Hepatocyte Growth Factor In Patients Research Articles

The use of elevated circulating hepatocyte growth factor (HGF) level as a potential prognostic biomarker in locally advanced pancreatic cancer.

429 Background: The hepatocyte growth factor (HGF)/c-MET pathway has pleiotropic functions in tumor progression including invasion and cancer cell survival. The potential use of circulating plasma HGF as a prognostic biomarker is not known. Methods: This was an analysis of plasma HGF in patients enrolled in a single arm phase II study (NCT01821729) of patients with previously untreated locally advanced pancreatic ductal adenocarcinoma (PDAC) treated with FOLFIRINOX and losartan followed by chemoradiotherapy before resection was attempted (Murphy JE et al., 2019). Eligible patients from the trial included those who had undergone baseline research labs including HGF. Circulating HGF was measured in the plasma on day 1 of treatment using ELISA, and the median value was used to define high vs low levels for the purpose of analysis. The association of elevated HGF with overall survival (OS) was analyzed by univariable and multivariable Cox regression, adjusting for tumor size (≤ versus > 40 mm) and serum CA19-9 (≤ versus > 37 U/mL). Results: There were 46 eligible patients with a median follow up of 31 months. The median age was 63 (range 42-78) and 52% were female (24/46). Median tumor size was 41.4 mm (range 18–68 mm). There were 41/46 patients (89.1%) with elevated baseline CA19-9. Median baseline HGF was 1,250.55 pg/mL (range 650.9–6,459.1). Median OS was 38.4 months for patients with baseline HGF at or below the median, and 19.3 months for those with elevated HGF. On univariate analysis, elevated HGF was associated with poorer OS (HR 2.28, 95% CI 1.06–4.87, p = 0.03). On multivariate analysis, after controlling for tumor size and baseline CA19-9, elevated plasma HGF remained significantly associated with poorer OS (HR 2.58, 95% CI 1.16–5.70, p = 0.02). Conclusions: In conclusion, elevated baseline circulating plasma HGF is an independent biomarker of poorer OS in patients with locally advanced PDAC treated with neoadjuvant therapy. Further randomized studies are needed to define the negative predictive biomarker value for high plasma HGF and identify the optimal HGF range as well as determine applicability to other stages of disease. These results support the continued investigation of plasma HGF in ongoing clinical trials with PDAC patients.

P-365 Association between baseline serum levels of miRNA-143 and hepatocyte growth factor in patients with RAS wild type metastatic colorectal cancer treated with first-line anti-EGFR therapy

Recently the prognostic role of microRNA-143 has been proven by ours and several studies and one meta-analysis. Additionally, high serum levels of hepatocyte growth factor (HGF) were found to be associated with resistance to anti-EGFR antibodies in KRAS wild-type metastatic colorectal cancer (mCRC). The possible interplay between miRNA-143 and HGF as predictive factors in RAS wild mCRC is unknown.

Phase Ⅰ/Ⅱ Clinical Trial for Regeneration of the Vocal Fold with Hepatocyte Growth Factor in Patients with Vocal Fold Scar and Sulcus

Phase Ⅰ/Ⅱ Clinical Trial for Regeneration of the Vocal Fold with Hepatocyte Growth Factor in Patients with Vocal Fold Scar and Sulcus

Evaluation of liver function by means of serum cytokeratin 18 and hepatocyte growth factor levels in patients with obstructive jaundice

Objective: To evaluate the serum levels of cytokeratin 18 (CK18) and hepatocyte growth factor (HGF) in obstructive jaundice patients before and after treatment and thereby to detect the possible role of CK18 and HGF in patients with obstructive jaundice.Patients and methods: Forty patients who had obstructive jaundice and 40 healthy control subjects were included in the study. Patients were treated using percutaneous, endoscopic or surgical approaches. Blood samples were obtained at the day before and 7 days after the intervention for obstructive jaundice. Serum HGF and CK18 concentrations were determined by ELISA method.Results: There were statistically significant decreases in HGF, CK18, total bilirubin and direct bilirubin serum levels, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase activities and white blood cell count when compared with pre-treatment levels.Conclusion: Evaluating pre- and post-treatment serum HGF and CK18 levels suggested that there was an apoptosis in obstructive jaundice patients and this apoptosis decreased after the decompression of the biliary tract. We also demonstrated that HGF levels were altered at biliary obstruction compared to healthy controls and the levels of this biomarker also decreased after decompression of biliary obstruction. We concluded that these biomarkers can be used as predictors of liver injury in biliary obstruction.

Differential expression of hepatocyte growth factor in patients with systemic sclerosis-associated pulmonary arterial hypertension

Introduction Non-invasive biomarkers are needed to identify pulmonary arterial hypertension (PAH) in systemic sclerosis (SSc) patients who may benefit from early intervention. We sought to identify novel cytokines that differentiate patients with incident SSc-PAH from those at high risk for PAH. Methods The Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma (PHAROS) Registry is a multicenter registry of SSc patients at high risk for PAH (at-risk) or with incident right-heart catheterization-confirmed PAH (definite PAH). Serum from 10 at-risk and 9 definite PAH patients were profiled with Bio-PlexTM bead arrays for 48 cytokines and chemokines. We also evaluated the longitudinal change in cytokine profiles from 3 at-risk patients who subsequently developed definite PAH. Results Clinical features of at-risk versus definite PAH patients were not significantly different except for right-ventricular systolic pressure on echocardiogram (34 ± 7 vs. 45 ± 8 mmHg, p = 0.006), left atrial diameter (2.9 ± 0.5 vs. 3.7 ± 0.4 cm, p = 0.02), 6-minute walk distance (508 ± 115 vs. 393 ± 70 m, p = 0.02), mean pulmonary artery pressure (18 ± 4 vs. 32 ± 6 mmHg, p = 0.01), and pulmonary vascular resistance (111 ± 48 vs. 272 ± 109 dyn/s/cm5, p = 0.009). Serum cytokine profiling identified hepatocyte growth factor (HGF) as the only cytokine significantly different between the at-risk and definite PAH groups (225.8 ± 55.0 vs. 361.6 ± 164.5 pg/mL, q<0.1%). Profiling of longitudinal samples of at-risk to definite PAH patients did not identify any significant changes in HGF or other cytokines over time. Conclusions Definite PAH patients expressed higher levels of HGF than at-risk patients. Further studies are needed to clarify the utility of HGF as a predictive biomarker for SSc-PAH.

Expression of hepatocyte growth factor and its receptor c -Met in colorectal cancer and their significances

Objective To investigate the expression of hepatocyte growth factor (HGF) and its receptor c-Met in colorectal cancer tissues and their clinical significances. Methods 100 patients with colorectal cancer who accepted treatment from March 2012 to 2015 February were collected. The immunohistochemical method was used to test the expression of HGF and c -Met in tumor tissues. The correlation of clinicopathological parameters and lymphatic microvessel density (LMVD) was analyzed. Results The positive expression rates of HGF in patients with or without lymph node metastasis were 100.0 % (35/35) and 41.5 % (27/65), the difference had statistical significance (χ2 = 6.99, P < 0.05). The positive expression rates of c-Met were 94.3 % (33/35) and 47.7 % (31/65), the difference was statistically significant (χ2 = 7.75, P < 0.05). The positive expression rates of HGF in patients with TNM stage Ⅰ+Ⅱ and Ⅲ+Ⅳ were 48.6 % (17/35) and 69.2 % (45/65), the difference had statistical significance (χ2= 5.94, P < 0.05). The positive expression rates of c-Met were 51.4 % (18/35) and 70.8 % (46/65), the difference was statistically significant (χ2 = 6.08, P < 0.05). The LMVD of patients with different lymph node metastasis,tumor stage,HGF and its receptor c-Met expression were statistically different (t values were 10.19, 10.08, 7.50, 5.07, all P < 0.05). Conclusion HGF and its receptor c-Met is closely related to the development of colorectal cancer. They can help the diagnosis, and be used as new targets in the treatment of colorectal cancer. Key words: Colorectal neoplasms; Hepatocyte growth factor; C-Met

Abstract A27: Analyses of the level of liver borne growth factors, IGF-1 and HGF in metastatic and non-metastatic uveal melanoma patient serum: Correlation with outcome

Abstract Background: Uveal melanoma arises from melanocytes in the uveal tract of the eye and is biologically different from cutaneous melanoma due to different genetic alterations and a propensity to metastasize to the liver. We hypothesize that growth factors synthesized in liver can play a significant role in this preferential homing of uveal melanoma metastasis. It is critical to explore the factors that can contribute to liver metastasis and identify targets. Further exploring the means to blocking them in a timely fashion is of high therapeutic value. IGF-1 (insulin like growth factor -1) and HGF (hepatocyte growth factor) are two major growth factors secreted from liver. The corresponding receptors, c-Met and IGF-1R have been detected in uveal melanoma tumors and also high protein expression was shown to be associated with poor survival. Therefore we initiated a study to determine the level of serum IGF-1 and HGF at sequential time points for primary and metastatic uveal melanoma patients, with the aim to test for correlation with clinical outcomes. Methods: Commercially available ELISA kits (Quantikine ELISA kits from R&amp;D) were used to measure the levels of IGF-1 and HGF in the serum of 12 uveal melanoma patients at different time points of their treatment and follow up at MD Anderson Cancer Center as a discovery cohort. Blood was drawn at first visit and then at surgery (if relevant) and post-surgery check up, followed by every six month visits or sooner. Serum was isolated from each blood draw and stored at -80 degrees until analysis. At the time of analysis, the serum samples were thawed overnight and used directly in ELISA for HGF and for the IGF-1 with pre-treatment to release the active IGF-1. Patients with detection of metastasis were followed after the diagnosis of metastasis. We compared six patients with metastasis with six others that were free of metastasis at last contact. The serum levels of IGF-1 and HGF were tabulated for each patient and each blood draw, and analyses initiated to test if the levels of IGF-1 or HGF in patients vary at baseline or over time relative to the outcome. Results: We observed a significantly higher level of serum HGF in all 12 patients in this study as compared to the reported normal levels in healthy individuals. Preliminary analyses do not point to an obvious pattern of IGF-1 or HGF serum levels or changes in levels that vary between the metastatic and non-metastatic patients over time. A drawback of the study is the small sample size. Another concern is the dynamic nature of the protein expression, which are being currently investigated. These studies would support additional analysis, and possibly more sensitive and selected marker tests. Supported by the MD Anderson Cancer Center SPORE in Melanoma P50 CA093459, the MD Anderson's Cancer Center Support Grant P30- CA016672, the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, and funds from the Polo on the Prairie event. Citation Format: Chandrani Chattopadhyay, Junna Oba, Bita Esmaeli, Julie A. Ellerhorst, Elizabeth A. Grimm. Analyses of the level of liver borne growth factors, IGF-1 and HGF in metastatic and non-metastatic uveal melanoma patient serum: Correlation with outcome. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A27.

Proinflammatory Cytokines (IL-1α, IL-6) and Hepatocyte Growth Factor in Patients with Alcoholic Liver Cirrhosis.

Background. The aim of the study was to assess the activity of interleukin-1α, interleukin-6, and hepatocyte growth factor protein (HGF) in serum of patients with alcoholic liver cirrhosis. Materials and Methods. Sixty patients with alcoholic liver cirrhosis treated in various hospitals were randomly enrolled. The stage of cirrhosis was assessed according to the Child-Turcotte-Pugh scoring system. The control group consisted of ten healthy persons without liver disease, who did not drink alcohol. Additionally, the group of alcoholics without liver cirrhosis was included in the study. The activity of interleukin-1α, interleukin-6, and HGF in blood plasma of patients and controls was measured using the sandwich enzyme immunoassay technique with commercially available quantitative ELISA test kits. Results. Higher concentrations of HGF protein were demonstrated in patients with Child class B and Child class C liver cirrhosis, compared to controls and alcoholics without liver cirrhosis. Moreover, significantly higher concentrations of HGF protein were found in patients with Child class C liver cirrhosis compared to patients with Child class A liver cirrhosis (p < 0.05). The concentrations of interleukin-1α in patients with Child class B and Child class C liver cirrhosis were significantly higher in comparison with controls. Significantly higher concentrations of interleukin-6 were demonstrated in Child class C, compared to Child class A.

Clinical significance of joint detection of serum VEGF, SIL-2R and HGF in patients with primary hepatocellular carcinoma before and after percutaneous microwave coagulation therapy.

To investigate the changes of serum vascular endothelial growth factor (VEGF), soluble interleukin-2 receptor (SIL-2R) and hepatocyte growth factor (HGF) contents in patients with primary hepatocellular carcinoma (HCC) before and after percutaneous microwave coagulation therapy (PMCT) and determine their clinical significance. Fasting venous blood (3 mL) from 81 patients with primary HCC diagnosed by pathology was collected in the mornings 1 day before PMCT, and 1 day, 7 days and 1 month after PMCT, and then the serum was separated and stored in -70°. The contents of VEGF, SIL-2R and HGF were detected by enzyme linked immunosorbent assay (ELISA). The serum VEGF, SIL-2R and HGF contents in 81 patients with primary HCC had obviously dynamic changes before and after PMCT. By comparison to 1 day after PMCT with pre-operation, there was no statistical significance regarding VEGF and SIL-2R contents (P>0.05), but HGF content showed significant difference (P<0.01). Compared with pre-operation, VEGF, SIL-2R and HGF contents 7 days and 1 month after PMCT all manifested significant differences (P<0.01). By comparison to 7 days with 1 month after PMCT, there was no statistical significance regarding the VEGF content (P>0.05), whereas SIL-2R and HGF contents showed significant change (P<0.01). The contents of serum VEGF, SIL-2R and HGF have obviously dynamic changes in primary HCC before and after PMCT, and their joint detection is expected to be an effective hematologic evaluation index of PMCT for primary HCC.

Prognostic Significance of Circulating Levels of Hepatocyte Growth Factor in Patients with Chagas’ Disease and Idiopathic Dilated Cardiomyopathy

Objectives: Hepatocyte growth factor (HGF) plays an important role in the improvement in cardiac function and remodeling in a variety of cardiovascular diseases. It is also a strong predictor of mortality in some heart failure (HF) patients. However, its prognostic value in patients with Chagas’ disease (CD) or idiopathic dilated cardiomyopathy (DCM) remains to be investigated. Methods and Results: In this prospective cohort study, HGF concentrations were measured in patients with CD (n = 91), DCM (n = 47), and control subjects (n = 25). While no difference was detected for patients with New York Heart Association class I–II, HGF was significantly increased in advanced HF patients (New York Heart Association class III–IV) in both CD and DCM groups, compared with healthy subjects. There was a strong correlation between HGF and left ventricular ejection fraction in CD patients. However, there was no correlation in patients with DCM. Despite its strong correlation with left ventricular ejection fraction in CD patients, HGF failed to predict mortality and necessity for heart transplant in both CD and DCM patients. Conclusions: Although HGF can be significantly increased in advanced HF patients with CD and DCM, its prognostic value for endpoints is minor. Therefore, the formerly described predictive power for HGF in HF might be restricted to specific etiologies of HF.

High concentration but low biological activity of hepatocyte growth factor in patients with chronic renal failure

Hepatocyte growth factor (HGF) is a renotropic, antifibrotic and regenerative factor with cytoprotective effects that is produced by mesenchymal cells and shows high affinity to components of extra cellular matrix, such as heparan sulphate proteoglycan (HS-PG), in healthy. Patients with chronic renal failure (CRF) suffer from a chronic inflammatory disorder. In order to assess the underlying mechanisms for development of CRF we aimed to assess the amounts and affinity of HGF in this patient group. Elisa, western blot and surface plasmon resonance (SPR) were used to study HGF in blood samples, as well as in isolated neutrophils, in CRF patients compared to healthy controls. Patients with CRF showed higher HGF levels in serum (P P < 0.0001), compared to healthy controls. Addition of protease inhibitors decreased the difference between patients with CRF compared to healthy individuals. HGF with potent regenerative function during injury lacks affinity to HSPG in patients with CRF that may depend on production of proteases from activated immune cells. This information might be used to highlight underlying mechanisms for chronicity and leading to new strategies for treatment of chronic injuries.

Hepatocyte growth factor in patients with coronary artery disease and its relation to periodontal condition

Hepatocyte growth factor (HGF) is an angiogenic, cardioprotective factor important for tissue and vascular repair. High levels of HGF are associated with chronic inflammatory diseases, such as coronary artery disease (CAD) and periodontitis, and are suggested as a marker of the ongoing atherosclerotic event in patients with CAD. Periodontal disease is more prevalent among patients with CAD than among healthy people. Recent studies indicate a reduced biological activity of HGF in different chronic inflammatory conditions. Biologically active HGF has high affinity to heparan sulfate proteoglycan (HSPG) on cell-membrane and extracellular matrix. The aim of the study was to investigate the serum concentration and the biological activity of HGF with ELISA and surface plasmon resonance (SPR), respectively, before and at various time points after percutaneous coronary intervention (PCI) in patients with CAD, and to examine the relationship with periodontal condition. The periodontal status of the CAD patients was examined, and the presence of P. gingivalis in periodontal pockets was analyzed with PCR. The HGF concentration was significantly higher, at all time-points, in patients with CAD compared to the age-matched controls (P< 0.001), but was independent of periodontal status. The HGF concentration and the affinity to HSPG adversely fluctuated over time, and the biological activity increased one month after intervention in patients without periodontitis. We conclude that elevated concentration of HGF but with reduced biological activity might indicate a chronic inflammatory profile in patients with CAD and periodontitis.

Multiple Myeloma Plasma Cell Expression of Hepatocyte Growth Factor mRNA Isoforms Correlates with Overall Survival In Myeloma Patients

AbstractAbstract 4983 Background:Full length Hepatocyte growth Factor (HGF) (consisting of four “kringle”-domains) is known to be produced by multiple myeloma plasma cells (MM PC) in vivo and HGF is among the 70 most up regulated genes in MM. Elevated serum levels of HGF are known to be an adverse prognostic factor and recently, MM PC expression of the HGF receptor cMET has been shown to be an adverse prognostic factor. Functionally, HGF inhibits osteoblastogenesis in vitro and promotes migration of MM PC. So far, studies on HGF and its impact in MM have focused on measuring full-length or all isoforms of HGF expression. However, naturally occurring shorter isoforms of HGF (known as NK1 and NK2) are known to work as partial inhibitors of full-length HGF (Otsuka et al, Mol and Cell Biol, 2000). We examined the HGF isoforms and cMET expression at the mRNA level in isolated MM PC of >150 newly diagnosed patients with MM, 18 MGUS patients and 8 healthy volunteers (HV) and associated it to overall survival (OS) and degree of osteolytic bone disease (OBD). Methods:Aberrant MM PCs (CD38++/CD19-/CD45-/i/CD56-/+/++) were sorted directly into PCR tubes by fluorescence activated cell sorting (FACS) using a FACS Aria (BDIS). In all cases a PC-purity above 98% was obtained. A cDNA archive was generated by global reverse transcription. By using a polyadenylating step 5x-oligo(dT)-transcript-poly(A)-3xcDNA were generated and finally amplified by PCR using a sequence independent X-(dT)24 primer. The conditions of the reverse transcriptase reaction is designed to limit the size of the first strand cDNA to 300–700 bases, which leads to a more uniform and unbiased amplification. Isoform specific primers were designed using the Primer Express program and experimentally tested. The HGF version covered full-length HGF (transcript variant 1 and 3), HGF2 covered the 2 kringle domain versions (transcript variant 2 and 4) and HGF5 covered the 1 kringle domain version (transcript variant 5). cMET only exists in one isoform. Quantitative PCR was performed using β-actin as internal reference gene, using the δCt method. Determination of positivity or negativity was made from a cut-off-value at 10E-05. OBD was evaluated by standard radiographic methods. The MM patients were treated with either high-dose melphalan with ASCT or melphalan-prednisone according to age recommendations. Results: At least one of the HGF isoforms were found to be expressed in PCxs from 43% of MM patients compared to 32% of MGUS patients, and 0% of HV. Full length HGF was expressed in 17 %, HGF2 in 29%, and HGF5 in 26% of the MM patients. Expression of any HGF variant was associated to an adverse OS (p=0.04) (Fig. 1). The quantitative expression of the transcript variant 5 associated negatively to OS (p=0.02), while expression of the other specific isoforms showed no association to OS. Thus, somehow surprisingly, MM PC expression of the shorter isoform of HGF (HGF5) was more predictive of poor prognosis.A tendency towards elevated expression of full-length HGF in patients with no OBD compared to limited or advanced was observed but did not reach statistically significance (p=0.13). Pre-liminary analysis of cMET expression data showed no correlation between MM PC cMet expression and degree of OBD. Further data on cMet will be presented at the meeting. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Hepatocyte growth factor in cerebrospinal fluid is associated with mortality and recurrence of glioblastoma, and could be of prognostic value

Malignant gliomas--glioblastoma multiforme and anaplastic astrocytoma--are among the most fatal forms of cancer in humans. It has been suggested that hepatocyte growth factor (HGF) is a reliable predictor of glioma malignancy; amounts of HGF are directly related to cellular proliferation, angiogenesis, low apoptotic rate, and poor prognosis (WHO III and IV). We measured the HGF content of cerebrospinal fluid (CSF) from patients with malignant glioma glioblastoma multiforme (WHO IV; n = 14), anaplastic astrocytoma (WHO III; n = 4), and meningioma (WHO I; n = 9), and from control subjects (n = 25), and found a high concentration of HGF in patients with malignant glioma. However, CSF concentrations from glioblastoma multiforme and anaplastic astrocytoma patients were not statistically significantly different (893 +/- 157 vs. 728 +/- 61, respectively; P > 0.01). A negative correlation between HGF and survival was found at five years of follow-up (R = -0.922, R (2) = 0.850, P < 0.001). Also, the HGF concentration in CSF was a reliable means of explaining the highly variable survival of patients with malignant glioma. CSF concentrations of HGF higher than 500 pg/ml were associated with increased mortality whereas values higher than 850 pg/ml were associated with a brief tumor-free period after surgery (9 +/- 0.6 vs. 6 +/- 0.6 months, respectively, P < 0.001). Our findings support the idea that measurement of HGF in CSF could be a useful tool for monitoring the biological activity of malignant glioma. The findings will ultimately need to be confirmed in a much larger study.

Dynamic Changes of Hepatocyte Growth Factor in Eosinophilic Meningitis Caused by Angiostrongylus cantonensis Infection

Hepatocyte growth factor (HGF) is a member of the angiogenic growth factor family, which exerts a variety of effects on epithelial, endothelial, and neuronal cells by binding to the c-MET receptor tyrosine kinase. It was reported that HGF attenuates cerebral ischemia-induced increase in permeability of the blood-brain barrier (BBB) and decreases in expression of tight junction proteins in cerebral vessels of rats. Studies on the localization of the c-Met/HGF receptor in the rat brain and the interaction with HGF after brain injuries show that HGF plays an important role as a neurotrophic factor in the brain. To assess the role of HGF in patients with eosinophilic meningitis, a retrospective, cohort study was conducted to measure the dynamic changes of HGF in the cerebrospinal fluid (CSF) and blood of nine patients with eosinophilic meningitis. The mean HGF(CSF) at presentation, 1 week, 2 weeks, and 3 weeks after admission was 539 pg/mL, 540 pg/mL, 376 pg/mL, and 279 pg/mL, respectively. The mean level of HGF(CSF) at presentation (539 +/- 242 pg/mL) and 1 week after admission (540 +/- 213 pg/mL) was significantly higher than in controls (162 +/- 207 pg/mL)(P = 0.02 and P = 0.01, respectively). The CSF/blood ratio of HGF at presentation (0.61) was higher when compared with physiologic situations in uninfected individuals (0.51). The levels of HGF in CSF were not correlated with the amount of CSF cells or proteins. All patients recovered without neurologic sequelae. These results indicate that high concentrations of HGF in the CSF occur in eosinophilic meningitis, and may have a role in protecting against endothelial injury and reducing BBB dysfunction.

The role of serum concentration of hepatocyte growth factor in clinical monitoring of oral squamous cell carcinoma

Background and Objectives: Generally, squamous cell carcinoma has a poor prognosis due to its tendency towards local invasion and subsequent metastasis, which is mediated by multiple factors and angiogenesis. Hepatocyte growth factor (HGF) is a potent mitogen for epithelial cells that regulates cell proliferation, migration, survival tumour angiogenesis and invasiveness. The aim of presented study was to determine serum concentration of HGF in patients with oral squamous cell carcinoma before and after initial treatment.

454 The Clinical Value of Hepatocyte Growth Factor in Patients with Peri-Ampullary Cancer Before and After Pancreaticoduodenectomy

454 The Clinical Value of Hepatocyte Growth Factor in Patients with Peri-Ampullary Cancer Before and After Pancreaticoduodenectomy

Evaluation of hepatocyte growth factor in patients with biliary atresia

Background Hepatocyte growth factor (HGF) is a potent mitogen for mature hepatocytes in primary culture and seems to be a trigger factor for liver regeneration and proliferation after liver injury. The aim of this study was to evaluate the expression of HGF in patients with biliary atresia (BA). Methods Plasma levels of HGF were determined using an enzyme-linked immunosorbent assay from 19 patients with BA, 10 at the time of Kasai procedure (KP) and 9 at liver transplantation (LT), and 10 patients with nonicteric choledochal cyst served as control. Hepatic HGF level was quantitatively estimated using enzyme-linked immunosorbent assay and Western blotting. Hepatocyte growth factor messenger RNA (mRNA) expression of liver was measured with quantitative reverse transcriptase polymerase chain reaction. Immunohistochemical study of liver sections was evaluated by HGF staining. Results Plasma HGF levels in LT patients were significantly higher than in KP patients (2977.30 ± 1251.42 vs 960.17 ± 559.82 pg/mL, P < .01). Western blots showed increased hepatic HGF levels in LT group than in KP group (2.02 ± 0.86 vs 1.44 ± 0.72 pg/ μg total protein, P < .05). However, there were no differences in HGF mRNA expression. Immunohistochemical study showed significantly increased HGF staining in hepatocytes of LT livers than of KP livers. Conclusions Elevation of plasma and liver HGF levels could be related to the progression of liver cirrhosis in patients with BA. Hepatocyte growth factor might have a protective role, probably through the induction of hepatocyte proliferation, during the development of BA-associated liver cirrhosis.

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.

Changes of clotting factors (7, 9 and 10) and hepatocyte growth factor in patients with thrombotic microangiopathy after bone marrow transplantation

To investigate risk factors for thrombotic microangiopathy (TMA) after bone marrow transplantation (BMT), the levels of three clotting factors (7, 9 and 10) and hepatocyte growth factor (HGF) were measured. Among 46 consecutive patients who underwent BMT, six developed TMA and 40 did not. The levels of the clotting factors and HGF did not differ significantly between the six patients with TMA and the 40 patients without it. In two patients who developed TMA during the earlyperiod after BMT, however, the levels of the three clotting factors were significantly decreased even before BMT, along with a significant increase of HGF. These findings suggest that patients with severe hepatic dysfunction before BMT, especially those with impaired protein synthesis, had an increased risk of developing TMA soon after BMT. It was also suggested that measurement of clotting factors (7, 9 and 10) and HGF may be useful to predict the occurrence of TMA in the early period after BMT.