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肥胖相关癌症风险的小鼠模型

Murine Models of Obesity-Related Cancer Risk.

作者信息

Raji Lukmon M, Siddique Monowarul M, Bohm Margaret S, Pierre Joseph F, Playdon Mary C, Summers Scott A, Li Bing, Cook Katherine L, Murphy E Angela, Makowski Liza

机构信息

University of Tennessee Health Science Center, Memphis, Tennessee, United States.

University of Utah, Salt Lake City, Utah, United States.

出版信息

Cancer Prev Res (Phila). 2025 Jun 13. doi: 10.1158/1940-6207.CAPR-24-0545.

Abstract

Obesity is a global menace that has impacted over 14% of adults worldwide and over a third of Americans. Importantly, obesity is associated with an increased risk of over 13 types of cancer and worse outcomes, including increased mortality. This review focuses on the importance of considering obesity and metabolic dysfunction in cancer risk as part of the National Cancer Institute's funded consortium known as the Metabolic Dysfunction and Cancer Risk Program (MeDOC). It describes previous and ongoing mouse models used in studies conducted by MeDOC consortium members, as well as other relevant studies. Most cancer studies examine tumor progression, metastasis, or recurrence, which are consequences following tumor onset; however, this approach does not consider risk per se. To truly model cancer risk, parameters to measure include the quantification of cancer onset, measured as incidence or latency. Investigators must be cognizant of many factors in study design, including the choice of cancer model and genetic strain. Preclinical approaches addressing risk typically include genetically engineered mouse models or the administration of irritants or carcinogens. We also discuss the transplantation of cells or tumors such as allografts or xenografts, with a focus on tumor rejection or regression to approximate cancer risk, not cancer progression. Herein, we highlight two cancers, breast and colorectal cancer, where risk is associated with obesity and discussed varied murine model approaches, as well as key findings that explore cancer risk, prevention, or interception.

摘要

肥胖是一种全球威胁,影响着全球超过14%的成年人以及超过三分之一的美国人。重要的是,肥胖与13种以上癌症的风险增加以及更差的预后相关,包括死亡率上升。本综述重点关注将肥胖和代谢功能障碍纳入癌症风险考量的重要性,这是美国国立癌症研究所资助的名为代谢功能障碍与癌症风险项目(MeDOC)的联盟的一部分。它描述了MeDOC联盟成员所进行研究中使用的既往和正在进行的小鼠模型,以及其他相关研究。大多数癌症研究考察肿瘤进展、转移或复发,这些都是肿瘤发生后的后果;然而,这种方法并未考虑风险本身。为了真正模拟癌症风险,要测量的参数包括癌症发生的量化,以发病率或潜伏期来衡量。研究人员在研究设计中必须认识到许多因素,包括癌症模型和遗传品系的选择。解决风险的临床前方法通常包括基因工程小鼠模型或给予刺激物或致癌物。我们还讨论了细胞或肿瘤的移植,如同种异体移植或异种移植,重点是肿瘤排斥或消退以近似癌症风险,而非癌症进展。在此,我们重点介绍两种与肥胖相关风险的癌症,即乳腺癌和结直肠癌,并讨论了各种小鼠模型方法以及探索癌症风险、预防或拦截的关键发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c6/12289351/183d0e472795/nihms-2096129-f0001.jpg

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