tbuckley/cabot-search huggingface dataset:
CBIO-25. HIGH EXPRESSION OF LGR5 MAINTAINS GLIOBLASTOMA STEM CELLS IN A PRONEURAL STATE AND PROMOTES SELF-RENEWAL AND INVASION
Authors: Yuan Xie, Anders Sundström, E-Jean Tan, Voichita Dana Marinescu, Naga Prathyusha Maturi, Malin Tirfing, Andries Blokzijl, Chuan Jin, Lei Chen, Magnus Essand, Fredrik Swartling, Sven Nelander, Yiwen Jiang, Lene Uhrbom
Journal: Neuro-Oncology (2017)

We have recently identified LGR5 as a marker of an immature, neural stem cell-like cell of origin for glioblastoma (GBM). Here we have further investigated the role of LGR5 in GBM. We have found that in a panel of 61 patient-derived GBM stem cell lines, LGR5 was differentially expressed and significantly enriched in those of the proneural subtype. High LGR5 expression in proneural GBM lines (LGR5high-PN) was associated with increased self-renewal and tumorigenicity compared to low expressing (LGR5low) and high expressing mesenchymal (LGR5high-MS) GBM cell lines. Knock-down of LGR5 gene expression in LGR5high-PN lines resulted in decreased self-renewal, while over-expression in both LGR5high-PN and LGR5low lines produced a higher self-renewal capacity of the cells. Furthermore, by comparing LGR5high-PN cells with and without si/shLGR5 we found that LGR5 also could regulate tumor cell invasion in vitro and in vivo. When analyzing transcriptome changes upon LGR5 depletion we detected a transition from the proneural to the mesenchymal subtype in LGR5high-PN GBM cells treated with shLGR5 that was coupled to an upregulation of genes of the TNFA/NFKB pathway. Taken together our data suggests that LGR5 could be an essential regulator of a subset of GBMs. To stratify patients carrying LGR5-dependent GBMs we have identified a number of additional candidate biomarkers, which together with LGR5 could help defining LGR5-driven GBM cells.
SCDT-14. PAM-OBG: A MAOB SENSITIVE PRODRUG INHIBITOR OF MGMT POTENTIATES CHEMORADIOTHERAPY
Authors: David Baskin, Martyn Sharpe
Journal: Neuro-Oncology (2017)

We have developed a prodrug version of the MGMT inhibitor, O6-benzylguanine, PAM-OBG. This prodrug is inert toward MGMT until oxidized by the enzyme MAOB. MAOB is highly elevated in glioma, and levels correlate with poor patient outcome, but is completely absent in human bone marrow. An examination of the enzyme kinetics of human recombinant MAOA and MAOB shows that PAM-OBG is only a good substrate for the latter. PAM-OBG has a Km of only 200 µM with respect to MAOB, whereas the Km is >750 µM for MAOA. PAM-OBG maturation, which gives rise to O6-benzylguanine, is therefore specific toward MAOB, with insignificant reactivity toward MAOA. The gliomal MAOB maturation of the prodrug into the active MGMT inhibitor, O6-benzylguanine, can be observed in vitro and in vivo, using intracranial mouse models of primary glioblastoma multiforme. We have potentiated the anti-GMB activity of DNA alkylating chemotherapeutics Carmustine and Lomustine by six-folds via the pre-administration of PAM-OBG into animals with intracranial tumors. We also demonstrate that PAM-OBG potentiates the action of chemoradiation, using temozolomide and 2Gy whole brain gamma radiation in intracranial mouse models of glioma. Thus, we demonstrate that in addition to its use as an adjuvant in salvage therapy with alkylating agents PAM-OBG may also prove to be highly efficacious in the treatment of GBM alongside Stupp protocol as standard chemoradiation therapy.
EXTH-25. MAXIMUM TOLERABLE DOSE AND EFFICACY OF RHENIUM-186 NANOLIPOSOMES ON WISTAR RATS FOR TREATMENT OF LEPTOMENINGEAL CARCINOMATOSIS
Authors: Maria Guerra Garcia, Beth Goins, Aleksandra Gruslova, Michael Garcia, Andrew Brenner
Journal: Neuro-Oncology (2017)

Leptomeningeal carcinomatosis (LMC) is a clinical complication with an incidence of 5% that occurs when cancer cells invade the leptomeninges and cerebrospinal fluid of patients suffering from malignant tumors. One of the current treatment options, external beam radiation, increases patient survival but is limited by its toxicity at doses higher than 80 Gy. Liposomal encapsulated cytarabine is also approved for this indication. A novel approach to treating primary brain tumors involves the injection of radioactive Rhenium-186 liposomes (RNL) via convection. A previously conducted study discovered that rats with glioblastoma were exposed to doses of up to 1850 Gy of the RNL and presented no overt clinical symptoms or evidence of toxicity. This project’s goal is to assess the potential of RNL as treatment for LMC. The first stage of this study focused on inducing LMC in 10-week-old Wistar rats by stereotaxically injecting approximately 2 x 106 rat C6-Luc glioma cells directly into their left brain ventricle (Quintessential Stereotaxic Injector) and subsequently using bioluminescence imaging (IVIS) to evaluate LMC development. The optimal coordinate for injection was found to be (-1.2 mm, -0.4 mm, -3.8 mm) with bregma being the point of origin. The second stage focused on determining the maximum tolerable radioactivity dose (MTD) of the RNL. Four groups of rats (n=3), including one control group, were intrathecally injected with varying radioactivity doses (0.099 mCi, 0.260 mCi, and 0.414 mCi) using the coordinates previously found. Even the rats administered with the maximum dose tested, 0.414 mCi (approximately 414 Gy), did not present symptoms (weight loss, neurological deficit, etc.) through sacrifice three months after treatment, which is favorable. Full results of the MTD of RNL when applied through the intraventricular route as well as efficacy for LMC will be presented.
The role of the clinical risk group classification system in the management of oncologic patients in need of high complexity of care. A pilot study in the local health unit “USL Umbria 2”
Authors: T. Marzulli, P. Manzi, E. Ricci, G. Alessandrini, M. De Giorgi, D. Franchini, D.M. Alessandra, M. Brugia, I. Fiaschini
Journal: Annals of Oncology (2017)
PATH-39. A NEW MOLECULAR PROGNOSTIC MARKER FOR MALIGNANT GLIOMA
Authors: Takanori Fukunaga, Yuki Fujita, Hideyuki Arita, Naoki Kagawa, Yasunori Fujimoto, Haruhiko Kishima, Toshihide Yamashita
Journal: Neuro-Oncology (2017)

Glioma is the most popular primary CNS tumor and especially, Glioblastoma multiforme (GBM), WHO Grade IV glioma, is the worst prognostic tumor in all systemic cancers. Despite maximum resection followed by chemoradiotherapy, the overall median survival is only about 15 months. To date, molecular research has been revealed some genes which might be important in glioma pathogenesis. Recent study identified somatic mutation in IDH1, which results in directly catalyzing α-ketoglutarate to 2-hydroxyglutarate. It causes epigenetic modiﬁcations, consequently regulate the molecular pathogenesis of glioma. IDH1 mutation is enriched in WHO grade Ⅱ, Ⅲ, and secondary GBM, younger individuals and coincident with increased patient survival. Moreover, a distinct subset of group displays global DNA hypomethylation with hypermethylation of promoter CpG islands (G-CIMP) shows significantly improved outcome, and G-CIMP is tightly associated with IDH1 mutation. The functional importance of G-CIMP, however, remains unclear. In this study, we picked up a specific gene in G-CIMP, investigated its function and influence to glioma, which has not been revealed before. Furthermore, we compared its expression between WHO grades, finally found the difference in overall survival depending on its expression. In conclusion, its gene may be a new prognostic marker for malignant glioma.
TMOD-39. IDENTIFICATION OF EFFICACIOUS AGENTS IN PEDIATRIC EPENDYMOMA THROUGH HIGH-THROUGHPUT DRUG SCREENING IN MATCHING PAIRS OF PATIENT DERIVED ORTHOTOPIC XENOGRAFT (PDOX) NEUROSPHERE AND MONOLAYER CELLS
Authors: Lei Guo, Huiyuan Zhang, Sibo Zhao, Yuchen Du, Lin Qi, Goeun Bae, Frank Braun, Mari Kogiso, Holly Lindsay, Sarah Injac, Patricia Baxter, Jack Su, Clifford Stephan, Peter Davies, Xiao-Nan Li
Journal: Neuro-Oncology (2017)

Ependymoma (EPN) is one of the most malignant tumors and recurrence occurs in almost 50% of patients. Recent transcriptional and copy number profiling of EPN has identified few driver genes and pointed to a balanced genomic profile. Since existing and emerging evidence implicating the ependymoma epigenome as a key player, our study tried to prove that epigenetic modifiers may offer new targeted therapeutic avenues for patients. Matching pairs of neurosphere and monolayer cell cultures from 6 molecularly characterized PDOX mouse models established from distinct sub-types of pediatric Ependymomas (RELPOS and PFA) were treated either with 60 epigenetic chemical compounds alone at 5 doses (0-10 uM) or together with 7853 drugs (mostly in clinical use or trials) for 7 days. Dose-response curves and active area under the curve (AAUC) were constructed to identify active drugs. Relatively long-term treatment (7 day screening) was achieved for high-throughput drug screening and revealed time- and dose-dependent effects of HDAC inhibitors, BRD4 inhibitors in all 6 pairs of neurosphere and monolayer cells. The same treatment strategy was also carried out by combined epigenetic chemical compounds and 7853 mostly used drugs in clinic to see if would yield synergistic or additive effects. It turned out that the combinations of HDAC inhibitor and Proteasome Inhibitor, Brd4 inhibitor and CDK Inhibitor, Brd4 inhibitor and Proteasome Inhibitor and Chk1 inhibitor and Wee1 Inhibitor have significant synergistic effects in tested neurosphere and monolayer Ependymoma cells. The combinations mentioned above could also reduce the colony formation of the monolayer Ependymoma cells. We showed that long-term treatment is feasible for high-throughput drug screening and several epigenetic modifiers have synergistic effects in Ependymomas. Neurospheres and monolayer cells do not always respond equally toward the same drugs, and effective targeting of both subpopulations may need to generate prolonged animal survival times.
P2.09-005 The C-reactive Protein/Albumin Ratio is a Novel Significant Prognostic Factor in Patients with Malignant Pleural Mesothelioma
Authors: S. Takamori, G. Toyokawa, T. Tagawa, F. Kinoshita, Y. Kozuma, T. Matsubara, N. Haratake, T. Akamine, F. Hirai, M. Takenoyama, Y. Ichinose, Y. Maehara
Journal: Journal of Thoracic Oncology (2017)
Trends in Inferior Vena Cava Filter Placement by Indication in the United States From 2005 to 2014
Authors: Mohammed J. Saeed, Tyson E. Turner, David L. Brown
Journal: JAMA Internal Medicine (2017)

Trends in Inferior Vena Cava Filter Placement by Indication in the United States From 2005 to 2014 Although a mortality benefit from inferior vena cava (IVC) filters has never been demonstrated, 1 their use in the United States increased from 2000 in 1979 to 104 114 in 2005. 2,3This study examines trends in inpatient IVC filter placement overall and by indication from 2005 to 2014.Methods | We used discharge data for adults (aged >18 years) from the Nationwide Inpatient Sample (January 1, 2005, to December 31, 2011) and the National Inpatient Sample (January 1, 2012, to December 31, 2014), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality (https://www.hcup-us.ahrq.gov/nisoverview.jsp).Inferior vena cava filter placement was identified by International Classification of Diseases, Ninth Revision, Clinical Modification procedure code 38.7.Contraindications to anticoagulation were as defined by Moore et al. 3 The Washington University Office of Human Research Protection granted this study a waiver from institutional review board oversight.We plotted weighted rates of total IVC filter placement, filter placement by venous thromboembolism (VTE) diagnosis (deep vein thrombosis [DVT] or pulmonary embolism [PE]), and filter placement by contraindication to anticoagulation.We calculated rates of DVT and PE per 100 000 hospital discharges by year.A map of IVC filter placement rates per 100 000 hospital discharges by US census division in 2014 was created to analyze geographic variation.SAS Enterprise Guide, version 7.1 (SAS Institute Inc) was used for all analyses.
Correction to: Genetic engineering of human NK cells to express CXCR2 improves migration to renal cell carcinoma
Authors: Veronika Kremer, Maarten A. Ligtenberg, Rosa Zendehdel, Christina Seitz, Annet Duivenvoorden, Erik Wennerberg, Eugenia Colón, Ann-Helén Scherman-Plogell, Andreas Lundqvist
Journal: Journal for ImmunoTherapy of Cancer (2017)

Unfortunately, after publication of this article [[1][1]], it was noticed that the name of Maarten A. Ligtenberg was displayed incorrectly as Maarten Ligtenberg. The correct author list can be seen above and the original article has been updated to reflect this. 1. 1.[↵][2]1. 2. Kremer V
MA 03.07 The Predictive Value of Interferon-γ Release Assays (IGRA) for Chemotherapy Response in Advanced Non-Small-Cell Lung Cancer Patients
Authors: H. Huang, C. Chiu, W. Su, J. Feng, C. Chiang, C. Lin, S. Lin, C. Cheng
Journal: Journal of Thoracic Oncology (2017)
P3.13-025 Spinal Cord and Cauda Equina Compression in Lung Cancer
Authors: H. Neji, M.A. Haouari, M. Attia, M. Affes, I. Baccouche, S. Hantous-Zannad, K. Ben Miled-M'Rad
Journal: Journal of Thoracic Oncology (2017)
Preliminary use of a double-flanged, fully covered, self-expandable, metal stent with cautery in endoscopic ultrasound-guided gastroenterostomy
Authors: Bowen Duan, Jintao Guo, Nan Ge, Xiang Liu, Sheng Wang, Guoxin Wang, Siyu Sun
Journal: Endoscopy (2017)

New approaches to endoscopic ultrasound-guided gastroenterostomy (EUS-GE) are under development, incorporating devices designed for transluminal therapy. Herein is the initial reported use of a novel, double-flanged, fully covered, self-expandable, metal stent with cautery, aimed at refining the EUS-GE procedure.
Segmented Filamentous Bacteria Provoke Lung Autoimmunity by Inducing Gut-Lung Axis Th17 Cells Expressing Dual TCRs
Authors: C. Pierce Bradley, Fei Teng, Krysta M. Felix, Teruyuki Sano, Debdut Naskar, Katharine E. Block, Haochu Huang, Kenneth S. Knox, Dan R. Littman, Hsin-Jung Joyce Wu
Journal: Cell Host & Microbe (2017)
ACTR-20. FINDING A PREDICTIVE MARKER FOR COMPLIANCE TO TTFIELDS THERAPY – THE COMPTUNE STUDY
Authors: Martin Proescholdt, Christian Doenitz, Youssef Shiban, Peter Hau, Kurt Putnik, Muehlberger Andreas
Journal: Neuro-Oncology (2017)

CONCLUSIONS: To our knowledge, this study represents the first report of lower EGFR amplification rates in patients from Asia with glioblastoma.This observation requires further study.
Pancreatic cancer: sharing a nutrition education project with the patients and their care givers
Authors: M.A. Satolli, C. Finocchiaro, P. Durelli, R. Spadi, A. Ponzetti, T. Monge, L. Brossa, E. Agnello, P. Franco, P. Strignano, S. Storto, M. Mistrangelo, M. Viale, L. Ciuffreda, O. Bertetto
Journal: Annals of Oncology (2017)
Nouveaux horizons, nouvelles ouvertures
Authors: S Handysides
Journal: Eurosurveillance (1999)

Ce mois-ci, Eurosurveillance publie un article qui merite quelques explications. L’asthme n’est pas une maladie infectieuse en tant que telle, mais certaines infections virales aigues peuvent precipiter les crises d’asthme. De meme, les bronchites aigues survenant chez les sujets asthmatiques peuvent etre plus longues a soulager et necessiter une prise en charge differente de celles des sujets non asthmatiques.
STEM-17. CHARACTERIZATION OF THE CELL SURFACE PROTEOME IN RECURRENT GLIOBLASTOMA INITIATING CELLS
Authors: Mathieu Seyfrid, Chirayu Chokshi, Laura Kuhlmann, Chitra Venugopal, Parvez Vora, Ankit Sinha, Vladimir Ignatchenko, Andrew Macklin, Thomas Kislinger, Sheila Singh
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in humans, bearing an overwhelmingly poor prognosis and characterized by a diverse cellular phenotype and genetic heterogeneity. Despite multimodal therapy, patients on average experience relapse at 9 months and median survival rarely extends beyond 15 months. Treatment of human GBM with standard-of-care (SOC) chemo-radiotherapy invariably leads to resistance. Poor patient survival correlates with marker expression of brain tumor-initiating cells (BTICs), which are implicated in therapeutic resistance and may explain tumor relapse. Targeting the cells that drive GBM formation as well as its inevitable and rapid recurrence post-therapy has remained a major challenge, likely due to intra-tumoral heterogeneity. Proteomic profiling constitutes a promising tool to identify novel cancer targets. In this study, we have adopted a non-biased mass spectrometry approach to identify cell surface peptides isolated from patient-derived GBM BTIC lines through a glycocapture approach. We have identified proteins that are differentially expressed in recurrent GBM BTICs compared to primary GBM BTICs. Moreover, we perform comparative proteomics from recurrent GBM BTICs generated from our in vivo mouse-adapted therapy model, which has the distinct advantage of generating recurrent, treatment-refractory GBM. Our surface proteomic profiling thus provides a comprehensive network of signaling molecules selectively enriched in recurrent GBM cells. Identification of cell surface proteins that may drive treatment resistance will contribute greatly to identify novel immunotherapeutic targets for GBM.
P1.15-014 Can Limited Resection Be Accepted as an Alternative Treatment Option for Patients with Early-Stage Small Cell Lung Cancer?
Authors: T. Koga, I. Kubota, F. Kosuke, M. Sanada, Y. Motooka, K. Yoshimoto, K. Shiraishi, K. Ikeda, J. Wakimoto, T. Mori, M. Suzuki
Journal: Journal of Thoracic Oncology (2017)
Un brote de Queratoconjuntivitis Adenovirus tipo 8 en una residencia de personas mayores en Madrid
Authors: J M Sendra Gutierrez, D Martin Rios, I Casas, P Sáez, A Tovar, C Moreno
Journal: Eurosurveillance (2004)

Este trabajo describe y analiza un brote de queratoconjuntivitis epidemica ocurrido entre 2001 y 2002 en una residencia de personas mayores en Leganes (ciudad del Sur de Madrid), siendo el primero que se publica en Espana con estas caracteristicas e identificacion de serotipo. Se describen las caracteristicas sociodemograficas, la curva epidemica y las tasas de ataque del brote. Las comparaciones de datos se realizan a traves del test de chi2 (test exacto de Fisher) para las variables cualitativas y el t-test para las cuantitativas. Los factores asociados a la enfermedad son estudiados mediante tablas de contingencia y modelos de regresion logistica. Se detectan un total de 102 casos de enfermedad, con una tasa de ataque del 36,4% para los residentes y 12,9% para los trabajadores, no encontrandose diferencias espaciales ni por profesiones. La curva epidemica muestra un modelo de transmision interpersonal. El analisis multivariante identifica entre los residentes los siguientes factores de riesgo: capacidad para deambular libremente a traves del edificio, incontinencia urinaria y utilizacion de bano compartido. En el 34,6% de las muestras conjuntivales analizadas se detecta un adenovirus serotipo 8 con identica secuencia genomica. El establecimiento de normas higienicas y sanitarias adecuadas para la limpieza de estos establecimientos y para el manejo de los residentes, asi como un diagnostico precoz y una buena coordinacion de los recursos materiales y humanos disponibles son factores clave en la prevencion y el control de estos brotes en comunidades cerradas.
P1.07-013 Detection of Genomic Alterations in Plasma Circulating Tumor DNA in Patients with Metabolically Active Lung Cancers
Authors: Z. Yuan, C. Zhou, L. Qi, A. Mahavongtrakul, Y. Li, D. Yan, Y. Rong, W. Ma, J. Gong, J. Li, M. Molmen, T.A. Clark, G.M. Frampton, M. Cooke, E.H. Moore, D.K. Shelton, R.D. Badawi, J.P. Gregg, P.J. Stephens, T. Li
Journal: Journal of Thoracic Oncology (2017)
EPID-13. A SINGLE INSTITUTION ANALYSIS: DETERMINING GENETIC VARIATION AND SURVIVAL OUTCOMES AMONG ASIAN AND NON-ASIAN NEUROSURGERY PATIENTS
Authors: Thien Nguyen, Courtney Duong, Lawrance Chung, John Sheppard, Yasmine Alkhalid, Vera Ong, Natalie Barnette, Carlito Lagman, Isaac Yang
Journal: Neuro-Oncology (2017)

Globally, brain cancer compromises 2% of all total emerging cancers, yet has one of the lowest survival five-year survival rates. Differences in clinical outcomes between brain tumor patients of different races remains poorly understood. A retrospective chart review was performed on brain tumor resection patients 18 years old. Demographics, treatment variables, and survival outcomes were collected. Primary outcomes were recurrence rate, progression free survival (PFS), and overall survival (OS). A total of 666 patients were included in final analysis. Females and males had nearly a 1:1 ratio (n = 345 and n = 321, respectively). Mean age was 51.3 (± 17.2) years. Females composed 64.3% (n = 54) of Asians patients; males constituted 35.7% (n = 30). Mean age of the Asians was 53.5 (± 16.5) years. Tumor pathologies included meningioma (n = 210 total) and glioblastoma (n = 192 total). There were 210 meningioma patients, of which Non-Asian patients comprised 81.43% of the group (n = 171) and Asian patients composed 18.57% (n = 39). We identified 192 glioblastoma patients in total. Non-Asian patients made up 92.7% of the glioblastoma cohort (n = 178) with the remaining 7.3% (n = 14) composed of Asian patients. There were no statistically significant differences between these groups in both cohorts in recurrence (P = .9052 and P = .7894, respectively), PFS (P = .6953 and P = .845, respectively), or OS (P = 1.0 and P = .9126, respectively). Studies evaluating the survival between patients of different racial backgrounds against several tumor varieties are rare. Patients of certain racial backgrounds may need additional care consideration despite the same mutational composition as their counterparts. Repeated studies using national databases, such as the SEER database, may yield more conclusive results.
P1.02-048 Somatic Mutation Analysis of RB1 Gene in Chinese Non-Small Cell Lung Cancer Patients
Authors: W. Wang, C. Xu, W. Zhuang, Z. Song, Y. Zhu, R. Chen, Y. Guan, X. Yi, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
MA 10.01 Durvalumab ± Tremelimumab with Platinum-Doublets in Non-Small Cell Lung Cancer: Canadian Cancer Trials Group Study IND.226
Authors: R. Juergens, D. Hao, S. Laurie, P. Ellis, M. Mates, P. Bradbury, M. Tehfe, C. Kollmannsberger, A. Arnold, J. Goffin, P. Wheatley-Price, J. Hilton, A. Robinson, D. Tu, P. Brown-Walker, L. Seymour
Journal: Journal of Thoracic Oncology (2017)
P3.05-012 Clinicopathological Determinants of Circulating Tumor DNA Detection in Early-Stage Non-Small Cell Lung Cancer
Authors: J.H. Cho, H.K. Kim, S. Lee, J.Y. Lee, Y.S. Choi, J.I. Zo, Y.M. Shim, J. Kim, S. Mortimer, J. Odegaard
Journal: Journal of Thoracic Oncology (2017)