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慢性应激与肿瘤的发生与演进

刘明心 谢雪梅 李强 许川

刘明心, 谢雪梅, 李强, 等. 慢性应激与肿瘤的发生与演进[J]. 四川大学学报(医学版), 2021, 52(1): 39-44. doi: 10.12182/20210160203
引用本文: 刘明心, 谢雪梅, 李强, 等. 慢性应激与肿瘤的发生与演进[J]. 四川大学学报(医学版), 2021, 52(1): 39-44. doi: 10.12182/20210160203
LIU Ming-xin, XIE Xue-mei, LI Qiang, et al. A Review of Chronic Stress and the Initiation and Evolution of Cancer[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 39-44. doi: 10.12182/20210160203
Citation: LIU Ming-xin, XIE Xue-mei, LI Qiang, et al. A Review of Chronic Stress and the Initiation and Evolution of Cancer[J]. JOURNAL OF SICHUAN UNIVERSITY (MEDICAL SCIENCE EDITION), 2021, 52(1): 39-44. doi: 10.12182/20210160203

栏目: 综 述

慢性应激与肿瘤的发生与演进

doi: 10.12182/20210160203
基金项目: 国家自然科学基金(No. 81873048)资助
详细信息
    作者简介:

    许川,教授,博士研究生导师,副主任医师,现任电子科技大学医学院附属肿瘤医院/四川省肿瘤医院临床研究中心主任。任中国临床肿瘤学会(CSCO)转化医学专家委员会常务委员、中国抗癌协会肿瘤支持治疗专业委员会委员、中国临床肿瘤学会(CSCO)患者教育专家委员会委员、中国医药教育协会肺癌医学教育委员会常务委员、中国抗癌协会(CACA)肿瘤营养专业委员会肿瘤免疫营养学组副组长、中国抗癌协会(CACA)肿瘤代谢专业委员会青年委员、细胞代谢与炎癌转化学组副组长、中国医学营养整合联盟理事、四川省抗癌协会理事会理事、国家自然科学基金青年与面上项目评审人。承担国家自然科学基金委、国家重点研发计划子课题、国家重点实验室科技开放项目及省部级、军队重点项目等科研课题十余项,负责维克森林大学转化医学科研项目1项;发表论文30余篇,参编专著4部,获得专利授权4项(PCT国际专利1项)。四川省海内外高层次人才引进“四川省特聘专家”、重庆市“巴渝学者”讲座教授,入选四川省杰出青年基金计划,电子科技大学青年人才学术托举工程杰出创新人才项目。获国家科学技术进步奖二等奖(2019年)、中华医学科技奖一等奖(2018年)。研究方向为肿瘤综合治疗、个体化与靶向治疗、免疫治疗等临床诊疗与转化医学

    通讯作者:

    E-mail:xuchuan100@163.com

A Review of Chronic Stress and the Initiation and Evolution of Cancer

More Information
  • 摘要: 慢性应激是指激活经典的下丘脑-垂体-肾上腺轴神经内分泌系统和交感神经系统而引发的机体持续非特异性适应性反应。现已证实,慢性应激可诱发肿瘤发生并促进肿瘤演进,特别是对机体的免疫功能和肿瘤微环境的重塑具有重要影响。然而,由于慢性应激自身机制复杂,个体耐受差异较大,导致其在肿瘤发生与演进中的研究证据尚不确切。因此,本文就慢性应激与肿瘤发生、演进的相关性研究进行综述,重点解析慢性应激促进肿瘤发生发展的分子机制,抑制机体免疫反应、重塑肿瘤免疫微环境的作用及机制,探讨健康人群与肿瘤患者的应激管理方案,以期为靶向慢性应激逆转肿瘤的新策略研究提供新的线索与方向。我们认为,靶向环磷酸腺苷/蛋白激酶A/环磷腺苷效应元件结合蛋白(cAMP/PKA/CREB)信号通路逆转肿瘤发生的治疗策略,应激、炎症与免疫以及肿瘤之间的关系,β受体拮抗剂的“抑癌”活性及其机制以及与不同联合治疗方案的选择,仍需进一步探索。健康的生活方式、积极的生活态度与专业的应激管理指导对肿瘤的防治来说至关重要。
  • 图  1  慢性应激参与肿瘤发生和发展的机制

    Figure  1.  The mechanism of chronic stress involved in tumor initiation and evolution

    A: Chronic stress promotes the occurrence and initiation of tumors by activating two classical stress pathways, hypothalamic-pituitary-adrenal axis (HPA axis) and sympathetic nervous system (SNS); B: Catecholamine promotes tumorigenesis through the cAMP/PKA/CREB signaling pathway. CRF: Corticotropin releasing factor; ACTH: Adrenocorticotropic hormone; βARs: β Adrenergic receptors; VEGF: Vascular endothelial growth factor; MMPs: Matrix metalloproteinases; PKA: Proteinkinase A.

    图  2  慢性应激抑制免疫应答,重塑肿瘤免疫微环境

    Figure  2.  Chronic stress inhibits the immune response and reshapes the tumor tomor immune microenvironment

    A: Immunotherapy can induce tumor cells releasing tumor-associated antigens, which subsequently activate dendritic cells (DCs) and cytotoxic T lymphocytes (CTLs) and ultimately kill tumor cells; B: Under chronic stress, glucocorticoids inhibit secretion of tumor-associated antigens and cytotoxic function of CTLs through multiple mechanisms, including down-regulation of interferon β and chemokine lignad 1/9/10 (CXCL1/9/10), etc.. HSP90: Heat shock proteins 90; IFN-γ: Interferon-γ.

    表  1  全身适应综合征

    Table  1.   General adaptation syndrome (GAS)

    StageTime of occurrenceCharacteristicsSignificance
    Alarm Appear after stress immediately Activating the sympathetic- adrenal medulla system;Increasing adrenal corticosteroids Defense mechanism;Last for a short time
    Resistance Appear after the warning response High level secretion of adrenal corticosteroids Increase the metabolic rate; Weaken inflammation and immune response
    Exhaustion Appears after stimulation of continuous and intensive stressors Continuous increase in levels of adrenal corticosteroids; Decrease in the number and affinity of glucocorticoid receptors The negative effects of the stress response start to appear, such as the related diseases, declined of organ function, even shock or death may occur
     It is not necessarily to occur in the same order, most of stressors only induce the appearance of alarm stage or resistance stage.
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  • 收稿日期:  2020-11-22
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