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| Establishment and identification of animal model of ovarian cancer xeno-transplantation#br# |
| LI Wei WANG Jiao SU Li▲ MIAO Jinwei WU Yumei |
| Department of Gynecologic Oncology, Beijing Obstetrics and Gynecology Hospital, Capital Medical University Beijing Maternal and Child Health Care Hospital, Beijing 100071, China |
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Abstract Objective To construct a patient-derived tumor xenograft (PDX) model for ovarian cancer research and individualized treatment. Methods Fresh surgically resected specimens from 10 patients with ovarian cancer (P0 generation) in Beijing Obstetrics and Gynecology Hospital, Capital Medical University from July 2017 to July 2018 were collected and it was inoculated to 30 non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice and one tumor tissue sample was inoculated subcutaneously in axillary back of three NOD/SCID mice. Tumor growth was monitored after inoculation and tumor subgeneration transplantation was performed (150 mice from P1 to 4 generations totally). At the end of passage, the pathological and immunohistochemical staining of transplanted tumor tissues were analyzed to verify the model construction. Results Specimens were successfully inoculated in four patients, and the success rate was 40%. A total of 110 ovarian cancer models were successfully constructed in generations P1 to 4, and the success rates of each generation were 26.6%, 83.3%, 88.3%, and 80.1%, respectively. After tumor tissue inoculation, the body weight of mice did not decrease significantly, but increased slowly after seven to ten days. Tumor histopathology showed that the transplanted tumor was roughly spherical in appearance, slightly hard in texture, with complete capsule and visible vascular texture on the surface. After dissection, the section was milky white and cystic. Some tumors contained mucus, and some tumors had liquefaction areas. Hematoxylin-eosin staining showed luminal glandular structure, irregular shape, less stroma, obvious atypia of epithelial cells, obvious nucleoli, and pathological mitosis, which was basically consistent with the structure and atypia of human ovarian cancer cells. Immunohistochemical staining showed positive expression of estrogen receptor, progesterone receptor, P53, P16, Ki67, WT1, and Pax8, while negative expression of vimentin, which was highly consistent with the tumor tissue from the patient. Conclusion The ovarian cancer PDX animal model has been successfully constructed, which provides a platform for clinical research and choosing individual treatment for ovarian cancer patients.
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[1] Dobbin ZC，Katre AA，Steg AD，et al. Using heterogeneity of the patient-derived xenograft model to identify the chemoresistant population in ovarian cancer [J]. Oncotarget，2014，5（18）：8750-8764.
[2] Narasimhulu DM，Khoury-Collado F，Chi DS. Radical surgery in ovarian cancer [J]. Curr Oncol Rep，2015，17（4）：439.
[3] Liu JF，Palakurthi S，Zeng Q，et al. Establishment of Patient-Derived Tumor Xenograft Models of Epithelial Ovarian Cancer for Preclinical Evaluation of Novel Therapeutics [J]. Clin Cancer Res，2017，23（5）：1263-1273.
[4] Hiroshima Y，Zhang Y，Zhang N，et al. Establishment of a Patient-Derived Orthotopic Xenograft（PDOX）Model of HER-2-Positive Cervical Cancer Expressing the Clinical Metastatic Pattern [J]. PlOS One，2015，10（2）：e0117417.
[5] Zhang P，Kovtun IV. Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts [J]. J Vis Exp，2020，（161）.doi：10.3791/60646.
[6] Magnotti E，Marasco WA. The latest animal models of ovarian cancer for novel drug discovery [J]. Expert Opin Drug Discov，2018，13（3）：249-257.
[7] Tudrej P，Kujawa KA，Cortez AJ，et al. Characteristics of in Vivo Model Systems for Ovarian Cancer Studies [J]. Diagnostics，2019，9（3）：120.
[8] Swick AD，Stein AP，Mcculloch TM，et al. Defining the boundaries and expanding the utility of head and neck cancer patient derived xenografts [J]. Oral Oncology，2017， 64：65-72.
[9] Zou JL，Liu Y，Wang JY，et al. Establishment and genomic characterizations of patient-derived esophageal squamous cell carcinoma xenograft models using biopsies for treatment optimization [J]. J Transl Med，2018，16（1）：15.
[10] Jung J，Jang K，Ju JM，et al. Novel cancer gene variants and gene fusions of triple-negative breast cancers（TNBCs）reveal their molecular diversity conserved in the patient-derived xenograft（PDX）model [J]. Cancer Letters，2018，428（1）：127-138.
[11] Burgenske DM，Monsma DJ，Mackeigan JP. Patient-derived xenograft models of colorectal cancer：procedures for engraftment and propagation [J]. Methods Mol Biol，2018，1765：307-314.
[12] Katsiampoura A，Raghav K，Jiang ZQ，et al. Modeling of patient derived xenografts in colorectal cancer [J].Mol Cancer Ther，2017，16（7）：1435-1442.
[13] Tamauchi S，Suzuki S，Xuboya C，et al. Establishment of a patient-derived xenograft model and cell line of malignant transformation of mature cystic teratoma of the ovary [J]. J Obstet Gynaecol Res，2021，47（2）：713-719.
[14] Vincent J，Craig SEL，Johansen ML，et al. Detection of Tumor-Specific PTPmu in Gynecological Cancer and Patient Derived Xenografts [J]. Diagnostics，2021，11（2）：181.
[15] Santiago-O’Farrill JM，Weroha SJ，Hou X，et al. Poly（adenosine diphosphate ribose）polymerase inhibitors induce autophagy-mediated drug resistance in ovarian cancer cells，xenografts，and patient-derived xenograft models [J]. Cancer，2020，126（4）：894-907.
[16] Gitto SB，Kim H，Rafail S，et al. An autologous humanized patient-derived-xenograft platform to evaluate immunotherapy in ovarian cancer [J]. Gynecol Oncol，2020， 156（1）：222-232.
[17] De Thaye E，Van de Vijver K，Van der Meulen J，et al. Establishment and characterization of a cell line and patient-derived xenograft （PDX） from peritoneal metastasis of low-grade serous ovarian carcinoma [J]. Sci Rep，2020， 10（1）：6688.
[18] Palmer AC，Plana D，Gao H，et al. A Proof of Concept for Biomarker-Guided Targeted Therapy against Ovarian Cancer Based on Patient-Derived Tumor Xenografts [J]. Cancer Res，2020，80（19）：4278-4287.
[19] Ito M，Hiramatsu H，Kobayashi K，et al. NOD/SCID/gamma(c)(null) mouse：An excellent recipient mouse model for engraftment of human cells [J]. Blood，2002，100（9）：3175-3182.
[20] Mortan CL，Honghton PJ. Establishment of human tumor xeno- grafts in immunodeficient mice [J]. Nat Protocol，2007，2（2）：247-250.
[21] Ibarrola-Villava M，Cervantes A，Bardelli A. Preclinical models for precision oncology [J]. Biochim Biophys Acta Rev Cancer，2018，1870（2）：239-246.
[22] Wu J，Zheng Y，Tian Q，et al. Establishment of patient-derived xenograft model in ovarian cancer and its influence factors analysis [J]. J Obstet Gynaecol Res，2019， 45（10）：2062-2073.
[23] Wang Z，Wang J，Fan J，et al. Risk factors for cervical intraepithelial neoplasia and cervical cancer in Chinese women：large study in Jiexiu，Shanxi Province，China [J]. J Cancer，2017，8（6）：924-932.
[24] Liu Y，Chanana P，Davila JI，et al. Gene expression differences between matched pairs of ovarian cancer patient tumors and patient-derived xenografts [J]. Sci Rep，2019，9（1）：6314.
[25] Li LY，Kim HJ，Park SA，et al. Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer [J]. Cancer Res Treat，2019， 51（3）：1117-1127. |
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