Fibrogenesis in inflammatory bowel diseases is a complex phenomenon aimed at mucosal repair. However, it may provoke intestinal fibrosis with the development of strictures which require surgery. Therefore, fibrogenes... Fibrogenesis in inflammatory bowel diseases is a complex phenomenon aimed at mucosal repair. However, it may provoke intestinal fibrosis with the development of strictures which require surgery. Therefore, fibrogenesis may be considered as a 'two-faced' process when related to chronic intestinal inflammation. Many types of cells may be converted into the fibrogenic phenotype at different levels of the intestinal wall. A complex interaction of cytokines, adhesion molecules and growth factors is involved in the process. We report an overview of recent advances in molecular mechanisms of stricturizing Crohn’s disease(CD) including the potential role of trasforming growth factor beta, protein kinase C and Ras, Raf and ERK proteins. Fibrotic growth factors such as vascular endothelial growth factor and platelet-derived growth factor, as well as the Endothelial-to-Mesenchymal Transition induced by transforming growth factor-β, are considered. Finally, our experience, focused on tumor necrosis factor α(the main cytokine of inflammatory bowel diseases) and the link between syndecan 1(a heparan sulphate adhesion molecule) and basic fibroblast growth factor(a strong stimulator of collagen synthesis) is described. We hypothesize a possible molecular pattern for mucosal healing as well as how its deregulation could be involved in fibrotic complications of CD. A final clinical point is the importance of performing an accurate evaluation of the presence of fibrotic strictures before starting anti-tumor necrosis α treatment, which could worsen the lesions.展开更多
AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of ...AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry.RESULTS: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-NeumannKeuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e. , basolateral area of the crypts and TNF-α very poorly expressed. CONCLUSION: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by posttranscriptional regulation.展开更多
Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To tes...Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To test the effect of liposomal surface density of AG73 peptides on cellular uptake, we synthesized AG73 peptide-conjugated polyethylene glycol(MW 2000)lipid and incorporated it into fluorescence dye-labeled anionic liposomes with different ligand densities(1, 2, or 5 mol% of total lipids). Cellular uptake of AG73-peptide–modified liposomes gradually increased in proportion to the surface ligand density. The percentages of cells positive for AG73-modified, fluorescent-dye–labeled liposomes were 19.8 ± 2.0%, 23.1 ± 5.0%,and 99.2 ± 1.0%, for ligand mole percentages of 1, 2, and 5, respectively. The cell-targeting ability of AG73-modified liposomes was not significantly altered by the serum content of culture media. In keeping with the observed enhanced cellular uptake, AG73-peptide–modified liposomes entrapping edelfosine exhibited greater cancer cell-killing effects compared with unmodified liposomes. Following intravenous administration into tumor-bearing mice,AG73-peptide–modified liposomes showed 2.1-fold greater accumulation in tumors than unmodified liposomes. These results support the feasibility of using syndecan 2–directed liposomes for delivery of edelfosine.展开更多
AIM: To evaluate the relationship of expression of paxillin,syndecan-1 and EMMPRIN proteins with clinicopathological features in hepatocellular carcinoma (HCC).METHODS: Fifty-one patients who underwent HCC resection w...AIM: To evaluate the relationship of expression of paxillin,syndecan-1 and EMMPRIN proteins with clinicopathological features in hepatocellular carcinoma (HCC).METHODS: Fifty-one patients who underwent HCC resection were recruited in the study. Paxillin, syndecan1 and EMMPRIN proteins in HCC tissues were detected with immunohistochemical staining.RESULTS: Of 51 cases of HCC, 23 (45%) exhibited paxillin protein positive expression. Of 42 cases of adjacent nontumor liver tissues, 24 (57%) exhibited positive expression.Positive paxillin protein expression was associated with low differentiation (r= 0.406, P= 0.004), with the presence of portal vein thrombosis (r = 0.325, P = 0.021), with extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51cases of HCC, 28 (55%) exhibited syndecan-1 protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 23 (55%) exhibited positive expression.Positive snydecan-1 protein expression was associated with well differentiation (r = 0.491, P = 0.001), with no extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51cases of HCC, 28 (55%) exhibited EMMPRIN protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 21 (50%) exhibited positive expression.Expression of EMMPRIN protein was not associated with serum AFP level, HBsAg status, presence of microsatellite nodule, tumor size, presence of cirrhosis and necrosis,differentiation, presence of portal vein thrombosis, extrahepatic metastasis, disease-free survival and overall survival (P＞0.05). Expression of paxillin protein was correlated conversely with the expression of syndecan-1protein in HCC (r = -0.366, P = 0.010).CONCLUSION: Expression of paxillin and syndecan-1proteins in HCC may affect its invasive and metastatic ability of the tumor. There may be a converse correlation between the expression of paxillin and syndecan-1 protein in HCC. Expression of EMMPRIN protein may be detected in HCC, but it may play little role in the invasion and metastasis of HCC.展开更多
文摘 Fibrogenesis in inflammatory bowel diseases is a complex phenomenon aimed at mucosal repair. However, it may provoke intestinal fibrosis with the development of strictures which require surgery. Therefore, fibrogenesis may be considered as a 'two-faced' process when related to chronic intestinal inflammation. Many types of cells may be converted into the fibrogenic phenotype at different levels of the intestinal wall. A complex interaction of cytokines, adhesion molecules and growth factors is involved in the process. We report an overview of recent advances in molecular mechanisms of stricturizing Crohn’s disease(CD) including the potential role of trasforming growth factor beta, protein kinase C and Ras, Raf and ERK proteins. Fibrotic growth factors such as vascular endothelial growth factor and platelet-derived growth factor, as well as the Endothelial-to-Mesenchymal Transition induced by transforming growth factor-β, are considered. Finally, our experience, focused on tumor necrosis factor α(the main cytokine of inflammatory bowel diseases) and the link between syndecan 1(a heparan sulphate adhesion molecule) and basic fibroblast growth factor(a strong stimulator of collagen synthesis) is described. We hypothesize a possible molecular pattern for mucosal healing as well as how its deregulation could be involved in fibrotic complications of CD. A final clinical point is the importance of performing an accurate evaluation of the presence of fibrotic strictures before starting anti-tumor necrosis α treatment, which could worsen the lesions.
文摘AIM: To investigate tumor necrosis factor-α (TNF-α), syndecan 1 and basic fibroblast growth factor (bFGF) balance in Crohn's disease (CD) strictures. METHODS: Our study was performed on 24 surgical specimens of CD fibrotic stenosis. Ten histological normal surgical samples were retrieved for both the large and small bowel from patients with benign conditions and healthy tissue represented control collection. Sex and age in controls did not differ from CD group. Three endoscopic biopsy specimens taken after informed consent in subjects with normal colon were also used as negative controls. TNF-α, syndecan 1 and bFGF were detected by both reverse transcriptase reverse transcriptase polymerase chain reaction after mRNA extraction (results expressed as fold-change) and immunohistochemistry.RESULTS: TNF-α did not show any significant difference between CD and control specimens (1.54 ± 1.19; P > 0.05). Very high levels of bFGF were observed in CD (11.76 ± 4.65; P < 0.001) unlike syndecan 1 which showed a moderate increase (5.53 ± 2.18; P < 0.005). analysis of variance (ANOVA) plus Student-NeumannKeuls showed: bFGF > syndecan 1 > TNF-α = control. Immunoreactivity for bFGF was observed in epithelial, stromal, endothelial cells and even in the muscular layer, whilst in normal tissue it was almost unexpressed. Syndecan 1 and TNF-α staining was confined to mucosal epithelial and stromal cells, while in controls syndecan 1 was found in its normal site, i.e. , basolateral area of the crypts and TNF-α very poorly expressed. CONCLUSION: Fibrotic stenosis of CD may be the final result of an irreversible transformation of different cells into fibrogenic phenotype no longer inhibited by posttranscriptional regulation.
文摘Here, we report that the modification of liposome surfaces with AG73 peptides enhances delivery of the lipophilic anticancer drug, edelfosine, to tumor cells overexpressing the cellsurface receptor, syndecan 2. To test the effect of liposomal surface density of AG73 peptides on cellular uptake, we synthesized AG73 peptide-conjugated polyethylene glycol(MW 2000)lipid and incorporated it into fluorescence dye-labeled anionic liposomes with different ligand densities(1, 2, or 5 mol% of total lipids). Cellular uptake of AG73-peptide–modified liposomes gradually increased in proportion to the surface ligand density. The percentages of cells positive for AG73-modified, fluorescent-dye–labeled liposomes were 19.8 ± 2.0%, 23.1 ± 5.0%,and 99.2 ± 1.0%, for ligand mole percentages of 1, 2, and 5, respectively. The cell-targeting ability of AG73-modified liposomes was not significantly altered by the serum content of culture media. In keeping with the observed enhanced cellular uptake, AG73-peptide–modified liposomes entrapping edelfosine exhibited greater cancer cell-killing effects compared with unmodified liposomes. Following intravenous administration into tumor-bearing mice,AG73-peptide–modified liposomes showed 2.1-fold greater accumulation in tumors than unmodified liposomes. These results support the feasibility of using syndecan 2–directed liposomes for delivery of edelfosine.
基金Supported by the Major Programs of Health Bureau of Guangdong Province, No. A200194
文摘AIM: To evaluate the relationship of expression of paxillin,syndecan-1 and EMMPRIN proteins with clinicopathological features in hepatocellular carcinoma (HCC).METHODS: Fifty-one patients who underwent HCC resection were recruited in the study. Paxillin, syndecan1 and EMMPRIN proteins in HCC tissues were detected with immunohistochemical staining.RESULTS: Of 51 cases of HCC, 23 (45%) exhibited paxillin protein positive expression. Of 42 cases of adjacent nontumor liver tissues, 24 (57%) exhibited positive expression.Positive paxillin protein expression was associated with low differentiation (r= 0.406, P= 0.004), with the presence of portal vein thrombosis (r = 0.325, P = 0.021), with extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51cases of HCC, 28 (55%) exhibited syndecan-1 protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 23 (55%) exhibited positive expression.Positive snydecan-1 protein expression was associated with well differentiation (r = 0.491, P = 0.001), with no extra-hepatic metastasis (r = 0.346, P = 0.014). Of 51cases of HCC, 28 (55%) exhibited EMMPRIN protein positive expression. Of 42 cases of adjacent non-tumor liver tissues, 21 (50%) exhibited positive expression.Expression of EMMPRIN protein was not associated with serum AFP level, HBsAg status, presence of microsatellite nodule, tumor size, presence of cirrhosis and necrosis,differentiation, presence of portal vein thrombosis, extrahepatic metastasis, disease-free survival and overall survival (P＞0.05). Expression of paxillin protein was correlated conversely with the expression of syndecan-1protein in HCC (r = -0.366, P = 0.010).CONCLUSION: Expression of paxillin and syndecan-1proteins in HCC may affect its invasive and metastatic ability of the tumor. There may be a converse correlation between the expression of paxillin and syndecan-1 protein in HCC. Expression of EMMPRIN protein may be detected in HCC, but it may play little role in the invasion and metastasis of HCC.
