tbuckley/cabot-search huggingface dataset:
PO44INVESTIGATION OF THE CLINICAL POTENTIAL OF AGENTS TARGETING EPIGENETIC MODIFICATIONS IN PAEDIATRIC EPENDYMOMA
Authors: H. Kings, R.J. Chapman, C. Mayne, H.A. Rogers, R.G. Grundy
Journal: Neuro-Oncology (2015)

INTRODUCTION: Alterations in epigenetic modifications are known to play a key role in many types of cancer. Agents targeting these modifications are in clinical development, with the most advanced targeting histone de-acetylation (HDACi) and DNA methylation. Ependymoma is the second most common malignant paediatric tumour of the central nervous system. Currently there are few effective adjuvant therapies and prognosis remains poor. Recent studies suggest epigenetic alterations may be important in ependymoma development. The studies demonstrated that HDACi and de-methylating agents both inhibited ependymoma cell growth and therefore could be a potential therapeutic target. HDACi were also shown to induce neuronal differentiation suggesting epigenetic modifications may inhibit differentiation of ependymoma cells. METHOD: The affect the HDACi Vorinostat and the de-methylating agent Decitabine on ependymoma cell line growth were measured using an MTT assay. To analyse effects on induction of differentiation, expression of differentiation markers were measured following Vorinostat or Decitabine treatment of ependymoma cells. RESULTS: Vorinostat and Decitabine both inhibited the growth of ependymoma cell lines. Evidence of differentiation was seen after treatment with both agents. Expression of differentiation markers following Vorinostat or Decitabine treatment is undergoing analysis. CONCLUSION: Agents targeting histone de-acetylation and DNA methylation inhibit the growth of ependymoma cells, which may in part be due to an induction of differentiation. The data supports the potential of using these agents as novel therapies for ependymoma treatment.
LG-17LOW GRADE GLIOMAS IN CHILDREN AND YOUNG ADULTS: AN INSTITUTIONAL EXPERIENCE OF BRAF GENE ALTERATIONS
Authors: Mamta Gurav, Hetakshi Kurani, Vickky Pandit, Vinayak Kadam, Anupurva Dutta, Omshree Shetty, Girish Chinnaswamy, Prakash Shetty, Aliasgar Moiyadi, Jayant Sastri Goda, Tejpal Gupta, Rakesh Jalali, Sridhar Epari
Journal: Neuro-Oncology (2016)
Toward Concurrent Testing for Somatic and Germline Variants in Cancer Patients
Authors: Diana Mandelker
Journal: Clinical Cancer Research (2016)

Sequencing for somatic alterations in patients' tumors is being increasingly clinically implemented to detect mutations that may guide therapy. Germline analysis of a cohort of patients undergoing tumor sequencing with matched normal has revealed that a small but significant percentage of these patients have germline variants that confer cancer susceptibility. Clin Cancer Res; 22(16); 3987-8. ©2016 AACRSee related article by Seifert et al., p. 4087.
New Approaches to Antiarrhythmic Therapy, Part II
Journal: Circulation (2001)

Cardiac arrhythmias complicate many diseases affecting the heart and circulation, and they incorporate a multiplicity of underlying mechanisms. The evolution of scientific knowledge has made the complex changes produced by cardiovascular disease sufficiently understood at the organ, cellular, and molecular levels such that there is a diversity of therapeutic targets for pharmacological therapy and/or prevention. Moreover, the approach of rational drug design in mechanism-specific and disease-specific fashions facilitates the targeting of therapy using the methods of molecular, structural, and translational biology. Additional approaches, using similar drug design strategies but based on gene therapy and transcriptional and translational modification, are on the horizon. Hence, there is reason to be optimistic regarding the design, testing, and clinical availability of novel antiarrhythmic therapies.
Withdrawal of Digoxin from Patients with Chronic Heart Failure Treated with Angiotensin-Converting-Enzyme Inhibitors
Authors: R B Devereux
Journal: New England Journal of Medicine (1993)

Background. Although digoxin is effective in the treatment of patients with chronic heart failure who are receiving diuretic agents, it is not clear whether the drug has a role when patients are receiving angiotensin-converting-enzyme inhibitors, as is often the case in current practice. Methods. We studied 178 patients with New York Heart Association class II or III heart failure and left ventricular ejection fractions of 35 percent or less in normal sinus rhythm who were clinically stable while receiving digoxin, diuretics, and an angiotensin-converting-enzyme inhibitor (captopril or enalapril). The patients were randomly assigned in a double-blind fashion either to continue receiving digoxin (85 patients) or to be switched to placebo (93 patients) for 12 weeks
Talimogene Laherparepvec in Combination With Ipilimumab in Previously Untreated, Unresectable Stage IIIB-IV Melanoma
Authors: Igor Puzanov, Mohammed M. Milhem, David Minor, Omid Hamid, Ai Li, Lisa Chen, Michael Chastain, Kevin S. Gorski, Abraham Anderson, Jeffrey Chou, Howard L. Kaufman, Robert H.I. Andtbacka
Journal: Journal of Clinical Oncology (2016)

Combining immunotherapeutic agents with different mechanisms of action may enhance efficacy. We describe the safety and efficacy of talimogene laherparepvec (T-VEC; an oncolytic virus) in combination with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 checkpoint inhibitor) in patients with advanced melanoma.
HG-87COMBINED APPLICATION OF TEMOZOLOMIDE AND THE ONCOLYTIC PARVOVIRUS H-1 INCREASES CYTOTOXIC EFFECTS IN CELL CULTURE AND ANIMAL MODELS OF PEDIATRIC GLIOBLASTOMA
Authors: Jeannine Lacroix, Rafael Josupeit, Domenico Sorrentino, Carsten Geiss, Barbara Leuchs, Pascal Johann, Jacques Grill, Olaf Witt, Jean Rommelaere, Christiane Dinsart
Journal: Neuro-Oncology (2016)
CLINICAL NOTES
Authors: JOSEPH PETRUS, JOSEPH PISETSKY
Journal: American Journal of Psychiatry (1952)

Although the number of cases is admittedly small, the results seem to indicate that 0.5 cc. of hyaluronidase solution, containing 150 TR units per cc., when injected subcutaneously into any area of pain and swelling following intravenous injection of 50% glucose, is sufficient to reduce the usual 1-or 2-week course of the condition to 1 or 2 days. This treatment also seems to prevent the development of such complications as progressive cellulitis, lymphangitis, and thrombophlebitis in such areas. For best results, the hyaluronidase should be injected as soon as possible after the development of the swelling, but delayed treatment, for as much as 48 hours, still seems to have some benefit.
The molecular pathology of lymphomas.
Authors: I R Kirsch, S Broder
Journal: Journal of Clinical Oncology (1986)

Article Tools Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.1986.4.3.271 Journal of Clinical Oncology - published online before print September 22, 2016 PMID: 3950671 The molecular pathology of lymphomas. I R KirschxI R KirschSearch for articles by this author , S BroderxS BroderSearch for articles by this author https://doi.org/10.1200/JCO.1986.4.3.271 First Page PDF © 1986 by American Society of Clinical Oncology
Outbreak of rotavirus gastroenteritis in a nursing home, Slovenia, December 2010
Authors: A Trop Skaza, L Beskovnik, T Zohar Cretnik
Journal: Eurosurveillance (2011)

A gastroenteritis outbreak affected 45 people (40 residents and five staff) in a nursing home for the elderly in the Celje region, north-east Slovenia, between 17 December and 31 December 2010. Rotavirus group A was laboratory confirmed in the stools of five ill individuals. The outbreak was identified when the number of affected persons was high but was successfully controlled after implementing preventive measures.
Angiotensin-converting enzyme polymorphism in patients with terminal renal failure.
Authors: A Schmidt, H P Kiener, U Barnas, I Arias, A Illievich, M Auinger, W Graninger, A Kaider, G Mayer
Journal: Journal of the American Society of Nephrology (1996)

An insertion/deletion polymorphism has been described for the gene that encodes the angiotensin-converting enzyme. The deletion allele is associated with higher angiotensin-converting enzyme plasma levels, which ultimately might lead to increased angiotensin II concentrations. Because angiotensin II is a mediator for progressive renal injury, this study determined the frequency of distribution of the angiotensin-converting enzyme insertion/deletion polymorphism in 106 hemodialysis patients and in a group of 95 healthy control patients. There was no difference between the two groups as far as the distribution of the insertion and deletion allele was concerned. Of the total hemodialysis population, 26.4% exhibited the deletion/deletion genotype, as compared with 37.9% of the healthy control population. Also, when patients with terminal renal failure as a result of glomerular disease were analyzed separately, the frequency of the deletion/deletion genotype was identical to that of the control group. Furthermore, the frequency of hypertension, coronary artery disease, left ventricular hypertrophy, and dilated cardiomyopathy, were analyzed according to the angiotensin-converting enzyme genotype, but the deletion allele could not be defined as a risk factor in the study's hemodialysis population. It was therefore concluded that the angiotensin-converting enzyme insertion/deletion polymorphism is not a major risk factor for development of end-stage renal failure. Additionally, in hemodialysis patients, there is no association between the risk for cardiovascular diseases and the angiotensin-converting enzyme genotype.
Polymyalgia Rheumatica and Giant Cell Arteritis
Authors: Frank Buttgereit, Christian Dejaco, Eric L. Matteson, Bhaskar Dasgupta
Journal: JAMA (2016)

<h3>Importance</h3> Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are related inflammatory disorders occurring in persons aged 50 years and older. Diagnostic and therapeutic approaches are heterogeneous in clinical practice. <h3>Objective</h3> To summarize current evidence regarding optimal methods for diagnosing and treating PMR and GCA. <h3>Evidence Review</h3> MEDLINE, EMBASE, and Cochrane databases were searched from their inception dates to March 30, 2016. Screening by 2 authors resulted in 6626 abstracts, of which 50 articles met the inclusion criteria. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool or American College of Cardiology Foundation/American Heart Association methodology. <h3>Findings</h3> Twenty randomized clinical trials for therapy (n = 1016 participants) and 30 imaging studies for diagnosis and/or assessing response to therapy (n = 2080 participants) were included. The diagnosis of PMR is based on clinical features such as new-onset bilateral shoulder pain, including subdeltoid bursitis, muscle or joint stiffness, and functional impairment. Headache and visual disturbances including loss of vision are characteristic of GCA. Constitutional symptoms and elevated inflammatory markers (&gt;90%) are common in both diseases. Ultrasound imaging enables detection of bilateral subdeltoid bursitis in 69% of PMR patients. In GCA, temporal artery biopsy remains the standard for definitive diagnosis. Ultrasound and magnetic resonance imaging (MRI) of large vessels revealing inflammation-induced wall thickening support the diagnosis of GCA (specificity 78%-100% for ultrasound and 73%-97% for MRI). Glucocorticoids remain the primary treatment, but the optimal initial dose and tapering treatment regimens are unknown. According to consensus-based recommendations, initial therapy for PMR is prednisone, 12.5 to 25 mg/day or equivalent, and 40 to 60 mg/day for GCA, followed by individualized tapering regimens in both diseases. Adjunctive methotrexate may reduce cumulative glucocorticoid dosage by 20% to 44% and relapses by 36% to 54% in both PMR and GCA. Use of tocilizumab as additional treatment with prednisone showed a 2- to 4-fold increase in remission rates of GCA in a randomized clinical trial (N = 30). <h3>Conclusions and Relevance</h3> Diagnosis of PMR/GCA is made by clinical features and elevated inflammatory markers. In PMR, ultrasound imaging may improve diagnostic accuracy. In GCA, temporal artery biopsy may not be required in patients with typical disease features accompanied by characteristic ultrasound or MRI findings. Consensus-based recommendations suggest glucocorticoids as the most effective therapy for PMR/GCA. Methotrexate may be added to glucocorticoids in patients at risk for relapse and in those with glucocorticoid-related adverse effects or need for prolonged glucocorticoid therapy.
Patterns of thought disorder associated with right cortical damage, schizophrenia, and mania
Authors: E K Daniels, M E Shenton, P S Holzman, L I Benowitz, M Coleman, S Levin, D Levine
Journal: American Journal of Psychiatry (1988)

The authors used the Thought Disorder Index to measure thought disorder in 23 patients with unilateral right hemisphere cortical damage, 20 patients with bipolar mania, and 25 patients with schizophrenia. There were no differences in the total amount of thought disorder in these groups, but each showed a unique pattern of thought disorder. Patients with right hemisphere damage displayed fragmented thinking, manic patients displayed playful thinking, and schizophrenic patients displayed idiosyncratic thinking. These findings support the view that thought disorder is manifested in different forms that are relatively specific to psychiatric or neurological condition.
Endothelial repair in stented arteries is accelerated by inhibition of Rho-associated protein kinase
Authors: Sarah T. Hsiao, Tim Spencer, Luke Boldock, Svenja Dannewitz Prosseda, Ioannis Xanthis, Francesco J. Tovar-Lopez, Heleen M. M. Van Beusekom, Ramzi Y Khamis, Nicolas Foin, Neil Bowden, Adil Hussain, Alex Rothman, Victoria Ridger, Ian Halliday, Cecile Perrault, Julian Gunn, Paul C. Evans
Journal: Cardiovascular Research (2016)

Stent deployment causes endothelial cells (EC) denudation, which promotes in-stent restenosis and thrombosis. Thus endothelial regrowth in stented arteries is an important therapeutic goal. Stent struts modify local hemodynamics, however the effects of flow perturbation on EC injury and repair are incompletely understood. By studying the effects of stent struts on flow and EC migration, we identified an intervention that promotes endothelial repair in stented arteries.In vitro and in vivo models were developed to monitor endothelialization under flow and the influence of stent struts. A 2D parallel-plate flow chamber with 100 μm ridges arranged perpendicular to the flow was used. Live cell imaging coupled to computational fluid dynamic simulations revealed that EC migrate in the direction of flow upstream from the ridges but subsequently accumulate downstream from ridges at sites of bidirectional flow. The mechanism of EC trapping by bidirectional flow involved reduced migratory polarity associated with altered actin dynamics. Inhibition of Rho-associated protein kinase (ROCK) enhanced endothelialization of ridged surfaces by promoting migratory polarity under bidirectional flow (P < 0.01). To more closely mimic the in vivo situation, we cultured EC on the inner surface of polydimethylsiloxane tubing containing Coroflex Blue stents (65 μm struts) and monitored migration. ROCK inhibition significantly enhanced EC accumulation downstream from struts under flow (P < 0.05). We investigated the effects of ROCK inhibition on re-endothelialization in vivo using a porcine model of EC denudation and stent placement. En face staining and confocal microscopy revealed that inhibition of ROCK using fasudil (30 mg/day via osmotic minipump) significantly increased re-endothelialization of stented carotid arteries (P < 0.05).Stent struts delay endothelial repair by generating localized bidirectional flow which traps migrating EC. ROCK inhibitors accelerate endothelial repair of stented arteries by enhancing EC polarity and migration through regions of bidirectional flow.
TB-03IMMUNOPHENOTYPING OF PEDIATRIC BRAIN TUMORS: CORRELATING IMMUNE INFILTRATE WITH HISTOLOGY, MUTATIONAL LOAD, AND SURVIVAL
Authors: Ashley Plant, Shohei Koyama, Glenn Dranoff, Mark Kieran, Jerome Ritz
Journal: Neuro-Oncology (2016)

TB-03. IMMUNOPHENOTYPING OF PEDIATRIC BRAIN TUMORS: CORRELATING IMMUNE INFILTRATE WITH HISTOLOGY, MUTATIONAL LOAD, AND SURVIVAL Ashley Plant1,2, Shohei Koyama1, Glenn Dranoff1,3, Mark Kieran1,2, and Jerome Ritz1; Dana Farber Cancer Institute, Boston, MA, USA; Boston Children’s Hospital, Boston, MA, USA; Novartis Institutes for Biomedical Research, Boston, MA, USA The immune landscape of pediatric brain tumors is not well understood. Early literature suggests a correlation between immune infiltrate and histology but its correlation with mutational burden and clinical course has not yet been evaluated. Here, paraffin embedded tissue from 40 pediatric glioblastoma tumors treated atDana FarberCancer Institutewere stained using immunohistochemistry for six immune markers thought to have staging or prognostic significance in other solid tumors including CD45, CD8, CD20, FoxP3, PD1, and PDL1. This data was then compared to mutational burden based on next generation sequencing for known genes involved in cancer pathways and correlation to median survival was evaluated. Subsequently, 40 low grade glioma samples were stained with the same IHC markers as a comparison sample. This data was supplemented with an extensive flow cytometry panel run on the tumor immune infiltrate of fresh tumor samples and also peripheral blood. The immune infiltrate in pediatric brain tumors does not appear to correlate as strongly with histology, grade, and mutational burden as seen in other solid tumors but may correlate with clinical outcome. Neuro-Oncology 18:iii169–iii173, 2016. doi:10.1093/neuonc/now084.3 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Lepanto I
Authors: Thomas B. Cole
Journal: JAMA (2012)

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
MB-73CASE REPORT: MULTIPLE PILOMATRIXOMAS IN A SURVIVOR OF WNT+ MEDULLOBLASTOMA LEADING TO THE DISCOVERY OF A GERMLINE APC MUTATION AND THE DIAGNOSIS OF FAMILIAL ADENOMATOSIS POLYPOSIS
Authors: Anne Bendel, Mary Skrypek, Melissa Hansen, Amy Wein, Mahmoud Nagib, William McDonald, Dinel Pond
Journal: Neuro-Oncology (2016)

MB-73. CASE REPORT: MULTIPLE PILOMATRIXOMAS IN A SURVIVOR OF WNT1 MEDULLOBLASTOMA LEADING TO THE DISCOVERY OF A GERMLINE APC MUTATION AND THE DIAGNOSIS OF FAMILIAL ADENOMATOSIS POLYPOSIS Anne Bendel1, Mary Skrypek1, Melissa Hansen1, Amy Wein1, Mahmoud Nagib2, William McDonald3, and Dinel Pond1; Children’s Hospitals and Clinics of Minnesota, Minneapolis/St. Paul, MN, USA; Neurosurgical Associates, Minneapolis, MN, USA; Abbott Northwestern Hospital, Minneapolis, MN, USA Pilmatrixoma is a benign neoplasm that arises from hair matrix cells and usually occurs as a solitary lesion. Solitary pilomatrixoma frequently harbors activating mutations in the B-catenin gene, leading to inhibition of B-catenin degradation and accumulation of nuclear B-catenin, which activates the WNT pathway and drives tumor formation. Multiple pilomatrixomas are rare, but can be seen in several conditions including familial adenomatous polyposis (FAP). The APC gene product is important in ubiquitin-mediated degradation of B-catenin; therefore some mutations of APC interfere with B-catenin degradation resulting in WNT activation and tumor formation, including formation of pilomatrixoma, colon cancer and other WNT driven tumors. We describe the caseofan11-year-oldgirl whodeveloped multiplepilomatrixomas on her head, neck and trunk 3 years following the diagnosis and treatment of a WNT+ medulloblastoma. Her family medical history is unknown due to being adopted from the Philippines. Because of the known association of multiple pilomatrixomas and FAP, and the known association of medulloblastoma and FAP, she underwent genetic testing and was found to have a pathogenic germline mutation of the APC gene (c.595dupG (p.Ala199Glyfs*53)) which is consistentwithadiagnosis ofautosomaldominant familial adenomatouspolyposis. The patient will now undergo regular surveillance for FAP related cancers, which may be potentially lifesaving. This is the first reported case of multiple pilomatrixomas in association with medulloblastoma. Neuro-Oncology 18:iii97–iii122, 2016. doi:10.1093/neuonc/now076.69 #The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.