tbuckley/cabot-search huggingface dataset:
Cooperative Inhibition of Renal Cancer Growth by Anti-Epidermal Growth Factor Receptor Antibody and Protein Kinase A Antisense Oligonucleotide
Authors: Fortunato Ciardiello, Rosa Caputo, Roberto Bianco, Vincenzo Damiano, Grazia Pomatico, Stefano Pepe, A. Raffaele Bianco, Sudhir Agrawal, John Mendelsohn, Giampaolo Tortora
Journal: JNCI Journal of the National Cancer Institute (1998)

Background: The expression of epidermal growth factor receptor (EGFR) and type I cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKAI) is associated with neoplastic transformation. By use of human renal cancer cell lines (i.e., 769-P, ACHN, A498, and SW839), we investigated the antiproliferative activity and the antitumor activity of an anti-EGFR humanized chimeric mouse monoclonal antibody, MAb C225, and a novel mixed backbone 18-mer antisense oligonucleotide, HYB 190, that targets expression of the RIα regulatory subunit of PKAI. Methods: The antiproliferative activity of MAb C225 and oligonucleotide HYB 190, alone or in combination, on different renal cancer cell lines was determined by monitoring cell growth in soft agar. In addition, the induction of apoptosis by treatment with the anti-EGFR antibody and/or antisense PKAI oligonucleotides was evaluated by flow cytometric analysis of fragmented DNA. The antitumor activity of MAb C225 and oligonucleotide HYB 190 was determined in athymic mice bearing established ACHN tumor xenografts. Cell proliferation and tumor growth data were evaluated for statistical significance using Student's t test; reported P values are two-sided. Results: MAb C225 and oligonucleotide HYB 190 inhibited colony formation in soft agar in a dose-dependent manner for all renal cancer cell lines tested. We observed a potentiation of growth inhibition and induction of apoptosis when 769-P cells and ACHN cells were treated with both agents. Combination treatment with MAb C225 and oligonucleotide HYB 190 caused regression of ACHN tumor xenografts, whereas single-agent treatment only delayed tumor growth. Conclusion: The combination of anti-EGFR MAb C225 and HYB 190 antisense PKAI oligonucleotides HYB 190 exhibited exhibited cooperative antiproliferative effects and cooperative antitumor effects on EGFR and PKAI-expressing human renal cancer cell lines. [J Natl Cancer Inst 1998;90:1087–94]
Expression and glycosylation of MUC1 in epidermolysis bullosa-associated and sporadic cutaneous squamous cell carcinomas
Authors: H.L. Cooper, I.S. Cook, J.M. Theaker, R. Mallipeddi, J. Mcgrath, P. Friedmann, E. Healy
Journal: British Journal of Dermatology (2004)

Background Cutaneous squamous cell carcinoma (SCC) is particularly problematic in certain patient groups, including patients with dystrophic or junctional epidermolysis bullosa (DEB/JEB). Theoretically, vaccination against a cell surface antigen which is expressed on this type of tumour could prevent SCC development, as well as treat primary and metastatic disease in this patient group. Preliminary studies have suggested that MUC1, a transmembrane glycoprotein, is overexpressed in sporadic cutaneous SCCs, and MUC1 has been used with some success as a target antigen for vaccine development in breast cancer, where it is expressed on > 50% of neoplastic cells in approximately 50–80% of tumours. Furthermore, aberrant glycosylation of MUC1 has been detected in this and other cancer types; however, the glycosylation status of MUC1 in cutaneous SCC is not known. Objectives To investigate the expression and glycosylation status of MUC1 in SCCs arising in patients with DEB and JEB, and for comparison in sporadic SCCs and sporadic Bowen's disease. Methods Immunohistochemical analysis of MUC1 in 30 SCCs from subjects with DEB/JEB, 55 sporadic SCCs and 30 sporadic lesions of Bowen's disease was carried out using four separate monoclonal antibodies which recognize different isoforms of MUC1. Results Expression of MUC1 was detected in 100% of SCCs arising in patients with DEB and JEB; > 50% of neoplastic cells stained positive for MUC1 in 57% of DEB/JEB SCCs, with over 95% of tumour cells immunopositive in 33% of cases. MUC1 expression was also observed in 95% of sporadic SCCs and 97% of Bowen's disease, with 36% of sporadic SCCs immunopositive for MUC1 in > 50% of tumour cells. Investigation of the glycosylation status showed that MUC1 was predominantly hyperglycosylated in the DEB/JEB and sporadic tumours. Conclusions The results demonstrate that a significant proportion of DEB/JEB and sporadic SCCs express MUC1 in > 50% of tumour cells. Therefore, MUC1 may be a suitable candidate antigen against which to develop a tumour vaccine for these patient groups.
Stratum corneum integrity as a predictor for peristomal skin problems in ostomates
Authors: H. Nybaek, S. Lophagen, T. Karlsmark, D. Bang Knudsen, G.B.E. Jemec
Journal: British Journal of Dermatology (2009)

Journal Article Stratum corneum integrity as a predictor for peristomal skin problems in ostomates Get access H. Nybaek, H. Nybaek Department of Dermatology, Roskilde Hospital, Koegevej 7–13, Roskilde 4000, Denmark Hanne Nybaek. E‐mail: hany@regionsjaelland.dk Search for other works by this author on: Oxford Academic Google Scholar S. Lophagen, S. Lophagen Department of Dermatology, Roskilde Hospital, Koegevej 7–13, Roskilde 4000, Denmark Search for other works by this author on: Oxford Academic Google Scholar T. Karlsmark, T. Karlsmark Department of Dermatology, Bispebjerg Hospital, Kopenhagen, Denmark Search for other works by this author on: Oxford Academic Google Scholar D. Bang Knudsen, D. Bang Knudsen Coloplast A/S, Humlebaek, Denmark Search for other works by this author on: Oxford Academic Google Scholar G.B.E. Jemec G.B.E. Jemec Department of Dermatology, Health Sciences Faculty, University of Copenhagen, Roskilde Hospital, Roskilde, Denmark Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 162, Issue 2, 1 February 2010, Pages 357–361, https://doi.org/10.1111/j.1365-2133.2009.09418.x Published: 01 February 2010
VOLUNTARY BREATHHOLDING. III. THE RELATION OF THE MAXIMUM TIME OF BREATHHOLDING TO THE OXYGEN AND CARBON DIOXIDE TENSIONS OF ARTERIAL BLOOD, WITH A NOTE ON ITS CLINICAL AND PHYSIOLOGICAL SIGNIFICANCE 1
Authors: Eugene B. Ferris, George L. Engel, Charles D. Stevens, Joseph Webb
Journal: Journal of Clinical Investigation (1946)

By means of underwater weighing during breathholding, after preliminary inhalation of gas mixtures containing varying concentrations of oxygen, it has been shown that the diffusion of oxygen from the lungs is influenced by the PO2 of the inspired air (1).It was also shown (2) that the duration of the maximum voluntary breathholding time was related to the PO2 of in- spired air.Others have shown that alveolar pCO2 plays an important role in altering the breathholding time (3 to 5).Thus, it is evident that both PO2 and pCO2 are factors which influ- ence the time that the breath can be held.Sev- eral investigators (6, 3) have studied alveolar gases during breathholding, and at the end of the apneic period produced by hyperventilation, but to our knowledge, the changes in the arterial blood have not been investigated.Despite the lack of knowledge concerning the physiologic changes which occur during breathholding, it is being used with increasing frequency as a clinical test (7 to 9).In order to clarify the influence of oxygen and CO2 in regulating the breathholding time, arterial blood gases have been studied during breath- holding and at the time when breathing is forced.These data throw considerable light on the inter- relation of oxygen and CO2 as factors which in- fluence respiration under the conditions studied, and on the factors which influence pulmonary diffusion of oxygen and CO2 during breath- holding.
Distinct Pathways Regulate Expression of Cardiac Electrical and Mechanical Junction Proteins in Response to Stretch
Authors: Kiyomi Yamada, Karen G. Green, Allen M. Samarel, Jeffrey E. Saffitz
Journal: Circulation Research (2005)

To define mechanisms regulating expression of cell–cell junction proteins, we have developed an in vitro system in which neonatal rat ventricular myocytes were subjected to pulsatile stretch. Previously, we showed that expression of the gap junction protein, connexin (Cx) 43, is increased by ≈2-fold after 1 hour of stretch, and this response is mediated by stretch-induced secretion of vascular endothelial growth factor (VEGF). Here, we report that the mechanical junction proteins plakoglobin, desmoplakin, and N-cadherin are also upregulated by pulsatile stretch but by a mechanism independent of VEGF or other secreted chemical signals. Stretch-induced upregulation of mechanical junction proteins was blocked by anti–β 1 and anti–β 3 integrin antibodies. Transfection of cells with adenovirus expressing GFP-FRNK, a dominant-negative inhibitor of focal adhesion kinase (FAK)-dependent signaling, blocked stretch-induced upregulation of Cx43 and mechanical junction proteins but did not block the ability of exogenous VEGF to upregulate Cx43 expression. Conditioned medium removed from uninfected cells after stretch increased Cx43 expression when added to nonstretched cells, and this effect was blocked by anti-VEGF antibodies, but stretch-conditioned medium from GFP-FRNK cells had no effect on Cx43 expression. The src kinase inhibitor 4-amino-5-(4-chloro-phenyl)-7-( t -butyl)pyrazolol[3,4- d ]pyrimidine blocked stretch-induced upregulation of mechanical junction proteins but not Cx43. Thus, stretch upregulates expression of both electrical and mechanical junction proteins via integrin-dependent activation of FAK. Stretch-induced upregulation of Cx43 expression is mediated by FAK-dependent secretion of VEGF. In contrast, stretch-induced upregulation of adhesion junction proteins involves intracellular mechanotransduction pathways initiated via integrin signaling and acting downstream of src kinase.
Lumbar Bone Marrow Microcirculation Measurements from Dynamic Contrast-Enhanced Magnetic Resonance Imaging Is a Predictor of Event-Free Survival in Progressive Multiple Myeloma
Authors: Jens Hillengass, Klaus Wasser, Stefan Delorme, Fabian Kiessling, Christian Zechmann, Axel Benner, Hans-Ulrich Kauczor, Anthony D. Ho, Hartmut Goldschmidt, Thomas M. Moehler
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with high temporal resolution enables the detection of microcirculation variables amplitude A and exchange rate constant kep. In this study, the prognostic value of the DCE-MRI variables for overall survival and event-free survival in patients with progressive multiple myeloma was investigated. Experimental Design: Between 1999 and 2001, 65 patients with progressive or relapse of multiple myeloma requiring therapy were investigated with DCE-MRI of the lumbar spine before start of therapy. The contrast uptake was quantified using a two-compartment model with the output variables amplitude A and exchange rate constant kep reflecting bone marrow microcirculation. The estimated median follow-up was 56 months. Event-free survival and overall survival were investigated for DCE-MRI variables and for established prognosis variables (β2-microglobulin, lactate dehydrogenase, albumin, and age). Results: Using a multivariate Cox regression model, β2-microglobulin and amplitude A of DCE-MRI were identified as statistically significant prognostic variable of event-free survival with Ps of 0.01 and 0.02, respectively. A statistical correlation of DCE-MRI variables with overall survival could not be found. The multivariate analysis of β2-microglobulin, age, lactate dehydrogenase, and albumin revealed β2-microglobulin as statistically significant prognostic factor for overall survival in this group of patients (P &amp;lt; 0.001). Conclusions: This analysis identifies contrast-enhanced DCE-MRI variable amplitude A reflecting increased bone marrow microcirculation and angiogenesis as a novel and possibly useful prognostic factor in patients with multiple myeloma. Prospective studies are currently done to further investigate this functional variable for prognosis and stratification of myeloma patients.
Recent advances in inflammatory bowel disease: mucosal immune cells in intestinal inflammation
Authors: M Zaeem Cader, Arthur Kaser
Journal: Gut (2013)

The intestine and its immune system have evolved to meet the extraordinary task of maintaining tolerance to the largest, most complex and diverse microbial commensal habitat, while meticulously attacking and containing even minute numbers of occasionally incoming pathogens. While our understanding is still far from complete, recent studies have provided exciting novel insights into the complex interplay of the many distinct intestinal immune cell types as well as the discovery of entirely new cell subsets. These studies have also revealed how proper development and function of the intestinal immune system is dependent on its specific microbiota, which appears to have evolutionarily co-evolved. Here we review key immune cells that maintain intestinal homeostasis and, conversely, describe how altered function and imbalances may lead to inflammatory bowel disease (IBD). We highlight the latest developments within this field, covering the major players in IBD including intestinal epithelial cells, macrophages, dendritic cells, adaptive immune cells, and the newly discovered innate lymphoid cells, which appear of characteristic importance for immune function at mucosal surfaces. We set these mucosal immune pathways in the functional context of IBD risk genes where such insight is available. Moreover, we frame our discussion of fundamental biological pathways that have been elucidated in model systems in the context of results from clinical trials in IBD that targeted key mediators secreted by these cells, as an attempt of 'functional' appraisal of these pathways in human disease.
Encapsulation of adenovirus serotype 5 in anionic lecithin liposomes using a bead-based immunoprecipitation technique enhances transfection efficiency
Authors: Natalie Mendez, Vanessa Herrera, Lingzhi Zhang, Farah Hedjran, Ralph Feuer, Sarah L. Blair, William C. Trogler, Tony R. Reid, Andrew C. Kummel
Journal: Biomaterials (2014)
Effects of administration of progenipoietin 1, Flt-3 ligand, granulocyte colony-stimulating factor, and pegylated granulocyte-macrophage colony-stimulating factor on dendritic cell subsets in mice
Authors: Meredith O'Keeffe, Hubertus Hochrein, David Vremec, Joanne Pooley, Robert Evans, Susan Woulfe, Ken Shortman
Journal: Blood (2002)
Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery
Authors: Greg A. Knock, Vladimir A. Snetkov, Yasin Shaifta, Svetlana Drndarski, Jeremy P.T. Ward, Philip I. Aaronson
Journal: Cardiovascular Research (2008)

AimsWe investigated the role of src-family kinases (srcFKs) in hypoxic pulmonary vasoconstriction (HPV) and how this relates to Rho-kinase-mediated Ca2+ sensitization and changes in intracellular Ca2+ concentration ([Ca2+]i).
Small molecular anti-cytokine agents
Authors: Gerd Wagner, Stefan Laufer
Journal: Medicinal Research Reviews (2005)

The recent successful introduction of the anti-cytokine biologicals Etanercept, Infliximab, Adalimumab, and Anakinra has stimulated the search for anti-cytokine small-molecules. A number of molecular targets have been identified for the development of such small molecular anti-cytokine agents. The focus of this review will be on those inhibitors of cytokine production, which target either p38 mitogen activated protein (MAP) kinase, TNF-α converting enzyme (TACE), or IL-1β converting enzyme (ICE). P38 MAP kinase occupies a central role in the signaling network responsible for the upregulation of proinflammatory cytokines like interleukin 1β (IL-1β) and TNF-α, and regulates their biosynthesis at both the transcriptional and translational level. TACE and ICE are two proteases required for the processing of proTNF-α and proIL-1β, respectively into their mature, proinflammatory form. Since the mid-1990s, a plethora of inhibitors of p38 MAP kinase, TACE, and ICE has been characterized in vitro, and individual representatives from all three inhibitor classes have in the meantime been advanced into clinical trials. This review will highlight the correlation between effective inhibition at the molecular target and cellular activity in functional assays of cytokine, particularly TNF-α and IL-1β, production. Structure–activity relationships (SAR) will be discussed regarding activity at the respective enzyme target, but also with regard to properties required for efficient in vitro and in vivo cellular activity (e.g., oral availability, solubility, cell penetration, etc.). © 2005 Wiley Periodicals, Inc. Med Res Rev
Monitoring Drug-Induced γH2AX as a Pharmacodynamic Biomarker in Individual Circulating Tumor Cells
Authors: Lihua H. Wang, Thomas D. Pfister, Ralph E. Parchment, Shivaani Kummar, Larry Rubinstein, Yvonne A. Evrard, Martin E. Gutierrez, Anthony J. Murgo, Joseph E. Tomaszewski, James H. Doroshow, Robert J. Kinders
Journal: Clinical Cancer Research (2010)

Circulating tumor cells (CTC) in peripheral blood of patients potentially represent a fraction of solid tumor cells available for more frequent pharmacodynamic assessment of drug action than is possible using tumor biopsy. However, currently available CTC assays are limited to cell membrane antigens. Here, we describe an assay that directly examines changes in levels of the nuclear DNA damage marker gammaH2AX in individual CTCs of patients treated with chemotherapeutic agents.An Alexa Fluor 488-conjugated monoclonal gammaH2AX antibody and epithelial cancer cell lines treated with topotecan and spiked into whole blood were used to measure DNA damage-dependent nuclear gammaH2AX signals in individual CTCs. Time-course changes in both CTC number and gammaH2AX levels in CTCs were also evaluated in blood samples from patients undergoing treatment.The percentage of gammaH2AX-positive CTCs increased in a concentration-dependent manner in cells treated with therapeutically relevant concentrations of topotecan ex vivo. In samples from five patients, percent gammaH2AX-positive cells increased post-treatment from a mean of 2% at baseline (range, 0-6%) to a mean of 38% (range, 22-64%) after a single day of drug administration; this increase was irrespective of increases or decreases in the total CTC count.These data show promise for monitoring dynamic changes in nuclear biomarkers in CTCs (in addition to CTC count) for rapidly assessing drug activity in clinical trials of molecularly targeted anticancer therapeutics as well as for translational research.
Global Impairment of Cardiac Autonomic Nervous Activity Late After Repair of Tetralogy of Fallot
Authors: Constantinos H. Davos, Periklis A. Davlouros, Roland Wensel, Darrel Francis, L. Ceri Davies, Philip J. Kilner, Andrew J. S. Coats, Massimo Piepoli, Michael A. Gatzoulis
Journal: Circulation (2002)

Sustained ventricular tachycardia (VT) and sudden cardiac death (SCD) remain devastating late complications after repair of Tetralogy of Fallot (ToF). Although heart rate variability (HRV) and baroreflex sensitivity (BRS) are recognized as independent markers of autonomic activity and strong predictors of SCD in major cardiovascular disease, little is known about their role in patients with tetralogy.We measured HRV and BRS in 45 ToF patients (27 male, age 35+/-12 years, 26+/-7 years after repair) and 45 matched healthy controls. Subjects underwent 20 minute of resting measurements of heart rate (ECG) and noninvasive beat-to-beat blood pressure recording (Finapres), with 5 minutes of 0.1Hz controlled breathing followed by cardiac MRI. BRS was computed by spectral analysis and the sequence and controlled breathing methods. All HRV time and frequency domain variables were measured. All BRS and HRV variables were significantly reduced in patients compared with controls (P<0.001 in all). HRV tended to increase with years from repair. BRS decreased with previous palliation and increasing patient age. Both HRV and BRS decreased with pulmonary regurgitation, elevated right ventricular end systolic volumes and reduced right and left ventricular ejection fraction. Finally, there was an inverse relation between QRS duration (predictor of sustained VT and SCD) and indices of HRV but no relation with indices of BRS.There is global impairment of autonomic nervous system regulation late after repair of tetralogy with marked reduction of BRS and HRV. This seems to relate to previous surgical intervention/s, their timing and current right and left-sided hemodynamics. Reduced HRV also related to markers of sustained VT and SCD, suggesting possible common pathogenic mechanisms. Further studies are required to examine the prognostic significance of impaired BRS and HRV in these patients.
PDGF-BB modulates hematopoiesis and tumor angiogenesis by inducing erythropoietin production in stromal cells
Authors: Yuan Xue, Sharon Lim, Yunlong Yang, Zongwei Wang, Lasse Dahl Ejby Jensen, Eva-Maria Hedlund, Patrik Andersson, Masakiyo Sasahara, Ola Larsson, Dagmar Galter, Renhai Cao, Kayoko Hosaka, Yihai Cao
Journal: Nature Medicine (2011)
Evaluation of Asymptomatic Solitary Hepatic Lesions
Authors: James H. Foster
Journal: Annual Review of Medicine (1988)

Clinical judgment and noninvasive radiologic imaging are the keystones to decision-making in the management of most patients with asymptomatic liver lesions. A knowledge of the natural history of the common lesions suggests a conservative approach to those that are benign and an aggressive approach to those that are malignant and still localized.
MYOCARDITIS AND PULMONARY ARTERITIS IN MICE ASSOCIATED WITH THE PRESENCE OF RICKETTSIA-LIKE BODIES IN POLYMORPHONUCLEAR LEUCOCYTES
Authors: Alwin M. Pappenheimer, Joan B. Daniels
Journal: The Journal of Experimental Medicine (1953)

A previously undescribed disease of mice, characterized by acute interstitial myocarditis, and by periarterial pulmonary lesions, is reported. The transmissibility of this disease has been shown, but a large proportion of inoculated mice appears to be resistant. Microorganisms, rickettsial in form but not positively identified as such, are consistently present in the lesions. They are found predominantly in the cytoplasm of polymorphonuclear leucocytes. Filtrates of fecal material from normal mice of the Harvard breeding stock may produce lesions in myocardium and pulmonary arteries indistinguishable from those occurring in this disease. Rickettsia-like bodies are also found in these lesions.