肠道菌群失衡和结直肠癌关系的研究进展

结直肠癌是最常见的恶性肿瘤之一,发病率逐年上升.研究表明肠道菌群失衡在结直肠癌的发生中可能发挥重要作用,肠道菌群可能通过肠道黏膜屏障受损、慢性炎症反应、细菌酶和毒性代谢产物作用等多种机制促进肿瘤的发生.近年来通过无菌动物实验、基因敲除动物实验以及新一代的高通量测序使人们对肠道菌群和大肠癌间关系的认识不断深化,继而从不同角度提出肠道菌群失衡导致结直肠癌发病的作用模式,本文将结合相关作用模式从肠道菌群先后影响结直肠癌不同发病阶段的角度阐述结直肠癌发生、发展过程中的相关机制,为进一步认识结直肠癌的发病机制和结直肠癌的早期诊疗提供新的思路.     

中药防治肠道菌群相关性结直肠癌的研究进展

结直肠癌发病率和死亡率居我国全部恶性肿瘤的第 3 和第 5 位,严重威胁居民健康。结直肠癌病因复杂,其中 肠道微生态是影响癌变过程的关键环节。肠道菌群是维持人体胃肠道及机体健康的重要因素,肠道微生物病原体在结直肠 癌发病机制包括微生物代谢、宿主免疫和炎症途径的调节、氧化应激与抗氧化防御调节、细菌基因毒素等环节。传统中药 给药方式主要为口服,中药进入胃肠道后不可避免与肠道微生物发生相互作用。中药主要通过调节肠道菌群结构,从而调 节宿主免疫功能,以及氧化应激与抗氧化防御调节等途径实现防治结直肠癌的作用。实验研究证实,中药对肠道微生态系 统的平衡具有很好的保护作用,对菌群失调具有改善作用;中药可以提高宿主抗癌免疫反应以及通过调节肿瘤微环境下的 骨髓来源的细胞功能发挥抗肿瘤疗效;促进有氧培养菌的耐酸能力并抑制了厌氧培养菌的耐酸能力,从而增强了整体肠道 菌群的抗氧化性。另外,中药亦能改善微生物的代谢、减轻代谢性炎症,以及抑制产生大肠杆菌的体外和体内基因毒性, 中草药的药效成分经肠道微生物转化后发挥抗炎、镇痛和抗肿瘤等药理作用。综上,肠道菌群在部分结直肠癌的发生发展 中具有重要作用,调节肠道菌群是中医药防治结直肠癌的重要靶标。     

肿瘤微环境在结直肠癌中的研究进展

肿瘤微环境（tumor microenvironment,TME）是目前研究的热点领域,结直肠癌的发生发展是一个多因素、多阶段、多环节参与的复杂过程,在此过程中肿瘤微环境中各种成分之间的相互作用起重要作用。目前认为结直肠癌肿瘤微环境中主要由肠道菌群微环境、炎症微环境及缺氧微环境三者共同作用、相互协调。本文就肠道菌群微环境、缺氧微环境及炎症微环境与结直肠癌的研究进展作一综述。     

高脂饮食、肠道菌群代谢与结直肠癌

结直肠癌是全球常见恶性肿瘤之一,在西方国家尤其常见。饮食是结直肠癌的重要影响因素之一。近年来,随着 我国社会经济的不断发展,结直肠癌发病率出现了逐年上升以及年轻化的现象,推测可能与西方高脂饮食流行、肥胖、运动缺 乏等因素相关。高脂饮食与结直肠癌的发生发展紧密相关。高脂饮食可引起肠道菌群结构改变,具体表现为肠道微生态多样 性的下降,以及拟杆菌属菌丰度降低和厚壁菌门细菌的富集,同时还可对肠道菌群代谢产生重要影响,产生大量次级胆汁酸、 脂肪酸和硫化物衍生物等。其中,过量的次级胆汁酸具有促进结直肠肿瘤发生发展的作用。次级胆汁酸可引起肠道上皮细胞 DNA损伤,加剧炎症反应,同时还可促进肠道类干性样细胞‐Lgr5（+）细胞的增殖,从而促进结直肠癌的发生发展。本文将围绕 高脂饮食对结直肠癌发生发展的影响、膳食脂肪对肠道菌群的影响、膳食脂肪对肠道菌群代谢的影响,以及结直肠癌的饮食预 防进行介绍和讨论。     

肠道菌群在肿瘤进程中的作用及其临床研究进展

肠道菌群在调控宿主的生长、发育、营养代谢以及免疫稳态方面具有重要的作用.近年来研究发现,肿瘤患者,特别是结直肠癌患者的肠道菌群多呈现失调的状态,而肠道菌群失调能够通过影响肠道代谢、肠道稳态以及肠道免疫等方面促进或者抑制肿瘤的发生发展.目前,通过干预肠道菌群来进行肿瘤治疗的临床实践已经显示出了良好的疗效和巨大的潜能.本文主要论述肠道菌群在肿瘤发生发展进程中的作用及其机制,以及目前利用肠道菌群治疗肿瘤的相关临床研究进展.     

肠道菌群与结直肠癌关系研究进展*

人体肠道菌群代谢成分通过与受体结合、刺激炎症因子分泌,与其他变化一起,引起炎症反应,最终导致结直肠癌（colorectal cancer ,CRC ）的发生。而肠道内的益生菌则通过屏障作用、抑制DNA 损伤等机制保护肠道黏膜,抵御CRC 的发生,并可被用于预防及辅助治疗CRC 。胃肠道手术可以影响肠道菌群的代谢,影响微生态平衡。本文将针对肠道菌群与结直肠癌关系的最近进展进行综述。     

通过宏基因组学研究肠道微生物对结直肠癌患者影响的最新进展

人类肠道微生物已越来越受到医学界的广泛关注,人类肠道微生物不仅在人类健康方面,而且在人类疾病的发生和发展方面都有很大的作用。人们不断发现微生物与癌症之间的联系,特别是肠道微生物群和肠道肿瘤之间的联系。宏基因组学作为微生物研究的一种重要研究方法,在微生物与结直肠癌研究中发挥越来越重要的作用。近年来,通过宏基因组学研究肠道微生物菌群的变化为结直肠癌的发生和发展提供了新的见解,并且强调了癌症微生物群中宿主-微生物和微生物间相互作用的重要性。本综述回顾了通过宏基因组学研究肠道微生物与结直肠癌之间的关系,希望为癌症预防、诊断和治疗提供新的机会。     

基于肠道菌群及其代谢物的结直肠癌生物标志物的研究进展

摘 要：肠道菌群是人体内最大和最复杂的微生物群落,与人体健康和疾病密切相关。结直肠癌是一种常见的消化道恶性肿瘤,其发生与进展受到多种因素的影响,其中肠道菌群及其代谢物是重要的调节因素之一。肠道菌群及其代谢物可以通过影响宿主的免疫系统、代谢途径、表观遗传学和信号通路等,促进或抑制结直肠癌的发生及进展。因此,肠道菌群及其代谢物可以作为结直肠癌的生物标志物,用于结直肠癌的筛查、诊断、分期、预后评估和治疗反应监测等。全文对目前已发现的与结直肠癌相关的肠道菌群及其代谢物的检测方法和临床应用的优势、问题以及未来发展方向作一综述,旨在为基于肠道菌群及其代谢物的结直肠癌防治提供参考。     

膳食模式、肠道菌群与结直肠癌

结直肠癌是一种发病率和致死率均极高的肿瘤疾病,其发生和发展由基因、环境、生活方式等多方面因素共同决 定,并往往伴随着肠道微环境的改变。膳食成分是调节肠道微环境的重要因素。现阶段,越来越多的研究关注了饮食模式、膳 食成分和结直肠癌间的关系。本文首先讨论了不同膳食模式对结直肠癌发生风险的影响,证明了西方饮食可能促进结直肠癌 的发生,而地中海饮食、能量限制饮食、素食饮食和生酮饮食对结直肠癌具有一定的预防和干预作用。进一步分析了各类膳食 成分如何通过直接作用或通过调节肠道菌群间接影响了结直肠癌的发生发展。其中,多酚类物质、胡萝卜素、膳食纤维等,可 以维持肠道稳态,改善肠道内炎症及氧化应激等,从而降低结直肠癌的发病风险。而特定膳食成分的缺失或过剩则可以改变 肠道微生物组成,诱导肿瘤相关微生物丰度的升高,造成有毒代谢产物的积累,进而促进肠道炎症和肿瘤的发生。最后,本文 提出了一套针对结直肠癌患者的个性化饮食干预策略思路。利用宏基因组、宏转录组、代谢组等多组学手段,结合人工智能分 析结直肠患者菌群组成及功能上的异常,进一步设计个性化的膳食模式,以实现患者肠道菌群的精准调节,并对结直肠癌患者 进行膳食干预。     

益生菌在肿瘤免疫治疗中的研究进展

肿瘤免疫治疗是利用免疫系统、恢复机体正常的抗肿瘤免疫反应,从而控制与清除肿瘤的一种治疗方法。肠道菌 群能够与宿主相互作用,共同维持机体的稳态与宿主健康,在人体生理活动过程中发挥着重要作用。肠道菌群影响肿瘤的发 生、发展,各类肿瘤患者肠道菌群的紊乱情况及潜在机制也逐渐被解析。同时在肿瘤免疫治疗过程中,患者肠道菌群也发挥了 重要作用,对免疫反应的调控也会直接影响肿瘤治疗效果。人为干预改变肠道菌群可作为提高肿瘤免疫治疗效果,实现肿瘤 精确和个性化治疗的新策略,单独或与常规免疫治疗联用,干预手段有抗生素、益生菌等。其中益生菌作为一类安全有效的微 生态制剂,在干预肠道菌群进行肿瘤免疫治疗方面具有较大的发展潜力,但仍需要更多临床数据支持及机制探讨。本文介绍 了肠道微生物组与肿瘤发生、发展的关系及其相关机制,并对益生菌在肿瘤免疫治疗中的研究进展进行探讨,为益生菌的应用 及益生菌干预肠道菌群影响宿主健康的机制研究提供理论支持。     

Religiosity and Physical and Emotional Functioning Among African American and White Colorectal and Lung Cancer Patients

The literature suggests that religiosity helps cope with illness. The present study examined the role of religiosity in functioning among African Americans and Whites with a cancer diagnosis. Patients were recruited from an existing study and mailed a religiosity survey. Participants (N = 269; 36% African American, 56% women) completed the mail survey, and interview data from the larger cohort was utilized in the analysis. Multivariate analyses indicated that in the overall sample religious behaviors were marginally and positively associated with mental health and negatively with depressive symptoms. Among women, religious behaviors were positively associated with mental health and negatively with depressive symptoms. Religiosity was not a predictor of study outcomes for men. Among African Americans, religious behaviors were positively associated with mental health and vitality. Among Whites, religious behaviors were negatively associated with depressive symptoms. These findings suggest a mixed role of religious involvement in cancer outcomes. The current findings may have applied potential in the areas of emotional functioning and depression.     

New and emerging radiosensitizers and radioprotectors

The combination of chemotherapy and radiation has led to clinical breakthroughs in several disease sites, and current work continues to define optimum combinations of proven chemotherapy as well as more recently available, noncytotoxic agents. Administration of systemic therapies allows modulation of radiation response to improve tumor control (radiosensitization) or to prevent normal tissue toxicity (radioprotection). Substantial progress has been made in identifying the targets of standard chemotherapeutic radiation sensitizers and protectors as well as in the introduction of a new generation of molecularly targeted therapies in combination with radiation. We have reviewed the most recent, predominantly early phase clinical trials combining systemic agents with radiation. Although the proof of an improved schedule ultimately needs to come from well-run Phase III trials, the search among schedules could be shortened by the use of surrogate endpoints such as presence of active drug metabolites in the tumor. This has been accomplished only in a few cases and needs to become a more standard part of radiation sensitizer and protector trials.     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

Occupational and environmental radiation and cancer

Epidemiologic evidence on the relation between occupational and environmental radiation and cancer is reviewed. Studies of pioneering radiation workers, underground miners, and radium dial painters revealed excess cancer deaths and contributed to the setting of radiation protection standards and to theories of carcinogenesis. Occupational exposures today are generally much lower than in the past, thus any associated increases in cancer will be difficult to detect. Pooling investigations of these more recently exposed workers, however, has the potential to validate current estimates of risk used in radiation protection. New information on the effects of chronic radiation exposure also may come from studies in the former Soviet Union of Chernobyl clean-up workers and of workers at the Mayak nuclear facilities. Studies of environmental radiation exposures, other than radon, are largely inconclusive, due mainly to the difficulties in detecting the low risks associated with low dose exposures. Thyroid cancer, however, has been linked to environmental radiation from the Chernobyl accident and from nuclear weapons tests. Low-level radiation released during normal operations at nuclear plants has not been found to increase cancer rates in surrounding populations. Radon, a human carcinogen, is the most ubiquitous exposure to human populations; remediating high residential-radon levels is recommended, recognizing that the exposure can never be removed completely because it occurs naturally.     

VEGF及KDR在大肠腺瘤和腺癌中的表达及意义

目的：探讨VEGF和KDR在大肠腺瘤和大肠腺癌中的表达及临床病理特征的关系。方法：大肠腺瘤和大肠腺癌组织标本各100例,采用免疫组织化学染色法检测VEGF和KDR在标本中的表达情况。结果：VEGF和KDR在大肠腺癌组中的阳性表达明显高于大肠腺瘤组（P〈0.05）;在正常大肠黏膜均未见VEGF和KDR表达的阳性染色;VEGF阳性表达组中KDR的阳性表达率为70%,显著高于VEGF阴性表达组中KDR的阳性表达率16%,两组比较有统计学意义（P〈0.01）。结论：大肠腺癌组织中KDR的表达与肿瘤大小、转移情况、浸润深度密切相关;VEGF和KDR在大肠腺瘤中的表达与患者的年龄、性别及分型均无相关性,而与增生程度相关（P〈0.05）。在大肠腺癌患者中VEGF及KDR表达更高,二者具有协同效应。     

肾上腺素能β受体与肿瘤生长及转移

大量研究表明肿瘤细胞可表达β受体，而一些神经递质、药物和社会心理因素可能通过β受体影响肿瘤的生长和转移，β受体激动剂、β受体阻滞剂以及抑郁等社会心理因素可加强或削弱这种作用。这为表达β受体肿瘤的治疗开辟了新的道路，提供了新的治疗靶点。     

Cell and tissue interactions in carcinogenesis and metastasis and their clinical significance

This review describes a new vision for future directions in the study of metastatic cancer biology and pathology. It is based upon clinical and experimental observations on the constituent cell lineages within a neoplasm and on tumour-host interactions. The vision incorporates information from studies in population biology, developmental biology and experimental pathology as well as investigations upon human malignant disease. The assembled information reveals that invasion and metastasis are supra-cellular manifestations of "emergent behavior" among combinations of normal and malignant cell lineages in vivo. Emergent behavior is a combinatorial interactive process in which a population displays new traits which cannot be achieved by individuals acting separately and which subside when the specific population mix disaggregates. Disruption of such pathological interactions in the field of a developing primary or secondary tumour is, therefore, required to disable the malignant population and arrest progression without tissue destruction. These conclusions originate, in part, from principles which govern the sociobiology and group behavior of bees, ants, fish, birds and human societies. In all these social organisms, external factors can disrupt signaling mechanisms and induce expanding self-perpetuating rogue behavior, leading to social disintegration. These principles also apply to cellular societies composing higher animals, which likewise need intrinsic rules to maintain social order and avoid anarchy, and recognition of this is essential for advancing future research on the mechanisms involved in carcinogenesis and metastasis. Summarised evidence is presented here to support the conclusion that miscommunications between cells and tissues in the region of the developing tumour and its metastases are the main direct perpetrators of malignant disease. Genetic lesions (mutations, deletions, translocations, reduplications, etc.), commonly seen in cancers, can significantly disrupt important molecular pathways in the networks of communications needed to sustain orderly tissue/organ structure and function. However, genetic lesions can also, themselves, be induced by abnormal cell interactions initiated by extrinsic carcinogenic agents such as chemicals, viruses, hormones and radiation. The evidence shows that, irrespective of the initiating cause, it is this miscommunication in the region of a developing tumour and its metastases that is ultimately responsible for the emergence and progression of the disease. The article describes how this information collectively, provides a framework for designing specific novel therapeutic approaches targeting the cell and tissue interactions driving tumour metastasis and its manifold effects on the whole body.     

Vitamin D and melanoma and non-melanoma skin cancer risk and prognosis: A comprehensive review and meta-analysis

Vitamin D is formed mainly in the skin upon exposure to sunlight and can as well be taken orally with food or through supplements. While sun exposure is a known risk factor for skin cancer development, vitamin D exerts anti-proliferative and pro-apoptotic effects on melanocytes and keratinocytes in vitro. To clarify the role of vitamin D in skin carcinogenesis, we performed a review of the literature and meta-analysis to evaluate the association of vitamin D serum levels and dietary intake with cutaneous melanoma (CM) and non-melanoma skin cancer (NMSC) risk and melanoma prognostic factors. Twenty papers were included for an overall 1420 CM and 2317 NMSC. The summary relative risks (SRRs) from random effects models for the association of highest versus lowest vitamin D serum levels was 1.46 (95% confidence interval (CI) 0.60–3.53) and 1.64 (95% CI 1.02–2.65) for CM and NMSC, respectively. The SRR for the highest versus lowest quintile of vitamin D intake was 0.86 (95% CI 0.63–1.13) for CM and 1.03 (95% CI 0.95–1.13) for NMSC. Data were suggestive of an inverse association between vitamin D blood levels and CM thickness at diagnosis. Further research is needed to investigate the effect of vitamin D on skin cancer risk in populations with different exposure to sunlight and dietary habits, and to evaluate whether vitamin D supplementation is effective in improving CM survival.