tbuckley/cabot-search huggingface dataset:
IMMU-05. IMMUNE STIMULATION AND IMMUNE CHECKPOINT INHIBITION PROVIDED BY A SINGLE AGENT: AN ONCOLYTIC HSV EXPRESSING A scFv ANTIBODY AGAINST PD-1
Authors: Carmela Passaro, Quazim Alayo, Hiroshi Nakashima, E Antonio Chiocca
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM), a deadly brain tumor, is resistant to current standard of care treatments including surgery and chemo-radiotherapy. This cancer is also characterized by a highly immunosuppressive microenvironment. Immune checkpoints inhibitors (such as the antiPD-1 antibody) efficiently restore T-cell activity and have been recently approved by the FDA for the treatment of several cancers. I hypothesize that an oncolytic HSV (oHSV), a self-replicating biologic agent for tumor, can disrupt the immunosuppressive GBM microenvironment and stimulate anti-tumor T cell immunity. Further, combining this with PD-1 blockade locally in the tumor maximizes antitumor immune effects. To test this hypothesis in immunocompetent mice models, I developed a new oHSV that expresses a single-chain variable fragment (scFv) antibody against mouse PD-1 to block the PD-L1:PD-1 axis signaling pathway. Preliminary experiments demonstrate that this new oHSV1 expressed and secreted the scFv antibody in several mouse glioma cell lines retaining the same cytotoxic activity of the parental virus. Moreover, the secreted scFv antibody were efficiently able to bind to the mouse PD-1. An in vivo orthotopic glioma mouse model resulted in a significant improvement of median survival time with oHSVscFvPD-1 compared to untreated mice (69 vs 22 days). Long-term survivors mice have been also re-challenged with the same mouse glioma cell line in the contralateral hemisphere showing a memory response against the tumor. Overall, the results obtained by my experiments could then justify testing the new oHSVscFvPD-1 virus in a phase I human clinical trial and/or lead to additional approach for the treatment of human glioblastoma.
PATH-10. MicroRNAs AS PREDICTORS FOR CNS RELAPSE OF SYSTEMIC DIFFUSE LARGE B-CELL LYMPHOMA
Authors: Nir Pillar, Osnat Bairey, Neta Goldschmidt, Yakov Fellig, Yevgenia Rosenblat, Itchak Shehtman, Danielle Haguel, Pia Raanani, Tali Siegal
Journal: Neuro-Oncology (2017)

Diffuse large B-cell lymphoma (DLBCL) represents a heterogeneous group of tumors with a high variance of genetic abnormalities, clinical features, response to treatment and prognosis. Systemic DLBCL is a potentially curable disease using current regimen of immunochemotherapy. Central nervous system (CNS) relapse is a complication that occurs in up to 7% of DLBCL patients and is associated with a high fatality rate. Early identification of molecular markers for CNS involvement may serve for the highly needed accurate stratification of patients into risk groups regarding CNS relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and are known to be involved in DLBCL pathophysiology. We utilized miRNA multiplex reading of systemic DLBCL samples with and without CNS relapse and detected two differentially expressed miRNAs, miR-20a and miR-30d, that predict for CNS involvement. Replication of these results in different samples was used for validation. MiR-20a belongs to the miR-17-92 cluster, and was shown to suppress apoptosis, and to promote cell proliferation, survival and tumorigenesis. MiR-20a was found to be upregulated in PCNSL compared to nodal DLBCL, possibly pointing on its involvement in CNS rooting. MiR-30d has been demonstrated to act as an oncogene in medulloblastoma, hepatocellular carcinoma and prostate cancer. It is possible that miR-30d contributes to the propensity of subsets of DLBCL to spread into the CNS since it is associated with regulation of cell proliferation and metastases. Bioinformatics miRNA-target enrichment analysis revealed a number of putative mechanisms for these miRNAs regulation of CNS relapse, including neuronal plasticity and WNT signaling pathway. Both mechanisms were described as partly responsible for continued tumor growth and recurrence in glioblastoma and secondary CNS tumors and may have a similar role in the unique properties of DLBCL clones that expand, spread and proliferate in the CNS.
TMOD-43. A PORCINE MODEL OF NEUROFIBROMATOSIS TYPE I-ASSOCIATED NERVOUS SYSTEM TUMORS
Authors: Sara Isakson, Alex Coutts, David Largaespada, Adrienne Watson
Journal: Neuro-Oncology (2017)

Neurofibromatosis Type I (NF1) is a common autosomal dominant cancer predisposition syndrome. Individuals with NF1 are prone to developing tumors of the nervous system, including neurofibromas, malignant peripheral nerve sheath tumors, astrocytomas, and gliomas. Traditional mouse models of NF1 provide some insight into the pathogenesis of NF1-associated tumors, but do not accurately model the broad spectrum of disease seen in human patients. We have developed the first porcine model of NF1 that exhibits hallmarks of the syndrome, including RAS hyperactivation in cultured fibroblasts and Schwann cells. The NF1+/- F0 minipigs are viable and exhibit germline transmission with Mendelian frequency to the F1 generation. In an ongoing longitudinal study, we have observed 100% penetrance of café au lait spots, a phenotype that has not been demonstrated in other animal models. A subset of NF1+/- minipigs also develop neurofibroma-like lesions. Magnetic resonance imaging and computed tomography have revealed evidence of central nervous system (CNS) lesions reminiscent of optic pathway gliomas seen in human patients, samples of which have been submitted for histopathologic confirmation. NF1+/- brain tissue is also being evaluated for other CNS manifestations of NF1 syndrome, including astrocytomas, astrogliosis, and neural degeneration. A separate cohort of animals is enrolled in studies to evaluate the behavior of NF1-targeted therapies in NF1+/- minipigs. Steady state pharmacokinetics of gabapentin, used to treat neuropathic pain, in NF1+/- and wild type littermate controls show peak plasma concentrations that are efficacious in humans. Single dose pharmacokinetics of PD0325901, a brain penetrant MEK inhibitor, similarly resulted in significant plasma concentrations. Pharmacokinetic and pharmacodynamic studies are currently underway for the MEK inhibitors Selumetinib and Trametinib. Our results suggest that NF1+/- minipigs may provide a useful preclinical disease model and could facilitate development of new imaging and surgical modalities for improved detection of nervous system tumors.
P3.16-021 Thoracic Morbidity and Mortality System in Analysis of Postoperative Complications After Pneumonectomy in NSCLC Patients
Authors: O. Pikin, A. Ryabov, V. Glushko, K. Kolbanov, A. Amiraliev, V. Barmin, O. Alexandrov
Journal: Journal of Thoracic Oncology (2017)
P1.01-062 KRAS Mutations (KRAS-Mut) and antiPD1/PDL1 Therapy in a Cohort of Lung Cancer (LC) Patients (P). Experience from a Single Institution
Authors: T. Morán, L. Vila, I. Teruel, C. Erasun, L. Angelats, S. España, C. Marc, N. Garcia-Balaña, J.M. Velarde, E. Carcereny
Journal: Journal of Thoracic Oncology (2017)
P3.01-088 Molecular Testing and First-Line Treatment of Patients with NSCLC. First Results from the German CRISP Study (AIO-TRK-0315)
Authors: F. Griesinger, W. Eberhardt, A. Nusch, M. Reiser, C. Losem, S. Ketzler-Henkel, M. Zahn, N. Marschner, M. Jänicke, A. Fleitz, L. Spring, J. Sahlmann, A. Karatas, A. Hipper, M. De Wit, M. Metzenmacher, C. Waller, J. Kern, W. Weichert, M. Sebastian, M. Thomas
Journal: Journal of Thoracic Oncology (2017)
Notificación de la infección por VIH en Europa occidental: sistemas nacionales y primeros datos europeos
Authors: A Infuso, F F Hamers, A M Downs, J Alix
Journal: Eurosurveillance (2000)

La declaracion de casos de sida ha sido una herramienta basica en la vigilancia de la infeccion por VIH en Europa occidental. Sin embargo, las tendencias actuales del sida estan siendo fuertemente modificadas por los avances experimentados en los tratamientos antiretrovirales que retrasan la evolucion de la enfermedad. Asi pues, estas tendencias no pueden utilizarse como indicadores de las tendencias de la transmision del VIH. La declaracion de todos los casos diagnosticados de infeccion por VIH se recomienda cada vez mas como un componente fundamental de la vigilancia (1). En 1999 se establecio un sistema europeo de declaracion de VIH, con la participacion de 39 paises de la Region Europea de la Organizacion Mundial de la Salud (OMS), para complementar la declaracion de sida. Este articulo describe los sistemas nacionales de declaracion de VIH vigentes en los paises de Europa occidental y presenta los primeros datos recogidos
TMOD-07. EVALUATING THE POWER OF PATIENT TUMOR-DERIVED ORTHOTOPIC XENOGRAFT (PDOX) MODELS OF PEDIATRIC BRAIN TUMORS TO PREDICT DRUG RESPONSES IN HUMANS
Authors: Sarah Injac, Yuchen Du, Mari Kogiso, Frank Braun, Lin Qi, Holly Lindsay, Sibo Zhao, Xiao-Nan Li
Journal: Neuro-Oncology (2017)
Line-assisted endoscopic complete closure of a large perforation during colonic endoscopic submucosal dissection
Authors: Hiroko Nakahira, Yoji Takeuchi, Jose Garcia, Yoshinori Morita, Noriya Uedo, Ryu Ishihara, Alberto Herreros de Tejada
Journal: Endoscopy (2017)

A 71-year-old woman was found to have a laterally spreading tumor (non-granular type) adjacent to a previous surgical anastomosis ([Fig. 1 a]). Endoscopic submucosal dissection (ESD) with carbon dioxide insufflation was attempted using an esophagogastroduodenoscope (GIF-H180J; Olympus Co., Tokyo, Japan) and a FlushKnife BT (DK2618JB15; Fujifilm Medical, Tokyo, Japan) during the fourth edition of International ESD Live Madrid 2016, endorsed by the European Society of Gastrointestinal Endoscopy. Severe fibrosis was found during the procedure and it was very difficult to approach the appropriate submucosal plane. While a switch to snare removal was being considered, a large perforation occurred as a result of the colonoscope being pushed in a retroflexed position ([Fig. 1 b]). As a result, the lesion was removed en bloc using an electrosurgical snare (so-called “hybrid ESD”), because it was essential to complete the procedure immediately.
P1.01-001 Depth of Target Lesion Response to Brigatinib and Its Association With Outcomes in Patients With ALK+ NSCLC in the ALTA Trial
Authors: D.R. Camidge, M. Tiseo, M. Ahn, K. Reckamp, K. Hansen, S. Kim, R. Huber, H. West, H. Groen, M. Hochmair, N. Leighl, S. Gettinger, C. Langer, L. Paz-Ares, E. Smit, E. Kim, W. Reichmann, D. Kerstein, D. Kim
Journal: Journal of Thoracic Oncology (2017)
P3.01-036 A Phase IIIb Open-Label, Single-Arm Study of Afatinib in EGFR TKI-Naïve Patients with EGFRm+ NSCLC: An Interim Analysis
Authors: Y. Wu, H. Tu, J. Feng, M. Shi, J. Zhao, Y. Wang, J. Chang, J. Wang, Y. Cheng, J. Zhu, E. Tan, K. Li, Y. Zhang, V. Lee, C. Yang, W. Su, C.L. Lam, B. Srinivasa, S. Rajappa, C. Ho, K.C. Lam, Y. Hu, S.A. Bondarde, X. Liu, J. Fan, D. Kuo, Y. Wang, K. Pang, C. Zhou
Journal: Journal of Thoracic Oncology (2017)
CSIG-39. Fyn, AN ONCOGENE THAT REDUCES GLIOBLASTOMA SURVIVAL YET SENSITIZES TO CHEMO-RADIOTHERAPY
Authors: Andrea Comba, Padma Kadiyala, Anna E Argento, Priti Patel, Felipe J Nunez, Meghna Saxena, Maria G Castro, Pedro R Lowenstein
Journal: Neuro-Oncology (2017)

Fyn, a Src family kinase member (SFK), has oncogenic activities. However, the function of Fyn in malignant brain tumors (GBM) remains contradictory. Bioinformatics network analysis of the transcriptome of GBM neurospheres suggested that Fyn is a highly connected node. Thus, Fyn was selected as a potential regulator of glioma behavior. We investigated the role of Fyn using in vitro and in vivo models. Fyn expression correlates positively with GBM cell aggressiveness. The analysis of the effects of Fyn knockdown in NP mouse glioma neurospheres showed that cell proliferation and migration was decreased compared to NP-control cells. Using an intracranial glioma model, we found that Fyn-knockdown glioma neurospheres displayed reduced tumor growth and prolonged survival compared with NP tumors. We also developed a stringent Fyn-deficient genetic model using the Sleeping Beauty transposase system. The tumors were induced by injecting plasmids encoding: N-Ras/shp53 (NP) or N-Ras/shp53/shFyn (NPF) into the neonatal periventricular region. Fyn knockdown (NPF) increased animal survival. The histopathological evaluation of gliomas indicates that loss of Fyn reduced malignant features such as pseudopalisades, necrosis, hyper vascularization and oncostreams. Nevertheless, the survival analysis of TCGA treated patient data indicates that GBM with lower levels of Fyn had reduced survival. Therefore, we evaluated the effects of therapies on Fyn knockdown cells. The analysis surprisingly showed that NPF neurospheres were more resistant to treatment than NP. Fyn loss decreases glioma aggressiveness but induces less response to therapies. These results indicate an important role for Fyn modulating many glioma cellular processes and its relevance as a novel regulator of GBM behavior and therapy response.
Abstract 1104: Polymer Injection Therapy to Reverse Remodel the Papillary Muscles: Efficacy in Reducing Mitral Regurgitation in a Chronic Ischemic Model
Authors: Jorge Solis-Martin, Benjamin Johnson, J. Luis Guerrero, Mark Handschumacher, Suzanne Sullivan, G.J.C Braithwaite, O.k. Muratoglu, G.j Vlahakes, Robert A Levine, Judy Hung
Journal: Circulation (2008)

Ischemic mitral regurgitation (IMR) relates to displacement of the papillary muscles from ischemic ventricular distortion. Recurrent IMR is frequent after annuloplasty, particularly when left ventricular remodeling continues to progress. Our hypothesis is that repositioning of the papillary muscles can be achieved by injection of polyvinyl-alcohol (PVA) polymer into the myocardium, in chronic MR with great left ventricle remodeling. Methods : we studied 8 sheep underwent ligation of circumflex branches to produce chronic ischemic MR over eight weeks. Once MR developed, PVA was injected into the myocardium underlying the infarcted PM. 2D and 3D echocardiograms were used pre infarct (baseline), pre PVA (Chronic MR) and post PVA. Hemodynamic data were obtained Results: One animal died, in the remaining 7 moderate MR developed. With PVA, the MR decreased significantly from moderate to trace-mild (vena contracta: 5.3 ± 0.9 mm vs 2.3 ± 0.9 mm, post MR vs post PVA; p&lt;0.001). This was associated with a decrease in infarcted papillary muscle-to-mitral annulus tethering distance (33.1 ± 4.6 to 27.4±4.1 mm, post MR vs post PVA, P&lt;0.05), tenting volume (2.1±0.3 to 1.6±0.4 mm, post MR vs post PVA, P&lt;0.05) and leaflet area (9.4 ± 0.8 to 8.2 ± 0.7 mm, post MR vs post PVA, P&lt;0.04). PVA was not associated with significant decreases in LVEF (41±2 % vs 39±2 %, p=ns). Conclusions : PVA polymer injections improve coaptation and reduce remodeling chronic MR without impairing LV systolic function. This new approach offers a potential alternative for relieving ischemic mitral regurgitation by correcting papillary muscle position, thus relieving tethering that causes ischemic mitral regurgitation.
IMMU-36. HYPERGLYCEMIA SUPPRESSES MACROPHAGE ACTIVITY AND INHIBITS GLIOMA INVASION IN DIABETIC MICE
Authors: Ian Zhang, Huili Liu, Hui Zhou, Leying Zhang, Behnam Badie, Darya Alizadeh
Journal: Neuro-Oncology (2017)

Patients with malignant glioma (MG) are often treated with corticosteroids to reduce cerebral edema, but chronic use of steroids may cause glucose intolerance and development of type 2 diabetes (Db). Individuals with Db not only have significantly higher likelihood of developing malignant tumors, but also, have a higher risk of cancer-related mortality than non-Db patients. The goal of this study was to evaluate the effect of hyperglycemia on glioma growth in mouse models. Because MG are heterogeneous tumors with both invasive and “nodular” phenotypes, two different syngeneic glioma models were examined in streptozotocin-induced Db mice. We found that in the GL261 gliomas that typically grow as “nodular” tumors, hyperglycemia activated receptor for advanced glycation endproducts (RAGE) by upregulating HMGB1 expression, and promoted tumor growth irrespective of tumor microenvironment (TME). Similarly, the K-Luc gliomas, which are invasive and elicit a robust macrophage infiltration, grew faster in subcutaneous (s.c.) location in Db mice. However, intracranial (i.c.) K-luc gliomas were smaller and less invasive in hyperglycemic mice. Our studies showed that a reduction in K-Luc growth in the brains of Db mice was mostly due to the abrogation of inflammatory responses and suppression of pro-inflammatory cytokines such as IL-1b and IL-6 in TME. We conclude that hyperglycemia may enhance glioma growth by activating the RAGE pathway and suppressing antitumor responses. But, suppression of tumor inflammation may also inhibit glioma growth by abrogating i.c. tumor invasion under hyperglycemic conditions.
Un brote de Salmonella typhimurium DT 104A asociado a un salami porcino tradicional, en Italia, durante la Pascua
Authors: I Luzzi, P Galetta, M Massari, Caterina Rizzo, A M Dionisi, E Filetici, A Cawthorne, A Tozzi, M Argentieri, S Bilei, L Busani, C Gnesivo, A Pendenza, A Piccoli, P Napoli, L Loffredo, M O Trinito, E Santarelli, M L Ciofi Degli Atti
Journal: Eurosurveillance (2007)

Las salmonelas entericas son una causa frecuente de infeccion gastrointestinal en Italia. S. typhimurium representa aproximadamente el 40% de las cepas aisladas y la mayoria de ellas pertenecen al fago tipo DT104. Describimos la investigacion de un brote de S. typhimurium DT104A, un subtipo nunca observado hasta ahora en Italia, que se produjo en Roma durante la primavera de 2004.
NIMG-99. P53 AMPLIFICATION MODIFIES THE GLIOBLASTOMA MICROENVIRONMENT: DIFFERENTIATING THE CONTRIBUTION OF CELLS VS EDEMA IN THE T2 WEIGHTED MRI SIGNAL
Authors: Pamela Jackson, Nathan Gaw, Andrea Hawkins-Daarud, Lauren DeGirolamo, Leslie Baxter, Kris Smith, Peter Nakaji, Samuel McGee, Kamala Clark-Swanson, Bernard Bendok, Teresa Wu, Leland Hu, Jing Li, Kristin Swanson
Journal: Neuro-Oncology (2017)

Patients with HGGs had extensive disturbances in functional connectivity, which extended far beyond the solid tumor mass, invariably affecting the non-lesional hemisphere.In contrast, patients suffering from LGGs showed less damage to functional connectivity, which was mostly confined to the lesion-bearing hemisphere.In general, the degree of damage to functional connectivity was likely dominated by tumor histology, e.g.HGGs caused far more extensive damage to functional connectivity than LGGs.CONCLU-SION: rsfMRI is a novel, non-invasive and easily implementable diagnostic tool in glioma patients which could discover characteristic disturbances in the non-lesional hemisphere of HGG patients.The correlation with tumor grading suggests that rsfMRI has great potential serve as an imaging biomarker for disease burden in glioma patients.
Guías BICHAT para el manejo clínico de la fiebre Q y de la fiebre Q relacionada con el bioterrorismo
Authors: P Bossi, A Tegnell, A Baka, F van Loock, A Werner, J Hendriks, H Maidhof, G Gouvras
Journal: Eurosurveillance (2004)

La fiebre Q es una zoonosis debida a Coxiella burnetii. Su interes como arma biologica en potencia radica en el hecho de que basta con aerosolizar unas pocas bacterias para contagiar al hombre. La contaminacion alimentaria es otra via de transmision de C. burnetii. Sin embargo, C. burnetii no resulta adecuada como agente infeccioso para ataques bioterroristas: su periodo de incubacion es prolongado, muchas infecciones son inaparentes y la mortalidad es baja. En el caso de un ataque bioterrorista con C. burnetii, las formas clinicas serian identicas a las observadas habitualmente con esta bacteria. Estas pueden ser asintomaticas, agudas, normalmente acompanadas de neumonia o hepatitis, o cronicas, por lo general manifestadas como endocarditis. Casi todos los casos de fiebre Q son asintomaticos y remiten espontaneamente sin tratamiento especifico. Sin embargo, el tratamiento puede acortar la duracion de la enfermedad y reducir el riesgo de complicaciones como la endocarditis. Se recomienda administrar tratamiento posterior a la exposicion en casos de ataques bioterroristas.
PDTM-27. DIANHYDROGALACTITOL (VAL-083) OVERCOMES CHEMORESISTANCE IN PEDIATRIC MALIGNANT BRAIN TUMORS AND DISPLAYS SYNERGY WITH TOPOISOMERASE INHIBITORS
Authors: Beibei Zhai, Anne Steino, Jeffrey Bacha, Dennis Brown, Jie Zhang, Theo Nicolaides, Mads Daugaard
Journal: Neuro-Oncology (2017)

More children die from brain cancer than from any other disease. Medulloblastoma (MB) and pediatric high-grade gliomas (pHGG) are the most common malignant brain cancers in children. Children with pHGG have few therapeutic options and 5-year survival is less than 20%. Treatment includes surgery, radiotherapy and various chemotherapeutic combinations often including topoisomerase inhibitors and/or temozolomide (TMZ). The expression of the DNA repair protein O6-methylguanine-DNA methyltransferase (MGMT) is strongly correlated with TMZ-resistance and is highly expressed in many pHGG, and deficient DNA mismatch repair (MMR) (25% of pHGG) confers a secondary mechanism of TMZ-resistance. VAL-083 is a novel bi-functional DNA targeting agent that readily crosses the blood-brain barrier and accumulates in brain tumor tissue. In prior NCI-sponsored clinical trials, VAL-083 was well-tolerated and demonstrated activity against pediatric brain tumors, including pHGG and MB. VAL-083 induces interstrand cross-links at N7-guanine, DNA double-strand breaks and irreversible S/G2-phase cell cycle arrest leading to persistent activation of the homologous recombination (HR) DNA repair pathway and cancer cell death. VAL-083 overcomes MGMT-related resistance mechanisms and is equally active against HGG cancer stem cells and non-stem cells, in vitro. Here, we report strong VAL-083 activity against pHGG (SF188), MB (Med8a) and adult HGG (T98G) cancer cells known to be radio- and chemoresistant, independent of p53 and MGMT status. Further, VAL-083 cytotoxicity was shown to be MMR-independent in two colorectal cancer cell lines. We also report strong synergy between VAL-083 and inhibitors of both topoisomerase I and II (camptothecin and etoposide) in A549 and PC3 cancer cell lines. Our results suggest a distinct anti-cancer mechanism for VAL-083 compared to standard MB/pHGG chemotherapy, resulting in the ability to overcome MGMT- and MMR-related chemoresistance and exhibiting synergy with topoisomerase inhibitors.