tbuckley/cabot-search huggingface dataset:
SURG-16. THE TREATMENT FOR PRIMARY CERVICAL SPINAL TUMORS
Authors: Kei Ando, Shiro Imagama, Masayoshi Morozumi
Journal: Neuro-Oncology (2017)

Primary tumors of the spine are uncommon and represent < 5% of all bone neoplasms as compared with secondary metastatic disease, multiple myeloma, and lymphoma. Moreover, the treatment of cervical spine tumors requires complex therapeutic and reconstructive strategies depending on the tumor’s pathology, location, aggressiveness, and proximity to the surrounding neurovascular structures, and influence the prognosis. A purpose of this study is to explore the clinical characters, surgical methods, and prognosis of the primary cervical spinal tumors. The subjects were 35 patients with an average age of 45 years, 20 male and 15 female. We examined the histological types, surgical methods, and prognosis. Malignant tumors were 11 including 4 chondromas, 3 chondrosarcomas, 1 angiosarcoma, fibrosarcoma, alveolar soft part sarcoma (ASPS), and epithelioid hemangioendothelioma. Intermediate tumors were two giant cell tumors (GCT), and benign tumors were 24 (8 osteochondromas, 6 osteoid osteomas, 3 Langerhans cell histiocytosis (LCH), 2 osteoblastoma, 1 Aneurysmal bone cyst (ABC), Pigmented villonodular synovitis (PVNS), and fibroma. As surgical methods, total resections with spinal reconstruction were performed in 21 cases (18 benign tumors, 2 GCT, and fibrosarcoma), subtotal resections in 10 cases (all of malignant tumors except for fibrosarcoma), and biopsies in 2 LCHs. Two cases (chondrosarcomas) underwent several surgeries for relapse. All of benign tumors showed no relapse and adequate bony healing. Eight of 11 malignant tumors were died on disease. Remaining 3 cases of disease free were 1 fibrosarcoma and 2 chordomas with adjuvant heavy particle beam therapy. Total resection has been difficult in some of these tumors, particularly malignant tumors, due to complicated anatomical features with vertebral artery and carotid sheath (highly risky anatomical region). The improvement of the further surgery technique and establishment of adjuvant therapy are expected in future.
TMOD-11. HUMAN STEM CELL BASED MODEL OF MEDULLOBLASTOMA
Authors: Miller Huang, Jignesh K Tailor, Qiqi Zhen, Emily K Nash, Joanna Phillips, Sorana Morrissy, Marcel Kool, Stefan M Pfister, Fredrik J Swartling, Michael D Taylor, Austin Smith, William A Weiss
Journal: Neuro-Oncology (2017)
P3.02-033 Pathological and Molecular Alterations after First and Second Generation EGFR-TKI Therapy in Patients with EGFR-Mutated Lung Adenocarcinomas
Authors: H. Uruga, T. Fujii, G. Yamamoto, S. Moriguchi, Y. Takahashi, K. Ogawa, R. Murase, S. Mochizuki, S. Hanada, H. Takaya, A. Miyamoto, N. Morokawa, K. Kishi
Journal: Journal of Thoracic Oncology (2017)
P1.09-007 Targeting MET/TAM Receptors in Mesothelioma: Are Multi-TKIs Superior to Specific TKI?
Authors: S. Gray, A. Baird, D. Easty, M. Jarzabek, L. Shiels, C. Wu, A. Soltermann, S. Raeppel, L. Macdonagh, M. Melovic, H. Lambkin, B. Stanfill, D. Nonaka, C. Goparju, B. Murer, D. O'Donnell, L. Mutti, M. Barr, S. Finn, S. Cuffe, H. Pass, K. O’Byrne, I. Schmitt-Opitz, A. Byrne
Journal: Journal of Thoracic Oncology (2017)
P2.01-017 Study on the Effect of Apatinib Salvage Treatment of Advanced Non-Small Cell Lung Cancer
Authors: Z. Xu, C. Xu, W. Wang, Q. Xu, W. Zhuang, Z. Song, Y. Zhu, M. Shi, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
Warfarin is associated with lower cancer incidence, finds study
Authors: Jacqui Wise
Journal: BMJ (2017)

Use of the anticoagulant warfarin was associated with a lower risk of new cancers in people over 50 in a large observational study published in JAMA Internal Medicine .1

Researchers used national registry data to identify 1 256 725 people born from 1924 to 1954 who were living in Norway from 2006 to 2012. Of this cohort, 92 942 (7.4%) were taking warfarin. Warfarin users were older, …
Evaluation of QoL as a predictor of chemotherapy-induced toxicity
Authors: S. Mariotti, V. Formica, R. Pellegrino, A. Nardecchia, J. Lucchetti, A.M. Morelli, A. Laudisi, C. Morelli, N. Renzi, V. Massimiliani, L. Donnarumma, S. Riondino, I. Portarena, M. Roselli
Journal: Annals of Oncology (2017)
Abstract #3024: Association between 8-oxoguanine DNA glycosilase (OGG1) activity, polymorphisms and expression DNA in healthy subjects
Authors: Giuseppe Matullo, Alessandra Allione, Simonetta Guarrera, Valeria Simonelli, Mariarosaria D'Errico, Silvia Polidoro, Valeria Romanazzi, Alessia Russo, Andrea Zijno, Marco Peluso, Paola Porcedda, Flavia Barone, Anna Minoprio, Laura Narciso, Filomena Mazzei, Eugenia Dogliotti
Journal: Cancer Research (2009)

A number of studies on the association between BER gene polymorphisms and cancer risk have been published, although the relation between BER phenotypic assays and polymorphisms has been investigated only in small studies. In order to investigate the role of SNPs/haplotypes on DNA repair phenotypes and their potential impact on cancer risk, we performed a BER genotype-phenotype correlation study. BER is a generic DNA repair system, which is rendered highly specific by the existence of different glycosilases which carries out the initial step of the pathway, i.e. recognition and removal of altered base. In particular 8-oxoguanine DNA glycosilase (OGG1) is responsible for the removal of 8-oxoguanine. Thirty ml of blood were collected by venipuncture from 225 healthy volunteers (mean age 24±6 ys) and PBMC were separated by Ficoll gradient centrifugation; cryopreserved cells were then stored in liquid nitrogen until use. The sampling was carried out between November and December 2007 and all the partecipants answered detailed questionnaires relating to smoking, alcohol consumption, dietary habits and lifestyle. To measure BER activity we performed an  in vitro  repair assay in which an oligonucleotide is constructed containing 8-oxoguanine at a specific site, and labelled at one end with a fluorescent dye. After incubation with the sample cell extract, the activity of the repair enzyme is detected by the analysis of the products of the cleaved oligonucleotide by PAGE and image analysis. Moreover we analyzed also 4 single nucleotide polymorphisms (SNPs) in  OGG1  gene (rs1052133, rs293795, rs293796, rs159153) and  OGG1  gene expression as measured by real-time PCR in PBMC.   Our data showed a large inter-individual variation of OGG1 activity (fmoles/microgram 2.25±0.52, range 0.86-3.65). A statistically significant association has been found between OGG1 enzyme activity and the  OGG1  rs1052133 (p Cys in position 326, with the Cys allele having a decreased activity. Moreover, we also observed a weak correlation between  OGG1  SNP rs293795 and  OGG1  expression levels (p=0.028, 0.039, 0.066, and 0.13 by using 4 different endogenous genes as reference, ABL, RPII, G6PD and GUS , respectively) in whole blood cells. Our results support to further investigate  OGG1  rs1052133 and rs293795 polymorphisms in cancer association studies due their functional role that possibly confers increased cancer risk in combination with other low-penetrance genotypes.   Citation Information:  In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 3024.
OA 17.03 First-Line Nivolumab plus Platinum-Based Doublet Chemotherapy for Advanced NSCLC: CheckMate 012 3-Year Update
Authors: R. Juergens, M. Hellmann, J. Brahmer, H. Borghaei, S. Gettinger, L. Chow, D. Gerber, S. Laurie, J. Goldman, F. Shepherd, W. Geese, T. Young, X. Li, S. Antonia
Journal: Journal of Thoracic Oncology (2017)
STEM-29. LAMINA ORGANIZATION PROMOTES MAINTENANCE OF BRAIN TUMOR INITIATING CELLS IN GLIOMA
Authors: Sisi Lai, Briana Prager, Xiuxing Wang, Jeremy Rich
Journal: Neuro-Oncology (2017)

Glioblastoma is one of the most aggressive tumors, containing self-renewing glioma stem cells (GSCs) at the apex of the tumor hierarchy that drive tumor growth. Global chromatin regulation contributes to development of the cellular hierarchy, suggesting that targeting chromatin regulators may disrupt GSCs. Nuclear peripheral anchoring of heterochromatin is mainly mediated by interactions with lamina structure Lamin A/C, Lamin B, and the inner nuclear membrane protein Lamin B Receptor (LBR). LBR mediates peripheral localization at early stages of development, and then Lamin A/C assumes tethering during terminal differentiation. Here, we report that GSCs preferentially express LBR at both the transcriptional and translational levels, whereas differentiated progeny preferentially express Lamin A/C, phenocopying developmental regulation. Interrogation of chromatin marks of active enhancer and promoters through histone 3 lysine 27 acetyl (H3K27ac) ChIP-Seq revealed stem cell specific activation peaks at LBR locus. Targeting LBR expression by RNA interference potently reduced GSC cellular proliferation, self-renewal in vitro, and tumor growth in vivo. Leveraging an in silico discovery approach based on promoter sequence analysis, we found that GABPB1 mediates upstream transcriptional regulation of LBR in GSCs. We are currently defining the specific anchored chromatin domains at the nuclear peripheral tethered by LBR required for GSC maintenance to better understand the lamina organization dependency in glioblastoma, potentially informing the development of novel targeted therapeutics.
O impacto da onda de calor sobre a mortalidade diaria na Inglaterra e Gales e a utilização de estimativas de mortalidade semanais rápidas
Authors: H Johnson, S Kovats, G McGregor, J Stedman, M Gibbs, H Walton
Journal: Eurosurveillance (2005)

Este artigo descreve a analise retrospectiva do impacto da onda de calor de 2003 sobre a mortalidade na Inglaterra e Gales, comparando-as com as estimativas rapidas da Oficina de estatisticas nacionais (Office for National Statistics, ONS), do sistema de notificacao em rotina dos obitos semanais. Os dados de mortalidade entre o 4 e o 13 Agosto de 2003, quando as temperaturas foram muito superiores as normais para Inglaterra, foram comparados com as medias para os mesmos periodos entre 1998 e 2002. A onda de calor de Agosto de 2003 foi associada com um aumento importante da mortalidade a curto prazo, especialmente em Londres. As concentracoes de ozono e de particulas no ar tambem alcancaram um nivel alto durante a onda de calor. Globalmente, foram observados na Inglaterra e Gales 2139 obitos em excesso (16%), sendo os maiores de 75 anos os mais afectados. A area de Londres, com um aumento de 59% de obitos nas pessoas de mais de 75 anos, foi a regiao mais afectada pela onda de calor. O excesso estimado de mortalidade foi superior ao de outras ondas recentes no Reino Unido. 
Cada semana a ONS transmete o numero estimado de obitos. A primeira indicacao clara de um aumento substancial foi publicada no 21 de Agosto de 2003. Foi obtida assim uma primeira avaliacao rapida do numero de obitos imputaveis a onda de calor. Ela reflete o padrao de obitos diarios associados aos dias mais quentes, mas subestima o excesso de mortalidade que foi detectado pela analise posterior.
Abstract 15273: Multidisciplinary Treatment for Fulminant Myocarditis
Authors: Shunsuke Saito, Koichi Toda, Teruya Nakamura, Shigeru Miyagawa, Yasushi Yoshikawa, Satsuki Fukushima, Keitaro Domae, Yasumasa Tsukamoto, Fusako Sera, Yasushi Sakata, Yoshiki Sawa
Journal: Circulation (2016)

Introduction: Fulminant myocarditis is one of the most challenging diseases to diagnose and treat. We sought to examine the outcomes of our multidisciplinary treatment strategy for fulminant myocar...
GENE-31. DETECTION OF MGMT PROMOTER METHYLATION LEVELS WITH MS-HRM IN PATIENTS WITH GLIOBLASTOMA
Authors: Shinji Yamashita, Kiyotaka Yokogami, Hideo Takeshima
Journal: Neuro-Oncology (2017)

The methylation status of O6-methylguanine-DNA methyltransferase (MGMT) gene promoter is not only the predictive marker in adult glioblastoma multiforme (GBM) but also acts as an information useful for clinical decision-making in elderly patients with GBM. Although pyrosequencing analysis has been introduced as the gold standard for evaluating the methylation status of MGMT, many institutions and studies still employ methylation-specific polymerase chain reaction (MSP) since this method is cost-effective and does not require special analyzers. Although MSP shows good correlation with the prognosis of GBM patients treated with Stupp protocol, it has some limitations, such as ambiguity in judgment and non-applicability for evaluating heterogeneously methylated samples. In this study, we focused on the methylation-sensitive high-resolution melting (MS-HRM) for an alternative to MSP. The methylation levels of 6 glioma cell lines were estimated by MS-HRM, and the data was validated by the bisulfite sequencing of cloned alleles, which is another gold standard for quantitatively evaluating methylation levels. Strong correlation was observed between MS-HRM and bisulfite sequencing, indicating that MS-HRM could be a reliable method for estimating methylation levels (Correlation coefficient for #1 primer: 0.959 and #2 primer: 0.960). Methylation levels of 75 samples from patients with GBM were estimated using MS-HRM and compared to that of the MSP data. MS-HRM is superior to MSP in discriminating between responders and non-responders to temozolomide (TMZ) (p value of log-rank test, PFS; MS-HRM: 0.00023, MSP: 0.0035, OS; MS-HRM: 0.00019, MSP: 0.00028). Taken together, our study suggests that MS-HRM is a superior method for detecting MGMT promoter methylation status as compared to MSP.
P1.05-006 Clinicopathological Features of Small-Sized Peripheral Squamous Cell Lung Cancer
Authors: T. Kosaka, S. Nakazawa, N. Kawatani, K. Obayashi, J. Atsumi, T. Yajima, K. Shimizu, A. Mogi, H. Kuwano
Journal: Journal of Thoracic Oncology (2017)
P2.03-034 EGFR Exon 19 Deletion Is Associated with Favorable Overall Survival After First-Line Icotinib Therapy in Advanced NSCLC Patients
Authors: C. Zhang, H. Hou, X. Cheng, D. Gong, H. Liu, H. Yu, W. Zhu, J. Zhu, K. Liu, H. Lv, N. Zhou, J. Cong, D. Liu, L. Yang, M. Jiang, Y. Zhang, L. Chen, Y. Zhu, X. Zhang
Journal: Journal of Thoracic Oncology (2017)
Incidencia del genotipo de Pekín de Mycobacterium tuberculosis en Elche, España: estudio de vigilancia de 13 años
Authors: E Garcia-Pachon, I Escribano, J C Rodriguez, M Ruiz, J M Ramos, J F Navarro, G Royo
Journal: Eurosurveillance (2007)

Las cepas de la familia del genotipo de Pekin de Mycobacterium tuberculosis se han relacionado con brotes epidemicos y multirresistencia. Realizamos un estudio de vigilancia retrospectivo de 13 anos (1993 – 2005) sobre la incidencia de esta cepa en Elche, Espana.
IMMU-27. OPTIMIZING THE COMBINATORY TREATMENT OF LOW-DOSE RADIATION AND INDOLEAMINE-2,3-DEOXYGENASE INHIBITION FOR GLIOBLASTOMA
Authors: Jonatan Ahlstedt, Crister Ceberg, Leif G Salford, Henrietta Nittby Redebrandt
Journal: Neuro-Oncology (2017)

In a previous study, we have found a synergistic effect of indoleamine-2,3-dioxygenase (IDO1)-inhibition using 1-DL-methyl-tryptophan (1-MT) in conjunction with single fraction radiotherapy (RT) for rat glioblastoma (GBM). Using an adaptation of a mathematical model describing synergistic effects of immunotherapy and RT by Serre et al, that is taking a variety of factors into account, we generated the hypothesis that tumor growth could be better attenuated by applying RT in two fractions of 8 Gy instead of one. Three publicly available databases of Affymetrix gene expression array data comparing GBM tissue or GBM stem cells to normal brain tissue were analyzed for difference in IDO1 expression. 12 Fischer 344 rats received intracranial NS1 syngeneic tumor cells and were divided in two groups. One group received combinatory treatment of two fractions of 8 Gy irradiation at day 7 and 14 post tumor graft, as well as intraperitoneal injections of 10 mg 1-MT daily for 10 days starting at day 7 post tumor graft. Survival was measured in number of days to symptom development. IDO1 expression in GBM tissue was significantly increased in two out of three data sets (log2 fold change 2.73, p<0.005, log2 fold change 0.8, p=0.027, log2 fold change 0.049, p=0.087 respectively). In the animal trial, 33 days after inoculation, all controls were dead and only one of six treated animals. Kaplan Meier survival analysis showed significant survival advantage in the treated group (log rank test, p<0.05). There is increasing evidence of immune evasion of glioblastoma utilizing IDO1 expression. Using a mathematical model as support for hypothesis generation, we studied two-fraction RT in combination with 1-MT treatment finding it prolongs life in rats carrying syngeneic glioblastomas. Going forward, this model may be used in hypothesis generation to find the optimal regimen of combinatory treatment for glioblastoma.
Sorveglianza della malaria in Italia: analisi del 1997 e dati provvisori per il 1998
Authors: R Romi, D Boccolini, G Majori
Journal: Eurosurveillance (1999)

La malaria e la patologia infettiva piu frequente tra quelle importate in Italia. Fino alla sua eradicazione, circa 50 anni fa, la malaria e stata endemica nella maggior parte del paese. Da allora, e stato istituito un sistema di sorveglianza allo scopo di identificare casi acquisiti localmente che potrebbero indicare un evento di trasmissione autoctona. Negli ultimi dieci anni, quasi tutte le infezioni di malaria notificate (99,7%) sono state acquisite durante viaggi in zone di endemia e solo pochi casi sono stati classificati come autoctoni (ma non introdotti) (1). Il numero totale di casi importati di malaria e aumentato da 191 nel 1986 a 791 nel 1996. A partire dal 1992, il numero dei casi tra i cittadini italiani si e pressoche stabilizzato, mentre i casi tra gli stranieri sono in continuo aumento (1).
Monogenic Diseases of DNA Repair
Authors: Guido Keijzers, Daniela Bakula, Morten Scheibye-Knudsen
Journal: New England Journal of Medicine (2017)

Maintenance of genomic integrity involves cellular processes tailored to specific types of DNA damage. Monogenic disorders in DNA-repair pathways lead to a spectrum of clinical phenotypes that are not always correlated with our understanding of the affected repair pathway.
Assessment of Fluorodeoxyglucose F18–Labeled Positron Emission Tomography for Diagnosis of High-Risk Lung Nodules
Authors: Amelia W. Maiga, Stephen A. Deppen, Sarah Fletcher Mercaldo, Jeffrey D. Blume, Chandler Montgomery, Laszlo T. Vaszar, Christina Williamson, James M. Isbell, Otis B. Rickman, Rhonda Pinkerman, Eric S. Lambright, Jonathan C. Nesbitt, Eric L. Grogan
Journal: JAMA Surgery (2017)

Clinicians rely heavily on fluorodeoxyglucose F18-labeled positron emission tomography (FDG-PET) imaging to evaluate lung nodules suspicious for cancer. We evaluated the performance of FDG-PET for the diagnosis of malignancy in differing populations with varying cancer prevalence.To determine the performance of FDG-PET/computed tomography (CT) in diagnosing lung malignancy across different populations with varying cancer prevalence.Multicenter retrospective cohort study at 6 academic medical centers and 1 Veterans Affairs facility that comprised a total of 1188 patients with known or suspected lung cancer from 7 different cohorts from 2005 to 2015.18F fluorodeoxyglucose PET/CT imaging.Final diagnosis of cancer or benign disease was determined by pathological tissue diagnosis or at least 18 months of stable radiographic follow-up.Most patients were male smokers older than 60 years. Overall cancer prevalence was 81% (range by cohort, 50%-95%). The median nodule size was 22 mm (interquartile range, 15-33 mm). Positron emission tomography/CT sensitivity and specificity were 90.1% (95% CI, 88.1%-91.9%) and 39.8% (95% CI, 33.4%-46.5%), respectively. False-positive PET scans occurred in 136 of 1188 patients. Positive predictive value and negative predictive value were 86.4% (95% CI, 84.2%-88.5%) and 48.7% (95% CI, 41.3%-56.1%), respectively. On logistic regression, larger nodule size and higher population cancer prevalence were both significantly associated with PET accuracy (odds ratio, 1.027; 95% CI, 1.015-1.040 and odds ratio, 1.030; 95% CI, 1.021-1.040, respectively). As the Mayo Clinic model-predicted probability of cancer increased, the sensitivity and positive predictive value of PET/CT imaging increased, whereas the specificity and negative predictive value dropped.High false-positive rates were observed across a range of cancer prevalence. Normal PET/CT scans were not found to be reliable indicators of the absence of disease in patients with a high probability of lung cancer. In this population, aggressive tissue acquisition should be prioritized using a comprehensive lung nodule program that emphasizes advanced tissue acquisition techniques such as CT-guided fine-needle aspiration, navigational bronchoscopy, and endobronchial ultrasonography.
P3.02-074 Podoplanin-Positive CAF Is Associated with a Higher Number of Single Nucleotide Variants in Cancer Cells in Lung Adenocarcinoma
Authors: S. Nakasone, S. Mimaki, T. Ichikawa, T. Sakai, S. Okada, K. Sekihara, T. Miyoshi, K. Tane, K. Aokage, K. Goto, K. Tsuchihara, M. Tsuboi, G. Ishii
Journal: Journal of Thoracic Oncology (2017)
CSIG-38. REVERSAL OF GLIOBLASTOMA REPLICATIVE IMMORTALITY IN A TERT PROMOTER MUTATION-DEPENDENT MANNER
Authors: Andrew Mancini, Ana Xavier-Magalhaes, Wendy Woods, Kien-Thiet Nguyen, Alexandra Amen, Andrew McKinney, Josie Hayes, Jun Song, Bruno Costa, Pablo Perez-Pinera, Joseph Costello
Journal: Neuro-Oncology (2017)

Hotspot mutations in the promoter region of the Telomerase Reverse Transcriptase (TERT) gene are the third most common recurrent mutation in cancer and occur in over 80% of IDH-wild type glioblastomas (GBMs). These single point mutations reactivate the telomerase complex, enabling cellular immortalization through the indefinite maintenance of telomere length. The transcription factor-binding site created by these point mutations specifically recruits the multimeric transcription factor GABP to the mutant TERT promoter. GABP is composed of the DNA-binding GABPα subunit and the trans-activating GABPβ subunit. GABP can form two transcription factor species – a dimer or a tetramer – depending on which of the structurally distinct GABPβ isoforms is incorporated into the complex. In this study, we show that depletion of the GABP tetramer-forming isoform GABPβ1L silences mutant TERT promoter in GBM cells. TERT promoter mutant cells lacking GABPβ1L fail to express TERT at levels sufficient for immortalization, thus leading to telomere shortening, DNA damage accumulation, and cell death in vitro. Additionally, mice bearing orthotopically xenografted TERT promoter mutant tumors lacking GABPβ1L had reduced tumor burden and prolonged survival in comparison to mice bearing GABPβ1L wild-type tumors. Importantly, loss of GABPβ1L has minimal phenotypic effects in a panel of TERT promoter wild-type cell lines, including a transformed human astrocyte line expressing TERT from its endogenous promoter. Exogenous expression of GABPB1L or TERT is sufficient to halt telomere degradation and loss of cell viability in GABPβ1L-deficient lines bearing the mutant TERT promoter. We have now begun to investigate upstream pathways that regulate GABP tetramer formation as well as co-factors required for GABP-mediated regulation of TERT as targets to reverse immortality in TERT promoter mutant GBM. Together, these results highlight the potentially widespread role of the GABP tetramer in enabling replicative immortality of TERT promoter mutant GBM.
A multiregional proteomic survey of the postnatal human brain
Authors: Becky C. Carlyle, Robert R. Kitchen, Jean E. Kanyo, Edward Z. Voss, Mihovil Pletikos, André M. M. Sousa, TuKiet T. Lam, Mark B. Gerstein, Nenad Sestan, Angus C. Nairn
Journal: Nature Neuroscience (2017)