tbuckley/cabot-search huggingface dataset:
Abstract #5683: Loss of function screen in rhabdomyosarcoma uncovers CRKL: Biological assessment confirms a role in tumor progression in vitro and in vivo
Authors: Choh Yeung, Vu Ngo, Xiao Wan, Su Young Kim, Patrick Grohar, Chand Khanna, Louis Staudt, Lee Helman
Journal: Cancer Research (2009)

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. The 2 major histologic subtypes of RMS include embryonal rhabdomyosarcoma (ERMS) that is characterized by LOH at 11p15 and alveolar rhabdomyosarcoma (ARMS) characterized by a Pax3/Pax7-forkhead fusion gene. We sought to identify genes that were necessary for survival of both subtypes of RMS cell lines using a loss of function shRNA screen. A tetracycline regulated shRNA library was delivered to RMS cell lines (ERMS and RMS) by retrovirus. Each shRNA retroviral vector contains a unique 60 nucleotide sequence, acting as a bar code, allowing abundance of shRNAs in a transduced cell population to be measured using microarrays of the barcode sequences. Missing bar codes from transduced cells with tetracycline-induced shRNA expression were interpreted as genes required for RMS cell survival. Thirty-nine genes were identified in this screen that appeared to be required for RMS cell line survival but did not affect the survival of four lymphoma cell lines. The CRKL gene was selected out of the thirty-nine for initial validation based on its role in RTK signaling. CRKL is an SH2/SH3 domain-containing adaptor protein involved in receptor tyrosine kinase (RTK) signaling pathways. RTK signaling pathways, such as the IGF, FGF, and c-met, have been previously reported to be activated in RMS cell lines. Validation of the role of CRKL in rhabdomyosarcoma survival and growth was confirmed using distinct shRNAs to CRKL in vitro and in tumor xenografts in vivo. Furthermore, over expression of CRKL enhanced RMS proliferation in vitro and tumor growth in mice. Finally because of the role of CRKL in RTK signaling we combined shCRKL with an IGFIR antibody and found this combination led to additive suppression of in vitro cell growth in RMS cell lines. Our results demonstrate that CRKL plays a role in RMS growth in vitro and in vivo and demonstrated the utility of high throughput shRNA screening approaches to identify \#8220;growth addiction pathways\#8221; in tumor cell lines. Finally, there appears to be an interaction between CRKL signaling and IGFIR signaling in RMS and the mechanism of this interaction is currently being pursued.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 5683.
Continuing medical education: Learning and change: implications for continuing medical education
Authors: R. D Fox, N. L Bennett
Journal: BMJ (1998)

<h3>Objectives</h3> Current guidelines restrict the use of inotropes for the treatment for heart failure (HF) unless the patients are hypotensive or hypoperfused because of safety concerns. This study sought to characterise the contemporary real-world use of inotropes and associated long-term outcomes according to systolic blood pressure (sBP) and perfusion status. <h3>Design</h3> A multicentre prospective cohort study. <h3>Setting</h3> This study was nested from the Kyoto Congestive Heart Failure registry, which included consecutive Japanese patients admitted for HF. <h3>Participants</h3> We categorised 3995 patients into two groups: sBP ≥90 mm Hg and warm profile group, and sBP &lt;90 mm Hg or cold profile group. In each group, patients were stratified across the use of inotropes within 24 hours of hospital presentation. <h3>Primary and secondary outcomes</h3> The primary outcome was all-cause death throughout follow-up. Secondary outcomes included cardiovascular death throughout follow-up, all-cause death during index hospitalisation and after discharge, and HF hospitalisation. <h3>Results</h3> A total of 793 patients (20%) presented with sBP &lt;90 mm Hg or cold profile, whereas 3202 patients had sBP ≥90 mm Hg and warm profile; 276 patients (35%) in the sBP &lt;90 mm Hg/cold group and 312 patients (10%) in the sBP ≥90 mm Hg/warm group received initial inotropic treatment. Adjusted excess risk of inotrope use relative to no inotrope for the primary outcome measure was significant in the sBP ≥90 mm Hg/warm group (adjusted HR), 1.36; 95% CI 1.09 to 1.72, p=0.006) but not in the sBP &lt;90 mm Hg/cold group (adjusted HR, 1.28, 95% CI 0.96 to 1.69, p=0.09). Risk for postdischarge all-cause death and HF hospitalisation was not significantly different between the patients with inotropes and no inotropes in both groups. <h3>Conclusion</h3> Inotrope use in the absence of hypotension and hypoperfusion is still common, but associated with a worse long-term prognosis. <h3>Trial registration number</h3> UMIN000015238.
Low Drug Attributability of Aplastic Anemia in Thailand
Authors: Surapol Issaragrisil, David W. Kaufman, Theresa Anderson, Kanchana Chansung, Tharatorn Thamprasit, Jittima Sirijirachai, Anong Piankijagum, Yaowarat Porapakkham, Sathit Vannasaeng, Paul E. Leaverton, Samuel Shapiro, Neal S. Young
Journal: Blood (1997)
Human Monocytes Constitutively Express Membrane-Bound, Biologically Active, and Interferon-γ–Upregulated Interleukin-15
Authors: Tiziana Musso, Liliana Calosso, Mario Zucca, Maura Millesimo, Daniela Ravarino, Mirella Giovarelli, Fabio Malavasi, Alessandro Negro Ponzi, Ralf Paus, Silvia Bulfone-Paus
Journal: Blood (1999)
Abstract 14880: Interleukin-18 in Radiation-induced Cardiomyopathy
Authors: Eleonora Mezzaroma, Ross B Mikkelsen, Stefano Toldo, Khushboo Sharma, Chiara Sonnino, Adolfo G Mauro, Carlo Marchetti, Asim Alam, Benjamin W Van Tassell, David A Gewirtz, Antonio Abbate
Journal: Circulation (2014)

Introduction: Thoracic radiation (XRT) used in treatment of cancer leads to the development of cardiomyopathy, characterized by increased myocardial and pericardial fibrosis. A close link between XRT injury, fibrosis and inflammation exists. Interleukin-18, a proinflammatory cytokines of the IL-1 family, has been shown to promote cardiac fibrosis. Hypothesis: IL-18 mediates myocardial and pericardial fibrosis following thoracic XRT. Methods: We exposed C57BL/6J female mice (N=6-12/group) to XRT 20 Gray (Gy). Echocardiography was performed to assess left ventricular (LV) ejection fraction (EF) at baseline, and 3 days and 4 months following XRT. LV catheterization was used to measure the LV end diastolic pressure (EDP), LV peak systolic pressure, +dP/dt and -dP/dt. Masson’s Trichrome was used to quantify interstitial fibrosis and pericardial thickening. Western Blot (WB) and Immunofluorescence (IF) were used to measure IL-18 levels in the heart after XRT. Sham-XRT mice were used as controls. Results: Thorac...
Inhibition of calcineurin combined with dasatinib has direct and indirect anti‐leukemia effects against BCR‐ABL1<sup>+</sup> leukemia
Authors: Lori A. Gardner, Jelena Klawitter, Mark A. Gregory, Vadym Zaberezhnyy, Dmitry Baturin, Daniel A. Pollyea, Naoko Takebe, Uwe Christians, Lia Gore, James DeGregori, Christopher C. Porter
Journal: American Journal of Hematology (2014)

Treatment of BCR-ABL1(+) leukemia has been revolutionized with the development of tyrosine kinase inhibitors. However, patients with BCR-ABL1(+) acute lymphoblastic leukemia and subsets of patients with chronic myeloid leukemia are at high risk of relapse despite kinase inhibition therapy, necessitating novel treatment strategies. We previously reported synthetic lethality in BCR-ABL1(+) leukemia cells by blocking both calcineurin/NFAT signaling and BCR-ABL1, independent of drug efflux inhibition by cyclosporine. Here, using RNA-interference we confirm that calcineurin inhibition sensitizes BCR-ABL1(+) cells to tyrosine kinase inhibition in vitro. However, when we performed pharmacokinetic and pharmacodynamic studies of dasatinib and cyclosporine in mice, we found that co-administration of cyclosporine increases peak concentrations and the area under the curve of dasatinib, which contributes to the enhanced disease control. We also report the clinical experience of two subjects in whom we observed more hematopoietic toxicity than expected while enrolled in a Phase Ib trial designed to assess the safety and tolerability of adding cyclosporine to dasatinib in humans. Thus, the anti-leukemia benefit of co-administration of cyclosporine and dasatinib is mechanistically pleiotropic, but may not be tolerable, at least as administered in this trial. These data highlight some of the challenges associated with combining targeted agents to treat leukemia.
Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma
Authors: Caryn S Ross-Innes, Jennifer Becq, Andrew Warren, R Keira Cheetham, Helen Northen, Maria O'Donovan, Shalini Malhotra, Massimiliano di Pietro, Sergii Ivakhno, Miao He, Jamie M J Weaver, Andy G Lynch, Zoya Kingsbury, Mark Ross, Sean Humphray, David Bentley, Rebecca C Fitzgerald, Stephen J Hayes, Yeng Ang, Ian Welch, Shaun Preston, Sarah Oakes, Vicki Save, Richard Skipworth, Olga Tucker, Jim Davies, Charles Crichton, Christian Schusterreiter, Tim Underwood, Fergus Noble, Bernard Stacey, Jamie Kelly, James Byrne, Annette Haydon, Donna Sharland, Jack Owsley, Hugh Barr, Jesper Lagergren, James Gossage, Andrew Davies, Robert Mason, Fuju Chang, Janine Zylstra, Grant Sanders, Tim Wheatley, Richard Berrisford, Tim Bracey, Catherine Harden, David Bunting, Tom Roques, Jenny Nobes, Suat Loo, Mike Lewis, Ed Cheong, Oliver Priest, Simon L Parsons, Irshad Soomro, Philip Kaye, John Saunders, Vincent Pang, Neil T Welch, James A Catton, John P Duffy, Krish Ragunath, Laurence Lovat, Rehan Haidry, Haroon Miah, Sarah Kerr, Victor Eneh, Rommel Butawan, Tom Roques, Michael Lewis, Edward Cheong, Bhasker Kumar, Laszlo Igali, Sharon Walton, Adela Dann, Peter Safranek, Andy Hindmarsh, Vijayendran Sudjendran, Michael Scott, Alison Cluroe, Ahmad Miremadi, Betania Mahler-Araujo, Barbara Nutzinger, Chris Peters, Zarah Abdullahi, Jason Crawte, Shona MacRae, Ayesha Noorani, Rachael Fels Elliott, Lawrence Bower, Paul Edwards, Simon Tavare, Matthew Eldridge, Jan Bornschein, Maria Secrier, Tsun-Po Yang, J. Robert O'Neill, Kasia Adamczuk, Pierre Lao-Sirieix, Nicola Grehan, Laura Smith, Suzy Lishman, Duncan Beardsmore, Sarah Dawson
Journal: Nature Genetics (2015)
Introduction of a dermatophyte polymerase chain reaction assay to the diagnostic mycology service in Scotland
Authors: C.L. Alexander, G.S. Shankland, W. Carman, C. Williams
Journal: British Journal of Dermatology (2010)

Journal Article Introduction of a dermatophyte polymerase chain reaction assay to the diagnostic mycology service in Scotland Get access C.L. Alexander, C.L. Alexander Scottish Parasite Diagnostic Laboratory, Stobhill Hospital, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar G.S. Shankland, G.S. Shankland Clinical Mycology, South Laboratory Building, Yorkhill Hospital, Glasgow G3 8SJ, U.K. Gillian S. Shankland. E‐mail:Gillian.Shankland@ggc.scot.nhs.uk Search for other works by this author on: Oxford Academic Google Scholar W. Carman, W. Carman Regional Virus Laboratory, Gartnavel General Hospital, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar C. Williams C. Williams Scottish Parasite Diagnostic Laboratory, Stobhill Hospital, Glasgow, U.K. Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 164, Issue 5, 1 May 2011, Pages 966–972, https://doi.org/10.1111/j.1365-2133.2010.10186.x Published: 01 May 2011
Abstract 5099: Automated rapid and accurate cell cycle analysis
Authors: Larisa Yurlova, Jacqueline Gregor, Oksana Sirenko, Evan Cromwell, Kourosh Zolghadr
Journal: Cancer Research (2014)

Abstract It is essential to have detailed information about compounds identified in screening campaigns during drug discovery and to know their influence on cell cycle progression or DNA repair. The discovery of Chromobodies® and advancements in High Content Imaging systems with improved optical properties and live cell capabilities has opened the door for new reliable and robust screening assays that provide these relevant high quality data. Chromobodies are a novel class of fluorescent antibodies, based on special heavy chain antibodies from camelids (VHHs). These unique nanoprobes can be transfected into cells as plasmid DNA similar to any conventional fusion protein. The cell expresses the fluorescent antibody-fragment thus enabling the non-invasive imaging of endogenous proteins and processes in real time. Therefore Chromobodies avoid any deleterious side effects from the traditional over-expression of a tagged protein. This is especially true for the essential components of the DNA replication, DNA repair and DNA methylation machinery: Proliferating Cell Nuclear Antigen (PCNA) and DNA Methyltransferase 1 (Dnmt1) . It has been shown that high over-expression of theses proteins can have adverse effects on normal progression through S phase. In this study we present a new method to evaluate cell cycle and DNA methylation. We developed Chromobodies directed against PCNA and Dnmt1. Transfecting these Chromobodies into cells circumvents the laborious and error-prone staining procedure with conventional antibodies. We demonstrate the flexible use of the Cell Cycle Chromobody cell line in conjunction with different automated high content imaging platforms. We show dose-dependent cell cycle inhibition caused by a number of anti-cancer drugs, DNA damage and apoptosis inducing compounds. Multiple analysis protocols enable the fast and accurate analysis with quantitative information on each sub phase of DNA replication for each individual cell. Moreover, by continuing to film cells, the exact length the cell cycle stages can also be extrapolated, thereby providing detailed temporal information on G1, S, G2 and M phase. Citation Format: Larisa Yurlova, Jacqueline Gregor, Oksana Sirenko, Evan Cromwell, Kourosh Zolghadr. Automated rapid and accurate cell cycle analysis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5099. doi:10.1158/1538-7445.AM2014-5099
Expression of GLUT1 in tumors promotes cancer cell survival
Authors: Xianhua Cao, Ping Wen, Zunyan Dai, Ying Huang, Wolfgang Sadee, Edward W. Martin, Peng George Wang, Duxin Sun
Journal: Cancer Research (2005)

2264  The glucose transporter GLUT1 is highly expressed in cancers through hypoxia-inducible factor 1 apha. The up-regulation of GLUT1 in cancer cells facilitates high glucose uptake in cancers, which may serve as a survival mechanism by increasing glycolysis in cancer cells under hypoxic condition. The purpose of this research is to determine the up-regulation of GLUT1 in cancer tissues in hypoxic condition and to study the role of GLUT1 in escaping hypoxia-induced apoptosis. GLUT1 expression was detected in cancer tissues and cancer cell lines (NCI 60 cancer cells) with immunostaining, Western blotting, real-time PCR, and DNA microarray. GLUT1 down-regulation was achieved through siRNA transfection. Early stage apoptosis was monitored with Annexin V-FITC staining. Glucose uptake was measured in GLUT1 siRNA knockdown and control cells with 3H-2-deoxy-glucose. Immunostaining experiments show that GLUT1 expression was significantly increased in hypoxic areas of colon and breast cancer tissues. GLUT1 mRNA was also highly expressed in cancer tissues and cancer cells. Cancer cells taken from the NCI-60 panel expressed various levels of GLUT1, with the highest expression in colon cancer cells SW620 (3.7-fold higher than pooled control cells). Four siRNA sequences were designed to knockdown GLUT1 expression in SW620 cells. Two siRNA sequences reduced GLUT1 expression by more than 65% mRNA and 75% protein at 36 hours after GLUT1 siRNA transfection, compared to control siRNA transfected cells. siRNA knockdown of GLUT1 alone induced significant apoptosis in SW620 cells, which was determined by annexin V staining. Yet, overall glucose uptake was not significantly altered in GLUT1 siRNA transfected cells, because of abundant expression of other glucose transporters. These results suggest that GLUT1 expression is up-regulated in cancers, especially in the hypoxic areas. In addition to permitting a high-rate glycolysis, GLUT1 expressions may provide a survival mechanism for cancer cells by escaping hypoxia-induced apoptosis. However, the mechanisms underlying GLUT1-mediated prevention of apoptosis and GLUT1 translocation between cell surface and intracellular vesicles need to be further investigated.
A phase 2 trial of CHOP chemotherapy followed by tositumomab/iodine I 131 tositumomab for previously untreated follicular non-Hodgkin lymphoma: Southwest Oncology Group Protocol S9911
Authors: Oliver W. Press, Joseph M. Unger, Rita M. Braziel, David G. Maloney, Thomas P. Miller, Michael LeBlanc, Ellen R. Gaynor, Saul E. Rivkin, Richard I. Fisher
Journal: Blood (2003)
Tumors of the Lower Respiratory Tract.
Authors: Thomas V. Colby, Michael N. Koss, Travis, William G., d.
Journal: Annals of Internal Medicine (1981)

Carter & Eggleston have made an excellent job of rewriting Tumors of the Lower Respiratory Tract.This 17th fascicle of the 2nd series replaces Liebow's 1952 edition and is a worthy successor.The all-too-common bronchogenic carcino- mas are of course well covered but these fascicles are just as much consulted for information on the oddities and I could detect no omissions in this area.The rarer neoplasms are dealt with succinctly and sections on inflammatory pseudo- tumours and hamartomas ensure full coverage of primary and secondary tumours of the lower respiratory tract, including the pleura.The nomenclature used follows the WHO classification fairly closely and seems eminently sensible.
Treatment outcomes for primary care patients with major depression and lifetime anxiety disorders
Authors: C Brown, H C Schulberg, M J Madonia, M K Shear, P R Houck
Journal: American Journal of Psychiatry (1996)

Major depression occurs with generalized anxiety disorder and panic disorder in up to 60% of psychiatric and primary care patients. This comorbidity has been associated with greater severity of depression, poorer psychosocial functioning, and poorer treatment outcomes in psychiatric samples. This study examined the clinical outcomes for depressed primary care patients with and without a lifetime anxiety disorder.A total of 157 primary care patients who met criteria for major depression were randomly assigned to standardized interpersonal psychotherapy or pharmacotherapy with nortriptyline and were assessed at baseline and at 4 and 8 months on severity of depression, psychosocial functioning, and health-related functioning.Depressed patients with a comorbid anxiety disorder presented with significantly more psychopathology and tended to prematurely terminate treatment more frequently than patients with major depression alone. Both standardized depression-specific treatments were effective for depressed patients with and without a comorbid generalized anxiety disorder, although time to recovery was longer for the former. Patients with lifetime panic disorder showed poor recovery in response to psychotherapy or pharmacotherapy.Standardized psychotherapy and pharmacotherapy are effective for patients with major depression with and without a generalized anxiety disorder. However, the longer time to recovery for the former group and lack of response to these treatments by patients with lifetime panic disorder suggest that primary care physicians should carefully assess history of anxiety disorder among depressed patients so as to select a proper intervention.
Abstract 203: Supporting the Potential Use of the Thoracic Impedance Signal to Detect Return of Spontaneous Circulation
Authors: Erik Alonso, Elisabete Aramendi, Unai Ayala, Digna González-Otero, Mohamud Daya, James K Russell
Journal: Circulation (2014)

Background: During resuscitation, checking for a carotid pulse to recognize cardiac arrest or detect the return of spontaneous circulation (ROSC) has been shown to be both inaccurate and time-consuming. More recently, an abrupt sustained increase in end-tidal carbon dioxide (EtCO2) to a normal value (35 to 40 mmHg) has been accepted as an indicator of ROSC. During ROSC the thoracic impedance (TI) signal shows a circulation component (ICC) with small fluctuations with each heartbeat. Mean amplitude of 40.04 mΩ has been reported for the ICC in pulse-generating rhythms, and 6.03 mΩ in pulseless electrical activity. Aim: To analyze the relationship between EtCO2 and ICC amplitude in order to assess the potential use of the TI for circulation detection during resuscitation. Methods: A sample of 203 ROSC segments (mean duration 8.9±4.2 s) containing ECG, TI and capnography signals were extracted from 40 cardiac arrest episodes recorded by Tualatin Valley Fire &amp; Rescue (Tigard, Oregon) using the Philips MRx devices. An adaptive scheme based on a least mean square algorithm was used to estimate the ICC from the TI using as reference the instants of the QRS complexes automatically detected in the ECG. The EtCO2 and the mean peak-to-trough amplitude of the ICC were computed per segment and their distributions analyzed. For all the segments, univariate linear regression was used to fit a model to predict the EtCO2 value, C, based on the amplitude of the ICC, A. The linearity was tested with the Pearson correlation coefficient, R. Results: Mean values were 54±20 mmHg and 53.1±34.1 mΩ for EtCO2 and ICC amplitude respectively. High levels of EtCO2 were clearly associated with high ICC amplitudes, although the linearity between EtCO2 and ICC amplitude was low (R=-0.22). Conclusion: High levels of EtCO2 are linked to high ICC amplitudes, which supports the potential use of TI signal as ROSC indicator in resuscitation scenarios where capnography is not available.
Change at last at WHO
Authors: F. Godlee
Journal: BMJ (1998)

Primary renal lymphoma (PRL) is defined as a non-Hodgkin’s lymphoma restricted to kidneys with the absence of extensive nodal disease. It is an exceedingly rare clinicopathological entity, accounting for 0.7% of extranodal lymphomas. Published medical literature regarding the natural history and clinical outcomes of PRL remains limited. We describe a case of a young patient who presented with left shoulder pain, continuous fever, and unexplained weight loss as atypical initial manifestations of bilateral PRL, confirmed with the standard set of investigations. Furthermore, this article reviews the literature and discusses various aspects of PRL, including pathophysiology, presentation patterns, imaging and pathological characteristics, management, and prognosis. This paper serves to provide an update and aims to enhance the understanding of PRL. Timely diagnosis and treatment are imperative to achieve improved outcomes. Clinicians should maintain a high index of suspicion in order to prevent morbidity and mortality associated with this serious disease.