Breast cancer organoids from a patient with giant papillary carcinoma as a high-fidelity model

Breast cancer organoids from a patient with giant papillary carcinoma as a high-fidelity model
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来自巨大乳头状癌患者的乳腺癌类器官作为高保真模型

DOI:
10.1186/s12935-020-01171-5
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发表时间:
2020-03-18
影响因子:
5.8
通讯作者:
Zhao, Zuowei
Zhao, Zuowei
中科院分区:
医学2区
文献类型:
--
作者:
Li, Xuelu;Pan, Bo;Zhao, Zuowei

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背景乳头状癌是一种少见的乳腺癌。此外,巨大乳腺乳头状癌患者在临床实践中极为罕见。为了提高对这些患者的治疗效果,迫切需要探索生物学和临床相关模型的疾病,以发现有效的drugs.MethodsWe收集手术肿瘤标本,从一个63岁的中国妇女已被诊断为乳腺乳头状癌。结果经H&E染色鉴定,乳头状癌类器官符合原发肿瘤的组织学特征,免疫组化检测,乳头状癌类器官中雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体(HER 2)和抗原Ki-67(Ki 67)。此外,我们进行了三维药物筛选,以检查内分泌药物(氟维司群,他莫昔芬)和靶向治疗药物(Palbociclib,依维莫司,BKM 120)在模拟体内环境中对乳腺乳头状癌的影响。我们的乳腺乳头状癌类器官的药物敏感性研究如下,氟维司群(IC500.275 μmol),帕博西尼(IC502.21 μmol),BKM 120(IC503.81 μmol),依维莫司(IC 504.45 μmol),Tamoxifen(IC 5019.13 μmol)。结论本实验结果表明,3-羟基-2-甲基-2-(4-甲基-2-苯基)-3-(4-甲基-2-苯基)-2-(体外培养乳腺乳头状癌患者的乳腺癌类器官可用于确定可能的治疗方法,并可普遍应用于探索乳腺乳头状癌的临床病理特征。
BackgroundPapillary carcinoma is an uncommon type of breast cancer. Additionally, patients with huge breast papillary carcinoma are extremely rare in clinical practice. To improve therapeutic effect on such patients, it is urgent to explore biologically and clinically relevant models of the disease to discover effective drugs.MethodsWe collected surgical tumor specimens from a 63-year-old Chinese woman who has been diagnosed breast papillary carcinoma. The tumor was more than 15 cm in diameter, and applied to establish patient-derived papillary carcinoma organoids that could continuously propagate for more than 6 months.ResultsThe papillary carcinoma organoids matched the histological characteristics of orginal tumor by H&E staining identification, and maintained the expression of the breast cancer biomarkers by IHC, including estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor (HER2) and antigen Ki-67 (Ki67). In addition, we performed a 3-D drug screening to examine the effects of endocrine drugs (Fulvestrant, Tamoxifen) and targeted therapy drugs (Palbociclib, Everolimus, BKM120) on breast papillary carcinoma in the mimic in vivo environment. The drug sensitivities of our breast papillary carcinoma organoids were investigated as follows, Fulvestrant (IC500.275 μmol), Palbociclib (IC502.21 μmol), BKM120 (IC503.81 μmol), Everolimus (IC504.45 μmol), Tamoxifen (IC5019.13 μmol).ConclusionsThese results showed that an effective organoid platform for 3-D in vitro culture of breast cancer organoids from patients with breast papillary carcinoma could be used to identify possible treatments, and might be commonly applied to explore clinicopathological characteristics of breast papillary carcinoma.