X盒结合蛋白1、免疫球蛋白结合蛋白在肝癌组织中的表达及意义

目的 检测X盒结合蛋白1( XBP1)、免疫球蛋白结合蛋白(Bip)在肝癌组织中的表达,探讨其在肝癌生长中的作用机制.方法 采用逆转录-聚合酶链反应(RT-PCR)法检测术中所取的42例肝癌标本、15例同个体癌旁1.0 cm肝组织和15例正常肝组织中XBP1、Bip的mRNA表达.应用Western blot法验证57例肝癌组织和正常肝组织标本中XBP1、Bip在蛋白水平的表达.结果 肝癌组织、癌旁肝组织、正常肝组织中XBP1 mRNA相对表达量分别为0.4396±0.0241、0.4152±0.0252、0.4095±0.0149,XBP1 mRNA在3组之间的表达呈下降趋势(P＜0.05);肝癌组织、癌旁肝组织、正常肝组织中Bip mRNA相对表达量分别为0.4772±0.0401、0.4332±0.0488、0.4301±0.0398,Bip mRNA在3组之间的表达呈下降趋势(P＜0.05).实验对肝癌组织和正常肝组织中XBP1和Bip的蛋白表达进行了定性验证:在肝癌组织和正常肝组织中均有两种蛋白的表达,但肝癌组织中的表达明显高于正常肝组织.结论 在肝癌的生长过程中存在未折叠蛋白反应(UPR)的激活.在肝癌组织中XBP1、Bip mRNA和蛋白的表达一致,均呈高表达.这些基因和蛋白表达的改变可能与肝癌的发生、生长及转移密切相关.     

免疫结核球蛋白、血管内皮生长因子-C在肝癌组织中的表达及意义

目的 检测免疫结核球蛋白(Bip)、血管内皮生长因子(VEGF)-C在肝癌组织中的表达,探讨其在肝癌生长中的作用机制.方法 采用逆转录-聚合酶链反应(RT-PCR)检测术中所取新鲜的42例肝癌标本、15例同个体癌旁1.0 cm肝组织和15例正常肝组织中Bip、VEGF-C的mRNA表达,应用Western blot方法验证57例肝癌组织和正常肝组织标本中Bip及VEGF-C在蛋白水平的表达.结果 肝癌组织、癌旁肝组织、正常肝组织中Bip mRNA相对表达量分别为0.4772±0.0401、0.4332±0.0488、0.4301±0.0398,Bip mRNA在3组之间的表达呈下降趋势(P＜0.05).肝癌组织、癌旁肝组织、正常肝组织中VEGF-C mRNA相对表达量分别为0.4447±0.0335、0.4195±0.0334、0.4019±0.0259,VEGF-C mRNA在3组之间的表达呈下降趋势(P＜0.05);实验对肝癌组织和正常肝组织中Bip和VEGF-C的蛋白表达进行定性验证:在肝癌组织和正常肝组织中均有两种蛋白的表达,但肝癌组织中的表达明显高于正常肝组织.结论 在肝癌的生长过程中存在未折叠蛋白反应(UPR)的激活.在肝癌组织中Bip、VEGF-C mRNA和蛋白的表达一致,均呈高表达.这些基因和蛋白表达的改变可能与肝癌的发生、生长及转移密切相关.     

血管内皮生长因子-C蛋白和mRNA在胆管癌中的表达及其意义

目的 检测胆管癌和癌旁0.5 cm胆管组织及手术切缘的正常胆管组织血管内皮生长因子(VEGF)-C蛋白及mRNA的表达,探讨其在胆管癌发生发展中的作用.方法 应用免疫组织化学过氧化物酶标记链霉卵白素法(SP)检测42例胆管癌组织及20例正常组织中VEGF-C蛋白的表达,同时应用逆转录-聚合酶链反应(RT-PCR)技术检测42例术中所取的新鲜的胆管癌、17例同个体癌旁胆管黏膜和20例正常胆管组织中VEGF-C的mRNA表达,并与临床资料进行相关分析.结果 正常胆管组织、癌旁组织、胆管癌组织中VEGF-C mRNA相对表达量分别0.6105±0.0577、0.6270 ±0.0664、0.6930±0.1078,VEGF-C mRNA在3组之间表达呈上升趋势(P＜0.05).VEGF-C蛋白表达趋势同其相对应的基因表达趋势一致,即VEGF-C mRNA在胆管癌组织中高表达(P＜0.05).胆管癌组织、正常胆管组织中VEGF-C表达的阳性率分别为83.33%和30.00%.结论 VEGF-C基因转录和蛋白可能参与了胆管癌的发生发展过程.     

微小RNA-181b及其靶基因肝癌缺失基因-1在肝癌发生中的作用

目的 探讨微小RNA(miRNA,miR)-181b对肝癌缺失基因-1(DLC-1)的调控及其在肝癌发病中的作用.方法 通过实时荧光定量聚合酶链反应(FQ-PCR)和Western blot检测4份正常肝脏组织,17份癌旁组织、肝癌组织及肝癌SMMC7721细胞、胚肝LO2细胞中miR-181b和DLC-1的mRNA和蛋白质表达水平.应用miR-181b抑制剂下调肝癌细胞SMMC7721中miR-181b表达后,实时定量聚合酶链反应和Westem blot检测SMMC7721细胞中DLC-1表达水平的变化.结果 miR-181b在正常肝组织、癌旁组织和肝癌组织中的相对表达量分别为0.162 ±0.004、0.175±0.021和0.656±0.034,肝癌组织高于正常肝组织(P＜0.05).miR-181b在SMMC7721细胞中的表达较LO2细胞上调(0.723±0.042和0.262±0.037,P＜0.01).DLC-1 mRNA在正常肝组织、癌旁组织和肝癌组织中的相对表达量分别为0.392±0.094、0.187 ±0.043和0.081 ±0.012,肝癌组织低于正常肝组织(P＜0.05);DLC-1蛋白在正常肝组织、癌旁组织和肝癌组织中的相对表达量分别为0.423±0.026、0.214±0.029和0.112±0.021,差异有统计学意义(P＜0.01).miR-181b抑制剂转染SMMC7721细胞后,DLC-1蛋白在空白组、转染组和阴性对照组的相对表达量分别为0.132±0.027、0.379±0.019和0.125±0.015,转染组较其他两组明显升高(P＜0.05).结论 miR-181b在肝癌组织中表达上调,其抑制DLC-1的表达可能是肝癌发生的重要机制.     

多梳基因Bmi-1在肝癌组织和门静脉癌栓组织中的表达及意义

目的 检测肝癌组织、癌旁肝组织、门静脉癌栓组织和正常肝组织中多梳基因Bmi-1 mRNA及其蛋白的表达,探讨Bmi-1与肝癌患者预后的关系.方法 回顾性分析2005年1月至2009年12月华中科技大学同济医学院附属同济医院收治的40例原发性肝癌患者的临床资料.收集患者手术标本,应用免疫组织化学法、Western blot和实时荧光定量PCR检测Bmi-1 mRNA和蛋白在肝癌组织(40例)、癌旁肝组织(40例)、门静脉癌栓组织(11例)和正常肝组织(10例)中的表达情况,分析Bmi-1与肝癌的临床病理特征关系.组间比较采用Nemenyi检验或Dunnett检验,不同病理因素与Bmi-1蛋白在肝癌组织中的表达差异比较采用x2检验或Fisher确切概率法,采用Kaplan-Meier法绘制生存曲线,生存分析采用Log-rank检验.结果 正常肝组织、癌旁肝组织、肝癌组织和门静脉癌栓组织中Bmi-1 mRNA的相对表达量中位数分别为0.96、2.60、7.51和29.95.免疫组织化学检测结果提示,正常肝组织、癌旁肝组织、肝癌组织和门静脉癌栓组织中Bmi-1蛋白高表达率分别为10.0％、20.0％、67.5％和100.0％,肝癌组织和门静脉癌栓组织Bmi-1蛋白高表达率均明显高于正常肝组织和癌旁组织(x2=17.25、22.77,22,04、23.95,P＜0.05);Bmi-1蛋白在11例伴有门静脉癌栓的肝癌组织中也呈高表达.Western blot结果与免疫组织化学检测结果相符合.Bmi-1 mRNA及其蛋白的表达与Edmondson分级和门静脉癌栓有关(x2=5.572,P ＜0.05);与肿瘤直径、血清AFP值及HBsAg无关(x2=0.000,0.019,0.663,P＞0.05).术后生存分析结果显示,Bmi-1高表达的患者预后不良.结论 Bmi-1与肝癌的发生、侵袭能力和门静脉癌栓形成有关;Bmi-1高表达比Bmi-1低表达的患者预后差.     

葡萄糖调节蛋白94在人肝癌组织中的表达及其临床意义

目的 探讨葡萄糖调节蛋白94(Crp94)mRNA及蛋白在肝癌组织和癌旁组织中的表达情况及其与肝癌发生的关系.方法 肝癌患者手术切除标本10例,应用半定量逆转录-聚合酶链反应(RT-PCR)分别检测肝癌组织和癌旁组织细胞Grp94 mRNA基因的相对表达量,并通过免疫组织化学SP法检测10例肝癌组织和癌旁组织标本Crp94蛋白的表达情况.结果 (1)半定量RT-PCR显示:Grp94 mRNA在肝癌组织中均呈高表达,相对表达量为0.7490±0.7508,而在对应的癌旁组织中呈低表达或无表达,相对表达量为0.446 62±0.50000两组之间差异有统计学意义(P《0.05).(2)免疫组织化学及图像分析结果显示:在肝癌组织和癌旁组织中Grp94蛋白平均灰度扫描值分别为158.0800±20.5952、122.2800±24.4148两组之间差异有统计学意义(P《0.01).结论 Grp94在肝癌中的表达明显增高,可能在肝癌的发生、发展过程中发挥重要作用.     

YB-1蛋白在肝癌细胞的表达部位及其意义

目的 探讨YB-1蛋白在肝细胞癌( Hepatocellular carcinoma,HCC)组织、2种肝癌细胞株、正常肝细胞株中的表达及其与肝癌患者临床参数的关系.方法 采用免疫组化检测YB-1蛋白在58例HCC组织及相应例癌旁组织、20例正常肝组织中的表达;用Western blot法检测上述HCC 组织、癌旁组织、正常肝组织及肝癌细胞株QGY-7701、SMMC-7721、正常肝细胞株L02中核移位YB-1蛋白表达.结果 免疫组化显示在HCC组织,YB-1蛋白主要表达于癌细胞胞浆,其阳性率(72.4％,42/58)明显高于癌旁(41.4％,24/58及正常肝组织(35.0％,7/2) (P＜0.05).其中18例(31.0％,18/58)HCC组织伴有明显YB-1核阳性表达,且核表达与HCC病理分级、门静脉癌栓、肿瘤大小相关(P＜0.05).Western blot检测同样证实核移位的YB-1蛋白在肝癌组织(0.474±0.107)显著高于癌旁组织及正常肝组织(P＜0.05).核移位的YB-1蛋白在2种肝癌细胞株中均高于正常肝细胞株(P＜0.05),其差异较织织更为明显.结论 YB-1蛋白在HCC中高表达及核移位可能促进了肝癌的发生发展,有可能成为肝癌治疗的新靶点.     

EphA7基因在原发性肝细胞癌中的表达及其临床意义

目的 探讨原发性肝细胞癌中EphA7 mRNA的表达及其临床意义.方法 应用逆转录-聚合酶链反应(RT-PCR)及实时荧光定量PCR法检测EphA7 mRNA在40例肝癌及相应的癌旁肝组织和10例正常肝组织中的表达,并分析其与肝癌临床病理因素之间的关系.结果 40例肝癌组织及相应的癌旁肝组织和10例正常肝组织中均有EphA7 mRNA的表达.实时荧光定量PCR分析显示EphA7 mRNA在肝癌组织(20.0711±32.0232)中的表达显著高于癌旁肝组织(4.5184±9.4738,P＜0.05)和正常肝组织(4.1764±4.7193,P＜0.05),而在癌旁肝组织和正常肝组织中的表达差异无统计学意义(P＞0.05).EphA7 mRNA的过表达与肝癌细胞的分化程度、门静脉癌栓的形成及淋巴结转移等临床病理因素有关(P＜0.05).结论 EphA7的过表达与原发性肝细胞癌的生物学行为密切相关,可能在肝癌的恶性转化、侵袭和转移过程中发挥作用.     

人内皮细胞高表达脂多糖相关因子1蛋白的纯化

目的探讨通过金属螯合亲和层析的方法获得高纯度的人内皮细胞高表达脂多糖相关因子1(EOLA1)蛋白的可行性。方法采用蛋白抽提试剂破菌方法抽提包涵体蛋白,初步纯化后在变性条件下用组氨酸标签结合树脂进行亲和层析,以透析方法复性,对纯化样品进行聚丙烯酰胺凝胶电泳及免疫印迹法、肽质量指纹谱鉴定。结果EOLA1蛋白在大肠杆菌中的表达主要以包涵体形式存在,初步纯化的包涵体中蛋白纯度>75%,亲和层析纯化后获得的蛋白纯度高达90%以上,肽质量指纹谱分析目的蛋白与理论蛋白肽段覆盖率较高。结论所应用的EOLA1蛋白纯化和复性方法简便有效,能够获得足量的高纯度EOLA1蛋白,有助于下一步制备EOLA1单克隆抗体及对相关基因进行功能研究。     

人内皮高表达脂多糖相关因子1蛋白亚细胞定位研究

目的 了解人内皮高表达脂多糖相关因子1(EOLA1)蛋白在内皮细胞中的亚细胞定位情况.方法 体外培养人脐静脉内皮细胞株ECV304,另构建增强型绿色荧光蛋白(EGFP)-EOLA1融合蛋白表达质粒.用脂质体分别将空质粒pEGFP-N2和融合蛋白表达质粒EGFP-EOLA1转染入ECV304细胞.继续培养48 h,取细胞,用蛋白质印迹法鉴定EGFP及EGFP-EOLA1融合蛋白的表达;采用激光共聚焦显微镜和免疫电镜技术,观察细胞中EOLA1蛋白的亚细胞定位情况.结果 经酶切和测序鉴定证实重组质粒EGFP-EOLA1构建成功.蛋白质印迹法检测结果显示,EGFP和EGFPEOLA1融合蛋白在转染细胞中成功表达.激光共聚焦显微镜下见转染空质粒的ECV304,绿色荧光遍布整个细胞,但无细胞核聚集现象;转染融合蛋白表达质粒的ECV304,绿色荧光也呈全细胞分布,且在胞核内明显聚集.透射电镜下见转染空质粒的细胞内无免疫沉积物,转染融合蛋白表达质粒的细胞质基质中有免疫沉积物.结论 EOLA1蛋白定位在ECV304细胞核与细胞质基质中,作为信号转导因子发挥作用.     

Dietary protein as a risk factor in gentamicin nephrotoxicity

The effects of dietary protein on renal function and structure, both prior to and after initiation of daily gentamicin treatment, were investigated. Male Sprague-Dawley rats were pair-fed on low-protein (LP, 5%), normal-protein (NP, 20%), or high-protein (HP, 60%) diets for 10 days prior to gentamicin treatment. Gentamicin was administered as daily subcutaneous injections (150 mg/kg) for 6 days. Immediately after beginning daily gentamicin injections some of the rats on NP diets were switched to LP or HP diets, and some of the rats on HP diets were switched to LP diets. Renal function was monitored by evaluating serum creatinine levels and 24-h urine volumes; renal histology was evaluated by light and electron microscopy; and gentamicin uptake was determined using radioimmunoassay. Our findings indicate that conditioning to higher dietary protein prior to gentamicin administration results in less uptake of gentamicin by the kidneys. If rats on HP diets are placed on LP coincident with gentamicin administration, there is a significant improvement in survival. Switching rats from NP to LP protein coincident with gentamicin administration does not improve renal function, histology, or survival. However, switching rats from NP to HP coincident with gentamicin administration significantly increases mortality. Maintaining rats on LP both prior to and after gentamicin administration results in a significant improvement in survival but does not improve renal function. These results indicate that dietary protein both prior to and following the administration of gentamicin can significantly affect the nephrotoxicity of gentamicin.     

深静脉血栓形成与凝血因子Ⅷ及蛋白C、蛋白S的相关性

目的 检测下肢深静脉血栓形成的患者血浆中凝血因子Ⅷ(FⅧ)及蛋白C、蛋白S水平的变化,探讨其与深静脉血栓形成的关系.方法 用ACL TOP型全自动血凝分析仪检测40例急件期深静脉血栓形成患者及40例健康体检者血浆中FⅧ及蛋白C、蛋白S的活性.结果 与正常对照组比较,病例组患者体内FⅧ的活性明显增高,是深静脉血栓形成的危险因素,OR值为11.0,95%可信区间为3.3～36.7,排除蛋白C、蛋白S降低的影响,则OR值为5.4,95%可信区间为1.6～18.2.两组比较,病例组中蛋白C和蛋白S的活性明显降低,差异有统计学意义(P<0.05).结论 深静脉血栓形成的患者体内FⅧ活性明显升高,而蛋白C及蛋白S的活性明显降低,凝血及抗凝系统的异常是深静脉血栓形成的高危因素之一.     

Proteomic profiling of urinary protein excretion in the factor H-deficient mouse

BACKGROUND: Since the 1970s a variety of experimental techniques have been employed in an attempt to identify urinary biomarkers of renal injury. While these approaches have met with some success, modern proteomic tools now permit broad based high-throughput analysis of the urinary proteome. METHODS: Using the ICAT isotopic labeling based LC/MS/MS approach, comparative urinary protein profiling was performed in a murine model of membranoproliferative glomerulonephritis. Paired samples were analyzed mice with a targeted deletion of the complement regulatory protein factor H (FH-/-) and control mice. RESULTS: 25 distinct urinary proteins were identified of which 7 were differentially expressed in the FH-/- mice. Two proteins were markedly altered in the urine of FH-/- mice compared to controls: uromodulin (5.5-fold lower) and the MHC class II molecule H2e (8.6-fold higher). Differential expression was confirmed by Western blot and RT-PCR. Immunofluorescent staining demonstrated a marked increased expression of H2e and a reduction of uromodulin expression in the tubular epithelium of FH-/- mice. CONCLUSIONS: These findings provide insight into early complement-dependent alterations in tubular protein expression which may play critical roles in the development of tubulointerstitial disease, and provide experimental support for the use of urinary proteomic profiling in murine models of renal injury.     

Leukocyte chemotactic factor 2: A novel renal amyloid protein

Renal amyloid deposits can often be seen in primary amyloidosis (immunoglobulin light chain disease) or in secondary forms such as reactive amyloidosis as well as in several hereditary forms where a variety of mutant proteins 'precipitate' as amyloid plaques. However, in rare cases, amyloidosis may be identified by renal biopsy, but no definitive diagnosis could be made. We have isolated amyloid fibrils from such a case in which the patient presented with nephrotic syndrome and subsequent azotemia requiring hemodialysis. Evaluation for amyloid deposition in other organ systems was negative and immunohistochemical analysis of the kidney deposits for known contributing proteins was unrevealing. Biochemical analysis of the fibrils identified a new amyloid subunit protein, leukocyte chemotactic factor 2, originally identified as a possible chemotactic and growth factor. A monoclonal antibody to this protein reacted specifically with the amyloid deposits in the glomeruli and interstitium by immunohistochemistry. This study emphasizes the importance of biochemical characterization of amyloid present in renal biopsies.     

Expression of vascular endothelial growth factor protein in human renal cell carcinoma

OBJECTIVE: To evaluate the effect of vascular endothelial growth factor (VEGF, one of the most important angiogenetic factors) in renal cell carcinoma (RCC) by analysing many RCCs for the expression of immunohistochemical (IHC) VEGF-staining related to clinicopathological findings and survival. PATIENTS AND METHODS: VEGF immunostaining was examined with the tissue microarray (TMA) method on tumour samples from 229 patients and validated in 71 by ordinary tissue sections (TS). IHC VEGF expression was quantified by estimating the volume density and staining intensity on a three-grade scale. RESULTS: In most RCCs there was VEGF staining in the cell cytoplasm and membrane. In cell membranes the VEGF expression declined with storage time. IHC VEGF expression analysed by TMA and TS gave corresponding results. There was no difference in VEGF expression among conventional, papillary and chromophobe RCCs. There were significant correlations between VEGF expression and tumour size and stage. In univariate analysis VEGF expression correlated with survival, especially in conventional RCCs; this prognostic information was lost in multivariate analysis. The VEGF staining intensity correlated only with VEGF expression but not with any clinicopathological factors. CONCLUSIONS: VEGF protein was present in most RCC cells. There was no difference in VEGF expression among the different RCC types. The correlation between VEGF expression and tumour stage and with prognosis indicates the significance of VEGF within tumour growth and progression in RCC.     

Nuclear protein as a prognostic factor of growth activity in prostatic adenocarcinoma

The value of nuclear protein (NP) as a prognostic parameter in prostatic adenocarcinoma was investigated. The NP and DNA contents of two prostatic tumour lines with a well-documented hormonal dependency (PC-82, PC-EW) were compared to the NP and DNA contents of two xenografts with only partial or no response to androgen deprivation (LNCaP, PC-133). After hormonal treatment the PC-82 and PC-EW tumours showed a significant decrease in the NP/DNA ratio, which coincided with a decrease in the proliferative activity [anti-bromodeoxyuridine 9BRDU] antibody-labelling index] of the same specimens. In the fast-growing LNCaP tumour an increased percentage of cells with high NP and DNA contents was found. The tumours PC-82, PC-EW, and PC-133 with lower proliferative activity showed lower nuclear protein and DNA contents. In a pilot study of 20 prostatic biopsies the amount of nuclear protein and DNA in grade 1–3 tumours as well as in dysplasia was measured. Statistically significant differences (P<0.002) were found between grade 1 and grade 3 tumours. The mean NP/DNA ratio was increased in high-grade malignancies. Nuclear protein appeared to be a potential parameter in predicting growth activity in prostatic carcinoma.     

Long-term effects of surgical angiogenic therapy with fibroblast growth factor 2 protein

OBJECTIVE: The long-term effects of surgical fibroblast growth factor 2 therapy are examined. METHODS: In a randomized, double-blind study, fibroblast growth factor 2 (10 microg or 100 microg) or placebo (n = 8 each) was delivered in the ungraftable myocardial territory of patients concomitantly undergoing coronary artery bypass grafting. Patients were followed up to 32.2 +/- 6.8 months postoperatively with clinical assessment and nuclear perfusion imaging. RESULTS: Baseline patient characteristics were similar between the 3 groups. There were 2 late deaths, one of pancreatic cancer and one of undetermined cause (both in the 100-microg fibroblast growth factor 2 group). Two patients (both in the control group) underwent a total of 6 repeat cardiac catheterizations for recurrent coronary events. Mean Canadian Cardiovascular Society angina class improved at late follow-up from baseline in all groups (P < or = .02); however, patients treated with either dose of fibroblast growth factor 2 had significantly more freedom from angina recurrence than those treated with placebo (P =.03). Late nuclear perfusion scans revealed a persistent reversible or a new, fixed perfusion defect in the ungraftable territory of 4 of 5 patients who received placebo versus only 1 of 9 patients treated with fibroblast growth factor 2 (P =.02). The overall sum of left ventricular stress perfusion defect scores was also lower in fibroblast growth factor 2-treated patients than in control subjects (1.3 +/- 1.4 vs 3.9 +/- 2.1, respectively; P =.04). A trend toward a higher late left ventricular ejection fraction was noted in fibroblast growth factor 2-treated patients (55.1% +/- 14.6% vs 44.3% +/- 6.5%, fibroblast growth factor 2-treated patients versus control subjects; P =.12). CONCLUSIONS: These data suggest that surgical angiogenic therapy with sustained-release fibroblast growth factor 2 may result in a prolonged myocardial revascularization effect that could translate into clinical benefit.     

Prognostic value of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 blood levels in breast cancer

High circulating insulin-like growth factor 1 (IGF-1) levels are firmly established as a risk factor for developing breast cancer, especially estrogen positive tumors. The effect of circulating IGF-1 on prognosis once a tumor is established is unknown. The authors explored the effect of IGF-1 blood levels and of it's main binding protein, IGFBP-3, on overall survival and occurrence of second primary breast tumors in breast cancer patients, as well as reproductive and lifestyle factors that could modify this risk. Patients were accrued from six hospitals in the Netherlands between 1998 and 2003. Total IGF-1 and IGFBP-3 were measured in 582 plasma samples.No significant association between IGF-1 and IGFBP-3 plasma levels and overall survival was found. However, in a multivariate Cox regression model including standard prognostic variables high IGF-1 levels were related to worse overall survival in patients receiving endocrine therapy (HR = 1.37, 95% CI: 1.11, 1.69, P 0.004). These data at least indicate that higher IGF-1 levels, and as a consequence most likely IGF-1-induced signaling, are related to a less favorable overall survival in breast cancer patients treated with endocrine therapy. Interventions aimed at reducing circulating levels of IGF-1 in hormone receptor positive breast cancer may improve survival.