatures generated by surface plasmon resonance of the GNPs during Raman imaging. These results suggest potential application of SERS for simultaneous detection and photothermal ablation of the tumors at a microscale range during surgical resection.
MA 14.12 Detecting Epidermal Growth Factor Receptor Mutation Status in Patients with Lung Adenocarcinoma Using Radiomics and Random Forest
Authors: T. Jia, J. Xiong, X. Li, J. Ma, Y. Ren, Z. Xu, X. Cai, J. Zhang, J. Zhao, X. Fu
Journal: Journal of Thoracic Oncology (2017)
TMIC-23. ENDOTHELIN B RECEPTOR EXPRESSION IN MALIGNANT GLIOMAS: THE PERIVASCULAR IMMUNE ESCAPE MECHANISM OF GLIOMAS
Authors: Shinji Nakashima, Naohisa Miyagi, Tetsuya Negoto, Nobuyuki Takeshige, Kiyohiko Sakata, Motohiro Morioka, Yasuo Sugita
Journal: Neuro-Oncology (2017)

In order to clarify the role of endothelin B receptors (ETBRs) in gliomas, we analyzed cell cultures and surgical specimens of gliomas using RT-PCR and immunohistochemistry. RT-PCR measured the absolute expression of ETBR mRNA in twelve samples, which included gliomas that were classified using the World Health Organization (WHO) classification system Grade I to IV, as well as two glioblastoma cell lines (CCF-STTG1 and U87-MG). Using immunohistochemistry, 77 glioma specimens were evaluated for their expression of ETBR and infiltrating T lymphocytes, including an analysis of cytotoxic T cells (CTLs) and regulatory T lymphocytes (Tregs). We reclassified these 77 gliomas based on WHO classification 2016. Isocitrate dehydrogenase 1 (IDH-1) mutations were identified in 21 cases. The number of ETBR-positive vessels in the glioblastomas (Grade IV) was significantly higher than in WHO Grade I gliomas, IDH mutant astrocytoma and oligodengroglioma. The ETBR expression rate (defined as the number of ETBR-positive blood vessels divided by the total number of blood vessels) in the glioblastomas was higher than the ETBR expression rate in the other gliomas. In addition, the cases which had an ETBR expression rate of 50% or higher exhibited fewer infiltrating CTLs and more infiltrating Tregs compared to the cases with an ETBR expression rate <50%. These results suggest that ETBR expression during neo-angiogenesis may interfere with the homing of CTLs around the tumor and be involved in the immune escape mechanism of gliomas.
GENE-54. A NOVEL MUTATION IN PRKCA IS THE MAJOR DRIVER OF CHORDOID GLIOMAS
Authors: Shai Rosenberg, Iva Simeonova, Franck Bielle, Maite Verreault, Isabelle Le Roux, Mailys Daniau, Arun Nadaradjane, Vincent Gleize, Sophie Paris, Yannick Marie, Marine Giry, Marc Polivka, Dominique Figarella Branger, Marie-Hélène Aubriot-Lorton, Chiara Villa, Alexandre Vasiljevic, Emmanuèle Lechapt-Zalcman, Michel Kalamarides, Karima Mokhtari, Stefano Pagnotta, Antonio Iavarone, Anna Lasorella, Emmanuelle Huillard, Marc Sanson
Journal: Neuro-Oncology (2017)

Chordoid glioma (ChG) is a characteristic, slow growing and well-circumscribed diencephalic tumor, whose mutational landscape is unknown. We analyzed primary chordoid glioma samples by whole exome sequencing, RNAseq, Sanger sequencing, RT-PCR and immunohistochemistry. We determined subcellular localization, kinase activity and effects on proliferation of wild-type and mutant PRKCA. We found that 14/15 ChG harbor the same PRKCAD463H mutation. PRKCA encodes the Protein kinase C (PKC) isozyme alpha (PKCα) and is mutated in a wide range of human cancers. However the hot spot ChG PRKCAD463H mutation is novel. Here we show that ChGs express the PRKCAD463H mutant at higher levels than the wild-type PRKCA gene. Pathway analysis of the expression data shows that PRKCAD463H is strongly associated with the activation of protein translation initiation (EIF2) pathway. Compared to wild type PKCα, the PKCα D463H mutant protein is depleted from the cell membrane in vitro and from adherens junctions in vivo and shows diffuse cytoplasmic localization. The PKCα D463H mutant exhibits increased kinase activity towards the PKCα substrate MARCKS (Myristoylated Alanine-Rich C Kinase Substrate) and enhances proliferation of human astrocytes. PRKCAD463H is the hallmark mutation of ChG and provides new targeting opportunities in ChG patients. Our results support a more complex change than a simple gain of function, and suggest that the mutation results in a neomorphic enzyme with very specific properties.
NIMG-71. DIFFUSION CHARACTERISTICS OF PEDIATRIC DIFFUSE MIDLINE GLIOMAS WITH HISTONE H3 K27M MUTATION USING APPARENT DIFFUSION COEFFICIENT HISTOGRAM ANALYSIS
Authors: Mariam Aboian, David A Solomon, Cassie Kline-Nunnally, Anna Vardapetyan, Elizabeth Tong, Yi Li, Erin Felton, Steve Braunstein, Sabine Mueller, Soonmee Cha
Journal: Neuro-Oncology (2017)

Diffuse midline gliomas with histone H3 K27M mutation are a new group of gliomas diagnostic entity as of the 2016 WHO guidelines. We previously showed no difference between wildtype and K27M mutant midline tumors in their enhancement patterns, border characteristics, and presence of necrosis on clinical protocol MRI. Herein, we evaluated the use of diffusion weighted imaging as a mechanism to distinguish histone H3 K27M mutant from wildtype midline gliomas. 44 pediatric patients (<21 years old) with diffuse midline gliomas were confirmed with histone H3 K27M mutation testing. In 31 eligible patients, whole tumor voxel based ADC histograms were generated and evaluated. Among 18 intratentorial and 13 supratentorial gliomas, 23 (74%) of the tumors were histone H3 K27M mutant. There was no difference between the K27M mutant and wildtype midline gliomas with respect to tumor ADC mean, median, minimum, maximum, or 1st to 99th percentiles. Average ADC values for diffuse midline gliomas were 1.28 x10-3 mm2/sec (95% CI 1.21, 1.34). Patients who survived less than one year after diagnosis have lower median ADC values (1.10 x 10-3 mm2/sec, 95% CI 0.90, 1.30) as compared to patients that survive more than a year (1.46 x 10-3 mm2/sec, 95%CI 1.19, 1.67, p=0.057). Analysis of diffusion characteristics in diffuse midline gliomas originating in the thalamus and pons did not identify a difference in ADC histogram parameters based on presence of histone H3 K27M mutation. However, patients with shorter survival exhibit reduced diffusion within the tumor as compared to longer survivors. Diffusion characteristics of pediatric diffuse gliomas identify a subgroup of patients with lower diffusivity that corresponds to lower overall survival at one year after diagnosis, while showing no difference in diffusion characteristics between histone H3 K27M mutant and wildtype midline tumors.
OA 18.06 Three-Dimensional Assessment of Spread Through Air Spaces in Lung Adenocarcinoma: Insights and Implications
Authors: Y. Yagi, K. Tabata, N. Rekhtman, T. Eguchi, X. Fu, J. Montecalvo, P. Adusumilli, M. Hameed, W. Travis
Journal: Journal of Thoracic Oncology (2017)
GENE-40. CIRCULATING TUMOR DNA ANALYSIS IN PATIENT-DERIVED XENOGRAFT MODELS OF GLIOBLASTOMA
Authors: Nieves Perdigones, Sydney Connor, Lauren Hartman, Tania Contente-Cuomo, George Reid, Havell Markus, Michael Berens, Harshil Dhruv, Muhammed Murtaza
Journal: Neuro-Oncology (2017)

Extracellular tumor-derived DNA in body fluids (also known as circulating tumor DNA or ctDNA) is being widely studied for noninvasive tumor genotyping, tracking clonal evolution, monitoring treatment response and early detection of cancer. In patients with glioblastoma (GBM), ctDNA is more readily detectable in cerebrospinal fluid as compared to blood plasma. In literature, sensitivity for mutation detection in DNA from CSF is ~60% compared to ~10% in plasma DNA. However, CSF is difficult to sample and other body fluids need to be studied carefully. To develop new strategies for plasma ctDNA detection and increase tumor DNA shedding into plasma in patients with GBM, we sought to utilize body fluid samples form patient derived xenograft (PDX) models. In this context, any human DNA detectable in mouse plasma is derived from the tumor xenograft. Hence, we developed a human-specific multiplexed droplet digital PCR assay to detect and accurately quantify plasma ctDNA in PDX models derived from patients with GBM. This assay is composed of 8 paired primer/probe sets, fluorescently labeled, with careful design accounting for unique diploid amplification, variable regions, cross amplification between species, and most common genomic aberrations in GBM. We will share results demonstrating the analytical validity of the assay as well as utility in testing approaches for increasing ctDNA yield and shedding from GBM tumors.
Tendencias de la infección genital por clamidias en el Centro-Oeste de Irlanda, 2001-2006
Authors: D Whyte, J Powell, M Horgan, N O’Connell, R FitzGerald, R Monahan, T Greally
Journal: Eurosurveillance (2007)

La infeccion genital por Chlamydia trachomatis (IGCT) es la infeccion de transmision sexual (ITS) bacteriana mas frecuente en Irlanda.
Coqueluche : une ancienne maladie de nouveau à l’ordre du jour
Authors: C H Wirsing von König, Marion Riffelman
Journal: Eurosurveillance (2007)

Dans ce numero d’Eurosurveillance, deux articles se font l’echo de donnees concernant la coqueluche. Dans d’autres editions de cette revue publiees en 2007 (janvier et mai), deux autres articles ont egalement traite des donnees epidemiologiques relatives a la coqueluche.