肠道微生物群在肿瘤中的作用和机制研究进展

肠道微生物群参与人类疾病的调控。随着宏基因组学和代谢组学技术的发展,肠道微生物群在癌症中的作用受到了研究者们的重视。相比于健康人群,不同癌症患者肠道微生物群的种类和丰度及其代谢产物存在差别,这提示我们可以借助肠道微生物群检测为癌症无创诊断提供更加敏感且易于被接受的新方法,以期实现癌症的早期诊断。不同的肠道微生物群和其代谢产物可能对肿瘤起着促进或抑制的作用,并且这一过程可能受到饮食、吸烟等其他因素的影响。相比于健康人群,癌症患者的肠道微生物群发生了变化,而这些变化还可以影响癌症患者对化疗或免疫治疗的反应。靶向肠道微生物群为癌症的诊断和治疗提供了新的思路和方法。本文综述了肠道微生物群在癌症中的作用和机制研究进展。     

磷脂酶D在肿瘤发生中的作用机制研究进展北大核心CSCD

0引言 磷脂酶D（phospholipase D,PLD）是调控机体磷脂代谢的重要酶类,近年来大量研究表明,PLD与细胞增殖和肿瘤形成密切相关。PLD在多种恶性肿瘤中表达和活性增高并促进肿瘤的增生和浸润;PLD水解产生磷脂酸作为推动肿瘤发生的第二信使,在涉及癌症的重要信号通路网中居于中心地位。因此,PLD在癌症发生发展中的作用机制与癌症的预防和治疗密切相关,并可能成为癌症治疗的新靶点。本文就PLD参与癌症中的信号转导机制作一综述。     

癌症相关代谢紊乱综合征

临床上晚期癌症患者多表现为厌食、体重下降、早饱感、虚弱乏力及免疫力下降,这是癌症相关的代谢紊乱综合征所引起的,即恶病质,成为癌症患者死亡的主要原因之一。癌症代谢紊乱综合征与饥饿所引发的代谢紊乱是不同的,后者消耗大量的脂肪组织来维持肌肉组织中的蛋白含量,而前者脂肪和蛋白质都大量消耗,其中以蛋白质的消耗最为严重,使机体功能受损。现在有许多机制来解释癌症代谢紊乱综合征的病因,主要认为是由机体反应细胞或肿瘤细胞自身所产生的多种代谢因子所导致的,如TNF-α、IL-1、IL-6等。一些激素如糖皮质激素、瘦素、Ghrelin等也越来越受到研究者的重视。研究发现在癌症代谢紊乱综合征中这些激素水平发生了变化,但这种变化在该代谢紊乱病因中所起的作用还不清楚。这些因素在癌症代谢紊乱综合征中所起的作用不是十分确定,而且对该综合征所涉及的信号通路的研究也尚无定论。这些都给临床治疗带来了很大困难,仅靠补充营养并不能有效地增加癌症患者骨骼肌的蛋白含量。约三分之一的癌症患者最终因代谢紊乱死亡而非肿瘤本身。因此需要对癌症代谢紊乱的病因及其发生、发展过程进行更深入的研究,这些问题的解决不仅将有助于提高癌症患者的生活质量,对临床治疗也会有较大的帮助。     

代谢综合征与乳腺癌的关系

代谢综合征(metabolic syndrome,MS)是以肥胖和胰岛素抵抗为中心的多种代谢性危险因素在个体内集结的状态,主要组分包括肥胖、高血糖、高胰岛素血症、血脂异常和高血压等。研究表明代谢综合征不仅是心血管病的危险因素,还与乳腺癌的发生和预后相关。本文综述代谢综合征与乳腺癌患病风险的关系及其致乳腺癌的可能机制,为乳腺癌的预防、治疗及预后提供新的策略。     

乙醛脱氢酶2型与乙醛在肿瘤发生发展中的作用

摘 要：乙醛脱氢酶2型(aldehyde dehydrogenase 2 family,ALDH2)是一种线粒体酶,其主要作用是将乙醛(acetaldehyde,ACE)代谢成乙酸,以供后续参与生物体的能量代谢与生物合成。在人群中,ALDH2活性位点存在高频率变异,致使该人群对酒精不耐受,易患急性酒精中毒等饮酒相关疾病。越来越多的证据显示,ALDH2基因的多样性在肿瘤的发生、生长、转移和抗药性中也发挥着重要作用。文章回顾了ALDH2以及其底物ACE在肿瘤研究中的最新进展,阐述了可调控其活性的药物及调控机制,并预测ALDH2可能成为癌症预后的标志物和癌症治疗的新靶点。     

粪便菌群移植在癌症治疗中的研究进展

大量研究证明,肠道菌群失衡与人类癌症之间有密切的关系。肠道菌群不仅在维持肠道屏障和代谢营养方面发挥作用,更重要的是,这些微生物有助于调节局部和全身免疫功能,进而参与机体癌症的发病机制。粪便菌群移植(FMT)是一种调节肠道菌群的方法,它的有效机制主要基于有益微生物的增强、微生物组多样性的增加以及正常菌群的恢复。最近有研究表明,以病原体数量明显增加和有益细菌水平相对降低为特征的微生物改变与胃肠道和胃肠道外癌症的发展有关,提示调节肠道菌群是治疗人类癌症具有前景的手段之一。本文围绕FMT在治疗消化系统癌症、非消化系统癌症和癌症相关并发症上的作用展开论述,总结FMT在癌症治疗方面的最新进展。     

自噬在癌症发生中的双重作用

自噬是一种在真核生物正常细胞和病理状态细胞中普遍存在的生理过程。它利用膜包被需要降解的细胞质、长寿蛋白和受损细胞器形成自噬体,与溶酶体融合后降解包含的内容物。自噬维持了细胞内蛋白质代谢平衡和内环境稳定,增强了细胞的胁迫适应。自噬缺失与许多疾病的发生有关,如肝功能衰竭、神经退行性病变、衰老和癌症。自噬与癌症的关系错综复杂,不同的组织和基因背景下,自噬对癌症发生所起的作用不同。自噬缺失后,细胞遭受氧化胁迫,DNA损伤累积,基因组稳定性下降,以及持续的炎症,从而导致癌症的发生。然而在特定的细胞类型、时期和微环境中,自噬为癌细胞生长提供所需的代谢物,有利于癌细胞氧化胁迫适应和转移,从而促进了癌症的发生。本文主要综述自噬在癌症发生中的双重作用及其可能的机制,并评价自噬干预在癌症临床辅助治疗中的可能应用。     

解耦联蛋白UCP1在肿瘤恶病质中的研究进展

解耦连蛋白(UCP1)是一种特殊的线粒体蛋白,能够促进线粒体的呼吸作用而产生热量消耗。UCP1是在棕色脂肪细胞中发现的第一个解耦蛋白,其定位于线粒体内膜,可以降低电子传递系统产生的质子(H+)梯度,更容易直接产生热量。棕色脂肪细胞的UCP1活动被认为是一种很有前途的对抗肥胖和代谢疾病的策略。癌症恶病质是一种以全身炎症、体重减轻、骨骼肌和脂肪组织萎缩为特征的消瘦综合征,其潜在的机制和有限的、可用的治疗选择是不明确的。癌症细胞中棕色脂肪样表型的异常表达先前已被证实与肿瘤生长有关。恶性肿瘤中褐色脂肪相关蛋白的表达可能与肿瘤的预后有关。全文主要从UCP1的表达、解耦联机制以及过程中与恶性肿瘤恶病质之间存在的联系等作一综述。     

Trousseau综合征的研究现状

 Trousseau综合征为癌症患者特殊的临床综合征,其定义是癌症患者在其发病过程中因为凝血和纤溶机制异常而出现的所有临床表现,是副肿瘤综合征的一种表现。明确其定义、临床表现、流行病学、发病机制、诊断及处理措施有助于肿瘤的治疗及改善患者生存质量。     

细胞色素P450酶、谷胱甘肽转移酶多态性及其与肿瘤的关系

肿瘤的发生机制目前尚不明确 ,一般认为是环境因素和遗传因素相互作用的结果。P45 0酶属Ⅰ相代谢酶 ,可代谢多种化学物和药物 ,并可形成致癌性的物质。人谷胱甘肽 S 转移酶 (GST)属Ⅱ相代谢酶 ,是催化谷胱甘肽 (GSH)与亲电子的外源物结合的二聚体酶 ,并可灭活外源物 ,促使它们排出体外 ,它们在人群中呈多态性分布。肿瘤的遗传易感性与代谢酶遗传多态性是密切相关的。通常情况下 ,大多数致癌物的形成 ,首先通过Ⅰ相代谢酶的活化 (如P45 0酶 ) ,灭活主要通过Ⅱ相代谢酶(如GST酶 )进行的。因此 ,Ⅰ相代谢酶与Ⅱ相代谢酶的多态性往往决定癌症的发生率及发生类型。     

代谢综合征与肺癌恶性程度的相关性探讨

目的:分析代谢综合征及其组分与肺癌恶性程度的相关性。方法:收集2017年01月至2019年04月我院收治的285例肺癌患者,根据是否合并代谢综合征,分为单纯肺癌组195例和肺癌合并代谢综合征组90例;根据是否合并心脑血管疾病,将90例代谢综合征合并肺癌患者分为肺癌并代谢综合征伴心脑血管疾病组65例及不合并心脑血管疾病组25例。采用独立样本t检验分析两组患者间的年龄差异;卡方检验分析两组患者性别、吸烟史、病理类型、肿瘤分期的差异;Logistic回归分析代谢综合征各组分与肺癌肿瘤分期的相关性。结果:肺癌合并代谢综合征组患者的肿瘤分期明显高于单纯肺癌组,且存在显著性差异(P<0.05);血压异常(P=0.000)和血脂异常(P=0.042)对于肿瘤分期有显著影响,血糖异常(P=0.429)和体质量指数(P=0.518)对肿瘤分期无显著影响;合并心脑血管疾病者其肿瘤分期较未合并基础疾病者无明显差异(P=0.234)。结论:肺癌伴有代谢综合征者肿瘤恶性程度高,高血压和高血脂是肿瘤分期的危险因素,合并心脑血管疾病者肿瘤分期与未合并者无统计学差异。     

Metabolic syndrome and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer death in the United States. Although many risk factors for HCC are well defined, including hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol, most series have indicated that 5% to 30% of patients with HCC lack a readily identifiable risk factor for their cancer. The majority of “cryptogenic” HCC in the United States is attributed to nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome. The metabolic syndrome is a constellation of problems that includes insulin resistance, obesity, hypertension, and hyperlipidemia. Increasingly, components of the metabolic syndrome are being linked to various forms of cancer with respect to both increased risk of disease and worsened outcome. In this review, the authors focused on the relation between metabolic syndrome and HCC. They investigated the increased risks of HCC among individuals with features of metabolic syndrome, potentially worsened cancer outcomes in these patients, possible pathogenic mechanisms to explain these relations, and treatment options for those with NAFLD and its progressive counterpart, nonalcoholic steatohepatitis. It is predicted that metabolic syndrome will lead to large increases in the incidence of HCC over the next decades. A better understanding of the relation between these 2 diseases ultimately should lead to improved screening and treatment options for patients with HCC. Cancer 2009. © 2009 American Cancer Society.     

Development of Metabolic Syndrome Associated to Cancer Therapy: Review

Long-term childhood cancer survivors are at great risk of developing late adverse effects after treatment, such as, reduced growth, obesity, decreased fertility, high blood pressure, cardiovascular diseases, impaired glucose, another form of cancer, among others organ dysfunctions, some of them are part of the metabolic syndrome. Metabolic syndrome and cancer connection is still not entirely understood, but there are some notions about it. Metabolic alterations produced during childhood cancer are more likely determined by treatments like radiotherapy, chemotherapy, glucocorticoids therapy, and surgery. Cancer treatment is associated to vascular alterations, hormone deficiencies, changes in insulin sensitivity, lipid metabolism, and inflammatory mediators. Obesity has been considered a crucial component in metabolic syndrome; obesity risk factors during childhood cancer include cranial radiation, female gender, and exposure to glucocorticoids such as dexamethasone. In addition, local radiotherapy or surgery may cause endocrine deficiencies, depends on the directly damage of endocrine organs. Patients who received some types of cancer treatment should be evaluated periodically to early diagnostic metabolic disorders associated to antineoplastic therapy.     

Cancer Cachexia: From Molecular Mechanisms to Patient's Care

Cancer cachexia is a disabling syndrome because of the complex interactions between the tumor, host metabolism, and proinflammatory cytokines that increases patients' morbidity and mortality. Considering the recent new definition and classification of cachexia, we aimed to review cancer cachexia from its underlying mechanisms to the clinical approach. Cancer cachexia is featured by a disruption in energy balance, metabolic changes, a decrease in fat mass, depletion of skeletal muscle mass, and perturbations in proinflammatory cytokines. Diagnostic effort should be focused on the recognition of precachexia to prevent or delay changes in body composition and nutritional complications secondary to cancer. From the point of disease diagnosis, every cancer patient needs continuous monitoring to receive effective, tailored nutritional and metabolic support. To date, practical guidelines to counteract cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. A single therapy may not be effective; only a multimodal approach involving different treatment combinations is more likely to be successful in the prevention and treatment of cancer cachexia.     

2011-2016年中国恶性肿瘤发病和死亡趋势分析及GM(1，1)模型预测

目的:分析2011-2016年中国恶性肿瘤发病和死亡趋势,预测2017-2021年恶性肿瘤发病和死亡情况。方法:基于国家癌症中心发布的2014-2019年中国肿瘤登记年报中恶性肿瘤相关数据信息,分析纳入登记年报的登记点数量变化,利用Joinpoint 对数线性模型和灰色预测模型GM(1,1)分别对2011-2016年恶性肿瘤发病率和死亡率进行趋势分析并对2017-2021年恶性肿瘤发病率和死亡率进行预测分析。结果:2011-2016年纳入中国肿瘤登记年报的全国范围内的肿瘤登记点数量从140个增加到487个。2011-2016年,恶性肿瘤发病中标率和世标率呈下降趋势,平均年度变化百分比（average annual percentage change,AAPC)值分别为-0.86%（P＜0.05）、-0.91%（P＜0.05）;死亡中标率和世标率呈明显下降趋势,AAPC值分别为-2.22%（P＜0.05）、-2.19%（P＜0.05）。2011-2016年各年龄段发病率和死亡率的趋势变化存在明显差异。灰色预测模型GM(1,1)预测2017年中国恶性肿瘤发病率为293.27/105,死亡率为176.92/105。结论:近年来我国恶性肿瘤发病率和死亡率保持相对稳定的高流行状态,肿瘤防控形势严峻,随着我国人口老龄化程度的加剧,中老年人群应作为肿瘤防控的重点人群。     

有氧糖酵解促进肿瘤转移及干性的研究进展

癌症已成为全球第二大死亡原因,是危害严重的全球健康问题。虽然医学发展迅速,治疗方法也在不断改进,可是由于肿瘤复发和远端转移的存在,目前肿瘤患者仍然预后不良,生存率无法提高。近期肿瘤细胞中的“代谢重编程”给我们提供了新的思路,肿瘤细胞中从氧化磷酸化到糖酵解的代谢转换可以影响肿瘤细胞干性,参与调节肿瘤的侵袭与远端转移。本文总结了近年来关于肿瘤细胞有氧糖酵解的相关研究,就肿瘤细胞中的糖代谢重编程、糖酵解对肿瘤细胞转移及干性的影响,以及潜在机制几方面进行综述,探讨靶向糖酵解联合治疗的可行性,希望有助于肿瘤细胞糖代谢后续的研究,为肿瘤治疗提供新的策略。     

Prevalence of the Metabolic Syndrome and Associated Factors in Korean Cancer Survivors

Background: This study was designed to evaluate prevalence of the metabolic syndrome among cancersurvivors compared to non-cancer controls from a population-based sample and to identify associated riskfactors. Materials and Methods: Data from the fourth Korean National Health and Nutrition ExaminationSurvey were analyzed to compare the prevalence of metabolic syndrome, as defined by 2009 consensuscriteria. Associated factors with were identified using multiple logistic regression analysis among cancersurvivors. Results: The prevalence of the metabolic syndrome in cancer survivors (n = 335) was similarto that in the non-cancer population (n = 10,671). However, gastric cancer survivors showed lower risk ofmetabolic syndrome than non-cancer controls (adjusted odds ratio [aOR] 0.42, 95% confidence interval [CI]0.20-0.86). Age of more than 60 years (aOR 4.83, 95% CI 1.94−12.03), BMI between 23 and 25 (aOR 6.71,95% CI 2.90−15.6), BMI more than 25 (aOR 12.23, 95% CI 5.20−28.77) were significantly associated withthe metabolic syndrome in cancer survivors. Conclusions: Cancer survivors are unlikely to have a higherrisk of the metabolic syndrome than non-cancer controls in Korea. This finding may be due to a relativelyhigh proportion of gastric cancer survivors in Korea than in Western countries. The risk for metabolicsyndrome among cancer survivors would appear to vary according to oncological and non-oncologicalfactors.     

The metabolic syndrome in long-term cancer survivors,an important target for secondary preventive measures

With increasing numbers of cancer survivors, attention has been drawn to long-term complications of curative cancer treatment, including a range of metabolic disorders. These metabolic disorders often resemble the components of the so-called metabolic syndrome, or syndrome X, which is an important risk factor for the development of cardiovascular disease. The mechanisms behind the development of metabolic disorders in cancer survivors have not been fully elucidated. However, association studies in the general population have demonstrated correlations between the components of the metabolic syndrome on the one hand and hormonal deficiencies, hypomagnesaemia, and endothelial dysfunction on the other. These latter disorders are regularly reported following curative cancer treatment and could, therefore, be important aetiologic factors in the development of the metabolic syndrome in cancer survivors. This review discusses data on the associations between the metabolic syndrome and treatment-related complications in cancer survivors and possibilities for preventive measures.     

2010-2018年重庆市恶性肿瘤发病死亡趋势分析

目的:分析重庆市2010-2018年恶性肿瘤发病死亡变化趋势。方法:收集整理2010-2018年重庆市肿瘤登记点恶性肿瘤发病死亡资料,采用SPSS 25.0分析恶性肿瘤发病率、中国人口标化发病率、世界人口标化发病率、年龄别发病率、死亡率、中国人口标化死亡率、世界人口标化死亡率、年龄别死亡率等。男性与女性、城市与农村发病率、死亡率的比较采用χ2检验,趋势变化采用年度变化百分比（APC）,对APC的检验采用t检验。结果:重庆市恶性肿瘤发病率、中标率与世标率分别由2010年的200.08/10万、147.03/10万、162.53/10万上升至2018年的289.63/10万、195.85/10万、209.74/10万,APC分别为5.02%(4.39%～5.65%)、4.29%(3.77%～4.81%)、3.87%(3.36%～4.39%),变化趋势均有统计学意义（P＜0.01）。恶性肿瘤发病率历年均是男性高于女性（P＜0.05）。2011年与2015年城市与农村地区恶性肿瘤发病率差异无统计学意义（P＞0.05）,其它年份恶性肿瘤发病率均是城市高于农村,差异有统计学意义（P＜0.05）。男性与女性、城市与农村恶性肿瘤发病率均明显上升（P＜0.05）。2010年重庆市恶性肿瘤死亡率、中标死亡率与世标死亡率分别为152.10/10万、103.49/10万、117.91/10万,2018年死亡率、中标死亡率与世标死亡率分别为184.77/10万、110.87/10万、125.53/10万,死亡率以年均3.15%(2.33%～3.98%)上升（t=4.03,P=0.005）。恶性肿瘤死亡率历年均是男性高于女性。2010-2018年男性与女性恶性肿瘤死亡率分别以3.46%(2.63%~4.29%)与2.63%(1.92%～3.36%)上升（t=4.36,P=0.003;t=3.43,P=0.011）。2010-2018年城市地区恶性肿瘤死亡率变化趋势差异无统计学意义（P＞0.05）。2010-2018年农村地区恶性肿瘤死亡率以年均3.05%(2.33%～3.77%)上升（t=4.03,P=0.005）。结论:重庆市恶性肿瘤发病率与死亡率呈快速上升的趋势,应针对危险因素进行干预和普及早诊早治,降低恶性肿瘤的发病率与死亡率。     

A retrospective review of the metabolic syndrome in women diagnosed with breast cancer and correlation with estrogen receptor

Women diagnosed with obesity and breast cancer have an increased risk of recurrence and death (Protani et al., Breast Cancer Res Treat 123:627–635, 1). Obesity is associated with the metabolic syndrome—a pathophysiologically distinct inflammatory process comprised of central obesity, insulin resistance, hypertension, and atherogenic dyslipidemia. The relationship of obesity as a risk factor for breast cancer is complex with a protective effect for younger women in contrast to a risk for older women (Kabat et al., Cancer Epidemiol Biomarkers Prev 18:2046–2053, 2; Ursin et al., Epidemiology 6:137–141, 3). The metabolic syndrome has been associated with the risk of cancer, and pro-inflammatory circulating factors may be associated with risk of more aggressive breast cancer (Capasso et al., Cancer Biol Ther 10:1240–1243, 4; Healy et al., Clin Oncol (R Coll Radiol) 22:281–288, 5; Laukkanen et al., Cancer Epidemiol Biomarkers Prev 13:1646–1650, 6). We conducted a retrospective review of 860 breast cancer patients to determine the relationship between estrogen receptor status and the metabolic syndrome. We collected the relevant metabolic diagnoses, medications, physical findings, and laboratory values and adapted the National Cholesterol Education Program criteria to define the metabolic syndrome retrospectively. No relationship was found between estrogen receptor status and the individual components of the metabolic syndrome. Based on findings in the medical records, 15% of the women with breast cancer had the metabolic syndrome, and 26% of the women were considered obese, 16% hyperglycemic, 54% hypertensive, and 30% dyslipidemic. The metabolic syndrome was associated with advanced age and African-American race (P < 0.001). When adjusted for age, race, and stage, the metabolic syndrome was marginally associated with estrogen receptor-positive tumors (P = 0.054). Our findings do not support the concern that the metabolic syndrome may contribute to more biologically aggressive breast cancer.