59 results on '"Möbs M"'
Search Results
52. Apoptosis induction by SAHA in cutaneous T-cell lymphoma cells is related to downregulation of c-FLIP and enhanced TRAIL signaling.
- Author
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Al-Yacoub N, Fecker LF, Möbs M, Plötz M, Braun FK, Sterry W, and Eberle J
- Subjects
- Aged, Aged, 80 and over, Down-Regulation drug effects, Female, Humans, Inhibitor of Apoptosis Proteins metabolism, Male, Middle Aged, Signal Transduction drug effects, Tumor Cells, Cultured, Up-Regulation drug effects, Vorinostat, Antineoplastic Agents pharmacology, CASP8 and FADD-Like Apoptosis Regulating Protein antagonists & inhibitors, Hydroxamic Acids pharmacology, Lymphoma, T-Cell, Cutaneous metabolism, Skin Neoplasms metabolism, TNF-Related Apoptosis-Inducing Ligand metabolism
- Abstract
Suberoylanilide hydroxamic acid (SAHA) has been approved for the treatment of cutaneous T-cell lymphoma (CTCL), but its mode of action remained largely elusive. As shown here in four CTCL cell lines, loss of cell viability correlated with significant time- and dose-dependent induction of apoptosis, whereas cytotoxicity was less pronounced. Both extrinsic and intrinsic apoptosis pathways were activated, as seen by processing of initiator caspases 8 and 9, loss of mitochondrial membrane potential, and cytochrome c release. Characteristically, antiapoptotic mediators such as Mcl-1, XIAP, survivin, and c-FLIP were downregulated. Consistent with its critical function, c-FLIP overexpression resulted in a significant decrease of SAHA-mediated apoptosis. Enhanced sensitivity to TRAIL (TNF-related apoptosis-inducing ligand) and enhanced TRAIL signaling was seen in CTCL cell lines with high sensitivity, whereas cell lines with moderate response were characterized by downregulation of TRAIL-R2 and weaker TRAIL expression. Comparable proapoptotic responses to SAHA and to the combination with TRAIL were seen in ex vivo tumor T cells of CTCL patients. Thus, activation of extrinsic apoptosis pathways, related to c-FLIP downregulation and enhanced TRAIL signaling, appeared as characteristic for CTCL cell responsiveness to SAHA. An improved understanding of the pathways may facilitate its targeted use and the selection of suitable combinations.
- Published
- 2012
- Full Text
- View/download PDF
53. [Cutaneous malignant lymphomas. Update on diagnosis and therapy of cutaneous T-cell lymphomas].
- Author
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Humme D, Möbs M, Pullmann S, Haidar A, Beyer M, Sterry W, and Assaf C
- Subjects
- Humans, Lymphoma, T-Cell diagnosis, Lymphoma, T-Cell therapy, Skin Neoplasms diagnosis, Skin Neoplasms therapy
- Abstract
Cutaneous T-cell lymphomas represent extranodal non-Hodgkin lymphomas of mature T-cells, which accumulate in the skin. They have been recognized as a heterogeneous group with distinct variability in clinical presentation and histopathology, with divergent biological behaviour and prognosis. Therefore the exact diagnosis is an important prerequisite for an adequate and stage-adapted treatment.
- Published
- 2012
- Full Text
- View/download PDF
54. Nonsteroidal anti-inflammatory drugs induce apoptosis in cutaneous T-cell lymphoma cells and enhance their sensitivity for TNF-related apoptosis-inducing ligand.
- Author
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Braun FK, Al-Yacoub N, Plötz M, Möbs M, Sterry W, and Eberle J
- Subjects
- CASP8 and FADD-Like Apoptosis Regulating Protein physiology, Caspases metabolism, Cell Line, Tumor, Cell Proliferation drug effects, Enzyme Activation drug effects, Humans, Lymphoma, T-Cell, Cutaneous pathology, Membrane Potential, Mitochondrial drug effects, NF-kappa B physiology, Skin Neoplasms pathology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Apoptosis drug effects, Lymphoma, T-Cell, Cutaneous drug therapy, Skin Neoplasms drug therapy, TNF-Related Apoptosis-Inducing Ligand pharmacology
- Abstract
Cutaneous T-cell lymphomas (CTCL) form a heterogeneous group of non-Hodgkin's lymphomas of the skin. In previous studies, we had characterized CTCL cells as resistant to the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), which correlated to pronounced expression of the caspase-8/-10 inhibitor c-FLIP. For identification of proapoptotic strategies in CTCL cells and for overcoming their death ligand resistance, we investigated the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) such as acetylsalicylic acid, sodium salicylate, and diclofenac (DF). These drugs strongly enhanced apoptosis, as well as decreased CTCL cell proliferation and vitality, and DF furthermore sensitized for TRAIL-induced apoptosis. Full activation of the caspase cascade (caspase-3, -8, -9) and decreased mitochondrial membrane potential were characteristic for NSAID treatment, whereas cytochrome c release was seen only for DF. Downregulation of Mcl-1 and enhanced surface expression of TRAIL were seen in response to NSAIDs. Most characteristic for apoptosis induction was the downregulation of c-FLIP. In agreement with the critical role of c-FLIP for apoptosis deficiency of CTCL cells, its overexpression decreased NSAID-mediated apoptosis and its downregulation by small hairpin RNA-enhanced apoptosis. The study provides a rationale for the use of NSAIDs as a new therapeutic option for CTCL patients. Supporting this concept, ex vivo lymphoma cells of CTCL patients also revealed significant sensitivity for NSAID treatment.
- Published
- 2012
- Full Text
- View/download PDF
55. Pathogenesis of Mycosis fungoides.
- Author
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Beyer M, Möbs M, Humme D, and Sterry W
- Subjects
- CD4-Positive T-Lymphocytes immunology, Cell Transformation, Neoplastic genetics, Cell Transformation, Neoplastic immunology, Cell Transformation, Neoplastic pathology, Chemokines blood, Cytokines blood, Epitopes immunology, Female, Human T-lymphotropic virus 1 pathogenicity, Humans, Lymphocyte Activation immunology, Male, Middle Aged, Mycosis Fungoides immunology, Mycosis Fungoides pathology, Neoplasm Staging, Phenotype, Skin pathology, Skin Neoplasms immunology, Skin Neoplasms pathology, T-Lymphocytes, Helper-Inducer immunology, T-Lymphocytes, Regulatory immunology, Chromosome Aberrations, Mycosis Fungoides diagnosis, Mycosis Fungoides genetics, Skin Neoplasms diagnosis, Skin Neoplasms genetics
- Abstract
Mycosis fungoides is the most common type of primary cutaneous lymphomas. The phenotype of the tumor cell corresponds to an effector/memory-type of helper T cell which, given its repertoire of homing receptors, is specialized for recirculation through the skin. In recent years genetic analyses have uncovered various chromosomal aberrations in the tumour cells of mycosis fungoides. Their relevance to the pathogenesis and clinical appearance are discussed in the following., (© The Authors • Journal compilation © Blackwell Verlag GmbH, Berlin.)
- Published
- 2011
- Full Text
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56. Genomic loss of the putative tumor suppressor gene E2A in human lymphoma.
- Author
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Steininger A, Möbs M, Ullmann R, Köchert K, Kreher S, Lamprecht B, Anagnostopoulos I, Hummel M, Richter J, Beyer M, Janz M, Klemke CD, Stein H, Dörken B, Sterry W, Schrock E, Mathas S, and Assaf C
- Subjects
- Base Sequence, Basic Helix-Loop-Helix Transcription Factors genetics, Cell Cycle genetics, Cell Line, Cell Proliferation, Comparative Genomic Hybridization, Cyclin-Dependent Kinase 6 metabolism, DNA Primers genetics, Electrophoretic Mobility Shift Assay, Flow Cytometry, Gene Expression Profiling, Genes, T-Cell Receptor beta genetics, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Leukocytes, Mononuclear, Molecular Sequence Data, Proto-Oncogene Proteins c-myc metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, ras Proteins metabolism, Basic Helix-Loop-Helix Transcription Factors deficiency, Gene Deletion, Gene Expression Regulation, Neoplastic genetics, Genome, Human genetics, Sezary Syndrome genetics, Signal Transduction genetics
- Abstract
The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity.
- Published
- 2011
- Full Text
- View/download PDF
57. Evaluation of T-cell clonality in archival skin biopsy samples of cutaneous T-cell lymphomas using the biomed-2 PCR protocol.
- Author
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Lukowsky A, Muche JM, Möbs M, Assaf C, Humme D, Hummel M, Sterry W, and Steinhoff M
- Subjects
- Biopsy, Humans, Lymphoma, T-Cell, Cutaneous pathology, Paraffin Embedding, Receptors, Antigen, T-Cell, alpha-beta genetics, Receptors, Antigen, T-Cell, gamma-delta genetics, Sensitivity and Specificity, Lymphoma, T-Cell, Cutaneous diagnosis, Pathology, Molecular methods, Polymerase Chain Reaction methods, Skin pathology, T-Lymphocytes
- Abstract
Recently, several European centers of lymphoma diagnosis and research developed various polymerase chain reaction (PCR) methods for clonality analysis in suspect T-cell and B-cell proliferations (Biomed-2 Concerted Action). They have mainly been applied to frozen material of systemic B-cell and T-cell malignancies. Thus far, only limited data exist with regard to cutaneous T-cell lymphoma (CTCL) and paraffin-embedded material. Thus, we applied the Biomed-2 T-cell receptor (TCR) gamma and TCRbeta PCR as well as an in-house TCRgamma PCR to a collection of 107 archival skin samples (84 CTCL, 3 systemic TCL and 20 controls). As a result, the Biomed-2 TCRgamma PCR revealed 81% clonality, the in-house TCRgamma method revealed 86% clonality, and the Biomed-2 TCRbeta revealed 78% clonality in CTCL samples generating at least the 300 bp fragment in the Biomed-2 control PCR. We found clonal TCRbeta rearrangements in 5 of 17 CTCL samples that were polyclonal in the Biomed-2 TCRgamma PCR. By combining all Biomed-2 assays, one or more clonal rearrangements were detected in 87% of CTCL and in all 3 systemic TCLs. By combining all TCR PCR assays applied here, clonality was shown in 90% of the CTCL cases. In conclusion, we showed that the Biomed-2 TCR PCR worked well with DNA from paraffin-embedded tissue, revealing a high-clonality detection rate in CTCL, and thus should be highly recommended for routine molecular analysis. In addition, the performance of our in-house TCRgamma assay verifies our previously published findings on clonally expanded T-cells in CTCL.
- Published
- 2010
- Full Text
- View/download PDF
58. Diagnostic tools in Sezary syndrome.
- Author
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Möbs M, Knott M, Fritzen B, Pullmann S, Sterry W, and Assaf C
- Subjects
- Gene Rearrangement, T-Lymphocyte, Humans, Sezary Syndrome genetics, Skin Neoplasms genetics, Sezary Syndrome pathology, Skin Neoplasms pathology
- Abstract
Primary cutaneous T-cell lymphomas (CTCL) mycosis fungoides (Mf) and Sézary syndrome (SS) belong to the group of non-Hodgkin lymphomas which are characterized by clonally proliferating CD4+ cells localized in the skin. SS is a leukemic variant of CTCL and is characterized by erythroderma, generalized lymphadenopathy, and circulating atypical T-cells with cerebriform nuclei, so-called Sézary cells. Palmoplantar hyperkeratosis, generalized alopecia, and severe pruritus are additional symptoms that are associated with SS. Patients have a poor prognosis with an estimated five year survival of 12.5 to 27 percent and estimated median survival of 14.5 to 18 months. The incidence of MF and also SS has increased with time and may be in part due to improved clinical awareness and especially advances in diagnostic testing.
- Published
- 2010
59. Zanolimumab, a human monoclonal antibody targeting CD4 in the treatment of mycosis fungoides and Sézary syndrome.
- Author
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Mestel DS, Beyer M, Möbs M, Steinhoff M, Sterry W, and Assaf C
- Subjects
- Antibodies, Monoclonal immunology, Antibodies, Monoclonal pharmacology, Antibodies, Monoclonal, Humanized, Clinical Trials as Topic, Humans, Quality of Life, Antibodies, Monoclonal therapeutic use, CD4 Antigens immunology, Mycosis Fungoides therapy, Sezary Syndrome therapy
- Abstract
Background: The most common type of primary cutaneous T cell-lymphomas (CTCLs), which are characterised by a clonal proliferation of malignant skin-homing CD4(+) lymphocytes, is mycosis fungoides (MF) and its rare leukaemic variant Sézary syndrome (SS)., Objective: Zanolimumab is a high affinity human monoclonal IgG1k antibody, targeting the CD4-molecule. It exhibits cytotoxic and antiproliferative effects and has previously shown efficacy in CTCLs., Methods: Literature and reference research was done by using Pubmed and updates of ongoing studies were taken from American Society of Clinical Oncology (ASCO) and American Society of Hematology (ASH )annual meeting abstracts., Results: This article gives an overview about efficacy, tolerability and safety as well as chemistry, pharmacodynamics and pharmacokinetics of zanolimumab in the treatment of CTCLs.
- Published
- 2008
- Full Text
- View/download PDF
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