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The effects of anti-histamines on signal transduction, transcription factors and cell death regulating genes in mycosis fungoides and the sézary syndrome

English title The effects of anti-histamines on signal transduction, transcription factors and cell death regulating genes in mycosis fungoides and the sézary syndrome
Applicant Kündig Thomas
Number 122221
Funding scheme Project funding
Research institution Dermatologische Klinik Universitätsspital Zürich
Institution of higher education University of Zurich - ZH
Main discipline Experimental Cancer Research
Start/End 01.12.2008 - 31.08.2011
Approved amount 229'992.00
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All Disciplines (2)

Discipline
Experimental Cancer Research
Cellular Biology, Cytology

Keywords (6)

anti-histamines; apoptosis; signal transduction; cutaneous T Cell lymphoma; Transcription factors; lymphoma

Lay Summary (English)

Lead
Lay summary
Project Title:The effects of anti-histamines on transcription factors and cell death regulating genes in Mycosis Fungoides and the Sézary SyndromeMain Applicant:PD Dr. Thomas M. Kündig, Head of Research, Department of Dermatology, Zurich University HospitalLead:Antihistamines are commonly used and well tolerated drugs. We found that already low antihistamine concentrations induce cell death in cutaneous T cell lymphomas (CTCL). Investigation of the mechanism of cell death might open new treatment alleys for this incurable disease.Background:The most common forms of CTCL are mycosis fungoides (MF) and its leukemic variant Sézary syndrome (SS). To date there is no cure for both diseases. We recently discovered that incubation with anti-histamines kills MF and SS cell lines. Cell death was observed at concentrations that were within the range of serum concentrations in patients, e.g. allergy patients treated with recommended doses of anti-histamines. As anti-histamines are very safe and well tolerated drugs, they would be well suited to treat MF and SS.Our previous research revealed that MF and SS cells contain constitutive NFkB (nuclear factor kappa B) and STAT (signal transducer and activator of transcription) transcription factor activities, increasing the expression of genes that protect MF and SS cells from apoptosis.Aim:We will test whether anti-histamines induce apoptosis of CTCL cells by inhibiting NFkB or other transcription factors pathways necessary for cell survival. The activity of cell survival promoting genes (bcl-2, bcl-xL, mcl-1, Flip, cIAP1 and cIAP2) will also be investigated. We will further evaluate which apoptosis pathways are activated by anti-histamines, and whether or not the Histamine H1 receptor or Ca2+ signaling is involved.Significance:Knowledge of the pathways inducing cell death of MF and SS cells will not only provide further insights into the pathogenesis of these diseases, but may also open new alleys treat these so far incurable diseases. In contrast to currently used cytotoxic drugs, antihistamines would represent a well tolerated treatment option.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Clemastine causes immune suppression through inhibition of extracellular signal-regulated kinase-dependent proinflammatory cytokines
Johansen P, Weiss A, Bünter A, Waeckerle-Men Y, Fettelschoss A, Odermatt B, Kündig TM (2011), Clemastine causes immune suppression through inhibition of extracellular signal-regulated kinase-dependent proinflammatory cytokines, in Journal of Allergy and Clinical Immunology.
Medication with antihistamines impairs allergen-specific immunotherapy in mice
Johansen P, Senti G, Maria Martínez Gómez J, Kündig TM (2008), Medication with antihistamines impairs allergen-specific immunotherapy in mice, in Clinical and Experimental Allergy, 38(3), 512-519.

Communication with the public

Communication Title Media Place Year
Media relations: print media, online media Do antihistamines make allergies worse? Nature, New York Times and other International

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