Serum hepatocyte growth factor concentration in patients with various degrees of chronic renal failure

Summary: Serum hepatocyte growth factor (HGF) concentrations were measured in healthy volunteers, chronic renal failure patients without renal replacement therapy and haemodialysis patients. Serum HGF concentrations in healthy volunteers, chronic renal failure patients and haemodialysis patients were 0.18 ± 0.04 (s.d.), 0.28 ± 0.06 and 0.46 ± 0.22 ng/mL, respectively. Serum HGF concentration in chronic renal failure patients was significantly higher than that in healthy volunteers. Serum HGF concentration in haemodialysis patients was significantly higher than those in healthy volunteers and chronic renal failure patients. There was no regression of serum HGF concentration on age, sex, history of haemodialysis, prehaemodialysis serum creatinine concentration, and serum tumour necrosis factor (TNF)-α concentration. We conclude that chronic renal disease and haemodialysis therapy are contributing factors to an increased serum HGF concentration.     

Serum hepatocyte growth factor levels in patients with renal diseases.

The serum levels of hepatocyte growth factor (HGF) were determined in patients with various renal diseases. In patients with acute-phase acute renal failure (ARF) and chronic tubulointerstitial nephritis (chronic TIN), the serum HGF levels were 0.55 +/- 0.24 and 0.44 +/- 0.37 ng/ml (mean +/- SD), respectively, and were significantly higher than that in the control group (0.12 +/- 0.12 ng/ml). The serum HGF level tended to be high also in patients with active-phase steroid-sensitive nephrotic syndrome (SSNS). The serum levels of HGF were not elevated in patients with IgA nephropathy (IgAN), Henoch-Sch?nlein purpura nephritis (HSPN), membranoproliferative glomerulonephritis (MPGN), poststreptococcal acute glomerulonephritis (PSAGN), unilateral renal atrophy, unilateral nephrectomy, or proximal tubular dysfunction. These observations suggest that glomerular disorders cause no apparent elevation of the serum HGF level, and that elevation of the serum HGF level may be associated with tubulointerstitial damage in renal diseases.     

Serum hepatocyte growth factor and clinical outcome in biliary atresia

Purpose

Biliary atresia (BA) remains one of the most intractable liver diseases leading to liver fibrosis. Serum hepatocyte growth factor (HGF) has been shown to increase in cirrhotic patients. The aim of this study was to investigate the possible role of HGF in BA.

Methods

Serum levels of HGF were determined using an enzyme-linked immunosorbent assay from 28 BA patients and 25 healthy children. The patients were categorized into 3 groups according to their clinical outcomes (good, fair, and poor): group A (good), jaundice-free patients (total bilirubin [TB] < 2.0 mg%); group B (fair), patients with mild to moderate jaundice (TB, 2 to 10 mg%); and group C (poor), patients with marked jaundice (TB > 10 mg%). Unpaired t test and analysis of variance (ANOVA) with post-hoc tests were used. Data were expressed as mean and SEM.

Results

Serum HGF levels in BA patients were higher than the controls (P = .02). Subgroup analysis found that there were 12 patients in group A, 8 patients in group B, and 8 patients in group C. The mean age of patients in groups A, B, and C were 5.34 ± 0.52, 7.45 ± 1.98, and 5.49 ± 1.57 years (P > .05). Serum HGF in controls and groups A, B, and C were 0.24 ± 0.03, 0.28 ± 0.04, 0.36 ± 0.09, and 0.56 ± 0.07 ng/mL, respectively. Serum HGF levels in BA patients with poor outcome were higher than patients with good outcome (P = .02). There was no difference in serum HGF of BA patients with fair outcome compared with other groups.

Conclusions

Serum HGF is elevated in BA. Furthermore, BA patients with poor outcome have significantly elevated HGF compared with patients with good outcome. Serum HGF levels may be predictive of prognosis with respect to the progression of liver dysfunction. However, the results of HGF in patients with fair outcome are inconclusive, probably because of the small sample size. Further studies are needed to elucidate the detailed mechanisms.     

肝细胞生长因子在胃癌病人血清中的表达及意义

目的:肝细胞生长因子(hepatocyte growth factor,HGF)是一种多肽生长因子,其促进细胞增殖,诱导细胞迁移、侵袭及参与血管生成,在肿瘤发生发展过程中具有重要作用。本研究通过检测胃癌病人血清HGF水平,分析其与胃癌临床病理特征的关系,并与常用肿瘤标志物CA19-9、CEA进行比较,探讨胃癌病人血清中HGF的表达及其临床意义。方法:用酶联免疫吸附夹心法检测80例胃癌病人术前血清HGF、CA19-9、CEA水平,并观察60例病人根治术后血清HGF变化。结果:胃癌病人血清HGF水平(2.94±2.67)μg/L明显高于正常对照组(1.02±0.31)μg/L(P=0.002);分层分析发现,随着疾病的进展,血清HGF水平逐渐升高[Ⅰ期(2.19±2.12)μg/L,Ⅱ期(2.53±2.38)μg/L,Ⅲ期(3.92±3.45)μg/L,Ⅳ期(4.13±3.71)μg/L];Ⅲ期和Ⅳ期分别与Ⅰ期进行比较,均有显著差异(P<0.05)。另外,80例病人血清HGF、CA19-9和CEA的阳性率分别为80%、16.2%和5.0%,HGF阳性率明显较高(P<0.01)。结论:胃癌病人血清HGF水平明显高于正常对照组,且血清HGF的表达水平与胃癌淋巴结及肝脏转移呈正相关.血清HGF表达水平可作为反映胃癌生物学行为和判断预后的参考指标。     

转染HGF基因对肝细胞的生物学效应

目的探讨肝细胞生长因子(hepatocyte growth factor，HGF)基因对肝细胞生长增殖能力的影响。方法通过脂质体介导法，将HGF基因导入肝细胞中。用荧光显微镜以及原位杂交观察到HGF基因表达。采用检测细胞生长曲线、Ki-67蛋白和嗜银蛋白免疫组化观察肝细胞生长增殖能力及DNA合成能力的变化。结果荧光显微镜观察可见到绿色荧光蛋白的表达，用原位杂交方法进一步证实了HGF蛋白在细胞中的表达。细胞生长曲线显示，转染HGF基因的肝细胞增殖速度明显增快，Ki-67蛋白和嗜银蛋白表达明显增多，提示转导HGF基因使肝细胞增殖活性增加。结论本实验显示转染的HGF可表达并有促细胞分裂活性。为进一步了解HGF分子生物学特性及治疗应用提供了理论基础。     

Serum hepatocyte growth factor activator (HGFA) in benign prostatic hyperplasia and prostate cancer

OBJECTIVES: Hepatocyte growth factor activator (HGFA) is responsible for proteolytic activation of the precursor form of hepatocyte growth factor (HGF). We attempted to clarify whether serum levels of HGFA could be used as a marker for prostate cancer. MATERIAL AND METHODS: Serum levels of total HGF and HGFA were measured by enzyme-linked immunosorbent assay in 99 healthy controls, 27 patients with benign prostatic hyperplasia (BPH) and 119 patients with prostate cancer. RESULTS:: The mean+/-S.D. serum levels of HGFA in untreated prostate cancer and BPH cases were 0.42+/-0.24 and 0.50+/-0.26 ng/ml, respectively (no significant difference). Serum HGFA was significantly elevated in hormone-refractory prostate cancer (stage D3) compared to other stages, while HGF did not significantly differ with regard to clinical stage. CONCLUSIONS: Serum HGFA tends was elevated in patients with advanced stage prostate cancer. Further studies in large groups of patients are needed to clarify the clinical value of HGFA.     

围术期小儿应激反应因素与调控

目的 小儿围术期应激反应的典型表现是神经内分泌系统、免疫系统和代谢系统的变化.术前焦虑、紧张等心理因素以及麻醉、手术创伤均可影响小儿围术期应激反应,而且应激反应的剧烈程度与围术期并发症的发生率密切相关.目的 通过综述比较,确定更能有效降低小儿围术期应激反应的麻醉药物、麻醉方法和术后镇痛方式.内容 综述小儿围术期应激反应的生物学特点以及小儿围术期心理状况、常用麻醉药物、麻醉方法对围术期应激反应的影响.趋向 深入研究比较不同术后镇痛方式对小儿术后应激反应的影响,以降低小儿术后相关并发症.     

围术期小儿应激反应因素与调控

目的 小儿围术期应激反应的典型表现是神经内分泌系统、免疫系统和代谢系统的变化.术前焦虑、紧张等心理因素以及麻醉、手术创伤均可影响小儿围术期应激反应,而且应激反应的剧烈程度与围术期并发症的发生率密切相关.目的 通过综述比较,确定更能有效降低小儿围术期应激反应的麻醉药物、麻醉方法和术后镇痛方式.内容 综述小儿围术期应激反应...     

Unexpected effect of haemodialysis on salivary hepatocyte growth factor.

Sir, Periodontal disease causing premature tooth loss is common andaggressive in younger and still dentulous patients undergoingmaintenance haemodialysis (HD) [1]. Recent studies showed thathepatocyte growth factor (HGF), a pluripotential, ubiquitousand mostly regenerative cytokine, is strongly involved in thepathogenesis and progression     

转肝细胞生长因子基因肝细胞模型的建立

目的：利用脂质体介导法在体外建立转肝细胞生长因子（HGF）基因的人肝细胞模型。方法：建立HGF真核细胞表达载体，利用脂质体介导法在体外将HGF基因转染入人肝细胞，利用荧光显微镜观察、免疫组织化学、原位杂交方法检测HGF真核细胞表达载体的转录和表达情况。结果：以阳离子脂质体LipofectAMINE为载体将HGF基因转染人肝细胞后，经400mg/L的G418筛选后可形成抗性克隆；Neo基因原位杂交结果显示转染基因的细胞有阳性表达；荧光显微镜下观察到有绿色荧光；免疫组织化学证实转染HGF基因的肝细胞有HGF蛋白的表达。结论：HGF基因可被成功转染入人肝细胞并能有效表达，这可能为肝病的基因治疗提供一种新途径。     

The role of hepatocyte growth factor in growth plate cartilage

To investigate the physiological role of hepatocyte growth factor (HGF) in endochondral bone formation, we examined the expression of HGF and its receptor c-met and the effects of HGF on growth plate chondrocytes. HGF was highly expressed in the prehypertrophic zone and hypertrophic zone in rat costal growth plate cartilage. The expression of HGF increased in rabbit chondrocytes as they matured in culture. Conversely, c-met expression was down regulated along maturation of growth plate chondrocytes. HGF had weak stimulatory effects on DNA and proteoglycan synthesis of growth plate chondrocytes. However, HGF strongly inhibited expression of terminal differentiation-related phenotypes, such as type X collagen and alkaline phosphatase (APase) synthesis and cartilage matrix mineralization. When HGF was removed from the cultures, cells quickly expressed type X collagen and APase. Once chondrocytes differentiated to mature chondrocytes, HGF did not inhibit further differentiation of these cells. These results suggested that HGF is a negative regulator of terminal differentiation of growth plate chondrocytes.. Received: Feb. 12, 1998 / Accepted: March 12, 1998     

Striking increase in circulating hepatocyte growth factor during enoxaparin-anticoagulated haemodialysis.

Sir, Hepatocyte growth factor (HGF) is a multipotent cytokine ofgrowing importance in tissue development, apoptosis, regenerationand repair of injuries. In chronic haemodialysis (HD) patients,serum HGF levels are increased, directly related to the extentof arteriosclerosis and chronic inflammation, and the prevalenceof cardiovascular disease and viral hepatitis, and may stimulateerythropoiesis [1,2]. They also independently predict mortalityin dialysis patients [2]. Increased HGF may thus be viewed asa marker of co-morbidity and     

Serum vascular endothelial growth factor predicts venous invasion in hepatocellular carcinoma: a prospective study

OBJECTIVE: To evaluate the correlation between serum vascular endothelial growth factor (VEGF) level and the clinicopathologic features in patients with hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: VEGF is an important angiogenic factor regulating tumor angiogenesis. A high serum VEGF level has been shown to be associated with tumor progression and metastasis in several human cancers, but its significance in HCC is unclear. The correlation between serum VEGF level and tumor pathologic features in patients with HCC has not been studied before. METHODS: Preoperative serum samples and tumor specimens were prospectively collected in 100 patients undergoing resection of HCC. Serum VEGF level was measured by enzyme-linked immunosorbent assay, and tumor VEGF expression was assessed by immunohistochemical study. Histopathologic examination was performed by a pathologist without prior knowledge of the serum VEGF level or tumor VEGF expression. RESULTS: Preoperative serum VEGF levels ranged from 15 to 1,789 pg/mL (median 269). When serum VEGF levels were compared between groups categorized by different clinicopathologic variables, significant correlation was found between a high serum VEGF level and absence of tumor capsule, presence of intrahepatic metastasis, presence of microscopic venous invasion, and advanced stage. There was a positive correlation between the serum VEGF level and tumor expression of VEGF as well as platelet count. When the 75th percentile serum VEGF level (500 pg/mL) was used as a cutoff level, the frequency of venous invasion in patients with a high serum VEGF level was significantly greater compared with patients with a low serum VEGF level. By multivariate analysis, a serum VEGF level of more than 500 pg/mL and tumor size more than 5 cm were independent preoperative factors predictive of microscopic venous invasion. During a median follow-up of 11.6 months, 48% of patients with a serum VEGF level of more than 500 pg/mL and 27% of those with a serum VEGF level of 500 pg/mL or less developed postoperative recurrence. CONCLUSIONS: These results show that a high preoperative serum VEGF level is a predictor of microscopic venous invasion in HCC, suggesting that the serum VEGF level may be useful as a biologic marker of tumor invasiveness and a prognostic factor in HCC.     

Relations between oxidative stress,hepatocyte growth factor,and liver disease in hemodialysis patients

BACKGROUND: Hepatocyte growth factor (HGF) and copper/zinc superoxide dismutase (Cu/Zn SOD) protect against tissue injury, including that due to oxidative stress (SOX). We studied whether they could be associated with each other, SOX markers, prevalence of viral hepatitis, and cardiovascular disease (CVD) and their laboratory surrogates in maintenance hemodialysis (HD) patients. METHODS: In 24 patients, pre-dialysis serum HGF, plasma Cu/Zn SOD, total lipid peroxides, and serum autoantibodies against oxidized LDL were measured by ELISAs. Viral hepatitis B and C markers were determined by third generation microparticle ELISAs, and CVD was identified on a clinical basis. Results: In HD patients, circulating HGF, Cu/Zn SOD, and the other SOX markers were higher than in healthy controls, and HGF directly correlated with Cu/Zn SOD levels (P = 0.0006). Both HGF (P = 0.021) and Cu/Zn SOD (P=0.017) were positively associated with prevalence of viral hepatitis and serum alanine aminotransferase activity (P = 0.021 and P=0.040, respectively). Presence of CVD directly correlated with HGF (P = 0.001) but not with Cu/Zn SOD levels (P = 0.087). Circulating HGF positively related to serum C-reactive protein (P = 0.043). In patients without viral hepatitis and CVD, both HGF and Cu/Zn SOD were lower than in those with, and higher than in healthy controls. CVD (P = 0.003) and viral hepatitis (P = 0.024) were independent predictors of increased HGF, while positive viral hepatitis marker predicted increased Cu/Zn SOD levels (P = 0.019) in HD patients. There were no associations between HGF and the SOX markers in controls. Conclusions: In maintenance HD patients, circulating Cu/Zn SOD and HGF levels are increased, likely as a part of the reparatory reaction against liver damage. Viral hepatitis status and liver function should be considered in further studies of Cu/Zn SOD in these subjects.     

Serum and drainage fluid vascular endothelial growth factor levels in early surgical wounds

BACKGROUND: Wound healing relies on a coordinated expression and release of growth factors controlling angiogenesis. We measured vascular endothelial growth factor (VEGF) levels in serum and early wound fluid following primary sutured and mesh repair of abdominal hernias. MATERIALS AND METHODS: Thirty-seven patients were studied measuring serum and wound drainage fluid VEGF by enzyme-linked immunosorbent assay preoperatively and on the 1st, 3rd, 5th and 7th postoperative days. RESULTS: Serum and wound fluid VEGF levels increased significantly by the 3rd postoperative day and continued to rise during the conduct of the study with wound fluid concentrations always exceeding serum levels. The kinetics of VEGF increases were similar in both types of hernia repair; however, serum and wound levels rose slightly earlier in the mesh repair group. CONCLUSIONS: Steadily increasing levels of VEGF are detected during the early proliferative phase of wound healing in both serum and wound fluid. It is unknown whether either is predictive for delayed hernia recurrence.     

乌司他丁预先给药对肝切除术大鼠氧化应激反应和肝细胞生长因子的影响

目的 探讨乌司他丁预先给药对肝切除术大鼠氧化应激反应和肝细胞生长因子(HGF)的影响.方法 健康清洁级雄性SD大鼠112只,体重230 ～ 280 g,3月龄,采用随机数字表法,将大鼠随机分为2组(n=56):肝切除术组(H组)和乌司他丁预先给药组(U组).2组切除肝左叶和中叶并阻断肝右叶和尾叶的血流进行缺血,30 min时恢复灌注,U组于缺血前5 min静脉注射乌司他丁50000U/kg.每组分别于缺血前、再灌注1、6、12、24和48 h时取8只大鼠,采集下腔静脉血样,测定血清ALT、AST和HGF水平,然后取肝右叶组织,测定肝细胞凋亡指数(AI)、SOD和髓过氧化物酶(MPO)活性、MDA含量、增殖细胞核抗原表达,计算肝再生度.每组取8只大鼠,记录术后7d内生存情况.结果 与H组比较,U组各时点ALT及AST活性、AI、髓过氧化物酶活性和MDA含量降低,HGF浓度、SOD活性、增殖细胞核抗原表达和肝再生度升高(P＜0.05),术后7d内生存率差异无统计学意义(P＞0.05).结论 乌司他丁预先给药可增强肝切除术大鼠肝再生功能,其机制与抑制氧化应激反应和促进HGF生成有关.     

Mechanism of surgical stress impairment of human perioperative natural killer cell cytotoxicity.

Natural killer (NK) cells are an important defense against intravascular tumor dissemination. Tumor embolization can occur at surgery, so we tested whether surgical stress decreased perioperative NK cell cytotoxicity, and examined the underlying mechanism of suppression. Patients with solid tumors underwent NK cell cytotoxicity assay just before and 24 hours after surgery in a 3-hour chromium 51 release assay. The NK cell cytotoxicity was significantly decreased postoperatively. We considered that surgical NK cell impairment might be due to (1) NK cell redistribution, (2) presence of suppressor cells, or (3) direct "toxic" effects on NK cells. Impaired NK cell cytotoxicity was not due to NK cell redistribution, because differential counts showed no significant changes in the percentage of large granular lymphocyte NK morphology. To isolate possible suppressor cells, postoperative cells from patients were selectively depleted of NK cells using anti-Leu-11b monoclonal antibody plus complement; these cells were then mixed with autologous preoperative cells. Postoperative NK cell cytotoxicity was markedly impaired, but the postoperative NK depleted cells did not suppress preoperative NK cells. We conclude that NK cell functional impairment from surgical stress is due to direct "toxic" effects on NK cells rather than either NK cell redistribution or the generation of NK-directed suppressor cells.