转化生长因子β1在胃癌患者血清和组织中的表达及意义

目的检测胃癌患者血清中转化生长因子β1(TGF-β1)水平及相对应的胃癌组织中TGF-β1的表达,探讨TGF-β1在胃癌发生、发展中的作用。方法应用酶联免疫吸附法测定56例胃癌患者、30例胃不典型增生(轻-中度)及20例健康对照组的血清TGF-β1水平,应用免疫组织化学SP法检测相应胃癌组织、胃不典型增生(轻-中度)组织及正常胃组织中TGF-β1的表达水平,分析其与胃癌病理特征的关系。结果胃癌组血清TGF-β1表达水平为(36.19±18.67)pg/mL,明显高于胃不典型增生(轻-中度)组及健康对照组(P<0.01),TGF-β1在胃癌组中的表达率为83.9%(47/56),在胃不典型增生(轻-中度)组及健康对照组中的表达率分别为43.3%(13/30)和10%(2/20),3组间差异有统计学意义(χ2=45.46,P<0.01);TGF-β1在胃癌患者血清和组织中的表达与胃癌的分化程度、浸润深度、淋巴结转移及临床分期(TNM)有关(P<0.05),而与胃癌的发生部位无关(P>0.05)。结论 TGF-β1过度表达与胃癌的发生和发展有一定关系,TGF-β1可作为反映胃癌恶性生物学行为的指标之一。     

转化生长因子β1mRNA检测方法的建立

目的：研究血吸虫病肝纤维化发病机理、确定肝纤维化活动程度、判断治疗效果和预后等，建立定量ＰＣＲ法。方法：从引物合成构建质粒始，建立ＲＴ－ＰＣＲ加ｄｏｔｂｌｏｔ法测ＰＢＭＣ中ＴＧＦ－β１ｍＲＮＡ水平，以构建的ＴＧＦ－β１质粒，精确定量后作标准对照，以看家基因β－ａｃｔｉｎ同管进行ＲＴ－ＰＣＲ为内对照，ｄｏｔｂｌｏｔ结果以多功能凝胶成像仪ＩＳ－１０００定量分析，检测梯度稀释的质粒和１１份不同血标本的复管。结果：８个梯度稀释的ＴＧＦ－β１质粒ＰＣＲ产物定量结果与原浓度对数成正比，１１份标本两次结果为１．７１±０．９０和１．５４±０．８８，显示较好的重复性和稳定性。结论：该方法可用于定量分析ＰＢＭＣ中ＴＧＦ－β１ｍＲＮＡ含量。     

The recombinant proregion of transforming growth factor beta1 (latency-associated peptide) inhibits active transforming growth factor beta1 in transgenic mice.

All three isoforms of transforming growth factors beta (TGF-betal, TGF-beta2, and TGF-beta3) are secreted as latent complexes and activated extracellularly, leading to the release of the mature cytokines from their noncovalently associated proregions, also known as latency-associated peptides (LAPs). The LAP region of TGF-beta1 was expressed in a baculovirus expression system and purified to homogeneity. In vitro assays of growth inhibition and gene induction mediated by TGF-beta3 demonstrate that recombinant TGF-beta1 LAP is a potent inhibitor of the activities of TGF-betal, -beta2, and -beta3. Effective dosages of LAP for 50% neutralization of TGF-beta activities range from 4.7- to 80-fold molar excess depending on the TGF-beta isoform and activity examined. Using 125I-labeled LAP, we show that the intraperitoneal application route is effective for systemic administration of LAP. Comparison of concentrations of LAP in tissues shows a homogenous pattern in most organs with the exception of heart and muscle, in which levels of LAP are 4- to 8-fold lower. In transgenic mice with elevated hepatic levels of bioactive TGF-betal, treatment with recombinant LAP completely reverses suppression of the early proliferative response induced by TGF-beta1 in remnant livers after partial hepatectomy. The results suggest that recombinant LAP is a potent inhibitor of bioactive TGF-beta both in vitro and in vivo, after intraperitoneal administration. Recombinant LAP should be a useful tool for novel approaches to study and therapeutically modulate pathophysiological processes mediated by TGF-beta3.     

老年男性骨质疏松症患者血清转化生长因子β1测定及其临床意义

目的探讨转化生长因子β1(TGF-β1)与老年男性骨质疏松症的相关性。方法测定老年男性骨质疏松组(36例)与年龄相匹配的对照组(40例)的血清TGF-β1水平及其他生化指标,同时用双能X线骨密度仪测定腰椎及股骨的骨密度及骨矿含量。结果骨质疏松组的腰椎、股骨各个测量部位的骨密度与对照组比较,差异具有统计学意义(P<0.05)。老年男性骨质疏松组TGF-β1含量明显低于对照组[分别为(9.82±6.15)ng/ml和(17.29±7.83)ng/ml,P<0.05]。而血钙、血磷、血碱性磷酸酶水平在2组间差异无显著性。骨质疏松组与对照组的腰椎、股骨各个测量部位的骨密度及骨矿含量均与血清TGF-β1呈正相关,而与血钙、血磷、血碱性磷酸酶水平无关。结论血清TGF-β1水平与骨密度及骨矿含量具有一定的相关性,测定血清TGF-β1水平有助于老年男性骨质疏松症的诊断。     

TGF-β1-509C/T基因多态性与胃癌幽门螺杆菌感染的相关性

目的研究TGF-β1基因-509位点C/T多态性,探讨其与胃癌易感性及幽门螺杆菌感染的关系。方法采用聚合酶链反应-限制性片段长度多态性方法,检测80例胃癌患者与102例正常对照者TGF-β1基因-509位点C/T等位基因及基因型分布,并分析该基因多态性与胃癌幽门螺杆菌感染的相关性。结果胃癌组和正常对照组TGF-β1基因型频率无显著性差异;与正常对照组相比,胃癌组TGF-β1-509位点T等位基因频率显著增高(P=0.044,OR=1.550,95%C I=1.010~2.379)。胃癌患者TGF-β1基因型及等位基因频率与是否感染幽门螺杆菌无关。结论TGF-β1基因-509位点T等位基因可能是胃癌的遗传易感基因,而该位点基因多态性可能与是否感染幽门螺杆菌无关。     

探讨TGFβ1、PDGF、VEGF对特发性肺纤维化诊断及病情评估的临床意义

目的探讨分泌转化生长因子-β、血小板衍生生长因子、血管内皮生长因子在特发性肺纤维化(IPF)患者支气管肺泡灌洗液(BALF)和血清中的表达水平及评估病情进展的临床意义。 方法选择2014年1月至2018年12月在我院呼吸科诊治的35例IPF患者作为观察组,18例肺结节病患者(Ⅰ期)作为对照组;采用免疫印迹观察TGFβ1、PDGF、VEGF在IPF患者血清中是否存在表达;用酶联免疫吸附法(ELISA)观察2组患者BALF和血清中TGFβ1、PDGF、VEGF的表达水平;最后分析IPF患者BALF和血清中TGFβ1、PDGF、VEGF表达水平与肺功能及血氧饱和度的相关性。 结果TGFβ1、PDGF、VEGF细胞印在IPF患者血清存在表达;与对照组相比,BALF及血清中的TGFβ1、PDGF、VEGF表达上调(P<0.05);IPF组患者BALF及血清中TGFβ1、PDGF、VEGF表达水平与肺功能中FVC%、FEV₁%和DLCO%呈负性相关(P<0.05);与血氧饱和度也呈显著负相关(P<0.05)。 结论IPF患者BALF和血清中TGFβ1、PDGF、VEGF的表达水平明显升高;TGFβ1、PDGF、VEGF与患者的肺功能及血氧饱和度呈负相关,可作为评估IPF患者病情的临床评价指标。     

The effect of transforming growth factor beta1 gene polymorphisms in ankylosing spondylitis

OBJECTIVES: To determine whether genetic polymorphisms in or near the transforming growth factor beta1 (TGFB1) locus were associated with susceptibility to or severity of ankylosing spondylitis (AS). METHODS: Five intragenic single-nucleotide polymorphisms (SNP) and three microsatellite markers flanking the TGFB1 locus were genotyped. Seven hundred and sixty-two individuals from 184 multiplex families were genotyped for the microsatellite markers and two of the promoter SNPs. One thousand and two individuals from 212 English and 170 Finnish families with AS were genotyped for all five intragenic SNPs. A structured questionnaire was used to assess the age of symptom onset, disease duration and disease severity scores, including the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index). RESULTS: A weak association was noted between the rare TGFB1 +1632 T allele and AS in the Finnish population (P = 0.04) and in the combined data set (P = 0.03). No association was noted between any other SNPs or SNP haplotype and AS, even among those families with positive non-parametric linkage scores. The TGFB1 +1632 polymorphism was also associated with a younger age of symptom onset (English population, allele 2 associated with age of onset greater by 4.2 yr, P = 0.05; combined data set, allele 2 associated with age of onset greater by 3.2 yr, P = 0.02). A haplotype of coding region SNPs (TGFB1 +869/+915+1632 alleles 2/1/2) was associated with age of symptom onset in both the English parent-case trios and the combined data set (English data set, haplotype 2/1/2 associated with age of onset greater by 4.9 yr, P = 0.03; combined data set, haplotype 2/1/2 associated with greater age of onset by 4.2 yr, P = 0.006). Weak linkage with AS susceptibility was noted and the peak LOD score was 1.3 at distance 2 cM centromeric to the TGFB1 gene. No other linkage or association was found between quantitative traits and the markers. CONCLUSION: This study suggests that the polymorphisms within the TGFB1 gene play at most a small role in AS and that other genes encoded on chromosome 19 are involved in susceptibility to the disease.     

Involvement of alphavbeta5 integrin-mediated activation of latent transforming growth factor beta1 in autocrine transforming growth factor beta signaling in systemic sclerosis fibroblasts

OBJECTIVE: To confirm the involvement of alphavbeta5 in the self-activation system in systemic sclerosis (SSc) fibroblasts. METHODS: Levels of alphavbeta5 expression were analyzed by immunoprecipitation. The promoter activity of the human alpha2(I) collagen gene was determined by transient transfection assay. Phosphorylation levels and DNA binding ability of Smad3 were investigated by immunoprecipitation and DNA affinity precipitation, respectively. The localization of active transforming growth factor beta (TGFbeta) was determined by coculture assay using TMLC cells (mink lung epithelial reporter cells that stably express a portion of the plasminogen activator inhibitor 1 promoter). The morphologic features of cells were determined by immunofluorescence analysis. RESULTS: Levels of alphavbeta5 expression were significantly elevated in SSc fibroblasts compared with normal fibroblasts. Treatment with anti-alphavbeta5 antibody or beta5 antisense oligonucleotide significantly reduced human alpha2(I) collagen gene promoter activity in SSc fibroblasts. In SSc fibroblasts pretreated with TGFbeta1 antisense oligonucleotide, the exogenous latent TGFbeta1 stimulation significantly increased human alpha2(I) collagen gene promoter activity; this effect was significantly reduced in the presence of anti-alphavbeta5 antibody. Phosphorylation levels and DNA binding ability of Smad3 in SSc fibroblasts were significantly reduced by treatment with beta5 antisense oligonucleotide. The luciferase activity of TMLC cells cocultured with SSc fibroblasts was significantly elevated compared with that of TMLC cells cocultured with normal fibroblasts and was significantly reduced in the presence of anti-alphavbeta5 antibody. Anti-alphavbeta5 antibody reversed the myofibroblastic features of SSc fibroblasts. CONCLUSION: Up-regulated expression of alphavbeta5 contributes to the establishment of autocrine TGFbeta signaling in SSc fibroblasts through activation of endogenous latent TGFbeta1.     

Associated changes of lipid peroxidation and transforming growth factor beta1 levels in human colon cancer during tumour progression

BACKGROUND: During neoplastic progression, alterations in transforming growth factor beta1 (TGF-beta1) dependent control of cell growth may be an important mechanism of selective proliferation of transformed cellular clones. Defective regulation of TGF-beta1 receptors has been reported to occur in a number of human malignant tumours while little is known of the actual levels of this growth inhibitory cytokine in cancer. On the basis of the demonstrated ability of major lipid peroxidation products such as 4-hydroxynonenal to modulate TGF-beta1 expression and synthesis, we speculated that decreased lipid oxidation, as frequently observed in neoplastic tissues, would contribute to the selective promotion of tumour growth through decreased expression of the cytokine within the tumour mass. AIMS: To seek a possible association between steady state levels of major aldehydic end products of lipid peroxidation and TGF-beta1 content in human colon cancer at different stages of growth. PATIENTS AND METHODS: Tissue biopsies from 15 adult patients with colon adenocarcinoma of different TNM and G stagings were compared with regard to lipid peroxidation aldehydes and net TGF-beta1 levels. For a more comprehensive analysis, cytokine type I and II receptors were measured in tumour biopsies. In one set of experiments, to support the conclusions, the apoptotic effect of TGF-beta1 was evaluated in a human colon cancer cell line, CaCo-2, retaining receptor changes consistent with those observed in cancer patients. RESULTS: With the exception of two extremely advanced cases (T4/G3) in which tissue levels of lipid peroxidation were within the normal range, 4-hydroxynonenal was significantly decreased in all other cancer specimens. Consistent with lipid peroxidation levels, TGF-beta1 protein was markedly decreased or even negligible compared with the corresponding normal tissue surrounding the tumour in all tested biopsies except for the two T4/G3 colon cancers in which cytokine content was again within the normal range. As regards TGF-beta1 receptors, both in tumour sections and CaCo-2 cells, downregulation was greater for TGF-beta1 receptor I than for receptor II. Of note, in CaCo-2 cells, incubation with appropriate doses of TGF-beta1 led to marked nuclear fragmentation and apoptosis. CONCLUSIONS: Evasion of human colon cancer cells from TGF-beta1 mediated growth inhibition appears to be due not only to downregulation of TGF-beta1 receptors, which is inconsistent and unrelated to cancer development, but also to the constant low concentration of this cytokine in the tumour mass. The associated levels of lipid peroxidation aldehydes, much lower than in control tissue, probably represent a lower stimulus for TGF-beta1 production in the neoplastic area and thus a favourable condition for neoplastic progression.     

放射治疗原发性肝癌对血清TGFβ1的影响

目的 观察原发性肝癌放射治疗前后血清转化生长因子β1（TGFβ1）的动态变化。方法 23例不能手术的原发性肝癌患者接受三维适形放射治疗。应用酶联免疫吸附试验法检测患者放射治疗前、放射治疗结束时、放射治疗后3个月和7例正常献血者的血清TGFβ1水平。结果 23例患者放射治疗前血清TGFβ1为151．16±18．28ng／ml，正常对照组为32．26±7．24ng／ml，两者差异有显著性意义（P〈0．01）。放射治疗结束时为98．42±16．12ng／ml，放射治疗结束后3个月时为112．78±17．36ng／ml，两者差异无显著意义，但比治疗前有下降，与放射治疗前有显著性差异（P〈0．01）。4例完全缓解的患者放射治疗后下降显著，15例治疗有效的患者TGFβ1于放射治疗后也下降。而治疗无效（稳定＋进展）者较放射治疗前下降不明显。2例患者于放射治疗后第7周和第12周发生放射性肝病，他们的TGFβ1水平在治疗前、治疗结束时和发生放射性肝病时分别为156．23ng／ml、151．25ng／ml、101．52ng／ml和99．67ng／ml、189．22ng／ml、196．17ng／ml。结论 检测原发性肝癌患者放射治疗前后血清TGFβ1的变化将有助于评价放射治疗的疗效和监测放射性肝病的发生，是一种有希望反映个体化放射治疗肝癌的生物学指标。     

转化生长因子β1和Smad4在胃癌中的表达

目的胃癌预后极差,是最为常见的肿瘤致死病因.转化生长因子信号转导通路具有一系列重要的细胞调节功能,包括细胞的生长、分化、粘附、转移、细胞外基质的形成和免疫功能.探讨转化生长因子-β1(TGF-β1)和Smad4与胃癌发生发展的关系.方法采用免疫组化和分子原位杂交的方法,对49例胃癌、20例萎缩性胃炎和17例正常胃黏膜的TGF-β1蛋白和Smad4 mRNA表达进行检测.结果胃癌组织中TGF-β1蛋白表达明显增强,其阳性率(79.6%)明显高于正常胃黏膜组(35.3%)及萎缩性胃炎组(40.0%),Smad4 mRNA表达则明显降低,其阳性率(57.1%)明显低于正常胃黏膜组(94.1%)及萎缩性胃炎组(85.0%),差异均有显著性(P＜0.01).胃癌组织的分化程度越低,TGF-β1蛋白的阳性率越高,Smad4 mRNA阳性率越低.结论TGF-β1蛋白的高表达和Smad4 mRNA的低表达,对细胞的恶性转化及增殖可能有一定的生物学意义.     

转化生长因子β1对原发性肝癌诊断价值的初步探讨

为了解转化生长因子β１（ＴＧＦβ１）在原发性肝癌中的诊断意义，用酶联免疫吸附试验法（ＥＬＩＳＡ）测定了４７例原发性肝癌（ＰＨＣ）、７７例其他各种肝病和消化道恶性肿瘤及２０例正常对照者的血清ＴＧＦβ１水平。结果：ＰＨＣ血清ＴＧＦβ１水平明显高于正常对照及其他各病组（Ｐ值分别＜０．０５或０．０１）。血清ＴＧＦβ１诊断ＰＨＣ的敏感性和特异性分别为７２．３％和７７．９％，甲胎蛋白（ＡＦＰ）阴性ＰＨＣ诊断阳性率为７８．６％，其中７例小肝癌有５例（７１．４％）血清ＴＧＦβ１阳性，与ＡＦＰ联合检测可提高ＰＨＣ诊断阳性率，达９３．６％。血清ＴＧＦβ１作为一种新的ＰＨＣ血清标志物应用于ＰＨＣ的诊断、监测和疗效判断，尤其是对ＡＦＰ阴性或早期肝癌的诊断，有重要临床意义。     

Arrest of endotoxin-induced hypotension by transforming growth factor beta1.

Septic shock is a cytokine-mediated process typically caused by a severe underlying infection. Toxins generated by the infecting organism trigger a cascade of events leading to hypotension, to multiple organ system failure, and frequently to death. Beyond supportive care, no effective therapy is available for the treatment of septic shock. Nitric oxide (NO) is a potent vasodilator generated late in the sepsis pathway leading to hypotension; therefore, NO represents a potential target for therapy. We have previously demonstrated that transforming growth factor (TGF) beta1 inhibits inducible NO synthase (iNOS) mRNA and NO production in vascular smooth muscle cells after its induction by cytokines critical in the sepsis cascade. Thus, we hypothesized that TGF-beta1 may inhibit iNOS gene expression in vivo and be beneficial in the treatment of septic shock. In a conscious rat model of septic shock produced by Salmonella typhosa lipopolysaccharide (LPS), TGF-beta1 markedly reduced iNOS mRNA and protein levels in several organs. In contrast, TGF-beta1 did not decrease endothelium-derived constitutive NOS mRNA in organs of rats receiving LPS. We also performed studies in anesthetized rats to evaluate the effect of TGF-beta1 on the hemodynamic compromise of septic shock; after an initial 25% decrease in mean arterial pressure, TGF-beta1 arrested LPS-induced hypotension and decreased mortality. A decrease in iNOS mRNA and protein levels in vascular smooth muscle cells was demonstrated by in situ hybridization and NADPH diaphorase staining in rats treated with TGF-beta1. Thus these studies suggest that TGF-beta1 inhibits iNOS in vivo and that TGF-beta1 may be of future benefit in the therapy of septic shock.     

The role of transforming growth factor beta in lung development and disease

Transforming growth factor (TGF) beta plays an important role in normal pulmonary morphogenesis and function and in the pathogenesis of lung disease. The effect of TGFbeta is regulated via a selective pathway of TGFbeta synthesis and signaling that involves activation of latent TGFbeta, specific TGFbeta receptors, and intracellular signaling via Smad molecules. All three isoforms of TGFbeta are expressed at high levels during normal lung development, being particularly important for branching morphogenesis and epithelial cell differentiation with maturation of surfactant synthesis. Small amounts of TGFbeta are still present in the adult lung, and TGFbeta is involved in normal tissue repair following lung injury. However, in a variety of forms of pulmonary pathology, the expression of TGFbeta is increased. These include chronic lung disease of prematurity as well as several forms of acute and chronic adult lung disease. While TGFbeta1 appears to be the predominant isoform involved, elevated levels of all three isoforms have been demonstrated. The increase in TGFbeta precedes abnormalities in lung function and detectable lung pathology, but correlates with the severity of the disease. TGFbeta plays a key role in mediating fibrotic tissue remodeling by increasing the production and decreasing the degradation of connective tissue via several mechanisms.     

Myocardial fibrosis in transforming growth factor beta(1)heterozygous mice

Aging is associated with an increase in myocardial extracellular matrix components and contractile dysfunction. Transforming growth factor- beta(1)(TGF- beta(1)) has been shown to regulate expression of collagen genes and extracellular matrix component synthesis in the heart, and may contribute to the increase in myocardial fibrosis with aging. Therefore, we examined whether TGF- beta(1)heterozygous mutant mice would exhibit less age-associated myocardial fibrosis than normal mice. Twelve heterozygous TGF- beta(1)(+/-) deficient mice and 26 wild-type controls were examined to determine if there was a difference in development of myocardial fibrosis or mortality at 24 months of age due to the loss of one TGF- beta(1)allele. Animals which survived to 24 months of age were killed, and morphometric and functional studies were performed in isolated perfused hearts and in hearts from 6 month old control mice. Pressure-volume relations of the LV were assessed in the isovolumic (balloon in LV) Langendorff preparation. Eleven of 12 (92%) TGF- beta(1)deficient mice survived to 24 months of age in comparison to 66% (12/18) age-matched controls (P<0.05). Hearts from the 24 month old TGF- beta(1)deficient mice exhibited a decrease in myocardial fibrosis (4+/-1 v. 10+/-1% average LV fibrosis in TGF- beta(1)(+/-) and age-matched controls, respectively (P<0.05) and greater compliance (i.e.,lower LV end-diastolic pressure at a given balloon volume), decreased myocardial stiffness, and shorter contractile duration in comparison to 24-month-old wild-type controls. This suggests that modulation of collagen production and/or degradation by TGF- beta(1)may contribute to changes in myocardial structure and function with age. Thus, loss of one TGF- beta(1)allele appears to ameliorate age associated myocardial fibrosis and improve LV compliance, which may contribute to increased survival over the life span of these mice.     

Insulin-like growth factor II and transforming growth factor beta 1 regulate insulin-like growth factor I secretion in mouse bone cells.

Bone cells in culture produce and respond to growth factors, suggesting that local as well as systemic factors regulate bone volume. Previous studies have shown that IGF-I is the major mitogen produced by mouse bone cells and that its production is regulated by systemic agents such as PTH and estrogen. Because IGF-II and transforming growth factor beta 1 have been shown, respectively, to increase and decrease MC3T3-E1 cell proliferation, we tested the hypothesis that these two growth factors modulate the production of IGF-I in this cell line. In order to eliminate artifacts owing to IGF binding proteins, conditioned media samples were pretreated with IGF-II before measurement of IGF-I by RIA. After 24 h treatment at a density of 2.5 x 10(4) cells/cm2, IGF-II (10 micrograms/l) induced a 2.2-fold increase compared with untreated control (9.5 +/- 1.5 vs 4.2 +/- 0.44 pg/micrograms protein, p less than 0.001), whereas transforming growth factor beta 1 (1 microgram/l) caused a 66% decrease in IGF-I production (1.5 +/- 0.3 vs 4.2 +/- 0.44 pg/micrograms protein, p less than 0.001). Both IGF-II and transforming growth factor beta 1 regulated IGF-I production in a dose-, time- and cell density-dependent manner. The lowest effective doses for IGF-II and transforming growth factor beta 1 were 1 and 0.01 microgram/l, respectively. These results support a role for IGF-II and transforming growth factor beta 1 as potent modulators of IGF-I secretion in mouse bone cells.(ABSTRACT TRUNCATED AT 250 WORDS)     

Serum levels of transforming growth factor beta1 are significantly correlated with venous invasion in patients with gastric cancer

BACKGROUND AND AIM: The significance of serum levels of transforming growth factor (TGF)-beta1 in the development of gastric cancer is unclear. The purpose of this study is to determine whether serum TGF-beta1 correlated with the clinicopathological findings of patients with gastric cancer. METHODS: Transforming growth factor-beta1 levels in the serum of 275 gastric cancer patients and 275 gender- and age-matched healthy controls were measured with enzyme-linked immunosorbent assay (ELISA) using a commercially available kit. RESULTS: The mean level of serum TGF-beta1 of gastric cancer patients (15.9 +/- 5.9 ng/mL) was significantly higher than that (13.9 +/- 7.4 ng/mL) of healthy controls (P < 0.01). The odds ratio for the subjects in the highest quartile (16.7 ng/mL or more) was 4.03 (95% confidence interval, 2.14-7.58), as compared with that for the subjects in the lowest quartile (0-9.5 ng/mL). Patients with venous invasion compared to those without venous invasion had significantly elevated serum TGF-beta1 (17.3 +/- 7.2 vs 15.0 +/- 5.1 ng/mL; P = 0.04). There were no statistically significant differences between the two groups categorized by histological type, lymph node metastasis and distant metastasis. Logistical regression analysis showed that venous invasion was significantly correlated with elevated serum TGF-beta1 levels (P = 0.02). CONCLUSIONS: The present study showed that an elevated serum TGF-beta1 level may be significantly correlated with venous invasion in gastric cancer patients.