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雄性和雌性BALB/c小鼠临床前结肠癌模型的标准化:从癌前病变到肿瘤病变的宏观和微观特征

Standardization of a Preclinical Colon Cancer Model in Male and Female BALB/c Mice: Macroscopic and Microscopic Characterization from Pre-Neoplastic to Tumoral Lesions.

作者信息

Correa Elizabeth, Rendón Juan Pablo, Bedoya-Betancur Vanesa, Montoya Juliana, Duque Julian Muñoz, Naranjo Tonny W

机构信息

Medical and Experimental Mycology Group, CIB-UPB-UdeA-UDES, Corporación para Investigaciones Biológicas, Carrera 72 A # 78B-141, Medellin 050034, Colombia.

Pathobiology Research Group QUIRON, Faculty of Agricultural Sciences, Universidad de Antioquia, Calle 70 # 52-21, Medellin 050036, Colombia.

出版信息

Biomedicines. 2025 Apr 11;13(4):939. doi: 10.3390/biomedicines13040939.

Abstract

This study standardized a chemically induced colorectal cancer (CRC) model using azoxymethane (AOM) and dextran sodium sulfate (DSS) in BALB/c mice, replicating the progression from preneoplastic lesions to adenocarcinoma observed in human colorectal carcinogenesis. The CCR-AOM/DSS model was standardized in male and female BALB/c mice. Two protocols were tested. Subsequently, the positive control group was established with nine evaluation points. Tumor progression was characterized histopathologically and corroborated by methylene blue staining and scanning electron microscopy. Two cycles of 2% DSS combined with a single injection of AOM (10 mg/kg) were necessary to induce adenocarcinoma in 100% of the mice, with no significant sex-based differences in tumor development. Females showed earlier tumor susceptibility under certain protocols. Inflammatory processes played a critical role in tumorigenesis, with neutrophil infiltration and fibrosis observed. : The findings align with previous reports, emphasizing the influence of DSS cycles, molecular weight, and mouse strain on model outcomes. This standardized model provides a reliable platform for the preclinical evaluation of novel preventive and therapeutic strategies for CRC.

摘要

本研究在BALB/c小鼠中使用氧化偶氮甲烷(AOM)和葡聚糖硫酸钠(DSS)标准化了一种化学诱导的结直肠癌(CRC)模型,该模型复制了在人类结直肠癌发生过程中观察到的从癌前病变到腺癌的进展过程。CCR-AOM/DSS模型在雄性和雌性BALB/c小鼠中进行了标准化。测试了两种方案。随后,建立了具有九个评估点的阳性对照组。通过组织病理学对肿瘤进展进行了表征,并通过亚甲蓝染色和扫描电子显微镜得到了证实。两个周期的2% DSS与单次注射AOM(10 mg/kg)相结合,是在100%的小鼠中诱导腺癌所必需的,肿瘤发生在性别上无显著差异。在某些方案下,雌性小鼠表现出更早的肿瘤易感性。炎症过程在肿瘤发生中起关键作用,观察到中性粒细胞浸润和纤维化。研究结果与先前的报告一致,强调了DSS周期、分子量和小鼠品系对模型结果的影响。这种标准化模型为CRC新型预防和治疗策略的临床前评估提供了一个可靠的平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a8e1/12024726/cfc198601a29/biomedicines-13-00939-g001a.jpg

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