tbuckley/cabot-search huggingface dataset:
EXTH-50. DEVELOPMENT OF INVESTIGATOR INITIATED CLINICAL TRIAL OF TERT-TARGETING THERAPY USING ERIBULIN MESYLATE IN PATIENTS WITH RECURRENT GLIOBLASTOMA
Authors: Masamichi Takahashi, Shunichiro Miki, Kohei Fukuoka, Yoshiko Maida, Mitsuhiro Hayashi, Akinobu Hamada, Ryo Nishikawa, Motoo Nagane, Takashi Maruyama, Akitake Mukasa, Yoshiki Arakawa, Hideyuki Arita, Natsuko Kitamura, Kan Yonemori, Kenji Tamura, Kenkichi Masutomi, Yoshitaka Narita, Koichi Ichimura
Journal: Neuro-Oncology (2017)

Despite of recent intense investigations, no effective molecular targeting therapy has been successfully developed in patients with glioblastomas (GBMs). Approximately 60–80% of GBM harbor mutations in the promoter region of telomerase reverse transcriptase (TERT), which leads to its upregulation. It has been reported recently that TERT has an RNA-dependent RNA polymerase (RdRP) activity and TERT-RdRP activity controls cell cycle and maintains stem cell phenotype, suggesting that TERT can be directly targeted to suppress tumor cell proliferation. We have previously identified eribulin mesylate, which is an FDA-approved drug used to treat breast cancer and liposarcoma, as a specific inhibitor of RdRP activity of TERT and investigated the antitumor efficacy of eribulin using multiple human GBM cell lines in preclinical mouse brain tumor models. All GBM cell lines tested in vitro that harbored TERT promoter mutations were highly sensitive to eribulin with IC50 below 1nM. Intraperitoneal administration of eribulin (0.5 mg/kg), which was equivalent to the dose used in human (1.4 mg/m2), significantly prolonged the survival of multiple mouse brain tumor models established with U87MG or LN229 (p<0.001 or 0.01, respectively). We also found that high concentration of eribulin was detected in the brain tumour tissues as early as 15 minutes after intravenous injection of eribulin and it remained even 24 hours later. Further, RdRP activity in tumor tissue was supressed with eribulin administration in dose-dependent manner. Based on these results, a mutli-center, open-labelled phase II investigator initiated clinical trial using eribulin mesylate in the patients with recurrent GBM after failing temozolomide and bevacizumab is being scheduled in Japan. This will be the first clinical trial that eribulin mesylate is used in the patients with primary brain tumor and the relationship of eribulin and TERT promoter mutations are investigated. Trial designs and further details will be presented at the meeting.
ACTR-57. DOES THE ADDITION OF VALPROIC ACID TO CONCURRENT RADIATION THERAPY AND TEMOZOLOMIDE IMPROVE PATIENT OUTCOME? – CORRELATIVE ANALYSIS OF RTOG 0525, SEER AND A PHASE II NCI TRIAL
Authors: Andra Krauze, Sten Myrehaug, Michael Chang, Diane Holdford, Sharon Smith, Joanna Shih, Philip Tofilon, Howard Fine, Lindsay Rowe, Mark R Gilbert, Kevin Camphausen
Journal: Neuro-Oncology (2017)

The addition of the antiepileptic agent valproic acid (VPA) to standard radiation therapy (RT) and temozolomide (TMZ) was evaluated in a two center, open-label, phase II study (NCI-06-C-0112). The intent of this current analysis was to compare patient outcome with modern era standard of care data (RTOG 0525) and general population data (SEER 2006–2013). 37 GBM patients were treated in a phase II NCI trial with daily VPA (25 mg/kg) in addition to concurrent RT and TMZ (2006–2013). 411 GBM patients were treated in standard TMZ dose arm of RTOG 0525 (2006–2008). Using the SEER database (2006–2013), adult patients with GBM were identified and 6402 were included in the analysis. Kaplan-Meier method was used to estimate OS and PFS. The effect of patient characteristics and clinical factors on OS and PFS was analyzed using univariate analysis, a Cox regression model and landmark analysis. Median OS in the NCI cohort was superior to the RTOG 0525 and SEER cohorts with a median OS of 29.6 months (21- 63.8), compared to 18.9 months (16.8–20.3) and 13.1 months (p= 0.007). Median PFS was superior in the NCI cohort, 10.2 months (6.6 – 49.6) as compared to RTOG 0525 with a median PFS of 7.5 months (6.9–8.2) (p = 004). In comparison to RTOG 0525, the population in the NCI cohort had better KPS and RPA, and a higher proportion of patients receiving bevacizumab (57% vs 28%), however with the exception of RPA (V), the effects of these factors on PFS and OS were not significantly different between the two cohorts. Previously reported improvements in PFS and OS with the addition of VPA to concurrent RT and TMZ in the NCI phase II study were confirmed in comparison to RTOG0525 and a contemporary SEER cohort.
O consumo de mariscos e a consciência do risco de adquirir hepatite A em famílias napolitanas – Itália, 1997
Authors: G Salamina, P D'Argenio
Journal: Eurosurveillance (1998)

Em 1996, cerca de 15% de todos os casos de hapatite A (n=8651), em Italia, foram originarios da regiao de Campania, tendo Napoles registado a incidencia mais elevada da regiao (34,9/100.000). Quase metade de todos os casos tinha entre 15 e 24 anos de idade. O consumo de bivalves, particularmente crus ou insuficientemente cozidos, e responsavel por cerca de 70% dos casos de hepatite A, notificados em Italia, nos ultimos anos (1,2) e varios surtos recentes de hepatite A estao ligados aquele consumo (3-5).
CMET-04. CEREBROSPINAL FLUID CIRCULATING TUMOR CELLS (CSF CTC) FOR PATIENT MONITORING AND RESPONSE TO TREATMENT
Authors: Rachna Malani, Martin Fleisher, Xuling Lin, Antonio Omuro, Morris D Groves, Nancy Lin, Michelle Melisko, Andrew B Lassman, Suriya Jeyapalan, Samuel Briggs, Lisa DeAngelis, Jeffrey Raizer, Elena Pentsova
Journal: Neuro-Oncology (2017)

The CellSearch system (Janssen Diagnostics, LLC) is an FDA-approved methodology for enumerating CTCs from blood in patients with breast, prostate and colon cancers. It has also been used to evaluate CSF CTC of patients with leptomeningeal metastasis (LM). We explored the use of CSF CTC enumeration over time in patients with LM receiving intrathecal (IT) therapy as a potential biomarker of treatment response. CSF from patients participating in an IRB-approved phase I/II dose escalation trial of IT trastuzumab for LM in HER2+ cancer (NCT01325207) was evaluated using the CellSearch system. Three ml CSF from a ventricular reservoir was collected for CSF CTC enumeration and cytology at pre-treatment Day 1 of each cycle. CSF was also analyzed for HER2 expression using HER2 antibodies. This was correlated with clinical and radiographic response. LM progression was defined as clinical or radiographic worsening. Fifteen patients with HER2+ LM (14 breast, 1 colon) were enrolled; 14 were women. Six patients had baseline positive CSF cytology; the remaining were diagnosed by MRI. Of the 15 patients, 10 had greater than 1 cycle of treatment to be evaluable; 5 patients progressed during cycle 1. Median CSF CTC at baseline was 22 per 3ml (range 0–200); 2 patients had no detectable CSF CTCs. A decrease in CSF CTC was observed in 5 patients after cycle 1 and remained low (mean =9.5, range 0–92) in 2 patients while disease was stable. 3 patients had a rise in CSF CTCs roughly 1 month prior to progression. In the 10 patients with HER2 analysis, number of CTCs correlated with HER 2 expression. CSF CTC HER2 expression provided further affirmation that CTCs are malignant. Changes in CSF CTC enumeration allow quantitative surveillance of treatment response or as an early biomarker of LM progression and should be further investigated.
MS 24.04 Possibility of Radiotherapy for GGO-Containing Tumors
Authors: H. Onishi, Y. Shioyama, Y. Matsumoto, K. Takayama, Y. Matsuo, A. Miyakawa, H. Yamashita, H. Matsushita, M. Aoki, K. Nihei, T. Kimura, H. Ishiyama, N. Murakami, K. Nakata, A. Takeda, T. Uno, T. Nomiya, T. Takanaka, Y. Seo, T. Komiyama, K. Marino, S. Aoki, K. Kuriyama
Journal: Journal of Thoracic Oncology (2017)
P3.01-050 A Real World Treatment Study of Osimertinib: ASTRIS Study Korean Subgroup Analysis
Authors: B.C. Cho, D. Kim, K. Park, J. Lee, S.S. Yoo, J. Kang, S.Y. Lee, C.H. Kim, S.H. Jang, Y. Kim, H. Yoon, S. Kim
Journal: Journal of Thoracic Oncology (2017)
Brief Report: Drugs Implicated in Systemic Autoimmunity Modulate Neutrophil Extracellular Trap Formation
Authors: Jorge A. Irizarry‐Caro, Carmelo Carmona‐Rivera, Daniella M. Schwartz, Sami S. Khaznadar, Mariana J. Kaplan, Peter C. Grayson
Journal: Arthritis & Rheumatology (2017)

Aberrant neutrophil extracellular trap (NET) formation has been implicated as a mechanism to induce autoreactivity in individuals at risk of autoimmune diseases. The objective of this study was to assess whether medications implicated in cases of drug-induced autoimmunity (hydralazine and procainamide) and medications less commonly associated with drug-induced autoimmunity (minocycline and clozapine) induce NET formation and/or prevent NET degradation.Human neutrophils were incubated with the drugs of interest and resultant NET formation was quantified by fluorescent microscopy. The ability of these drugs to interfere with NET degradation by serum nuclei was assessed. Pathways of drug-induced NET formation were studied with pharmacologic inhibitors of reactive oxygen species (ROS), peptidylarginine deiminases (PADs), and muscarinic receptors, and by assessment of intracellular calcium levels by flow cytometry. To determine if NET protein cargo varies by drug stimulus and/or neutrophil source, proteomic analysis of NET lysates induced by specific medications was compared using neutrophils from healthy donors and from patients with autoimmune diseases.Hydralazine and procainamide significantly induced NET formation while minocycline and clozapine did not. None of the medications significantly impaired NET degradation. NETosis induced by these drugs required NADPH oxidase and PAD4 activation. Procainamide triggered NETs via muscarinic receptor engagement on neutrophils, while hydralazine modulated calcium release from intracellular stores. Differences in protein cargo, particularly histone content, were observed in NETs induced by hydralazine and procainamide.Medications commonly implicated in drug-induced autoimmunity trigger NET formation displaying distinct protein cargo, via common and specific pathways. NETosis may play a role in the pathogenesis of drug-induced autoimmunity.
P3.01-006 Osimertinib in Pretreated EGFR T790M-Positive Non-Small Cell Lung Cancer Patients with Leptomeningeal Carcinomatosis
Authors: B. Liao, C. Lin, J. Lee, C. Ho, K. Chen, Y. Chen, H. Lien, J. Shih, C. Yu, J.C. Yang
Journal: Journal of Thoracic Oncology (2017)
Epidemia de parotiditis en Portugal pese a la alta cobertura de vacunación - informe preliminar
Authors: J A Dias, M Cordeiro, M A Afzal, M G Freitas, M. R. Morgado, J. L. Silva, L. M. Nunes, M. G. Lima, F Avilez
Journal: Eurosurveillance (1996)

En 1987, se anadio la vacuna trivalente de sarampion, parotiditis y rubeola (SPR) al Programa Nacional de Inmunizacion de Portugal (PNI). Todas las vacunas se administran gratuitamente en centros sanitarios, pero pese a ello en 1995 comenzo una epidemia de parotiditis, al norte de Portugal en un principio y en la actualidad se ha propagado a otras zonas.
P1.14-016 Assessing the Feasibility of FLT-PET for Evaluation of Non-Small Cell Lung Cancer (NSCLC) Treated with Stereotactic Body Radiotherapy (SBRT)
Authors: H. Raziee, A. Hope, A. Bezjak, A. Sun, J. Cho, J. Bissonnette, D. Vines, B. Driscoll, M. Giuliani
Journal: Journal of Thoracic Oncology (2017)
Trends in the choice of first line treatment for hormone - responsive (HR+), human epidermal growth factor receptor - 2 negative (HER2-) metastatic breast cancer (MBC) patients (pts): results of a multicentric Italian observational study
Authors: A. D' Alonzo, C. Bighin, F. Puglisi, L. Gerratana, M. De Laurentis, A. Fontana, P. Pugliese, A. Ferzi, F. Montemurro, G. Arpino, F. Poggio, M. Vaglica, C. Dellepiane, E. Blondeaux, C. Benedetta, F. Cognetti, O. Garrone, A. Turletti, S. Pastorino, L. Del Mastro
Journal: Annals of Oncology (2017)
Multiscale network modeling of oligodendrocytes reveals molecular components of myelin dysregulation in Alzheimer’s disease
Authors: Andrew T. McKenzie, Sarah Moyon, Minghui Wang, Igor Katsyv, Won-Min Song, Xianxiao Zhou, Eric B. Dammer, Duc M. Duong, Joshua Aaker, Yongzhong Zhao, Noam Beckmann, Pei Wang, Jun Zhu, James J. Lah, Nicholas T. Seyfried, Allan I. Levey, Pavel Katsel, Vahram Haroutunian, Eric E. Schadt, Brian Popko, Patrizia Casaccia, Bin Zhang
Journal: Molecular Neurodegeneration (2017)

Oligodendrocytes (OLs) and myelin are critical for normal brain function and have been implicated in neurodegeneration. Several lines of evidence including neuroimaging and neuropathological data suggest that Alzheimer's disease (AD) may be associated with dysmyelination and a breakdown of OL-axon communication. In order to understand this phenomenon on a molecular level, we systematically interrogated OL-enriched gene networks constructed from large-scale genomic, transcriptomic and proteomic data obtained from human AD postmortem brain samples. We then validated these networks using gene expression datasets generated from mice with ablation of major gene expression nodes identified in our AD-dysregulated networks. The robust OL gene coexpression networks that we identified were highly enriched for genes associated with AD risk variants, such as BIN1 and demonstrated strong dysregulation in AD. We further corroborated the structure of the corresponding gene causal networks using datasets generated from the brain of mice with ablation of key network drivers, such as UGT8, CNP and PLP1, which were identified from human AD brain data. Further, we found that mice with genetic ablations of Cnp mimicked aspects of myelin and mitochondrial gene expression dysregulation seen in brain samples from patients with AD, including decreased protein expression of BIN1 and GOT2. This study provides a molecular blueprint of the dysregulation of gene expression networks of OL in AD and identifies key OL- and myelination-related genes and networks that are highly associated with AD.
P3.01-023 First-line Afatinib for Non-Small Cell Lung Cancer in Real World Practice
Authors: Y. Kim, J. Sun, K. Park, S.E. Park, S. Lee, M. Ahn, J.S. Ahn, S.W. Lim, H. Lee, J.H. Cho, H.K. Kim
Journal: Journal of Thoracic Oncology (2017)
P3.16-008 Thymidine Phosphorylase Influences Clinical Outcome Following Surgery in Patients with Stage I and II Non-Small Cell Lung Cancer
Authors: N. Himuro, T. Suzuki, Y. Niiya, T. Minakata, Y. Oshima, D. Kataoka, S. Yamamoto, M. Kadokura
Journal: Journal of Thoracic Oncology (2017)
Final results from CAMEO-PRO study: complementary and alternative medicine in oncology. physicians inform oncological patients
Authors: C. Bozza, L. Gerratana, D. Basile, E. De Carlo, F. Cortiula, N. Pella, M.G. Vitale, M. Bartoletti, S. Russo, M. Bonotto, M. Cinausero, V. Fanotto, G. Pelizzari, A.M. Minisini, C. Andreetta, M. Mansutti, D. Iacono, R. Sottile, G. Fasola, F. Puglisi
Journal: Annals of Oncology (2017)
EXTH-74. IMPAIRED PARP1 DNA REPAIR DEFINES CHEMO-SENSITIVITY IN IDH1 MUTANT CELL
Authors: Yanxin Lu, Yang Liu, Jing Wu, Chunzhang Yang
Journal: Neuro-Oncology (2017)

Mutations in isocitrate dehydrogenase (IDH1/2) are the most prevalent genetic abnormalities in lower grade gliomas. The presence of IDH mutations in glioma is prognostic for better clinical outcomes with longer patient survival, and greater sensitivity to chemotherapy. In the present study, we explore the molecular mechanism that determines the chemo-sensitivity in IDH1-mutated glioma cells, and seek for potential therapeutic strategy by targeting DNA repair pathway in IDH1-mutated cells. We established IDH1-mutated cell lines by introducing pathogenic IDH1 mutations into glioma cells via lentivirus. We confirmed the metabolic deficiency and enhanced chemo-sensitivity in cells expressing IDH1 mutant enzyme. Further, we measured the intracellular level of nicotinamide adenine dinucleotide (NAD+), Poly (ADP-ribose) polymerase (PARP)-associated DNA repair and DNA damage level in these cells when treated with temozolomide (TMZ). Moreover, we evaluated a PARP inhibitor Olaprib and its synergic effect on TMZ-associated cytotoxicity. Our results show that the IDH1-mutated cells are more vulnerable to chemotherapy. TMZ treatment resulted in over 20-fold increase of cell death in IDH1-mutated cells compared with wild type counterpart. IDH1-mutated cells exhibited over 1.3-fold DNA damage and over 1.42-fold cellular apoptosis under TMZ treatment. Accordingly, IDH1-mutated cells produced 83.8% less poly (ADP-ribose) polymer (pADPR), an important substrate for PARP-associated DNA repair, during TMZ treatment, suggesting that their incompetence to maintain genomic integrity was due to decreased availability of NAD+. Targeting the PARP-associated DNA repair pathway using Olaprib potentiated TMZ-induced cytotoxic effects by 2.16 fold in IDH1 mutated cells. Our findings demonstrate that metabolic defects in IDH1-mutated cells affect PARP-associated DNA repair pathway via NAD+ depletion, and therefore enhance chemotherapy sensitivity. Targeting PARP-associated DNA repair pathway may represent a novel therapeutic approach for IDH1-mutated gliomas.
EXTH-38. AXL INHIBITION BY R428 ATTENUATES TEMOZOLOMIDE INDUCED pAXL EXPRESSION IN PATIENT DERIVED METASTATIC BRAIN CANCER CELLS
Authors: Amber Lacrosse, Noah Wlodarski, Santhi Konduri, George Bobustuc, Richard Rovin, Amin Kassam
Journal: Neuro-Oncology (2017)

As patients with cancer are living longer, the incidence of brain metastasis is rising. Current treatment options for metastatic brain tumors are very limited. Axl, a receptor tyrosine kinase, has been reported as a key mediator for epithelial-mesenchymal transition (EMT), a process necessary for metastasis to occur. Increases of Axl expression have also been linked to highly aggressive and treatment resistance glioblastoma. A small molecule inhibitor of AXL (R428 – also known as BGB324) is currently in early phase clinical trials for non-small cell lung cancer and acute myeloid leukemia. Temozolomide (TMZ) is the standard chemotherapy of choice for primary brain tumors. We generated a patient derived cell line from a breast cancer metastasis to brain. The brain metastasis was (Her2, ER, PR negative). After confirming the cell line expressed Axl through Western blot and flow cytometry, we tested whether R428 alone or in combination with TMZ had any effect on Axl and pAxl expression. We also determined the impact of R428 and TMZ on cell proliferation. Interestingly, our data indicates a robust, inverse correlation between Axl and pAxl expression in response to TMZ treatment. As expected, R428 alone effectively inhibited the expression of pAxl and significantly attenuated TMZ mediated increases of pAxl expression in our patient-derived cell line. Additionally, our data suggests that increases in pAxl by TMZ may stimulate mechanisms that facilitate TMZ resistance. We will discuss the mechanisms and combination therapeutic effect on tumor growth during the meeting.
P1.07-016 Comparison of PD-L1 Immunohistochemical Staining between EBUS-TBNA and Resected Non-Small Cell Lung Cancer Specimens
Authors: K. Sakata, D. Midthun, J. Mullon, R. Kern, D. Nelson, E. Edell, J. Jett, M.C. Aubry
Journal: Journal of Thoracic Oncology (2017)
La rage vulpine en France
Authors: B Toma
Journal: Eurosurveillance (2005)

La rage vulpine est apparue en France en mars 1968, ou elle a represente un probleme de sante publique jusqu’en 1998. Pendant les deux premieres decennies, et en depit des mesures appliquees, la rage vulpine y a connu un developpement tant pour la surface de la zone d’enzootie que pour le nombre de cas de rage. Ces dernieres comportaient des operations de reduction de la densite des populations vulpines, la vaccination obligatoire des carnivores domestiques dans la zone d’enzootie et la mise en place de prophylaxie humaine. Le recours a la vaccination orale du renard, appliquee a grande echelle a partir de 1989-1990, a permis de faire reculer le front et de diminuer l’incidence annuelle jusqu’a atteindre l’eradication fin 1998. La comparaison des resultats obtenus au cours de ces deux periodes d’application de strategies differentes est spectaculaire. La France demeure exposee au risque de la rage de chiropteres et au risque des cas accidentels de rage canine importee de pays d’enzootie.
MA 07.06 Detection of Mechanisms of Resistance to ALK Inhibitors in Routine Practice: A Retrospective Study
Authors: P. Jamme, C. Descarpentries, M. Wislez, E. Dansin, V. Grégoire, S. Baldacci, F. Escande, N. Mathiot, M. Kyheng, Z. Kherrouche, M.C. Copin, A. Cortot
Journal: Journal of Thoracic Oncology (2017)
Persistence of Penicillin Allergy—Reply
Authors: Jason A. Trubiano, N. Franklin Adkinson, Elizabeth Jane Phillips
Journal: JAMA (2017)

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P3.01-056 Intracranial Activity of Osimertinib in Naïve EGFRm T790M(-)And Treated EGFRm T790M(+) NSCLC Patients with Asymptomatic Brain Metastases
Authors: N. Peled, H. Nechushtan, M. Ilouze, E. Dudnik, E. Inbar
Journal: Journal of Thoracic Oncology (2017)
P1.16-027 Robotic Surgery, VATS, and Open Surgery for Early Stage Lung Cancer: Comparison of Costs and Outcomes at a Single Institute
Authors: P. Novellis, E. Bottoni, E. Voulaz, U. Cariboni, A. Testori, L. Giordano, E. Dieci, L. Granato, E. Vanni, M. Montorsi, M. Alloisio, G. Veronesi
Journal: Journal of Thoracic Oncology (2017)
Hairy cell leukemia 2018: Update on diagnosis, risk-stratification, and treatment
Authors: Xavier Troussard, Edouard Cornet
Journal: American Journal of Hematology (2017)

Hairy cell leukemia (HCL) and HCL-like disorders, including HCL variant (HCL-V) and splenic diffuse red pulp lymphoma (SDRPL), are a very heterogeneous group of mature lymphoid B-cell disorders, characterized by the identification of hairy cells, a specific genetic profile, a different clinical course and the need for appropriate treatment.Diagnosis of HCL is based on morphological evidence of hairy cells, an HCL immunologic score of 3 or 4 based on the CD11C, CD103, CD123, and CD25 expression, the trephine biopsy which makes it possible to specify the degree of tumoral medullary infiltration and the presence of BRAF V600E somatic mutation.Progression of patients with HCL is based on a large splenomegaly, leukocytosis, a high number of hairy cells in the peripheral blood and the immunoglobulin heavy chain variable region gene mutational status. VH4-34 positive HCL cases are associated with poor prognosis RISK ADAPTED THERAPY: Purine analogs (PNA) are indicated in symptomatic first line HCL patients. The use of PNA followed by rituximab represents an alternative option.It is based on the use of BRAF inhibitors associated or not with MEK inhibitors, recombinant immunoconjugates targeting CD22 or BCR inhibitors.