tbuckley/cabot-search huggingface dataset:
The Interferon Stimulated Gene 12 Inactivates Vasculoprotective Functions of NR4A Nuclear Receptors
Authors: Nikolina Papac-Milicevic, Johannes M. Breuss, Jan Zaujec, Lubos Ryban, Tatiana Plyushch, Gabriel A. Wagner, Sabine Fenzl, Paul Dremsek, Muris Cabaravdic, Marianne Steiner, Christopher K. Glass, Christoph J. Binder, Pavel Uhrin, Bernd R. Binder
Journal: Circulation Research (2012)

Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection.The underlying mechanisms that regulate the activity of NR4A1 during vascular injury are not clear. We therefore searched for modulators of NR4A1 function that are present during vascular inflammation.We report that the protein encoded by interferon stimulated gene 12 (ISG12), is a novel interaction partner of NR4A1 that inhibits the transcriptional activities of NR4A1 by mediating its Crm1-dependent nuclear export. Using 2 models of vascular injury, we show that ISG12-deficient mice are protected from neointima formation. This effect is dependent on the presence of NR4A1, as mice deficient for both ISG12 and NR4A1 exhibit neointima formation similar to wild-type mice.These findings identify a previously unrecognized feedback loop activated by interferons that inhibits the vasculoprotective functions of NR4A nuclear receptors, providing a potential new therapeutic target for interferon-driven pathologies.
Noninvasive assessment and monitoring of the pulmonary circulation
Authors: A. Vonk-Noordegraaf, S. A. van Wolferen, J. T. Marcus, A. Boonstra, P. E. Postmus, J. W. L. Peeters, A. J. Peacock
Journal: European Respiratory Journal (2005)

In pulmonary vascular disease, changes in the pulmonary vascular bed will lead to altered pulmonary haemodynamics. This review describes the application of several physiological principles to measure these changes noninvasively by means of novel techniques. Flow characteristics of blood through the pulmonary vascular bed alter in pulmonary vascular disease. Recent developments in magnetic resonance imaging and computed tomography make it possible to visualise and quantify these abnormal flow patterns. Information regarding pulmonary perfusion can also be obtained by measuring the electrical impedance changes in the lung by electrical impedance tomography. A more indirect approach to measure the pulmonary blood flow is the measurement of the absorption of acetylene, a perfusion limited gas. Information on the pulmonary vascular bed can also be obtained by the measurement of exhaled products of the pulmonary vascular endothelium, such as nitric oxide. Although all the techniques described offer new ways to diagnose or monitor pulmonary vascular disease, clinical data on these techniques are limited. Further improvement and evaluation of the clinical value of these techniques are therefore obligatory before they can be used in clinical practice.
Intraluminal irradiation for the palliation of lung cancer with the high dose rate micro-Selectron.
Authors: P A Burt, B R O'Driscoll, H M Notley, P V Barber, R Stout
Journal: Thorax (1990)

Fifty patients with inoperable, symptomatic endobronchial carcinoma were treated by a single exposure of intraluminal radiotherapy. A high dose rate afterloading system (the micro-Selectron-HDR) was used to minimise radiation exposure for staff. Haemoptysis was relieved in 24 of 28 patients, breathlessness in 21 of 33 patients, and cough in nine of 18 patients. Radiological collapse resolved in 11 of 24 patients. Treatment was given on an outpatient basis and was well tolerated. Intraluminal radiotherapy appears to offer an effective alternative to conventional fractionated external beam radiotherapy.
DAS-driven therapy versus routine care in patients with recent-onset active rheumatoid arthritis
Authors: Y P M Goekoop-Ruiterman, J K de Vries-Bouwstra, P J S M Kerstens, M M J Nielen, K Vos, D van Schaardenburg, I Speyer, P E H Seys, F C Breedveld, C F Allaart, B A C Dijkmans
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: To compare the efficacy of Disease Activity Score (DAS)-driven therapy and routine care in patients with recent-onset rheumatoid arthritis. Methods: Patients with recent-onset rheumatoid arthritis receiving traditional antirheumatic therapy from either the BeSt study, a randomised controlled trial comparing different treatment strategies (group A), or two Early Arthritis Clinics (group B) were included. In group A, systematic DAS-driven treatment adjustments aimed to achieve low disease activity (DAS ⩽2.4). In group B, treatment was left to the discretion of the treating doctor. Functional ability (Health Assessment Questionnaire (HAQ)), Disease Activity Score in 28 joints (DAS28) and Sharp/van der Heijde radiographic score (SHS) were evaluated. Results: At baseline, patients in group A (n = 234) and group B (n = 201) had comparable demographic characteristics and a mean HAQ of 1.4. Group A had a longer median disease duration than group B (0.5 vs 0.4 years, p = 0.016), a higher mean DAS28 (6.1 vs 5.7, p&lt;0.001), more rheumatoid factor-positive patients (66% vs 42%, p&lt;0.001) and more patients with erosions (71% vs 53%, p&lt;0.001). After 1 year, the HAQ improvement was 0.7 vs 0.5 (p = 0.029), and the percentage in remission (DAS28 &lt;2.6) 31% vs 18% (p&lt;0.005) in groups A and B, respectively. In group A, the median SHS progression was 2.0 (expected progression 7.0), in group B, the SHS progression was 1.0 (expected progression 4.4). Conclusions: In patients with recent-onset rheumatoid arthritis receiving traditional treatment, systematic DAS-driven therapy results in significantly better clinical improvement and possibly improves the suppression of joint damage progression.
Tumor-fighting T cells lose their way
Authors: Rebecca Blank
Journal: The Journal of Experimental Medicine (2008)

![Graphic][1] 

Imiquimod induces the expression of E-selectin (yellow) on blood vessels in skin tumors. Like a tourist without a map, tumor-fighting T cells have a hard time finding their destination without directions. According to Clark et al. (page 

[2221][2]), dismantling these
Markers of Response for the Antiangiogenic Agent Bevacizumab
Authors: Diether Lambrechts, Heinz-Josef Lenz, Sanne de Haas, Peter Carmeliet, Stefan J. Scherer
Journal: Journal of Clinical Oncology (2013)

Bevacizumab is the first antiangiogenic therapy proven to slow metastatic disease progression in patients with cancer. Although it has changed clinical practice, some patients do not respond or gradually develop resistance, resulting in rather modest gains in terms of overall survival. A major challenge is to develop robust biomarkers that can guide selection of patients for whom bevacizumab therapy is most beneficial. Here, we discuss recent progress in finding such markers, including the first results from randomized phase III clinical trials evaluating the efficacy of bevacizumab in combination with comprehensive biomarker analyses. In particular, these studies suggest that circulating levels of short vascular endothelial growth factor A (VEGF-A) isoforms, expression of neuropilin-1 and VEGF receptor 1 in tumors or plasma, and genetic variants in VEGFA or its receptors are strong biomarker candidates. The current challenge is to expand this first set of markers and to validate it and implement it into clinical practice. A first prospective biomarker study known as MERiDiAN, which will treat patients stratified for circulating levels of short VEGF-A isoforms with bevacizumab and paclitaxel, is planned and will hopefully provide us with new directions on how to treat patients more efficiently.
Fabrication of a phospholipid membrane-mimetic film on the luminal surface of an ePTFE vascular graft
Authors: Sumanas W. Jordan, Keith M. Faucher, Jeffrey M. Caves, Robert P. Apkarian, Shyam S. Rele, Xue-Long Sun, Stephen R. Hanson, Elliot L. Chaikof
Journal: Biomaterials (2006)
Impact of surveillance for Barrett's oesophagus on tumour stage and survival of patients with neoplastic progression
Authors: F Kastelein, S H van Olphen, E W Steyerberg, M C W Spaander, M J Bruno
Journal: Gut (2015)

<h3>Objective</h3> Endoscopic surveillance for Barrett9s oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of evidence that it prevents advanced oesophageal adenocarcinoma (OAC). The aim of this study was to evaluate the impact of endoscopic BO surveillance on tumour stage and survival of patients with neoplastic progression. <h3>Design</h3> 783 patients with BO of at least 2 cm were included in a multicentre prospective cohort and followed during surveillance according to the American College of Gastroenterology guidelines. Cases of high-grade dysplasia and OAC were identified during follow-up. OAC staging was performed according to the 7th UICC-AJCC classification. Survival data were collected and crosschecked using death and municipal registries. Data from patients with OAC in the general population were obtained from the Dutch cancer registry. We compared survival of patients with BO with neoplastic progression during surveillance with those of patients without neoplastic progression and patients with OAC in the general population. <h3>Results</h3> 53 patients with BO developed high-grade dysplasia or OAC during surveillance. Thirty-five (66%) were classified as stage 0, 14 (26%) as stage 1 and 4 (8%) as stage 2. OAC was diagnosed at an earlier stage during BO surveillance than in the general population (p&lt;0.001). Survival of patients with BO with neoplastic progression was not significantly worse than those of patients without neoplastic progression and similar to survival of patients with stage 0 or stage 1 OAC in the general population. <h3>Conclusions</h3> OAC is detected at an earlier stage during BO surveillance than in the general population with good survival rates.
Unexpected Structural and Functional Consequences of the R33Q Homozygous Mutation in Cardiac Calsequestrin
Authors: Nicoletta Rizzi, Nian Liu, Carlo Napolitano, Alessandra Nori, Federica Turcato, Barbara Colombi, Silvio Bicciato, Diego Arcelli, Alessandro Spedito, Mario Scelsi, Laura Villani, Giovanni Esposito, Simona Boncompagni, Feliciano Protasi, Pompeo Volpe, Silvia G. Priori
Journal: Circulation Research (2008)

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disorder characterized by life threatening arrhythmias elicited by physical and emotional stress in young individuals. The recessive form of CPVT is associated with mutation in the cardiac calsequestrin gene (CASQ2). We engineered and characterized a homozygous CASQ2(R33Q/R33Q) mouse model that closely mimics the clinical phenotype of CPVT patients. CASQ2(R33Q/R33Q) mice develop bidirectional VT on exposure to environmental stress whereas CASQ2(R33Q/R33Q) myocytes show reduction of the sarcoplasmic reticulum (SR) calcium content, adrenergically mediated delayed (DADs) and early (EADs) afterdepolarizations leading to triggered activity. Furthermore triadin, junctin, and CASQ2-R33Q proteins are significantly decreased in knock-in mice despite normal levels of mRNA, whereas the ryanodine receptor (RyR2), calreticulin, phospholamban, and SERCA2a-ATPase are not changed. Trypsin digestion studies show increased susceptibility to proteolysis of mutant CASQ2. Despite normal histology, CASQ2(R33Q/R33Q) hearts display ultrastructural changes such as disarray of junctional electron-dense material, referable to CASQ2 polymers, dilatation of junctional SR, yet normal total SR volume. Based on the foregoings, we propose that the phenotype of the CASQ2(R33Q/R33Q) CPVT mouse model is portrayed by an unexpected set of abnormalities including (1) reduced CASQ2 content, possibly attributable to increased degradation of CASQ2-R33Q, (2) reduction of SR calcium content, (3) dilatation of junctional SR, and (4) impaired clustering of mutant CASQ2.
Drilling Down to the Causes of Racial Disparities in Lung Cancer
Authors: K. Hede
Journal: JNCI Journal of the National Cancer Institute (2010)

A recent study of early-stage lung cancer patients found that African Americans are statistically significantly less likely than whites to receive definitive — i.e., potentially curative — surgery. That finding, which the Journal of the American Medical Association published in June, appeared soon after an American Lung Association (ALA) report that also underscored the need for systematic change in the approach to lung cancer in African Americans. Together, the two reports confi rm the disparity between blacks and whites in lung cancer rates, treatment, and outcomes while exploring some of the reasons — biological, clinical, and socioeconomic — that may explain these differences. African Americans are more likely to develop lung cancer and less likely to respond to available treatments than whites. Cigarette smoking rates can’t account for the disparity, because although white men smoke 30% – 40% more cigarettes, African American men have a higher incidence of lung cancer (75 per 100,000 vs. 64 per 100,000). According to a meta-analysis published in the September 2008 issue of PLoS Medicine , the disparity exists even among nonsmokers (16 per 100,000 among blacks vs. 12 per 100,000 among whites). This disproportionate burden prompted the April 2010 ALA report, which called for a concerted effort to examine underlying biological differences; to reduce cigarette advertising, particularly for menthol cigarettes, in African American communities ( see sidebar); and to educate physicians on how to overcome communication barriers with African American patients.
Associations Among -TrCP, an E3 Ubiquitin Ligase Receptor, -Catenin, and NF- B in Colorectal Cancer
Authors: A. Ougolkov, B. Zhang, K. Yamashita, V. Bilim, M. Mai, S. Y. Fuchs, T. Minamoto
Journal: JNCI Journal of the National Cancer Institute (2004)

The ubiquitin-proteasome pathway is important in regulating protein signaling pathways that are involved in tumorigenesis. beta-transducin repeat-containing proteins (beta-TrCP) are components of the ubiquitin ligase complex targeting beta-catenin and IkappaBalpha for proteasomal degradation and are thus a negative regulator of Wnt/beta-catenin signaling and a positive regulator of NF-kappaB signaling. We analyzed expression of beta-TrCP in colorectal cancers and its association with types of beta-catenin subcellular localization, an indirect measure of activation.Levels of beta-TrCP1 mRNA and protein were measured by quantitative reverse transcription-polymerase chain reaction and immunoblotting, respectively, in samples of tumor and normal tissues from 45 patients with colorectal cancer. Types of beta-catenin activation (diffuse or invasion edge) and NF-kappaB activation were examined by immunohistochemistry. Apoptosis was determined by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling (TUNEL) assay. All statistical tests were two-sided.Compared with the beta-TrCP1 levels in normal tissues, 25 (56%) of 45 tumors had increased beta-TrCP1 mRNA and protein levels. Of the 22 (49%) tumors with beta-catenin activation, 12 had the diffuse type (i.e., nuclear accumulation throughout the tumor) and 10 had the invasion edge type (i.e., nuclear accumulation predominantly in the tumor cells that formed the invasion edge). Increased beta-TrCP1 levels were statistically significantly associated with beta-catenin activation (P =.023) and decreased apoptosis (P =.035). beta-TrCP accumulated in the nuclei of tumor cells that contained increased levels of beta-TrCP1 mRNA and the active form of NF-kappaB. Higher levels of beta-TrCP1 mRNA were detected in primary tumors of patients who had metastases (0.960 arbitrary units, 95% confidence interval = 0.878 to 1.042) than in the tumors of patients who did not (0.722 arbitrary units, 95% confidence interval = 0.600 to 0.844; P =.016).In colorectal cancer, increased expression of beta-TrCP1 is associated with activation of both beta-catenin and NF-kappaB, suggesting that the integration of these signaling pathways by increased beta-TrCP expression may contribute to an inhibition of apoptosis and tumor metastasis.
Lung Perfusion Imaging Can Risk Stratify Lung Cancer Patients for the Development of Pulmonary Complications after Chemoradiation
Authors: Isis W. Gayed, Joe Chang, E Edmund Kim, Rodolfo Nuñez, Beth Chasen, H Helen Liu, Katsuhiro Kobayashi, Yujing Zhang, Zhongxing Liao, Salman Gohar, Melinda Jeter, Louise Henderson, William Erwin, Ritsuko Komaki
Journal: Journal of Thoracic Oncology (2008)
The Transcription Factors Egr2 and Egr3 Are Essential for the Control of Inflammation and Antigen-Induced Proliferation of B and T Cells
Authors: Suling Li, Tizong Miao, Meera Sebastian, Punamdip Bhullar, Emma Ghaffari, Mengya Liu, Alistair L.J. Symonds, Ping Wang
Journal: Immunity (2012)

Lymphocytes provide optimal responses against pathogens with minimal inflammatory pathology. However, the intrinsic mechanisms regulating these responses are unknown. Here, we report that deletion of both transcription factors Egr2 and Egr3 in lymphocytes resulted in a lethal autoimmune syndrome with excessive serum proinflammatory cytokines but also impaired antigen receptor-induced proliferation of B and T cells. Egr2- and Egr3-defective B and T cells had hyperactive signal transducer and activator of transcription-1 (STAT1) and STAT3 while antigen receptor-induced activation of transcription factor AP-1 was severely impaired. We discovered that Egr2 and/or Egr3 directly induced expression of suppressor of cytokine signaling-1 (SOCS1) and SOCS3, inhibitors of STAT1 and STAT3, and also blocked the function of Batf, an AP-1 inhibitor, in B and T cells. Thus, Egr2 and Egr3 regulate B and T cell function in adaptive immune responses and homeostasis by promoting antigen receptor signaling and controlling inflammation.
Initial Worldwide Experience With the WATCHMAN Left Atrial Appendage System for Stroke Prevention in Atrial Fibrillation
Authors: Peter B. Sick, Gerhard Schuler, Karl Eugen Hauptmann, Eberhard Grube, Steve Yakubov, Zoltan G. Turi, Gregory Mishkel, Steve Almany, David R. Holmes
Journal: Journal of the American College of Cardiology (2007)
Red‐cell hypoplasia and increased bone marrow reticulin in systemic lupus erythematosis: Reversal with corticosteroid therapy
Authors: Jack Cavalcant, Richard K. Shadduck, Alan Winkeistein, Zella Zeigler, Harvey Mendelow
Journal: American Journal of Hematology (1978)

Abstract A 29‐year‐old Chinese male developed severe aregenerative anemia. The bone marrow was diffusely hypercellular with increased marrow reticulin and a persistent failure of eryihroid differentiation beyond the pronormoblast stage. Although he did not manifest classic features of systemic lupus erythematosus, multiple serologic studies were in accord with this diagnosis. The patient's defect in erythropoiesis was studied by an in vitro technique for the growth of erythroid colonies. Despite the severe erythroid hypoplasia, the patient's marrow yielded abundant large erythroid colonies. Serum erythropoietin activity was high as judged by use of this in vitro assay. Although the patient's native serum did not affect colony formation, a separated IgG fraction was markedly inhibitory to colony growth. This suggests that the erythroid hypoplasia may have resulted from a unique autoantibody. The patient's hematologic abnormalities completely reversed following treatment with corticosteroids.
Cancer Medicine, 4th Edition, Vols. I and II James F. Holland, Robert C. Bast, Jr., Donald L. Morton, Emil Frei III, Donald W. Kufe, Ralph R. Weichselbaum, eds. Baltimore: Williams &amp; Wilkins, 1997. Vol. I, 1800 pp., $189; Vol. II, 1800 pp., $189. ISBN 0-683-04095-2
Authors: E. J. Seifter
Journal: JNCI Journal of the National Cancer Institute (1998)
Primary intestinal diffuse large B-cell non-Hodgkin's lymphoma: Clinical features, management, and prognosis of 66 patients
Authors: E.M. Ibrahim, A.A. Ezzat, A.N. El-Weshi, J.M. Martin, Y.M. Khafaga, W. Al Rabih, D.S. Ajarim, M.O. Al-Foudeh, E. Zucca
Journal: Annals of Oncology (2001)
A Sex-Specific MicroRNA-96/5-Hydroxytryptamine 1B Axis Influences Development of Pulmonary Hypertension
Authors: Emma Wallace, Nicholas W. Morrell, Xudong D. Yang, Lu Long, Hannah Stevens, Margaret Nilsen, Lynn Loughlin, Kirsty M. Mair, Andrew H. Baker, Margaret R. MacLean
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Females are predisposed to pulmonary arterial hypertension (PAH); evidence suggests that serotonin, mutations in the bone morphogenetic protein receptor (BMPR) II gene, and estrogens influence development of PAH. The 5-hydroxytryptamine 1B receptor (5-HT1BR) mediates human pulmonary artery smooth muscle cell (hPASMC) proliferation.Objectives: We aimed to determine whether selected microRNAs (miRNAs) expressed in PASMCs are influenced by sex, BMPR-II mutations, and estrogens, and contribute to PASMC proliferation in PAH.Methods: Expression levels of miRNAs targeting genes related to PAH, estrogen, and serotonin were determined by quantitative RT-PCR in hPASMCs and mouse PASMCs harboring a heterozygous mutation in BMPR-II (BMPR-IIR899X+/− PASMCs). miRNA-96 targets 5-HT1BR and was selected for further investigation. miRNA target validation was confirmed by luciferase reporter assay. Precursor miRNA-96 was transfected into hPASMCs to examine effects on proliferation and 5-HT1BR expression. The effect of a miRNA-96 mimic on the development of hypoxic pulmonary hypertension in mice was also assessed.Measurements and Main Results: miRNA-96 expression was reduced in BMPR-IIR899X+/− PASMCs from female mice and hPASMCs from female patients with PAH; this was associated with increased 5-HT1BR expression and serotonin-mediated proliferation. 5-HT1BR was validated as a target for miRNA-96. Transfection of precursor miRNA-96 into hPASMCs reduced 5-HT1BR expression and inhibited serotonin-induced proliferation. Restoration of miRNA-96 expression in pulmonary arteries in vivo via administration of an miRNA-96 mimic reduced the development of hypoxia-induced pulmonary hypertension in the mouse.Conclusions: Increased 5-HT1BR expression may be a consequence of decreased miRNA-96 expression in female patient PASMCs, and this may contribute to the development of PAH.