tbuckley/cabot-search huggingface dataset:
ACTR-40. STEREOTACTIC RADIOSURGERY AND TUMOR TREATING FIELDS IN SMALL CELL LUNG CANCER PATIENTS WITH LIMITED BRAIN METASTASES: A PILOT AND FEASIBILITY TRIAL
Authors: Caleb Dulaney, John Fiveash, Peng Li, Hunter Boggs
Journal: Neuro-Oncology (2017)

Small cell lung cancer (SCLC) spreads to the brain in 40% of patients. Historically, whole brain radiation has been used to treat brain metastases. In cases of limited brain metastases from other malignancies, stereotactic radiosurgery (SRS) is supplanting whole brain radiation due to lower rates of neurocognitive toxicity with similar survival. Tumor treating fields (TTFields) are safe and effective in patients with primary brain tumors, and TTFields are being investigated in patients with non-small cell lung cancer brain metastases. The purpose of this single-center trial is to determine the rate of brain relapse in patients with small cell lung cancer metastases treated with SRS and TTFields. Twenty patients with 1–10 newly diagnosed brain metastases from SCLC will receive SRS followed by TTFields and supportive care. Patients are followed every two months until second cerebral progression. The objectives are to determine the safety and feasibility of SRS and TTFields in this population and to determine the rate of brain relapse. Endpoints are time to first cerebral progression, rate of local brain failure, rate of distant brain failure, rates of toxicity, and neurocognitive and quality of life outcomes using the following instruments: HVLT-R, COWAT, TMT, and EORTC QLQ. Treatment consists of continuous TTFields at 200 kHz applied to the brain within 7 days of SRS. This frequency is based on in vivo data showing the optimum frequency for a SCLC cell line to be 200 kHz. The TTFields unit is a portable device that uses four transducer arrays that are covered by a wig or hat to allow for normal daily activity. Patients receive best standard of care for systemic disease. The trial is designed to assess feasibility, potential toxicity, and efficacy of this treatment approach.
SORLA attenuates EphA4 signaling and amyloid β–induced neurodegeneration
Authors: Timothy Y. Huang, Yingjun Zhao, Lu-lin Jiang, Xiaoguang Li, Yan Liu, Yu Sun, Juan C. Piña-Crespo, Bing Zhu, Eliezer Masliah, Thomas E. Willnow, Elena B. Pasquale, Huaxi Xu
Journal: The Journal of Experimental Medicine (2017)

Sortilin-related receptor with LDLR class A repeats (SORLA, SORL1, or LR11) is a genetic risk factor associated with Alzheimer's disease (AD). Although SORLA is known to regulate trafficking of the amyloid β (Aβ) precursor protein to decrease levels of proteotoxic Aβ oligomers, whether SORLA can counteract synaptic dysfunction induced by Aβ oligomers remains unclear. Here, we show that SORLA interacts with the EphA4 receptor tyrosine kinase and attenuates ephrinA1 ligand-induced EphA4 clustering and activation to limit downstream effects of EphA4 signaling in neurons. Consistent with these findings, SORLA transgenic mice, compared with WT mice, exhibit decreased EphA4 activation and redistribution to postsynaptic densities, with milder deficits in long-term potentiation and memory induced by Aβ oligomers. Importantly, we detected elevated levels of active EphA4 in human AD brains, where EphA4 activation is inversely correlated with SORLA/EphA4 association. These results demonstrate a novel role for SORLA as a physiological and pathological EphA4 modulator, which attenuates synaptotoxic EphA4 activation and cognitive impairment associated with Aβ-induced neurodegeneration in AD.
QLIF-10. ILLNESS COMMUNICATION, SPOUSAL SUPPORT AND SYMPTOM BURDEN IN COUPLES COPING WITH GLIOMA
Authors: Kathrin Milbury, Gabriel Lopez, Shiao-Pei Weathers, Obumneke Eto, Jing Li, Lorenzo Cohen
Journal: Neuro-Oncology (2017)

Effective symptom communication may decrease distress in patients and their spouses/partners. However, couples tend to experience barriers to open communication particularly when the patient faces a poor prognosis. Besides the high symptom burden in glioma patients, partners are also at risk of experiencing physical and psychological symptoms, which may impact their relationship. Thus, this cross-sectional survey study aims to examine symptom burden in both patient and partners, their perceptions of each other’s symptoms and if concordance in symptom ratings is a function of illness communication and spousal support. The larger goal is to identify targets for dyadic symptom management interventions. Adult patients with a low or high grade glioma diagnosis currently received any type of cancer treatment with a consenting partner were eligible and approached during routine clinic visits. Fifty patients (43% female, mean age=57 years; 63% high grade) and partners (57% female; mean age=56 years) completed measures of cancer symptoms (ESAS), psychological distress (BSI), spousal support (SRI), and illness communication (CCAT_PF). Dyadic analyses using multi-level modeling and appropriate covariates revealed that partner perception of patient symptoms were significantly correlated with patients’ own ratings (P<.0001). In contrast, patients tended to underestimate partners’ symptom burden revealing low concordance ratings. The concordance findings were moderated by illness communication (P<.05) and spousal support (P<.0001) so that couples who reported open illness communication revealed greater concordance and partners who were identified as supportive by the patient revealed greater concordance with patient symptom ratings. Importantly, the higher couples’ concordance, the lower their psychological distress (P<.05). In conclusion, these findings suggest that effective illness communication and spousal support may play a role in the symptom management of couples coping with glioma. Dyadic behavioral interventions targeting communication and support skills training may improve symptom management in patients and reduce psychological distress in both members of the dyad.
Enquête transfrontalière sur la survenue d’une épidémie à Shigella sonnei chez un groupe de touristes norvégiens après un voyage en Russie
Authors: B Schimmer, H Meldal, N G Perederij, L Vold, M A Petukhova, D Grahek-Ogden, K Nygård
Journal: Eurosurveillance (2007)

Au debut du mois de septembre 2006, l’Institut norvegien de la sante publique a eu connaissance de la multiplication d’infections a Shigella sonnei (shigellose) parmi 23 touristes norvegiens au retour d’un voyage en bus entre Kirkenes (Norvege) et Mourmansk (Russie).
The role of treatments in IDH mutant molecular astrocytomas
Authors: S. Minichillo, E. Franceschi, A. Mura, A. Tosoni, G. Tallini, A. Pession, M. Foschini, C. Bortolotti, D. Danieli, A. Talacchi, L. Cirillo, M. Di Battista, G. Genestreti, S. Bartolini, A. Paccapelo, A.A. Brandes
Journal: Annals of Oncology (2017)
Vers une utilisation prudente des antibiotiques en médecine humaine dans l’Union Européenne, 2005
Authors: G Werner, S Bronzwaer
Journal: Eurosurveillance (2007)

Les exces et prescriptions inadaptees d’antibiotiques representent un veritable danger de sante publique, en contribuant a l’apparition de bacteries resistantes. En 2001, la Commission europeenne a lance un programme destine a combattre la menace de la resistance aux antibiotiques en sante humaine, animale et vegetale. Ce programme comprenait plusieurs volets: recueils de donnees, surveillance, recherche, activites de sensibilisation et suppression progressive de l’utilisation des antibiotiques veterinaire a des fins non medicales.
A Randomized Trial on the Safety and Efficacy of Early Start of Iron Chelation Therapy with Deferiprone in Newly Diagnosed Children with Transfusion Dependent Thalassemia
Authors: Mohsen Saleh Elalfy, Vasilios Berdoukas, Fernando Tricta, Amira Adly, Nyeria Hazza, Hanem Awed, Basma Helal, Mohamed Tarif Salam
Journal: Blood (2016)
PATH-34. H3F3A AND TERT PROMOTER MUTATIONS ARE POOR PROGNOSTICATORS IN PEDIATRIC LOW-GRADE GLIOMAS
Authors: Kay Ka-Wai Li, Rui Yang, Aden Ka-Yin Chan, Nellie Yuk-Fei Chung, Zhifeng Shi, Jingsong Wu, Ho-Keung Ng
Journal: Neuro-Oncology (2017)

Pediatric low-grade gliomas (pLGG) is a heterogeneous group of tumors that exhibits different molecular signatures compared to adult counterpart and accounts for 30-50% of childhood CNS tumors. Majority pLGG rarely undergo malignant progression and remain stable for many years. Others experience tumor recurrence or progression with poor outcomes. This study aims to investigate the roles of BRAF V600E, H3F3A K27M/G34R, and TERT promoter mutations and KIAA1549:BRAF fusion in prognostication of pLGG. A total of 170 cases, including 60 diffuse astrocytoma, 6 ganglioglioma, 16 oligodendroglioma, 16 oligoastrocytoma, 51 pilocytic astrocytoma, 4 pilomyxoid astrocytoma, and 17 pleomorphic xanthoastrocytoma, were included in this study. Direct sequencing revealed BRAF V600E, H3F3A K27M/G34R, and TERT promoter mutations in 8.8% (15/170), 9.4% (16/170), and 2.9% (5/170) cases respectively. All mutations were mutually exclusive except one tumor. KIAA1549:BRAF fusion was detected in 25.8% (39/151) of pLGG as examined by fluorescence in situ hybridization. Two of KIAA1549:BRAF fusion-positive tumors had either BRAF V600E or H3F3A mutation. The 5-, and 10-year overall survival in this cohort were excellent and were 85.6% and 84.5% respectively. Survival analysis revealed that H3F3A and TERT mutation were significantly associated with shorter PFS (p=0.0013 and p<0.0001) and OS (p<0.0001, median survival 44 months vs not reached; and p<0.0001, median survival 27 months vs not reached). Within grade II diffuse astrocytoma, H3F3A and TERT mutation remained as poor prognostic indicators (PFS: 0.0041 and 0.018; OS: 0.0010 and 0.012). Among pleomorphic xanthoastrocytoma, BRAF V600E mutation exhibited a trend toward shorter PFS (p=0.055). Our results indicated that H3F3A and TERT promoter mutation testing may be required in the management of pLGG.
P2.12-006 Evaluation of New 25G Needle in EBUS-TBNA Comparing Conventional 22G Needle in Diagnosis for Nodal Metastasis of Lung Cancer
Authors: Y. Sakairi, T. Nakajima, Y. Yonemori, T. Kaiho, K. Ohashi, Y. Sata, Y. Shiina, T. Toyoda, A. Hata, H. Tamura, T. Fujiwara, H. Wada, H. Suzuki, M. Chiyo, I. Yoshino
Journal: Journal of Thoracic Oncology (2017)
P1.03-039 Therapeutic Inhibition of the Cancer Stem Cell Marker, ALDH1, a Promising Mechanism by Which Cisplatin Sensitivity Can Be Restored in NSCLC
Authors: L. Mac Donagh, S. Gray, S. Cuffe, S. Finn, S. Nicholson, R. Ryan, V. Young, N. Leonard, K. O’Byrne, M. Barr
Journal: Journal of Thoracic Oncology (2017)
Maladies à prévention vaccinale : une surveillance régionale peut aider à améliorer la comparabilité des données entre pays
Authors: J C Desenclos
Journal: Eurosurveillance (2001)

La maniere dont la surveillance d’une maladie donnee est realisee en Europe varie d’un pays a l’autre. Toutes les etudes menees jusqu’a present ont abouti a ce constat, les variations entre pays etant liees a de nombreux facteurs, parmi lesquels l’organisation du systeme de sante occupe une place preponderante.
P1.16-017 Middle Term Survival Outcome of Single Port Video Assisted Thoracoscopic Anatomic Lung Resection: Two Center Experience
Authors: C.F. Wu, M. De La Torre, R. Fernandez, M. Delgado, E. Fieira, C. Wu, M. Hsieh, M. Paradela, Y. Liu, D. Gonzalez-Rivas
Journal: Journal of Thoracic Oncology (2017)
Smoldering myocarditis following immune checkpoint blockade
Authors: Timothy G. Norwood, Brian C. Westbrook, Douglas B. Johnson, Silvio H. Litovsky, Nina L. Terry, Svetlana B. McKee, Alan S. Gertler, Javid J. Moslehi, Robert M. Conry
Journal: Journal for ImmunoTherapy of Cancer (2017)

<h3>Background</h3> Severe myocarditis associated with electrical conduction abnormalities and occasionally heart failure has been well documented following treatment with immune checkpoint blockade with an estimated incidence of less than 1%. However, the incidence, early detection, and management of less severe immune-related myocarditis are unknown since most immunotherapy trials have not included routine cardiac monitoring. Herein, we provide the first description of subclinical or smoldering myocarditis with minimal signs and symptoms following immune checkpoint blockade with a single dose of ipilimumab and nivolumab. <h3>Case presentation</h3> Our patient was diagnosed with immune checkpoint blockade-induced myocarditis based upon an acute rise in serum cardiac troponin I beginning 2&nbsp;weeks after the initial dose of ipilimumab/nivolumab consistent with the reported median onset of clinical myocarditis at 17&nbsp;days, as well as a lack of other causes despite extensive cardiac evaluation. The patient initially presented with intractable nausea with no known gastrointestinal etiology. High dose glucocorticoid therapy led to rapid resolution of nausea and a four-fold decrease in troponin I over 4&nbsp;days. Serum troponin I spiked again following a steroid taper to 13 times the upper limit of normal with endomyocardial biopsy revealing collagen fibrosis and lymphocytic inflammation predominantly comprised of CD8+ T cells consistent with chronic smoldering myocarditis. Serum anti-striated muscle antibodies were also detected with no evidence of rhabdomyolysis. Serum cardiac troponin I levels as an indicator of ongoing myocyte damage gradually improved with chronic prednisone at 10&nbsp;mg daily. Late addition of intravenous immunoglobulin was associated with rapid normalization of creatine kinase-myocardial band. <h3>Conclusions</h3> This case demonstrates that subclinical, smoldering myocarditis may occur following immune checkpoint blockade, with evidence of both humoral and cell-mediated immunity responsive to corticosteroid therapy. This experience supports early monitoring for myocarditis with serial electrocardiograms and serum troponin I determinations in large, prospective cohorts of patients receiving combination immune checkpoint blockade as early detection and initiation of immunosuppression may forestall fulminant presentation of this disease and limit myocardial damage.
EXTH-37. TARGETING GLIOMA STEM CELLS THROUGH COMBINED BMI1 AND EZH2 INHIBITION
Authors: Xun Jin, Leo Kim, Qiulian Wu, Lisa C Wallace, Briana Prager, Tanwarat Sanvoranart, Ryan Gimple, Stephen Mack, Tyler E Miller, Ping Huang, Jill Barnholtz-Sloan, Shideng Bao, Andrew Sloan, Jeremy Rich
Journal: Neuro-Oncology (2017)

Glioblastomas are lethal cancers defined by angiogenesis and pseudopalisading necrosis. Here, we demonstrate that these features are associated with distinct transcriptional programs, with vascular regions showing a proneural profile and hypoxic regions a mesenchymal pattern. As these regions harbor glioma stem cells (GSCs), we investigated the epigenetic regulation of these two niches. Proneural, perivascular GSCs activated EZH2, whereas mesenchymal GSCs in hypoxic regions expressed BMI1 protein, which promoted cellular survival under stress. Using both genetic and pharmacologic inhibition, we found that proneural GSCs are selectively sensitive to EZH2 disruption, whereas mesenchymal GSCs are sensitive to BMI1 inhibition. Given that glioblastomas contain both proneural and mesenchymal GSCs, combined EZH2 and BMI1 targeting proved more effective than either agent alone both in culture and in vivo, suggesting that strategies that simultaneously target multiple epigenetic regulators within glioblastomas may be necessary to overcome resistance to therapies caused by intratumoral heterogeneity.
Pathogenetic mutations in BRCA related triple negative breast cancer
Authors: F. Bini, Z. Ballatore, F. Bianchi, E. Maccaroni, L. Belvederesi, C. Brugiati, S. Pagliaretta, A. Murrone, A. Savini, M. Pistelli, R. Bracci, R. Berardi
Journal: Annals of Oncology (2017)
La légionellose associée au voyage chez des touristes européens en Espagne - commentaire du centre coordinateur EWGLI
Authors: C Joseph
Journal: Eurosurveillance (1997)

Cet article interessant analyse les donnees sur les cas de legionelloses associes au voyage en Espagne et souligne des problemes importants pour EWGLI (European Working Group for Legionella Infections), notamment les declarations de cas incompletes, observees particulierement dans les premieres annees du systeme, qui rendent difficile l'interpretation des donnees. Le programme informatique de EWGLI est en cours de reecriture pour prendre en compte de nouveaux developpements du systeme et ameliorer les methodes d'analyse. Il sera distribue a tous les centres en 1997.
P1.01-071 High Dose IVAA Synergy with mEHT in Patients with Stage III-IV NSCLC: A Phase I Study
Authors: J. Ou, X. Zhu, Y. Lu, C. Zhao, H. Zhang, X. Wang, X. Zhang, T. Zhang, C.L.K. Pang
Journal: Journal of Thoracic Oncology (2017)
RTHP-17. IDH GENE MUTATION STATUS PLAYS NO IMPACT ON SURVIVAL IN PATIENTS WITH GLIOBLASTOMA AT A FIRST PROGRESSION
Authors: Yusuke Tabei, Motoo Nagane
Journal: Neuro-Oncology (2017)

Mutation in the isocitrate dehydrogenase (IDH) gene has established as a favorable prognostic factor for newly diagnosed glioblastoma (GBM). However, there have been few reports assessing whether the mutation is a prognostic factor for recurrent GBM. In the present study, we examined overall survival (OS) in newly diagnosed and recurrent GBM according to differences in IDH mutation. We assessed 147 cases of primary GBM (pGBM) and secondary GBM (sGBM) who were received surgical treatment at Kyorin University Hospital or related facilities from 2000 to 2015. 122 patients were confirmed recurrence. IDH1/2 gene mutation status confirmed by direct sequencing using the Sanger method. Survival was retrospectively analyzed with the Kaplan-Meier method. IDH1 mutation was noted in nineteen of 147 patients and IDH2 mutation was not observed in any patient with mutant IDH (mIDH). Median OS (mOS) from onset of glioma was 18.3 months in the case of wild type IDH (wtIDH) GBM and 47.5 months for mIDH GBM; the latter was significantly longer (p=0.028). mOS after initial progression was 10.5 months for wtIDH GBM (109 patients) and 10.1 months for mIDH GBM (13 patients); no significant differences were noted (p=0.559). Even in the cases of pGBM, mOS after initial progression was 10.5 months for wtIDH GBM and 13.5 months for mIDH GBM; no significant differences were noted (p=0. 747). After diagnosis of sGBM who received adjuvant therapy at the time of the initial onset, mOS was 10.1months. Conclusion: The results of the present study suggest that IDH mutation is not a prognostic factor for recurrent GBM. Although sGBM has conventionally been considered to have a favorable prognosis, it appears that the OS of patients with sGBM is equivalent to that after recurrence of pGBM in our series.
Serum Response Factor Is Essential for Maintenance of Podocyte Structure and Function
Authors: Bing Guo, Qing Lyu, Orazio J. Slivano, Ronald Dirkx, Christine K. Christie, Jan Czyzyk, Aram F. Hezel, Ali G. Gharavi, Eric M. Small, Joseph M. Miano
Journal: Journal of the American Society of Nephrology (2017)

Export Podocytes contain an intricate actin cytoskeleton that is essential for the specialized function of this cell type in renal filtration. Serum response factor (SRF) is a master transcription factor for the actin cytoskeleton, but the in vivo expression and function of SRF in podocytes are unknown. We found that SRF protein colocalizes with podocyte markers in human and mouse kidneys. Compared with littermate controls, mice in which the Srf gene was conditionally inactivated with NPHS2-Cre exhibited early postnatal proteinuria, hypoalbuminemia, and azotemia. Histologic changes in the mutant mice included glomerular capillary dilation and mild glomerulosclerosis, with reduced expression of multiple canonical podocyte markers. We also noted tubular dilation, cell proliferation, and protein casts as well as reactive changes in mesangial cells and interstitial inflammation. Ultrastructure analysis disclosed foot process effacement with loss of slit diaphragms. To ascertain the importance of SRF cofactors in podocyte function, we disabled the myocardin-related transcription factor A and B genes. Although loss of either SRF cofactor alone had no observable effect in the kidney, deficiency of both recapitulated the Srf-null phenotype. These results establish a vital role for SRF and two SRF cofactors in the maintenance of podocyte structure and function.
CMET-32. THE EFFECT OF IMMUNOTHERAPY TREATMENT ON LOCAL CONTROL FOR MELANOMA BRAIN METASTASES TREATED WITH STEREOTACTIC RADIOSURGERY
Authors: Luke Pearson, Steven Nguyen, Andrew Keller, Sean All, Hanisha Patel, Naren Ramakrishna
Journal: Neuro-Oncology (2017)

We evaluated the local control of melanoma brain metastases (MBM) following stereotactic radiosurgery (SRS) in the setting of treatment with or without sequential/concurrent immunotherapy. A single-institution IRB-approved retrospective review was conducted on 69 MBM patients with 230 total metastases treated with SRS between November 2008 to February 2017. We compared local control of metastases in the setting of no immunotherapy versus sequential/concurrent immunotherapy (ipilimumab, nivolumab, and pembrolizumab). Local failure was defined as an increase of at least 20% in the sum of longest diameter of a metastasis and its perpendicular diameter. Statistical analysis was performed using Kaplan-Meier estimates with log-rank testing using SPSS. The 6-month LC rate for all lesions was 76.8%. Fifty of the 69 patients (73.9%) received either ipilimumab, nivolumab, or pembrolizumab treatments (133 of 230 metastases). The 6-month LC rate for these metastases was 80.5%. In comparison, the 6-month LC rate for metastases in the cohort not treated with immunotherapy was 58.9% (p = 0.02). Patient pre-treatment characteristics including GPA score, number of brain metastases treated, and treatment volume were not significantly different between the immunotherapy and non-immunotherapy treatment groups. The 6-month LC rates for metastases receiving: (1) immunotherapy both before and after any SRS treatment (n = 55 metastases), (2) before SRS (n = 37 metastases), and (3) after SRS (n = 66 metastases) were (1) 86.5%, (2) 69.2%, and (3) 77.9%, respectively (p = 0.44). Addition of immunotherapy in melanoma brain metastases treated with stereotactic radiosurgery may improve local intracranial tumor control. Our study suggests that local control is not significantly impacted by whether immunotherapy is administered concurrently or sequentially to radiosurgery. Additional studies on volumetric response and radiation necrosis rates following combined radiosurgery/immunotherapy are underway.
P3.02-065 Lung Adenocarcinoma Patient with EGFR Kinase Domain Duplication (KDD) and Its Response to Icotinib: A Case Report
Authors: W. Wang, C. Xu, Q. Tan, Z. Song, W. Zhuang, Y. Chen, L. Xiong, G. Chen, M. Fang, T. Lv, Y. Song
Journal: Journal of Thoracic Oncology (2017)
TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications
Authors: Andrea Olschewski, Emma L. Veale, Bence M. Nagy, Chandran Nagaraj, Grazyna Kwapiszewska, Fabrice Antigny, Mélanie Lambert, Marc Humbert, Gábor Czirják, Péter Enyedi, Alistair Mathie
Journal: European Respiratory Journal (2017)

TWIK-related acid-sensitive potassium channel 1 (TASK-1 encoded by KCNK3) belongs to the family of two-pore domain potassium channels. This gene subfamily is constitutively active at physiological resting membrane potentials in excitable cells, including smooth muscle cells, and has been particularly linked to the human pulmonary circulation. TASK-1 channels are sensitive to a wide array of physiological and pharmacological mediators that affect their activity such as unsaturated fatty acids, extracellular pH, hypoxia, anaesthetics and intracellular signalling pathways. Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. Furthermore, mutations in KCNK3 have been identified as a rare cause of both familial and idiopathic pulmonary arterial hypertension. This review summarises our current state of knowledge of the functional role of TASK-1 channels in the pulmonary circulation in health and disease, with special emphasis on current advancements in the field.