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R Tauber, J Gschwend, K Scheidhauer, M Eiber, M Krönke
Radium-223 dichloride (Xofigo®, Alpharadin) is approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases and no known visceral metastases. As a calcium mimetic, it is integrated into osteoplastic bone lesions and emits alpha particles with high energy which leads to local destruction of tumor cells. In the 2013 published ALSYMPCA trial, a significant advantage for overall survival and quality of life in comparison to placebo was found. Recent data suggest an increased potential in combination with next generation hormonal treatment...
January 2017: Der Urologe. Ausg. A
J Krönke, F Kuchenbauer, M Kull, V Teleanu, L Bullinger, D Bunjes, A Greiner, S Kolmus, S Köpff, M Schreder, L-O Mügge, C Straka, M Engelhardt, H Döhner, H Einsele, F Bassermann, R Bargou, S Knop, C Langer
Lenalidomide is an immunomodulatory compound with high clinical activity in multiple myeloma. Lenalidomide binding to the Cereblon (CRBN) E3 ubiquitin ligase results in targeted ubiquitination and degradation of the lymphoid transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) leading to growth-inhibition of multiple myeloma cells. Recently, Basigin (BSG) was identified as another protein regulated by CRBN that is involved in the activity of lenalidomide. Here, we analyzed the prognostic value of IKZF1, IKZF3, CRBN and BSG mRNA expression levels in pretreatment plasma cells from sixty patients with newly diagnosed multiple myeloma uniformly treated with lenalidomide in combination with intensive chemotherapy within a clinical trial...
December 26, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Farida Djouad, Natacha Ipseiz, Patricia Luz-Crawford, Carina Scholtysek, Gerhard Krönke, Christian Jorgensen
Peroxisome proliferator-activated receptors (PPARs) have emerged as key regulators of physiological and immunological processes. Recently, one of their members PPARβ/δ has been identified as major player in the maintenance of bone homeostasis, by promoting Wnt signalling activity in osteoblast and mesenchymal stem cells (MSC). PPARβ/δ not only controls the fate of MSC but also regulates their immunosuppressive properties by directly modulating their NF-κB activity. In this review, we discuss how the regulation of PPARβ/δ provides an innovative strategy for an optimisation of MSC-based therapy...
November 30, 2016: Biochimie
M Stock, A Distler, J Distler, C Beyer, G Ruiz-Heiland, N Ipseiz, M Seeling, G Krönke, F Nimmerjahn, G Schett
No abstract text is available yet for this article.
November 16, 2016: Osteoarthritis and Cartilage
René Pfeifle, Tobias Rothe, Natacha Ipseiz, Hans U Scherer, Stephan Culemann, Ulrike Harre, Jochen A Ackermann, Martina Seefried, Arnd Kleyer, Stefan Uderhardt, Benjamin Haugg, Axel J Hueber, Patrick Daum, Gordon F Heidkamp, Changrong Ge, Sybille Böhm, Anja Lux, Wolfgang Schuh, Iryna Magorivska, Kutty S Nandakumar, Erik Lönnblom, Christoph Becker, Diana Dudziak, Manfred Wuhrer, Yoann Rombouts, Carolien A Koeleman, René Toes, Thomas H Winkler, Rikard Holmdahl, Martin Herrmann, Stephan Blüml, Falk Nimmerjahn, Georg Schett, Gerhard Krönke
The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the TH17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, TH17 cells regulated the expression of β-galactoside α2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged...
January 2017: Nature Immunology
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
Max Wolff, Klaus-Martin Krönke, John Venz, Anja Kräplin, Gerhard Bühringer, Michael N Smolka, Thomas Goschke
Self-control is commonly assumed to depend on executive functions (EFs). However, it is unclear whether real-life self-control failures result from deficient EF competencies or rather reflect insufficient conflict-induced mobilization of executive control, and whether self-control depends more critically on function-specific EF competencies or general executive functioning (GEF), that is, common competencies that underlie all EFs. Here we investigated whether failure-related action versus state orientation, a personality trait related to the conflict-induced mobilization of cognitive control, moderates the effect of general and function-specific control competencies on self-control...
December 2016: Journal of Experimental Psychology. General
Brandi Wynne, Trinity Kronk, Otor Al-Khalili, Benjamin Ko, Franziska Theilig, Douglas Eaton, Robert Hoover
OBJECTIVE: Hypertension is characterized by increased sodium reabsorption along the aldosterone-sensitive distal nephron (ASDN) and systemic inflammation. Interleukin-6 (IL-6) is a possible mediator, signaling via the transmembrane IL-6 receptor alpha (IL-6Rα); however, whether IL-6Rα is present in the distal convoluted tubule (DCT) is unknown. Increased sodium reabsorption is not always correlated with increased aldosterone (Aldo). Thus, understanding how Aldo-independent sodium reabsorption occurs is critical...
September 2016: Journal of Hypertension
Stefanie Lindner, Jan Krönke
Thalidomide was sold in the 1950s as a sedative and was also used by pregnant women to treat morning sickness. It became notorious for causing severe birth defects and was removed from the market. More than four decades later, thalidomide had a renaissance in the treatment of cancer. Thalidomide and its more potent analogs, lenalidomide and pomalidomide, are nowadays approved treatments for multiple myeloma and myelodysplastic syndrome with deletion of chromosome 5q. In addition, thalidomide and its analogs inhibit release of tumor necrosis factor-α and increase interleukin-2 (IL-2) and interferon-γ release from T cells...
December 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
Jochen A Ackermann, Katharina Hofheinz, Mario M Zaiss, Gerhard Krönke
12/15-Lipoxygenase (12/15-LOX) mediates the enzymatic oxidation of polyunsaturated fatty acids, thereby contributing to the generation of various bioactive lipid mediators. Although 12/15-LOX has been implicated in the pathogenesis of multiple chronic inflammatory diseases, its physiologic functions seem to include potent immune modulatory properties that physiologically contribute to the resolution of inflammation and the clearance of inflammation-associated tissue damage. This review aims to give a comprehensive overview about our current knowledge on the role of this enzyme during the regulation of inflammation and immunity...
July 30, 2016: Biochimica et Biophysica Acta
Velizar Shivarov, Anna Dolnik, Katharina M Lang, Jan Krönke, Florian Kuchenbauer, Peter Paschka, Verena I Gaidzik, Hartmut Döhner, Richard F Schlenk, Konstanze Döhner, Lars Bullinger
No abstract text is available yet for this article.
July 28, 2016: Haematologica
Daniel N Meijles, Lampson M Fan, Maziah M Ghazaly, Brendan Howlin, Martin Krönke, Gavin Brooks, Jian-Mei Li
BACKGROUND: The NADPH oxidase, by generating reactive oxygen species, is involved in the pathophysiology of many cardiovascular diseases and represents a therapeutic target for the development of novel drugs. A single-nucleotide polymorphism, C242T of the p22(phox) subunit of NADPH oxidase, has been reported to be negatively associated with coronary heart disease and may predict disease prevalence. However, the underlying mechanisms remain unknown. METHODS AND RESULTS: With the use of computer molecular modeling, we discovered that C242T single-nucleotide polymorphism causes significant structural changes in the extracellular loop of p22(phox) and reduces its interaction stability with Nox2 subunit...
June 14, 2016: Circulation
Marie-Luise Hütter-Krönke, Axel Benner, Konstanze Döhner, Jürgen Krauter, Daniela Weber, Margit Moessner, Claus-Henning Köhne, Heinz A Horst, Ingo G H Schmidt-Wolf, Mathias Rummel, Katharina Götze, Elisabeth Koller, Andreas L Petzer, Hans Salwender, Walter Fiedler, Heinz Kirchen, Detlef Haase, Stephan Kremers, Matthias Theobald, Axel C Matzdorff, Arnold Ganser, Hartmut Döhner, Richard F Schlenk
Outcome of patients with primary refractory acute myeloid leukemia remains unsatisfactory. We conducted a prospective phase II clinical trial with gemtuzumab ozogamicin (3 mg/m(2) intravenously on day 1), all-trans retinoic acid (45 mg/m(2) orally on days 4-6 and 15 mg/m(2) orally on days 7-28), high-dose cytarabine (3 g/m(2)/12 h intravenously on days 1-3) and mitoxantrone (12 mg/m(2) intravenously on days 2-3) in 93 patients aged 18-60 years refractory to one cycle of induction therapy. Primary end point of the study was response to therapy; secondary end points included evaluation of toxicities, in particular, rate of sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation...
July 2016: Haematologica
P Luz-Crawford, N Ipseiz, G Espinosa-Carrasco, A Caicedo, G Tejedor, K Toupet, J Loriau, C Scholtysek, C Stoll, M Khoury, D Noël, C Jorgensen, G Krönke, F Djouad
OBJECTIVES: To define how peroxisome proliferator-activated receptor (PPAR) β/δ expression level in mesenchymal stem cells (MSCs) could predict and direct both their immunosuppressive and therapeutic properties. PPARβ/δ interacts with factors such as nuclear factor-kappa B (NF-κB) and regulates the expression of molecules including vascular cell adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1. Since these molecules are critical for MSC function, we investigated the role of PPARβ/δ on MSC immunosuppressive properties...
December 2016: Annals of the Rheumatic Diseases
S Bohl, S von Harsdorf, M Mulaw, S Hofmann, A Babiak, C P Maier, J Schnell, L-M Hütter-Krönke, K Scholl, V Wais, R F Schlenk, L Bullinger, M Ringhoffer, H Döhner, D Bunjes, M Bommer, F Kuchenbauer
No abstract text is available yet for this article.
July 2016: Bone Marrow Transplantation
Kristin Jakobshagen, Beate Ward, Nikola Baschuk, Sebastian Huss, Anna Brunn, Monika Malecki, Michael Fiolka, Gunther Rappl, Diana Corogeanu, Ulrike Karow, Petra Schiller, Hinrich Abken, Lukas C Heukamp, Martina Deckert, Martin Krönke, Olaf Utermöhlen
The immunoregulatory cytokine IL-10 suppresses T-cell immunity. The complementary question, whether IL-10 is also involved in limiting the collateral damage of vigorous T cell responses, has not been addressed in detail. Here, we report that the particularly strong virus-specific immune response during acute primary infection with the lymphocytic choriomeningitis virus (LCMV) in mice is significantly further increased in Il10-deficient mice, particularly regarding frequencies and cytotoxic activity of CD8(+) T cells...
November 2015: American Journal of Pathology
Max Wolff, Klaus-Martin Krönke, Thomas Goschke
Although cognitive control is commonly identified as the basis of self-controlled behavior, correlations found between trait self-control and laboratory measures of cognitive control such as Stroop interference are typically low. Based on the notion that self-control requires the ability to refrain from rewarded behaviors, and inspired by the recent finding that Stroop interference is modulated by reward associations, we propose the idea that the modulation of interference by reward associations (MIRA) is a cognitive marker of trait self-control...
November 2016: Psychological Research
Yubin Luo, Guang-Liang Chen, Nicole Hannemann, Natacha Ipseiz, Gerhard Krönke, Tobias Bäuerle, Luis Munos, Stefan Wirtz, Georg Schett, Aline Bozec
The effect of metabolic stress on the bone marrow microenvironment is poorly defined. We show that high-fat diet (HFD) decreased long-term Lin(-)Sca-1(+)c-Kit(+) (LSK) stem cells and shifted lymphoid to myeloid cell differentiation. Bone marrow niche function was impaired after HFD as shown by poor reconstitution of hematopoietic stem cells. HFD led to robust activation of PPARγ2, which impaired osteoblastogenesis while enhancing bone marrow adipogenesis. At the same time, expression of genes such as Jag-1, SDF-1, and IL-7 forming the bone marrow niche was highly suppressed after HFD...
November 3, 2015: Cell Metabolism
Rebecca Kronk, Yvonne Weideman, Leah Cunningham, Lenore Resick
BACKGROUND: This article describes the use of photo-elicitation as a qualitative research method that captured transformational outcomes of baccalaureate nursing students who participated in a 10-day global service-learning experience in Nicaragua. METHOD: All participants (N = 8) took photographs as a natural way of capturing moments, scenes, and events that occurred during their immersion experience. Four weeks after the trip, each student selected photographs that were a meaningful visual representation of their experience and participated in a semistructured interview conducted by one of the three faculty investigators...
September 2015: Journal of Nursing Education
Klaus-Martin Krönke, Max Wolff, Annika Benz, Thomas Goschke
Although many smokers try to quit, relatively few are successful in their attempts. Here we investigated whether the ability to quit smoking is related to behavioral and neural measures of cognitive control. A functional magnetic resonance imaging study with a counting Stroop task was used to measure cognitive control in ex-smokers (N=10) who had successfully quit smoking and smokers (N=10) who continuously failed to quit smoking. Behavioral results showed a significant Stroop effect in ex-smokers and smokers...
October 30, 2015: Psychiatry Research
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