Autor: |
Yukari Oda, Kaoru Niimi, Kosuke Yoshida, Satoshi Tamauchi, Akira Yokoi, Yuko Yasui, Yuki Nishiko, Mayu Shibata, Yusuke Shimizu, Masato Yoshihara, Yoshiki Ikeda, Nobuhisa Yoshikawa, Kimihiro Nishino, Eiko Yamamoto, Hiroaki Kajiyama |
Jazyk: |
angličtina |
Rok vydání: |
2023 |
Předmět: |
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Zdroj: |
BMC Cancer, Vol 23, Iss 1, Pp 1-12 (2023) |
Druh dokumentu: |
article |
ISSN: |
1471-2407 |
DOI: |
10.1186/s12885-023-11626-3 |
Popis: |
Abstract Background Non-gestational choriocarcinoma (NGC) is a rare subtype of malignant germ cell tumour and there is no consensus on its treatment. The lack of suitable preclinical models for NGC is a challenge in drug discovery research. Patient-derived xenograft (PDX) models recapitulate the tumour microenvironment of the original cancer tissue. Therefore, they have received considerable attention for studies on rare cancer. Here, we aimed to establish a PDX model from a patient with recurrent NGC. Methods Fresh NGC tumour tissue was immediately transplanted into a severely immune-deficient mouse (NOD.Cg-Prkdc scid 1l2rg tm1Wjl/SzJ) and maintained for more than three in vivo passages. Subsequently, we evaluated the molecular characteristics of the PDX model using immunohistochemistry, polymerase chain reaction, and RNA sequencing. Moreover, the PDX tumours were transplanted into BALB/c nude mice, and we evaluated their sensitivity for cisplatin and methotrexate. Results The PDX tumour maintained the morphological features of NGC. Moreover, Immunohistochemistry revealed that the human chorionic gonadotropin, cytokeratin 7, and EpCAM expression levels were similar to those in the primary tumour. Furthermore, serum human chorionic gonadotropin levels were elevated in both the primary tumour and the PDX models. Additionally, using PCR analysis with species-specific primers, we confirmed that the PDX tumour contained human genes and was derived from human tissue. Moreover, the gene expression profile of the NGC was compared with that of epithelial ovarian cancer samples and cell lines, and 568 dysregulated genes in the NGC were extracted. The expression of the dysregulated genes in PDX was significantly correlated with that in the primary tumour (R2 = 0.873, P |
Databáze: |
Directory of Open Access Journals |
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