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研究女性肥胖和乳腺癌的临床前模型:考虑因素、注意事项和工具。

Preclinical Models to Study Obesity and Breast Cancer in Females: Considerations, Caveats, and Tools.

机构信息

Department of Nutrition, Texas A&M University, College Station, TX, USA.

Department of Pathology, University of Oklahoma Health Science Center, Stephenson Cancer Center, Harold Hamm Diabetes Center, Oklahoma City, OK, USA.

出版信息

J Mammary Gland Biol Neoplasia. 2020 Dec;25(4):237-253. doi: 10.1007/s10911-020-09463-2. Epub 2020 Nov 4.

DOI:10.1007/s10911-020-09463-2
PMID:33146844
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8197449/
Abstract

Obesity increases the risk for breast cancer and is associated with poor outcomes for cancer patients. A variety of rodent models have been used to investigate these relationships; however, key differences in experimental approaches, as well as unique aspects of rodent physiology lead to variability in how these valuable models are implemented. We combine expertise in the development and implementation of preclinical models of obesity and breast cancer to disseminate effective practices for studies that integrate these fields. In this review, we share, based on our experience, key considerations for model selection, highlighting important technical nuances and tips for use of preclinical models in studies that integrate obesity with breast cancer risk and progression. We describe relevant mouse and rat paradigms, specifically highlighting differences in breast tumor subtypes, estrogen production, and strategies to manipulate hormone levels. We also outline options for diet composition and housing environments to promote obesity in female rodents. While we have applied our experience to understanding obesity-associated breast cancer, the experimental variables we incorporate have relevance to multiple fields that investigate women's health.

摘要

肥胖会增加乳腺癌的风险,并与癌症患者的不良预后相关。为了研究这些关系,人们使用了多种啮齿动物模型;然而,由于实验方法的关键差异以及啮齿动物生理学的独特方面,这些有价值的模型的实施方式存在差异。我们结合了肥胖和乳腺癌临床前模型开发和实施方面的专业知识,传播了将这些领域整合在一起的研究的有效实践。在这篇综述中,我们根据经验分享了模型选择的关键考虑因素,重点介绍了使用临床前模型研究肥胖与乳腺癌风险和进展之间关系的重要技术细节和技巧。我们描述了相关的小鼠和大鼠模型,特别是强调了乳腺肿瘤亚型、雌激素产生以及操纵激素水平的策略方面的差异。我们还概述了促进雌性啮齿动物肥胖的饮食组成和饲养环境的选择。虽然我们已经将经验应用于理解肥胖相关的乳腺癌,但我们纳入的实验变量与研究女性健康的多个领域都有关联。

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Breast Cancer Res. 2020 Jun 23;22(1):68. doi: 10.1186/s13058-020-01300-y.
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Association between BMI, vitamin D, and estrogen levels in postmenopausal women using adjuvant letrozole: a prospective study.使用辅助来曲唑的绝经后女性体重指数、维生素D与雌激素水平之间的关联:一项前瞻性研究。
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The Association between Obesity and Premenopausal Breast Cancer According to Intrinsic Subtypes - a Systematic Review.
巴多昔芬/共轭雌激素在肥胖相关乳腺癌风险模型中的代谢和转录效应
JCI Insight. 2025 Mar 6;10(8). doi: 10.1172/jci.insight.182694. eCollection 2025 Apr 22.
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Effects of follicle-stimulating hormone on energy balance and tissue metabolic health after loss of ovarian function.促卵泡生成素对卵巢功能丧失后能量平衡和组织代谢健康的影响。
Am J Physiol Endocrinol Metab. 2024 May 1;326(5):E626-E639. doi: 10.1152/ajpendo.00400.2023. Epub 2024 Mar 27.
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