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转移性卵巢颗粒细胞瘤的小鼠手术模型

A mouse surgical model for metastatic ovarian granulosa cell tumor.

作者信息

Nadeau Marie-Eve, Kaartinen M Johanna, Laguë Marie-Noëlle, Paquet Marilène, Huneault Louis M, Boerboom Derek

机构信息

Department of Clinical Sciences, College of Veterinary Medicine, University of Montréal, St Hyacinthe, Québec, Canada.

出版信息

Comp Med. 2009 Dec;59(6):553-6.

PMID:20034430
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2798836/
Abstract

We recently described a genetically engineered mouse model that develops ovarian granulosa cell tumors (GCTs) that mimic many aspects of the advanced human disease, including distant dissemination. However, because the primary tumors killed their hosts before metastases were able to form, the use of these mice to study metastatic disease required the development of a simple, reliable, and humane surgical protocol for the excision of large GCTs from debilitated mice. Here we describe a protocol involving multimodal anesthesia, tumor removal through ventral midline celiotomy and perioperative fluid therapy, and analgesia that led to the postoperative survival of more than 90% of mice, despite the removal of tumors representing as much as 10% of the animal's body weight. Intraabdominal recurrence of the GCT did not occur in surviving animals, but most developed pulmonary or adrenal metastases (or both) by 12 wk after surgery. We propose that this mouse model of metastatic GCT will serve as a useful preclinical model for the development of novel treatment modalities and diagnostic techniques. Furthermore, our results delineate anesthetic and surgical principles for the removal of large abdominal tumors from mice that will be applicable to other models of human cancers.

摘要

我们最近描述了一种基因工程小鼠模型,该模型会发展出卵巢颗粒细胞瘤(GCT),其模仿了晚期人类疾病的许多方面,包括远处转移。然而,由于原发性肿瘤在转移灶形成之前就杀死了宿主,因此使用这些小鼠来研究转移性疾病需要开发一种简单、可靠且人道的手术方案,用于从虚弱的小鼠身上切除大型GCT。在此,我们描述了一种方案,该方案涉及多模式麻醉、通过腹正中剖腹术切除肿瘤以及围手术期液体治疗和镇痛,尽管切除的肿瘤重达动物体重的10%,但仍使超过90%的小鼠术后存活。存活的动物未出现GCT腹腔内复发,但大多数在手术后12周时出现了肺部或肾上腺转移(或两者皆有)。我们认为,这种转移性GCT小鼠模型将作为开发新型治疗方法和诊断技术的有用临床前模型。此外,我们的结果阐明了从小鼠身上切除大型腹部肿瘤的麻醉和手术原则,这些原则将适用于其他人类癌症模型。

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引用本文的文献

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Anti-VEGFA Therapy Reduces Tumor Growth and Extends Survival in a Murine Model of Ovarian Granulosa Cell Tumor.抗血管内皮生长因子 A 治疗可减少卵巢颗粒细胞瘤小鼠模型中的肿瘤生长并延长生存期。
Transl Oncol. 2013 Jun 1;6(3):226-33. doi: 10.1593/tlo.13136. Print 2013 Jun.

本文引用的文献

1
Dysregulation of WNT/CTNNB1 and PI3K/AKT signaling in testicular stromal cells causes granulosa cell tumor of the testis.睾丸间质细胞中WNT/CTNNB1和PI3K/AKT信号通路失调会导致睾丸颗粒细胞瘤。
Carcinogenesis. 2009 May;30(5):869-78. doi: 10.1093/carcin/bgp051. Epub 2009 Feb 23.
2
Synergistic effects of Pten loss and WNT/CTNNB1 signaling pathway activation in ovarian granulosa cell tumor development and progression.Pten缺失与WNT/CTNNB1信号通路激活在卵巢颗粒细胞瘤发生发展中的协同作用。
Carcinogenesis. 2008 Nov;29(11):2062-72. doi: 10.1093/carcin/bgn186. Epub 2008 Aug 6.
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Clinical and pathological predictive factors in women with adult-type granulosa cell tumor of the ovary.卵巢成人型颗粒细胞瘤女性患者的临床及病理预测因素
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Granulosa cell tumor of the ovary.卵巢颗粒细胞瘤
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Ferret, rabbit, and rodent anesthesia.雪貂、兔子和啮齿动物麻醉。
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