Serum Hepatocyte Growth Factor Research Articles

A Critical Role for Matrix Metalloproteinases in Liver Regeneration

Matrix metalloproteinases (MMPs), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) are mediators of liver regeneration. To determine whether MMPs are required for normal hepatic regeneration, we performed 67% hepatectomies on mice treated with a broad-spectrum MMP-inhibitor, and assessed the effect on liver regeneration and urinary MMP activity. Mice were subjected to sham operations, 67% hepatectomy, or 67% hepatectomy plus treatment with the broad-spectrum MMP inhibitor Marimastat. Urine collected preoperatively and for 8 d postoperatively was tested for MMP-2 and MMP-9 activity using zymography. Serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, TNF-alpha, IL-6, and hepatocyte growth factor levels were measured. Liver sections were analyzed by CD31 immunohistochemistry and microvessel density. Mitotic index and proliferating cell nuclear antigen labeling index were determined. The mean regenerating liver weight on postoperative day 8 was 0.72 +/- 0.01 grams for the hepatectomy Marimastat group, and 0.83 +/- 0.02 grams for the hepatectomy control group (P < 0.001). Urinary MMP-9 activity was elevated during hepatic regeneration, and decreased on postoperative day 8 when the liver returned to its preoperative mass. In contrast, urine from hepatectomy Marimastat mice, in which liver regeneration was successfully inhibited, showed consistently low levels of MMP-2 and MMP-9 activity. The hepatectomy Marimastat group also exhibited elevated serum IL-6 levels on post-operative day 8, while serum TNF-alpha soluble receptor II levels were unchanged. Hepatocyte growth factor levels were not significantly different between the control hepatectomy and hepatectomy Marimastat groups at days 2, 4, and 8. Liver microvessel density was reduced in the hepatectomy Marimastat group at day 4. Mitotic index and proliferating cell nuclear antigen index were significantly decreased in the Marimastat hepatectomy group at post-operative day 2. The broad-spectrum MMP-inhibitor Marimastat inhibits liver regeneration. Microvessel density is reduced at day 4. Furthermore, urinary MMP-9 is elevated during liver regeneration, and this effect is not observed when regeneration is inhibited by the broad-spectrum MMP-inhibitor Marimastat.

Prognostic significance of serum hepatocyte growth factor in clear cell renal cell carcinoma: comparison with serum vascular endothelial growth factor

No adequate serum predictive biomarker currently exists, which can identify the activity of renal cell carcinoma (RCC). We investigate the association of serum hepatocyte growth factor (HGF) and serum vascular endothelial growth factor (VEGF) levels with clinicopathologic parameters in untreated clear cell RCC patients. We measured serum levels of HGF and VEGF in 45 patients with untreated clear cell RCC and 45 healthy controls using an enzyme-linked immunosorbent assay (ELISA). Patients with clear cell RCC had significantly higher serum HGF and VEGF concentrations than healthy subjects: median, 1070.7 versus 728.3 pg/ml (p<0.0001) for HGF; and median, 397.5 versus 245.6 pg/ml (p=0.0003) for VEGF. We found a significant correlation between serum level of HGF and clinical stage and tumor grade. Survival of patients with high serum HGF (>1150 pg/ml) was significantly reduced compared to patients with low serum HGF concentrations (p=0.0044). In patients with nuclear grade 2 or high stage RCC, the higher serum HGF group exhibited significantly lower cause-specific survival (p=0.0087 and p< 0.05, respectively). No significant difference was observed between serum VEGF levels and cause-specific survival rate. Serum HGF might be a diagnostic and prognostic indicator in clear cell RCC, especially for patients with grade 2 or high stage RCC.

Effects of adenoviral-mediated hepatocyte growth factor on liver regeneration after massive hepatectomy in rats.

Resection is the only curative treatment for liver metastasis of colorectal cancers. Despite the supreme regenerative potential of the liver, major hepatectomy sometimes leads to liver failure, and the limitation of resectable liver volumes makes advanced tumors inoperable. This study was attempted to promote liver regeneration using hepatocyte growth factor (HGF) gene transfection by venous-administered adenovirus and to improve the survival of rats after massive hepatectomy. The adenovirus that encodes HGF was administered to rats before 85%-hepatectomy. The administration of HGF gene improved the survival of rats after massive hepatectomy, while the administration of control adenovirus deteriorated their survival. Gene transfection of HGF showed up-regulation of serum HGF, stimulation of hepatocellular proliferation and rapid liver regeneration. Moreover, HGF administration reduced apoptosis of hepatocytes. The administration of HGF gene prevented liver dysfunction after major hepatectomy and may be a new assist for surgery.

Clinical, Prognostic and Possible Therapeutic Relevance of Angiogenesis in Non-Hodgkin's Lymphoma.

Considering that angiogenesis may have importance in the pathogenesis of non-Hodgkin's lymphomas (NHL), the aims of this study were to correlate hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (FGF) serum levels and microvessel density (MVD) with cell origin, biological behavior, tumor load and prognosis in NHL.Materials and methods: Eighty-seven consecutive previously untreated NHL patients had serum samples collected and were included in the study. Thirty-seven (42%) of them also had additional serum follow-up samples. Control group was composed by ten healthy blood donors. HGF, VEGF and FGF serum levels were determined by ELISA. MVD was measured by CD34 staining in patients with available paraffin blocks.Results: HGF mean serum level was significantly higher in both early and advanced NHL Ann Arbor stages when compared to control group. HGF was also significantly higher in both aggressive and indolent NHL when compared to control group. Furthermore, mean serum level of HGF in aggressive NHL was significantly higher than in indolent NHL. Regarding International Prognostic Index (IPI), mean serum levels of HGF at diagnosis was significantly higher for patients with IPI > 2 when compared to IPI <=2. FGF mean serum level was also significantly higher in early and advanced NHL stages when compared to controls. We also observed that FGF mean serum level was significantly higher in indolent NHL when compared to control group. Regarding VEGF, serum levels were significantly higher in aggressive NHL when compared to control group. Sequential analyses of HGF, VEGF and FGF serum levels in NHL showed that serum HGF and VEGF levels decreased significantly after 6 months of treatment completion. When we analyzed MVD, no associations between patient's groups were found, even when stage, biologic behavior or cell origin were taken into account. We did not find correlation among MVD and serum levels of HGF, VEGF and FGF at diagnosis either.Conclusions: Our findings suggest that HGF seems to play an important role in NHL pathogenesis because:1.its serum level is associated to tumor load and aggressiveness;2.it can be correlated to treatment response.In face of these results, we could suggest that HGF is a potential target for therapeutic intervention in NHL.

Serum Apoptosis Markers in Acute Liver Failure: A Pilot Study

We sought to determine whether circulating apoptotic markers are altered in acute liver failure (ALF), differ with etiology, or predict clinical outcome in this condition. Serum levels of soluble Fas (sFas), tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF), and interleukin-6 (IL-6) were measured in 67 acute liver failure patients, as well as controls. In a subset of the groups, we measured serum M-30 antigen, an exposed neoepitope from caspase cleavage. We also assessed M-30 immunoreactivity in liver tissue of ALF patients and controls. Median levels for TNF-alpha, HGF, IL-6, and M-30 antigen were at least 10-fold greater in ALF than in hepatitis C virus or normal controls (P < .0001). Median day 1 sFas, day 3 sFas, and day 1 HGF levels varied according to etiology of acute liver failure (P = .004, P = .011, and P = .019, respectively), with values for drug-induced liver injury and acetaminophen-related ALF higher than other etiologies. Median M-30 antigen levels were significantly higher in patients who were transplanted and/or died (2183 U/L) than spontaneous survivors (1004 U/L) (P = .026). M-30 immunoreactivity in liver tissue was significantly greater in ALF patients than HCV controls (P = .004). TNF-alpha, HGF, IL-6, and M-30 antigen were significantly elevated in ALF. High levels of sFas and HGF might help to confirm a diagnosis of drug-induced liver injury or acetaminophen-related ALF. Higher levels of M-30 antigen are associated with poor clinical outcomes in ALF.

Hepatocyte growth factor and interleukin-6 in combination with prostate volume are possible prostate cancer tumor markers in patients with gray-zone PSA levels

The aim was to assess whether hepatocyte growth factor (HGF) and interleukin (IL)-6 in combination with prostate volume are able to accurately detect prostate cancer in patients with gray-zone prostate-specific antigen (PSA) levels. A total of 159 patients with PSA levels of <10 ng ml(-1) were enrolled. Forty-two (35.3%) were diagnosed with prostate cancer, whereas 117 (64.7%) had no cancer and were used as benign group. HGF and IL-6 density (HGFD and IL-6D, respectively) values were calculated by dividing serum HGF and IL-6 levels with prostate volume. Median IL-6 (2.3 pg ml(-1)) levels for the prostate cancer group were significantly higher than those for the benign group before adjustment for age (1.7 pg ml(-1)) (P=0.0098). After age adjustments, median IL-6 (2.17 pg ml(-1)), HGFD (0.00972 ng ml(-1) cm(-3)), and IL-6D (0.0848 pg ml(-1) cm(-3)) values for the prostate cancer group were significantly higher than those for the benign group (IL-6, 1.78 pg ml(-1); HGFD, 0.00732 ng/ml/cc; and IL-6D, 0.049 pg/ml/cc; P=0.0416, 0.007 and 0.0005, respectively). In receiver operating characteristic analyses, the areas under the curves for HGFD (0.64) and IL-6D (0.68) were significantly greater than those for HGF (0.52) and IL-6 (0.61) (P=0.0006 and 0.019, respectively). With an HGFD cutoff value of 0.00392 ng ml(-1) cm(-3) (sensitivity=100%, specificity=11%), 11.1% of the benign group were able to avoid unnecessary biopsies without missing prostate cancer. HGF and IL-6 levels in combination with prostate volume were shown to be useful parameters for prostate cancer screening in patients with gray-zone PSA levels.

Changes of serum hepatocyte growth factor before and after percutaneous coronary intervention in patients with unstable angina pectoris and significance there

To investigate the effect of unfitrate heparin (UFH) and low molecular weight heparin (LMWH) on the expression of serum hepatocyte growth factor (HGF) during percutaneous coronary intervention (PCI). Seventy patients with chronic unstable angina pectoris were divided into 2 groups: PCI group (n = 49, with at least one main coronary artery branch with stenosis > or = 70%) and non-PCI group (n = 21, with the main coronary artery branch with stenosis < 70%). UFH was used at the beginning of coronary angiography in both groups and LMWH was used after PCI only in the PCI group. The serum level of HGF was measured before, during, and 1 and 7 days after PCI; and cardiac troponin 1 (cTnI) was measured before and 1 day after PCI in all 70 patients. The serum level of HGF of the PCI group increased during and immediately after PCI (12 322 +/- 3723 ng/L and 13 566 +/- 3767 ng/L respectively), both significantly higher than that before the procedure (1736 +/- 604 ng/L, both P < 0.0001), The serum level of HGF of the non-PCI group increased during and immediately after the procedure (10 928 +/- 2196 ng/L and 11 457 +/- 2298 ng/L respectively), both significantly higher than that before the procedure (967 +/- 349 ng/L, both P < 0.01). However, there were no significant differences in the HGF levels during and after the procedure between the PCI and non-PCI groups. The serum HGF returned to the normal level 24 h after the procedure in both groups. The serum GHF 7 days after the procedure of the cTnI (-) PCI group was significantly lower than that before the procedure (P < 0.01), however, the serum GHF 7 days after the procedure of the cTnI (+) PCI group remained relatively high, not significantly different from that before the procedure. There is an enhanced secretion of cardiac HGF in the patients with severe coronary artery disease. UFH promotes the release of serum HGF in the patients with chronic unstable angina pectoris undergoing PCI, which indicates some other biological effects in addition to its anticoagulant property. The delayed fall of serum HGF after PCI has relationship with minor myocardial infarction.

Bladder Cancer Cell Invasion Is Enhanced by Cross-Talk with Fibroblasts Through Hepatocyte Growth Factor

To examine the effects of fibroblast-derived humoral factors, especially hepatocyte growth factor (HGF), on the invasive potential of bladder cancer cells. Stromal cells in cancer tissue are thought to play an important role in the transformation and invasion of cancer cells. The influence of fibroblast cells (TIG-1 cells) and HGF on the invasive potential of bladder cancer cells (5637, T24, J82, HT1376, and MGHU-1 cells) was evaluated by in vitro cell invasion assay. The expression of HGF and c-Met, which is the receptor of HGF, was examined by reverse transcriptase-polymerase chain reaction. To clarify the relationship between the serum HGF level and invasive bladder cancer, we measured the serum concentrations of HGF in patients with bladder cancer without metastatic disease and normal controls, using an enzyme-linked immunosorbent assay. The in vitro cell invasion assay showed that the number of invading bladder cancer cells was significantly increased by the conditioned medium (CM) of the fibroblast cells. HGF neutralization antibody partially inhibited the enhancement of invasiveness by fibroblast CM. The CM of fibroblasts cultured with bladder cancer CM stimulated cancer cell invasion more strongly (with increased HGF secretion) than did the CM of fibroblasts cultured without bladder cancer CM. The serum HGF levels were significantly greater in patients with muscle-invasive bladder cancer (regardless of tumor size) than in patients with non-muscle-invasive bladder cancer. The present results have suggested that bladder cancer cell invasion is enhanced by cross-talk with fibroblasts through humoral factors, including HGF. Elucidation of this mechanism could lead to novel therapeutic strategies for bladder cancer.

Serum hepatocyte growth factor as a marker of tumor activity in head and neck squamous cell carcinoma

Hepatocyte growth factor (HGF) has previously been reported to be elevated in the serum of patients with malignancy, including breast, colorectal and gastric cancers. Here, we evaluated the correlation between serum HGF and the progression of head and neck squamous cell carcinoma (HNSCC). The mean serum HGF levels in 71 healthy control subjects, 78 patients with primary HNSCC, and eight patients with recurrent HNSCC were 0.538+/-0.163, 0.701+/-0.252, and 0.925+/-0.349ng/ml, respectively. The increase in the HGF level was significantly correlated with tumor stage progression. The HGF level had decreased to normal at 1 month after curative resection of the tumors. During follow-up for several months, the HGF level significantly increased in recurrent HNSCC patients, whereas there was no increase in nonrecurrent patients. Our data suggest that serum HGF is significantly corrected with tumor progression and may be a strong predictor of recurrence in HNSCC.

Serum Hepatocyte Growth Factor and Vascular Endothelial Growth Factor in Children with Acute Liver Failure

Hepatocyte growth factor (HGF), a potent mitogen, and vascular endothelial growth factor (VEGF), a potent angiogenic factor, may play roles in hepatocyte regeneration in patients with acute liver failure (ALF). The aim of this study was to investigate serum levels of HGF and VEGF in children with ALF. Serum samples were collected on admission from 25 children with ALF (median age, 11.1 y; range, 1.3-17.1 y; 11 male, 14 female) and 12 normal children (9.1 y; range, 5.4-15.4 y; 6 male, 6 female). Aetiology of ALF was 13 non-A to E hepatitis, 3 viral, 3 toxic, and 6 other. HGF and VEGF in sera were assayed by enzyme-linked immunosorbent assay. Median HGF levels in patients (10,157 pg/mL; range, 3412-73,420 pg/mL) were significantly higher than in controls (855 pg/mL, 510-1253 pg/mL; P < 0.001). Median VEGF levels in patients (164 pg/mL, 0-1588 pg/mL) were not significantly different from those in controls (214 pg/mL, 11-527 pg/mL). There was no relationship of HGF or VEGF levels to the aetiology of liver failure. There was a positive correlation between serum HGF and international normalized ratio (r = 0.73, P < 0.001), but not with levels of serum aspartate aminotransferase, bilirubin, or VEGF. There was no correlation between VEGF levels and international normalized ratio, aspartate aminotransferase or bilirubin. Serum levels of HGF but not VEGF are increased in children with acute liver failure.

Significance of serum hepatocyte growth factor levels in patients with hepatocellular carcinoma undergoing hepatic resection

Hepatocyte growth factor (HGF) is a potent hepatocyte mitogen and may stimulate the proliferation and invasiveness of human hepatocellular carcinoma (HCC) cells through the c-met receptor. This study evaluates the significance of serum HGF levels in patients undergoing HCC resection. The peripheral and portal sera and HCC and non-tumorous tissues of 40 HCC patients, with tumor TNM stage I (n=12), II (n=17), and III (n=11) diseases, who underwent hepatic resection were prospectively collected. Serum HGF levels were determined by enzyme-linked immunosorbent assay. The c-met protein expressions were examined by immunohistochemistry. Median follow-up time was 69 months. The prehepatectomy portal HGF levels (median, 622pg/mL) were significantly higher than peripheral HGF levels (564pg/mL) (P=0.026). The posthepatectomy portal HGF levels (699pg/mL) were significantly higher than prehepatectomy portal HGF levels (P<0.001). C-met expression was detected in 87.5% HCC and in 85.0% non-tumorous liver tissues. By Cox multivariate analysis, posthepatectomy portal HGF level >699pg/mL (P<0.001), multiple tumors (P=0.042), and TNM stages II (P=0.019) and III (P=0.009) were independent factors related with survival. Patients with a posthepatectomy portal HCG level >699pg/mL and with a positive c-met expression in HCC tissue have the worst survival. In HCC patients, high peripheral and portal HGF serum levels related with poor prognosis after hepatic resection. Hepatocyte growth factor and c-met receptor can be targets of future HCC postoperative treatment.

Decreased serum levels of hepatocyte growth factor in male adults with high-functioning autism

Background The mechanisms underlying the pathophysiology of autism are currently unknown. Given the role of hepatocyte growth factor (HGF) in brain development, we hypothesized that HGF plays a role in the pathophysiology of autism. In this study, we studied whether serum HGF levels are altered in subjects with high-functioning autism. Methods Using an enzyme-linked immunosorbent assay (ELISA), we measured serum levels of HGF in 17 male adults with high-functioning autism and age-matched 18 male healthy subjects. Results The serum levels (503.5 ± 160.5 pg/mL (mean ± SD)) of HGF in the subjects with high-functioning autism were significantly (Mann–Whitney U = 34.0, p < 0.001) lower than those (817.6 ± 232.4 pg/mL (mean ± SD)) of control subjects. However, there were no correlations between serum HGF levels and clinical variables in the patients. Conclusions This study suggests that reduced HGF levels may play a role in the pathophysiology of high-functioning autism.

Hepatocyte growth factor as a second trimester marker for preeclampsia

PREECLAMPSIA CHRISTOPHER ROBINSON, DONNA JOHNSON, Medical University of South Carolina, Obstetrics and Gynecology, Charleston, South Carolina OBJECTIVE: Hepatocyte growth factor (HGF), a hormone produced by placental trophoblasts, is recognized as an important cytokine involved in placental development. HGF knockout animal models display a phenotype of placental insufficiency. HGF has been shown to be reduced in human serum at the onset of clinical preeclampsia. This study was undertaken to determine if serum HGF levels are altered in the second trimester prior to the onset of clinical preeclampsia. STUDY DESIGN: Following IRB approval, serum drawn from 15-20 weeks gestation was obtained from 70 C storage for healthy controls and patients who developed severe preeclampsia as defined by ACOG criteria. Patients were matched for age and gestational age at blood draw. HGF concentration was quantitated by ELISA and reported as mean G standard deviation in pg/mL. Statistical analysis was performed with independent sample T test, chi square, and Fisher’s exact test where appropriate. RESULTS: 44 controls and 37 patients with severe preeclampsia were enrolled. Age (p=0.48) and gestational age at blood draw (p=0.27) were both similar between groups. However, HGF was not different in second trimester serum in patients who later developed severe preeclampsia compared to healthy normotensive patients (1330 G 690 vs. 1130 G 580, p=0.27). CONCLUSION: Although HGF has been reported to be altered in serum of patients who have clinical manifestations of preeclampsia, it does not appear to be altered earlier as measured in the second trimester. HGF alone is not a candidate marker for early detection of preeclampsia as measured in the second trimester.

Evaluation of interleukin-6, interleukin-10 and human hepatocyte growth factor as tumor markers for hepatocellular carcinoma

Aim Serum α-fetoprotein (AFP) is the most important tumor marker for hepatocellular carcinoma (HCC). Previous reports indicated that HCC was also associated with increased levels of interleukin (IL)-6, IL-10 and hepatocyte growth factor (HGF). This study investigated the role of these cytokines as tumor markers for HCC. Method A total of 128 adults were prospectively enrolled and categorized into four groups: normal subjects ( n = 29), chronic hepatitis B or C ( n = 50), non-HCC tumors ( n = 23) and HCC ( n = 26). Serum AFP, IL-6, IL-10 and HGF levels were determined in all subjects. Results The expression of IL-6 or IL-10 (≥3 pg/ml), or high level of HGF (>1000 pg/ml) or AFP (>20 ng/ml) was observed in only 0–3% of normal subjects. Patients with HCC more frequently had higher IL-6 and IL-10 levels ( p < 0.05), whereas HGF levels in HCC patients were not significantly elevated compared to patients with chronic hepatitis or non-HCC tumors. Among patients with low (<20 ng/ml) AFP level, IL-6 or IL-10 expression was significantly associated with the existence of HCC ( p < 0.05). Patients with large (>5 cm) HCC more often had increased IL-6, IL-10 or AFP levels ( p values all <0.05). Conclusions Serum levels of IL-6 and IL-10 are frequently elevated in patients with HCC but not in benign liver disease or non-HCC tumors. IL-6 and IL-10 may help identify a subset of HCC patients with low AFP level, and may serve as complementary tumor markers in these patients.

Low molecular weight heparin prevents hepatic fibrogenesis caused by carbon tetrachloride in the rat

In this study, we investigated the effect of dalteparin sodium, a low molecular weight (LMW)-heparin, on hepatic fibrogenesis caused by chronic carbon tetrachloride (CCl4) administration in the rat. Female Wistar rats were given a single, or repeated intraperitoneal injections of CCl4 (1ml/kg, twice per week) and dalteparin (50IU/kg, daily) for 7 weeks. Dalteparin did not prevent acute CCl4-induced hepatic necrosis and elevation in serum aminotransferases levels; however, proliferating cell nuclear antigen (PCNA)-positive hepatocytes were dramatically increased 24h after simultaneous administration of CCl4 and dalteparin. Interestingly, serum hepatocyte growth factor (HGF) levels 12h after injection of CCl4 were almost doubled when dalteparin was given simultaneously. Hepatic fibrosis following 7-week CCl4 treatment was markedly ameliorated by daily co-administration of dalteparin. Indeed, dalteparin largely inhibited CCl4-induction of smooth muscle alpha-actin expression, alpha1(I)procollagen and transforming growth factor (TGF)-beta1 mRNA levels in the liver. Further, dalteparin blunted platelet-derived growth factor (PDGF)-induced increases in 5-bromo-2'deoxyuridine (BrdU) uptake in 3-day cultured hepatic stellate cells (HSCs) in a dose-dependent manner. Dalteparin enhances hepatic regeneration and minimizes hepatic fibrogenesis caused by chronic CCl4 treatment. The mechanism underlying these effects most likely involves both up-regulation of HGF and inhibition of HSC proliferation.

The significance of serum hepatocyte growth factor levels in planning follow-up of postoperative jaundice-free patients with biliary atresia

Purpose The aim of this study was to clarify the significance of serum hepatocyte growth factor (HGF), interleukin (IL)-6, and IL-1 receptor antagonist (ra) levels in the evaluation of disease status in jaundice-free survivors with biliary atresia after Kasai operation. Patients and Methods Serum concentrations of HGF, IL-6, and IL-ra were measured in 31 long-term jaundice-free patients with biliary atresia after Kasai operation and 29 controls. Patients were divided into 4 groups: group A (n = 8), normal liver function; group B (n = 9), mild liver dysfunction without portal hypertension; group C (n = 9), moderate liver dysfunction with controllable portal hypertension; and group D (n = 5), receiving liver transplantation. Results Serum IL-6 levels were significantly higher in patients than in controls. There was no difference in serum IL-6 levels among groups B, C, and D. Serum IL-1ra levels were elevated according to liver dysfunction. Serum HGF levels in group D were significantly higher than in controls and the other groups. Serum hyarulonic acid levels were positively correlated with serum levels of IL-1ra and HGF. Conclusions Elevation of serum IL-1ra and HGF levels correlated with the progression of liver fibrosis and dysfunction. In particular, serum HGF levels could be used as a predictor for requiring liver transplantation.

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy

Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.

Combined Measurement of Hepatocyte Growth Factor and Carcinoembryonic Antigen as a Prognostic Marker for Patients with Dukes A and B Colorectal Cancer: Results of a Five-Year Study

There is no marker capable of differentiating patients with Dukes A and B colorectal cancer with aggressive diseases from those with indolent diseases. We evaluated the results of five years of actuarial survival data to determine whether serial monitoring of serum hepatocyte growth factor could provide prognostic information on these patients. Blood samples of 147 colorectal cancer patients were obtained and the serum concentration of hepatocyte growth factor was measured. Elevated serum hepatocyte growth factor levels were associated with stage progression. Although the overall positive rate of hepatocyte growth factor in the patients was the same as that of the carcinoembryonic antigen, the positive rate of hepatocyte growth factor in the Dukes A patients was two times higher than that of the carcinoembryonic antigen, and nearly 40 percent of the carcinoembryonic antigen-negative patients had a positive serum hepatocyte growth factor in the Dukes A and B classification. In this subgroup, patients with positive serum hepatocyte growth factor or carcinoembryonic antigen levels had a poorer prognosis, whereas positive serum hepatocyte growth factor level after surgery could predict disease recurrence. A combination of serum hepatocyte growth factor and carcinoembryonic antigen tests might be useful for selecting patients with aggressive diseases in Dukes A and B classification.

Serum levels of hepatocyte growth factor (HGF) and epidermal growth factor (EGF) as prognostic factors in malignant pleural mesothelioma (MPM)

10080 Background: MPM is an uncommon but extremely aggressive tumor of the serosal surfaces, which has been closely linked to asbestos exposure. Several in-vitro studies have demonstrated that HGF enhances MPM cell proliferation, migration, and invasiveness and the presence of EGF is closely related to the process of cell differentiation and the synthesis of glycosaminoglycans in MPM cells. Few studies have measured the blood levels of these growth factors in tumor patients and assessed their correlation with clinical outcome. This pilot study was designed to investigate the potential value of serum EGF and HGF measurements for the diagnosis and the prediction of survival in MPM patients. Methods: Baseline serum EGF and HGF levels (ng/ml) were determined using an ELISA method in 81 newly diagnosed MPM patients (mean age 67.5±11.0 years) and 48 patients with benign respiratory diseases (BRD; mean age 64.3±13.5 years). Results: HGF and EGF median concentrations in MPM (1.6 ng/ml and 0.5 ng/ml, respectively) were not statistically different from concentrations in BRD (1.2 ng/ml and 0.4 ng/ml). Median follow-up for MPM patients was 27 months, while overall median survival was 11.8 months. At univariate analysis, only high EGF serum levels were associated with an unfavorable survival outcome. Using a cut-off point for EGF of 0.5 ng/ml (corresponding to the median of marker concentration in MPM), the survival rate in patients with higher serum EGF was significantly worse than that in patients with lower levels (median 10.7 vs. 13.0 months, p=0.01). Multivariate analysis, after adjusting for age, sex, histology and platelet count, confirmed the independent predictive value of serum EGF concentration as a negative prognostic factor (p=0.01). Conclusions: High pre-treatment levels of serum EGF are associated with an adverse prognostic impact on survival in MPM patients. No significant financial relationships to disclose.

Clinical significance of circulating hepatocyte growth factor, a new risk marker of carotid atherosclerosis in patients with Type 2 diabetes

Recent studies have provided increasing evidence that hepatocyte growth factor (HGF) has a pathophysiological role in the development of diabetic complications. We set out to determine the relationship between serum HGF and risk factors for macroangiopathy including carotid atherosclerosis. Carotid atherosclerosis is an established and important risk factor for both cerebral and coronary artery diseases. We studied 89 patients (48 males, 41 females, mean age 62.5 +/- 10.3 years) with Type 2 diabetes (DM). Serum levels of HGF correlated positively with both intimal-media thickness (IMT) (r = 0.24, P = 0.0248) and plaque score (r = 0.27, P = 0.0126). In multiple regression analysis, serum HGF was associated independently with IMT (standardized beta = 0.28, P = 0.0499). We also found that both IMT and plaque score were higher in patients with ischaemic heart disease (IHD) than in patients without IHD, and that plaque score in patients with lacunar infarcts was higher than in patients without lacunar infarcts. Serum HGF concentration may be a new marker of atherosclerotic complications in patients with Type 2 DM.