tbuckley/cabot-search huggingface dataset:
TMOD-34. DNA HELICASES HELB AND ATRX MAINTAIN GLIOMA STEM CELLS
Authors: Qiulian Wu, Briana Prager, Tanwarat Sanvoranart, Shideng Bao, Jeremy Rich
Journal: Neuro-Oncology (2017)

Glioma stem cells (GSCs) represent highly tumorigenic, self-renewing cells that contribute to tumor invasion, angiogenesis, and therapeutic resistance. Using comparative gene expression analysis from validated GSC models, we found two DNA helicases – DNA helicase B (HELB) and ATP-dependent helicase (ATRX) – were preferentially expressed in GSCs relative to matched differentiated glioma cells (DGCs). While ATRX mutation has been associated with diffuse astrocytomas, its role in the glioma cellular hierarchy has not been investigated to date, whereas HELB has not been studied in gliomas. We confirmed the differential expression of HELB and ATRX using RT-PCR and immunoblotting of matched GSC and DGC cultures, as well as neural stem cells, with concordance in active histone marks measured by histone 3 lysine 27 acetyl (H3K27ac). Targeting either HELB or ATRX in GSCs reduced cellular proliferation, induced apoptosis, and blocked self-renewal. In contradistinction, HELB overexpression in DGCs or neural stem cells increased cellular proliferation. Supporting the potential therapeutic value of these targets, the survival of mice bearing intracranial GSCs was significantly extended upon targeting of either HELB or ATRX. Clinical significance of HELB was noted with an association with the mesenchymal transcriptional subgroup of glioblastoma and reduced survival. Collectively, these results suggest that GSCs may preferentially express helicases due to differences in proliferation and endogenous DNA damage relative to the tumor bulk, potentially informing the development of novel therapeutic targeting of therapeutically resistant glioblastoma cells.
PDTM-18. INVESTIGATING INTRA-CAVITY NEURAL STEM CELL THERAPY FOR POST-SURGICAL DISEASE IN A NOVEL SURGICAL RESECTION/RECURRENCE MODEL OF MEDULLOBLASTOMA
Authors: Onyinyechukwu Okolie, Elizabeth Finch, David Irvin, Juli Bago, Kevin Sheets, Andrew Satterlee, Raluca Dumitru, Simon Khagi, Scott Elton, Matthew Ewend, Shawn Hingtgen
Journal: Neuro-Oncology (2017)

Cytotoxic neural stem cells (NSCs) are a promising treatment for Medulloblastoma (MB), the most common primary pediatric brain tumor. Surgical resection is part of the clinical standard of care for MB, yet tumoricidal NSC therapy for post-operative MB remains unexplored. In this study, we developed an image-guided model MB surgical resection/recurrence and investigated multiple aspects of intra-cavity NSC therapy for post-operative MB. To create the first image-guided resection model of orthotopic MB, human MB cells (D283 and Daoy) engineered to express fluorescent and bioluminsescent optical reporters were orthotopically xenografted into the brain of Nude mice. Image-guided surgical resection was used to resect the established tumor and track recurrence. Brain-derived NSCs and novel induced NSCs (iNSCs) generated from pediatric skin were engineered to express cytotoxic agents, seeded into the post-operative cavity, and used to investigate intra-cavity therapy for post-surgical MB. Image-guided surgery reduced 92% of the MB volumes, and we discovered the rate of post-operative MB regrowth increased 3-fold compared to pre-resection growth. In vivo, real-time kinetic imaging showed that NSCs rapidly to MB, migrating 1.6-fold faster and 2-fold farther in the presence of tumors, and migrated through the cerebellum of mice to populate MB in the contra-lateral hemisphere. Using the resection/recurrence model, we found that seeding of cytotoxic NSCs into the post-operative surgical cavity decreased MB volumes 15-fold and extended median survival 133%. As a novel autologous therapy, we found that iNSCs homed to MB cells, while intracavity iNSC therapy suppressed post-surgical tumor growth and prolonged survival of MB-bearing mice by 123%. We report a novel image-guided model of MB resection/recurrence and provide new evidence that cytotoxic NSCs/iNSCs delivered into the surgical cavity effectively target residual MB foci, providing a new treatment option to MB patients.
Bald is beautiful: No more. The stigma of alopecia during chemotherapy: Brindisi oncology department experience
Authors: D. Loparco, L. Orlando, M. Caloro, P. Fedele, P. Schiavone, A. Quaranta, C. Caliolo, M. Cinefra, P. Ferrara, L.L. Falcone, V. Capone, C. Destro, A. Morleo, A. Ricco, V. Bonuso, G. Lotti, M. D'amico, P. Rizzo, A. Marino, S. Cinieri
Journal: Annals of Oncology (2018)
Voters back Obamacare in local and state elections
Authors: Owen Dyer
Journal: BMJ (2017)

Strong support for Democrats in local and statewide elections on 7 November left Republicans looking further than ever from their goal of repealing Barack Obama’s 2010 healthcare legislation, the Affordable Care Act.

The election had been billed by pundits as a referendum on Donald Trump’s governing style, but healthcare seemed to weigh just as heavily on voters’ minds.

Exit polling in the hard fought Virginia governor’s race showed that Obamacare, which for seven years was seen as a drag anchor on Democratic electoral fortunes, is now the party’s strongest selling point.

From a menu of five issues, 39% of Virginia voters said that healthcare was the most important, dwarfing any other concern. Only …
Efficacy and safety of the combination of pertuzumab (P) plus trastuzumab (T) plus docetaxel (D) for HER-2 positive metastatic breast cancer (MBC) in pretreated patients (pts) with trastuzumab in the neo/adjuvant setting: a retrospective real-life study
Authors: G. Ricciardi, C. Ficorella, L. Iezzi, P. Marchetti, L. Pizzuti, A. Prestifilippo, S. Schifano, S. Maimone, V. Adamo
Journal: Annals of Oncology (2017)
Progression after the next line of therapy (PFS2) and updated OS among patients (pts) with advanced NSCLC and PD-L1 tumor proportion score (TPS) ≥50% enrolled in KEYNOTE-024.
Authors: Julie R. Brahmer, Delvys Rodriguez-Abreu, Andrew George Robinson, Rina Hui, Tibor Csõszi, Andrea Fülöp, Maya Gottfried, Nir Peled, Ali Tafreshi, Sinead Cuffe, Mary O'Brien, Suman Rao, Katsuyuki Hotta, Melanie A. Leiby, Jessica McLean, Yue Shentu, Reshma A. Rangwala, Martin Reck
Journal: Journal of Clinical Oncology (2017)

9000 Background: In KEYNOTE-024 (NCT02142738), pembrolizumab (pembro) was superior to chemotherapy (chemo) as first-line (1L) therapy for advanced NSCLC with PD-L1 TPS ≥50% and no sensitizing EGFR mutations or ALK translocations. After a median follow-up of 11.2 mo, HR was 0.50 for PFS by independent central radiologic review ( P&lt; 0.001) and 0.60 for OS ( P= 0.005). Here we present PFS2 and updated OS. Methods: 305 pts were randomly assigned to pembro 200 mg Q3W (n = 154) or investigator (INV)-choice platinum-doublet chemo with optional pemetrexed maintenance for nonsquamous histology (n = 151). Pts in the chemo arm could cross over to pembro upon PD. Poststudy anticancer therapy and INV-assessed outcomes were collected. Kaplan-Meier PFS2 and OS were calculated in all allocated pts. PFS2 was defined as time from randomization to PD per INV after start of 2L+ therapy or death, whichever occurred first; pts alive and without 2L+ PD were censored at last known survival. Kaplan-Meier OS was defined as time from randomization to death. There was no adjustment for multiplicity (cutoff: Jan 5, 2017). Results: 2L+ therapy was received by 48 (31.2%) pts in the pembro arm and 97 (64.2%) in the chemo arm, including 80 pts who crossed over from chemo to pembro per protocol and 14 pts who received anti–PD-1 therapy outside of crossover. 56 (36%) 1L pembro pts were on 1L pembro therapy or in follow-up as of data cutoff. Updated median OS and PFS2 results are in the Table. Conclusions: Fewer pembro pts received 2L+ therapy vs chemo pts because of the significant improvement in PFS observed for pembro in the 1L setting. Median PFS2 was substantially improved for pembro (not reached [NR]) vs chemo (8.6 mo). Updated OS with median follow-up of 19 mo maintained consistent superiority of 1L pembro, despite increased crossover from 1L chemo. Clinical trial information: NCT02142738. [Table: see text]
IMMU-06. GCN2 KINASE IS ESSENTIAL FOR ADAPTIVE T-CELL IMMUNITY IN GLIOMA
Authors: Aida Rashidi, Jason Miska, Katarzyna Pituch, Deepak Kanojia, Aurora Lopez-Rosas, Yu Han, Julius W Kim, Wojciech K Panek, Megan Muroski, Maciej S Lesniak
Journal: Neuro-Oncology (2017)

GCN2 Kinase is a stress sensing enzyme that is activated upon amino acid depletion, shutting down global gene expression as a means of energy conservation. This gene has been implicated as the mechanistic explanation for how tryptophan depletion by indolamine 2-3-dioxygenase (IDO1) induces immunosuppression. The role that this pathway has in glioma immunosuppression is unknown. In this study we addressed T-cell responses in the absence of GCN2 in glioma bearing mice. Interestingly, after flow cytometric analysis of the brain infiltrating lymphocytes, there is a drastic decrease in the total T-cell infiltration in GCN2 knock out (KO) mice as compared to the wild-type mice, despite an increased survival benefit (p= 0.0066). In-vitro live/dead staining highlighted an increase in CD8 T-cell death, especially in the context of tryptophan depletion. Intracellular cytokine analysis revealed a significant decrease in T-cell activation and cytokine production by GCN2 deficient mice, arguing against T-cell mediated immunity influencing enhanced animal survival in these mice. Therefore, we analyzed the myeloid cells in the tumor bearing brain and we discovered that myeloid derived suppressor cells (MDSCs), in GCN2 KO mice had significant decrease in their expression of monocytic MDSCs (LY6C+), compared to the wild-type mice. To address the activity of the MDSCs, we co-cultured bone marrow derived MDSCs with OVA pulsed OT1 splenocytes, and our data demonstrate a significant decrease in the suppressive activity of the MDSCs from GCN2 KO as compared to wild-type mice, which potentially explains the increased survival of GCN2 KO mice with glioma. In conclusion, our data demonstrate that the GCN2 pathway is critical for CD8 T-cell function and fitness in the context of glioma, and must be taken into consideration as GCN2 inhibitors are currently in development for cancer therapy.
MA 12.10 Clinical Utility of Plasma EGFR T790M Mutation Detection in Advanced Non-Small Cell Lung Cancer Patients According to RECIST Criteria
Authors: L. Barrera, J.R. Borbolla-Escoboza, E. Montes-Servin, E.O. Macedo-Perez, F. Barron, C. Molina Romero, J. Hernandez Martinez, O. Arrieta
Journal: Journal of Thoracic Oncology (2017)
Epidemiological information is key when interpreting whole genome sequence data – lessons learned from a large Legionella pneumophila outbreak in Warstein, Germany, 2013
Authors: Markus Petzold, Karola Prior, Jacob Moran-Gilad, Dag Harmsen, Christian Lück
Journal: Eurosurveillance (2017)

Introduction Whole genome sequencing (WGS) is increasingly used in Legionnaires’ disease (LD) outbreak investigations, owing to its higher resolution than sequence-based typing, the gold standard typing method for Legionella pneumophila, in the analysis of endemic strains. Recently, a gene-by-gene typing approach based on 1,521 core genes called core genome multilocus sequence typing (cgMLST) was described that enables a robust and standardised typing of L. pneumophila . Methods : We applied this cgMLST scheme to isolates obtained during the largest outbreak of LD reported so far in Germany. In this outbreak, the epidemic clone ST345 had been isolated from patients and four different environmental sources. In total 42 clinical and environmental isolates were retrospectively typed. Results : Epidemiologically unrelated ST345 isolates were clearly distinguishable from the epidemic clone. Remarkably, epidemic isolates split up into two distinct clusters, ST345-A and ST345-B, each respectively containing a mix of clinical and epidemiologically-related environmental samples. Discussion/conclusion : The outbreak was therefore likely caused by both variants of the single sequence type, which pre-existed in the environmental reservoirs. The two clusters differed by 40 alleles located in two neighbouring genomic regions of ca 42 and 26 kb. Additional analysis supported horizontal gene transfer of the two regions as responsible for the difference between the variants. Both regions comprise virulence genes and have previously been reported to be involved in recombination events. This corroborates the notion that genomic outbreak investigations should always take epidemiological information into consideration when making inferences. Overall, cgMLST proved helpful in disentangling the complex genomic epidemiology of the outbreak.
P1.02-058 Molecular Characteristics and Outcome of Chinese Patients with Non-Small Cell Lung Cancer Harboring NFE2L2 Mutations
Authors: W. Wang, C. Xu, W. Zhuang, Z. Song, Y. Zhu, R. Chen, Y. Guan, X. Yi, Y. Chen, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
SCDT-36. NOVEL MODULAR, PERMANENTLY IMPLANTED COLLAGEN-BASED DEVICE FOR INTRAOPERATIVE BRACHYTHERAPY IN PATIENTS WITH CENTRAL NERVOUS SYSTEM TUMORS
Authors: Emad Youssef, Peter Nakaji, Teresa Thomas, Heyoung McBride, Evan Fram, David Brachman
Journal: Neuro-Oncology (2017)

Brachytherapy (BT) is a current standard of care treatment for many non-central nervous system (CNS) tumors, but is rarely used for as an adjuvant CNS tumor treatment. Combining surgical resection with adjuvant BT in brain tumors represents an attractive therapeutic option as immediate post resection radiation could evince a higher therapeutic ratio in rapidly proliferating tumors, BT using a short-range isotope exposes less normal tissue to radiation than EBRT (possibly limiting neurocognitive deficits), and source placement under intraoperative visualization allows more precise identification of the area at risk than does post-operative treatment imaging. Major challenges in brain brachytherapy have been 1) the occurrence of radiation "hot spots" and "cold spots" resulting from uneven spacing of radiation sources (called "seeds") and direct seed-to-brain contact, and 2) the poor handling qualities of the seeds themselves, 4.5 mm x 0.8 mm radioactive cylindrical titanium capsules. Radiation hot spots and direct seed-to-brain contact can result in excess radiation and injury, and radiation cold spots that receive too little radiation may lead to tumor persistence. To overcome these draw-backs we designed the GammaTile™. The GammaTile™ is a modular, permanently implanted collagen-based device designed to function simultaneously as a three-dimensional spacer and multi-seed carrier, preventing seeds from harmful direct contact with the brain, maintaining source geometry, eliminating seed migration, and facilitating rapid implant completion. We utilized Cesium-131, a low energy (28 kV), short half-life (9.7 days) isotope as rapid decay may offer a biological advantage in treatment of rapidly proliferating tumors. Using GammaTile™, the radiation dose in the first few millimeters of the operative bed is 90-120 Gy, 1.5-2 times greater than the 60Gy typically achieved by fractionated EBRT. We have initiated a proof of concept trial of resection plus BT (NCT#03088579) utilizing a prototype device which has enrolled >100 patients to date.
The combination of mucus-degrading gram-negative bacteria and reduced antimicrobial peptides drives adipose tissue inflammation and non-alcoholic fatty liver disease progression in mice lacking NLRP3-inflammasome
Authors: I. Pierantonelli, C. Rychlicki, D.M. Giordano, A. Giordano, S. Uzzau, A. Gastaldelli, L. Sartini, L. Trozzi, A. Benedetti, M. Marzioni, S. Cinti, G.S. Baroni
Journal: Journal of Hepatology (2017)
P1.16-006 Less Is More: video Assisted Thoracic Surgery (VATS) vs Open Thoracotomy in the Management of Resectable Lung Cancer
Authors: S. Shaheen, B. Jabo, M. Kaur, M. Senthil, S. Mirshahidi, S. Zaheer, H. Mirshahidi
Journal: Journal of Thoracic Oncology (2017)
Les formes classiques et émergentes du botulisme : situation actuelle en Italie
Authors: P Aureli, L Fenica, G Franciosa
Journal: Eurosurveillance (1999)

Le botulisme est une maladie rare, grave et neuroparalysante. Quatre formes sont decrites chez l’homme : le botulisme d’origine alimentaire, le botulisme par blessure, decrit plus recemment, le botulisme du nourrisson et le botulisme infant-like de l'adulte. Ces deux dernieres formes sont parfois regroupees sous le terme descriptif botulisme toxemique intestinal, signifiant infection intestinale par des bacteries neurotoxiques de l’espece Clostridium tant chez le jeune enfant que chez l’adulte. Trois especes de Clostridium ont jusqu’a present ete associees a ces quatre formes de botulisme chez l’homme : C. botulinum, la forme classique, qui produit les toxines de type A, B, E et F, et deux souches rares, C. butyricum et C. baratii qui produisent respectivement des toxines botulinum-like de type E et F. Les deux formes, classique et emergente, sont survenues en Italie.
Diecisiete años de formación en Epidemiología de Campo en Veyrier-du-Lac, 1984-2000
Authors: P Malfait, B Helynck
Journal: Eurosurveillance (2001)

A comienzos de los anos ochenta, los profesionales de la salud publica organizaron seminarios destinados a evaluar la formacion de epidemiologos en Francia, en los que se pusieron de manifiesto las deficiencias existentes en la ensenanza de la epidemiologia de campo. Hasta entonces, la epidemiologia en Francia se limitaba principalmente a la investigacion. La evolucion de la practica de la salud publica, que exigia cada vez mas justificar las decisiones con datos epidemiologicos, hizo necesaria la creacion de una red de epidemiologos de campo debidamente formados para trabajar con metodos estandarizados.
Vaccination avec les vaccins conjugés contre le pneumocoque et le méningocoque et le vaccin contre la varicelle en Italie
Authors: F D'Ancona, V Alfonsi, M R Caporali, A Ranghiasci, M L Ciofi Degli Atti
Journal: Eurosurveillance (2007)

Le vaccin conjugue antipneumococcique heptavalent (PCV-7), le vaccin conjugue contre le meningocoque C (MenC) et le vaccin contre la varicelle ont recemment ete introduits dans l’UE. En Italie, l’utilisation de ces vaccins etait jusqu’a present recommandee chez des groupes specifiques. Avec la decentralisation du systeme de sante, la decision de recommander la vaccination chez d’autres populations cible peut etre prise par les autorites sanitaires regionales. 
Une etude a ete realisee pour faire le point sur les recommandations actuellement en place dans les 21 regions d’Italie. 
En novembre 2005, un questionnaire standardise a ete envoye a toutes les autorites sanitaires regionales. Ce questionnaire portait sur les recommandations existantes au niveau regional, la population ciblee par la vaccination, l’acces au vaccin gratuit ou a un cout reduit par rapport a celui applique dans les pharmacies. Les informations rapportees sur ces questionnaires ont ete analysees au mois de mai 2006. 
Les 21 autorites regionales ont complete et envoye le questionnaire, puis ont ete contactees pour le suivi. Sur les 21 regions, 20 disposaient de recommandations sur au moins l’un des trois vaccins. Toutes fournissaient le PCV gratuitement aux groupes specifiques. La vaccination contre le meningocoque et la varicelle etait recommandee dans respectivement 17 et 19 regions. Les recommandations pour les autres groupes de population etaient tres variables selon les regions : vaccination gratuite de tous les nourrissons pour les PCV et MenC dans neuf regions, vaccination contre la varicelle chez les enfants de deux ans dans trois regions. Ces differentes recommandations peuvent mener a d’importantes variations des taux de couverture vaccinale dans le pays, entrainant differents niveaux de controle de la maladie. Il est donc essentiel d’evaluer correctement les taux de couverture vaccinale pour la vaccination contre le pneumocoque, le meningocoque et la varicelle, ces vaccinations ne faisant pas l’objet d’une surveillance en routine au niveau national.
ACTR-13. EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) AMPLIFICATION RATES OBSERVED IN SCREENING PATIENTS FOR RANDOMIZED CLINICAL TRIALS IN GLIOBLASTOMA
Authors: Martin van den Bent, Lisa A Roberts-Rapp, Peter J Ansell, James Lee, Jim Looman, Earle Bain, Christopher Ocampo, Kyle D Holen, Erica J Gomez, Andrew B Lassman
Journal: Neuro-Oncology (2017)

EGFR is a key oncogenic target for the treatment of glioblastoma. EGFR amplification is detected in ~50% of tumors. Depatuxizumab mafodotin (depatux-m), formerly called ABT-414, is a tumor-specific antibody-drug conjugate that preferentially targets tumors with EGFR amplification. Herein, we report the frequency of EGFR amplification in 2 large-scale glioblastoma clinical trials of depatux-m. As of May 1, 2017, testing for EGFR amplification status was performed centrally in 2077 glioblastoma samples during screening for 2 randomized glioblastoma trials with depatux-m: INTELLANCE 1 (NCT02573324) for newly diagnosed patients (n=1001), and INTELLANCE 2 (NCT02343406) for recurrent disease (n=1076). EGFR amplification, required for eligibility in both trials, was determined by fluorescence in situ hybridization and defined as at least 2 copies in at least 15% of cells. EGFRvIII mutation data will be reported at the meeting. Out of 2077 total patients, 1084 were positive for EGFR amplification (52.2%), similar to published rates. Per world region number and frequency of EGFR amplification was as follows: Africa (4/9; 44.4%), Americas (238/451; 52.8%), Asia (69/201; 34.3%), Europe (672/1190; 56.5%), Middle East (21/40; 52.5%), Oceania (80/186; 43.0). 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.
Malaria e turismo: analisi retrospettiva dei casi tedeschi di malaria importati dalla Repubblica Dominicana
Authors: J Richter, A Sagir, A. Schöneberg, K Alpers, D Häussinger
Journal: Eurosurveillance (2001)

Questo rapporto riguarda la malaria acquisita tra luglio 1999 e marzo 2000 da turisti tedeschi presso localita turistiche precedentemente non-endemiche nella Repubblica Dominicana. La malaria da Plasmodium falciparum e endemica nelle province occidentali e nell'hinterland della Repubblica Dominicana. Per contro, il rischio di contrarre la malaria e sempre stato considerato cosi basso nelle principali localita turistiche nella parte orientale del paese che non e stata raccomandata la chemioprofilassi antimalarica (1).
P2.01-024 Expression of miR-106 Paralogs Improves Prognostic Value of Mesenchymal Signatures but Only miR-106b Promotes Invasiveness
Authors: Sonia Kung, Katey Enfield, David Rowbotham, Erin Marshall, Alice Holly, Chiara Pastrello, Brenda Minatel, Graham Dellaire, Jason Berman, Igor Jurisica, Calum Macaulay, Stephen Lam, Wan Lam
Journal: Journal of Thoracic Oncology (2017)
P3.07-009 PI3K/mTOR Pathway Alterations May Mediate PD-1/PD-L1 Blockade Resistance in Non-Small Cell Lung Cancer
Authors: T. Shou, X. Wu, Y. Shang, F. Gao, W. Wang, Z. Zhang, B. Wang, Y. Wang, J. Shi, M. Yao, A. Wang, K. Wang
Journal: Journal of Thoracic Oncology (2017)
Histamine-releasing factor: a promising therapeutic target for food allergy
Authors: Marsha Wills-Karp
Journal: Journal of Clinical Investigation (2017)

The prevalence of food allergies has been increasing at an alarming rate over the last few decades. Despite the dramatic increase in disease prevalence, the development of effective therapies has not kept pace. In this issue of the JCI, Ando et al. provide a causal link between histamine-releasing factor (HRF) interactions with IgE and food allergy in a murine model. Successful oral immunotherapy of both egg-allergic human patients and food-allergic mice was associated with sustained suppression of HRF-reactive IgE levels. These results support a role for HRF-IgE interactions in the amplification of intestinal inflammation and suggest HRF as a therapeutic target in food allergy.