RESUMO
To establish precise diagnostic algorithms and standardised treatment of sarcomas in specialized centers, the interdisciplinary research group KoSar (sarcoma competence network) has been funded by German Cancer Aid. A sarcoma tissue repository and a diagnostic reference center have been set up, presently containing about 1000 accurately diagnosed sarcomas of different entities. Significant gene expression profiles for synovial sarcomas, leiomyosarcomas, myxoid liposarcomas and a small profile for myxofibrosarcomas as well as a new classification of angiosarcomas were defined. We systematically searched for activated signal transduction pathways in sarcoma cell lines and xenograft transplant models and candidate targets for molecular therapies were identified. Based on these results first clinical studies have been initiated by the German Interdisciplinary Sarcoma Study Group (GISG).
Assuntos
Sarcoma/genética , Sarcoma/patologia , Animais , Pesquisa Biomédica , Linhagem Celular Tumoral , Comportamento Cooperativo , Avaliação Pré-Clínica de Medicamentos , Fibrossarcoma/diagnóstico , Fibrossarcoma/tratamento farmacológico , Fibrossarcoma/genética , Fibrossarcoma/patologia , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Comunicação Interdisciplinar , Leiomiossarcoma/diagnóstico , Leiomiossarcoma/tratamento farmacológico , Leiomiossarcoma/genética , Leiomiossarcoma/patologia , Lipossarcoma Mixoide/diagnóstico , Lipossarcoma Mixoide/tratamento farmacológico , Lipossarcoma Mixoide/genética , Lipossarcoma Mixoide/patologia , Técnicas de Diagnóstico Molecular , Terapia de Alvo Molecular , Transplante de Neoplasias , Sarcoma/diagnóstico , Sarcoma/tratamento farmacológico , Sarcoma Sinovial/diagnóstico , Sarcoma Sinovial/tratamento farmacológico , Sarcoma Sinovial/genética , Sarcoma Sinovial/patologia , Transdução de Sinais/genéticaRESUMO
Interleukin (IL)-22 production triggered by innate immune mechanisms has been identified as key to efficient intestinal anti-bacterial host defence and preservation of homeostasis. We hypothesized that glucocorticoid therapy may impair IL-22 expression, which should promote intestinal epithelial damage with the potential of subsequent bacterial translocation. High-dose corticosteroid therapy in Crohn's disease has been associated with an increased rate of abscess formation and ultimately with a higher risk of developing postoperative infectious complications, including abdominal sepsis. Thus, we sought to investigate effects of the prototypic glucocorticoid dexamethasone on IL-22 production in the context of bacterial infection. Enhanced IL-22 plasma levels were detectable in rat sepsis. Moreover, heat-inactivated Staphylococcus epidermidis, used as a prototypic activator of innate immunity, induced robust production of IL-22 by human peripheral blood mononuclear cells (PBMC). Here, we report for the first time that dexamethasone mediates remarkable suppression of IL-22 as detected in S. epidermidis-activated PBMC and rat sepsis, respectively. The data presented herein suggest that insufficient IL-22 function may contribute to impaired intestinal host defence in the context of corticosteroid therapy.
