tbuckley/cabot-search huggingface dataset:
CSIG-14DE-DIFFERENTIATION OF ASTROCYTES INTO GLIOBLASTOMA STEM CELLS THROUGH CORE PATHWAY MUTATIONS
Authors: Ralf Schmid, Mark Vitucci, Robert McNeill, Ryan Bash, Andrea Werneke, Lauren Huey, Kristen White, Matthew Ewend, Jing Wu, C. Ryan Miller
Journal: Neuro-Oncology (2015)

BACKGROUND: Glioma stem cells isolated from human glioblastomas are resistant to radiation and cytotoxic chemotherapy and may drive tumor recurrence. Treatment efficacy may depend on the presence of glioma stem cells, expression of DNA repair enzymes such as methylguanine methyltransferase (MGMT), or transcriptome subtype. METHODS: To model genetic alterations in the core signaling pathways of human glioblastoma, we induced conditional Rb knockout, Kras activation, and Pten deletion mutations in cortical murine astrocytes. Serial neurosphere culture, multi-lineage differentiation, and orthotopic transplantation into immuno-competent mice were used to assess whether these mutations induced their de-differentiation into glioma stem cells. Efficacy of radiation and temozolomide was examined in vitro and in an allograft model in vivo. The effects of radiation on transcriptome subtype was examined by expression profiling. RESULTS: Rb knockout astrocytes gained unlimited self-renewal and multi-lineage differentiation capacity, in both the presence and absence of Kras and/or Pten mutations. Only triple mutant astrocytes formed serially-transplantable glioblastoma allografts. Triple mutant astrocytes were sensitive to radiation, but expressed Mgmt and were resistant to temozolomide. In allografts, radiation therapy induced a transient inhibition of tumor growth and a significant increase in survival. Transcriptome analyses showed that allografts were enriched for human proneural GBM signatures and that radiation induces a mesenchymal shift in transcriptome phenotype, similar to its effects in human GBM. CONCLUSIONS: A defined set of core signaling pathway mutations induces de-differentiation of cortical murine astrocytes into glioma stem cells and confers in vivo tumorigenicity. This non-germline genetically engineered mouse model mimics human proneural glioblastoma on histopathological, molecular, and treatment response levels. Our model may be useful in dissecting the genetic and cellular mechanisms of treatment resistance and developing more effective therapies.
The Influence of Polymorphisms of Interleukin-17F Genes on the Susceptibility and Clinical Significanse of Chronic Idiopathic Thrombocytopenic Purpura.
Authors: Takayuki Saitoh, Tetsuhiro Kasamatsu, Akihiko Yokohama, Hiroshi Handa, Norifumi Tsukamoto, Masamitsu Karasawa, Hatsue Ogawara, Yoshihisa Nojima, Hirokazu Murakami
Journal: Blood (2008)
Clinical Characteristics and Predictive Factors of Peripheral Neurophaty in Multiple Myeloma Patients Treated with Bortezomib and/or Imids
Authors: Vincenzo Federico, Russo Eleonora, Andrea Truini, Anna Levi, Fabiana Gentilini, Giulia Biagioli, Caterina Leoni, Robin Foà, Maria Teresa Petrucci
Journal: Blood (2012)
PTH-117 Appraising and Improving Junior Doctors Management of Acute Variceal Bleeds: A Quality Improvement Project
Authors: A Elzubeir, N Shah
Journal: Gut (2016)

<h3>Introduction</h3> Acute gastrointestinal bleeding is a medical emergency. Some 44% of bleeds are caused by peptic ulcer disease but the most severe haemorrhage and highest mortality is seen amongst those with bleeding oesophageal or gastric varices.<sup>1</sup> Competent triage and assessment are cornerstones of its initial management, with emphasis on identifying sick patients with life threatening haemodynamic compromise, and then initiating appropriate and timely resuscitation being of paramount importance in the patient’s outcome. In a national audit, variceal bleeding accounted for just over 10% of all UK admissions, with just fewer than 50% presenting outside normal working hours.<sup>2</sup> The average mortality for a variceal bleed is reported to be up to 20%, with studies confirming a 2–3 fold increase in mortality amongst inpatients.<sup>2</sup> Therefore it is paramount that all junior are able to recognise and manage suspected variceal bleeds appropriately. <h3>Methods</h3> An initial questionnaire was distributed and completed by 67 junior doctors (FY1-FY2) at the University Hospitals of Leicester in November 2015, all with jobs involving the acute medical take and providing ward cover. Junior doctors perceived confidence and knowledge was sampled in a range of key areas i.e. management pre and post endoscopy, senior support and escalation, blood transfusion targets and use of risk stratification tools such as the Blatchford score. Following evaluation of the initial questionnaire a dedicated teaching programme was delivered to 65 junior doctors, whom were subsequently re-surveyed. <h3>Results</h3> Following introduction of the teaching session all junior doctors expressed improved confidence in managing variceal UGIB’s- improved from 8% to 41% of junior doctors feeling confident. Additionally there were significant improvements identified in all areas. Notably; correct pre-endoscopic management improved to 94% (from 36%), appropriate transfusion targets improved from 45% to 76%, knowledge and use of risk stratification scores improved to 88% (from 3%). With inappropriate pre-endoscopic use of proton pump inhibitors falling from 25% to 0%. <h3>Conclusion</h3> Adopting a focused teaching programme for junior doctors on the management of acute variceal bleeds designed around pre-identified areas of weakness has proven to increase both knowledge and confidence in its specific management. Junior doctor teaching on core medical emergencies such as UGIB’s should perhaps be incorporated into trust induction programmes to ensure junior doctors are as prepared as possible on their first day in clinical practice. <h3>References</h3> 1 Management of acute upper and lower gastrointestinal bleeding. A national clinical guideline. SIGN. September 2009. 2 UK comparartive audit of upper gastrointestinal bleeding and the use of blood. British. <h3>Disclosure of Interest</h3> None Declared
X-Ray Induced Photodynamic Therapy: A Combination of Radiotherapy and Photodynamic Therapy
Authors: Geoffrey D. Wang, Ha T. Nguyen, Hongmin Chen, Phillip B. Cox, Lianchun Wang, Koichi Nagata, Zhonglin Hao, Andrew Wang, Zibo Li, Jin Xie
Journal: Theranostics (2016)

Conventional photodynamic therapy (PDT)'s clinical application is limited by depth of penetration by light. To address the issue, we have recently developed X-ray induced photodynamic therapy (X-PDT) which utilizes X-ray as an energy source to activate a PDT process. In addition to breaking the shallow tissue penetration dogma, our studies found more efficient tumor cell killing with X-PDT than with radiotherapy (RT) alone. The mechanisms behind the cytotoxicity, however, have not been elucidated. In the present study, we investigate the mechanisms of action of X-PDT on cancer cells. Our results demonstrate that X-PDT is more than just a PDT derivative but is essentially a PDT and RT combination. The two modalities target different cellular components (cell membrane and DNA, respectively), leading to enhanced therapy effects. As a result, X-PDT not only reduces short-term viability of cancer cells but also their clonogenecity in the long-run. From this perspective, X-PDT can also be viewed as a unique radiosensitizing method, and as such it affords clear advantages over RT in tumor therapy, especially for radioresistant cells. This is demonstrated not only in vitro but also in vivo with H1299 tumors that were either subcutaneously inoculated or implanted into the lung of mice. These findings and advances are of great importance to the developments of X-PDT as a novel treatment modality against cancer.
Transcriptional Induction of Periostin by a Sulfatase 2–TGFβ1–SMAD Signaling Axis Mediates Tumor Angiogenesis in Hepatocellular Carcinoma
Authors: Gang Chen, Ikuo Nakamura, Renumathy Dhanasekaran, Eriko Iguchi, Ezequiel J. Tolosa, Paola A. Romecin, Renzo E. Vera, Luciana L. Almada, Alexander G. Miamen, Roongruedee Chaiteerakij, Mengtao Zhou, Michael K. Asiedu, Catherine D. Moser, Shaoshan Han, Chunling Hu, Bubu A. Banini, Abdul M. Oseini, Yichun Chen, Yong Fang, Dongye Yang, Hassan M. Shaleh, Shaoqing Wang, Dehai Wu, Tao Song, Ju-Seog Lee, Snorri S. Thorgeirsson, Eric Chevet, Vijay H. Shah, Martin E. Fernandez-Zapico, Lewis R. Roberts
Journal: Cancer Research (2016)

Abstract Existing antiangiogenic approaches to treat metastatic hepatocellular carcinoma (HCC) are weakly effectual, prompting further study of tumor angiogenesis in this disease setting. Here, we report a novel role for sulfatase 2 (SULF2) in driving HCC angiogenesis. Sulf2-deficient mice (Sulf2 KO) exhibited resistance to diethylnitrosamine-induced HCC and did not develop metastases like wild-type mice (Sulf2 WT). The smaller and less numerous tumors formed in Sulf2 KO mice exhibited a markedly lower microvascular density. In human HCC cells, SULF2 overexpression increased endothelial proliferation, adhesion, chemotaxis, and tube formation in a paracrine fashion. Mechanistic analyses identified the extracellular matrix protein periostin (POSTN), a ligand of αvβ3/5 integrins, as an effector protein in SULF2-induced angiogenesis. POSTN silencing in HCC cells attenuated SULF2-induced angiogenesis and tumor growth in vivo. The TGFβ1/SMAD pathway was identified as a critical signaling axis between SULF2 and upregulation of POSTN transcription. In clinical HCC specimens, elevated levels of SULF2 correlated with increased microvascular density, POSTN levels, and relatively poorer patient survival. Together, our findings define an important axis controlling angiogenesis in HCC and a mechanistic foundation for rational drug development. Cancer Res; 77(3); 632–45. ©2016 AACR.
SAT0594 Choice of Biological Agents in The Public Health Sector of Tucuman, Argentina
Authors: V. Bellomio, M. Espindola, M. Guardia, G. Lavado, H. Jovanovics, M. Montero
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The province of Tucuman is located northwest of Argentina and has a population of 1,448,716 inhabitants, according to the last census. Within the public health sector, access to high-cost medication in patients with rheumatic diseases depends on the provincial government. Since 2012 it carries a registration and monitoring of patients with autoimmune diseases treated with biological drugs in this province <h3>Objectives</h3> To determine the preference of biological agents prescribing for patients with Rheumatoid Arthritis (RA), Spondyloarthritis (SpA), Juvenile Idiopathic Arthritis (JIA), Systemic Lupus Erythematosus (SLE) and other connective tissue diseases and describe the reason for change of therapy <h3>Methods</h3> A descriptive cross-sectional study was conducted. Registration of children and adult patients, assisted in public hospitals, with drug treatment with high-cost was done in PRIS (Integrated Health Programs) belonging to the Provincial Health System TUCUMAN, from January 2012 to June 2015. In Tucuman, biological drugs are indicated only by rheumatologists, monthly record and approval is based on local recommendations of the Argentine Society of Rheumatology. Demographics data, pathology, drug start, drug switch (2nd, 3rd or 4th choice), kind of switch, continuation or discontinuation of treatment were analyzed. <h3>Results</h3> Of 445 registered patients with high-cost drugs, we excluded those with no rheumatic disease (example Vogt-Koyanagi-Harada), primary osteoporosis, and 1 patient with Graft vs Host Disease (sclerodermiform syndrome treated with etanercept). Treatments were then analyzed in 393 patients, 84% women, mean age 47.7 ± 13.7 years, whose diagnoses were: 321 RA (81.7%), 38 SpA (9.6%), 13 JIA (3.3%), 12 SLE (3.1%) and the rest consisting of other connective tissue diseases (vasculitis, MTDC, ITCD). In RA the first biological drug applied was: etanercept (36%), adalimumab (25%) and tocilizumab (10%). The average treatment time with the first biological agent was 18 ± 14.6 months; 63% received treatment continuously. Required switch to another drug 68 patients (21.2%) being the most frequent cause secondary failure and the most frequently prescribed drug rituximab or tocilizumab. The same trend is maintained then the 2nd switch. Only one patient received in 3 years 5 biological agents (4 switch). In patients with SLE, rituximab and belimumab were treatments in equal proportion (50%). In patients with SpA, etanercept was the first drug prescribed and adalimumab in 2nd place. <h3>Conclusions</h3> In this register of patients treated with biological drugs in Tucuman, the drug of start choice was etanercept; 21.2% needed to change therapy and the most frequent cause was secondary failure. <h3>Disclosure of Interest</h3> None declared
Prospective Evaluation of Immunophenotype In Correlation to Genotype In Previously Untreated Adult Patients with Acute Myeloid Leukemia In the Context of the WHO Classification
Authors: Michela Tassara, Konstanze Döhner, Christine Schöpflin, Anke Schmid, Heinz A. Horst, Gerhard Held, Marie Lilienfeld-Toal, Sibylla Wilhelm, Andrea Kündgen, Katharina Götze, Mathias J. Rummel, David Nachbaur, Walter Fiedler, Michael Lübbert, Helmut R. Salih, Jörg Westermann, Arnold Ganser, Hartmut Döhner, Richard F. Schlenk
Journal: Blood (2010)
Characterisation of the Laminin 10/11 Binding Site on the Lutheran Glycoprotein Suggests a Novel Type of Protein-Protein Interaction.
Authors: Tosti J. Mankelow, Nicholas Burton, Fanney O. Stefansdottir, Frances A. Spring, Stephen F. Parsons, C. Fredrik Gilstring, R. Leo Brady, Mohandas Narla, Joel Anne Chasis, David J. Anstee
Journal: Blood (2006)
Gonadal Function in Survivors After Hodgkin Lymphoma (HL) Treatment within the German Hodgkin Study Group (GHSG) HD13–15 Trials.
Authors: Karolin Behringer, Horst Mueller, Helen Goergen, Indra Thielen, Angelika Eibl, Volker Stumpf, Carsten Wessels, Martin Wiehlpuetz, Johannes Rosenbrock, Teresa Halbsguth, Katrin S. Reiners, Thomas Schober, Joerg H Renno, Michael von Wolff, Katrin van der Ven, Marietta Kuehr, Michael Fuchs, Volker Diehl, Andreas Engert, Peter Borchmann
Journal: Blood (2012)
Human dendritic cells stimulated with a novel peanut protein express high levels of retinaldehyde dehydrogenase 2 and induce RA-sensitive genes in naive T-cells
Authors: B. Ruiter, G. Grishina, den Hartog S. Jager, E. Knol, P. Ozias-Akins, H. Sampson, W. Shreffler
Journal: Allergy (2012)
Combined BIOMED-2 Clonality Assays for IGH and IGK and Assessment of t(14;18) on Formalin-Fixed, Paraffin Embedded Tissues Effectively Separates Primary Cutaneous B Cell Lymphomas from Reactive Cutaneous Lymphoid Hyperplasia.
Authors: Anjali V. Morales, Katie Seo, Daniel A. Arber, Sabine Kohler, Youn H. Kim, Uma Sundram
Journal: Blood (2007)
ΔNp73/TAp73 Expression Ratio Is Associated with Poor Outcome in Acute Promyelocytic Leukemia,
Authors: Antonio R Lucena-Araujo, Alexandre Krause, Rafael Henriques Jacomo, Priscila S Scheucher, Guilherme A dos Santos, Helder H Paiva, Patricia V Palma, Raul AM Melo, Rosane Bittencourt, Ricardo Pasquini, Katia BB Pagnano, Evandro M. Fagundes, Maria L. Chauffaille, Carlos S Chiattone, Robert E. Gallagher, Bob Lowenberg, Raul Ribeiro, Francesco Lo-Coco, Miguel A. Sanz, Roberto P. Falcao, Eduardo M Rego
Journal: Blood (2011)
Long-Term Outcomes in Patients With Aortic Regurgitation and Preserved Left Ventricular Ejection Fraction
Authors: Amgad Mentias, Ke Feng, Alaa Alashi, L. Leonardo Rodriguez, A. Marc Gillinov, Douglas R. Johnston, Joseph F. Sabik, Lars G. Svensson, Richard A. Grimm, Brian P. Griffin, Milind Y. Desai
Journal: Journal of the American College of Cardiology (2016)
Primary Trombocythemia in Children and Adolescents Includes Different Subtypes Compared to Adult Essential Thrombocythemia
Authors: Fiorina Giona, Marica Laurino, Luciana Teofili, Sara Capodimonti, Maurizio Martini, Giovanna Palumbo, Maria Luisa Moleti, Deborah Marzella, Daniela Diverio, Maria Grazia Mascolo, Luigi Maria Larocca, Robin Foà
Journal: Blood (2014)
lncRNAs as Novel Indicators of Patients' Prognosis in Stage I Epithelial Ovarian Cancer: A Retrospective and Multicentric Study
Authors: Paolo Martini, Lara Paracchini, Giulia Caratti, Maurizia Mello-Grand, Robert Fruscio, Luca Beltrame, Enrica Calura, Gabriele Sales, Antonella Ravaggi, Eliana Bignotti, Franco E. Odicino, Enrico Sartori, Patrizia Perego, Dionyssios Katsaros, Ilaria Craparotta, Giovanna Chiorino, Stefano Cagnin, Laura Mannarino, Lorenzo Ceppi, Costantino Mangioni, Chiara Ghimenti, Maurizio D'Incalci, Sergio Marchini, Chiara Romualdi
Journal: Clinical Cancer Research (2016)

Purpose: Stage I epithelial ovarian cancer (EOC) represents about 10% of all EOCs and is characterized by good prognosis with fewer than 20% of patients relapsing. As it occurs less frequently than advanced-stage EOC, its molecular features have not been thoroughly investigated. We have demonstrated that in stage I EOC miR-200c-3p can predict patients' outcome. In the present study, we analyzed the expression of long non-coding RNAs (lncRNA) to enable potential definition of a non-coding transcriptional signature with prognostic relevance for stage I EOC.Experimental Design: 202 snap-frozen stage I EOC tumor biopsies, 47 of which relapsed, were gathered together from three independent tumor tissue collections and subdivided into a training set (n = 73) and a validation set (n = 129). Median follow up was 9 years. LncRNAs' expression profiles were correlated in univariate and multivariate analysis with overall survival (OS) and progression-free survival (PFS).Results: The expression of lnc-SERTAD2-3, lnc-SOX4-1, lnc-HRCT1-1, and PVT1 was associated in univariate and multivariate analyses with relapse and poor outcome in both training and validation sets (P < 0.001). Using the expression profiles of PVT1, lnc-SERTAD2-3, and miR-200c-3p simultaneously, it was possible to stratify patients into high and low risk. The OS for high- and low-risk individuals are 36 and 123 months, respectively (OR, 15.55; 95% confidence interval, 3.81-63.36).Conclusions: We have identified a non-coding transcriptional signature predictor of survival and biomarker of relapse for stage I EOC. Clin Cancer Res; 23(9); 2356-66. ©2016 AACR.
Depletion of PHLPP1 and 2 by Bcr-Abl Promotes CML Cell Proliferation through the Continuous Phosphorylation of Akt.
Authors: Isao Hirano, Satoki Nakamura, Tomonari Takemura, Daisuke Yokota, Takaaki Ono, Kazuyuki Shigeno, Shinya Fujisawa, Kaori Shinjo, Kazunori Ohnishi
Journal: Blood (2009)
Out-of-Pocket Spending and Financial Burden Among Medicare Beneficiaries With Cancer
Authors: Amol K. Narang, Lauren Hersch Nicholas
Journal: JAMA Oncology (2016)

<h3>Importance</h3> Medicare beneficiaries with cancer are at risk for financial hardship given increasingly expensive cancer care and significant cost sharing by beneficiaries. <h3>Objectives</h3> To measure out-of-pocket (OOP) costs incurred by Medicare beneficiaries with cancer and identify which factors and services contribute to high OOP costs. <h3>Design, Setting, and Participants</h3> We prospectively collected survey data from 18 166 community-dwelling Medicare beneficiaries, including 1409 individuals who were diagnosed with cancer during the study period, who participated in the January 1, 2002, to December 31, 2012, waves of the Health and Retirement Study, a nationally representative panel study of US residents older than 50 years. Data analysis was performed from July 1, 2014, to June 30, 2015. <h3>Main Outcomes and Measures</h3> Out-of-pocket medical spending and financial burden (OOP expenditures divided by total household income). <h3>Results</h3> Among the 1409 participants (median age, 73 years [interquartile range, 69-79 years]; 46.4% female and 53.6% male) diagnosed with cancer during the study period, the type of supplementary insurance was significantly associated with mean annual OOP costs incurred after a cancer diagnosis ($2116 among those insured by Medicaid, $2367 among those insured by the Veterans Health Administration, $5976 among those insured by a Medicare health maintenance organization, $5492 among those with employer-sponsored insurance, $5670 among those with Medigap insurance coverage, and $8115 among those insured by traditional fee-for-service Medicare but without supplemental insurance coverage). A new diagnosis of cancer or common chronic noncancer condition was associated with increased odds of incurring costs in the highest decile of OOP expenditures (cancer: adjusted odds ratio, 1.86; 95% CI, 1.55-2.23;<i>P</i> &lt; .001; chronic noncancer condition: adjusted odds ratio, 1.82; 95% CI, 1.69-1.97;<i>P</i> &lt; .001). Beneficiaries with a new cancer diagnosis and Medicare alone incurred OOP expenditures that were a mean of 23.7% of their household income; 10% of these beneficiaries incurred OOP expenditures that were 63.1% of their household income. Among the 10% of beneficiaries with cancer who incurred the highest OOP costs, hospitalization contributed to 41.6% of total OOP costs. <h3>Conclusions and Relevance</h3> Medicare beneficiaries without supplemental insurance incur significant OOP costs following a diagnosis of cancer. Costs associated with hospitalization may be a primary contributor to these high OOP costs. Medicare reform proposals that restructure the benefit design for hospital-based services and incorporate an OOP maximum may help alleviate financial burden, as can interventions that reduce hospitalization in this population.