脂联素对高脂饮食诱导的胰岛素抵抗子宫内膜癌裸鼠移植瘤生长的影响

目的 探讨脂联素对高脂饮食诱导裸鼠胰岛素抵抗子宫内膜癌移植瘤生长的影响。方法 40只裸鼠随机分成高脂组和普食组,每组20只,分别喂养高脂饲料（high-fat diet,HFD）和普通饲料（normal diet,ND）,10周后测定裸鼠空腹血糖（fasting blood glucose,FBG）和空腹血胰岛素（fasting serum insulin,FINS）水平,计算胰岛素抵抗指数（HOMA-IR）,建立胰岛素抵抗裸鼠模型。第11周接种子宫内膜癌HEC-1B细胞,待瘤体长至0.5 cm时,两组随机选取10只裸鼠腹腔注射脂联素（adiponectin,APN）分为HFD+APN组、ND+APN组;其余裸鼠分别注射0.9%氯化钠分为HFD组、ND组;14周后,测定各组血糖和血脂的代谢情况。结果 高脂组裸鼠10周后的平均体重、体长、FBG、FINS、HOMA-IR均大于普食组,糖耐量试验和胰岛素耐量试验结果显示血糖水平亦高于普食组（均P＜0.05）;接种子宫内膜癌HEC-1B细胞后均成瘤,建模成功。HFD+APN组和ND+APN组移植瘤平均重量和体积增长速度均分别低于HFD组和ND组（均P<0.05）。HFD组和HFD+APN组14周后的FINS、HOMA-IR、TC和TG均较ND组和ND+APN明显升高（均P<0.01）,且HFD组明显高于HFD+APN组（均P<0.01）;HFD+APN组的血脂联素水平低于ND+APN组（P<0.01）,HFD组则低于ND组（P<0.05）。结论 脂联素可改善高脂饮食导致的胰岛素抵抗,抑制子宫内膜癌移植瘤生长。     

脂联素及其受体与子宫内膜癌关系的研究进展

脂联素是脂肪细胞分泌的一种内源性细胞因子,与肥胖相关疾病如子宫内膜癌等密切相关.子宫内膜癌患者血清中脂联素呈低水平状态.脂联素通过其受体参与糖脂代谢、抗炎、抗肿瘤等生理过程.本文就脂联素及其受体的基因结构、生物学作用、其作用于子宫内膜癌的相关机制做一论述.     

血清脂联素水平与肿瘤关系的实验研究

目的：探讨脂联素作为血清学标志物在肿瘤诊断和治疗中的价值。方法：用酶联免疫吸附试验对292例不同肿瘤患者和60名健康人血清中脂联素水平进行检测。结果：正常男女之间血清脂联素水平无差别;60名乳腺癌患者血清平均脂联素水平明显低于30名健康女性平均血清脂联素水平,66名结肠癌患者血清平均脂联素水平明显低于60名健康对照者,胃癌患者血清中脂联素水平与正常人血清脂联素水平无明显差别;肝癌和肺癌患者血清脂联素平均水平略高于正常人,但无统计学意义。结论：乳腺癌和结肠癌患者血清脂联素低于正常人;肝癌、肺癌、胃癌患者体内脂联素与正常人无明显差别。循环系统中低水平脂联素可能是某些肿瘤的危险因素。     

子宫内膜癌与胰岛素抵抗的研究进展

胰岛素抵抗（insulin resistance,IR）是指部分胰岛素与其特异性受体结合后产生的生物学效应较正常者低。研究发现IR不仅能够引起机体血糖代谢的异常,同时也引起机体其他方面的代谢紊乱。除了高胰岛素血症对子宫内膜癌的影响外,IR引起的代谢改变对子宫内膜癌亦产生影响。二甲双胍通过激活AMPK促进葡萄糖的利用,LKB1作为其上游的调节因子,能在多种细胞内磷酸化和活化AMPK,从而起到下调血糖的作用。     

小檗碱对多囊卵巢综合征大鼠的胰岛素抵抗及瘦素、脂联素水平的影响

目的探讨小檗碱对多囊卵巢综合征大鼠的空腹血糖(FPG)、空腹胰岛素(FINS)、瘦素(LPN)、脂联素(APN)水平的影响。方法采用Poresky造模法,制作多囊卵巢综合征大鼠模型,造模后将大鼠随机分为正常对照组、模型对照组、二甲双胍组、小檗碱组,每组15只。观察药物干预21天后各组大鼠体重、FPG、FINS、LPN、APN的变化,并计算胰岛素敏感性指数(IRI)。结果与模型对照组比较,小檗碱组和二甲双胍组大鼠体重、IRI、LPN水平均下降(P﹤0.05);APN水平上升;小檗碱组APN水平变化较二甲双胍组更为明显(P﹤0.05)。结论小檗碱可能通过降低体重、增加胰岛素敏感性、调节瘦素和脂联素水平,从而改善大鼠生殖功能。     

脂联素与肿瘤相关性的研究进展

脂肪组织已经不是普通意义上的脂肪仓库,而成为一个内分泌器官。脂肪细胞分泌的众多脂肪因子当中,脂联素(adiponectin)是惟一一个随着脂肪组织体积变大在血液循环中浓度反而降低的因子。脂联素不但在糖类和脂类代谢过程中起到重要作用,目前也认为和一些恶性肿瘤有关。大量的临床试验和基础研究表明,肿瘤患者血清脂联素水平偏低,并且肿瘤细胞表达脂联素受体。因此,脂联素可能通过与脂联素受体结合并激活受体和信号传导通路的下游,直接作用于肿瘤细胞,或者通过抗血管生成,诱导肿瘤细胞凋亡和其他机制调节细胞增殖,从而导致肿瘤的发生。通过研究脂联素,可以发现肥胖和肿瘤之间的关系。     

脂联素与乳腺癌的相关性

 脂联素是至今发现的惟一与肥胖呈负相关的脂肪细胞特异性蛋白,具有增强胰岛素敏感性、抗动脉硬化、抗炎作用。最近有研究报道,脂联素与多种肥胖相关恶性肿瘤的发生发展密切相关,尤其是绝经后乳腺癌。肥胖是乳腺癌发生的独立危险因素,近来关于脂联素与乳腺癌的关系及其作用机制、信号通路的研究有很大进展。     

脂联素与肿瘤相关关系的研究现状

脂联素是由脂肪细胞特异分泌的一种生物活性分子，与肥胖、胰岛素抵抗等多种疾病相关。近几年关于脂联素与乳腺癌、子宫内膜癌、子宫平滑肌瘤、白血病、结肠直肠癌、胃癌、前列腺癌等几种恶性肿瘤的相关关系及其作用机制的研究取得了较大的进展．     

脂联素与肿瘤相关关系的研究现状

脂联素是由脂肪细胞特异分泌的一种生物活性分子,与肥胖、胰岛素抵抗等多种疾病相关。近几年关于脂联素与乳腺癌、子宫内膜癌、子宫平滑肌瘤、白血病、结肠直肠癌、胃癌、前列腺癌等几种恶性肿瘤的相关关系及其作用机制的研究取得了较大的进展。     

脂联素受体的表达与大肠癌分期和分级的关系

 目的
探讨脂联素受体表达水平与大肠癌病理学分级、临床分期间的关系。方法应用免疫组织化学SP法检测 71例大肠癌
组织、20例大肠腺瘤和71例大肠正常黏膜组织中脂联素受体的表达情况,以Image-Pro Plus图像分析软件进行半定
量测定。结果脂联素受体在大肠癌中低表达,其表达水平和大肠癌的Dukes分期、淋巴结转移和病理学分级密切相
关。肿瘤的Dukes分期越晚、淋巴结发生转移者及分化程度越低,其脂联素受体的阳性表达率越低,表达程度越差
。健康对照组、腺瘤组中脂联素受体均匀表达于大肠黏膜组织腺管的腺胞细胞膜及细胞质;腺癌组中脂联素受体在
肿瘤细胞的细胞膜及细胞质少量表达,腺癌组与健康对照组、腺瘤组比较差异均具有统计学意义(P均＜0.005）,
健康对照组与腺瘤组比较差异无统计学意义(P>0.05）,其中脂联素受体在健康对照组的阳性表达率明显高于腺癌
组(98.59% vs.74.65%脂联素受体1和97.18% vs.70.42%脂联素受体2）,在Dukes分期、肿瘤的病理学分级及有无淋
巴结转移间的比较差异也具有统计学意义(P<0.05）。结论脂联素的表达水平降低与大肠癌及其分化水平、Dukes分
期和淋巴结转移具有一定的负相关关系,它有望成为临床上治疗和监测大肠癌的重要手段之一。     

Serum leptin,adiponectin and endometrial cancer risk in Chinese women

Objective

To investigate the relationship between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women.

Methods

We conducted a case-control study of a total of 516 Chinese women to detect the relationships between serum concentrations of leptin or adiponectin, and endometrial carcinoma in Chinese women. The study subject constituted 206 cases of endometrial cancer and 310 normal controls.

Results

Patients with endometrial carcinoma had higher serum leptin concentrations than controls (28.8±2.2 ug/L vs. 19.8±1.4 ug/L; p<0.001). The adiponectin levels in patients were lower than in controls with borderline statistical significance (2,330.7±180.5 ug/L vs. 2,583.9±147.2 ug/L; p=0.078). Logistic regression analysis confirmed the associations between leptin or adiponectin, and endometrial carcinoma after adjustment for age, body mass index, fasting insulin, serum glucose, cholesterol, triglycerides, and high-density lipoprotein cholesterol (odds ratio for the top tertile vs. the bottom tertile: leptin 2.05; 95% confidence interval [CI], 1.28 to 3.29; p<0.001; adiponectin 0.52; 95% CI, 0.32 to 0.83; p<0.001).

Conclusion

Increased leptin or decreased adiponectin levels are associated with endometrial carcinoma.     

Significance of Serum Adiponectin and Insulin Resistance Levels in Diagnosis of Egyptian Patients with Chronic Liver Disease and HCC

One possible hypothesis for pathogenesis of hepatocellular carcinoma is deregulated expressed adipokines(adipose tissue cytokines). Chronic inflammation in the cirrhotic liver adipose tissue is associated with a modificationin adipokine secretion. Changes in serum levels of adiponectin are known to be associated with the development ofinsulin resistance. Increased insulin resistance is a pathophysiological feature of nonalcoholic fatty liver disease(NAFLD), one of the most common causes of chronic liver disease. In addition, it was suggested that liver cancerdevelopment is probably connected with insulin resistance. The aim of this study is to evaluate the significance ofserum Adiponectin level and insulin resistance in patients with chronic liver disease and hepatocellular carcinoma.Patient and Methods: 100 patients were enrolled in this cross sectional study and divided as following: Group I: 52HCV patients with chronic liver disease (CLD).Group II: 48 patients with hepatocellular carcinoma (HCC). For allsubjects, Serum Adiponectin and Insulin Resistance parameters (Fasting serum Insulin, Fasting serum Glucose, HOMAIR) were measured. Results: Serum Adiponectin was significantly lower in patients with hepatocellular carcinoma(p=0.000 ) and it is inversely correlated to tumor size and the number (p= 0.0001).Meanwhile, Insulin Resistanceparameters (Fasting s. Insulin, Fasting s. Glucose, HOMA IR) were significantly higher in HCC patients than CLDpatients (p= 0.0001). Conclusion: Insulin Resistance is significantly associated with the development of HCC. Serumlevel of Adiponectin may guard against HCC development among patients with chronic liver disease.     

Insulin resistance and endometrial cancer risk: A systematic review and meta-analysis

AimIt has been suggested that chronic hyperinsulinemia from insulin resistance is involved in the etiology of endometrial cancer (EC). We performed a systematic review and meta-analysis to assess whether insulin resistance is associated with the risk of EC.MethodsWe searched PubMed-Medline, Embase, Scopus, and Web of Science for articles published from database inception through 30th September 2014. We included all observational studies evaluating components defining insulin resistance in women with and without EC. Quality of the included studies was assessed by Newcastle–Ottawa scale. Random-effects models and inverse variance method were used to meta-analyze the association between insulin resistance components and EC.ResultsTwenty-five studies satisfied our inclusion criteria. Fasting insulin levels (13 studies, n = 4088) were higher in women with EC (mean difference [MD] 33.94 pmol/L, 95% confidence interval [CI] 15.04–52.85, p = 0.0004). No differences were seen in postmenopausal versus pre- and postmenopausal subgroup analysis. Similarly, non-fasting/fasting C-peptide levels (five studies, n = 1938) were also higher in women with EC (MD 0.14 nmol/L, 95% CI 0.08–0.21, p < 0.00001). Homeostatic model assessment - insulin resistance (HOMA-IR) values (six studies, n = 1859) in EC patients were significantly higher than in women without EC (MD 1.13, 95% CI 0.20–2.06, p = 0.02). There was moderate-to-high heterogeneity among the included studies.ConclusionCurrently available epidemiologic evidence is suggestive of significantly higher risk of EC in women with high fasting insulin, non-fasting/fasting C-peptide and HOMA-IR values.     

子宫内膜癌多药耐药基因(MDRI)的表达及其意义

目的探讨子宫内膜癌多药耐药基因（ＭＤＲ１）的表达及其意义。方法利用逆转录聚合酶链反应（ＲＴ－ＰＣＲ），对３７例初治子宫内膜癌、１０例正常子宫内膜及１０例正常子宫肌层组织ＭＤＲ１基因的表达进行检测，同时用ＭＴＴ法对宫内膜癌进行肿瘤细胞体外药敏试验。结果３７例子宫内膜癌和１０例正常子宫内膜组织ＭＤＲ１表达均为阳性，ＭＴＴ药敏试验表明绝大多数子宫内膜癌对化疗药物具有交叉耐药性。结论子宫内膜癌对化疗的耐药可能是一种固有性ＭＤＲ，这可能与ＭＤＲ１基因的表达有关。     

Serum Adiponectin Level Association with Breast Cancer Risk: Evidence from a Case-Control Study

Background: Adiponectin is a protein, synthesized by adipose tissue, which has a questionable role in breastcancer pathogenesis. This study focused on serum levels of adiponectin among cases and controls, and its possibleassociation with breast cancer risk. Materials and Methods: This case-control study covered 175 diagnosedbreast cancer patients with positive histopathology from Breast Clinic, surgical unit-1, Civil Hospital, Karachiand 175 healthy controls from various screening programs. Blood samples were obtained after an overnightfast and later analyzed. Results: Fasting blood glucose was significantly raised, while serum adiponectin wassignificantly decreased in breast cancer cases when compared to control subjects. To find the precise influenceof serum adiponectin on the risk of breast cancer, subjects were divided in to quartiles based on serum levelsof adiponectin. It is observed that risk of breast cancer decreased with rising quartile. Q2 (25th-50th) had thehighest OR=1.76 (CI: 0.93- 3.34), Q3 (50th-75th) has OR= 0.89 (CI: 0.48-1.64), while subjects in the highestquartile Q4 (>75th) had significantly (p< 0.05) decreased risk of breast cancer having OR=0.06 (CI: 0.02-0.15),when compared to the lowest quartile. Conclusions: We demonstrated a statistically significant association ofelevated serum adiponectin with decreased risk of breast cancer. This signifies a protective role of adiponectinvia an intricate mechanism of masking mitogenic growth factors in breast carcinogenesis.     

绝经与子宫内膜癌预后的关系

目的探讨绝经前后妇女子宫内膜癌的临床病理特征以及绝经能否作为子宫内膜癌的预后因素。方法将212例子宫内膜癌患者按是否绝经分为2组：未绝经组78例，绝经组134例。分析两组患者的临床病理特征及预后。结果未绝经组与绝经组相比，不孕患者比例低（分别为14．1％和19．2％）。高血压患者比例低（分别为4．5％和33．6％），组织分级低（G3分别为12．3％和26．2％）、深肌层浸润少见（分别为9．0％和29．1％），复发少（分别为5．1％和12．7％），生存率高。上述各项均有显著性差异（P〈0．05）。结论未绝经子宫内膜癌者的预后较好，与临床病理特点有关。绝经可以作为子宫内膜癌的1个独立的预后因素。     

子宫内膜病变组织中脆性组氨酸三联体基因的表达及临床研究

目的探讨脆性组氨酸三联体基因(FHIT)在子宫内膜癌及子宫内膜不典型增生组织中的表达及其与临床意义。方法以75例子宫内膜不典型增生及75例子宫内膜癌患者作为研究组,选取60例同期正常子宫内膜组织作为对照组,采用免疫组织化学(SP)方法,检测研究组与对照组中子宫内膜组织中FHIT的表达情况。并分析FHIT表达与子宫内膜癌病理分期、组织学分级的关系。结果正常子宫内膜、子宫内膜不典型增生、子宫内膜癌组织FHIT阳性表达率分别为96.67%、57.33%、34.67%(P<0.05)。高、中、低分化子宫内膜腺癌患者FHIT阳性表达率分别为61.54%、34.04%、13.33%,三者间有显著差异(P<0.05),Ⅰ期、Ⅱ期、Ⅲ期患者FHIT表达无显著差异。轻、中、重度子宫内膜不典型增生患者FHIT阳性率分别为64.71%、57.57%、52.00%。结论 FHIT作为1种肿瘤抑制基因蛋白,可能成为临床判断子宫内膜不典型增生预后转归的预测因素。     

影响子宫内膜癌患者术后放疗效果的相关因素分析

目的 分析影响子宫内膜癌患者术后放疗效果的相关因素.方法 随机抽取行子宫内膜癌术后放疗患者80例,综合分析患者的年龄、病理分型分期、转移与否以及患者月经情况对术后放疗效果的影响.结果 80例患者随访2年,7例死亡,2年总生存率为91.3%,11例复发,复发率为13.8%,10例发生转移,转移率为12.5%.单因素分析结果显示:病理分期和淋巴结转移影响术后放疗效果(P<0.05);患者年龄、绝经与否以及病理分型与术后放疗效果不存在明显相关性(P>0.05).Logistic多因素分析显示,病理分期和淋巴结转移是患者术后放疗的独立危险因素(P<0.05);患者年龄、绝经与否以及病理分型与术后放疗效果无明显相关性(P>0.05).结论 子宫内膜癌病理分期和淋巴结转移是影响术后放疗效果的独立危险因素,值得关注.