학술논문

Histologic and molecular analysis of patient derived xenografts of high-grade serous ovarian carcinoma
Document Type
Report
Source
Journal of Hematology & Oncology. September 21, 2016, Vol. 9 Issue 1
Subject
Chemotherapy -- Research -- Health aspects -- Usage
Xenotransplantation -- Usage -- Health aspects -- Research
Cancer -- Chemotherapy
Ovarian cancer -- Research -- Diagnosis -- Care and treatment
Health
Health care industry
Diagnosis
Care and treatment
Usage
Research
Health aspects
Language
English
ISSN
1756-8722
Abstract
Background Patient derived xenografts (PDX) are generated by transplanting the original patient's tumor tissue into immune-deficient mice. Unlike xenograft models derived from cell lines, PDX models can better preserve the histopathology from the original patient and molecular pathways. High-grade serous carcinoma (HGSC) is a deadly form of ovarian/fallopian tube cancer whose response to current chemotherapies varies widely due to patient variability. Therefore, a PDX model can provide a valuable tool to study and test treatment options for each individual patient. Methods In this study, over 200 PDX tumors from nine HGSC were analyzed to investigate the nature and behavior of PDX tumors originating from HGSC. PDX tumors were serially passaged (from P0 to P4) and tumors were grafted orthotopically under the ovarian bursa or subcutaneously. Results Comparative analysis of the histology and molecular markers of tumors from over 200 PDX tumor-bearing mice, revealed that the tumors maintained similar histologies, stem cell populations, and expression for the majority of the tested oncogenic markers, compared to the primary tumors. However, a significant loss of steroid hormone receptors and altered expression of immunoresponsive genes in PDX tumors were also noted. Conclusion Our findings provide substantial new information about PDX tumor characteristics from HGSC which will be valuable towards the development of personalized therapy and new drug development for HGSC. Keywords: High-grade serous carcinoma, Patient-derived xenograft, Intrabursal engraft histology, Immunohistochemistry
Author(s): Ruifen Dong[sup.1,2] , Wenan Qiang[sup.1,3] , Haiyang Guo[sup.5] , Xiaofei Xu[sup.1,2] , J. Julie Kim[sup.3] , Andrew Mazar[sup.4] , Beihua Kong[sup.2] and Jian-Jun Wei[sup.1,3] Background Epithelial ovarian cancer (EOC) [...]