糖尿病与恶性肿瘤关系的研究进展

目前,恶性肿瘤已成为人类死亡的第1位或第2位原因且有逐年上升的趋势,严重威胁人类健康和生命,肿瘤病因学成为目前的研究热点之一。糖尿病是一组以慢性血糖水平增高为特征的代谢性疾病,其发病率亦逐年增加,在发达国家已成为继心血管病和肿瘤之后的第三大非传染病。恶性肿瘤与糖尿病之间的关系受到了诸多学者的关注。本文简述此领域研究的进展。     

NLRP6在肿瘤中的研究进展

核苷酸结合寡聚化结构域样受体（nucleotide-binding and oligomerization domain-like receptors,NLRs）是一种模式识别受体,其中NLRP6是NLRs家族的新成员,可与caspase-1和含半胱天冬酶激活和募集结构域（caspase activation and recruitment domain,CARD）的凋亡相关颗粒样蛋白（apoptosis-associated speck-like protein containing a CARD,ASC）构成蛋白复合物,在维持肠道上皮完整性和调控肠道菌群中均有重要的作用。已有研究初步证实,NLRP6在多种恶性肿瘤中扮演重要角色。本文着重介绍NLRP6的结构、功能、激活机制以及其在各种肿瘤中的研究进展。     

糖尿病与肿瘤

糖尿病与肿瘤是密切相关的慢性疾病.流行病学研究表明,糖尿病患者不仅罹患胰腺癌、肝癌、乳腺癌、结直肠癌和尿道癌等肿瘤的风险增高,且其死亡风险也相应增加.胰岛素在新陈代谢和有丝分裂中起重要作用.在肿瘤发生发展中,胰岛素可通过受体和受体后水平活化机制发挥作用,故高胰岛素血症是最可能导致糖尿病患者发生肿瘤的危险因素.此外,降糖药物、肥胖、高血糖症和氧化应激也可能是糖尿病患者肿瘤危险性增高的因素.     

糖尿病与肿瘤

糖尿病与肿瘤是密切相关的慢性疾病。流行病学研究表明,糖尿病患者不仅罹患胰腺癌、肝癌、乳腺癌、结直肠癌和尿道癌等肿瘤的风险增高,且其死亡风险也相应增加。胰岛素在新陈代谢和有丝分裂中起重要作用。在肿瘤发生发展中,胰岛素可通过受体和受体后水平活化机制发挥作用,故高胰岛素血症是最可能导致糖尿病患者发生肿瘤的危险因素。此外,降糖药物、肥胖、高血糖症和氧化应激也可能是糖尿病患者肿瘤危险性增高的因素。     

雷公藤红素与肿瘤代谢的关系研究进展

雷公藤红素是一种中草药活性成分,具有广泛的治疗特性及较高的药用价值,通常用于治疗自身免疫性疾病、代谢性疾病及肿瘤。雷公藤红素可以通过多种途径抑制肿瘤的发生、发展,尤其与肿瘤代谢密切相关,对肿瘤细胞的糖代谢、脂类代谢、氨基酸代谢及肿瘤微环境产生重要影响。雷公藤红素导致线粒体功能障碍以改变葡萄糖代谢途径,使肿瘤细胞供能不足;通过诱导肝内Sirt1的表达影响肿瘤宿主的脂类代谢;抑制吲哚胺2,3双加氧酶（IDO）表达和色氨酸分解代谢来抑制结直肠癌,与IDO的抑制剂D-1MT联用控制胰腺癌;在肿瘤微环境中,雷公藤红素可通过抑制NLRP3炎性小体及重塑免疫抑制治疗黑色素瘤。根据最新研究报道,肠道菌群的高度代谢可以提高雷公藤红素在体内的功效,影响肿瘤发展。本文从代谢的角度阐述雷公藤红素对肿瘤的主要作用及机制,为其药理作用的深入研究提供科学依据。     

2型糖尿病与乳腺癌关系的研究进展

目的:总结国内外关于2型糖尿病与乳腺癌关系方面的研究进展。方法:应用PubMed和CNKI期刊全文数据库检索系统,以"2型糖尿病、乳腺癌"为关键词,检索2006-01-2012-10的有关文献。纳入标准:1)关于2型糖尿病和乳腺癌的流行病学文献;2)关于2型糖尿病和乳腺癌相关的基础研究和临床研究文献。根据纳入标准,符合分析的文献51篇。结果:2型糖尿病增加乳腺癌的发病和总死亡风险,在绝经后期女性中尤为显著。2型糖尿病与乳腺癌通过高血糖、高胰岛素血症、胰岛素样生长因子、脂肪细胞因子及内源性性激素等机制发生联系。这些机制在分子水平上相互联系,针对这些机制中某些靶点的抑制剂或单克隆抗体在基础实验和(或)临床试验中取得一定程度的进展。结论:2型糖尿病和乳腺癌相关的具体机制需要更多的基础研究和大型前瞻性临床试验来揭示,这些抑制剂或单克隆抗体有望为难治性乳腺癌提供新的选择,更有利于乳腺癌的个体化治疗。     

慢性心理应激对肿瘤影响的研究进展

摘 要：慢性心理应激能够显著影响肿瘤的发生发展，包括促进肿瘤发生、肿瘤细胞增殖侵袭、肿瘤血管生成和逃避免疫系统监测。应激反应是主要由下丘脑-垂体-肾上腺（hypothalamic-pituitary-adrenal axis，HPA）轴和交感神经系统（sympathetic nervous system，SNS）介导的生物过程。 SNS和HPA轴的激活导致神经递质和激素（例如儿茶酚胺和糖皮质激素）的释放，而SNS和HPA轴的长时间激活，增加了免疫系统暴露于升高的激素水平的风险，并且导致机体炎症因子的紊乱和肠道菌群失调，以及诱导肿瘤耐药。     

肿瘤代谢重编程及其与肠道菌群关系的研究进展

肿瘤发生、发展过程中,其代谢表型通常会发生改变.除了传统营养物质(葡萄糖、脂质、谷氨酰胺)来源的代谢重编程外,乳酸、乙酸、酮体、外源蛋白质等也能被肿瘤细胞重新摄取利用.健康的肠道菌群维持着体内稳态和肠道正常功能,在调控宿主能量代谢、促进食物消化以及调节免疫等方面有着重要的生理意义.然而肠道菌群的代谢产物能够重塑肿瘤营养...     

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。     

2 型糖尿病与结直肠癌关系的临床研究*

目的:探讨2 型糖尿病（T2DM）与结直肠癌发病和转移的关系。方法:收集广西医科大学第一附属医院2001年1 月至2006年12月间收治的结直肠癌患者852 例和非肿瘤患者940 例的临床资料。比较两组在性别、肿瘤部位、糖尿病病程和肝转移等方面的差异,并对相关危险因素进行分析。结果:T2DM患者结直肠癌发病的危险显著高于非T2DM 患者,其OR值为2.466,男性T2DM 患者发生结直肠癌的危险高于女性,差异无统计学意义（OR值2.775 vs 2.070,P=0.394）。 患有左半结肠癌的患者发生T2DM的比例最高,但与患有右半结肠癌和直肠癌者无显著性差异。T2DM病程在10～20年组发生结直肠癌的危险性最高,其OR值为4.696。T2DM合并结直肠癌患者发生肝脏转移危险性高于非T2DM合并结直肠癌患者,其OR值为2.888。结论:T2DM可能是结直肠癌发生的危险因素之一,在T2DM病程小于20年以内这种危险性随着病程的增加而增加;T2DM合并结直肠癌患者更容易发生肝脏转移。      

Diabetes mellitus contribution to the remodeling of the tumor microenvironment in gastric cancer

Compelling pieces of evidence derived from both clinical and experimental research has demonstrated the crucial contribution of diabetes mellitus (DM) as a risk factor associated with increased cancer incidence and mortality in many human neoplasms, including gastric cancer (GC). DM is considered a systemic inflammatory disease and therefore, this inflammatory status may have profound effects on the tumor microenvironment (TME), particularly by driving many molecular mechanisms to generate a more aggressive TME. DM is an active driver in the modification of the behavior of many cell components of the TME as well as altering the mechanical properties of the extracellular matrix (ECM), leading to an increased ECM stiffening. Additionally, DM can alter many cellular signaling mechanisms and thus favoring tumor growth, invasion, and metastatic potential, as well as key elements in regulating cellular functions and cross-talks, such as the microRNAs network, the production, and cargo of exosomes, the metabolism of cell stroma and resistance to hypoxia. In the present review, we intend to highlight the mechanistic contributions of DM to the remodeling of TME in GC.     

2型糖尿病合并甲状腺癌的发生率及预后相关影响因素分析

目的 探讨2型糖尿病合并甲状腺癌的发生率及预后的相关影响因素.方法 以534例住院2型糖尿病患者为研究对象,回顾分析其空腹血糖、餐后2 h血糖、胰岛素(FINS)以及甲状腺彩超检查的结果,对2型糖尿病患者的甲状腺癌发生率及预后相关因素进行分析.结果 2型糖尿病患者甲状腺癌的发生率为19.7%,女性的发生率为12.4%,高于男性6.4%,且随年龄的增加甲状腺癌的发病率增加.单因素分析结果表明,影响2型糖尿病合并甲状腺癌患者3年生存率的主要相关因素为性别、年龄、病理类型、淋巴结转移、临床分期、病程和胰岛素依赖.多因素回归分析结果显示,病理类型、临床分期、病程、胰岛素抵抗是影响2型糖尿病合并甲状腺癌患者预后的独立因素(P<0.05).结论 2型糖尿病患者的甲状腺癌的患病率较高,病理类型、临床分期、病程、胰岛素抵抗可能是2型糖尿病患者甲状腺癌预后的独立影响因素.临床实践中,应及时对患者进行甲状腺癌筛查,早发现早治疗,以减少甲状腺癌的发生.     

糖尿病患者基因多态性与乳腺癌发病及预后的相关性

Objective To analyze the effects of fat mass and obesity-associated (FTO) gene, IL-6, and HSP-60 gene polymorphism on the incidence rate and prognosis of breast cancer (BCa) for patients with type 2 diabetes mellitus (T2DM). Methods A total of 1551 patients with BCa were included in the experimental group and 1605 women of the same age who participated in physical examination were included in the control group. The clinical data of the 3156 participants were collected through the baseline data questionnaire, and the genotypes of FTO, IL-6, and HSP-60 single-nucleotide polymorphism (SNP) were determined through blood sample detection. The predictive value of the three SNPs for the incidence risk of BCa for T2DM patients was evaluated. The OS of 1168 patients with BCa was obtained through follow-up, and the effects of the three SNPs and T2DM on OS of BCa patients were evaluated. Results The three loci were FTO rs3751812, IL-6 rs1800796, and HSP-60 rs2605039. The BCa incidence rate for T2DM women with wild homozygous SNP genotype was significantly higher than that for non-T2DM women (FTO: χ2=3.530, P=0.013; IL-6: χ2=6.288, P=0.029; HSP-60: χ2=4.926, P=0.005). The three wild homozygous genotypes were independent risk factors that influenced the incidence rate of BCa (all P<0.05). Patients with HSP-60 rs2605039 (GT+TT) genotype had better OS (P=0.031). Conclusion FTO, IL-6, and HSP-60 gene polymorphisms have certain value in BCa prediction for T2DM patients. Patients with BCa and HSP-60 rs2605039 GT+TT genotype have high OS. © 2023, CHINA RESEARCH ON PREVENTION AND TREATMENT. All rights reserved.     

Demographic Characteristics,Survival and Prognostic Factors of Early Breast Cancer Patients with Type 2 Diabetes Mellitus: A Hospital-Based Cohort Study

Objective: With increasing prevalence of type 2 diabetes mellitus and breast cancer in Iran, we aimed to search hospital registries of breast cancer patients to investigate type 2 diabetes mellitus association with survival outcomes of early breast cancer after adjustment of confounding factors. Methods: In a retrospective cohort study conducted from July 2003 to Feb 2014 and followed up until death or December 2016, female patients with early breast cancer who have been treated for the first time at the Cancer Institute of Iran, were divided to diabetic and non-diabetic groups. Primary and secondary outcomes were relapse free survival (RFS) and overall survival (OS). SPSS version 23 was used for analysis of data. Other variables included age, tumor stage, hormone receptor status, tumor subtype, and patient’s body mass index (BMI). Result: From a total of 1021 patients, 218 (21.4%) had type 2 diabetes mellitus. Diabetic patients had a higher mean age (53.31 vs 47.00), higher mean BMI (31.13 vs 29.15), lower HER2 expression (20.8% vs 32.1%) and higher frequency of luminal A subtype (61.1% vs 51.0). Overall, after adjustment of other variables, diabetes status did not affect RFS or OS independently. However, in luminal A subgroup, patients with diabetes mellitus had significantly lower survival outcomes of OS (135.277 vs 154.701) and RFS (114.107 vs 133.612) as well as OS higher hazard ratio of 1.830 and RFS hazard ratio of 1.663 compared to non-diabetic patients. BMI, hormone receptor status and tumor stage significantly affected the survival of the patients. Conclusion: In the present study, in addition to known breast cancer risk factors, BMI and type 2 diabetes mellitus had an independent impact on survival of the patients, highlighting the importance of health issues such as obesity and diabetes suboptimal performance in the treatment outcomes of early breast cancer patients in Iran.     

胃癌合并2型糖尿病患者临床特征及预后分析

目的： 探讨胃癌患者合并2型糖尿病的临床特征,分析糖尿病对胃癌患者预后的影响。方法：对2003年1月至2011年7月期间我院收治的胃癌患者的临床病例资料进行回顾性分析,共纳入252例患者,按照是否存在糖尿病将胃癌患者分为合并糖尿病组（85例）和未合并糖尿病组（167例）,比较两组患者的临床特征,分析两组患者的总生存率。结果：两组患者在性别、年龄、文化程度、发病部位、手术方式等方面差异无统计学意义（P>0.05）,但两组的分化程度、肿瘤分期存在差异（P<0.05）,合并糖尿病组患者的肿瘤分化程度较低。合并糖尿病组总体中位生存期为43.8个月,5年生存率为30.5%;未合并糖尿病组总体中位生存期为58.2个月,5年生存率为41.4%;经Log rank检验两组患者总生存率比较差异有统计学意义（χ2=10.076,P=0.002）。糖尿病、分化程度、临床分期是影响胃癌患者生存的独立影响因素。结论：2型糖尿病可影响胃癌患者的预后,糖尿病与胃癌预后的关系有待更深入的研究。     

2型糖尿病血糖、血脂代谢情况与甲状腺癌发病的相关性

目的 探讨2型糖尿病血糖、血脂代谢情况与甲状腺癌发病的相关性.方法 将467例门诊确诊为2型糖尿病的患者纳入研究组,同时将同期健康体检者200例纳入对照组.检测入选者血清血糖(GLU)、胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)和促甲状腺激素(TSH)水平并进行统计分析.结果 观察组甲状腺癌的发病率为9.2%,显著高于对照组的1.5%,差异有统计学意义(P<0.05).观察组血清TC、TG和LDL-C明显高于对照组,HDL-C明显低于对照组,差异有统计学意义,P<0.05.观察组患者血清FT3显著高于对照组,TSH显著低于对照组,差异有统计学意义(P<0.05).结论 2型糖尿病患者血糖和血脂紊乱会增加甲状腺癌的发病率,可能是通过影响甲状腺激素的分泌实现的.     

1205例2型糖尿病患者的恶性肿瘤流行病学特征

[目的]探究2型糖尿病患者的恶性肿瘤流行特征,为做好糖尿病患者恶性肿瘤的综合防治提供依据.[方法] 2005～2011年闵行区被诊断为2型糖尿病且先后被诊断为恶性肿瘤的患者1 205例.采用SPSS 13.0软件对l 205例2型糖尿病患者在患糖尿病后恶性肿瘤的发生及流行情况进行描述与分析.[结果]2型糖尿病和恶性肿瘤高发于50～80岁.2型糖尿病中以结直肠癌的发病率最高,除乳腺癌、前列腺癌性别特异外,女性甲状腺癌患病率高于男性,男性结直肠癌、肺癌、胃癌、肝癌、胰腺癌、膀胱癌均高于女性.2型糖尿病的恶性肿瘤患者一半以上在糖尿病确诊5年内发生,且分期较晚.[结论]2型糖尿病患者恶性肿瘤发病风险较高,建议确诊糖尿病后将胃癌、结直肠癌、甲状腺癌和乳腺癌等易发恶性肿瘤的筛查纳入其定期体检.     

An Investigation into Disease Progression and the Correlation between Diabetes Mellitus and Hepatocellular Carcinoma

ABSTRACT Diabetes mellitus has been associated with an increased risk of hepatocellular carcinoma in recent studies of patients. At the same time, advanced hepatocellular carcinoma itself can cause glucose intolerance and can aggravate diabetes. Diabetes mellitus inducing hepatocellular carcinoma may result in changes in the following aspects: dysfunction of organism, endocrine hormone balance and interactions, endothelins and so on. One way, diabetes mellitus may induce hepatocellular carcinoma through the effects of chemotherapeutics and other adjuvant drugs. This review outlines the relationship between diabetes mellitus and the risk of hepatocellular carcinoma as well as treatments for hepatocellular carcinoma, which may be helpful for clinicians.     

血清可溶性白细胞介素2受体与恶性肿瘤相关性研究

目的　探讨血清可溶性白细胞介素２ 受体（ＳＩＬ－ ２Ｒ）与恶性肿瘤临床分期、临床疗效的关系。方法　采用双抗体夹心ＥＬＩＳＡ法测定了８２例恶性肿瘤患者血清ＳＩＬ－ ２Ｒ水平。结果　８ 种不同恶性肿瘤患者血清ＳＩＬ－ ２Ｒ水平（６０８．０±２７５．７～１１３５．０±６５７．６Ｕ／ｍ ｌ）较之健康对照组（２５０．０±１２８．９Ｕ／ｍ ｌ）均明显升高,且与临床分期及临床疗效密切相关。结论　血清ＳＩＬ－ ２Ｒ检测有助于判断恶性肿瘤患者临床疗效、病情严重程度及估计预后。