tbuckley/cabot-search huggingface dataset:
PATH-18. MOLECULAR AND GENETIC ANALYSIS IDENTIFIES IDH MUTATION AS A KEY FACTOR OF LONG-TERM SURVIVAL IN GLIOBLASTOMA PATIENTS
Authors: Franziska Loebel, Sebastian Friedrich Winter, Julia Onken, Daniel Cahill, Arend Koch, Jorg Dietrich
Journal: Neuro-Oncology (2017)

Despite improved treatment modalities, glioblastoma multiforme (GBM) remains the most malignant brain tumor with a median overall survival (OS) of 15-18 months. However, some patients show remarkably longer OS, although the underlying factors associated with prolonged survival remain largely unknown. Mutations of isocitrate dehydrogenase (IDH) have been associated with improved prognosis in low-grade gliomas. Here, we investigate the influence of IDH-mutational status and other molecular-genetic factors on long-term survival in GBM patients. Long-term survival (LTS) was defined as OS >3 and very long-term survival (VLTS) as >5 years after initial diagnosis. Long-term survivors were identified retrospectively and their clinical and pathology data were analyzed. Molecular-genetic and pathological factors were determined via standard genetic profiling methods. Kaplan-Meier and multi-variate analysis were used to identify factors associated with LTS/VLTS. We identified a total of 65 LTS (including 26 VLTS) patients. Median age was 45.5 years (range 18.5-72.4). Patients were predominantly male (62.5%). Tumors were located mainly in the frontal lobes (52.3%) and the right hemispheres (64.4%). IDH-mutation was present in the majority of LTS (75.4%) and nearly all (92.3%) of VLTS patients, and included mainly R132H mutations and only two R132C mutations. 60% of LTS and 69.3% of VLTS patients showed MGMT promoter methylation. 1p/19q co-deletion was found in 36.9% of LTS and 46.1% of VLTS. The majority of LTS (58.5%) and VLTS (53.8%) were TP53-wildtype. The confirmed IDH-wildtype cases were mostly MGMT promoter methylated and TP53-wildtype. IDH-mutation seems to be a key factor in long-term survival and especially very-long-term survival of GBM patients. Other molecular factors such as MGMT promoter methylation, TP53-wildtype status and 1p/19q-co-deletion also appear to be favorable prognostic factors for LTS and VLTS, underscoring the value of molecular analysis of tumor tissue for patient management and prognostication.
NIMG-85. PBR28 PET-MRI IN GBM PATIENTS TREATED WITH IMMUNOTHERAPY OR SUSPECTED PSUEDOPROGRESSION
Authors: Vyshak Chandra, Stephanie Salcedo, Yi-Fen Yen, Jonathan Cardona, Andrew Beers, Ciprian Catana, Jayashree Kalpathy-Cramer, William T Curry, Elizabeth Gerstner
Journal: Neuro-Oncology (2017)

Increases in contrast enhancement due to treatment related inflammation creates a significant clinical conundrum for neuro-oncologists. Our goal was to use simultaneous PBR28 PET-MRI to measure TSPO, a marker of microglia activation as well glioma cells, in patients with glioblastoma (GBM). In this pilot study, patients who received immunotherapy for recurrent GBM or newly diagnosed GBM with suspected pseudoprogression after completion of temozolomide+radiation were recruited at a single institution between 2014-2017. Simultaneous MR-PET scans were conducted at the time of suspected pseudoprogression or pre-and post-immunotherapy. During each scan, [11C] PBR was injected intravenously, and median SUV within the enhancing tumor was calculated. 6 patients have been enrolled to date, 3 male and 3 female, with median age of 66 (58-75). 5/6 patients (83%) had GBM and suspected pseudoprogression, and 1 patient had GBM treated with immunotherapy. In the patients with suspected pseudoprogression, 2/5 (40%) patients were determined to have pseudoprogression, and median tumor SUV for these patients was 0.92. 3/5 (60%) patients had true tumor progression and their median SUV was 0.50. One patient underwent resection after one cycle of TMZ, with pathology revealing pseudoprogression. This patient had an SUV of 0.93. In one immunotherapy treated GBM patient, median SUV changed from 0.65 to 0.81. This patient was determined to not be responding to immunotherapy. Patients with pseudoprogression had increased PBR28 uptake compared to patients with true disease progression suggesting a possible role for PBR28 PET in distinguishing pseudoprogression from true tumor progression. With these encouraging results, further investigation is ongoing to fully characterize the value of PBR28 PET-MRI and updated results will be presented.
EXTH-85. MAGMAS INHIBITION AS A POTENTIAL TREATMENT STRATEGY IN MALIGNANT GLIOMA
Authors: Daniela A Bota, Naomi Lomeli, Kaijun Di, Bhaskar Das
Journal: Neuro-Oncology (2017)

Magmas (mitochondria-associated protein involved in granulocyte-macrophage colony-stimulating factor signal transduction) is a nuclear gene that encodes for the mitochondrial import inner membrane translocase subunit Tim16. Magmas is highly conserved and ubiquitously expressed in all mammalian cells, and is essential for cell viability. Its expression levels are increased in a significant proportion of human prostate cancers, independently of mitochondria content. In addition, Magmas mRNA is over expressed in two ACTH-secreting pituitary adenoma cell lines as compared to normal pituitary in mouse, as well as in 47 out of 64 pituitary adenomas compared to normal pituitary in human. Moreover, Magmas silencing sensitizes to pro-apoptotic stimuli and induces a G0/G1 accumulation. Based on the above findings, we believed that inhibition of Magmas by small molecule inhibitors could be beneficial for glioma treatment. In this study, we tested the capability of a Magmas inhibitor-BT#9 to cross the blood brain barrier in mice. The anti-tumor effect of BT#9 was investigated using glioma cell lines. Our in vivo results showed that while the plasma level of BT#9 reaches a Cmax within 5 minutes and is obviously eliminated by 720 minutes, brain levels of BT#9 increase over the first 240 minutes after IV exposure and then slowly decrease, indicating that BT#9 may cross the blood brain barrier. In vitro study using glioma cell lines revealed that Magmas inhibition by BT#9 significantly decreased cell proliferation, induced apoptosis along with vacuole formation, blocked migration and invasion. Since Magmas is a ROS regulator, BT#9 treatment resulted in a decrease in respiratory function of glioma cells. This is the first study about the role of Magmas in glioma. Our findings suggest that Magmas plays a key role in glioma cell survival and targeting Magmas by Magmas inhibitor has the potential to become an therapeutic strategy in gliomas.
P3.01-073 TPX-0005 with an EGFR Tyrosine Kinase Inhibitor (TKI) Overcomes Innate Resistance in EGFR Mutant NSCLC
Authors: R. Rosell, N. Karachaliou, J.J. Cui, I. Chaib, J. Berenguer, J. Bratch, X. Li, J. Yang, A. Drozdowskyj, C. Codony Servat, J. Codony Servat, A. Giménez-Capitán, S. Viteri, M. Molina-Vila, G. López-Vivanco, A. Vergnenegre, J.M. Sánchez-Torres, M. Provencio, F. De Marinis, A. Passaro, E. Carcereny, N. Reguart, R. García Campelo, S. Ignatius Ou, A. Cardona, P. Cao
Journal: Journal of Thoracic Oncology (2017)
Cluster di malattia dei legionari associati ai viaggi in Spagna, gennaio 2001- luglio 2003
Authors: R Cano, N Prieto, C Martin, C Pelaz, S Mateo
Journal: Eurosurveillance (2004)

E' ampiamente dimostrato che la sorveglianza epidemiologica ed il controllo della legionellosi sono attivita necessarie nell'ambito della sanita pubblica e della collaborazione fra i paesi. Nel quadro della rete EWGLINET, sono state elaborate delle linee guida europee per il controllo e la prevenzione della malattia dei legionari associata ai viaggi che stabiliscono i criteri di notifica e di risposta in presenza di casi singoli o di cluster. Questo articolo presenta i dati relativi a 46 cluster di legionellosi verificatisi in Spagna tra gennaio 2001 e luglio 2003.
STEM-35. GTP CYCLOHYDROLASE I IN TUMOR INITIATING CELL MAINTENANCE AND GLIOBLASTOMA GROWTH: FUNCTIONS AND MECHANISMS
Authors: Anh Tran, Kiera Walker, David Harrison, Wei Chen, James Mobley, Lauren Hocevar, James Hackney, Randee Sedaka, Jennifer Pollock, Victor Darley-Usmar, Sara Cooper, Yancey Gillespie, Anita Hjelmeland
Journal: Neuro-Oncology (2017)

Glioblastoma (GBM), or grade IV astrocytoma, is a deadly disease due in part to the high degree of intratumoral heterogeneity that contributes to treatment failures. One cellular subset enriched for the capacity to propagate tumor growth and promote therapeutic resistance is brain tumor initiating cells (BTICs). The aim of the study was to define the roles of GTP cyclohydrolase 1 (GCH1) in regulation of BTIC phenotypes via reactive species. We examined GCH1 mRNA and protein expression in patient-derived xenografts, clinical samples and glioma gene expression datasets. GCH1 levels were modulated using lentiviral expression systems, and effects on cell growth, self-renewal, reactive species production and in vitro animal survival were determined. We found that GCH1 RNA and protein expression were increased in BTICs in comparison to non-BTICs, but that GCH1 was not exclusive to the BTIC fraction. Indeed, GCH1 was elevated in GBM in comparison to normal brain. Overexpression of GCH1 in GBM cells increased cell growth in vitro and decreased survival in an intracranial GBM mouse model. In contrast, GCH1 knockdown with short hairpin RNA in GBM cells led to growth inhibition in vitro as well as increased survival in animal models. Mechanistically, GCH1 increased CD44 expression and was critical for controlling reactive species balance, including suppressing reactive oxygen species production. In silico analyses demonstrated that higher GCH1 levels in glioma patients correlate with higher glioma grade, recurrence and worse survival. Together, our data suggest that upregulation of GCH1 in BTICs promotes tumor maintenance and is a key regulator of reactive oxygen species in GBM.
MA 09.08 Receipt of Chest Radiation and Immune-Related Pneumonitis in Patients with NSCLC Treated with Anti-PD-1/PD-L1
Authors: K.R. Voong, S. Hazell, C. Hu, J. Hayman, R. Hales, K. Marrone, C. Hann, D. Ettinger, J. Feliciano, V. Rowe, R. Kelly, J. Brahmer, P. Forde, J. Naidoo
Journal: Journal of Thoracic Oncology (2017)
P2.07-062 PIVOT-02: Phase 1/2 Study of NKTR-214 and Nivolumab in Patients with Locally Advanced or Metastatic Solid Tumor Malignancies
Authors: V. Papadimitrakopoulou, N. Tannir, C. Bernatchez, C. Haymaker, S. Bentebibel, B. Curti, M. Wong, I. Gergel, M. Tagliaferri, J. Zalevsky, U. Hoch, S. Aung, M. Imperiale, D. Cho, S. Tykodi, I. Puzanov, H. Kluger, M. Hurwitz, P. Hwu, M. Sznol, A. Diab
Journal: Journal of Thoracic Oncology (2017)
P3.02-069 58 Cases of EGFR/ALK Gene Status Analysis in Pulmonary Sarcomatoid Carcinoma
Authors: Y. Huang, C. Xu, W. Wang, W. Zhuang, Z. Song, Y. Chen, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
PUB079 Detection of the EGFR P.(T790M) Mutation by Different Methods: A Small Comparison Case Study
Authors: H. Wang, A. Spatz, M. Aguirre, J. Agulnik, V. Cohen, D. Small, C. Pepe, L. Sakr, G. Kasymjanova, A. Wang, S. Owen, M. Tsao, L. Kempen
Journal: Journal of Thoracic Oncology (2017)
P3.02-039 Acquired Resistance to EGFR-TKI in the Uncommon EGFR Mutation, G719S
Authors: A. Osoegawa, T. Hashimoto, Y. Takumi, R. Kobayashi, M. Miyawaki, H. Takeuchi, T. Okamoto, K. Sugio
Journal: Journal of Thoracic Oncology (2017)
P3.01-009 Clinical Efficacy of Icotinib in Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Exon 18 E709X Mutations
Authors: C. Xu, W. Wang, W. Zhuang, Z. Song, R. Chen, Y. Guan, G. Chen, X. Yi, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
Wnt/β-Catenin Signaling in Liver Development, Homeostasis, and Pathobiology
Authors: Jacquelyn O. Russell, Satdarshan P. Monga
Journal: Annual Review of Pathology Mechanisms of Disease (2017)

The liver is an organ that performs a multitude of functions, and its health is pertinent and indispensable to survival. Thus, the cellular and molecular machinery driving hepatic functions is of utmost relevance. The Wnt signaling pathway is one such signaling cascade that enables hepatic homeostasis and contributes to unique hepatic attributes such as metabolic zonation and regeneration. The Wnt/β-catenin pathway plays a role in almost every facet of liver biology. Furthermore, its aberrant activation is also a hallmark of various hepatic pathologies. In addition to its signaling function, β-catenin also plays a role at adherens junctions. Wnt/β-catenin signaling also influences the function of many different cell types. Due to this myriad of functions, Wnt/β-catenin signaling is complex, context-dependent, and highly regulated. In this review, we discuss the Wnt/β-catenin signaling pathway, its role in cell-cell adhesion and liver function, and the cell type-specific roles of Wnt/β-catenin signaling as it relates to liver physiology and pathobiology.
Une épidémie de tularémie par transmission aérienne en France, août 2004
Authors: V Siret, D Barataud, M Prat, V Vaillant, S Ansart, A Le Coustumier, J Vaissaire, F Raffi, M Garré, I Capek
Journal: Eurosurveillance (2006)

Quinze cas de tularemie ont ete identifies apres un sejour dans un moulin amenage en habitation, en Vendee, entre le 9 et le 12 aout 2004. 
Une visite du moulin ainsi que des enquetes descriptive, de cohorte retrospective et environnementale, ont ete realisees. Les 39 personnes ayant sejourne dans le moulin entre le 24 juillet et le 11 aout ont ete interrogees sur leurs symptomes et leurs expositions (alimentaires, animales), et loisirs.
Un cas etait defini par une personne ayant eu de la fievre et presentant une serologie positive (seroconversion ou augmentation significative du titre d’anticorps ou titre unique) ≥ 40. Francisella tularensis a ete recherchee par culture et PCR dans l’eau d’alimentation du moulin, le bois de chauffage et chez les animaux domestiques.
Quinze cas de tularemie (38%) ont ete confirmes dont 12 (80%) presentant une forme pulmonaire. Aucun cas n’a ete hospitalise. 
La presence au moulin au diner du 4 aout etait fortement associee a la maladie (pl10-8). Un des trois chiens presents dans la saller a manger ce jour-la avait une serologie positive pour F. tularensis. 
Les analyses environnementales ont ete negatives. 
Ces investigations ont confirme la survenue de 15 cas groupes de tularemie, infectes le soir du 4 aout dans un moulin en Vendee, zone endemique pour la tularemie. Ces investigations ont egalement montre l’existence en France de formes pulmonaires non specifiques et sans gravite.
La forme pulmonaire de l’infection chez les cas humains et la serologie positive du chien suggerent une contamination par inhalation de particules contaminees presentes dans le pelage du chien et mises en suspension lorsque le chien s’ebroue.
PUB057 Neutrophil to Lymphocyte Ratio Predicts Survival in Advanced NSCLC Patients Treated with Second-Line PD-1 Immune Checkpoint Inhibitors
Authors: S. Labomascus, I. Fughhi, P. Bonomi, M. Fidler, J. Borgia, S. Basu, M. Hoch, M. Batus
Journal: Journal of Thoracic Oncology (2017)
MA 19.03 Nintedanib + Pemetrexed/Cisplatin in Malignant Pleural Mesothelioma (MPM): Phase II Biomarker Data from the LUME-Meso Study
Authors: A. Nowak, F. Grosso, N. Steele, S. Novello, S. Popat, L. Greillier, T. John, N. Leighl, M. Reck, N. Pavlakis, J.B. Sørensen, D. Planchard, G. Ceresoli, B. Hughes, J. Mazieres, M. Socinski, A. Salnikov, T. Kitzing, J. Braunger, K. Pietzko, G. Scagliotti
Journal: Journal of Thoracic Oncology (2017)
A Multigene Score based on gene-expression profiling as a prognostic tool in women with early stage, hormone receptor-positive/Her2-negative breast cancer
Authors: B. Conte, F. Poggio, V. Guarneri, E. Rota Caremoli, A. Rocca, F. Montemurro, M. De Laurentiis, O. Garrone, M. Giordano, G. Bisagni, F. Riccardi, L. Amaducci, A. Ferzi, N. La Verde, F. Cognetti, C. Bighin, B. Cardinali, U. Pfeffer, M. Lambertini, L. Del Mastro
Journal: Annals of Oncology (2017)
MA 13.01 Clinical and Pathological Variables Influencing Noninvasive Detection of Early Stage Lung Cancer Using Circulating Tumor DNA
Authors: J. Chabon, A. Chaudhuri, T. Azad, D. Kurtz, H. Stehr, C.L. Liu, J. Schroers Martin, D. Merriott, J. Carter, K. Ayers, A. Mansfield, J. Jen, H. Ren, R. West, V. Nair, J. Shrager, J. Neal, H. Wakelee, B. Loo, A. Alizadeh, M. Diehn
Journal: Journal of Thoracic Oncology (2017)
MA 20.06 Discerning Lung Cancer Cell Patterns with Confocal Endomicroscopy
Authors: M. Diez-Ferrer, B. Torrejon, N. Baixeras, E. Minchole, R.M. Ortiz, N. Cubero, R. Lopez-Lisbona, J. Dorca, A. Rosell
Journal: Journal of Thoracic Oncology (2017)
DDIS-01. INHIBITION OF BRAIN TUMOR INITIATING CELL GROWTH VIA NOVEL GLUCOSE TRANSPORTER ANTAGONISTS
Authors: Catherine Libby, Sixue Zhang, Gloria Benavides, Yanjie Li, Matthew Redmann, Anh Tran, Arphaxad Otamias, Victor Darley-Usmar, Mareck Napierla, Jianhua Zhang, Wei Zhang, Anita Hjelmeland
Journal: Neuro-Oncology (2017)

The heterogeneous nature of glioblastoma has hampered the development of new effective therapeutic options. This heterogeneity is partially attributed to a subset of tumor cells known as brain tumor initiating cells (BTICs) that are highly tumorigenic and have some properties of neural stem cells. BTICs display metabolic plasticity, but, like many cancer cells, can have a reliance on aerobic glycolysis. Elevated expression of the glucose transporters GLUT1 and GLUT3 is present in many cancer types, with GLUT3 being preferentially expressed in BTICs to promote survival in low nutrient microenvironments. Through structure-based virtual screening, we identified potential novel GLUT inhibitors. The screening of 13 compounds identified two that can preferentially inhibit the growth of BTICs with minimal toxicity to non-neoplastic astrocytes and neurons. These compounds, SR37683 and SR37684, also inhibit glucose uptake and reduce glycolytic metabolism in Seahorse assays. We intend to identify a potential new therapeutic option targeting metabolic reprogramming for the treatment of glioblastoma, as well as other tumor types.
P2.14-006 A Pilot, Randomized Trial of Daily Lisinopril vs Placebo to Prevent Radiation-Induced Pulmonary Distress (Alliance MC1221)
Authors: T. Sio, P. Atherton, W. Zhen, Y. Garces, D. Ma, S. Van Der Veen, A.K. Ganti, S. Schild, R. Miller
Journal: Journal of Thoracic Oncology (2017)
Inhibition of mTOR activity potentiates 2-DG-induced cell death in hypoxic cells via down-regulation of HIF-1α
Authors: Medhi Wangpaichitr, Johnathan Maher, Metin Kurtoglu, Niramol Savaraj, Theodore Lampidis
Journal: Cancer Research (2007)

4463   Hypoxic regions found in most solid tumors often contain cells which are resistant to various cancer therapies. However, hypoxia also forces cells to rely mainly on the catabolism of glucose through glycolysis for ATP production and survival, and thereby creates a therapeutic window that can be exploited by glycolytic inhibitors, i.e. 2-deoxyglucose (2-DG). Previously we reported that 2-DG is toxic to tumor cells growing in vitro under hypoxic conditions. Moreover, it was found that when hypoxia inducible factor (HIF-1) was attenuated using siRNA directed against this transcription factor in cells growing under hypoxia, sensitivity to 2-DG increased. Since HIF-1α translation is regulated by the major translational controller, mammalian target of rapamycin (mTOR), we examined the effects of blocking mTOR with a water soluble analog of rapamycin (CCI-779) and found that HIF-1α was down-regulated which coincided with increased sensitivity to 2-DG. A significant increase in trypan blue positive cells (indicating death) was observed when CCI-779 was combined with 2-DG as compared to 2-DG alone in the small cell lung cancer line, SCLCB, growing under hypoxic conditions for 72 hrs. At 6 and 8mM of 2-DG, 45 and 60% of these cells were dead while when combined with a non-toxic dose of CCI-779 (0.1µg/ml) cell death increased to 80 and 90% respectively. In addition, using HIF+ (Hepa-1) and HIF- (C4) cell lines growing under hypoxia, we found that in the C4 line, CCI-779 did not increase the toxicity of 2-DG whereas in the Hepa-1 cell line it did. Although blockage of mTOR leads to numerous downstream consequences, the fact that it did not increase 2-DG sensitivity in the HIF- cell line indicates that HIF is responsible for a level of resistance to 2-DG. Since CCI-779 is currently under clinical trials (Phase III), its activity in inhibiting HIF may prove to be beneficial to patients when combined with 2-DG, which is also in clinical trials (Phase I).
P3.01-016 Factors Associated with Symptoms Improvement and HRQoL for First-Line EGFR-TKIs in NSCLC: A Multicenter Prospective SMILE Study
Authors: Y. Wei, W. Huang, T. Liu, J. Shieh, C. Chian, M. Wu, C. Chang, C. Lin, J. Ko, C. Lin, T. Hsia
Journal: Journal of Thoracic Oncology (2017)
NIMG-88. RADIONOMIC ANALYSIS OF WHO GRADE 2 AND 3 GLIOMAS WITH GENETIC SUBGROUP PREDICTION
Authors: Manabu Kinoshita, Hideyuki Arita, Masamichi Takahashi, Yoshitaka Narita, Yuzo Terakawa, Naohiro Tsuyuguchi, Yoshiko Okita, Masahiro Nonaka, Shusuke Moriuchi, Junya Fukai, Shuichi Izumoto, Kenichi Ishibashi, Yoshinori Kodama, Kanji Mori, Kohichi Ichimura, Yonehiro Kanemura
Journal: Neuro-Oncology (2017)

Genetic alterations found in WHO grade 2 and 3 gliomas include IDH1/2 and TERT promoter mutations and 1p19q co-deletion, which alterations are known to have great impact on the prognosis of the patient. In this research, the authors attempted to test the hypothesis that genetic alterations could contribute to the locations and heterogeneity of the tumor by analyzing 191 WHO grade 2 and 3 gliomas via MR radionomics. 191 WHO grade 2 and 3 gliomas were retrospectively collected and the genomic DNA of the tumor was sequenced for IDH1/2 and TERT promoter mutations. Treatment naive MR images were also collected. T2 weighted, T1 weighted, FLAIR and Gd-enhanced T1 weighted images were collected for analysis. Voxel-based lesion mapping (VLM), and redionomics analysis was performed for all images and were further challenged to construct a model that predicts genetic alterations within the tumor. 126 patients were allocated as training set and 65 for validation set. Patient cohort was divided into the following 3 groups; IDH mt/TERTp wt, IDH mt/TERTp mt and IDH wt. A multi-regression model was constructed using the training set to predict the 3 genetic subgroups and the validation set was used for model validation. VLM revealed that IDH mt/TERTp wt gliomas dominated temporal lobe involvement while IDH mt/TERTp mt occupied the frontal lobe. IDH wt tumors, on the other hand, located at much posterior lobes and centered at the deep white matter. 15 radionomic features were identified for model construction to predict 3 genetic subgroups of WHO grade 2 and 3 gliomas. When these 15 texture elements were used to construct a prediction model of the 3 genetic subgroups, AUCs calculated from the training set ranged from 0.7 to 0.75. Accuracy for prediction was 63% for the training set and 60% for the validation set.