胰岛素样生长因子家族测定对肝脏疾病的临床评估

研究表明胰岛素样生长因子家族与肝脏疾病关系密切，本文综述胰岛素样生长因子家族的结构、分布、生物学活性及多种受体和信号传导作用；胰岛素样生长因子-Ⅰ与肝硬化的关系研究表明，它可作为反映肝细胞活性的间接指标。并对预后有重要提示作用；胰岛素样生长因子-Ⅱ在肝癌的发生和发展有重要意义。对其在肝癌的作用机制进行了探讨。并发现胰岛素样生长因子-Ⅱ的敏感性更高。     

胰岛素样生长因子Ⅱ受体与肝癌

胰岛素样生长因子Ⅱ（IGF-Ⅱ）受体是一种多配体,多功能的膜蛋白,与肝癌等多种肿瘤的发生,发展有关。近年的研究表明,IGF-Ⅱ受体在肝癌细胞中高表达与HBV-DNA整合及HBxAg的表达密切相关;IGF-Ⅱ受体参与调控癌前病变肝细胞的异常增殖。本文综述了IGF-Ⅱ受体与肝癌的关系。     

高胰岛素血症与糖尿病癌症联系及临床应用

近年来糖尿病与肿瘤的关联已引起国内外学界的广泛关注.糖尿病患者肿瘤的发生及其死亡风险显著增加,而与肥胖相关的高胰岛素血症及其胰岛素/胰岛素样生长因子(IGF)是其关联的重要生物学联系.     

降糖药物的新成员——类胰岛素生长因子1

众所周知，介导生长激素治，疗生长激素缺乏或其他身材矮小症的介导物为类胰岛素生长因子（IGF-1），因其分子结构与人胰岛素分子有许多相同之处，故名之为类胰岛素生长因子。     

胰岛素样生长因子与乳腺癌

胰岛素样生长因子 ( Insulin- like growth factors,IGFs)家族最初是由 Salman和 Daughaday于 195 7年发现的 ,因其在基因结构上与胰岛素原具有高度同源性 ,具有类似胰岛素的作用而得名。 IGFs系统是一个庞大的家族 ,包括 IGF- 和 IGF- 两类生长因子 ;两类受体有 型胰岛素样生长因子受体 ( IGF- R)和 型胰岛素样生长因子受体 ( IGF- R) ,以及胰岛素样生长因子结合蛋白 ( IGFBPs)。IGF- 和 IGF- 分别通过同细胞膜上的相关受体 ( IGF- R,IGF- R)结合 ,引发相继的生物学效应。在循环中 ,它们通常是同它们的特异性结合…     

IGF-1、IGF-BP-1、IGF-BP-3与糖尿病及糖尿病微血管并发症

糖尿病影响循环中胰岛素样生长因子的水平和活性,不同类型的糖尿病对胰岛素样生长因子活性的影响是不同的.糖尿病患者体内胰岛素样生长因子的紊乱,可能参与糖尿病肾病、糖尿病视网膜病变的发生、发展.胰岛素样生长因子结合球蛋白-1可能对微血管病变起保护作用,胰岛素样生长因子结合球蛋白-3参与微血管病变的发病机制不明.     

胰岛素样生长因子1在心力衰竭中的研究进展

胰岛素样生长因子1(IGF-1)是体内一种结构和功能与胰岛素具有显著相似性的重要细胞因子,能在大多数组织中表达,属于胰岛素家族的一种活性蛋白多肽。它通过与自身特异性受体结合,发挥重要的生理功能。近年来,随着对IGF-1与心血管疾病关系研究的深入,发现IGF-1能够促进心肌细胞增殖,增强心肌收缩力,抑制心肌细胞凋亡等,与心力衰竭(HF)发生发展及指导其治疗密切相关。     

胰岛素类似物的潜在致癌作用

近年来，越来越多的糖尿病患者使用胰岛素类似物控制血糖，联用超短效和超长效胰岛素类似物能更好地模拟生理性胰岛素释放，使血糖更平稳，但胰岛素类似物结构上的改变也导致了其生物学效应的改变，它们与胰岛素样生长因子-1（IGF-1）受体的亲和力也有异于普通胰岛素，其促有丝分裂活性的改变可能影响乳腺和肠道等部位恶性肿瘤的发生率。     

肝硬化生长激素-胰岛素样生长因子轴的基础与临床研究

生长激素(GH)是由脑腺垂体前叶嗜酸性粒细胞分泌的一种含191个氨基酸的蛋白质多肽。肝脏是生长激素最主要的靶器官。生长激素可直接与靶组织特异性受体结合发挥其生物学作用；另一方面，生长激素又可通过生长激素-肝-胰岛素样生长因子轴(GH—IGF轴)，刺激肝、肾及其他部位产生胰岛素样生长因子(insulin—like growth factors，IGFs)而间接发挥其生物学效应。     

重视糖尿病与癌症关系的研究

糖尿病,尤其是2型糖尿病,易并发癌症,主要是胰腺癌、肝癌、结肠直肠癌、乳腺癌、子宫内膜癌等,且致死亡率增加,其确切原因不明.可能与高胰岛素血症及胰岛素样生长因子的促生长及促有丝分裂作用有关.最近对某些长效胰岛素类似物的这一作用提出疑问,但目前尚无可靠证据证明这一点.二甲双胍似可能有保护作用.     

The role of the insulin-like growth factor system in colorectal cancer: review of current knowledge

Background The insulin-like growth factor system, which includes insulin-like growth factors (IGF-I and IGF-II), IGF receptors (IGF-IR and IGF-IIR) and IGF binding proteins (IGFBPs), plays an important role in epithelial growth, anti-apoptosis and mitogenesis. There is a growing body of evidence showing that IGFs control growth and proliferation of several types of cancer. This review introduces the latest information on the biology of the IGF system and its pathophysiological role in the development of colorectal cancer.Discussion The growth promoting effects of IGF-I and IGF-II on cancer cells are mediated through the IGF-IR, which is a tyrosine kinase and cancer cells with a strong tendency to metastasise have a higher expression of the IGF-IR. Most of the IGFs in circulation are bound to the IGFBPs, which regulate the bioavailability of the IGFs. All IGFBPs inhibit IGF action by high affinity binding, while some of them also potentiate the effects of IGFs. Colon cancer cells produce specific proteases that degrade the IGFBP so that the IGF will be free to act on the cancer cell in an autocrine manner. Therefore, the IGFBPs play a crucial role in the development of the cancer.Conclusion The current knowledge about the link between IGFs and colon cancer is mainly based on in vitro investigations. Further in vivo study is needed to understand the exact role of the IGF system, especially its binding proteins, so that they can be manipulated for the prevention and treatment of colorectal cancer.     

Insulin-like growth factor system gene expression in cervical scrapes from women with squamous intraepithelial lesions and cervical cancer

BACKGROUND: There is ample evidence that the insulin-like growth factors (IGF) system is involved in the development of several types of cancer. The aim of this study was to evaluate the expression levels of IGF-I, IGF-II, IGF binding protein 3 (IGFBP-3) and IGF-I receptor (IGF-IR) in exfoliated cervical cells in cervical carcinogenesis. METHODS: mRNA levels of IGF-I, IGF-II, IGFBP-3 and IGF-IR were assessed by real-time PCR in 105 cervical scrapes obtained from 16 patients diagnosed with low-grade squamous intraepithelial lesions (LSIL), 24 with high-grade SIL (HSIL), 23 with cervical cancer, and 42 from controls with normal Papanicolau (Pap) test. RESULTS: IGF-I mRNA levels were very low and no significant differences were seen between control and other groups. IGF-II mRNA levels were significantly lower in LSIL than in control group (median [arbitrary units]: 0.38 vs. 2.42, P=0.006) but its expression in HSIL and cervical cancer was similar to the one observed in controls. IGFBP-3 mRNA levels were significantly lower in cancer than in controls (median [arbitrary units]: 0.43 vs. 0.73, P=0.03). We observed a decrease in IGF-IR gene expression as the SIL degree increased (median for controls, LSIL, HSIL, and cervical carcinoma [arbitrary units]: 31.24, 9.08, 8.95, and 3.56, respectively). IGF-IR mRNA levels were significantly lower in HSIL and cervical cancer in comparison with controls (P=0.043 and P<0.001, respectively). CONCLUSIONS: The present observations suggest that a reduced expression of IGFBP-3 and IGF-IR can be associated with progression to cervical cancer; the specific role played by the IGF-IR in this process remains unclear.     

Possible roles of insulin,IGF-1 and IGFBPs in initiation and progression of colorectal cancer

AIM: To investigate the roles of serum insulin, insulinlike growth factor-1(IGF-1), and insulin-like growth factor binding proteins(IGFBPs) in the initiation and progression of colorectal cancer. METHODS: We determined serum insulin, IGF-1 and IGFBPs levels in 615 colorectal cancer patients and 650 control healthy donors by enzyme-linked immunosorbent assay(ELISA). In the meantime, their body mass index(BMI) and waist-to-hip ratio(WHR) were measured. RESULTS: Serum levels of insulin and IGF-1 as well as IGF-1/IGFBP-3 ratio in pre-operation patients were significantly elevated, but the level of IGFBP-3 was significantly decreased compared with normal controls and post-operation patients(P < 0.05 and P < 0.001,respectively). There is no significant difference(P > 0.05) in the levels of insulin, IGF-1, IGFBP-1, IGFBP-3 and IGF-1/IGFBP-3 between the patients with and without hepatic as well as distal abdominal metastases. WHR and BMI of colon cancer patients were positively and significantly correlated with the levels of insulin and IGF-1/IGFBP-3. In contrast, WHR and BMI were negatively correlated with IGFBP-3 level. CONCLUSION: The elevation of insulin, IGF-1 as well as IGF-1/IGFBP-3 ratio and the reduction of IGFBP-3 may be related to the initiation of colorectal cancer, but they are not related to the progression and outcome of the disease.     

Attenuation of IGF-I receptor signaling inhibits serum-induced proliferation of prostate cancer cells

Objective

Several studies showed that high serum levels of insulin-like growth factor-I (IGF-I) correlate with an increased risk for prostate cancer, although the causal role of IGF-I remains to be established. In this study, we addressed the role of IGF-I as a serum factor on the growth of two androgen-independent cell lines (Du145 and PC3) and one androgen-dependent cell line (LNCaP).

Design

We investigated the effects of a blocking antibody against the IGF-I receptor (αIR3) on DNA synthesis in prostate cancer cells cultured in the presence of recombinant human IGF-I or normal human serum (NHS).

Results

We show that in all three prostate cancer cell lines, NHS exerts a markedly stronger stimulating effect on DNA synthesis than IGF-I, and that the effect of NHS can be completely abrogated by an antibody against the IGF-I receptor (αIR3). Using pharmacological inhibitors of the two canonical IGF-I receptor signaling pathways, we show that the phosphatidylinositol-3′-kinase (PI3K) and the Mek–Erk pathways are not required for the stimulating effect of NHS.

Conclusion

Our observations indicate that the stimulating effect of NHS is completely dependent on IGF-I receptor signaling transduction and that IGF-I stimulates DNA synthesis in prostate cancer cells in strong synergy with other serum factors. We speculate that the role of other serum factors could explain the discrepancy between the results observed in different animal models to study the function of IGF-I in prostate cancer.     

肺癌胰岛素样生长因子-2基因印迹的研究

目的探讨胰岛素样生长因子-2(IGF2)基因印迹(genomicimprinting)与肺癌发生发展过程的关系。方法于2003年1月至2004年1月,对大连医科大学附属第一医院胸外科手术切除的标本,根据IGF2基因第9外显子具有ApaI位点多肽性,利用聚合酶链反应(PCR)技术结合限制性片段长度多态性(RFLP)技术,诊断的32例肺癌患者及其对应的癌周正常肺组织进行了IGF2基因印迹的研究。结果12例患者为杂合子信息个体(37·5%),其中10例为IGF2双等位基因表达,即发生了基因印迹缺失(LOI,83·3%),而且这10例病人中有4例的癌周正常肺组织表现为IGF2弱的双等位基因表达。结论IGF2基因的印迹缺失参与了肺癌的发生发展过程。     

非小细胞肺癌中IGF1、IGFBP2表达与预后的相关性分析

目的探讨非小细胞肺癌组织胰岛素样生长因子1(IGF1)、胰岛素样生长因子结合蛋白2(IGFBP2),蛋白表达与患者临床病理特征及预后的关系。方法将226例确诊的非小细胞肺癌患者癌组织为非小细胞肺癌组;选取其癌旁正常组织为癌旁对照组。检测癌组织及癌旁正常组织IGF1、IGFBP2蛋白表达水平;分析非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达相关性及其与预后的关系;并分析影响非小细胞肺癌患者预后的因素。结果非小细胞肺癌组IGF1、IGFBP2蛋白高表达率高于癌旁对照组(P<0.05)。非小细胞肺癌患者癌组织IGF1、IGFBP2蛋白表达与肿瘤大小、淋巴结转移、组织分化程度、TNM分期有关(P<0.05)。非小细胞肺癌患者癌组织IGF1与IGFBP2蛋白表达呈正相关(r=0.472,P<0.05)。IGF1、IGFBP2高表达患者五年生存率(33.33%、29.41%)低于低表达患者(69.23%、73.33%)(P均<0.05)。IGF1高表达、IGFBP2高表达、TNMⅢ~Ⅳ期是影响非小细胞肺癌患者死亡的独立危险因素(P<0.05)。结论IGF1、IGFBP2可能在非小细胞肺癌发生发展过程中发挥重要作用,且IGF1、IGFBP2高表达与患者不良预后有关。     

胰岛素样生长因子系统在肿瘤转移中的研究进展

胰岛素样生长因子(IGFs)系统由具有特定功能的配体(IGF-I和IGF-II)、受体(IGFR)和结合蛋白(IGFBPs)组成,在促有丝分裂,细胞转化和抑制凋亡中起重要作用,这些作用主要由IGF-I受体介导。IGFBPs是IGFs活性的调节因子。近年来研究表明IGFs系统与肿瘤的浸润和转移关系密切。     

胰岛素样生长因子-Ⅰ受体与胃癌发生发展关系的研究

目的 研究胰岛素样生长因子-Ⅰ受体(IGF-IR)与胃癌发生发展的关系.方法 应用免疫组化法检测40例手术切除胃癌组织及其远端正常胃黏膜中IGF-IR表达水平.Western印迹法检测胃癌细胞系SGC7901和MGC803中IGF-IR的表达水平.设计并体外合成靶向IGF-ⅠR的小干扰RNA,将其转染到MGC803细胞中,Western印迹法检测转染后48 h IGF-ⅠR蛋白表达水平,MTT法检测细胞增殖能力,细胞计数并描记生长曲线.结果 胃癌组织IGF-IR表达阳性率为75.5%,显著高于远端正常胃黏膜(25%,P＜0.01).IGF-IR表达与TNM分期和淋巴结转移相关(P＜0.05),但与性别、年龄、分化程度、肿瘤浸润深度无关(P＞0.05).胃癌细胞株中有IGF-ⅠR高表达,小干扰RNA1组IGF-ⅠR表达抑制率可高达89.80%±4.10%,转染后第5天细胞增殖降至最低点(为空细胞组的29.0%±4.0%),同期细胞数降至对照组的21.15%±1.10%.结论 IGF-ⅠR在胃癌细胞中过表达,应用RNA干扰技术可有效沉默IGF-IR基因,抑制肿瘤细胞的增殖.     

Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer

Insulin-like growth factors are potent mitogenic factors in human lung cancer in vitro, acting via specific receptors. Using monoclonal antibodies we demonstrate the expression of insulin-like growth factor receptor I in bronchial epithelial cells of normal lung and in primary lung cancer (22/24 cases), being most prominent in squamous cell carcinoma. Electron microscopy on lung cancer cell lines reveals a distinct reaction pattern on the plasma membrane. Immunoreaction with a specific antibody directed against the insulin-like growth factor receptor II suggests a weak expression in primary lung cancer. Our findings underline the significance of the autocrine pathway of insulin-like growth factors in lung cancer.Abbreviations IGF insulin-like growth factor