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结直肠癌发生和生长中的自催化组织聚合反应机制

Autocatalytic Tissue Polymerization Reaction Mechanism in Colorectal Cancer Development and Growth.

作者信息

Boman Bruce M, Guetter Arthur, Boman Ryan M, Runquist Olaf A

机构信息

Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Newark, DE 19718, USA.

Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.

出版信息

Cancers (Basel). 2020 Feb 17;12(2):460. doi: 10.3390/cancers12020460.

Abstract

The goal of our study was to measure the kinetics of human colorectal cancer (CRC) development in order to identify aberrant mechanisms in tissue dynamics and processes that contribute to colon tumorigenesis. The kinetics of tumor development were investigated using age-at-tumor diagnosis (adenomas and CRCs) of familial adenomatous coli (FAP) patients and sporadic CRC patients. Plots of age-at-tumor diagnosis data as a function of age showed a distinct sigmoidal-shaped curve that is characteristic of an autocatalytic reaction. Consequently, we performed logistics function analysis and found an excellent fit ( < 0.05) of the logistic equation to the curves for age-at-tumor diagnoses. These findings indicate that the tissue mechanism that becomes altered in CRC development and growth involves an autocatalytic reaction. We conjecture that colonic epithelium normally functions as a polymer of cells which dynamically maintains itself in a steady state through an autocatalytic polymerization mechanism. Further, in FAP and sporadic CRC patients, mutation in the adenomatous polyposis coli () gene increases autocatalytic tissue polymerization and induces tumor tissues to autocatalyze their own progressive growth, which drives tumor development in the colon.

摘要

我们研究的目的是测量人类结直肠癌(CRC)发展的动力学,以确定组织动力学和过程中导致结肠肿瘤发生的异常机制。利用家族性腺瘤性息肉病(FAP)患者和散发性CRC患者肿瘤诊断时的年龄(腺瘤和CRC)来研究肿瘤发展的动力学。肿瘤诊断年龄数据作为年龄的函数绘制的曲线显示出一条独特的S形曲线,这是自催化反应的特征。因此,我们进行了逻辑函数分析,发现逻辑方程与肿瘤诊断年龄曲线拟合良好(<0.05)。这些发现表明,在CRC发展和生长过程中发生改变的组织机制涉及自催化反应。我们推测,结肠上皮通常作为细胞聚合物发挥作用,通过自催化聚合机制动态维持自身的稳态。此外,在FAP和散发性CRC患者中,腺瘤性息肉病大肠杆菌()基因突变增加了自催化组织聚合,并诱导肿瘤组织自催化其自身的渐进性生长,从而推动结肠肿瘤的发展。

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