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Title :Trabectedin arrests a doxorubicin-resistant PDGFRA-activated liposarcoma patient-derived orthotopic xenograft (PDOX) nude mouse model
Authors :Kiyuna, Tasuku
Tome, Yasunori
Murakami, Takashi
Kawaguchi, Kei
Igarashi, Kentaro
Miyake, Kentaro
Miyake, Masuyo
Li, Yunfeng
Nelson, Scott D.
Dry, Sarah M.
Singh, Arun S.
Russell, Tara A.
Elliott, Irmina
Singh, Shree Ram
Kanaya, Fuminori
Eilber, Fritz C.
Hoffman, Robert M.
Issue Date :20-Aug-2018
Abstract :Background: Pleomorphic liposarcoma (PLPS) is a rare, heterogeneous and an aggressive variant of liposarcoma. Therefore, individualized therapy is urgently needed. Our recent reports suggest that trabectedin (TRAB) is effective against several patient-derived orthotopic xenograft (PDOX) mouse models. Here, we compared the efficacy of first-line therapy, doxorubicin (DOX), and TRAB in a platelet-derived growth factor receptor-α (PDGFRA)-amplified PLPS. Methods: We used a fresh sample of PLPS tumor derived from a 68-year-old male patient diagnosed with a recurrent PLPS. Subcutaneous implantation of tumor tissue was performed in a nude mouse. After three weeks of implantation, tumor tissues were isolated and cut into small pieces. To match the patient a PDGFRA-amplified PLPS PDOX was created in the biceps femoris of nude mice. Mice were randomized into three groups: Group 1 (G1), control (untreated); Group 2 (G2), DOX-treated; Group 3 (G3), TRAB-treated. Measurement was done twice a week for tumor width, length, and mouse body weight. Results: The PLPS PDOX showed resistance towards DOX. However, TRAB could arrest the PLPS (p < 0.05 compared to control; p < 0.05 compared to DOX) without any significant changes in body-weight. Conclusions: The data presented here suggest that for the individual patient the PLPS PDOX model could specifically distinguish both effective and ineffective drugs. This is especially crucial for PLPS because effective first-line therapy is harder to establish if it is not individualized.
URL :https://doi.org/10.1186/s12885-018-4703-0
Type Local :雑誌掲載論文
ISSN :1471-2407
Publisher :Springer Nature
URI :http://hdl.handle.net/20.500.12000/47548
Citation :BMC Cancer Vol.18
Appears in Collections:Peer-reviewed Journal Articles (Faculty of Medicine)

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