tbuckley/cabot-search huggingface dataset:
NIMG-09. CHARACTERIZING GLIOMA MICROENVIRONMENT WITH ULTRA-HIGH GRADIENT DIFFUSION MRI
Authors: Ina Ly, Barbara Wichtmann, Susie Huang, Aapo Nummenmaa, Ovidiu Andronesi, Qiuyun Fan, William T Curry, Daniel Cahill, Brian Nahed, Alexandra Golby, Tracy Batchelor, Jayashree Kalpathy-Cramer, Bruce Rosen, Elizabeth Gerstner
Journal: Neuro-Oncology (2017)

The infiltrating nature of gliomas, particularly into the peritumoral area, is a major barrier to improving clinical outcome as microscopic disease remains even after apparent gross total resection. T1 post-contrast and T2/FLAIR MRI do not capture full tumor extent. A better imaging biomarker is needed to improve differentiation between tumor, peritumoral area and normal brain. 5 pre-surgical patients with non-enhancing, FLAIR-hyperintense lesions suspicious for glioma underwent ultra-high gradient diffusion MRI on the Connectome MRI scanner with maximum gradient strength of 300 mT/m, enabling mapping of cellular microstructures on micron-level scale. The FLAIR area was defined as the tumor region of interest (ROI). Radiographically normal appearing brain up to 1 cm around the FLAIR area was defined as the peritumoral ROI. Using a novel 3-compartment diffusion model, the volume fraction of water (VFW) was calculated within restricted (intracellular), hindered (extracellular) and free (CSF) spaces. VFW in the tumor, peritumoral ROI, contralateral normal white matter (WM) and cortex were compared. Within the tumor ROI, median VFW in the restricted compartment was decreased vs. peritumoral ROI (↓35%), WM (↓48%) and cortex (↓18%) while median VFW in the hindered compartment was increased vs. peritumoral ROI (↑30%), WM (↑56%) and cortex (↑8%). Within the peritumoral ROI, median VFW in the hindered compartment was increased compared to WM (↑22%). All patients had confirmed IDH-mutant gliomas. Using ultra-high gradient diffusion MRI and a novel diffusion model, we detected distinct diffusion patterns in the tumor and peritumoral area not seen on conventional MRI. Lower VFW in the restricted compartment within the tumor may reflect decreased intracellular water mobility due to enlarged nuclei. Higher VFW in the hindered compartment within tumor and peritumoral area may reflect higher tissue permeability and edema. Longitudinal validation studies are underway to elucidate microenvironment changes in response to treatment.
P2.02-007 Molecular Spectrum of STK11 Gene Mutations in Patients with Non-Small-Cell Lung Cancer in Chinese Patients
Authors: X. Chen, C. Xu, W. Wang, W. Zhuang, Z. Song, Y. Zhu, Y. Chen, R. Chen, Y. Guan, X. Yi, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
Role of DCE-MR imaging of the breast in predicting breast cancer subtypes: where are we going?
Authors: L. Bastianelli, M. Pistelli, G.M. Giuseppetti, M. De Lisa, M. Macchini, M. Ponziani, A. Della Mora, L. Cantini, F. Merloni, A. Savini, R. Berardi
Journal: Annals of Oncology (2017)
La vigilancia de la rabia, la evolución de la rabia animal y la profilaxis post-exposición humana en Polonia, 1990-2004
Authors: M Sadkowska-Todys, M Rosinska, M Smreczak, M Czerwinski, J F Zmudzinski
Journal: Eurosurveillance (2005)

El articulo siguiente describe los cambios recientes en la situacion epizootica y epidemiologica de la rabia en Polonia. Se llevo a cabo un analisis de los datos de vigilancia pasiva de los casos animales y de los tratamientos post-exposicion en el hombre, con el objetivo de valorar el impacto de la introduccion de una vacuna de cultivos celulares en el hombre y la implementacion de un programa de vacunacion de los zorros. El exito del programa de vacunacion de los animales salvajes fue evidente los tres ultimos anos, consiguiendo reducir nueve veces el numero de casos de rabia animal. Sin embargo, hasta el momento, la tendencia decreciente de los casos de rabia animal no parece tener efecto en la frecuencia de utilizacion de la profilaxis post-exposicion en humanos. Ademas, se produjeron dos casos de rabia humana autoctona en pacientes que no habian recibido la vacuna post-exposicion. Esto ultimo confirma que la rabia debe seguir siendo considerada como un problema de salud publica en Polonia.
Benign pleural schwannoma presenting with a large, blood-stained pleural effusion
Authors: Anna C Bibby, Richard Daly, Eveline Internullo, Anthony J Edey, Nicholas A Maskell
Journal: Thorax (2017)

A previously fit and well 43-year-old man presented with 8 weeks of worsening breathlessness and a dry cough. He was an ex-smoker of 10 pack-years with no history of asbestos exposure, thoracic radiation or recent trauma.

Chest radiograph and CT thorax are shown in figure 1. Pleural aspiration was undertaken and 1.5 L of blood-stained fluid was removed, with symptomatic improvement. The fluid was exudative, with lactose dehydrogenase (LDH) 437U/L (serum 374U/L) and protein 47g/L (serum 77g/L). Infection was excluded by negative microbiological culture and normal inflammatory markers. Cytology revealed numerous red blood cells, scattered lymphocytes and eosinophils, but no malignant cells.



Figure 1 
(A) Posterior–anterior chest radiograph showing moderate left-sided pleural effusion and an indistinct opacity at the left hilum with mediastinal shift to the right. (B) Coronal CT images showing a round, encapsulated extrapulmonary mass, with cystic areas within in, surrounded by a pleural effusion. (C) Coronal positron emission tomography-CT images demonstrating high SUV uptake within …
METB-16. ACQUISITION OF WARBURG PHENOTYPE IN IDH1-MUTATED GLIOMA AS A MECHANISM OF MALIGNANT TRANSFORMATION
Authors: Victor Ruiz Rodado, Tomohiro Seki, Tyrone Dowdy, Adrian Lita, Orieta Celiku, Kazu Yamamoto, Keita Saito, Alejandra Cavazos Saldana, Aiguo Li, Murali Krishna Cherukuri, Mark Gilbert, Mioara Larion
Journal: Neuro-Oncology (2017)

The Warburg effect is one of the hallmarks of cancer metabolism and its prevalence includes gliomas. The formation of lactate and upregulation of glycolysis has been the basis of many studies that either use 18FDG PET or lactate as a readout of cancer progression. However, IDH1-mutated gliomas have been reported to have low glycolytic rates and minimal lactate production, due to the hypermethylation of the promoter region of LDHA. We postulated that initially, IDH1-mutated gliomas form very little lactate, but as they progress towards glioblastomas lactate production increases. TS603 and BT142 cell lines harboring IDH1 mutation were cultured in DMEM/F12+ N2 supplement, glutamine, FGF and EGF, then either harvested for metabolomics and methylation analyses or (250,000 cells) were injected into 6-week-old SCID mice brains. MRI was used to monitor tumor size; when tumors reached 100 mm3, mice were injected in the tail vain with 96 mM 1-13C pyruvate which was hyperpolarized using Oxford Hypersense hyperpolarizer and chemical shift images were acquired immediately. Metabolite quantification was done using the Agilent LC/MS 6545 QTOF mass spectrometer. DNA methylation analysis was performed using Illumina Human Methylation 450 Bead Chip. Our results demonstrate a unique example of IDH1-mutant glioma that transformed to a highly glycolytic, Warburg-like glioma that was associated with loss of global methylation and increased expression of glycolytic enzymes. Moreover, the glycolytic enzyme expression of the aggressive cell line correlates with the subset of patients that are IDH1 mutated and low-G-CIMP in TCGA database. The results of this study represent an example of malignant transformation that is linked with loss of methylation as a primary step in the mechanism by which IDH1-mutated low grade gliomas transform towards glioblastomas.
Une pseudo-épidémie d’infections humaines à A/H5N1 en Grèce et ses implications en santé publique
Authors: G Spala, T Panagiotopoulos, N Mavroidi, X Dedoukou, A Baka, P Tsonou, E Triantafyllou, A Mentis, V Kyriazopoulou, A Melidou, S Tsiodras
Journal: Eurosurveillance (2006)

La recente et large dissemination geographique du virus de la grippe aviaire A/H5N1 hautement pathogene a des consequences importantes en sante publique. En Grece, l’infection de plusieurs oiseaux migrateurs a ete confirmee en fevrier et mars 2006. L’obj
How are junior doctors supposed to learn without the opportunity?
Authors: Eugene Y H Yeung
Journal: BMJ (2017)

Glass quotes some of his colleagues’ dissatisfying comments about junior doctors.1 But I wonder how many of his colleagues did anything to change the training of their juniors. 

Did these surgical consultants give their medical students and foundation year doctors enough hands-on experience and teaching on suturing? Many juniors are keen to practise clinical procedures, such as suturing …
Abstract 18269: Invasive Treatment of ST-Elevation Acute Coronary Syndrome in Russian Hospitals is Predominantly Used in Lower Risk Patients
Authors: Alexey D Erlikh, Nikolay A Gratsiansky
Journal: Circulation (2012)

Introduction . Inhospital mortality of patients with ST-elevation (STE) acute coronary syndrome (ACS) in Russia is generally very high while it is reported to be low in patients subjected to primary percutaneous coronary interventions (pPCI) in invasive institutions. Hypothesis . Low mortality in STEMI patients treated with pPCI is at least partially explained by selection of patients with lower risk. Methods . To test this hypothesis we studied data from two independent Russian prospective ACS registries which were organized upon initiative of their participants - RECORD (2007-2008 years, 18 hospitals from 13 cities) and RECORD-2 (2009-2011 years, 7 hospitals from 7 cities). Results . There were 967 STEACS patients included in both registries (≥ 65 years - 41%, Killip class ≥ II - 21%). Hospitals with ability to apply invasive treatment (invasive hospitals) recruited 79% of patients. The rate of pPCI was 36% (in invasive hospitals - 46%). Rates of pPCI in invasive hospitals in patients aged ≥ 65 and &lt; 65 years were 33% and 54%, respectively (p&lt;0.0001); in patients with Killip class ≥ II and I - 34% and 49%, respectively (p=0.002); in patients with high and non-high risk of inhospital death according to GRACE score - 35% and 51%, respectively (p&lt;0.0001). Overall inhospital mortality was 11%. Rates of death in patients aged ≥ 65 and &lt; 65 years were 21% and 5%, respectively (p&lt;0.0001), in patients with Killip class ≥ II and I - 32% and 6%, respectively (p&lt;0.0001). Among patients aged 65 years and older inhospital mortality was significantly lower in those treated with pPCI than in patients treated without pPCI (11% and 23%, respectively, p=0.01). Among patients aged &lt; 65 years there was no significant difference in hospital mortality between patients subjected and not subjected to pPCI (5% in both groups, p=0.8). Conclusions . Data from limited size independent Russian ACS registries RECORD and RECORD-2 show that in high risk patients with STEACS (≥ 65 years old, Killip ≥ II, high risk by GRACE score) rate of pPCI was significantly lower than in non-high risk patients. However association of pPCI with lower hospital mortality was found only in patients aged ≥ 65 years.
Avaliação do impacto sobre a mortalidade da onda de calor de 2003 na França
Authors: P Pirard, S Vandentorren, M Pascal, K Laaidi, A Le Tertre, S Cassadou, M Ledrans
Journal: Eurosurveillance (2005)

Entre o 2 e o 15 de Agosto de 2003, a Franca experimentou um periodo de calor de intensidade exceptional. Todas as regioes francesas foram afetadas por essa onda de calor, que provocou um excesso de 14 800 obitos entre o 1° e o 20 de Agosto. O aumento no numero de obitos seguia a mesma curva que o aumento das temperaturas. A mortalidade observada tornou a seu nivel normal na ultima decada do mes de Agosto e durante os tres meses posteriores. O impacto sanitorio dessa onda de calor foi variavel seguindo as cidades. Todo o excesso de mortalidade observado nao pode ser explicado so pela duracao e a intensidade excepcional das temperaturas minimas. As mulheres de mais de 75 anos foram as mais afetadas. As taxas de mortalidade mais importantes foram observadas em obitos associados com o calor. Frente ao impacto sanitario dessa onda de calor, as autoridades sanitarias francesas implementaram em 2004 um sistema de alerta nacional como tambem um plano de acao preventivo em cada regiao.
STEM-37. GENETIC EDITING OF NEURAL STEM CELLS FOR INTRANASAL THERAPEUTIC DELIVERY TO MALIGNANT BRAIN TUMORS
Authors: Dou Yu, Julius W Kim, Deepak Kanojia, Yu Han, J Michael Mathis, Chin-Tu Chen, Karen Aboody, Maciej S Lesniak, Irina Balyasnikova
Journal: Neuro-Oncology (2017)

Intranasal delivery of Neural stem cells (NSCs) or mesenchymal stem cells (MSCs) bypasses the blood brain barrier and confers therapeutic benefits in concert with radiation and oncolytic virotherapy in mouse models bearing human glioma xenografts. However, anatomical differences between human and rodent nasal passages pose a challenge to clinical translation of this technology. Human nasal epithelium has greater innervation by the trigeminal nerves, whereas the olfactory nerves dominate this area in rodents. Although the trigeminal route has been implicated in rodent models of intranasal stem cell delivery, definitive therapeutic applications of intranasal stem cell delivery targeting the trigeminal route are yet to be explored. Leveraging our mesoporous nanoparticle (MSN)-based radiolabeling technology, we discovered differential intranasal brain entry routes by NSCs and MSCs with MSN-Zr89 enabled Positron Emission Tomography (PET) imaging. MSCs preferred the trigeminal route, whereas NSCs predominantly migrated through the olfactory route. We hypothesize that the chemotactic cytokine receptor expression profiles of NSCs and MSCs are major determinants of the migratory path choice in response to diverse brain micro-environmental cues. We additionally postulate that genetic editing of receptors for trigeminal ganglia related cytokines can augment stem cell-tumor tropism via the trigeminal route. Based on comparative cytokine antibody array analysis of the trigeminal ganglia and olfactory bulbs of athymic nude mice, we identified epidermal growth factor (EGF) as the chemotactic cytokine that gates the trigeminal nerve route of brain entry. The expression differences in EGF receptor (EGFR) in MSCs and NSCs are consistent with our observation. We then utilized clustered regularly interspaced palindromic repeats (CRISPR)-based endogenous gene activation to significantly upregulate the EGFR expression levels in NSCs, resulting in improved chemotactic migration capacity toward EGF in vitro, and boosted intranasal brain entry via the trigeminal nerve in vivo. This discovery establishes a robust therapeutic strategy to develop toward clinical translation.
EXTH-31. RNA NANOPARTICLE-BASED TARGETED GENE THERAPY FOR GLIOBLASTOMA
Authors: Tae Jin Lee, Ji Young Yoo, Balveen Kaur, Carlo Croce, Peixuan Guo
Journal: Neuro-Oncology (2017)

Systemic administration of therapeutic siRNA/microRNA for targeted treatment of glioblastoma, one of the most deadly cancers, requires robust and efficient delivery platform without immunogenicity. Here we report newly emerged multivalent naked RNA nanoparticle (RNP), named FA-pRNA-3WJ, based on pRNA 3-way-junction (3WJ) from bacteriophage phi29 to target glioblastoma cells with folate (FA) ligand and deliver siRNA/microRNA for tumor cell killing. Systemically injected FA-pRNA-3WJ RNPs successfully targeted and delivered siRNA into brain tumor cells in mice, and efficiently reduced luciferase reporter gene expression (4-fold lower than control). The FA-pRNA-3WJ RNP also can target human patient-derived glioblastoma stem cells, thought to be responsible for tumor initiation and deadly recurrence, without accumulation in adjacent normal brain cells, nor other major internal organs. FA-3WJ-LNA-miR21 specifically targeted and delivered anti-miR-21 LNA and knocked down miR-21 expression in glioblastoma cells in vitro and in vivo with favorable biodistribution. Systemically injected FA-3WJ-LNA-miR21 RNP efficiently rescued PTEN and PDCD4, resulting in glioblastoma cell apoptosis and tumor growth regression. This RNA nanotechnology was employed even to regulate the anchoring of nanoparticles on the surface of extracellular vesicles (EVs) for specific cancer targeting and intracellular trafficking. Taking advantage of the RNA aptamer ligand for specific targeting and EVs for efficient membrane fusion, EGFRapt-pRNA-3WJ RNP was constructed and anchored onto EVs loaded with survivin siRNA. In the preliminary animal tests, systemic administration of the EV-siSurvivin coated with EGFRapt-pRNA-3WJ RNP inhibited tumor growth in orthotopic breast cancer xenograft mouse model by successfully downregulating the Survivin expression. The studies are indicative of the clinical benefit of FA-3WJ RNP based tumor targeting and gene therapy for the successful targeted therapy of primary and recurrent glioblastoma.
P2.01-049 Long Progression Free Survival and Overall Survival in Advanced NSCLC Patients with EGFR Mutation and Complete Response with TKI Treatment
Authors: O. Macedo-Pérez, I. Lyra-González, D. Marroquín-Flores, G. Cruz-Rico, L. Ramírez-Tirado, L. Valdez-Rojas, A. Tabares-Nañez, J. Gonzales-Nogales, O. Arrieta
Journal: Journal of Thoracic Oncology (2017)
Abstract 20268: Prevalence and Management of Adult Obesity in a Large Academic Health System
Authors: Neha J Pagidipati, Matthew Phelan, Karen Chiswell, Eric D Peterson
Journal: Circulation (2017)

Introduction: Though the prevalence of obesity is rising, little data exists on the real-world management of obese patients. Methods: Adults in the Duke Primary Care system who had at least 2 body-...
P3.05-010 NOTCH 1 and NOTCH 3 Expressions for Early Stage of Non-Small Cell Lung Cancer
Authors: E.K. Cho, S.Y. Ha, J. Lee, S.Y. Kyung, S.M. Kang, H.K. Ahn, Y.J. Kim, J.W. Park, S.H. Jung
Journal: Journal of Thoracic Oncology (2017)
DRES-02. FGFR1 DRIVES RESISTANCE TO PI3K INHIBITORS VIA UP-REGULATION OF AURORA A/PLK1/CDK1 AXIS IN GLIOBLASTOMA
Authors: Xiaolong Li, Chen Zhang, Emmanuel Martinez-Ledesma, Feng Gao, W K Alfred Yung, Dimpy Koul
Journal: Neuro-Oncology (2017)

Activation of PIK3CA, the gene encoding phosphoinositide-(3)-kinase (PI3K) is frequently found in glioblastoma multiforme (GBM). However, single agent targeted cancer therapies have limited success. Such poor response is likely due to intrinsic as well as adaptive and acquired factors. The goal of this study is to elucidate what drives adaptive and acquired resistance to PI3K inhibitors in GBM. To accomplish this, we developed 3 in vivo GSCs (Glioma Stem-like Cells) xenograft models of BKM-120, a monospecific PI3K inhibitor resistance. The resistant cells were first molecularly characterized by RNA-Seq analysis and compared with that from the parental lines. High Throughput Drug Screening with BKM120 and a kinase inhibitor drug library was also performed with the resistant cells. Integrated analysis of the two data sets identified multiple interesting combinations. Activation of the Aurora kinase A (Aurora A)/Polo-like kinase 1 (Plk1)/cyclin-dependent kinase (CDK) signaling pathway was predominant in all 3 resistant GSCs. Targeting PI3K together with Aurora A, Plk1 or CDK1 had a synergistic growth inhibitory effect. In addition, the combined inhibition of Plk1 and PI3K resulted in tumor growth suppression and prolonged survival in vivo. Further, we showed that Aurora A/Plk1/CDK1 axis was regulated by upstream fibroblast growth factor receptor 1 (FGFR1). Inhibition of FGFR1 overcame the resistance as shown by downregulation of Aurora A/Plk1/CDK1. Our data suggest that Aurora A axis activated by FGFR1 serves as a major survival signal upon PI3K inhibition and offer a preclinical proof of concept for a strategy of co-targeting PI3K and in parallel activated Aurora A pathway to attain synergistic control in human GBM.
PATH-20. COMPREHENSIVE GENOMIC PROFILING COMPARING PRIMARY CNS LYMPHOMA TO SYSTEMIC DIFFUSE LARGE B CELL LYMPHOMA REVEALS BIOMARKERS INDICATING POTENTIAL BENEFIT FROM IMMUNE CHECKPOINT INHIBITORS
Authors: Eric Severson, Jo-Anne Vergilio, Laurie Gay, Sugganth Daniel, Julia Elvin, James Suh, Mandy Covert, Charlotte Brown, Vincent Miller, Philip Stephens, Jeffrey Ross, Shakti Ramkissoon
Journal: Neuro-Oncology (2017)

B-Cell Primary CNS Lymphoma (PCL) is Diffuse Large B-cell Lymphoma (DLBCL) confined to the CNS. Less than 50% of PCL patients achieve complete remission with current therapies. Comprehensive genomic profiling (CGP) may suggest novel treatment modalities including use of immune checkpoint inhibitors (ICPI). DESIGN: 24 cases of B-cell PCL and 432 cases of DLBCL were evaluated by CGP of 405 genes via DNAseq for all classes of genomic alterations and 265 genes via RNAseq for fusions (FoundationOne Heme). Tumor mutational burden (TMB) was calculated from 1.23 Mb of sequenced DNA. The PCL cohort was 50% male and 50% female, aged 21 to 84 with a median age of 66, while the DLBCL cohort was 64% male and 36% female, aged 14 to 88 with a median age of 63. Genomic alterations with significant differences between PCL and DLBCL included MYD88 (50.0% vs 17.6%), ETV6 (38% vs 2.3%), PIM1 (25.0% vs 7.6%), PRDM1 (25.0% vs 5.8%), CXCR4 (16.7% vs 2.5%), TP53 (16.7% vs 40.3%), and CREBBP (0.0% vs 21.5%) (p<0.05 by two-tailed Fisher Exact Test). Median TMB was similar (median 9.2 vs 10 mutations/mb) and the percent of TMB-high cases (>20 mutations/mb) were not statistically different (33% vs 19%). Two PCL cases were PD-L1 (CD274) amplified with TMBs of 64 and 10 mutations/mb. CGP of PCLs reveals biomarkers predictive of ICPI efficacy including TMB-high (33%) and CD274 amplification (8%). These results could be used to refer patients to clinical trials such as NCT02779101 employing ICPI treatment in PCL. This is the first series of PCL to report mutational burden and demonstrate a significantly increased frequency of ETV6, CXCR4 and PIM1 genomic alterations in comparison to DLBCL. Given the limitations of standard of care for PCL, CGP can potentially identify new therapeutic approaches in this rare form of lymphoma.