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上皮性卵巢癌患者来源异种移植模型用于临床前研究。

Patient-Derived Xenograft Models of Epithelial Ovarian Cancer for Preclinical Studies.

机构信息

Department of Obstetrics and Gynecology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.

Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Cancer Res Treat. 2017 Oct;49(4):915-926. doi: 10.4143/crt.2016.322. Epub 2017 Jan 4.

Abstract

PURPOSE

Patient-derived tumor xenografts (PDXs) can provide more reliable information about tumor biology than cell line models. We developed PDXs for epithelial ovarian cancer (EOC) that have histopathologic and genetic similarities to the primary patient tissues and evaluated their potential for use as a platform for translational EOC research.

MATERIALS AND METHODS

We successfully established PDXs by subrenal capsule implantation of primary EOC tissues into female BALB/C-nude mice. The rate of successful PDX engraftment was 48.8% (22/45 cases). Hematoxylin and eosin staining and short tandem repeat analysis showed histopathological and genetic similarity between the PDX and primary patient tissues.

RESULTS

Patients whose tumors were successfully engrafted in mice had significantly inferior overall survival when compared with those whose tumors failed to engraft (p=0.040). In preclinical tests of this model, we found that paclitaxel-carboplatin combination chemotherapy significantly deceased tumor weight in PDXs compared with the control treatment (p=0.013). Moreover, erlotinib treatment significantly decreased tumor weight in epidermal growth factor receptor-overexpressing PDX with clear cell histology (p=0.023).

CONCLUSION

PDXs for EOC with histopathological and genetic stability can be efficiently developed by subrenal capsule implantation and have the potential to provide a promising platform for future translational research and precision medicine for EOC.

摘要

目的

与细胞系模型相比,患者来源的肿瘤异种移植(PDX)可以提供更可靠的肿瘤生物学信息。我们为卵巢上皮癌(EOC)开发了 PDX,其在组织病理学和遗传学上与原发患者组织相似,并评估了它们作为转化 EOC 研究平台的潜力。

材料和方法

我们通过将原发性 EOC 组织植入雌性 BALB/C-裸鼠的肾包膜下成功建立了 PDX。PDX 成功植入的比率为 48.8%(22/45 例)。苏木精和伊红染色和短串联重复分析显示 PDX 与原发患者组织之间在组织病理学和遗传学上具有相似性。

结果

与肿瘤未能植入的患者相比,肿瘤成功植入小鼠的患者总生存明显较差(p=0.040)。在该模型的临床前测试中,我们发现与对照治疗相比,紫杉醇-卡铂联合化疗显著降低了 PDX 中的肿瘤重量(p=0.013)。此外,表皮生长因子受体过表达的具有透明细胞组织学特征的 PDX 中,厄洛替尼治疗显著降低了肿瘤重量(p=0.023)。

结论

通过肾包膜下植入可以高效地开发具有组织病理学和遗传稳定性的 EOC PDX,并有可能为未来的转化研究和 EOC 的精准医学提供有前景的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68e4/5654149/8c2b2ba3f7cb/crt-2016-322f1.jpg

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