PDF(Pubmed)
Abstract：
BACKGROUND: Sexual dimorphism significantly influences cancer incidence and prognosis. Notably, females exhibit a lower risk and favorable prognosis for non-reproductive cancers compared to males, a pattern observable beyond the scope of risk behaviors such as alcohol consumption and smoking. Colorectal cancer, ranking third in global prevalence and second in mortality, disproportionately affects men. Sex steroid hormones, particularly estrogens and androgens, play crucial roles in cancer progression, considering epidemiological in vivo and in vitro, in general estrogens imparting a protective effect in females and androgens correlating with an increasing risk of colorectal cancer development.
METHODS: The hormonal impact on immune response is mediated by receptor interactions, resulting in heightened inflammation, modulation of NF-kB, and fostering an environment conducive to cancer progression and metastasis. These molecules also influence the enteric nervous system, that is a pivotal in neuromodulator release and intestinal neuron stimulation, also contributes to cancer development, as evidenced by nerve infiltration into tumors. Microbiota diversity further intersects with immune, hormonal, and neural mechanisms, influencing colorectal cancer dynamics. A comprehensive understanding of hormonal influences on colorectal cancer progression, coupled with the complex interplay between immune responses, microbiota diversity and neurotransmitter imbalances, underpins the development of more targeted and effective therapies.
CONCLUSIONS: Estrogens mitigate colorectal cancer risk by modulating anti-tumor immune responses, enhancing microbial diversity, and curbing the pro-tumor actions of the sympathetic and enteric nervous systems. Conversely, androgens escalate tumor growth by dampening anti-tumor immune activity, reducing microbial diversity, and facilitating the release of tumor-promoting factors by the nervous system. These findings hold significant potential for the strategic purposing of drugs to fine-tune the extensive impacts of sex hormones within the tumor microenvironment, promising advancements in colorectal cancer therapies.
METHODS: The hormonal impact on immune response is mediated by receptor interactions, resulting in heightened inflammation, modulation of NF-kB, and fostering an environment conducive to cancer progression and metastasis. These molecules also influence the enteric nervous system, that is a pivotal in neuromodulator release and intestinal neuron stimulation, also contributes to cancer development, as evidenced by nerve infiltration into tumors. Microbiota diversity further intersects with immune, hormonal, and neural mechanisms, influencing colorectal cancer dynamics. A comprehensive understanding of hormonal influences on colorectal cancer progression, coupled with the complex interplay between immune responses, microbiota diversity and neurotransmitter imbalances, underpins the development of more targeted and effective therapies.
CONCLUSIONS: Estrogens mitigate colorectal cancer risk by modulating anti-tumor immune responses, enhancing microbial diversity, and curbing the pro-tumor actions of the sympathetic and enteric nervous systems. Conversely, androgens escalate tumor growth by dampening anti-tumor immune activity, reducing microbial diversity, and facilitating the release of tumor-promoting factors by the nervous system. These findings hold significant potential for the strategic purposing of drugs to fine-tune the extensive impacts of sex hormones within the tumor microenvironment, promising advancements in colorectal cancer therapies.
摘要：
背景：性别二态显著影响癌症发病率和预后。值得注意的是,与男性相比，女性对非生殖癌症的风险较低，预后良好，一种超出危险行为范围的模式，如饮酒和吸烟。结直肠癌,全球患病率排名第三，死亡率排名第二，不成比例地影响男性。性类固醇激素,特别是雌激素和雄激素，在癌症进展中发挥关键作用，考虑到体内和体外的流行病学，一般来说，雌激素对女性具有保护作用，雄激素与结直肠癌发展风险增加相关。
方法：激素对免疫反应的影响是由受体相互作用介导的，导致炎症加剧，NF-kB的调制，营造有利于癌症进展和转移的环境。这些分子也影响肠神经系统，这是神经调质释放和肠道神经元刺激的关键，也有助于癌症的发展，如神经浸润到肿瘤中所证明。微生物多样性进一步与免疫相交，荷尔蒙，和神经机制，影响结直肠癌动力学。全面了解激素对结直肠癌进展的影响，再加上免疫反应之间复杂的相互作用，微生物群多样性和神经递质失衡，支持更有针对性和更有效的治疗方法的发展。
结论：雌激素通过调节抗肿瘤免疫反应来降低结直肠癌的风险，增强微生物多样性，并抑制交感神经和肠神经系统的促肿瘤作用。相反，雄激素通过抑制抗肿瘤免疫活性来促进肿瘤生长，减少微生物多样性，并促进神经系统释放肿瘤促进因子。这些发现为药物的战略目的提供了巨大的潜力，以微调性激素在肿瘤微环境中的广泛影响。结肠直肠癌治疗有希望的进展。
方法：激素对免疫反应的影响是由受体相互作用介导的，导致炎症加剧，NF-kB的调制，营造有利于癌症进展和转移的环境。这些分子也影响肠神经系统，这是神经调质释放和肠道神经元刺激的关键，也有助于癌症的发展，如神经浸润到肿瘤中所证明。微生物多样性进一步与免疫相交，荷尔蒙，和神经机制，影响结直肠癌动力学。全面了解激素对结直肠癌进展的影响，再加上免疫反应之间复杂的相互作用，微生物群多样性和神经递质失衡，支持更有针对性和更有效的治疗方法的发展。
结论：雌激素通过调节抗肿瘤免疫反应来降低结直肠癌的风险，增强微生物多样性，并抑制交感神经和肠神经系统的促肿瘤作用。相反，雄激素通过抑制抗肿瘤免疫活性来促进肿瘤生长，减少微生物多样性，并促进神经系统释放肿瘤促进因子。这些发现为药物的战略目的提供了巨大的潜力，以微调性激素在肿瘤微环境中的广泛影响。结肠直肠癌治疗有希望的进展。
