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化学诱导的散发性结直肠癌啮齿动物模型概述:组织病理学和转化视角。

An overview of chemically induced rodent models for sporadic colorectal cancer: Histopathological and translational perspectives.

机构信息

Department of Pathology, Botucatu Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil.

Experimental Research Unit (UNIPEX), Multimodel Drug Screening Platform - Laboratory of Chemically Induced and Experimental Carcinogenesis (MDSP-LCQE), Botucatu Medical School, São Paulo State University (UNESP), Botucatu, SP, Brazil.

出版信息

Histol Histopathol. 2024 Jun;39(6):691-702. doi: 10.14670/HH-18-692. Epub 2023 Dec 18.

Abstract

Globally, colorectal cancer (CRC) is one of the most frequently diagnosed human gastrointestinal neoplasia and the second leading cause of cancer-related death in both men and women. Despite considerable efforts currently devoted to the study of the biology and treatment of CRC, patient prognosis and survival are still poor. Sporadic CRC is a complex multistep disease and usually emerges in the setting of lifestyle and dietary changes mainly observed in industrialized countries with high human development index (HDI) (westernized style). The molecular pathogenesis of sporadic CRC presents genetic heterogeneity with and mutations usually detected during the progression of this malignancy. The establishment of sporadic CRC models has become essential for both basic and translational research to improve our understanding of the pathophysiology, unravel new molecular drivers, and preventive/therapeutic improvement of this malignancy. Chemically induced rodent models of sporadic CRC recapitulate most key morphological and genetic/epigenetic events observed during the promotion and progression of this malignancy, establishing effective diagnostic and prevention strategies to be translated into clinical practice. The present review gathers the main features of the state-of-the-art evidence on chemically induced rodent models, widely applied for translational modelling of sporadic CRC with a specific focus on histopathology and prevention perspectives. Our narrative review reinforces the persistent value of these bioassays and encourages the use of multimodel strategies for further investigations.

摘要

在全球范围内,结直肠癌(CRC)是最常见的人类胃肠道肿瘤之一,也是男性和女性癌症相关死亡的第二大主要原因。尽管目前人们在研究 CRC 的生物学和治疗方面做出了相当大的努力,但患者的预后和生存率仍然很差。散发性 CRC 是一种复杂的多步骤疾病,通常在生活方式和饮食变化的背景下出现,这些变化主要发生在人类发展指数(HDI)较高的工业化国家(西化模式)。散发性 CRC 的分子发病机制具有遗传异质性,通常在这种恶性肿瘤的进展过程中检测到 和 突变。散发性 CRC 模型的建立对于基础研究和转化研究都至关重要,这有助于我们更好地理解其病理生理学,揭示新的分子驱动因素,并改善这种恶性肿瘤的预防/治疗效果。化学诱导的散发性 CRC 啮齿动物模型再现了在这种恶性肿瘤的促进和进展过程中观察到的大多数关键形态学和遗传/表观遗传事件,为转化到临床实践中建立有效的诊断和预防策略提供了依据。本综述汇集了关于化学诱导的散发性 CRC 啮齿动物模型的最新证据的主要特征,这些模型广泛应用于散发性 CRC 的转化模型研究,特别关注组织病理学和预防视角。我们的叙述性综述强调了这些生物测定法的持续价值,并鼓励使用多模型策略进行进一步研究。

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