-
[show abstract]
[hide abstract]
ABSTRACT: ABSTRACT Plasminogen activator inhibitor-1 (PAI-1) plays an important role in the silica-induced pulmonary fibrosis. The effect of silica on the expression of PAI-1 was investigated in human lung epithelial cells (A549). Silica induced PAI-1 expression in a concentration-(50-200 mug/mL) and time-(4-24 h) dependent manner in A549 cells. Furthermore, the roles of mitogen-activated protein kinase (MAPK)/activator protein-1 (AP-1) signaling pathways in silica-induced PAI-1 expression were examined. We found that silica (200 mug/mL) treatment for 4 to 24 h resulted in AP-1 activation in A549 cells. Cells were pretreated with the AP-1 inhibitor curcumin (10, 25, 50 muM), and silica-induced PAI-1 expression was reduced by 20%, 63%, and 65%, respectively. In addition, dominant-negative mutant c-Jun (TAM67) down-regulated silica-induced PAI-1 expression by 59%. P38 kinase inhibitor SB203580 (20 muM) and Erk inhibitor PD98059 (50 muM) suppressed silica-induced PAI-1 expression by 35% and 51%, respectively. Additionally, PD98059 but not SB203580 inhibited the AP-1 DNA binding activity induced by silica. The results suggest that the PAI-1 expression induced by silica may be involved in the activation of MAPKs/AP-1 signaling pathways in human lung epithelial cells.
Toxicology mechanisms and methods 01/2008; 18(7):561-7. · 1.03 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To elucidate the relationship between expression of p16 and cyclinD1 proteins and evaluate the role of p16 gene exon 2 mutation in hepatocellular carcinogenesis.
Streptavidin-peroxidase conjugated method(SP) was used to detect expressions of p16 and cyclinD1 proteins in 44 cases of hepatocellular carcinoma(HCC), and polymerase chain reaction single-strand conformation polymorphism analysis(PCR-SSCP) to detect p16 gene mutation in exon 2 in 12 cases of HCC and liver tissues adjacent to HCC.
Expression rate and positive signal intensity of p16 protein in HCC were significantly lower(P < 0.01) and those of cyclinD1 protein in HCC were significantly higher (P < 0.05) than those in pericarcinomatous tissues. Of 12 fresh HCC tissues, p16 gene mutation in exon 2 was found in 2 cases, whereas that was not found in pericarcinomatous tissues.
1. Inactivation or/ and deletion of p16 protein may be one of important reasons which result in proliferation unbalance of cells. 2. p16 gene mutation in exon 2 presents in HCC, but it does not frequently occur in Chinese hepatocarcinogenesis. 3. p16 gene abnormality and cyclinD1 over expression may coact in HCC.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 12/2001; 26(6):527-30.
-
[show abstract]
[hide abstract]
ABSTRACT: To detect the expressions of p-MAPK, cyclin D1 and p53 protein, and investigate their relationship in osteosarcomas.
SP immunohistochemical technique was used to detect the expressions of of p-MAPK, cyclin D1 and p53 protein among the 58 osteosarcomas and 14 osteoid osteomas samples.
The positive rates of p-MAPK, cyclin D1 and p53 protein were 77.6% (45/58), 60.3% (35/58) and 44.8% (26/58) respectively in 58 osteosarcomas, and 21.4% (3/14), 21.4% (3/14) and 7.1% (1/14) in 14 osteoid osteomas. Their positive rates and expressive intensities in osteosarcomas were higher than those in osteiod osteomas. Their positive correlation was significantly observed between p-MAPK and cyclin D1 proteins (P < 0.01), and wasn't observed between p-MAPK and p53 proteins (P < 0.05) in osteosarcomas.
MAPK phosporylation may be one of causes for activation of cyclin D1, which play an important role in osteosarcogenesis. The mutation of p53 oncogene may not result in osteosarcogenesis by MAPK signaling pathway. Detecting p-MAPK by immunohistochemistry may be one of diagnostic indexes for osteosarcoma and benign osteoma.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 08/2001; 26(4):325-7.
-
[show abstract]
[hide abstract]
ABSTRACT: To investigate hepatocarcinogenesis by detecting the effect of HCV NS3 protein on expression of inducible nitric oxide synthase (iNOS) mRNA in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissues(PCLT).
The expression of HCV NS3 protein and iNOSmRNA was detected by immunohistochemical technique (SP method) and in situ hybridization in specimens of HCC and PCLT from 52 patients with HBV(-). The relationship between the positive rate and the signal strength was tested statistically.
The positive rate of HCV NS3 protein in HCC was lower (46.2% vs. 67.3%), and signal strength was weaker than those in PCLT. The signal strength of HCV NS3 protein was correlated with the degree of carcinomatous cells differentiation in HCC (P < 0.01). The positive rates (80.8% and 90.4%) of iNOSmRNA in HCC and PCLT had no statistical difference. Signal intensity of iNOSmRNA in HCC was weaker than that in PCLT. The higher HCVNS3 protein expression level was, the stronger iNOSmRNA signals in PCLT (P < 0.01). In particular, the localization and patterns of HCV NS3 protein were much similar to those of iNOSmRNA in the PCLT of some patients.
HCV NS3 protein may exert its hepatocarcinogenic effect in the early stage on host cells by increasing product of nitric oxide, which may bring about transformation of hepatocytes.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 06/2001; 26(3):192-4.
-
[show abstract]
[hide abstract]
ABSTRACT: Expression of phosphorylated Stat3 (p-Stat3), c-fos and c-jun proteins was detected by immunohistochemical technique in 55 hepatocellular carcinomas (HCC) and their surrounding liver tissues. The results showed that the positive rates and signal intensity of p-Stat3, c-fos and c-jun protein in HCCs were significantly higher than those in pericarcinomatous tissues. The expressive intensity of c-fos and c-jun proteins was positively related to p-Stat3 expression in HCCs, whereas the positive correlation of expressive intensity was only observed between c-jun protein and p-Stat3 in pericarcinomatous tissues. The data suggest that the phosphorylation of Stat3 may be an early event in hepatocarcinogenesis; the overexpression of p-Stat3 protein, which activates c-fos and c-jun genes, may contribute to malignant transformation of hepatocytes; hepatocytes which expressed p-Stat3, c-fos or c-jun proteins may be potentially malignant pre-cancer cells in pericarcinomatous liver tissues.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 03/2001; 26(1):17-9.
-
[show abstract]
[hide abstract]
ABSTRACT: To study the effect of phosphorylation of MAPK and Stat3 and the expression of c-fos and c-jun proteins on hepatocellular carcinogenesis and their clinical significance.
SP immunohistochemistry was used to detect the expression of p42/44(MAPK), p-Stat3, c-fos and c-jun proteins in 55 hepatocellular carcinomas (HCC) and their surrounding liver tissues.
The positive rates and expression levels of p42/44(MAPK), p-Stat3, c-fos and c-jun proteins in HCCs were significantly higher than those in pericarcinomatous liver tissues (PCLT). A positive correlation was observed between the expression of p42/44(MAPK) and c-fos proteins,and between p-Stat3 and c-jun but there was no significant correlation between p42/44(MAPK) and p-Stat3 in HCCs and their surrounding liver tissues.
The abnormalities of Ras/Raf/MAPK and JAKs/Stat3 cascade reaction may contribute to malignant transformation of hepatocytes. Hepatocytes which are positive for p42/44(MAPK), c-fos or c-jun proteins may be potential malignant pre-cancerous cells. Activation of MAPK and Stat3 proteins may be an early event in hepatocellular carcinogenesis.
World Journal of Gastroenterology 03/2001; 7(1):33-6. · 2.47 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: This paper was to evaluate the role of p53 mutation, and p53 and MDM2 proteins expression in hepatocarcinogenesis.
Using streptavidin-peroxidase conjugation method (SP), the expression of p53 and MDM2 proteins was observed in 61 cases of primary hepatocarcinomas (HCC) and 59 cases of corresponding paracancerous tissue, among which p53 mutations in exons 5-8 were detected in 21 cases by polymerase chain reaction single-strand confirmation polymorphism analysis (PCR-SSCP).
Positive nuclear p53 and MDM2 immunostainings were demonstrated in 57.38% (35/61) and 26.23% (16/61) of HCC, and 1.69% (1/59) and 3.39% (2/59) of corresponding paracancerous tissue, respectively. The expressions of p53 and MDM2 proteins in HCCs were significantly higher than those in paracancerous tissues (P < 0.01). The expressions of p53 and MDM2 were not significantly correlated (P > 0.05). There were 42.86% (9/21) mutations in exon 7 of p53 gene and no mutation was observed in exons 5, 6, 8 in HCCs and in paracancerous tissues. In cases of p53 mutations, there were 66.67% (6/9) of p53 overexpression and 11.11% (1/9) of overexpression of both p53 and MDM2. MDM2 overexpression also appeared in 25% (3/12) of cases without mutation.
Mutation of p53 gene and functional inactivation of p53 resulting from MDM2 overexpression play an important role in carcinogenesis of HCC. It is possible that p53 mutations and MDM2 overexpression induced by other mechanisms are involved in carcinogenesis of HCC.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 02/2001; 26(1):13-6.
-
[show abstract]
[hide abstract]
ABSTRACT: This paper was to investigate the relationship between expression of p-MAPK and oncogenesis of breast cancer.
Immunohistochemical technique was used to detect the expression of p-MAPK and c-fos and c-jun proteins in 68 cases of breast cancers, 42 cases of pericarcinomatous tissues and 7 cases of normal breast tissues.
Positive stainings of p-MAPK, c-fos, and c-jun were localized in cancer cell nuclei. The positive rates of p-MAPK, c-fos, and c-jun were 86.8% (59/68), 82.4% (56/68), and 77.9% (53/68), respectively, which were much higher than that in pericarcinomatous tissues (P < 0.01). Of some cases, p-MAPK positive staining was also found in the nuclei of the fibroblastic and angioendothelial cells of cancer stroma.
Activated or overexpressive MAPK activates the immediately-early oncogenes(c-fos, c-jun), which might play an important role in carcinogenesis of breast cancer and be an early event of oncogenesis of breast cancer.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 02/2001; 26(1):10-2.
-
[show abstract]
[hide abstract]
ABSTRACT: The relationship between vascular endothelial growth factor (VEGF) expression and microvessel density was studied with immunohistochemical method in hepatocellular carcinoma (HCC) and pericarcinomatous liver tissue. The positive rate of VEGF in HCCs was significantly lower than in surrounding liver tissues (66.7% vs. 85.4%, P < 0.05). There was no significant difference between HCC and pericarcinomatous liver tissue on expressive intensity of VEGF. The positive signal of VEGF was mainly localized in cytoplasma of cancer cells, pericarcinomatous hepatocytes, and vascular endothelial cells. The microvessel density in HCC was higher than in pericarcinomatous liver tissue and closely correlated to differentiated degree of cancer cells (rs = 0.5870; rs = 0.8235). The poorer cancer cell differentiation, the higher microvessel density. The results suggest that VEGF may not be the sole factor that stimulates angiogenesis in HCC genesis and development. To detect microvessel density in judging prognosis and biological behavior of HCC is more important than that of VEGF.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 05/2000; 25(2):132-4.
-
[show abstract]
[hide abstract]
ABSTRACT: The expressions of p42/44 mitogen-activated protein kinase(p42/p44MAPK) and cyclin D1 protein were detected by SP immunohistochemical technique in 40 cases of Hodgkin's disease(HD) and 13 cases of reactive hyperplasia(RH). The results showed that p42/p44MAPK and cyclin D1 protein were both overexpressed in RS/H cells of HD(positive rates were 72.5% and 70% respectively), and their positive rates were positively correlated(P < 0.01). The data suggest that MAPK cascades signal transduction may play an important role in genesis of HD. MAPK may induce overexpression of cyclin D1 protein and result in persistent proliferation and progression of RS/H cells.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 03/2000; 25(1):6-8.
-
[show abstract]
[hide abstract]
ABSTRACT: Deresining must be performed for HE, specific histochemical staining and immunohistochemical detection on semithin-sections embedded-epoxy resin. The deresining process in general methods had to take 24 hours, and the semithin-sections were easily separated from slides. An improved method was introduced in this paper, by which deresining time was only 5 minutes, and it could also avoid the separation of semithin-sections from the slides. The staining result was very good, and the resolving power of images was high.
Hunan yi ke da xue xue bao = Hunan yike daxue xuebao = Bulletin of Hunan Medical University 03/2000; 25(1):85-6.
