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铂敏感型高级别浆液性输卵管癌原位模型

An orthotopic model of platinum-sensitive high grade serous fallopian tube carcinoma.

作者信息

Khabele Dineo, Fadare Oluwole, Liu Annie Y, Wilson Andrew J, Wass Erika, Osteen Kevin, Crispens Marta A

机构信息

Department of Obstetrics and Gynecology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

出版信息

Int J Clin Exp Pathol. 2012;5(1):37-45. Epub 2011 Jan 1.

PMID:22295145
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3267484/
Abstract

Fallopian tube carcinoma (FTCA) is a very rare cancer type, but may be a useful platform for investigating high grade serous tumors of the pelvis that originate from a serous tubal intraepithelial carcinoma (STIC) precursor. Metastatic tumors from a patient diagnosed with Stage IIIC high grade serous FTCA (P0) were transplanted via intraperitoneal (IP) injection into a small cohort of mice (passage, P1). Patient information was obtained from the medical record. Tumors were grown, harvested and re-implanted or archived through P3. The P3 cohort was treated with saline (n=8) or cisplatin, 5 mg/kg (n=8), weekly for 4 weeks. After sacrifice, tumors from each passage and treatment group were passaged further, frozen or paraffin embedded. The patient underwent optimal cytoreductive surgery for Stage IIIC high grade serous FTCA in the presence of a STIC. The FTCA, areas of STIC and normal appearing FT stained positive for p53, PAX8, pH2AX and mib-1. The patient remained in remission 9 months after platinum-based chemotherapy. IP tumor propagation was readily achieved up to P3 in the mice. Similar to the patient, orthotopic tumors were identified along peritoneal and mesenteric surfaces. Tumor histopathological and molecular features were confirmed and maintained through P3. The P3 cisplatin-treated mice had fewer tumor implants, higher levels of pH2AX and lower levels of mib-1 expression compared to controls. This orthotopic model of platinum sensitive high grade serous FTCA is a viable platform to study the biology and treatment of FTCA and other STIC-related pelvic serous carcinomas.

摘要

输卵管癌(FTCA)是一种非常罕见的癌症类型,但可能是研究起源于浆液性输卵管上皮内癌(STIC)前体的盆腔高级别浆液性肿瘤的有用平台。一名被诊断为IIIC期高级别浆液性FTCA(P0)的患者的转移性肿瘤通过腹腔内(IP)注射移植到一小群小鼠中(传代,P1)。患者信息从病历中获取。肿瘤生长、收获后重新植入或存档至P3。P3队列用生理盐水(n = 8)或顺铂5 mg/kg(n = 8)治疗,每周一次,共4周。处死小鼠后,每个传代和治疗组的肿瘤进一步传代、冷冻或石蜡包埋。该患者在存在STIC的情况下接受了针对IIIC期高级别浆液性FTCA的最佳细胞减灭术。FTCA、STIC区域和外观正常的FT对p53、PAX8、pH2AX和mib-1染色呈阳性。该患者在铂类化疗后9个月仍处于缓解期。在小鼠中很容易实现IP肿瘤传代至P3。与患者相似,在腹膜和肠系膜表面发现了原位肿瘤。肿瘤的组织病理学和分子特征在P3之前得到确认并保持。与对照组相比,P3顺铂治疗的小鼠肿瘤植入物较少,pH2AX水平较高,mib-1表达水平较低。这种铂敏感的高级别浆液性FTCA原位模型是研究FTCA和其他STIC相关盆腔浆液性癌的生物学和治疗的可行平台。

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