tbuckley/cabot-search huggingface dataset:
PDCT-08. SUPERIOR OUTCOME FOR BRAF V600E PEDIATRIC GLIOMAS TREATED WITH TARGETED BRAF INHIBITION
Authors: Liana Nobre, Michal Zapotocky, Vijay Ramaswamy, Scott Ryall, Julie Bennett, Julia Balaguer Guill, Lorena Baroni, Ute Bartels, Miriam Bornhorst, Daniel Boue`, Murali Chintagumpala, Ofelia Cruz, Sonika Dahiya, Peter Dirks, Ira Dunkel, David Eisenstat, Elizabeth Finch, Jonathan Finlay, Didier Frappaz, Maria Luisa Garre, Karen Gauvain, Anne Grete Bechensteen, Jordan Hansford, Peter Hauser, Annie Huang, Matthias Karajannis, Gurcharanjeet Kaur, Valerie Larouche, Alvaro Lassaletta, Sarah Leary, Frank Lin, Tara McKeown, Til Milde, Andres Morales La Madrid, Helena Morse, Naureen Mushtaq, Diana Osorio, Roger Packer, Zdenek Pavelka, Duarte Salgado, Magnus Sabel, Palma Solano, Jack Su, David Sumerauer, Helen Toledano, Cornelis van Tilburg, Bev Wilson, Eric Bouffet, Cynthia Hawkins, Uri Tabori
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Children with pediatric low grade glioma’s (PLGG) harboring BRAF V600E mutation have poor outcome due to relative resistance to chemo-radiation and higher risk of malignant transformation. However, the role of targeted BRAF inhibition in these tumors is poorly defined. METHODS We assembled an international cohort of children with BRAF V600E mutant gliomas treated with BRAF inhibition, from 29 centers participating in the PLGG taskforce, and collected response, survival and molecular parameters. RESULTS Sixty-seven patients were treated with BRAFi (56 PLGG and 11 high grade gliomas) for a median time of 17.4 months (6 – 61 months), with 13 PLGG treated upfront. Objective responses was observed in 80% of PLGG patients compared to 28% with conventional chemotherapy (p&lt; 0.001). Rapid responses were observed in most PLGG patients (median of 4 months), sustained in 86% of tumors up to 5 years while on therapy. In contrast, only 36% of PHGG responded to BRAFi with all but one tumor progressing within 18 months. Seventeen patients with PLGG discontinued BRAFi and 76.5% (13/17) progressed rapidly after discontinuation (median time 2.3 months). However, upon re-challenge with BRAFi therapy, 90% achieved an objective response. Poor prognostic factors to conventional therapies such as concomitant homozygous deletion of CDKN2A or H3K27M mutation were not associated with lack of response to BRAFi. Overall these responses translated to 2-year progression-free survival of 0.636 (95%CI 0.505–0.802) and 0.43 (95% CI 0.32–0.57) for BRAFi and chemotherapy treated BRAF V600E PLGG respectively (p=0.003). CONCLUSION The use of BRAFi results in objective, robust and durable responses in BRAF V600E PLGG and is associated with favorable survival. Larger prospective studies will be required to determine appropriate regiments, and long-term functional outcomes with BRAFi therapy in childhood gliomas.
TMIC-65. GLOBAL PROFILING OF IMMUNE RESPONSE OF MICROGLIA AND MACROPHAGES IN PRECLINICAL MODEL OF GLIOBLASTOMA.
Authors: Kacper Walentynowicz, Natalia Ochocka, Paweł Segit, Jakub Mieczkowski, Bartosz Wojtaś, Bartłomiej Gielniewski, Kacper Kostyra, Szymon Baluszek, Bogusław Kostkiewicz, Bozena Kaminska
Journal: Neuro-Oncology (2019)

Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor showing the poorest prognosis. Despite extensive research, no significant improvement in glioma therapy. GBM microenvironment has been shown to contribute to the aggressiveness of the tumor and influences overall survival. Tumor associated microglia and macrophages (TAMs) contribute to the biggest portion of tumor infiltrative cellular component, and may drive the immune response within the tumor. Their influence in the preclinical studies has not been fully described. Reliable animal models are crucial to facilitate translational research and drug discovery. In the present study, we employed animal xenograft model, where human GBM cells were stereotactically implanted into the mouse brain. Early and late stage responses of TAMs were studied using RNA-seq. Epigenetic changes within the TAMs were assessed using Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) and Chromatin Immunoprecipitation sequencing (ChIP-seq) for four histone modifications (active transcription H3K4me3, H3K27ac, and repressed H3K9me3, H3K27me3) to further identify molecular alterations responsible for transcriptomic profiles. To facilitate translational discovery and heterogenous population of infiltrative cells, we isolated human CD11b cells from GBM patients and performed single cell RNA-seq (scRNAseq) using 10X Genomics platform. Moreover, we compared profiles of CD11b cells in the xenograft model with syngeneic immunocompetent model to further characterize commonly used models. Preliminary analysis shows critical differences between the models. Gain of global activation of genes has not been identified in the xenograft model. Differences in critical pathways in naïve microglia were identified, between the two studied models. Such global and extensive analysis allows us to compare preclinical models of GBM and clinical samples, and identify common pathways that can serve as potential therapeutic targets. This study was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 665735 (Bio4Med) and National Science Centre grant 2017/27/B/NZ3/01605.
MNGI-08. PHARMACOKINETIC ANALYSIS OF 68GA-DOTATOC IN MENINGIOMAS USING PET/CT FOR ASSESSMENT OF SOMATOSTATIN RECEPTORS AND CORRELATION WITH ANGIOGENESIS, INFLAMMATION AND PROLIFERATION
Authors: Asma Bashir, Mark Bitsch Vestergaard, Tina Binderup, Helle Broholm, Lisbeth Marner, Morten Ziebell, Kåre Fugleholm, Andreas Kjær, Ian Law
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND A quantitative correlative analysis between 68Ga-DOTATOC accumulation using PET/CT and somatostatin receptor subtype 2 (SSTR2) in meningiomas was conducted. The possible contributions of angiogenesis and inflammation were investigated as well. METHODS Fifteen patients with newly (n = 12) and recurrent (n = 3) meningiomas were prospectively assigned to a 60-minute dynamic 68Ga-DOTATOC PET/CT scan prior to surgery. PET data included measurements of maximum and mean standardized uptake value (SUVmax, SUVmean) with/without normalisation to different reference tissues, and quantitative measures derived from kinetic modeling using a reversible two-tissue compartment model with the fractional blood volume (VB) included in the model. The SSTR2-expression was determined by immunohistochemistry and quantitative polymerase chain reaction (qPCR), while biomarkers of inflammation (macrophage-specific marker CD68, interleukin-18 [IL18]) and angiogenesis (endothelial marker CD34, vascular endothelial growth factor-A [VEGF-A]), were assessed by qPCR only. RESULTS Twelve patients (80%) were diagnosed with World Health Organization (WHO) grade I meningioma and three with WHO grade II (20%). No significant differences in SSTR2-expression was seen between WHO grades or subtypes (P ≥ 0.05; Mann-Whitney, Kruskal-Wallis). Upon stratification of patients based on the median SUVs (SUVmax, 20.9; SUVmean, 9.9), SSTR2-expression was seven-fold increased in patients with SUVs above the medians compared to patients with SUVs below the medians. Spearman’s rank correlation coefficient revealed significant correlations between SSTR2-expression, and SUVmean (r = 0.532, P = .041) and mean tumor-to-neck muscle ratio (TNMRmean) (r = 0.593, P = .020). 68Ga-DOTATOC uptake was additionally associated with VB and VEGF-A (P &lt; 0.01), while no association with inflammatory biomarkers were found. In univariate linear regression analysis, SUVmean and TNMRmean remained the optimal surrogate biomarkers for SSTR2-expression (P &lt; .0001). CONCLUSIONS 68Ga-DOTATOC accumulation in meningiomas is more complex than previously reported, and may not be limited to the SSTR2-density but also be associated with the vascular component.
A piece of my mind. Keola and the kahuna
Authors: D. J. Elpern
Journal: JAMA (1989)

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 HomeNew OnlineCurrent IssueFor Authors 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Genomic profiling of non-oncogene-addicted aNSCLC using liquid biopsy. A single institution Italian experience
Authors: R. Di Liello, G. Viscardi, F. Sparano, C.M. Della Corte, M.L. Iacovino, F. Paragliola, V. Famiglietti, A. Di Liello, F. Ciardiello, F. Morgillo
Journal: Annals of Oncology (2019)
WHO-Defined Chronic Myelomonocytic Leukemia-2 (CMML-2) Patients Rapidly Progress to AML Suggesting This Entity Represents a Transitory Clinical State
Authors: Anthony M. Hunter, Najla Al Ali, David A Sallman, Kendra L. Sweet, Andrew T Kuykendall, Chetasi Talati, Alan F. List, Jeffrey E. Lancet, Rami S. Komrokji, Eric Padron
Journal: Blood (2019)
Reversible DNA Hypermethylation of the Interleukin-15 (IL-15) Promoter Induces IL-15 Expression, Drives the Pathogenesis of T-Cell Large Granular Lymphocytic Leukemia and Provides a Potential Therapeutic Approach Using 5-Azacitidine
Authors: Jonathan E Brammer, Amy E Boles, Anthony Mansour, Aharon G. Freud, Monique Mathé-Allainmat, Agnès Quéméner, Erwan Mortier, Pierluigi Porcu, Anjali Mishra
Journal: Blood (2019)
Genetic and Genomic Characterisation of Older Adults with Acute Lymphoblastic Leukemia Treated on the UKALL14 and UKALL60+ Clinical Trials
Authors: Thomas Creasey, Emilio Barretta, Amy A. Kirkwood, Claire Schwab, Pip Patrick, Laura Clifton-Hadley, Bela Wrench, Tobias F Menne, Andrew K McMillan, Nicholas J. Morley, John A Snowden, Christine J. Harrison, Daniel A. Leongamornlert, Elli Papaemmanuil, Clare J Rowntree, David I Marks, Adele K. Fielding, Anthony V. Moorman
Journal: Blood (2019)
miR‐145‐5p profibrotic activity in RDEB
Authors: A.G. Condorelli, E. Logli, F. Cianfarani, M. Teson, A. Diociaiuti, M. El Hachem, G. Zambruno, D. Castiglia, T. Odorisio
Journal: British Journal of Dermatology (2019)

Recessive dystrophic epidermolysis bullosa (RDEB) is a rare and highly disabling genetic disease. RDEB hallmarks are skin fragility, constant blistering, and defective wound healing leading to inflammation and fibrosis, which means tissue hardening. Fibrosis underlies major RDEB complications, including limb deformities and cancer, and preventing it is a strategy to improve the disease course. Despite the identification of several molecules that are deregulated in RDEB fibrosis, the disease mechanisms are not fully known. Our genetic code contains the information to produce RNA molecules, called messenger RNAs, which serve to build the proteins forming our body. However, a large family of RNA molecules, called microRNAs, are not transformed into proteins, but regulate the amount of proteins produced. The altered function of microRNAs contributes to the development of many diseases. This study, performed at Bambino Gesù Children's Hospital in Italy, aimed to identify and characterize the role of microRNAs that are altered in RDEB patients and contribute to their skin fibrosis. This laboratory study used a cell type, the fibroblast, which populates the skin and is a major player in fibrosis. The authors observed that some microRNAs are more abundant in fibroblasts obtained from RDEB patients as compared to cells from healthy individuals, and demonstrated that one of them, the miR‐145‐5p, fuels fibrosis. The researchers switched off the miR‐145‐5p in RDEB fibroblasts and then studied fibroblast ability to contract, proliferate, and move, all activities that are increased in fibrosis. Blocking miR‐145‐5p reduced the contractility, proliferation and migration of RDEB fibroblasts, and determined the reduction of various contractile and pro‐fibrotic (fibrosis causing) molecules. In conclusion, the authors have discovered a novel microRNA that contributes to the development of fibrosis in RDEB, and described its mode of action. These findings help us to understand more about the disease and possible targets for future treatment.
Use of CD70 Targeted Chimeric Antigen Receptor (CAR) T Cells for the Treatment of Acute Myeloid Leukemia (AML)
Authors: Mark Leick, Irene Scarfò, Bryan D. Choi, Rebecca Larson, Amanda A Bouffard, Ana Castano, Maria L. Cabral, Andrea Schmidts, Matthew J. Frigault, Marcela V. Maus
Journal: Blood (2019)
Need for routine examination of left ventricular ejection fraction in patients with AML
Authors: Hiba M. Khan, Kelda M. Gardner, Carole Shaw, Anna B. Halpern, Emily M. Huebner, Mary-Elizabeth M. Percival, Sarah Mirahsani, Mohamed L. Sorror, Pamela S. Becker, Roland B. Walter, Elihu H. Estey
Journal: Leukemia (2019)
circGSK3β promotes metastasis in esophageal squamous cell carcinoma by augmenting β-catenin signaling
Authors: Xueting Hu, Duoguang Wu, Xiaotian He, Huiying Zhao, Zhanghai He, Jiatong Lin, Kefeng Wang, Wenjian Wang, Zihao Pan, Huayue Lin, Minghui Wang
Journal: Molecular Cancer (2019)

Abstract Background Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn much attention in the pathogenesis of human cancers. However, the role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we aimed to identify novel circRNAs that regulate ESCC progression and explored their regulatory mechanisms and clinical significance in ESCC. Methods Differentially expressed circRNAs between ESCC and paired adjacent normal tissues were identified using microarrays. The effects of a specific differentially expressed circRNA (circGSK3β) on tumor progression were explored in vitro and in vivo. Plasma samples from patients with ESCC, benign lesions and healthy controls were subjected to droplet digital PCR (ddPCR) analyses for circGSK3β, and the detection rates of plasma circGSK3β for ESCC were investigated. Results We demonstrated that upregulated expression of circGSK3β was positively associated with advanced clinical stage and poor outcome in patients with ESCC. We further revealed that circGSK3β promoted ESCC cell migration and invasion via direct interaction with GSK3β and inhibiting GSK3β activity, providing a novel mechanism of circRNA in cancer progression. Importantly, we identified that circGSK3β expression in plasma was a biomarker for detection of ESCC and early stage of ESCC with the area under curve (AUC) of 0.782 and 0.793, respectively. Conclusions CircGSK3β exerts critical roles in promoting ESCC metastasis and may serve as a novel therapeutic target for ESCC patients. The plasma level of circGSK3β have potential to serve as a novel diagnostic and prognostic biomarker for ESCC detection.
Wearable Organic Electrochemical Transistor Patch for Multiplexed Sensing of Calcium and Ammonium Ions from Human Perspiration
Authors: Scott T. Keene, Daragh Fogarty, Ross Cooke, Carlos D. Casadevall, Alberto Salleo, Onur Parlak
Journal: Advanced Healthcare Materials (2019)

Abstract Wearable health monitoring has garnered considerable interest from the healthcare industry as an evolutionary alternative to standard practices with the ability to provide rapid, off‐site diagnosis and patient‐monitoring. In particular, sweat‐based wearable biosensors offer a noninvasive route to continuously monitor a variety of biomarkers for a range of physiological conditions. Both the accessibility and wealth of information of sweat make it an ideal target for noninvasive devices that can aid in early diagnosis of disease or to monitor athletic performance. Here, the integration of ammonium (NH 4 + ) and calcium (Ca 2+ ) ion‐selective membranes with a poly(3,4‐ethylenedioxythiophene):poly(styrenesulfonate)‐based (PEDOT:PSS) organic electrochemical transistor (OECT) for multiplexed sensing of NH 4 + and Ca 2+ in sweat with high sensitivity and selectivity is reported for the first time. The presented wearable sweat sensor is designed by combining a flexible and stretchable styrene‐ethylene‐butene‐styrene substrate with a laser‐patterned microcapillary channel array for direct sweat acquisition and delivery to the ion‐selective OECT. The resulting dermal sensor exhibits a wide working range between 0.01 × 10 −3 and 100 × 10 −3 m , well within the physiological levels of NH 4 + and Ca 2+ in sweat. The integrated devices are successfully implemented with both ex situ measurements and on human subjects with real‐time analysis using a wearable sensor assembly.
Dead/H-Box Helicase 11 (DDX11) Mutations Correlate with Increased Relapse Risk in Persons with Acute Myeloid Leukaemia and Promote Proliferation and Survival of Human AML Cells in Vitro and in Immune Deficient Mice
Authors: Ya-Lan Zhou, Li-Xin Wu, Robert Peter Gale, Zi-Long Wang, Jin-Lan Li, Hao Jiang, Qian Jiang, Bin Jiang, Shan-Bo Cao, Ying Sun, Feng Lou, Chengcheng Wang, Yan-Rong Liu, Yu Wang, Ying-Jun Chang, Lanping Xu, Xiaohui Zhang, Kaiyan Liu, Guorui Ruan, Xiaojun Huang
Journal: Blood (2019)
Customisation of therapeutic strategy in metastatic colorectal cancer by use of liquid biopsies: Updated results of an observational study
Authors: M. Kastrisiou, G. Zarkavelis, A. Kougioumtzi, C. Tzallas, E. Saloustros, A. Kotsakis, E. Papadopoulou, G. Nasioulas, A. Batistatou, A. Magklara, G. Pentheroudakis
Journal: Annals of Oncology (2019)
EXTH-72. MANZAMINE A-DERIVED COMPOUNDS AS POTENTIAL ANTI-BRAIN TUMOR AGENTS AND IT MECHANISM STUDY
Authors: Chiung-Yin Huang, Pin-Yuan Chen, Kuo-Chen Wei, Tsong-Long Hwang
Journal: Neuro-Oncology (2019)

Abstract Glioma is a severe disease with poor prognosis. Chemotherapy plays an important role but very few drugs are effective. There are two major issues: (1) the specialized blood-brain barrier blocks most large molecules from penetrating into target area; (2) tumor cells frequently develop drug resistant. Therefore, developing new chemotherapeutic agents for malignant brain tumor treatment may significantly improve the current difficulties. Compounds derived from nature products have been considered as potential sources for new discovery of anti-cancer drug. Manzamine A-derived compounds, showed significant anticancer activities against colon adenocarcinoma DLD cells, lung large cell carcinoma NCI-H661 cells, and hepatoma HepG2/A2 cells. In this study, we used in vitro model for screening these compounds and discovered both cytotoxic and anti-proliferative effects against brain tumor cells, such as A172, U87MG, and GL261 cell lines. We then used animal models to test the toxicities and treatment effect of compound A3 in vivo, and delivered the agent by convection-enhanced delivery to improve drug concentration in brain. Survival benefit for brain tumor-bearing animal was found for optimal dosage of compound A3. Details of anti-tumor mechanism need further evaluation.
Rivaroxaban and Extended Thromboprophylaxis in Acutely Ill Medical Patients with History of Cancer: Insights from the Magellan and Mariner Studies
Authors: Alex C. Spyropoulos, Concetta Lipardi, Alexander T Cohen, Biljana Vučković, Jianfeng Xu, Wentao Lu, Theodore E. Spiro, Elliot S. Barnathan, Gary E. Raskob
Journal: Blood (2019)
Enabling Gene-Edited, Regulatory-like, T Cells (edTreg) for Treatment of IPEX and Other Autoimmune Disorders
Authors: Yuchi Honaker, Karen Sommer, Noelle Dahl, Yufei Xiang, Christina Lopez, Samuel Scharffenberger, Michelle Christian, Troy R. Torgerson, Andrew M. Scharenberg, David J. Rawlings
Journal: Blood (2019)
DDIS-04. INTERFERON-β SENSITIZES HUMAN GLIOBLASTOMA CELLS TO THE CYCLIN-DEPENDENT KINASE INHIBITOR, TG02
Authors: Emilie Le Rhun, Birthe Lohmann, Mirka Epskamp, Michael Weller
Journal: Neuro-Oncology (2019)

Abstract Novel treatments for glioblastoma, the most common malignant primary brain tumor, are urgently needed. Type I interferons (IFN) are natural cytokines primarily involved in defense against viral infections, but may also play a role in the control of cancer, notably in the suppression of the cancer stem cell phenotype. TG02 is a novel orally available cyclin-dependent kinase 9 inhibitor which induces glioma cell apoptosis without profound caspase activation and is currently being explored in early clinical trials in newly diagnosed and recurrent glioblastoma. Here we used human glioma-initiating cell line models to explore whether IFN-β modulate the anti-glioma activity of TG02. Pre-exposure to IFN-β sensitized human glioma models to a variable extent to subsequent exposure to TG02. Combination treatment was associated with increased DEVD-amc cleaving activity that was blocked by BCL2. However, BCL2 did not protect from the synergistic effects of IFN and TG02 on glioma cell growth, furthermore, although IFN strongly induced pro-apoptotic XIAP-associated factor (XAF) expression, disrupting XAF expression did not abrogate the synergy with TG02 either. Consistent with that, caspase 3 gene silencing did not abrogate effects of TG02 or IFN-β alone or in combination. Finally, we observed that IFN-β may indeed modulate the effects of TG02 up-stream in the signaling cascade since inhibition of RNA polymerase II phosphorylation, a direct readout of TG02 pharmacodynamic activity, was facilitated in glioma cells pre-exposed to IFN-β. In summary, these data suggest that type I IFN may be combined with TG02 to limit glioblastoma growth but the well characterized effects of IFN and TG02 on apoptotic signaling are dispensable for synergistic control of tumor growth. Instead, exploring how IFN signaling primes glioma cells for TG02-mediated direct target inhibition may help to design novel, more effective pharmacological approaches to glioblastoma.
Evaluation of Virus-Specific T Cell Responses in Patients Affected with Myeloproliferative Neoplasms Treated with Ruxolitinib
Authors: Elisa Rumi, Chiara Cavalloni, Giuditta Comolli, Virginia Valeria Ferretti, Irene Cassaniti, Daniela Pietra, Chiara Trotti, Michele Ciboddo, Melania Degli Antoni, Milena Furione, Fausto Baldanti, Luca Arcaini, Mario Cazzola
Journal: Blood (2019)