tbuckley/cabot-search huggingface dataset:
DRES-07. MODULATION OF INFLAMMATION PROFILES AND AHR SIGNALING IN HUMAN GLIOBLASTOMA MULTIFORME CELL LINES BY INDIRUBIN DERIVATIVES E804 AND 7BIO
Authors: Micaela R Scobie, Charles D Rice
Journal: Neuro-Oncology (2017)

Glioblastoma Multiforme (GBM) is a highly invasive brain tumor that affects approximately 18,000 people annually in the US alone. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that binds endogenous, indole-derived ligands as well as many planar xenobiotics. In addition to regulating drug and xenobiotic metabolism, AHR signaling is involved in hematopoiesis, immune function, cell cycling, and inflammation. As new treatment options for GBM are developed, inflammation is emerging as a concern in the success of these new modalities. Indirubin and many of its derivatives bind AHR with different affinities based on their structure activity relationships (SAR). Depending on the SAR, AHR activation has a range of effects on cell physiology. We examined the effects of two indirubin derivatives: Indirubin-3’-(2,3 dihydroxypropyl)-oximether (E804) and 7-Bromoindirubin-3’-oxime (7BIO) on AHR activity and inflammation profiles in LN-18 and T98G human glioma cell lines. CYP1B1 gene expression, a marker for AHR activation, is induced in both cell lines, and most potently by E804. Using a commercial cancer-inflammation qPCR array, we showed that gene expression profiles indicative of pro-inflammation are highly suppressed by E804, with 7BIO having little effect. Of note, this suppression of pro-inflammatory gene expression occurred in LN-18 cells, but not T98G cells. IL6 protein secretion, an iconic inflammatory cytokine, was decreased by E804 as compared to the control at two time points and in both cell lines. Furthermore, in LN-18 cells, 7BIO reduced the expression of indoleamine dioxygenase (IDO1), a key enzyme for glioma survival. In contrast, however, IDO1 expression was induced in 7BIO-treated T98G cells. Moreover, expression of the regulatory transcription factor STAT3 was reduced by E804, but not by 7BIO in both cell lines. Thus, E804 is both an AHR ligand and inhibitor of STAT3, and may have potential in future treatments for GBM.
PDCT-05. MOLECULAR DIAGNOSTICS REVEAL 60% HIGHER SURVIVAL FOR MOLECULARLY-VERIFIED VERSUS HISTOPATHOLOGICALLY-DIAGNOSED PEDIATRIC SUPRATENTORIAL CENTRAL NERVOUS SYSTEM EMBRYONAL TUMORS AND PINEOBLASTOMAS; A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP ACNS0332 TRIAL
Authors: Eugene Hwang, Marcel Kool, Peter Burger, David Capper, Lukas Chavez, Sebastian Brabetz, Chris Williams-Hughes, Catherine Billups, Linda Heier, Alok Jaju, Jeff Michalski, Yimei Li, Tianni Zhou, Sarah Leary, Nancy Heideman, Andreas von Deimling, David Jones, Amar Gajjar, Roger Packer, Stefan M Pfister, James Olson
Journal: Neuro-Oncology (2017)

Children with high-risk medulloblastoma, supratentorial primitive neuroectodermal tumors (CNS-PNETs) and pineoblastomas (PBLs) have had poor survival despite intensive treatment. The Children’s Oncology Group trial ACNS0332 evaluated the efficacy of adding carboplatin or isotretinoin to standard therapy. Emerging genomic data revealed diagnostic heterogeneity that was not appreciated at the time of trial inception, so CNS-PNET/PBL enrollment was discontinued and the data for that group is reported here. In this phase 3 prospective trial, children were randomly assigned to receive carboplatin during radiation and/or adjuvant isotretinoin in addition to standard intensive chemotherapy. DNA methylation profiling, retrospectively completed on consenting patients, was used for molecular tumor classification. 85 participants with institutionally-diagnosed CNS-PNETs/PBLs were enrolled; however, methylation profiling revealed a broad spectrum of discrepant molecular diagnoses. Out of 60 patients with available tissue, 31 were non-pineal in location, of which 22 (71%) represented tumors not intended for trial inclusion, including 18 high-grade gliomas (HGG), 2 atypical teratoid rhabdoid tumors, and 2 ependymomas. Outcomes across tumor types were strikingly different, and patients with embryonal tumors/PBLs exhibited 5-year EFS/OS rates of 62.8 ± 9.9% and 78.5 ± 8.3%, respectively, while patients with molecularly-classified HGG had an EFS/OS of 5.6 ± 3.8% and 12.0 ± 6.5%, respectively. Although the study was likely underpowered due to the early closure of CNS-PNET/PBL enrollment, there was no evidence that carboplatin or isotretinoin significantly altered outcomes for these patients. Survival for patients with HGG were similar to studies that do not use craniospinal irradiation or intensive chemotherapy. This trial highlights the challenges of histology-based pathology for brain tumors in children and indicates that molecular profiling should become a standard component of initial diagnosis. For patients with CNS-PNETs/PBLs, prognosis is considerably better than previously assumed when molecularly-confirmed HGG were removed from the cohort. Identification of molecular HGG will spare affected children from unhelpful intensive treatment.
P1.01-057 Nivolumab in Previously Treated Advanced Non-Small-Cell Lung Cancer (NSCLC)
Authors: J. Rogado, V. Pacheco-Barcia, M.D. Fenor De La Maza, J.M. Serra, P. Toquero, B. Vera, B. Obispo, R. Mondéjar, A. Ballesteros, O. Donnay, R. Colomer, J.M. Sánchez-Torres
Journal: Journal of Thoracic Oncology (2017)
PUB044 Diagnostic Value of FR+-CTCs Detected by LT-PCR for Lung Cancer in SPN and Tumor Invasiveness in Adenocarcinoma (T≪3cm)
Authors: Q. Zhou, L. Wang, J. Huang, M.L. Liao, H. Jian, J. Lou, S. Lu, Q. Luo
Journal: Journal of Thoracic Oncology (2017)
GENE-41. EPIGENETIC DOWN-REGULATION OF THE METALLOTHIONEIN FAMILY IN ISOCITRATE DEHYDROGENASE (IDH) MUTANT GLIOMAS
Authors: Byram Ozer, Reshmi Chowdhury, Tie Li, Yvonne Bui, Nhung Nguyen, William Yong, Linda Liau, Phioanh Nghiemphu, Timothy Cloughesy, Albert Lai
Journal: Neuro-Oncology (2017)

IDH mutant gliomas demonstrate a CpG island methylator phenotype (G-CIMP) thought to be triggered by oncometabolite D-2HG as a consequence of down-regulation of TET and JHDM. As identified here, G-CIMP includes members of the heavy metal-binding metallothionein 1 (MT1) family involved in protective stress responses. Although epigenetic regulation of MT1 family members has been linked to many different cancers, the role of MT1 in gliomas is unknown. To confirm the epigenetic regulation of MT1 family members in IDH mutant gliomas and elucidate the cellular phenotype of MT1 silencing. We integrated our RRBS methylation data with TCGA gene expression data to screen for hypermethylated, low-expressing molecular targets stratified by IDH status. The screen revealed MT1 family members as highly relevant, which was verified by bisulfite sequencing of additional patient samples. Glioma cell lines were tested for MT1 expression and promoter methylation, and the LN18 line was selected for its constitutive promoter methylation and gene product down-regulation. MT1G and MT1M were selected for over-expression in LN18 cells, and cellular stresses by serum-starvation, irradiation, and chemotherapy exposure were probed by MTT assays. An integrated screen found three MT1 family members (E, G, and M) have hypermethylated promoters with low gene expression in IDH mutated gliomas. These results were validated in 60 UCLA patient samples (p<0.001). Among glioma cell lines, LN18 was found to have constitutively silenced MT1 secondary to promoter hypermethylation. Restoration of MT1G and MT1M in LN18 led to resistance to serum-starvation (MT1G>MT1M) and chemoresistance to carboplatin (MT1M>MT1G), but had no effect on DNA damage from irradiation or to alkylating agent damage from temozolomide. IDH mutated gliomas down-regulate MT1 family members by epigenetic mechanisms. MT1 down-regulation leads to increased sensitivity to metabolic stress and metal-based chemotherapies, and may explain the slower growth of IDH mutated gliomas.
MA 05.07 Whole Body PD-1 and PD-L1 PET in Pts with NSCLC
Authors: A. Niemeijer, E. Smit, G. Van Dongen, A.D. Windhorst, M. Huisman, N. Hendrikse, I. Bahce, D. Lueng, R. Smith, W. Hayes, L. Wilson, S. Bonacorsi, D. Donnelly, P. Morin, A. Poot, D. Vugts, E. Thunnissen, J. De Langen
Journal: Journal of Thoracic Oncology (2017)
P3.16-004 Surgery for Patients with Lung Cancer Associated with Interstitial Pneumonia
Authors: Y. Azuma, H. Otsuka, T. Makino, S. Koezuka, K. Isobe, S. Sakamoto, N. Tochigi, K. Shibuya, S. Homma, A. Iyoda
Journal: Journal of Thoracic Oncology (2017)
P1.03-016 Video-Thoracoscopic Pulmonary Resection Avoids Delay and Increase Adjuvant Chemotherapy Compliance for Non-Small Cell Lung Carcinoma
Authors: A. Ozturk, Ç. Tezel, R. Evman, I. Kolbaş, V. Baysungur, H. Kıral, L. Alpay, I. Yalçınkaya
Journal: Journal of Thoracic Oncology (2017)
EXTH-65. AS1411 ENHANCES CYTOTOXICITY OF SapC-DOPS VIA SURFACE PHOSPHATIDYLSERINE ELEVATION IN GLIOBLASTOMA
Authors: Nikhil Shukla, Harold Davis, Subrahmanya Vallabhapurapu, Xiaoyang Qi
Journal: Neuro-Oncology (2017)

Glioblastoma multiforme (GBM) remains a common and deadly primary brain tumor. Current treatment includes surgical resection with adjuvant chemotherapy and radiotherapy. However, median survival remains less than 15 months mainly due to tumor recurrence and drug resistance. SapC-DOPS, also called BXQ-350, is a stable protein-lipid nanovesicle that has been shown to have anti-GBM activity and is now in a Phase 1 clinical trial. SapC-DOPS selectively targets phosphatidylserine (PS) which is abnormally exposed on the cancer cell surface. It is known that the antitumor efficacy of SapC-DOPS is correlated with the level of surface PS on GBM cells. AS1411, a stable G-rich DNA oligo and the first aptamer to progress to clinical trials, has anticancer activity via a methuosis-induction pathway. The aptamer predominantly functions via nucleolin binding in tumor cells. However, methuosis-induced cell death by AS1411 in GBM cells has not previously been described. Our morphologic analyses of U87-MG cells treated with AS1411 showed vacuolization similar to the known methuosis inducer, MIPP. Utilizing flow-cytometry we demonstrated that treatment of U87-MG cells with AS1411 induced a time-dependent increase in surface PS, with greater than 2-fold increase in surface PS at the 72-hour time point (p < 0.005). Interestingly, AS1411 mediated increase in surface PS resulted in enhanced response to SapC-DOPS. Combination treatment with various concentrations of SapC-DOPS and AS1411 showed increased antitumor effects against U87-MG cells (p < 0.01). Our study elucidates a potential role of AS1411 in sensitizing GBM to SapC-DOPS through surface PS elevation. This combination therapy may provide a new clinical modality for treating GBM patients.
Brote de gastroenteritis por calicivirus asociado al consumo de frambuesas congeladas
Authors: A Pönka, L Maunula, C. H. von Bonsdorff, O Lyytikaïnen
Journal: Eurosurveillance (1999)

Los virus pequenos de estructura redonda (small round structured virus -SRSV-, por ejemplo: calicivirus, astrovirus y enterovirus) son la causa mas frecuentes de brotes de gastroenteritis no bacteriana en todo el mundo (1,2). Se ha documentado la transmision de los SRSV por agua y por varios alimentos, incluidos ensaladas, productos de pasteleria, frutas recien cortadas, pollos, ostras y mejillones. Salvo en los brotes transmitidos por agua y los asociados al consumo de marisco, la contaminacion virica de alimentos casi siempre se atribuye a una infeccion de los manipuladores de alimentos. El reciente desarrollo de metodos moleculares para la deteccion y diferenciacion de los SRSV ha aumentado la sensibilidad y la especificidad del diagnostico de las gastroenteritis viricas (3,4).
Bladder-sparing trimodality approach for unfit for surgery and cisplatin treatment elderly patients with muscle-invasive bladder cancer (MIBC): results from a monocentric experience
Authors: A. Rozzi, M. Nappa, A.M. Costa, B. Spigone, P.T. Falbo, S. Di Nicola, F. De Marco, M. Corona, A. Iannace, G. Lanzetta
Journal: Annals of Oncology (2017)
The Evolution of Human Skin Color
Authors: Apoorva Trivedi, Jinal Gandhi
Journal: JAMA Dermatology (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Dermatology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Dermatology journal
Biallelic interferon regulatory factor 8 mutation: A complex immunodeficiency syndrome with dendritic cell deficiency, monocytopenia, and immune dysregulation
Authors: Venetia Bigley, Sheetal Maisuria, Urszula Cytlak, Laura Jardine, Matthew A. Care, Kile Green, Merry Gunawan, Paul Milne, Rachel Dickinson, Sarah Wiscombe, David Parry, Rainer Doffinger, Arian Laurence, Claudia Fonseca, Oda Stoevesandt, Andrew Gennery, Andrew Cant, Reuben Tooze, A. John Simpson, Sophie Hambleton, Sinisa Savic, Gina Doody, Matthew Collin
Journal: Journal of Allergy and Clinical Immunology (2017)
EXTH-13. IN VIVO THERAPEUTIC POTENTIAL OF IL13-LIPDXR IN A MALIGNANT PERIPHERAL NERVE SHEATH TUMOR MOUSE MODEL
Authors: A B Madhankumar, Becky Slagle-Webb, Oliver Mrowczynski, Vagisha Ravi, Elias Rizk, Alexandre Bourcier, Russell Payne, James Connor
Journal: Neuro-Oncology (2017)

Malignant peripheral nerve sheath tumor is a soft tissue sarcoma that poses tremendous challenges for effective therapy. Several therapeutic approaches using drugs such as doxorubicin and rapamycin have been tried in the past with minimum success. Therapeutic resistant property mediated by MDR proteins, in combination with DNA damage repair was proposed as a major cause leading to therapeutic inefficacy of chemotherapeutics in MPNST tumors. To overcome this issue, we encapsulated doxorubicin in lipid nanovesicles and targeted to IL13Rα2, a receptor that is selectively overexpressed in several malignant peripheral nerve sheath tumor cell lines. In the present investigation, a MPNST mouse model was developed using STS26T-Luc cell line stably transfected with luciferase reporter gene. These cells were implanted into the sciatic nerve that could be imaged by Intravital Imaging Spectroscopy (IVIS). After confirming the tumor formation, the mice were injected with 7 mg/kg body weight of (a) IL13 linked liposomal doxorubicin (IL3LIPDXR) (b) unconjugated liposomal doxorubicin (LIPDXR) and (c) control mice injected with equal volume of saline. The mice were treated weekly once for 7 weeks. The mice which received IL13LIPDXR and LIPDXR showed significant reduction in tumor volume compared to the control group. Among the targeted and non-targeted liposomes, IL13LIPDXR showed rapid tumor regression. However, beyond 4 weeks, the drug was ineffective in shrinking or maintaining the tumor volume. This concludes that although the targeted delivery of doxorubicin, seems to be effective initially however in the later course of treatment they are ineffective in controlling the tumor progression. Approaches such as combining doxorubicin with a small molecule Ras inhibitor or other agents in the liposome formulation which are currently underway may help to improve the therapeutic efficacy.
STEM-33. LOSS OF FUBP1 IMPAIRS TERMINAL NEURONAL DIFFERENTIATION AND PREDISPOSES NEURAL PROGENITORS FOR TRANSFORMATION
Authors: Inah Hwang, Dongqing Cao, Do-Yeon Kim, Tuo Zhang, Jian Hu, Yu Yao, Jihye Paik
Journal: Neuro-Oncology (2017)

Loss of terminal differentiation capacity through genetic mutations is a selected genetic event in tumorigenesis. 1p19q co-deletion associated recurrent mutations of far upstream element-binding protein 1 (FUBP1) have been reported from genomic analysis of low- grade oligodendroglioma. It is frequently overexpressed in many human cancers and strongly correlated with disease progression. However, left unanswered is how FUBP1 serves uniquely as a tumor suppressor in the central nervous system. Here we show that expression of FUBP1 is dynamically regulated during neurogenesis, marking specific stages of neuronal differentiation. Loss of FUBP1 in neural stem/progenitor cells (NPC) increased the number of cells fail to terminally differentiate. Knockdown of FUBP1 further blocks differentiation and promotes tumorigenesis collaboratively with the expression of neomorphic isocitrate dehydrorgenase 1 mutant IDH1R132H. Mechanistically FUBP1 is necessary for mini exon 8a splicing of neurospecific isoform of histone demethylase LSD1 (nLSD1). It binds to intron 8 of LSD1 together with a neuron-specific splicing complex containing NOVA1 and 2 and works synergistically with SRRM4 for the inclusion of mini exon 8a. The expression level of nLSD1 is decreased upon loss of FUBP1 in neural progenitors, impairing the terminal neuronal differentiation and maturation. Reinforcing nLSD1 expression in FUBP1-downregulated NPC restores terminal differentiation, establishing nLSD1 as an obligatory effector of FUBP1-dependent neuronal differentiation. Together, these findings establish a direct role for FUBP1 in neuronal differentiation and also uncover the mechanism for its tumor suppressor function in the nervous system.
A prospective study of travellers' diarrhoea: analysis of pathogen findings by destination in various (sub)tropical regions
Authors: T. Lääveri, K. Vilkman, S.H. Pakkanen, J. Kirveskari, A. Kantele
Journal: Clinical Microbiology and Infection (2017)

Eighty million travellers visiting (sub)tropical regions contract travellers' diarrhoea (TD) each year, yet prospective data comparing the prevalence of TD pathogens in various geographical regions are scarce. Our recent study using modern molecular methods found enteropathogenic (EPEC) and enteroaggregative (EAEC) Escherichia coli to be the most frequent pathogens, followed by enterotoxigenic E. coli (ETEC) and Campylobacter. We revisited our data to compare the findings by geographical region.A total of 459 prospectively recruited travellers provided stool samples and completed questionnaires before and after visiting destinations in various geographical regions. A multiplex quantitative real-time PCR assay was used to analyse Salmonella, Yersinia, Campylobacter jejuni/Campylobacter coli, Shigella, Vibrio cholerae, EPEC, EAEC, ETEC, enterohaemorrhagic E. coli and enteroinvasive E. coli.TD was contracted by 69% (316/459) of the subjects; EPEC and EAEC outnumbered ETEC and Campylobacter in all regions. Multiple pathogens were detected in 42% (133/316) of the samples. The proportions of all pathogens varied by region. The greatest differences were seen for Campylobacter: while relatively frequent in South Asia (n = 11; 20% of the 55 with TD during travel) and Southeast Asia (15/84, 15%), it was less common in East and West Africa (5/71, 7% and 1/57, 2%) and absent in South America and the Caribbean (0/40).EPEC and EAEC outnumbered ETEC and Campylobacter everywhere, yet the proportions of pathogen findings varied by region, with ETEC and Campylobacter rates showing the greatest differences. The high frequency of multibacterial findings in many regions indicates a need for further investigation of the clinical role of each pathogen.
Cardiac Tissue Characterization and Imaging in Autoimmune Rheumatic Diseases
Authors: Sophie I. Mavrogeni, Petros P. Sfikakis, Loukia Koutsogeorgopoulou, George Markousis-Mavrogenis, Theodoros Dimitroulas, Genovefa Kolovou, George D. Kitas
Journal: JACC. Cardiovascular imaging (2017)
La notificación electrónica mejora la oportunidad y la exhaustividad de la declaración de las enfermedades infecciosas, Países Bajos, 2003
Authors: M Ward, P Brandsema, E van Straten, A Bosman
Journal: Eurosurveillance (2005)

En 2002, la introduccion en los Paises Bajos del sistema de notificacion OSIRIS, en linea, via Internet, reemplazo totalmente el sistema basado en formularios impresos. Los objetivos de OSIRIS eran mejorar la oportunidad y la exhaustividad de los datos de vigilancia de las enfermedades infecciosas declaradas por las autoridades regionales al nivel nacional. 
Comparamos los retrasos en la declaracion de 2001 por el sistema convencional con los de OSIRIS en 2003. Se compararon dos tipos de retrasos: el retraso total, definido como el tiempo transcurrido entre el inicio de sintomas y la declaracion al nivel nacional; y el retraso central definido como el tiempo transcurrido entre la declaracion regional y nacional. Los valores medianos para cada sistema fueron comparados con el test de Wilcoxon Rank. Tambien se compararon las declaraciones electronicas recibidas por OSIRIS en 2003 con las declaraciones 2001 del sistema anterior teniendo en cuenta la cumplimentacion de los campos de datos especificos. La significacion estadistica de las proporciones de los campos completados en cada sistema se determino con el test exacto de Fischer y el test de Mantel-Haenzel con la correccion de Yates.
Los resultados mostraron que el retraso central mediano entre el sistema convencional y el sistema OSIRIS se habia reducido significativamente para todas las enfermedades, pasando respectivamente de 10 dias (rango intercuartil 4) en 2001 a un dia (rango intercuartil 1) en 2003. Excepto por los casos de malaria, el retraso total desde la aparicion de los primeros sintomas hasta la declaracion nacional, se habia reducido tambien de forma significativa. Ademas, las declaraciones OSIRIS contenian informaciones mas completas que las tradicionales. En total, en 2003, el 92,3% de los campos de datos estudiados estaban rellenos, comparado con 81,3% en 2001.
Este informe confirma las ventajas de la declaracion electronica de datos de vigilancia de las enfermedades infecciosas en terminos de plazos y exhaustividad.
OA 07.03 Circulating Tumor DNA Mutant Allele Frequency and Tumor Burden as Biomarkers for Response to Immune Checkpoint Blockade
Authors: Y.K. Chae, A. Davis, S. Agte, A. Pan, N. Mohindra, V. Villaflor, F. Giles
Journal: Journal of Thoracic Oncology (2017)