Hepatocyte growth factor profile with breast cancer.

Background: The multifunctional hepatocyte growth factor (HGF) is the ligand of c-Met receptor; it plays important role in mammary differentiation. HGF-Met signaling is a critical downstream function of c-Src-Stat3 pathway in mammalian tumorigenesis. Aim: Evaluation of tissue c-Met receptor hepatocyte growth factor receptor (HGFR) and serum level of HGF in female breast ductal carcinoma. Materials and Methods: Sixty-eight premenopausal females were divided as 30 control females subdivided into: [Group 1] 15 healthy volunteer females and [Group 2] five with fibrocystic disease and 10 having fibroadenoma of the breast and patients group [Group 3] consisted of 38 female patients with breast ductal carcinoma. Thorough clinical examination, preoperative fine needle aspiration cytology, estimation of fasting serum glucose, urea, creatinine, and uric acid levels, alanine aminotransferase activities, C-reactive protein, HGF level, before surgery and histopathological examination of the breast masses, and immunohistochemical detection of HGFR were done. Results and Conclusions: Significant increase in serum HGF levels were found in patients with breast cancer as compared with controls. Significant increase was also seen in patients with breast cancer with and without lymph node metastasis when each subgroup was compared with controls. Serum level of HGF is an independent prognostic indicator of breast cancer. Fibrocystic disease of the breast showed weak HGFR expression, while in normal tissue, HGFR was scanty; meanwhile, breast invasive ductal carcinoma showed homogenous strong reaction to HGFR. HGF is only one of a number of key factors involved in breast cancer and preoperative high serum HGF levels and malignancy occur usually together.

Lupus nephropathy: clinical, immunohistochemistry and quantitative morphometric analysis studies

Lupus nephritis includes a wide range of parenchymal injuries and severity. Better predictors to outcome are needed for patients newly diagnosed with lupus nephritis, so that an appropriate management strategy may be selected. This study aimed to determine whether the ratio of hepatocyte growth factor [HGF] to transforming growth factor beta 1 [TGF beta1] in lupus nephritis could be a prognostic factor for response to therapy with cyclophosphamide and steroids at six months. Also, to determine whether a simple automated system for objective scoring of biopsies of lupus nephritis could be a prognostic factor for response to therapy with cyclophosphamide and steroids at 6 months. Consequently, renal biopsy findings and clinical parameters of thirty parasites-free patients with new onset lupus nephritis were recorded. Histopathologic, clinical, immune-histochemical and morphometric data at baseline served to define the predictive value for outcome after 6 months of therapy. The results showed a significant positive relationship between response to therapy and HGF IS [P= 0.007], HGF ES [P= 0.026], HGF IS/ TGFbeta1 IS ratio [P= 0.022] and HGF ES/ TGFbeta1 ES ratio [P= 0.001]. A significant inverse relationship was proved between response to therapy and TGFbeta1 IS [P= 0.025] as well as TGFbeta1 ES [P= 0.017]. Also, a significant inverse relationship was present between response to therapy and nuclear index, tubular index and matrix index [P = 0.03, 0.03 and 0.029 respectively]

Does Immunohistochenaical expression of hepatocvte growth factor [HGF] and Telomerase correlate with Ki67 proliferative index in cases of undifferentiated pleomorphic sarcoma [malignant fibrous histiocytoma]?

The latest World Health Organization classification of soft tissue tumors and bone considered MFH a synonym for pleomorphic undifferentiated sarcoma. Hepatocyte growth factor [HGF]/scatter factor [SF] is a cytokine, mainly synthesized by cells of mesenchymal origin acting predominantly on epithelial cells. It has been shown that HGF has proliferative, mitogenic, motogenic, morphogenic and angiogenic activities in various epithelial tissues. Because HGF is ubiquitously expressed in mesenchymal tissues and released to th'e extracellular compartment, paracrine and br autocrine signaling would be a possible mechanism of tumorigenesis in mesenchymal tumors that express the HGF receptor. Telomerase, a highly conserved enzyme, is a specialized cellular reverse transcriptase catalyzing the synthesis and extension of telomeric DNA with its own RNA template. Telomerase compensates for telomere loss due to the end replication problem. Activation of telomerase and stabilization of telomeres are consistent with the hypothesis that telomere maintenance is essential for attainment of immortality in cancer cells. The present study aimed at evaluating and correlating the immunohistochemical expression of HGF, hTERT with ki67 proliferative index in undifferentiated pleomorphic sarcoma [UPS] or malignant fibrous histiocytoma, and investigating their interrelation with some clinicopathological parameters such as age, sex, tumor size, site, and metastases. The present study included 20 cases of undifferentiated pleomorphic sarcoma [UPS] [or storiform-pleomorphic MFH]. They were subjected to immunohistochemical stain using; HGF, hTERT, and Ki67. Positive immunohistochemical expression of HGF was detected in 18 out of 20 studied specimens [90%]. Four specimens [20%] showed 1+ positivity, 5 specimens [25%] showed 2+ positivity and, 9 specimens [45%] showed 3+ positivity. Positive immunohistochemical expression of hTERT was detected in 17 out of 20 studied specimens [85%]. Three specimens [15%] showed 1+positivity, 6 specimens [30%] showed 2+ positivity and, 8 specimens [40%] showed 3+ positivity. Positive immunohistochemica] expression of ki67 was detected in 16 out of 20 studied specimens [80%]. The ki67 proliferative score was as follows: seven specimens [35%] showed 1+ positivity, 4 specimens [20%] showed 2+ positivity and, 5 specimens [25%] showed 3+ positivity. The ki67 proliferative index ranged from 5% up to 90% [mean=40.75%]. The relation between HGF positivity and ki67 proliferative score was statistically significant. [P=0.012]. No statistical significant relation was detected between HGF positivity and hTERT positivity [P=0.225]. Another statistical significant relation was detected between high positivity of hTERT and moderate or high proliferative score of ki67. [2+ or 3+positivity] [P=0.012]. Our findings indicate that the HGF plays an important role in promoting cell proliferation of human MFH tissues. lmmunohistochemical expression of hTERT is considered as a Sensitive marker of malignancy, but its value as a prognostic marker needs further evaluation. Also increased expression of HGF and hTERT were significantly associated with increased ki67 proliferative score

Hepatocyte growth factor [HGF], HGF activator [HGFA] and c-met expression in rheumatoid synovial tissues in relation to disease activity

We examined the localization and mRNA expression of HGF, HGFA and c-Met in synovial tissues [ST] in rheumatoid arthritis [RA] in relation to disease activity to characterize its biologic function in that disease. Immunohistochemical staining and RT-PCRfor HGF, HGFA and c-Met were performed on ST specimens from 34 RA-patients and 20 osteoarthritis [OA] controls. Synovial fluid [SF] samples were taken from all RA and OA for measuring HGF with ELISA technique. Immunohistochemical staining of RAST revealed that HGFA and c-Met were strongly expressed infibroblasts, macrophages, endothelial cells and less so on synovial lining cells. But HGF was expressed faintly in macrophages andfibroblasts. While, in OAST, HGFA and c-Met were detected in the same cells as RAST but in a different distribution. HGF was localized in vascular endothelial cells. RT-PCR showed HGF, HGFA and c-Met mRNA in all RAST and all OAST. HGF levels in SF samples were higher in RA patients [range 5.6-39.2 ng/ml and mean 26.3 +/- 1.2 ng/ml] than OA controls [range 4.2-37.5 ng/ml and mean 11.2+2.4 ng/ml]. The differences were statistically significant [p<0.001]. A non-significant correlation was found between HGF-SF levels and disease activity score [DAS] [p>0.5]. HGFA, HGF and c-Met mRNA are expressed in ST in RA and OA. Lack of correlation between HGF-SF levels and DAS indicated that HGF played a regulatory role in the immunopathogenesis of RA

insight on serum levels of hepatocyte growth factor and anti-platelet antibodies in various hepatic insults and their correlation with concomitant thrombocytopenia

Many recent studies have shown that hepatocyte growth factor [HGF] is a potent mitogen in vivo. HGF play an important role in liver regeneration because it is increased after liver injury and higher levels are maintained in serum during liver regeneration. This study was designed to evaluate serum levels of hepatocyte growth factor [HGF] and blood positivity for anti-platelet antibodies [APA] in children with acute and chronic liver diseases [CLD] of varied etiology and to correlate their levels with concomitant thrombocytopenia. The study included 50 patients and 20 control children. There were 20 patients with acute viral hepatitis [AVH] and 30 patients with CLD [10 chronic viral hepatitis, 10 metabolic liver diseases, and 10 autoimmune liver diseases]. Venous blood sample was collected for complete blood count, liver function tests and for ELISA estimation of serum HGF and detection of blood positivity for APA. All liver function tests were significantly [p<0.05] increased in patients compared to control Platelet count was significantly [p<0.05] decreased in patients with chronic viral hepatitis [CVH] and autoimmune LD compared to both control and AVH groups. Serum HGF level was significantly elevated in all patients [PI =0.006] compared to control levels and in patients with autoimmune LD compared to patients with AVH [P2=0.013], CVH [P3=0.02] and metabolic LD [P4=0.03]. There was a positive significant correlation between serum levels of HGF and serum total bilirubin, ALT and blood positivity for APA. The APA was detected in 25 patients' blood samples with a significantly higher frequency in patients with autoimmune LD. Using the receiver operating characteristic [ROC] curve analysis revealed that blood positivity for APA is a specific, while thrombocytopenia is sensitive indicators for liability of occurrence of bleeding episodes. It could be concluded that serum levels of HGF were elevated in all forms of hepatic insults and correlate with the extent of hepatic derangement as judged by serum levels of total bilirubin and serum ALT. Moreover, 50% of patients with chronic liver diseases were found positive for APA that correlate with serum levels of HGF and the extent of concomitant thrombocytopenia and could be considered as a specific predictor for the occurrence of bleeding episodes in these patients

Hepatocyte growth factor in serum and bronchoalveolar lavage fluid versus exhaled nitric oxide in systemic lupus erythematosus

The present study tried to evaluate the clinical significance of hepatocyte growth factor [HGF] in the serum and bronchoalveolar lavage fluid [BALF] in systemic lupus erythematosus [SLE] patients and their relation to nitric oxide [NO] in exhaled air. Forty SLE patients were investigated along with ten apparently healthy individuals. The patients' group was divided into two groups: group [A] Inactive SLE patients without pulmonary affection [n=14] and group [B] SLE patients with pulmonary affection [n=26]. The last group was further classified into 4 sub groups: - B1= Active SLE patients without interstitial lung disease [ILD], B2= Active SLE patients with interstitial lung disease + Alveolitis [ILD +A], B3: Inactive SLE patients without ILD and B4= Inactive - SLE patients with ILD. All patient and control groups were evaluated for chest X-ray, pulmonary function tests and high-resolution computerized tomography [HRCT], along with systemic lupus erythematosus [SLE routine laboratory investigations. Measurement of HGF Levels in serum and BALF by Immunoassay and exhaled nitric oxide [NO] was measured by chemiluminescence. There were abnormal pulmonary function tests in 65% [26/40] of SLE patients and abnormal HRCT in the form of ILD in 32.5[13/40] of SLE patients. The exhaled NO showed a significant elevation in patients with activity especially those with evidence of active inflammation of the lung. There was no significant elevation of exhaled NO for patients with ILD without evidence of active inflammation. The level of HGF in serum and BALF showed a significant elevation in patients with activity especially with the presence of active lung inflammation. Also, there was a significant elevation of serum HGF and BALF-HGF for patients with ILD without evidence of inflammation. The level of HGF in serum and BALF showed significant elevation in patients as compared with control subjects. HGF levels in BALF of patients was more elevated than HGF levels in serum of patients groups. HGF in serum and BALF was increased in patients with pulmonary fibrosis and correlated with clinical parameters. Measurement of exhaled NO is a simple and non-invasive method to detect the presence of inflammatory lung disease

Effect of renal transplantation on serum hepatocyte growth factor levels in hemodialysis patients with HCV infection

Hepatocyte growth factor [HGF] acts as an activator of mitogenesis, motogenesis, and morphogenesis, and as a potent survival factor. It is one of the cytokines that has proven to be involved in the regeneration of renal tubule cells following injury. The purpose of this study was to evaluate the effect of renal transplantation on serum hepatocyte growth factor levels in hemodialysis patients with HCV infection.74 subjects with HCV infection were enrolled in the study, they were further subdivided into three groups: Control group [n=10]; hemodialysis group [HD] [n= 30] and renal transplant recipient group [n=34]. Serum hepatocyte growth factor [HGF] determination was performed using quantitative sandwich enzyme immunoassay. Our study revealed that serum levels of HGF, in HD patients showed a significant increase as compared to control [p<0.001] and renal transplant groups [p<0.001]. In HD patients serum HGF levels showed a positive correlation with both serum creatinine levels [r =0.874, p< 0.001] and urea levels [T= 0.559, p< 0.001] but did not correlate with ALT levels or duration of HD. Serum HGF values in renal transplant recipients showed no statistically significant changes as compared to controls and did not correlate with either creatinine, urea, ALT and cyclosporine blood levels. We concluded that serum HGF was elevated in HD patients, which may be attributed to the increased production of HGF in response to the chronic renal injury, the effect of heparin, or reduced removal of serum HGF in CRF patients. Serum levels of HGF in renal transplant recipients showed no statistically significant changes as compared to controls and no correlation with cyclosporine blood levels as patients had good allograft function and cyclosporine blood levels were properly monitored. Although serum HGF values in HD patients are elevated, levels return back to normal in renal transplant recipients with good allograft function

diagnostic and prognostic value of serum hepatocyte growth factor during acute myocardial infarction

Hepatocyte growth factor [HGF] is a mesenchyme derived growth factor originally identified in the plasma of partially hepatectomized rats and later isolated from rat platelets and human plasma HGF has marked and varied ejects on epithelial cells, endothelial cells and other cell types including morphogenic and mitogenic activity. Plasma HGF concentration has been reported to be increased in response to tissue damage such as liver and kidney diseases. HGF also act as a growth factor for vascular tissues, and its mitogenic activity is the most potent among various known growth factors. Plasma HGF concentrations are reported to be increased in cardiovascular diseases such as acute myocardial infarction. It has been found that HGF can induce angiogenesis in ischemia diseases. The aim of this study is to investigate the clinical significance of circulating HGF in patients with acute myocardial infarction to fulfill this aim we studied 25 patients with acute myocardial infarction [acute MI] and 10 normal control subjects. All studied cases underwent thorough clinical examination and laboratory Investigations as blood picture, liver function, kidney function tests and abdominal sonogram. Specific tests necessitate venous blood samples drawn from the infarct patients at 1,7,14, 21 days after the onset of MI to measure serum HGF, plasma C-reactive protein and creatine phosphokinase. Also, echocardiogram to calculate left ventricular mass and to assess left ventricular end diastolic volume changes as a reflexion of ventricular dilatation at day 1 and 3 weeks after MI. Echocardiograms were done only for patients group. We excluded any patient suffering from liver disease, renal diseases, systemic illness or malignancy. Our results showed that serum HGF values within seven days were significantly higher than those of control subjects and decreased by day 14 and there were significant correlation between plasma creatinine phosphokinase and serum HGF on day 1; and also between C reactive protein and serum HGF. Also, we found that, serum HGF was high in patients with progression of ventricular enlargement in the course of acute myocardial infarction. So, we conclude that early serum HGF concentration reflect the extent of myocardial damage in acute myocardial infarction patients. Inflammation after acute MI is supposed to be involved in enhanced HGF production. Also, HGF may play an important role in ventricular remodelling after acute MI

Measurement of gastric mucosal hepatocyte growth factor in helicobacter pylori gastritis

Hepatocyte growth factor [H.G.F.] which was originally identified as a growth factor for hepatocytes, has been shown to have the potentiality to stimulate the growth of gastric epithelial cells and also, can enhance motility of epithelial cells i.e. [mitogen and motogen effects]. Cell proliferation is increased in gastric mucosa infected by Helicobacter pylori [H.P.]. However, the mechanism of that proliferation is not well understood, it was supposed that mucosal inflammation by Helicobacter pylori pruduces interleukin IB which may induce H.G.F. production yielding mucosal proliferation; also, it was found that H.G.F. stimulates the production of prostaglandin E2 which may play a role in gastric mucosal cell proliferation. Was to study and measure gastric mucosal H.G.F in presence and absence of helicobacter pylori gastritis to fulfill this aim, we studied two groups of patients, one group including 30 patients with H.P-gastritis and another group including 10 patients as a control group complaining of dyspepsia without H.P. infection [negative controls], both groups were age and sex matched, both groups were subjected to thorough clinical assessment, pelviabdominal ultrasonogram, routine lab investigations. Also, upper G.I.T. endoscope with antral and fundal biopsies for histopathological examination to detect HP and to show the degree of gastritis associated and also to do immunohistochemical studies for detection of H.G.F in gastric mucosa. In our study, we found a significant correlation between the degree of severity of gastritis caused by H.P. and the degree of staining of HGF- receptor in antral mucosa, so, the more severe the inflammation, the more H.G.F production in the mucosa. Gastric mucosal H.G.F. increases in H.P. gastritis, and its increase is directly related to the degree of gastritis. The production of H.G.F which is a protective protein to maintain homeostasis and the integrity of gastric mucosa by inducing cell proliferation to replace damaged gastric mucosa by Helicobacter cytotoxic activities

Increased serum levels of hepatocyte growth factor [HGF] in type 2 diabetes mellitus associated with ischemic heart disease is a good predictor biochemical marker for diagnosis of coronary atherosclerosis

Atherosclerotic cardiovascular complications are the major causes of morbidity and mortality in type 2 diabetes mellitus. Injury of endothelial cells has been postulated as the initial trigger of progression of atherosclerosis in diabetes mellitus. It has been hypothesized that HGF might contribute to the protection or repair of vascular endothelial cells. Therefore, this study was designed to find out how much type 2 diabetes with and without ischemic heart disease affect the level of HGF and to find out any relationship between the change in serum HGF and development of coronary atherosclerosis. HGF levels were measured by ELIZA in the serum of 16 healthy volunteers and 44 type 2 diabetic subjects.13 of them had ischemic heart disease with coronary atherosclerosis, other 15 had ischemic heart disease with normal coronary angiogram while the remaining 16 diabetic subjects has no ischemic heart disease and without any complications. IN addition to, ultrasonographic measurements of the combined thickness of the common carotid intima and media [CCA-IMT] was done to all subjects to examine early vessel wall changes in atherosclerosis. Serum HGF levels were statistically significantly decreased and the mean CCA-IMT were significantly increased in uncomplicated diabetic subgroup [group II] compared to controls [P<0.05] on the other hand, we found that serum HGF levels were statistically significantly increased and the mean CCA-IMT were significantly increased in other two diabetic subgroups [diabetics with ischemic heart disease] [group III and IV] compared to controls [P < 0.05, P<0.01] respectively. Also, we found that serum HGF levels and the mean CCA-IMT were statistically significantly increased in diabetics with ischemic heart disease and with coronary atherosclerosis compared to diabetic with ischemic heart disease and with normal coronary angiogram [P<0.05]. Clycozylated haemoglobin [HbAIC] was significantly increased in diabetic subgroups compared to controls [P<0.05, P<0.05 and P<0.01] respectively. And in diabetics with coronary atherosclerosis compared to those without [P<0.05]. HDL-C was significantly decreased in diabetic with ischemic heart disease and with coronary atherosclerosis compared to those without [P<0.05]. Significant negative correlation were obtained between serum HGF and each of HbA1c [r=-0.614, P<0.01] and CCA-IMT [r=-0.66, P<0.01] in uncomplicated diabetics and significant positive correlation between serum HGF and each of HbA1c [r=+0.62, P<0.01] and CCA-IMT [r+0.68, P<0.01] in diabetics with ischemic heart disease with and without coronary atherosclerosis. At the same time, we found significant positive correlation between CCA-IMT and each of age of diabetics [r=+0.43, P<0.05], duration of diabetes [r+0.41, P<0.05] and HbA1c [r=+0.71, p<0.01] in all diabetic subgroups. We can conclude that serum HGF decreased in uncomplicated diabetics and increased in diabetic with ischemic heart disease especially those with coronary atherosclerosis. increased serum HGF may be involved in the pathogenesis of atherosclerosis in type 2 diabetes and can be used as a useful test for predicting these atherosclerotic lesions. Treatment strategies to decrease HGF in type 2 diabetics complicated with atherosclerotic vascular disease by the use of growth modulating factors may prove to be useful to prevent and slow the progression of atherosclerosis in type 2 diabetes mellitus