tbuckley/cabot-search huggingface dataset:
Um surto de queratoconjunctivite a Adenovirus tipo 8 num lar de 3ra idade em Madrid
Authors: J M Sendra Gutierrez, D Martin Rios, I Casas, P Sáez, A Tovar, C Moreno
Journal: Eurosurveillance (2004)

Este estudo descreve e analisa um surto de queratoconjunctivite epidemica que ocorreu entre 2001 e 2002 num lar de 3ra idade em Leganes (cidade no sul de Madrid), sendo o primeiro publicado em Espanha com estas caracteristicas e identificacao de serotipo. 
Estao descritas as caracteristicas sociodemograficas dos casos, a curva epidemica e as taxas de ataque do surto. As comparacoes foram realizadas com o test de chi2 (test exacto de Fischer) para as variaveis qualitativas e o t-test para as quantitativas. Os factores associados a doenca foram estudiados atraves de quadras de contingencia e modelos de regressao logistica.
Um total de 102 casos foram detectados, com uma taxa de ataque de 36,4% para os residentes e 12,9% para os trabalhadores, sem diferencas espaciais ou profissionais. A curva epidemica mostra um modelo de transmissao interpessoal. A analise multivariante identificou entre os residentes os seguintes factores de risco: capacidade de se deslocar livremente dentro do edificio, incontinencia urinaria e utilisacao comun dos banheiros. Nas 34,6% amostras conjunctivais analisadas detecta-se um adenovirus serotipo 8 com uma sequencia genomica identica. O estabelecimento de normas higienicas e sanitarias adequadas para a limpeza de estes lares e para o tratamento dos residentes, assim como um diagnostico precoce e uma boa coordinacao sao factores essenciais para a prevencao e o controlo de estes surtos em comunidades fechadas.
P3.16-007 Incidence and Outcomes of Positive Parenchymal Margins after Lung Resection – an Analysis of 1428 Cases
Authors: P. Villeneuve, A. Kinio, C. Anstee, A. Seely, D. Maziak, F. Shamji, S. Sundaresan, S. Gilbert
Journal: Journal of Thoracic Oncology (2017)
RTHP-08. HIPPOCAMPAL AVOIDANCE WHOLE BRAIN RADIATION THERAPY (HA-WBRT) PLUS SIMULTANEOUS INTEGRATED BOOST (SIB) TO GROSS DISEASE: AN ALTERNATIVE TO WHOLE BRAIN RADIATION (WBRT) WITH STEREOTACTIC RADIOSURGERY (SRS)?
Authors: Emily Schapira, William L Hwang, Stephen Zieminski, Yi Wang, William Mehan, Henning Willers, Kevin Oh, Melin Khandekar, Helen A Shih
Journal: Neuro-Oncology (2017)

WBRT with SRS offers improved intracranial disease control relative to SRS alone but poorer neurocognitive outcomes. HA-WBRT + SIB is an attractive alternative to WBRT with SRS due to omission of a separate stereotactic procedure, reduced treatment time, and potentially safer treatment of large tumors that are poor candidates for SRS. We performed a single-institution, retrospective review of patients treated with HA-WBRT + SIB. Toxicity was graded according to CTCAE v4.0. We identified 24 patients treated with HA-WBRT + SIB between 2014 and 2017 with a median of three SIBs (range: 1 – 12 SIBs) occupying a median volume of 8.9 cm3 (range: 0.6 – 127.0 cm3). Median hippocampal volume was 4.8 cm3 (range: 3.1 – 6.9 cm3). The most common fractionation was HA-WBRT 30 Gy in 15 fractions with SIB to 37.5 Gy using intensity-modulated radiation therapy (n=14) or volumetric-modulated arc therapy (n=10) planning. Median D99% to bilateral hippocampi was 8.0 Gy +/- 0.9 Gy. Median age was 65.7 years. Median follow-up was 6.3 months (range: 0.8 – 34.1 months). The most common diagnosis was non-small cell lung cancer (n=17). The one-year intracranial disease control rate was 70.8%. One patient had hippocampal failure, and two patients had peri-hippocampal failure within five mm of the hippocampal border. VMAT reduced average treatment time per fraction by 48% relative to IMRT (11.0 min vs 21.1 min, p < 0.001). No toxicity greater than grade two was observed. HA-WBRT + SIB is well-tolerated and achieves high intracranial disease control for brain metastases. A prospective comparison of HA-WBRT + SIB versus WBRT with SRS with endpoints of neurocognitive function and intracranial disease control is warranted.
CSIG-28. ASSOCIATION BETWEEN THE EXPRESSION OF FAT1 AND ANTI-INFLAMMATORY SIGNALING MOLECULES IN HUMAN GLIOMA
Authors: Khushboo Irshad, Chitrangda Srivastava, Nargis Malik, Chitra Sarkar, Deepak Gupta, Ashish Suri, Parthaprasad Chattopadhyay, Subrata Sinha, Kunzang Chosdol
Journal: Neuro-Oncology (2017)

Tumor-related inflammation plays a critical role during glioma pathogenesis. Previous report published from our lab has demonstrated the functional role of a novel gene, FAT1, in maintenance of pro-inflammatory microenvironment in human glioma. Subsequently, in the present study, we investigated the association of FAT1 with anti-inflammatory signaling pathways, like TGF-β and IL-10, in human glioma tissues and U87MG/A172 cell lines. To study the functional link, FAT1 gene knockdown was done in U87MG/A172 cells and primary cultures of glioma tumors. mRNA expression of FAT1 and genes belonging to TGF-β and IL-10 pathways was done in fresh-frozen glioblastoma specimens (n=16) by RT-PCR. Gene expression ratios were correlated using Spearman’s analysis. In-vitro primary cultures of surgical gliomas were generated and checked for FAT1 expression level. In primary cultures as well as U87MG/A172, siFAT1 transfection was done to analyze the effect of FAT1 knockdown on anti-inflammatory genes’ expression. Gene expression correlation analysis done using fresh-frozen glioblastoma tissues indicated a positive association between upregulated FAT1 and increased expression of TGF-β2 (p=0.02) and Serpine1 (a TGF-β pathway read-out; p=0.07). Upon FAT1 knockdown, TGF-β2 and Serpine1 levels were observed to decrease in siFAT1-transfected glioma cells as compared to siControl cells. However, FAT1 knockdown led to upregulation of SOCS3, an IL-10 pathway-related gene which facilitates anti-inflammatory response in glioma cell by inhibiting IL-6 signaling. Since FAT1 expression correlated positively with the expression of TGF-β2, FAT1 might have potential involvement in TGF-β2-mediated immunosuppressive microenvironment in glioma. Moreover, it is likely that FAT1 also augments the pro-inflammatory glioma microenvironment in part via SOCS3, which correlated negatively with FAT1 expression. Hence, FAT1 possibly participates in the anti-inflammatory branch of glioma-related inflammation via two diverse mediators, viz, TGF-β2 and SOCS3, which entail further analysis for clarifying the contribution of FAT1 to glioma hallmarks. FUNDING: SERB, DST, India
Reply to Francesco Massari, Vincenzo Di Nunno, and Andrea Ardizzoni's Letter to the Editor re: Robert J. Motzer, Alain Ravaud, Jean-Jacques Patard, et al. Adjuvant Sunitinib for High-risk Renal Cell Carcinoma After Nephrectomy: Subgroup Analyses and Updated Overall Survival Results. Eur Urol 2018;73:62–8
Authors: Robert J. Motzer, Bernard Escudier, Alain Ravaud
Journal: European Urology (2017)
P1.03-022 A Phase 1B Study of TRC105 in Combination with Paclitaxel/Carboplatin and Bevacizumab in Patients with Stage 4 Non-Squamous Cell Lung Cancer
Authors: F. Robert, C. Theuer, M. Jerome, J. Keef, D. Miley
Journal: Journal of Thoracic Oncology (2017)
CSIG-08. MUTANT IDH1 CO-OPERATES WITH ATRX LOSS TO DRIVE THE ALTERNATIVE LENGTHENING OF TELOMERE (ALT) PHENOTYPE IN GLIOMA
Authors: Joydeep Mukherjee, Tor-Christian Aase Johannessen, Shigeo Ohba, Tracy Chow, Lindsey Jones, Ajay Pandita, Russell O Pieper
Journal: Neuro-Oncology (2017)

A subset of human tumors use a recombination-based alternative lengthening of telomere (ALT) pathway to resolve telomeric dysfunction in the absence of TERT activation. In these tumors, which include lower-grade astrocytomas (LGA) and secondary glioblastoma (sGBM), the ALT phenotype is associated with loss-of-function mutations in p53 and ATRX, although these mutations alone are insufficient to drive the process. Because LGA and sGBM also exhibit R132H IDH1 mutations, we examined the possible role of mutant IDH1 in driving ALT-based gliomagenesis. In p53/pRb-deficient human astrocytes, we found that neither expression of mutant IDH1 nor genetic deletion of ATRX was sufficient to drive the ALT phenotype. Combined expression of mutant IDH1 and loss of ATRX, however, resulted in the creation of tumorigenic cells with the ALT phenotype. The tumorigenic IDH1-mutant, ATRX-deficient ALT cells, as well as human IDH1-mutant LGA xenograft cells, consistently downregulated both RAP1 and XRCC1. Furthermore, exogenous re-expression of XRCC1 and/or RAP1 suppressed the ALT phenotype and tumor cell viability. Mechanistically, suppression of RAP1, a component of the telomere-capping shelterin complex, caused telomere dysfunction. Downregulation of XRCC1, a key component of the alternative non-homologous end joining (aNHEJ) pathway, suppressed aNHEJ-mediated lethal fusion of dysfunctional telomeres, and instead allowed IDH1-mutant, ATRX-deficient cells to use homologous recombination and ALT to resolve telomeric dysfunction and escape cell death. These studies show that mutant IDH1 expression initiates telomeric dysfunction and alters DNA repair pathway preference at telomeres, and in doing so co-operates with p53 and ATRX loss to allow cells to overcome a critical bottleneck in gliomagenesis. Agents that alter the linkage between mutant IDH1 and DNA repair pathway preference may therefore be of particular interest in mutant IDH1 driven glioma.
Association Between Inflammatory Markers and Progression to Kidney Dysfunction: Examining Different Assessment Windows in Patients With Type 1 Diabetes
Authors: Nathaniel L. Baker, Kelly J. Hunt, Danielle R. Stevens, Gabor Jarai, Glenn D. Rosen, Richard L. Klein, Gabriel Virella, Maria F. Lopes-Virella
Journal: Diabetes Care (2017)

To determine whether biomarkers of inflammation and endothelial dysfunction are associated with the development of kidney dysfunction and the time frame of their association.Biomarkers were measured at four time points during 28 years of treatment and follow-up in patients with type 1 diabetes in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) cohort. In addition to traditional biomarkers of inflammation (C-reactive protein and fibrinogen), we measured interleukin-6 (IL-6) and soluble tumor necrosis factor receptors 1 and 2 (sTNFR-1/2), markers of endothelial dysfunction (soluble intracellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin [sE-selectin]), and fibrinolysis (total and active plasminogen activator inhibitor-1 [PAI-1]). Renal outcomes were defined as progression to incident chronic kidney disease (stage 3 or more severe) or macroalbuminuria (albumin excretion rate ≥300 mg/24 h). Prospective multivariate event-time analyses were used to determine the association of each biomarker with each subsequent event within prespecified intervals (3-year and 10-year windows).Multivariate event-time models indicated that several markers of inflammation (sTNFR-1/2), endothelial dysfunction (sE-selectin), and clotting/fibrinolysis (fibrinogen and PAI-1) are significantly associated with subsequent development of kidney dysfunction. Although some markers showed variations in the associations between the follow-up windows examined, the results indicate that biomarkers (sTNFR-1/2, sE-selectin, PAI-1, and fibrinogen) are associated with progression to chronic kidney disease in both the 3-year and the 10-year windows.Plasma markers of inflammation, endothelial dysfunction, and clotting/fibrinolysis are associated with progression to kidney dysfunction in type 1 diabetes during both short-term and long-term follow-up.
TMOD-10. MOLECULAR CHARACTERIZATION OF A NOVEL HUMAN CLIVAL CHORDOMA XENOGRAFT MODEL DEMONSTRATES INHERENT TUMOR GENOMIC INSTABILITY
Authors: Ali Haider, Roberto Jose Diaz, Amanda Luck, Nesrin Sabha, Andrew Bondoc, Brian Golbourn, Daniel Picard, Marc Remke, James Loukides, Christian Smith, Michael Cusimano, James Rutka
Journal: Neuro-Oncology (2017)

Patient-derived xenografts (PDXs) retain the genotype of the parental tumors more readily than tumor cells maintained in culture. In order to study the genetics of clival chordoma in the absence of prior radiation we sought to establish a PDX following the primary resection of a clival chordoma. Epicranial grafting of a primary clival chordoma was performed in NOD/SCID mice. Tumors have been passaged serially in mice for 7 generations. Physaliferous cell architecture was demonstrated in the regenerated tumors, which stained positive for Brachyury, Cytokeratin, and S100. The tumors demonstrated bone invasion. Single-nucleotide polymorphism analysis of the tumor xenograft was compared to the parental tumor. We identified homozygous amplification of the T-gene (brachury) and heterozygous loss of CDKN2A. We also identified heterozygous loss of the tumor suppressor FHIT gene, although protein expression was preserved. Accumulation of copy number losses and gains over three generations showed for the first time that there is inherent genomic instability in chordoma. In conclusion, this PDX reproduces the phenotype of clival chordoma. This study is the first to show chromosomal genomic instability in a chordoma that is serially propagated through multiple generations. The genomic instability observed in chordoma may serve as the biological basis for resistance to chemotherapy as is observed for other forms of cancer.
NCOG-03. PERSONALITY TRAITS IN PATIENTS WITH NEUROEPITHELIAL TUMORS – A PROSPECTIVE STUDY
Authors: Jens Gempt, Stefanie Bette, Jennifer Albertshauser, Jasmin Hernandez Cammardella, Corinna Gradtke, Benedikt Wiestler, Lucas Schirmer, Yu-Mi Ryang, Bernhard Meyer, Florian Ringel
Journal: Neuro-Oncology (2017)

Aim of this study was to analyze personality traits in patients with neuroepithelial brain tumors. Personality alteration is a common feature in brain tumor patients, but not much is known about associations between specific personality changes and brain tumors. We assessed potential factors influencing personality such as tumor location, tumor grade and tumor volume and compared them with neuropsychological tests. 73 patients with intrinsic brain tumors were included in this prospective study. Pre- and postoperatively and 3 and 9 months after surgery, the following data were acquired: mini-mental state examination (MMSE), short form health survey (SF-36), Beck’s Depression Inventory II (BDI-II), and the NEO Five-Factor Inventory (NEO-FFI) for the five factors of personality (openness, agreeableness, neuroticism, extraversion, and conscientiousness). Patients with intrinsic brain tumors showed lower scores regarding the factor openness and a decrease of conscientiousness over time compared to the norm population. No significant influencing factors (tumor entity, location) were found regarding personality traits; just a slight correlation between tumor volume and the factor openness was observed. Compared to the normal population, brain tumor patients had higher scores of BDI-II, with a significant preference for women and KPS. Neuroticism was associated with depression and lower mental health, whereas conscientiousness and extraversion show an opposed association. Patients with intrinsic brain tumors have differences in personality traits compared to the control population, with an emphasis on the factor openness. No significant confounding factors like tumor grade, entity, or location were found for personality traits.
TMIC-49. POTASSIUM CHANNEL KIR4.1 AND GLUTAMINE SYNTHETASE ARE DYSREGULATED IN GLIOMA
Authors: Lucas Schirmer, Friederike Liesche, Melanie Barz, Stefanie Bette, Benedikt Wiestler, Rajneesh Srivastava, Claus Zimmer, Florian Ringel, David Rowitch, Bernhard Meyer, Bernhard Hemmer, Jürgen Schlegel, Jens Gempt
Journal: Neuro-Oncology (2017)

The potassium channel KIR4.1 (KCNJ10) and the glutamate catalyzing enzyme glutamine synthetase (GS) are highly expressed in glial cells of the central nervous system. Both glial proteins play important roles in the maintenance of neuronal activity and neurotransmission. Dysfunction of both proteins can result in altered neuronal excitability and may lead to excitotoxicity. We analyzed 35 snap frozen tissue blocks (glioblastoma [GBM], n=22; low grade astrocytoma (LGA), n=8; oligodendroglioma (OG), n=3; oligoastrocytoma, n=2). All glioma samples had a matching tissue specimen from both the tumor core and the adjacent normal-appearing infiltration zone. Molecular subtyping (MGMT, IDH1/2, 1p/19q) was available from tumor specimens. We combined conventional histology and immunohistochemistry with gene expression analysis and western blot. In preliminary analysis, we found downregulation of KIR4.1 and GS in the tumor core of GBM samples as compared to matching infiltration zone tissue of the same patients. In addition, KIR4.1 transcript levels were reduced in GBM core tissue as compared to LGA tumor core. The pan-astroglial protein AQP4 was not different between tumor core and infiltration zone. We observed a tendency that reduced GS transcript levels were associated with increased epileptic activity in GBM patients. In summary, we found that both KIR4.1 and GS were downregulated in tumor core versus infiltration zone tissue. Enhanced neuronal excitability and increased risk for epileptic activity might be associated with lack of KIR4.1 and GS activity.
STEM-41. A SUBSET OF GBM BRAIN TUMOR STEM CELL LINES ARE UNIQUELY DEPENDENT ON GLUTAMINE METABOLISM FOR AMINO ACID SYNTHESIS
Authors: Ian Restall, H Artee Luchman, Samuel Weiss
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) is the most aggressive adult primary brain tumor. Despite a treatment regimen involving surgical resection, chemotherapy, and radiation, GBM patients have a median survival of approximately 15 months. This poor outcome highlights the need for improved therapeutic approaches for GBM patients. A subpopulation of cells that exhibit stem cell properties, termed brain tumor stem cells (BTSCs), are hypothesized to be the source of recurrence and resistance due to their inherent ability to resist treatment, invade into normal tissue, and re-populate a tumor. We have recently found that a subset of BTSC lines are uniquely dependent on glutamine metabolism for survival and maintenance of their stem cell properties. This dependence on glutamine differs from the more conventional view that cancer cells rely on increased glucose metabolism. Inhibiting glutamine metabolism in the sensitive subset of BTSC lines, by targeting the enzyme glutaminase (GLS) that deaminates glutamine to produce glutamate, results in decreased growth, viability, and self-renewal. We have found that inhibition of GLS decreases intracellular glutamate levels and leads to amino acid depletion. Replenishing the amino acid pool using bovine serum albumin rescues the decrease in BTSC growth following GLS inhibition. Intriguingly, the sensitive subset of BTSC lines have low expression of the glutamate transporter termed excitatory amino acid transporter 2 (EAAT2), limiting their glutamate uptake. We are exploring the relationship between reduced glutamate uptake and glutamine dependence; specifically, by asking whether GLS inhibition-resistant BTSC lines become glutamine-dependent after exposure to glutamate transport inhibitors. Taken together, our findings point to a unique dependence on glutamine metabolism for amino acid synthesis, in a subset of BTSC lines. Our long-term goal is to pursue this glutamine dependence as a novel therapeutic strategy to target the cells at the root of this aggressive and lethal disease.
P1.02-030 The Effect of Chronic Obstructive Pulmonary Disease on the Tumor Stroma in Non-Small Cell Lung Cancer
Authors: Y. Ohshio, K. Hayashi, K. Okamoto, R. Kaku, Y. Kataoka, Y. Kawaguchi, M. Ohshio, T. Igarashi, M. Hashimoto, K. Teramoto, J. Hanaoka
Journal: Journal of Thoracic Oncology (2017)
P2.16-027 Comparison of Single Chest Tube Versus Double Chest Tube Drainage After Lung Resection for the Treatment of Non-Small Cell Lung Cancer
Authors: T. Gil, Z. Grochowski, J. Warmus, W. Gocyk, B. Staniec, K. Bederski, P. Kocoń, J. Włodarczyk, P. Hajder, B. Kołodziejczyk, J. Kużdżał
Journal: Journal of Thoracic Oncology (2017)
PTH-044 Risk of stenosis and outcomes following endoscopic resection of large colorectal lesions involving more than 75% of the luminal circumference
Authors: A Emmanuel, S Gulati, M Burt, B Hayee, A Haji
Journal: Gut (2017)

Introduction  Little is known about the risk of stenosis and outcomes following endoscopic resection of colorectal lesions which leave extensive mucosal defects. A limited number of studies suggest significant stenosis rates, although reported outcomes and suggested management are conflicting. We determined the risk of stenosis and outcomes of endoscopic resection leaving mucosal defects≥75% of the circumference.  Method  Patients who underwent endoscopic resection using endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD) and hybrid techniques of colorectal lesions≥2 cm were included. Patients were grouped according to circumferential extent of the mucosal defect. Surveillance colonoscopy was performed at 3 and 12 months. Clinicopathological characteristics and outcomes were compared between groups.  Results  435 lesions≥2 cm were resected using EMR (n=342), ESD (n=45) or hybrid techniques (n=48). Circumferential extent of the mucosal defect was ≥75% in 41 patients. 8 were fully circumferential: 1 caecal lesion and the rest in the recto-sigmoid and rectum. 3 circumferential lesions contained deeply invasive adenocarcinoma and 1 benign lesion ultimately required surgery. 41 lesions with a mucosal defect ≥75% of the circumference had a mean size of 100.5 mm vs 49.0 mm for other lesions (p  Conclusion  The majority of patients with these extensive complex lesions can successfully be treated with endoscopic resection and avoid surgery. However, these patients have a significantly greater risk of complications and recurrence and should be managed in a tertiary institution. Although there is a significant risk of stenosis, it appears that most cases are asymptomatic and spontaneously improve with expectant management.  Disclosure of Interest  None Declared
Chemical Studies on the Components of Normal and Neoplastic Tissues V. The Relative Arginase Activity of Certain Tumors and Normal Control Tissues
Authors: Greenstein, Jesse P., Jenrette, Wendell V., Mider, G. Burroughs, White, Julius
Journal: JNCI Journal of the National Cancer Institute (1941)

Journal Article Chemical Studies on the Components of Normal and Neoplastic Tissues V. The Relative Arginase Activity of Certain Tumors and Normal Control Tissues Get access Jesse P. Greenstein, Jesse P. Greenstein research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Wendell V. Jenrette, Wendell V. Jenrette junior physiologist National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar G. Burroughs Mider, G. Burroughs Mider research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar Julius White Julius White research fellow National Cancer Institute, National Institute of Health, United States Public Health Service Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 1, Issue 5, April 1941, Pages 687–706, https://doi.org/10.1093/jnci/1.5.687 Published: 01 April 1941