tbuckley/cabot-search huggingface dataset:
Knockdown of SOX2OT inhibits the malignant biological behaviors of glioblastoma stem cells via up-regulating the expression of miR-194-5p and miR-122
Authors: Rui Su, Shuo Cao, Jun Ma, Yunhui Liu, Xiaobai Liu, Jian Zheng, Jiajia Chen, Libo Liu, Heng Cai, Zhen Li, Lini Zhao, Qianru He, Yixue Xue
Journal: Molecular Cancer (2017)

Abstract Background Accumulating evidence has highlighted the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of glioblastoma stem cells (GSCs). Here, we elucidated the function and possible molecular mechanisms of the effect of lncRNA-SOX2OT on the biological behaviors of GSCs. Results Real-time PCR demonstrated that SOX2OT expression was up-regulated in glioma tissues and GSCs. Knockdown of SOX2OT inhibited the proliferation, migration and invasion of GSCs, and promoted GSCs apoptosis. MiR-194-5p and miR-122 were down-regulated in human glioma tissues and GSCs, and miR-194-5p and miR-122 respectively exerted tumor-suppressive functions by inhibiting the proliferation, migration and invasion of GSCs, while promoting GSCs apoptosis. Knockdown of SOX2OT significantly increased the expression of miR-194-5p and miR-122 in GSCs. Dual-luciferase reporter assay revealed that SOX2OT bound to both miR-194-5p and miR-122. SOX3 and TDGF-1 were up-regulated in human glioma tissues and GSCs. Knockdown of SOX3 inhibited the proliferation, migration and invasion of GSCs, promoted GSCs apoptosis, and decreased TDGF-1 mRNA and protein expression through direct binding to the TDGF-1 promoter. Over-expression of miR-194-5p and miR-122 decreased the mRNA and protein expression of SOX3 by targeting its 3’UTR. Knockdown of TDGF-1 inhibited the proliferation, migration and invasion of GSCs, promoted GSCs apoptosis, and inhibited the JAK/STAT signaling pathway. Furthermore, SOX3 knockdown also inhibited the SOX2OT expression through direct binding to the SOX2OT promoter and formed a positive feedback loop. Conclusion This study is the first to demonstrate that the SOX2OT-miR-194-5p/miR-122-SOX3-TDGF-1 pathway forms a positive feedback loop and regulates the biological behaviors of GSCs, and these findings might provide a novel strategy for glioma treatment.
NIMG-82. PREDICTING ISOCITRATE DEHYDROGENASE GENOTYPE IN GLIOMAS USING FET PET RADIOMICS
Authors: Philipp Lohmann, Christoph Lerche, Elena Bauer, Jan Steger, Gabriele Stoffels, Tobias Blau, Veronika Dunkl, Christian P Filss, Carina Stegmayr, Bernd Neumaier, Nadim J Shah, Gereon Fink, Karl-Josef Langen, Norbert Galldiks
Journal: Neuro-Oncology (2017)
RARE-07. BEVACIZUMAB COMBINED WITH RADIOTHERAPY AS SALVAGE THERAPY FOR PEDIATRIC REFRACTORY DIFFUSE INTRINSIC BRAINSTEM GLIOMA
Authors: Linbo Cai, Juan Lee, Mingyao Lai, Jiangfen Zhou, Changguo Shan, Weiping Hong
Journal: Neuro-Oncology (2017)

Some newly diagnosed pediatric diffuse intrinsic brainstem glioma (DIPG) are with a wide range of infiltration, which may progress rapidly and cannot tolerate radiotherapy (RT). We define these DIPGs with symptoms rapidly deteriorated before or during radiotherapy with or without imaging progress as refractory DIPGs. New active treatment are required to treat these pediatric refractory DIPG. The purpose of the study was to assess the efficacy and toxicity of bevacizumab (BeV) combined with RT as salvage therapy in children with refractory DIPGs. 14 patients younger than 14 years old with newly diagnosed DIPG were enrolled. Their symptoms rapidly deteriorated before or during radiotherapy with or without imaging progress. Bevacizumab combined with RT as salvage treatment was given. Their clinical features, MRI images and clinical test result was recorded and retrospectively analysed. The effect of combined treatment was evaluated according to the RANO criterion. The patient’s progression-free survival and overall survival time was assessed by Kaplan - Meier method. With the combined treatment, 12 cases in 14 received radiographic and clinical symptoms improved and the total effective rate was 92.9%. The proportion of patients using dexamethasone was 100%(14/14) before combined treatment and decreased to 14.3%(2/14) 2 weeks later after that. Progression-free survival time was ranged from 0-14 months, median PFS time was 3 months. Overall survival time was ranged from 1 to 19 months, the median OS time was 6 months. Three cases underwent 1°myelosuppression, 1 case underwent 1°hypertension. There’s no hematuria, proteinuria, liver and kidney function damage and other side effects. Bevacizumab combined radiotherapy as a salvage treatment is effective for pediatric refractory DIPG, but does not improve the poor prognosis.
TMOD-31. RARE SOX9+ CELLS BEHIND MYC-DRIVEN MEDULLOBLASTOMA RECURRENCE
Authors: Sara Bolin, Vasil Savov, Anna Borgenvik, Alexandra Garancher, Gabriela Rosén, Aldwin Suryo Rahmanto, Sonja Hutter, Jessica Rusert, Grammatiki Fotaki, Rebecca Hill, Adrian Dubuc, Marc Remke, Matko Čančer, Vijay Ramaswamy, Steve Clifford, Olle Sangfelt, Ulrich Schüller, Michael Taylor, Robert Wechsler-Reya, Holger Weishaupt, Fredrik Swartling
Journal: Neuro-Oncology (2017)

Tumor recurrence is the leading cause of death among children with medulloblastoma, the most frequent type of malignant pediatric brain tumor. The mechanisms behind medulloblastoma recurrence are not fully understood. We found that the transcription factor SOX9 marks quiescent brain tumor stem cells and is suppressed by MYC overexpression in aggressive Group 3 tumors. By using an inducible Tet-OFF transgenic (GTML) mouse model for malignant MYCN-driven Group 3 tumors and human Group 3 MYC-driven PDX models we identified rare SOX9+, slow-cycling brain tumor cells that are more resistant to standard chemotherapy. Dox treatment normally cures GTML transgenic animals that developed aggressive medulloblastoma by turning MYCN off. However, when crossing the Tet-OFF GTML model with a Tet-ON rtTA-Sox9 model we can redirect MYCN expression to the SOX9 promoter ultimately driving brain tumor recurrence from rare SOX9+ cells with 100% penetrance. These recurrent tumors were actively disseminating from the hindbrain to the spinal cord and into the forebrain. Expression profiling comparing primary to recurrent tumors shows that recurring tumors maintain their molecular subgroup but have severely defective DNA repair system and present an increased inflammatory immune response. By overexpressing SOX9 into human Group 3 MB cells MYC was directly inhibited and decreased cell proliferation while promoting migration and metastasis. Paired primary and recurrent human Group 3 and Group 4 tumor biopsies further showed significantly higher levels of SOX9 at recurrence. Finally, PDX models of Group 3 tumors showed increased levels of SOX9 positivity in metastatic compartments. To summarize, our data clarify important and complex mechanisms by which dormant medulloblastoma cells fail to respond to standard therapy and generate relapses.
Brote de triquinosis en la región francesa de Midi-Pyrénées, enero-marzo de 1998
Authors: S Haeghebaert, M Servat, C Duchen, J C Minet, A EAgrech, I Thièse, C Leclerc, V Vaillant, C Hemery, E Maillot, C Soulé, E Pozio, P Massip, J. F. Magnaval, J C Desenclos
Journal: Eurosurveillance (1998)

El 2 de marzo de 1998, las autoridades sanitarias del departamento de Tarn et Garonne (Francia) notificaron dos brotes de triquinosis en su territorio a la Red Nacional de Salud Publica (Reseau National de Sante Publique, RNSP). El 3 de marzo se inicio una investigacion epidemiologica para determinar la extension del brote, identificar su origen, vehiculo alimentario y proponer medidas de control.
RTHP-16. PATTERNS OF TREATMENT AND OUTCOMES OF 1p19q CO-DELETED GLIOMAS
Authors: Debra Yeboa, James Yu, Jason Huse, Marta Penas-Prado, Erik Sulman, Joseph Contessa
Journal: Neuro-Oncology (2017)

Molecular markers are redefining classification of lower grade gliomas and ushering in a paradigm shift in their management. Our objective was to evaluate histologic grade on patterns of care and treatment outcomes for 1p19q co-deleted gliomas. We evaluated 737 patients in the National Cancer Database diagnosed with 1p19q co-deleted gliomas from 2004 through 2012 and treated with surgery followed by radiation therapy (RT), chemotherapy (CT), or combined-modality therapy. Patients with grade II tumors were more likely to receive surgery only than those with grade III tumors (58.1% vs. 14.8%, p<0.001), whereas those with grade III tumors were more likely to receive combined-modality therapy (52.2% vs. 6.1%, p<0.001). Among 472 patients with available follow-up, grade predicted overall survival, with an 8% difference at 2 years (98.2% grade II vs. 90.6% grade III, p<0.001). In a Cox multivariable proportional hazards model adjusting for patient and treatment factors, age (>59 yrs vs. <40 yrs; hazard ratio [HR] 15.66, 95% confidence interval [CI] 3.68–66.61, p<0.001), grade (III vs. II; HR 5.84, 95% CI 1.91–17.81, p=0.001), and histology (oligodendroglioma vs. other; HR 0.23, 95% CI 0.10–0.53, p=0.001) were associated with survival. Outcomes after surgery alone were different for grade II and grade III tumors (99.3% grade II vs. 75.7% grade III survival at 2 years, p<0.001), but the addition of post-operative therapy closed the gap between grades. Longer follow-up and additional molecular characterization is needed to further determine the influence of tumor grade in the management of type I 1p19q co-deleted glioma.
P2.02-039 Spatial Heterogeneity of Immunological Markers Between Cores and Complete NSCLC Sections Using Multispectral Fluorescent IHC
Authors: G. Peters, M. Ameratunga, D. Tutuka, M. Walkiewicz, P. Russell, S. Knight, P. Mitchell, T. John
Journal: Journal of Thoracic Oncology (2017)
P3.13-004 Prospective Study of Sequential Ultra-Low then Standard Dose 18F-FDG PET/CT Scans for Lung Lesion Detectability
Authors: J. Schaefferkoetter, D. Townsend, M. Conti, X.M. Shi, R. Soo, J. Tam, A. Sinha, I. Tham
Journal: Journal of Thoracic Oncology (2017)
CBIO-05. UNDERSTANDING MECHANISMS OF IDH-MUTANT, 1p19q INTACT GLIOMA PROGRESSION THROUGH USE OF LATEST-GENERATION MASS SPECTROMETRY
Authors: Angela Cho, Sarah Hayes, Amanda Hudson, Emily Colvin, Helen Wheeler, Viive Howell
Journal: Neuro-Oncology (2017)

Gliomas are the most common primary brain tumors in adults. Driver mutations in Isocitrate Dehydrogenase 1 and 2 (IDH1/2) result in overproduction of an oncometabolite, 2-hydroxy-keto glutartate with subsequent downstream Tp53 mutations or loss of 1p19q. IDH-mutated low grade gliomas have a relatively indolent clinical course; however over time they migrate to a higher grade. Initial standard of care involves surgery with the addition of radiation and alkylating chemotherapy for more aggressive lesions. Molecular studies of recurrent lesions have documented numerous DNA mutations consistent with alkylating agent damage in those treated with chemotherapy. To ascertain the natural history of progressive IDH mutated 1p19q intact tumors this study compared differences in the proteomic profiles of 6 matched pairs of primary and recurrent lesions from patients who had NOT received chemotherapy. Three patients presented with grade 2 lesions and following resection were observed. Time to recurrence (TTR) was 38, 30 and 14 months respectively. Three patients presented with grade 3 lesions and received radiotherapy alone following surgery. Their TTR was 99, 52 and 71 months. Protein was extracted from frozen specimens and following quality control analyzed by SWATH-MS (on a Sciex TripleToF 6600). Overall, 1781 proteins were identified by SWATH-MS analysis. Of those proteins, 40 were significantly differentially expressed (FC ≥2-fold; p ≤ 0.05) between primary and recurrent specimens. In both datasets, these key proteins were associated with activation of the Acute Phase Response, Cell Death and Survival and Cellular Compromise, Development and Movement. Proteins significantly differentially expressed included PTPRZ1, GLS, IGFBP7 and LUM, which are involved in tumor cell proliferation and migration, angiogenesis and chemotherapy resistance. The identification of differentially expressed proteins will improve our understanding of the mechanisms driving recurrence and progression of gliomas and may also reveal potential novel targets for additional therapies for this deadly cancer.
MA 17.11 Prediction of Response to Trimodality Therapy Using CT-Derived Radiomic Features in Stage III Non-Small Cell Lung Cancer (NSCLC)
Authors: P. Jain, U. Ahmad, S. Murthy, K. Stephans, M. Khorrami, A. Madabhushi, V. Velcheti
Journal: Journal of Thoracic Oncology (2017)
Elevated expression of matrix metalloproteinase-9 in cutaneous squamous cell carcinoma may reflect increased tumor invasiveness
Authors: Anthony O’Grady, Cara Dunne, Mary Leader, Gillian Murphy, Elaine Kay
Journal: Cancer Research (2006)

4357   Squamous cell carcinoma (SCC) of the skin is a malignant epidermal neoplasm with the capacity for local destruction and metastatic disease. Bowen’s disease (BD) is a form of squamous cell carcinoma  in situ , with atypical keratinocytes proliferating through the full thickness of the epidermis which if left untreated may develop into invasive disease. It is estimated that up to 40% of transplant recipients develop malignancies of the skin such as BD and invasive SCC within the first 5 years following transplantation. Transplant associated skin cancers have contributed substantially to global increases in skin cancer incidence, morbidity and mortality. The matrix metalloproteinases (MMPs) and their inhibitors are critical regulators of extracellular matrix composition during tumor invasion and metastasis. The purpose of this study was to elucidate the expression and cellular localisation of MMP-9 and its preferential inhibitor tissue inhibitor of metalloproteinase-1 (TIMP-1) in 24 cutaneous pre-invasive (Bowen’s disease) and 23 invasive squamous cell carcinoma from renal transplant recipients and a non-transplanted population using immunocytochemistry and  in situ  hybridization. Evaluation of the results was based on a semi-quantitative scoring system encompassing the percent and intensity of positive tumor cells and adjacent stromal cell staining. Increased MMP-9 expression was observed in SCC when compared with BD. The intensity of MMP-9 expression correlated with the degree of cellular atypia, inflammation and localisation at the invasive tumor front. Acantholytic cells in invasive SCC stained more intensely. The presence of TIMP-1 in vessel endothelial cells and stromal cells was similar in all cases. These results and our previous findings of an increase in microvessel density in SCC compared with BD further support a role for MMP-9 in triggering the angiogenic switch. The increased expression of MMP-9 in certain BD and absence of any significant TIMP-1 response may highlight those  in  situ  tumors that are more likely to progress to invasive SCC. A recent report of the upregulation of TIMP-1 and downregulation of MMP-9 following topical imiquimod treatment of malignant melanoma suggest a possible therapeutic intervention for the treatment of non-melanoma skin cancer overexpressing MMP-9.
P1.07-023 The Correlation Between B7-H4 Expression and Survival of Non-Small Cell Lung Cancer Patients Treated with Nivolumab
Authors: C. Genova, S. Boccardo, P. Bruzzi, M. Mora, E. Rijavec, G. Rossi, F. Biello, G. Barletta, M. Tagliamento, M.G. Dal Bello, A. Alama, S. Coco, I. Vanni, F. Grossi
Journal: Journal of Thoracic Oncology (2017)
Aflibercept efficacy according to sidedness, RAS and BRAF mutations. Findings from the VELOUR trial in second line therapy of advanced colorectal cancer patients
Authors: E. Maiello, V. Pomella, P. Wirapati, M. Di Bartolomeo, M.G. Zampino, F. Leone, T.P. Latiano, F. Pietrantonio, P.S. Ravenda, D. Marino, S. Tejpar
Journal: Annals of Oncology (2017)
Science Requires Open Discourse
Authors: Mitchell H. Katz, Rita F. Redberg
Journal: JAMA Internal Medicine (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 Internal Medicine 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 Internal Medicine journal
Un brote regional de S. Typhimurium en Dinamarca : identificación de la fuente por tipado MLVA
Authors: M Torpdahl, G Sørensen, S Ethelberg, G Sandø, K Kammelgard, L Jannok Porsbo
Journal: Eurosurveillance (2006)

En Dinamarca, dentro del sistema nacional de vigilancia microbiologica de las infecciones entericas, se realiza el sub-tipado de todos los aislamientos de S. Typhimurium por lisotipado, tipado por antibiograma y electroforesis en campo pulsado (PFGE). 
Sin embargo, para ciertos lisotipos, no es suficiente la capacidad discriminatoria del PFGE, y resulta imposible separar los aislamientos asociados de los no asociados. Por eso, desde 2004, fue aplicado el metodo de sub-tipado MLVA (multiple locus variable number of tandem repeats analysis) para la vigilancia de los aislamientos de S. Typhimurium. De esta manera se identifico un brote de 26 casos de S. Typhimurium en Mayo y Junio de 2005. Los aislamientos eran totalmente sensibles a todos los antimicrobianos, y tenian uno de los lisotipos mas frecuentes en Dinamarca (DT12) y el mismo perfil PFGE. Se analizaron por MLVA y PFGE las cepas de S. Typhimurium procedentes de la vigilancia de rutina en animales y alimentos para compararlas con los aislamientos humanos. Los resultados del tipado mostraron una semejanza perfecta (mismos PFGE y MLVA) entre los aislamientos humanos y un aislamiento procedente de una granja porcina y del matadero correspondiente, localizado en la region donde ocurrio el brote. En cambio, los otros aislamientos DT12 analizados que tenian el mismo perfil en PFGE, tenian tipos MLVA diferentes. La hipotesis que la granja porcina sea la fuente de las infecciones humanas fue reforzada por informaciones proporcionadas por los pacientes. La venta de la carne de esa granja fue prohibida el 29 de Junio. El analisis por MLVA puede contribuir eficazmente en la vigilancia asi como a las investigaciones de brotes de S. Typhimurium. Sin este metodo de tipado no hubiera sido posible detectar el brote, ni tampoco se hubiera descubierto la fuente de infeccion.
CSIG-20. INHIBITION OF AKT/SURVIVIN AND AKT/ID3 PATHWAYS BY CELECOXIB, A SELECTIVE COX-2 INHIBITOR, MAY HAVE PROMISING THERAPEUTIC POTENTIAL IN LOW-GRADE GLIOMA
Authors: Izumi Yamaguchi, Aya Sato, Yoshifumi Mizobuchi, Kohei Nakajima, Toshitaka Fujihara, Kenji Shono, Keiko Kitazato, Akiko Sumi, Shinji Nagahiro
Journal: Neuro-Oncology (2017)

Approximately half of the patients with low-grade glioma (LGG) treated surgically suffer recurrence or metastasis. Malignant transformation sometimes occurs after several years and no effective drug treatment has been established yet. Though the selective COX-2 inhibitor celecoxib showed anti-tumor effects against several malignant tumors, its effects against LGG remain to be established. To test our hypothesis that the celecoxib has an anti-tumor effect in LGG, we used human glioma and GBM cell lines (1321N1, SW1088, U87MG, U251MG, and NHA). First, we confirmed the high expression of COX-2 in 12 tissue samples from glioma patients: astrocytoma (glioma grade II, n=2), anaplastic astrocytoma (glioma grade III, n=5), and glioblastoma (glioma grade IV, n=5). We also found that the COX2 expression in LGG cell lines was higher than that in the non-neoplastic region and in normal brain cells. We demonstrated that celecoxib suppressed LGG cell proliferation in a dose-dependent manner. Next, we investigated the mechanisms underlying the anti-tumor effects and found that celecoxib inhibited the generation of prostaglandin E2 and induced apoptosis and cell-cycle arrest. Finally we manifested that celecoxib inhibits the activation of the AKT/survivin and AKT/ID3 pathways in LGG. These findings suggest that celecoxib may have promising therapeutic potential and that early celecoxib treatment to patients with LGG may be beneficial.
PATH-38. COMPREHENSIVE GENOMIC PROFILING OF OLIGODENDROGLIOMAS REFINES TUMOR DIAGNOSES AND IDENTIFIES PATIENTS FOR TARGETED THERAPIES AND IMMUNE CHECKPOINT INHIBITORS
Authors: Shakti Ramkissoon, Lee Albacker, Eric Severson, Caitlin Connelly, Adrienne Johnson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Charlotte Brown, Mandy Covert, Alexa Schrock, Garrett Frampton, Siraj Ali, Philip Stephens, Vincent Miller, Jeffrey Ross
Journal: Neuro-Oncology (2017)

Oligodendrogliomas (ODG) are diffusely infiltrating gliomas characterized by IDH mutations and 1p/19q co-deletion. Distinguishing between diffuse gliomas can be challenging based solely on microscopic features and lead to misclassification of glioma lineage. Genomic profiling of oligodendrogliomas is critical to ensuring diagnostic accuracy and identifying therapeutic options for patients with progressive and/or malignant tumors. DESIGN: Comprehensive genomic profiling (CGP) was performed on FFPE material acquired from 200 consecutive submitted cases of locally diagnosed ODG. CGP identifies tumor mutational burden, microsatellite instability status (MSI) and all classes of genomic alterations in 315 cancer-associated genes including a validated novel algorithm that accurately determines 1p/19q co-deletion status. Among the 202 ODG samples, 1p/19q co-deletion was identified in 152 (75.2%) of cases and in these tumors, the most frequently altered genes were TERT, IDH1/2, CIC, FUBP1, PIK3CA/PIK3R1 and NOTCH1/2. Notably in these tumors activating alterations were frequently detected in PI3K pathway genes including PIK3CA (19.5%), PIK3R1 (7.5%) and PTEN (1.3%). Of the 50 (24.8%) ODG negative for 1p/19q co-deletion (24.8%), the genomic profiles supported astrocytic lineage gliomas (IDH1, TP53, ATRX, TERT, CDKN2A/B and PTEN mutations) warranting tumor reclassification. Among the 1p/19q co-deleted ODG, the median TMB was 2.7 mutations/Mb (range <1 to 818 mutations/Mb) with 8.6% (n=13) of tumors demonstrating hypermutation (≥20 mutations/Mb). MSI-High status was not detected in any ODG. By characterizing 1p/19q co-deletion and genomic profiles of diffuse gliomas, CGP ensures diagnostic accuracy by distinguishing between oligodendroglial and astrocytic lineage tumors. CGP identified pathways for therapeutic intervention in 1p/19q positive ODG including IDH, PI3K pathway and NOTCH1/2 inhibitors. We also report that a subpopulation of oligodendrogliomas with high TMB may benefit from immune checkpoint inhibitors.