Immunohistochemical profiling of caspase signaling pathways predicts clinical response to chemotherapy in primary nodal diffuse large B-cell lymphomas
| Autor: | Patty M. Jansen, Johan H. J. M. van Krieken, Jettie J.F. Muris, Saskia A. G. M. Cillessen, Joost J. Oudejans, N. Mehdi Jiwa, Hanneke C. Kluin-Nelemans, J. Alain Kummer, Wim Vos, Chad Gundy, Gert J. Ossenkoppele, Inge S. van Houdt, Chris J.L.M. Meijer |
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| Přispěvatelé: | Damage and Repair in Cancer Development and Cancer Treatment (DARE), Stem Cell Aging Leukemia and Lymphoma (SALL) |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Male
Genetics and epigenetic pathways of disease [NCMLS 6] CASP8 and FADD-Like Apoptosis Regulating Protein C-FLIP Apoptosis Biochemistry ACTIVATION Medicine ELDERLY-PATIENTS Caspase Etoposide Molecular diagnosis prognosis and monitoring [UMCN 1.2] INDUCED APOPTOSIS Aged 80 and over Caspase-9 Caspase 8 biology Caspase 3 Intracellular Signaling Peptides and Proteins DEATH Hematology Middle Aged Immunohistochemistry Caspase 9 XIAP Treatment Outcome Proto-Oncogene Proteins c-bcl-2 Caspases Female Lymphoma Large B-Cell Diffuse Poly(ADP-ribose) Polymerases Signal Transduction Adult EXPRESSION Lymphoma B-Cell Age-related aspects of cancer [ONCOL 2] Adolescent Immunology X-Linked Inhibitor of Apoptosis Protein Inhibitor of apoptosis Translational research [ONCOL 3] Humans NON-HODGKINS-LYMPHOMA REED-STERNBERG CELLS Aged Hereditary cancer and cancer-related syndromes [ONCOL 1] business.industry Proteins Cell Biology medicine.disease Antineoplastic Agents Phytogenic biology.protein Cancer research Caspase 10 FLICE-INHIBITORY PROTEIN business Diffuse large B-cell lymphoma RESISTANCE |
| Zdroj: | Blood, 105, 2916-23 Blood, 105(7), 2916-2923. AMER SOC HEMATOLOGY Blood, 105, 7, pp. 2916-23 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | Contains fulltext : 47593.pdf (Publisher’s version ) (Closed access) We used biopsy specimens of primary nodal diffuse large B-cell lymphoma (DLBCL) to investigate whether the inhibition of caspase 8 and/or 9 apoptosis signaling pathways predicts clinical outcome. Expression levels of cellular FLICE inhibitory protein (c-Flip) and numbers of active caspase 3-positive lymphoma cells were used to determine the status of the caspase 8-mediated pathway. Expression levels of Bcl-2 and X-linked inhibitor of apoptosis (XIAP) were used to determine the status of the caspase 9-mediated pathway. Expression of c-Flip, XIAP, Bcl-2, and caspase 3 activity all provided prognostic information. According to these immunohistochemical parameters, inhibition of either or both caspase signaling pathways was detected in all patients. Three groups of patients were identified, one with a caspase 8 inhibition profile, one with caspase 8 and 9 inhibition profiles, and one with a caspase 9 inhibition profile. Caspase 9 inhibition was strongly associated with poor response to chemotherapy and usually with fatal outcome, whereas caspase 8 inhibition was associated with excellent clinical outcome. Thus, our data strongly suggest that inhibition of the caspase 9-mediated pathway, but not the caspase 8-mediated pathway, is a major cause for therapy resistance in patients with nodal DLBCL. |
| Databáze: | OpenAIRE |
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