a systems biology approach to characterize the regulatory networks leading to trabectedin resistance in an in vitro model of myxoid liposarcoma系统生物学的方法来描述监管网络导致trabectedin阻力在黏液样脂肪肉瘤的体外模型.pdfVIP

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2017-09-07 发布于上海
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a systems biology approach to characterize the regulatory networks leading to trabectedin resistance in an in vitro model of myxoid liposarcoma系统生物学的方法来描述监管网络导致trabectedin阻力在黏液样脂肪肉瘤的体外模型.pdf

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a systems biology approach to characterize the regulatory networks leading to trabectedin resistance in an in vitro model of myxoid liposarcoma系统生物学的方法来描述监管网络导致trabectedin阻力在黏液样脂肪肉瘤的体外模型

A Systems Biology Approach to Characterize the Regulatory Networks Leading to Trabectedin Resistance in an In Vitro Model of Myxoid Liposarcoma 1 2 1 1 1 3 Sarah Uboldi , Enrica Calura , Luca Beltrame , Ilaria Fuso Nerini , Sergio Marchini , Duccio Cavalieri , 1 4 4 5 1 Eugenio Erba , Giovanna Chiorino , Paola Ostano , Daniela D’Angelo , Maurizio D’Incalci *, Chiara Romualdi2 1 Department of Oncology, Mario Negri Institute for Pharmacological Research, Milan, Italy, 2 Department of Biology, University of Padova, Padova, Italy, 3 Department of Computational Biology, Research and Innovation Centre, San Michele all’Adige, Trento, Italy, 4 Fondazione Edo ed Elvo Tempia Valenta, Cancer Genomics Laboratory, Biella, Italy, 5 Experimental Endocrinology and Oncology, CNR, Naples, Italy Abstract Trabectedin, a new antitumor compound originally derived from a marine tunicate, is clinically effective in soft tissue sarcoma. The drug has shown a high selectivity for myxoid liposarcoma, characterized by the translocation t(12;16)(q13; p11) leading to the expression of FUS-CHOP fusion gene. Trabectedin appears to act interfering with mechanisms of transcription regulation. In particular, the transactivating activity of FUS-CHOP was found to be impaired by trabectedin treatment. Even after prolonged response resistance occurs and thus it is important to elucidate the mechanisms of resistance to trabectedin. To this end we developed and characterized a myxoid liposarcoma cell line resistant to trabectedin (402-91/ET), obtained by exposing the parent