血清脂联素水平与I型子宫内膜癌的相关性研究

目的 探讨血清脂联素水平与I型子宫内膜癌的关系。方法 回顾性分析我院收治的34例新发I型子宫内膜癌患者和24例正常子宫内膜患者的临床资料,检测空腹血清葡萄糖、空腹血胰岛素、血清脂联素水平,采用logistic回归分析血清脂联素水平与子宫内膜癌发生的关系。结果  I型子宫内膜癌患者血清脂联素水平与肿瘤FIGO分期、组织学分化程度、肌层浸润深度、宫颈受累、淋巴结转移情况无关（P>0.05）。单因素logistic回归分析结果显示,以脂联素高水平组为对照,脂联素低水平组罹患子宫内膜癌的风险高于高水平组（OR=8.125,95% CI：1.874~35.233,P=0.005）;中水平组罹患子宫内膜癌的风险高于高水平组（OR=4.024,95% CI：1.060~15.278,P=0.041）。调整空腹胰岛素水平或HOMA-IR指数等可能混杂因素后,这种关系依然存在。结论 血清脂联素水平越低,罹患子宫内膜癌的风险越高,低血清脂联素水平可能促进子宫内膜癌发生发展。     

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。     

PGC-1α和ERRγ在子宫内膜癌组织中的表达及临床意义

目的:探讨过氧化物酶体增殖物激活受体辅激活因子1α(PGC-1α)及雌激素受体相关受体γ(ERRγ)在子宫内膜组织中的表达和临床意义及两者的相关性.方法:采用免疫组织化学链霉亲和素-生物素-过氧化物酶复合物技术(streptavidin biotin-peroxidase complex method,SABC)检测子宫内膜癌组织80例、正常子宫内膜组织15例、子宫内膜增生症25例中的PGC-1 α和ERRγ的表达情况,分析其与临床病理参数的关系.结果:子宫内膜癌组织中,PGC-1α的阳性表达率为53.75％,ERRγ的阳性表达率为56.25％,显著高于正常子宫内膜组织及子宫内膜增生症,差异有统计学意义(P＜0.05).在子宫内膜癌组织中,PGC-1α和ERRγ的阳性表达率Ⅲ+ ⅣV期组高于Ⅰ+Ⅱ期组、肌层浸润深度≥1/2组高于＜1/2组,差异有统计学意义(P＜0.05),ERRγ的阳性表达率在ER(+)组高于ER(-)组,差异有统计学意义(P =0.043).在子宫内膜癌组织中PGC-1α和ERRγ表达呈正相关(rs=0.243,P＜0.05).结论:PGC-1α和ERRγ在子宫内膜癌中常呈阳性表达,且与恶性程度相关,二者表达具有相关性,PGC-1α和ERRγ有望成为预测子宫内膜癌恶性程度的潜在生物学指标.     

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。     

血清脂联素水平与子宫内膜癌患者胰岛素抵抗指数的关系分析

目的探讨血清脂联素水平与子宫内膜癌患者胰岛素抵抗指数的相关性及其临床意义。方法选取135例子宫内膜癌患者为研究对象，选择门诊体检的健康妇女135例为对照组，对2组人员的血清脂联素、空腹胰岛素和空腹血糖进行检测。采用稳态模型评估法对胰岛素抵抗指数（HOMA—IR）进行计算，对比观察血清脂联素水平与胰岛素抵抗指数之间的关联性。结果观察组空腹胰岛素水平为（11．3±2．7）μIU／mL，正常组为（6．2±1．6）μIU／mL，观察组明显高于正常组，（P〈0．05）；观察组血糖水平为（7．6±2．9）mmol／L，正常组为（4．6±0．7）mmol／L，2组比较差异有统计学意义（P〈0．05）；脂联素在正常组中的表达为（6．8±1．1）mg／L，显著低于观察组的（15．3±2．3）mg／L，2组比较差异显著（P〈0．05）；观察组和对照组的HOMA-IR分别为（3．5±1．8）和（1．1±0．7），2组比较差异显著（P〈0．05）。脂联素水平越低。HOMA．IR越高，两者呈明显负相关（γ=-0．379，P〈0．05）。结论子宫内膜癌患者脂联素水平降低，导致胰岛素抵抗增强，促进肿瘤细胞增殖，迁移及转化，是发病的危险因素。     

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。     

子宫内膜癌雌、孕激素受体和C-erbB-2检测的临床意义

目的 检测子宫内膜癌组织中雌激素受体(ER)、孕激素受体(PR)及癌基因蛋白C-erbB-2表达的阳性率并探讨其与预后的关系.方法 用免疫组织化学法对32份子宫内膜癌标本进行了ER、PR及C-erbB-2的检测.结果 子宫内膜癌组织中ER、PR、C-erbB-2的阳性率分别为53.1%、50.0%、46.9%.ER、PR的阳性表达率与癌组织的细胞分化程度有关,随着子宫内膜癌组织学分级的增高,ER、PR阳性表达率逐渐降低,C-erbB-2的阳性表达率与肿瘤病理分级呈正相关,与ER、PR表达呈负相关.结论 ER、PR、C-erbB-2均反映了子宫内膜癌的生物学行为,其测定对预测预后、指导选择内分泌治疗具有重要意义.     

孕激素及其受体拮抗剂治疗子宫内膜癌

子宫内膜癌是起源于子宫内膜的恶性肿瘤,其发病与雌激素长期刺激有关.近年来激素治疗越来越受到人们关注.孕激素和孕激素受体拮抗剂米非司酮均可抑制子宫内膜癌细胞生长,有望成为子宫内膜癌治疗的新的辅助手段.现综述孕激素及米非司酮治疗子宫内膜癌的研究进展.     

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。     

葡萄糖转运蛋白1和磷脂结合蛋白-1在子宫内膜癌中的表达及意义

背景与目的:探讨葡萄糖转运蛋白1(GLUT1)和磷脂结合蛋白.1(Annexin-1)在子宫内膜癌组织中的表达情况及其与临床病理参数之间的关系.材料与方法:采用免疫组化S-P法检测65例子宫内膜癌、27例非典型增生和21例增生期子宫内膜组织中GLUT1和Annexin-1的表达.结果:在增生期子宫内膜、非典型增生、子宫内膜癌的GLUT1阳性表达率分别为28.6%、59.3%、81.5%,呈递增趋势,组间两两比较,差异均具有统计学意义(P<0.05);Annexin-1阳性表达率分别为85.7%、55.6%、49.2%,呈下降趋势,其中子宫内膜癌与增生期子宫内膜比较差异有统计学意义(P<0.05).GLUT1高表达与子宫内膜癌的组织分级、肌层浸润深度有关(P<0.05),与病理分期、淋巴结是否转移、组织学类型无关(P>0.05);Annexin-1低表达与上述的临床病理参数皆无关(P>0.05).子官内膜癌中GLUT1与Annexin-1呈负性相关(r=-0.540,P=0.000).结论:Annexin-1低表达和GLUT1高表达可能对子宫内膜癌的发牛和发展具有促进作用,二者对子宫内膜癌早期诊断和预后预测有一定意义.     

Expression of adiponectin receptors, AdipoR1 and AdipoR2, in normal colon epithelium and colon cancer tissue

Adiponectin is secreted by adipocytes and is a key hormone responsible for insulin sensitization. Recent studies have shown that plasma adiponectin is decreased in patients with breast, endometrial and gastric cancer. However, the effect of adiponectin on colorectal carcinogenesis is controversial. It is now well known that the adiponectin receptor exists in two isoforms, adiponectin receptor 1 (AdipoR1) and adiponectin receptor 2 (AdipoR2). We examined the expression of the adiponectin receptors on normal colon mucosa and colon cancer tissues in a human study using real-time RT-PCR, Western blotting and immunohistochemical staining. Adiponectin receptors, AdipoR1/AdipoR2, were expressed in normal colon epithelial and colon cancer cells. Furthermore, laser microdissection was performed to confirm our results. These results suggest that adiponectin may exert some effects on normal colon epithelium or colon cancer cells directly through adiponectin receptors. Further studies are required to elucidate the function of the AdipoRs activated by adiponectin and the downstream mechanisms of AdipoRs in colon cancer cells.     

Adiponectin and breast cancer

Adiponectin, an adipose tissue-derived hormone, has been studied intensively for the past decade because of its anti-inflammatory, anti-atherogenic, and anti-diabetic properties. Recent advances suggest that adiponectin also plays an important role in the development and progression of various cancers, especially obesity-related cancers. In this review, the authors focus on the potential role of adiponectin in breast cancer, an obesity- and endocrine-associated tumor. Epidemiological studies have shown that plasma adiponectin level is a risk factor for breast cancer in post-menopausal women. Adiponectin and its receptors are expressed on both breast cancer line cells and tumor tissues. Furthermore, exogenous adiponectin has exhibited therapeutic potential in animal models. Underlying mechanisms include the inhibition of cell proliferation and promotion of apoptosis, the regulation of tumorigenic-related factors, and the suppression of angiogenesis. The signaling pathways linking adiponectin with tumorigenesis might provide potential drug targets for the future. However, more convincing evidence is needed to fully elucidate the exact role of adiponectin in breast cancer, since both its beneficial effects and possible mechanisms remain controversial.     

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.     

Adiponectin与肿瘤

adiponectin作为脂肪细胞分泌的一种多肽激素,在肿瘤发生中起着重要的抑制作用,它主要是通过与血管发生的相关活性负调控肿瘤的发生发展,并通过结合某些肿瘤细胞中的adiponectin受体或者激活其下游信号通路而直接作用于肿瘤细胞。鉴于adiponectin抑制血管生成的特性以及启动caspase家族诱导细胞凋亡的作用,有望成为一种新的肿瘤治疗药物。     

Adiponectin Receptor Expression in Human Malignant Tissues

Adiponectin has been proposed to be a mediator of obesity-associated malignancies and to have direct antineoplastic effects acting via adiponectin receptors AdipoR1 and AdipoR2. We describe herein the expression of AdipoR1 and AdipoR2 in several cancers not previously studied. We used immunohistochemistry to assess expression of adiponectin receptors in archival specimens of renal cell carcinoma (n?=?64), hepatocellular carcinoma (n?=?123), melanoma (n?=?20), cholangiocarcinoma (n?=?20), transitional cell carcinoma of the bladder (n?=?24), ovarian epithelial carcinoma (n?=?63), cervical squamous cell carcinoma (n?=?49), and adrenocortical carcinoma (n?=?48). To compare expression in malignant versus nonmalignant tissues, we also studied AdipoR1 and AdipoR2 expression in pairs of renal cell carcinoma and adjacent healthy kidney tissue specimens by immunohistochemistry. We also studied mRNA expression in 45 specimens of renal cell carcinoma by real-time polymerase chain reaction. Finally, we utilized Western blotting to confirm the presence of adiponectin receptors and subsequently studied cell signaling pathways of adiponectin in the renal cancer cell line 786-O. Cancers associated with obesity were significantly more likely to express AdipoR1 than cancers not associated with obesity. Of the specimens of renal cell carcinoma, which is strongly associated with obesity, 93.8% expressed AdipoR1 compared to 44.9% of the specimens of cervical cell carcinoma, which is not associated with obesity (p?相似文献   

Adipo-R1 and Adipo-R2 Expression in Colorectal Adenomas and Carcinomas

Background: Human adiponectin (ApN), a 30 kDa glycoprotein of 244-amino acids which is predominantlyproduced by adipocytes, exerts its effects via two receptors, namely adiponectin receptor-1 (adipo-R1) andadiponectin receptor-2 (adipo-R2) with differential binding affinity to globular adiponectin. Adiponectin receptorexpression has been studied in several cancer tissues. However, there are no studies of colorectal adenomas whichare considered to be precursors for colorectal carcinoma (CRC). Objectives: In the present study, the expression ofadipo-R1 and adipo-R2 was investigated immunohistochemically in colorectal adenomas and colorectal carcinomatissues in an attempt to determine associations with these tumors. Materials and Methods: The study enrolled 50CRC patients with tumor resection and 82 patients who were diagnosed with adenomatous polyps, classified asnegative for neoplasia, low-grade dysplasia (L-GD) or high- grade dysplasia (H-GD). Results: Expression of bothadipo-R1 and adipo-R2 was found to be significantly lower in the CRCs than in colorectal adenomas (tubular andtubulovillous, p=0.009 and p<0.001, respectively). Adipo-R1 and adipo-R2 expression was also significantly lowerin the CRC group when compared with the groups of patients with low grade dysplasia, high-grade dysplasiaor no neoplasia (p=0.012 and p<0.001, respectively). In addition, it was observed that adipo-R2 expression wasgenerally positive in the non-neoplastic group irrespective of the adipo-R2 expression. In the L-GD, H-GD andCRC groups, the adipo-R2 result was positive whenever adipo-R1 result was positive but some patients withnegative adipo-R1 had positive adipo-R2 (p<0.001, p=0.004, p<0.001, respectively). Conclusions: This studyindicated that ApN may play a role in the progression of colorectal adenomatous polyps to carcinoma throughactions on adipo-R1 and adipo-R2 receptors.     

舌癌组织缺氧微环境中脂联素的表达与调控

  目的  脂联素（adiponectin,APN）是一种内源性细胞因子,与多种肿瘤的发生发展密切相关。本研究旨在检测舌癌APN及其受体（AdipoR1和AdipoR2）的组织学表达分布特征,探讨APN在局部组织中的表达是否受到缺氧诱导因子HIF-1α的调控。  方法  采用免疫组织化学检测舌癌组织中APN及其受体的表达分布特征;慢病毒包装HIF-1α shRNA载体并转染舌癌细胞构建稳定沉默HIF-1α的细胞系;应用RT-PCR和蛋白质印迹法（Western blot）检测APN及其受体mRNA和蛋白在缺氧条件下的表达变化。  结果  在肿瘤发生早期,即当肿瘤体积较小（T1和T2期）或未发生淋巴结转移（N0期）时,肿瘤组织APN及AdipoR1的表达与癌旁正常上皮相比上调（P < 0.05, < 0.01）,AdipoR2的表达无显著改变。将舌癌细胞缺氧后APN及AdipoR1的表达分别上调,但AdipoR2的表达不变。敲低HIF-1α表达后缺氧处理可同时下调APN及AdipoR1表达。  结论  舌癌局部缺氧微环境下,APN-Adi-poR1信号通路被激活,该过程受到HIF-1α的调控。      

Role of tumor necrosis factor-alpha and its receptors in human benign breast lesions and tumors (in situ and infiltrative)

The aim of the present study was to characterize the expression pattern of tumor necrosis factor (TNF)-alpha and its receptors in breast samples (benign diseases, in situ carcinomas and infiltrating carcinomas), and to compare these results with those obtained previously for interleukin-6, p53 and p21 using the same samples in order to elucidate the effects of these cytokines on the proliferation-apoptosis equilibrium. Immunoexpression of TNF-alpha and its receptors (TNFRI and TNFRII) were studied by western blotting and immunohistochemistry. The percentage of samples positive for TNF-alpha and TNFRII was higher in in situ carcinoma than in benign breast diseases, and TNFRII was even higher in infiltrating tumors. The percentage of samples positive for TNFRI was similar in the three groups. For the three proteins and in the three patient groups, immunoreactions were observed in the peripheral cytoplasm. In the positive samples, immunostaining for TNF-alpha was more intense in infiltrating tumors than in the other two patient groups, whereas immunostaining for both receptors was higher in in situ carcinoma than in benign breast diseases, and even higher in infiltrating tumors. Comparing the TNF-alpha results with previous results for mtp53, p21 and interleukin-6, we found an association between the expression of these four proteins and increasing malignancy. TNF-alpha might be an important factor in breast cancer promotion as its proliferation and survival effects seems to be enhanced through the increased expression of TNFRII. Also, the pro-apoptotic pathway of TNFRI could be inhibited by p21 (which appeared increased in breast cancer), altering TNFRI effects in promoting the expression of several factors, such interleukin-6, which contribute to tumor promotion.     

Epidermal growth factor prolongs survival time of tumor-bearing mice

We observed that human epidermal growth factor (hEGF) alone prolonged the survival time of mice bearing various murine syngeneic tumors as well as athymic nude mice bearing human xenografts. No changes in the subcutaneous solid tumor mass volume were observed. Prolongation of survival time by hEGF was observed in mice bearing murine epidermoid carcinoma (BSC) and human gastric carcinoma (KATO III), but not in murine epidermoid carcinoma (KLN205) or human epidermoid carcinoma (A431). Human tumor cells such as A431, KATO III, and murine tumor cells, KLN205, BSC had roughly 2 X 10(6), 3 X 10(4), 1.3 X 10(3) and 1 X 10(3) EGF receptors/cell, respectively. Although KLN205 and BSC tumor cells maintained nearly the same number of EGF receptors, the effects of hEGF were very different. Although A431 tumor cells had nearly 100 times more receptors than KATO III cells, the prolongation of survival time of mice bearing A431 by hEGF was no better than that of mice bearing KATO III. Accordingly, it appears that this prolongation of survival time by hEGF is independent of the number of EGF receptors on tumor cells. In addition, hEGF was shown to inhibit experimental pulmonary metastasis of murine BSC tumor, but was ineffective with murine KLN205 tumor. These results suggest that prolongation of survival time by hEGF may result from the inhibition of tumor cell metastasis and EGF may play a role in preventing the metastasis of certain malignant neoplasms unrelated to its effects through the EGF receptor on tumor cells.