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Hokkaido University Collection of Scholarly and Academic Papers >
Graduate School of Medicine / Faculty of Medicine >
Peer-reviewed Journal Articles, etc >
Extramammary Paget's disease patient-derived xenografts harboring ERBB2 S310F mutation show sensitivity to HER2-targeted therapies
| Title: | Extramammary Paget's disease patient-derived xenografts harboring ERBB2 S310F mutation show sensitivity to HER2-targeted therapies |
| Authors: | Maeda, Takuya Browse this author | | Kitamura, Shinya Browse this author | | Nishihara, Hiroshi Browse this author | | Yanagi, Teruki Browse this author →KAKEN DB |
| Issue Date: | 3-Sep-2020 |
| Publisher: | Nature Publishing Group |
| Journal Title: | Oncogene |
| Volume: | 39 |
| Start Page: | 5867 |
| End Page: | 5875 |
| Publisher DOI: | 10.1038/s41388-020-01404-x |
| Abstract: | Although the prognosis of advanced extramammary Paget's disease (EMPD) is poor, there have been no preclinical research models for the development of novel therapeutics. This study aims to establish a preclinical research model for EMPD. We transplanted EMPD tissue into immunodeficient NOD/Scid mice. Histopathological and genetic analyses using a comprehensive cancer panel were performed. For in vivo preclinical treatments, trastuzumab, lapatinib, docetaxel, or eribulin were administered to patient-derived xenograft (PDX) models. Tissue transplanted from the EMPD patient was enlarged in NOD/Scid mice and was transplanted into further generations. Both the transplantation of PDX intonu/numice and the reanimation of the cryopreserved xenografted tumors in NOD/Scid mice were successful. We also established an EMPD-PDX-derived primary cell culture. Histopathologically, the xenografted tumors were positive for CK7, which was consistent with the patient's tumors. Genetically, the pathogenic mutationERBB2S310F was detected in the patient's tumors (primary intraepidermal lesion, metastatic lymph node) and was observed in the xenografted tumors even after continued passages. The xenografted tumors responded well to trastuzumab and lapatinib therapy. Also, cytotoxic agents (docetaxel and eribulin) were effective against the xenografted tumors. This PDX model (EMPD-PDX-H1) could be a powerful tool for the research and development of EMPD treatments. |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/80541 |
| Appears in Collections: | 医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 柳 輝希
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