人肝癌组织胰岛素样生长因子Ⅱ基因启动子表达及其意义

人胰岛素样生长因子Ⅱ（IGF-Ⅱ）是一种重要的胎儿生长因子，其基因含4个不同的启动子（P1～P4）。在生长发育过程中，4个启动子不同的生物活性，具有组织特异性和发育阶段独立性表达特征，P2～P4为胚胎型启动子，P1为成人型启动子。在胎肝和新生儿肝中IGF-Ⅱ mRNA表达量最高，其中P3活性最大，其次分别为P4及P2，P1失活，在成人肝脏中IGF-Ⅱ mRNA表达量显著下调，约为新生儿峰值的1／10，其中P1活性最大，依次为P4、P2及P3，约70％成人肝脏P3呈关闭状态，仅30％成人呈微量表达。近年研究发现，IGF-Ⅱ在模型动物肝脏和人类肝脏的癌前病变及肝癌组织中呈过量表达，但不同学者报道的IGF-Ⅱ异常表达量及阳性率差异较大，且多数为IGF-Ⅱ蛋白水平的定性研究。我们分析了乙型肝炎病毒（HBV）阳性肝癌的P1～P4调控的IGF-Ⅱ转录子表达水平的变化及其与临床病理特征的关系，旨在阐明IGF-Ⅱ基因启动子在肝癌癌变中的作用及其临床意义。     

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。     

人肝癌胰岛素样生长因子2基因的表达和印迹状态的改变

目的 研究人肝细胞性肝癌(HCC)的发生与胰岛素样生长因子2(IGF2)的表达及其印迹变化之间的关系。方法 采用RT-PCR半定量法和限制性酶切片断长度多态性分析法(RFLP),对40例HCC组织标本(其中33例有癌旁组织),检测IGF2的相对表达量,观察肝癌组织中IGF2基因印迹状态的改变。结果 HCC中IGF2的相对表达量,在各病例间的变化较大;癌组织中的表达(1.5431±1.4316)明显高于癌旁肝组织(0.6517±0.6666),t=3.695,P<0.001;癌组织和癌旁组织均有病例发生基因印迹丢失(LOI)。结论 HCC的发生与IGF2的异常表达增高有关;IGF2的LOI可能是HCC的癌前表现之一。     

胰岛素样生长因子与脑缺血

胰岛素样生长因子（insulin-like growth factor,IGFs）包括IGF-Ⅰ、IGF-Ⅱ及des-Ⅰ GF-Ⅰ,是一类多肽类生长因子,存在于多种组织中,也存在于脑组织,是一类重要的调节神经生长及修复的生物活性物质,近年实验研究发现IGFs及其受体及IGFs结合蛋白参与脑缺血损伤的病理过程,脑缺血后IGFs及其受体在脑皮层及纹状体系统表达增加,参与脑缺血后内源性的神经保护机制,是潜在的脑缺血缺氧的神经保护剂.     

肺癌患者胰岛素样生长因子1和胰岛素样生长因子结合蛋白3的表达及其临床意义

目的 分析肺癌患者血清和支气管肺泡灌洗液（BALF）中胰岛素样生长因子1（IGF-1）、胰岛素样生长因子结合蛋白3（IGFBP-3）的表达,探讨其在肺癌诊断和预后中的临床意义.方法 运用免疫放射法检测80例非小细胞肺癌患者和14名健康者（对照组）外周血血清与BALF中IGF-1、IGFBP-3的水平.结果 肺癌组血清和BALF中IGF-1表达显著高于对照组（P＜0.01）,IGFBP-3的表达显著低于对照组（P＜0.05）,同时IGF-1/IGFBP-3升高（P＜0.01）.IGF-1、IGF-1/IGFBP-3在有淋巴结转移、远处转移和TNMⅢ～Ⅳ的肺癌患者血清、BALF中明显高于无转移者和TNMⅠ～Ⅱ期者（P＜0.05）,而IGFBP3下降明显高于无转移者及TNMⅠ～Ⅱ期者（P＜0.05）.肺癌组血清IGF-1、IGFBP-3浓度与BALF中的浓度呈正相关（P ＜0.01）;患者血清BALF中IGF-1与IGFBP-3浓度呈负相关（P＜0.05）.结论 非小细胞肺癌患者血清和支气管肺泡灌洗液中IGF-1、IGFBP-3的表达对肺癌的诊断、判断预后有重要临床意义.     

胰岛素样生长因子Ⅱ基因在大鼠INS-1细胞中表达的调控

目的 研究不同浓度葡萄糖对INS－1细胞IGF－Ⅱ基因表达的调节及对INS－1细胞增殖的作用，并比较其对IGF－Ⅱ与胰岛素基因表达的关系。方法 采用Northern杂交分析IGF－ⅡmRNA表达，用^3H-胸腺嘧啶掺入法检测细胞增生。结果 IGF－Ⅱ在INS－1细胞中表达。当葡萄糖浓度为10－20mmol/L时，IGF－ⅡmNRA表达量提高3倍以上。佛波醇十四乙酸对INS－1细胞的IGF－ⅡmNRA的表达及增生不起作用，而Forskolin可抑制INS－1细胞的IGF－Ⅱ mRNA表达。结论 高浓度葡萄糖促进INS－1细胞中IGF－Ⅱ mRNA表达，低浓度的葡萄糖环境中胰岛素mRNA的表达量高。     

胰岛素样生长因子与肺癌

胰岛素样生长因子(IGFs)是一组小分子多肽类物质。可以通过内分泌、自分泌和旁分泌的途径发挥促有丝分裂，细胞转化和抑制凋亡的作用。这些作用主要由IGF-1受体介导，由胰岛素样生长因子结合蛋白调节。多年的基础和临床研究已经表明：胰岛素样生长因子与多种肿瘤的发生发展关系密切。针对IGFs轴已开展了许多治疗性的研究。本文综述了近年来IGFs的研究现状以及与肺癌关系的研究进展。     

胰岛素样生长因子调节系统与骨

综述了前列腺素、白细胞介素、转化生长因子和肿瘤坏死因子等细胞因子对胰岛素样生长因子 (IGFs)调节系统的影响 ,及其基因分子生物学的调节机制。同时系统激素如生长激素、雌激素、降钙素和甲状旁腺激素等也能影响IGF调节系统。IGF调节系统与成骨细胞和破骨细胞的功能及其成骨和破骨偶联有着密切关系 ,其中IGF可能发挥着核心作用。     

胰岛素样生长因子与肺癌

胰岛素样生长因子 (IGFs)是一组小分子多肽类物质。可以通过内分泌、自分泌和旁分泌的途径发挥促有丝分裂 ,细胞转化和抑制凋亡的作用。这些作用主要由IGF 1受体介导 ,由胰岛素样生长因子结合蛋白调节。多年的基础和临床研究已经表明 :胰岛素样生长因子与多种肿瘤的发生发展关系密切。针对IGFs轴已开展了许多治疗性的研究。本文综述了近年来IGFs的研究现状以及与肺癌关系的研究进展     

胰岛素样生长因子Ⅱ及其受体基因在肝癌和癌旁肝组织中的表达

为了探讨胰岛素样生长因子Ⅱ（ｉｎｓｕｌｉｎｌｉｋｅｇｒｏｗｔｈｆａｃｔｏｒⅡ，ＩＧＦⅡ）及其受体（ＩＧＦⅡＲ）在肝癌发生及发展过程中的作用，我们采用原位分子杂交技术，对肝癌和癌旁肝组织中ＩＧＦⅡ、ＩＧＦⅡＲ基因的表达进行了观察，发现ＩＧＦ...     

胰岛素样生长因子-I对糖尿病大鼠心脏功能的影响

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Western印迹方法测定血清中胰岛素样生长因子结合蛋白-3水平

目的　研究正常人及生长激素分泌异常病人血清中胰岛素样生长因子结合蛋白３（ Ｉ Ｇ Ｆ Ｂ Ｐ３） 的水平。方法　本文采用 Ｗｅｓｔｅｒｎ 印迹方法测定２０ 例正常人,３３ 例活动性肢端肥大症病人和３４ 例特发性生长激素缺乏症（ Ｉ Ｇ Ｈ Ｄ） 病人血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 水平。结果　正常成人血清中存在五种分子量不同的 Ｉ Ｇ Ｆ Ｂ Ｐ, Ｉ Ｇ Ｆ Ｂ Ｐ３ 含量为最高。本文测定了２０ 例正常成人和６７ 例生长激素分泌异常患者血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 的相对光密度（ Ｒ Ｏ Ｄ） ,正常人血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 含量为（１ ．１ ±０ ．４） Ｒ Ｏ Ｄ,活动性肢端肥大病人为（２ ．７ ±１ ．２） Ｒ Ｏ Ｄ,明显高于正常成人（ Ｐ＜ ０ ．０１） , Ｉ Ｇ Ｈ Ｄ 病人为（０ ．４ ±０ ．２） Ｒ Ｏ Ｄ,明显低于正常成人（ Ｐ＜ ０ ．０１） 。血清生长激素与 Ｉ Ｇ Ｆ Ｂ Ｐ３ 、胰岛素样生长因子 Ｉ与 Ｉ Ｇ Ｆ Ｂ Ｐ３ 均呈正相关（ Ｐ＜０ ．０５） 。结论　 Ｗｅｓｔｅｒｎ 印迹测定血清 Ｉ Ｇ Ｆ Ｂ Ｐ３ 正常值和病理值提示 Ｉ Ｇ Ｆ Ｂ Ｐ３ 浓度的变化与生长激素功能状态密切相关,并依赖 Ｇ Ｈ。     

Circulating insulin-like growth factors may contribute substantially to insulin receptor isoform A and insulin receptor isoform B signalling

Background

Only a fraction of circulating insulin-like activity is due to insulin itself. The aim of this study was to determine total serum insulin-like activity mediated via the insulin receptor isoform A (IR-A) and isoform B (IR-B) by using kinase receptor activation (KIRA) assays specific for the IR-A and IR-B.

Methods

The IR-A and IR-B KIRA assays use human embryonic kidney cells which have been transfected with the human IR-A or IR-B gene and quantify serum-mediated phosphorylation of the IR.

Results

Both IR KIRA assays were sensitive (detection limit 32 pmol/L) and precise (intra- and inter assay CV: <12% and <15%). The EC₅₀s of insulin, IGF-I and IGF-II were 1.4, 11.2 and 6.7 nmol/L for the IR-A KIRA assay, and 1.3, 31.0 and 15.7 nmol/L for the IR-B KIRA assay.The operational range of both assays allowed for determination of total insulin-like activity in human serum. Analysis of serum samples showed that there was a significant positive correlation between serum insulin-like and immunoreactive insulin concentrations (IR-A: r = 0.56, p = 0.01, IR-B: r = 0.68, p = 0.001). Importantly, addition of IGF-I or IGF-II antibodies to human serum samples could substantially decrease the endpoint signal in both KIRA assays.

Conclusions

We showed that serum IGF-I and IGF-II may substantially contribute to IR signalling. Since IR isoform specific KIRA assays also take into account the contribution of IGFs present in serum on IR signalling, they may help to gain more insight into the roles of IGF mediated IR-A and IR-B activation in health and disease.     

宫内发育迟缓大鼠第36周胰岛素合成相关基因的表达

目的研究宫内发育迟缓（IUGR）大鼠第36周胰腺组织中胰岛素合成相关基因表达的变化。方法将20只体重250-270g的8-10周健康雌性SD大鼠,饲养于无特定病原体（SPF）级动物房,适应性饲养2周后将雌雄鼠合笼,以发现阴栓当天记为雌鼠受孕第1天,雌鼠受孕后随机数字表法分为造模组（n=10）和对照组（n=10）。采用孕中晚期热量限制的方法建立IUGR大鼠模型。造模组孕鼠自妊娠11d起给予对照组总热量50％饲料,新生鼠出生体重低于对照组新生鼠平均体重2个标准差者人选为IUGR组;对照组新生鼠即为正常组,对照组孕鼠自由进食。两组每窝各保留8只新生鼠继续饲养,仔鼠21d断奶后以标准饲料喂养至36周。选取第36周（中老年阶段）雄鼠为研究对象,实施腹腔葡萄糖耐量及胰岛素释放试验,运用逆转录聚合酶链反应（RT-PCR）方法检测胰腺组织中胰岛素合成相关基因[胰岛素基因1（Insulinl）、胰岛素基因2（Insulin2）以及胰-十二指肠同源盒基因-1（PDX-I）]的表达情况。两组间比较采用t检验分析。结果第36周,IUGR组大鼠胰重及胰重／体重比值明显低于正常组[分别为（4971±525）比（5844±398）mg和（0．58±0．05）％比（0．69±0．04）％,t=-2．65、-3．39,均P〈0．05]。糖负荷后各时点（30、60、120、180min）血糖值IUGR组均明显高于正常组[分别为30min：（17．9±1．5）比（16．1±1．1）mmol／L,60min：（13．4±1．1）比（11．7±1．4）mmol／L,120min：（10．1±0．8）比（8．6±1．0）mmol／L,180min：（8．9±1．0）比（7．6±0．9）mmol／L,t=2．31、2．37、2．77、2．34,均P〈0．05];糖负荷后各时点胰岛素分泌水平两组大鼠差异无统计学意义（t=1．66、-0．10、-0．65、-0．83、-0．58,均P〉0．05）。IUGR组大鼠胰腺组织中Insulinl基因表达较正常组明显减少（0．79±0．17比1．25±0．28,t=-2．78,P〈0．05）,而Insulin2、PDX-1基因表达差异均无统计学意义（t=-1．65、-1．46,均P〉0．05）。结论IUGR大鼠第36周糖耐量减退,胰腺组织中Insulinl基因表达下调。     

Clinical and histological coexistence of inflammatory pseudotumour of the lymph nodes and rheumatoid arthritis

Inflammatory pseudotumour (IPT) of the lymph nodes is an uncommon, self-limiting, non-neoplastic proliferation of spindle cells, associated with a polymorphous inflammatory cell infiltrate embedded in a collagen-rich stroma and a variable degree of fibrosis, arising in the nodal parenchyma. Its clinical picture is characterised by site-specific signs and the presence, in most cases, of constitutional symptoms. The pathogenesis of IPT is unknown, but it has been interpreted as an aberrant reactive condition of the nodal connective framework, possibly related to viral infections or chronic inflammatory conditions. Its prognosis is usually favourable. We here report the simultaneous onset of seronegative rheumatoid arthritis (RA) and nodal IPT in a 31-year-old woman. Notably, in the nodal biopsy the coexistence of rheumatoid nodules, as well as histological and immunohistochemical features of IPT, was observed. To our knowledge, such an association has not been previously reported and the hypothesis that IPT could represent an unusual epiphenomenon of an RA-related chronic inflammatory response is suggested.Abbreviations RA Rheumatoid arthritis - IPT Inflammatory pseudotumour - IMT Inflammatory myofibroblastic tumours - ALK Anaplastic lymphoma kinase - MCP Metacarpophalangeal - PIP Proximal interphalangeal - ESR Erythrocyte sedimentation rate - EBV Epstein-Barr virus - 6-MP 6-methylprednisolone - MTX Methotrexate     

Frequency distribution of tissue mast cells and eosinophilic granulocytes in tumor-draining axillary and paracolic lymph nodes

Summary The frequency distribution of tissue mast cells and eosinophilic granulocytes in tumor-draining lymph nodes was evaluated. In total 483 axillary lymph nodes draining invasive ductal breast cancer and 162 paracolic lymph nodes draining infiltrating adenocarcinoma of the large bowel were analyzed. Significantly higher number of sinus mast cells were found in axillary lymph nodes as compared with the paracolic ones whereas eosinophilic granulocytes were more frequent in paracolic than in axillary lymph nodes. Concerning both cell systems no significant differences could be demonstrated when all lymph nodes from nodal-negative cases were compared with the lymph nodes from cases with regional lymph node metastases. Tumor-free axillary lymph nodes, however, showed a significantly higher mast cell content in the sinus and medulla than did lymph nodes bearing metastases. The number of eosinophilic granulocytes did not differ in either lymph node group.Supported by the Schleswig-Holsteinische Krebsgesellschaft e. V. and the Tumor-Zentrum Kiel e. V.     

CT diagnosis of 52 patients with lymphoma in abdominal lymph nodes

INTRODUCTION Abdominal lymphoma is clinically not uncommon and lymphoma in the abdominal lymph nodes (LALN) is most frequently encountered[1]. Though it may be part of a systemic lymphoma, single onset of LALN is not rare. LALN can be divided into Hodgkin…     

经支气管淋巴结针吸活检164例结果分析

目的 评价经支气管淋巴结针吸活检(TBNA)在纵隔肺门肿大淋巴结诊断中的作用.方法 选胸部CT检查发现纵隔肺门淋巴结肿大、估计支气管镜检查不能发现气道内新生物的患者,在支气管镜检查过程中完成TBNA操作.TBNA取出的每份标本分送呼吸科实验室和病理科细胞学室检查.结果 (1)人选的164例患者中80例诊断肺癌,69例诊断肺部良性疾病,其他类型恶性肿瘤2例,13例最终无明确诊断.(2)164例患者共穿刺260个部位,463针,其中TBNA穿刺成功445针(96.1%).(3)80例肺癌患者中,TBNA总结果 阳性66例(82.5%),其中25例患者TBNA结果 是惟一病理学证据.80例肺癌患者共穿刺122枚淋巴结,其中TBNA结果 阳性80枚(65.6%).(4)TBNA结果 的阳性率在小细胞肺癌(SCLC)和直径≥3 cm淋巴结中阳性率稍高,但差异无统计学意义.(5)2006年6月1日-2007年12月31日,64例(64/87,73.5%)患者可获得明确组织学标本.其中TBNA穿刺物病理诊断结节病阳性率为53.3%(8/15),诊断肺癌阳性率为78.6%(33/42).(6)100例(61.0%)患者穿刺部位少量出血.结论 TBNA安全性好,对肺癌的诊断和分期判定有很大帮助,对肺部良性疾病的诊断亦有一定帮助.     

超声支气管镜下弹性成像技术在纵隔淋巴结性质判定中的价值

目的探讨超声支气管镜下弹性成像技术单独及联合胸部CT、常规超声在气管周围的纵隔及肺门淋巴结性质判定中的价值。 方法选取2016年6月至2018年3月期间在南京医科大学附属南京医院呼吸内科气管镜室拟行EBUS-TBNA检查的患者。记录目标淋巴结的胸部CT、常规超声及超声弹性成像各参数,根据EBUS-TBNA的病理阳性结果或者阴性结果进行一年的随访作为诊断的金标准。构建各个特征参数的受试者工作特征曲线,得到曲线下面积和最佳截断值,并计算出最佳截断值时各个参数的诊断准确率、灵敏度、特异度、阳性预测值、阴性预测值等指标。 结果共入组78例患者,117枚淋巴结：①胸部CT在判定淋巴结性质中,淋巴结短径≥10 mm,边界清楚,质地不均匀这三个特征具有统计学意义(P<0.05),其中质地不均匀的AUC最高,为0.711;②常规超声判定淋巴结性质时,淋巴结短径≥10 mm,边界清楚,低回声,形状呈类圆形这四个特征具有统计学意义(P<0.05),其中边界清楚的AUC最高,为0.655;③超声弹性成像图像应用图像类型、超声弹性评分、应变率比值以及蓝色面积比四种方法判断淋巴结性质,AUC分别是0.843,0.820,0.717,0.877;其中蓝色面积比的AUC最高;④联合胸部CT的淋巴结质地不均匀,常规超声的淋巴结边界清楚以及超声弹性成像的图像类型进行统计分析,得出准确率、灵敏度、特异度、阳性预测值、阴性预测值分别是85.5%,85.7%,87.9%,100%,100%,AUC为0.932。 结论超声弹性成像对于肺门及纵隔淋巴结的性质判断的诊断价值高于胸部CT及常规超声。三者联合能够明显提高淋巴结的恶性检出率。     

Binding and biological effects of insulin,insulin analogues and insulin-like growth factors in rat aortic smooth muscle cells. Comparison of maximal growth promoting activities

Summary Binding and growth promoting effects of insulin, insulin analogues modified in the B chain, proinsulin, insulin-like growth factor-I and -II were studied in cultured rat aortic smooth muscle cells. Specific binding of¹²⁵I-insulin was 0.9±0.2% of total ¹²⁵I-insulin added, and the IC₅₀-value was estimated to 8.9 pmol/1. The insulin analogue B10 Asp tended to be more potent than insulin in displacing ¹²⁵I-insulin, B28 Asp was equipotent, B9 Asp/B27 Glu was approximately 100 times less potent and insulin-like growth factor-I more than 1000 times less potent than insulin. Specific binding of ¹²⁵I-insulin-like growth factor-I after 4 h incubation at 10 °C was five times higher than the specific binding of insulin (4.4±0.4% of total ¹²⁵I-insulin-like growth factor-I added), and the IC₅₀-value was 0.3 nmol/l. Insulin was approximately 500 times less potent than insulin-like growth factor-I in displacing ¹²⁵I-insulin-like growth factor-I. The insulin analogue B10 Asp was slightly more potent and analogue B28 Asp was equipotent with insulin. Analogue B9 Asp/B27 Glu was ten times less potent and proinsulin was more than ten times less potent than insulin. The order of potency was similar for ³H-thymidine incorporation into DNA: insulin-like growth factor-I > B10 Asp > insulin-like growth factor-II > insulin > B28 Asp > B9 Asp/B27 Glu > proinsulin. The maximal effect of insulin-like growth factor-I on ³H-thymidine incorporation was 71±16% higher than the maximal effect of insulin. The maximal effect of insulin-like growth factor-II was at least as high as the effect of insulin-like growth factor-I. Furthermore, the maximal effect of B10 Asp was 62±10% higher than the maximal effect of insulin. Insulin-like growth factor-I and B10 Asp tended to increase cell number more than insulin. In conclusion, this study shows that insulin analogues interact with different potencies with receptors for insulin and insulin-like growth factor-I in vascular smooth muscle cells and that insulin-like growth factors and the insulin analogue B10 Asp have more pronounced growth effects than insulin. Substitution of the amino acid Asp for His at position B10 in insulin makes the molecule more similar to insulin-like growth factor-I, chemically and probably also biologically.