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通过抑制mTORC1信号通路完全清除人卵巢皮质组织碎片中的尤因肉瘤转移灶

Complete Purging of Ewing Sarcoma Metastases from Human Ovarian Cortex Tissue Fragments by Inhibiting the mTORC1 Signaling Pathway.

作者信息

Peek Ronald, Eijkenboom Lotte L, Braat Didi D M, Beerendonk Catharina C M

机构信息

Department of Obstetrics and Gynecology, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands.

出版信息

J Clin Med. 2021 Sep 24;10(19):4362. doi: 10.3390/jcm10194362.

Abstract

Restoration of fertility by autologous transplantation of ovarian cortex tissue in former cancer patients may lead to the reintroduction of malignancy via the graft. Pharmacological ex vivo purging of ovarian cortex fragments prior to autotransplantation may reduce the risk of reseeding the cancer. In this study we have investigated the capacity of Everolimus (EVE), an inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway, to eradicate Ewing's sarcoma (ES) from ovarian tissue by a short-term ex vivo treatment. Exposure of experimentally induced ES tumor foci in ovarian tissue to EVE for 24 h completely eliminated the malignant cells without detrimental effects on follicle morphology, survival or early folliculogenesis. This indicates that effective purging of ovarian cortex tissue from contaminating ES tumor foci is possible by short-term exposure to EVE.

摘要

对既往癌症患者进行卵巢皮质组织自体移植以恢复生育能力,可能会通过移植物再次引入恶性肿瘤。自体移植前对卵巢皮质碎片进行药理学体外净化,可能会降低癌症复发的风险。在本研究中,我们研究了雷帕霉素复合物1(mTORC1)信号通路抑制剂依维莫司(EVE)通过短期体外处理从卵巢组织中根除尤因肉瘤(ES)的能力。将实验诱导的卵巢组织中的ES肿瘤灶暴露于EVE 24小时,可完全消除恶性细胞,且对卵泡形态、存活或早期卵泡发生无不利影响。这表明通过短期暴露于EVE,可以有效地清除卵巢皮质组织中的ES肿瘤灶。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81b6/8509560/309a95168e7d/jcm-10-04362-g001.jpg

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