AIM:To clarify the clinicopathological significance of laminin-5 γ2 (LNγ2) and β3 (LNβ3) chains and MMP7 expression in biliary tract cancer.METHODS: We analyzed the association between immunohistochemically detect...AIM:To clarify the clinicopathological significance of laminin-5 γ2 (LNγ2) and β3 (LNβ3) chains and MMP7 expression in biliary tract cancer.METHODS: We analyzed the association between immunohistochemically detected LNγ2, LNβ3, and MMP7 expression in biliary tract cancer and clinicopathological characteristics. Activity of MMP7 was analyzed by casein zymography. An in vitro invasion assay after treatment with MMP7-specific siRNA was performed.RESULTS: LNγ2 expression was predominantly observed in carcinoma cells at the invasive front. LNγ2 expression was seen in 57% of patients with biliary tract cancer, and was associated with depth of invasion, histologic type, and advanced stage. The expression pattern of LNβ3 was classified into two types: invasive front dominant type (38%) and diffuse type (28%).The invasive front dominant type was associated with histologic type and advanced stage. MMP7 positivity was correlated with LNγ2 or LNβ3 expression but not with clinicopathological characteristics. Active MMP7 detected by casein zymography was correlated with depth of invasion and advanced stage. Downregulation of MMP7 expression by siRNA resulted in a significant decrease in biliary tract cancer cell invasion in vitro.CONCLUSION: Our results suggest that LNγ2 and LNβ3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.展开更多
Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess t...Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 γ2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 γ2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 γ2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116 patients with advanced (stages II-IV) esophageal SCC using the tissue microarray-based immunohistochemistry and analyzed the correlation of the expressions with clinicopathologic characteristics and survival. We found that in normal esophageal tissues, laminin-5 γ2 chain was expressed in the basement membrane, whereas in esophageal SCC tissues, laminin-5 γ2 chain was expressed in the cytoplasm of carcinoma cells, with a positive rate of 72.4%. SPARC was not detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in 84.6% of esophageal SCC cases and in cancer cells in 7.8% of esophageal SCC cases. There was a significant correlation between laminin-5 γ2 chain and stromal SPARC expression in esophageal SCC (Spearman's rho = 0.423, P < 0.001). The expressions of both laminin-5 γ2 chain and stromal SPARC were correlated with survival (P = 0.032 and P = 0.034, respectively). In stage-II esophageal SCC, the expression of laminin-5 γ2 chain was significantly correlated with survival (P = 0.023), while the expression of SPARC was not significantly correlated with survival (P = 0.154). Patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis than did those lacking elevated levels of laminin-5 γ2 chain expression and/or elevated levels of SPARC expression (P = 0.001). In stage-II esophageal SCC, patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis (P < 0.001). These results suggest that laminin-5 γ2 chain and SPARC may play roles in the progression of esophageal SCC and their simultaneous expression is correlated with poorer prognosis, especially in patients with stage-II SCC.展开更多
Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRN...Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exog- enous LN5 and gefitinib to A549 lung cancer cell line, and Western-blotting was performed to investigate the phosphorylation level of EGFR,Ak, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut- point group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib. Conclusion: Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.展开更多
Hepatocellular carcinoma is difficult to treat,primarilybecause the underlying molecular mechanisms drivingclinical outcome are still poorly understood.Growingevidence suggests that the tissue microenvironmenthas a ro...Hepatocellular carcinoma is difficult to treat,primarilybecause the underlying molecular mechanisms drivingclinical outcome are still poorly understood.Growingevidence suggests that the tissue microenvironmenthas a role in the biological behavior of the tumor.Themain clinical issue is to identify the best target fortherapeutic approaches.Here,we discuss the hypothesis that the entire tissue microenvironment might beconsidered as a biological target.However,the tissuemicroenvironment consists of several cellular and biochemical components,each of which displays a distinctbiological activity.We discuss the major components ofthis environment and consider how they may interactto promote tumor/host crosstalk.展开更多
Granular cell ameloblastoma is a rare,benign neoplasm of the odontogenic epithelium.A case of massive granular cell ameloblastoma in a 44-year-old Thai female is reported.Histopathological features displayed a follicu...Granular cell ameloblastoma is a rare,benign neoplasm of the odontogenic epithelium.A case of massive granular cell ameloblastoma in a 44-year-old Thai female is reported.Histopathological features displayed a follicular type of ameloblastoma with an accumulation of granular cells residing within the tumor follicles.After treatment by partial mandibulectomy,the patient showed a good prognosis without recurrence in a 2-year follow-up.To characterize the granular cells in ameloblastoma,we examined the expression of basement membrane(BM) proteins,including collagen type IV,laminins 1 and 5 and fibronectin using immunohistochemistry.Except for the granular cells,the tumor cells demonstrated a similar expression of BM proteins compared to follicular and plexiform ameloblastomas in our previous study,whereas the granular cells showed strong positivity to laminins 1 and 5 and fibronectin.The increased fibronectin expression in granular cells suggests a possibility of age-related transformation of granular cells in ameloblastoma.展开更多
A randomized, monocentric, double-blind, intra-individual excipient-controlled comparative study was performed to evaluate the efficacy and tolerance of an active peptide (laminin 5 fragment [LN-5]) formulated in cosm...A randomized, monocentric, double-blind, intra-individual excipient-controlled comparative study was performed to evaluate the efficacy and tolerance of an active peptide (laminin 5 fragment [LN-5]) formulated in cosmetic balm, versus excipient in inter-toe cracks. Two products were tested on 10 healthy volunteers. Each of them suffered from this particular superficial wound characterized by a peeling off a skin tab between at least two inter-toe spaces. The duration of this study belonged of 28 days with an intermediate visit to D14. Initial and outcome evaluation was performed using a 4-grade-scale depending on the severity of the inter-toe cracks. Tolerance and healing were assessed using macrophotographs. At D14 and D 28, the difference of cure between the 2 treatments was in favor of the peptide active product. The clinical score showed a best efficiency of the active compared with the excipient;indeed a significant difference between D28 and D0 was observed for the active ingredient. Active product repairs more quickly inter-toes cracks than the excipient and we noted the complete disappearance of the “severe” and “moderate” stages from the 14th day. This study showed clearly a fast (in 14 days) and beneficial effect of the application of LN-5 compared with the excipient, on the cutaneous repair of inter-toes cracks. Since LN-5 fragment is capable of producing immediate biological activity and reinforcing the dermal-epidermal junction, it can accelerate tissue repair.展开更多
基金Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture,Sports,Science and Technology of Japan (H.Y. and K.I.)Grants-in-Aid for Cancer Research and for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health,Labor and Welfare of Japan (H.Y. and K.I.)
文摘AIM:To clarify the clinicopathological significance of laminin-5 γ2 (LNγ2) and β3 (LNβ3) chains and MMP7 expression in biliary tract cancer.METHODS: We analyzed the association between immunohistochemically detected LNγ2, LNβ3, and MMP7 expression in biliary tract cancer and clinicopathological characteristics. Activity of MMP7 was analyzed by casein zymography. An in vitro invasion assay after treatment with MMP7-specific siRNA was performed.RESULTS: LNγ2 expression was predominantly observed in carcinoma cells at the invasive front. LNγ2 expression was seen in 57% of patients with biliary tract cancer, and was associated with depth of invasion, histologic type, and advanced stage. The expression pattern of LNβ3 was classified into two types: invasive front dominant type (38%) and diffuse type (28%).The invasive front dominant type was associated with histologic type and advanced stage. MMP7 positivity was correlated with LNγ2 or LNβ3 expression but not with clinicopathological characteristics. Active MMP7 detected by casein zymography was correlated with depth of invasion and advanced stage. Downregulation of MMP7 expression by siRNA resulted in a significant decrease in biliary tract cancer cell invasion in vitro.CONCLUSION: Our results suggest that LNγ2 and LNβ3, in conjunction with MMP7, play a key role in the progression of biliary tract cancer.
基金supported by National Natural Science Foundation of the People's Republic of China(No.30670964,30770973)Beijing Hope Run Special Fund(No.LC2007B51)
文摘Previous studies have shown that the expressions of the γ2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 γ2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 γ2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 γ2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116 patients with advanced (stages II-IV) esophageal SCC using the tissue microarray-based immunohistochemistry and analyzed the correlation of the expressions with clinicopathologic characteristics and survival. We found that in normal esophageal tissues, laminin-5 γ2 chain was expressed in the basement membrane, whereas in esophageal SCC tissues, laminin-5 γ2 chain was expressed in the cytoplasm of carcinoma cells, with a positive rate of 72.4%. SPARC was not detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in 84.6% of esophageal SCC cases and in cancer cells in 7.8% of esophageal SCC cases. There was a significant correlation between laminin-5 γ2 chain and stromal SPARC expression in esophageal SCC (Spearman's rho = 0.423, P < 0.001). The expressions of both laminin-5 γ2 chain and stromal SPARC were correlated with survival (P = 0.032 and P = 0.034, respectively). In stage-II esophageal SCC, the expression of laminin-5 γ2 chain was significantly correlated with survival (P = 0.023), while the expression of SPARC was not significantly correlated with survival (P = 0.154). Patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis than did those lacking elevated levels of laminin-5 γ2 chain expression and/or elevated levels of SPARC expression (P = 0.001). In stage-II esophageal SCC, patients with elevated levels of laminin-5 γ2 chain and SPARC expressions had a poorer prognosis (P < 0.001). These results suggest that laminin-5 γ2 chain and SPARC may play roles in the progression of esophageal SCC and their simultaneous expression is correlated with poorer prognosis, especially in patients with stage-II SCC.
基金Supported by grants from the National Natural Science Foundation of China (No. 30772531)Guangdong Provincial Medical Science and Technology Research Foundation (No. B2006001)China Postdoc toral Science Foundation (No. 20060400212)
文摘Objective: To investigate whether laminin 5 (LN5) might be a predictor in lung cancer patient treated with gefitinib and estimate the underlying mechanisms. Methods: LN5 and epidermal growth factor receptor (EGFR) mRNA expression level were detected in the tumor tissues of lung cancer patients who underwent surgery resection prior to gefitinib treatment. EGFR exon 19 and 21 mutation status was also detected in these specimens. The association between LN5, EGFR mRNA expression level, EGFR mutation and gefitinib treatment response were evaluated. In vitro study were carried by adding exog- enous LN5 and gefitinib to A549 lung cancer cell line, and Western-blotting was performed to investigate the phosphorylation level of EGFR,Ak, and Erk. Results: The disease control rate according to LN5 mRNA level was 52.9% for the below cut- point group, and 17.6% for the above cut-point (P = 0.009). The in vitro study showed that exogenous LN5 can neutralize the inhibition of phosphor-Akt by gefitinib. Conclusion: Patients with lower LN5 mRNA level would likely benefit from gefitinib. In vitro study indicated that the inhibition of Akt induced by gefitinib might be reversed by LN5. These results provide important insights into the molecular mechanisms underlying sensitivity to gefitinib in lung cancer patients.
基金Supported by EU-Marie Curie Initial Training Network(ITN),FP7-PEOPLE-2012-ITN 2012,Grant Agreement No.316549
文摘Hepatocellular carcinoma is difficult to treat,primarilybecause the underlying molecular mechanisms drivingclinical outcome are still poorly understood.Growingevidence suggests that the tissue microenvironmenthas a role in the biological behavior of the tumor.Themain clinical issue is to identify the best target fortherapeutic approaches.Here,we discuss the hypothesis that the entire tissue microenvironment might beconsidered as a biological target.However,the tissuemicroenvironment consists of several cellular and biochemical components,each of which displays a distinctbiological activity.We discuss the major components ofthis environment and consider how they may interactto promote tumor/host crosstalk.
文摘Granular cell ameloblastoma is a rare,benign neoplasm of the odontogenic epithelium.A case of massive granular cell ameloblastoma in a 44-year-old Thai female is reported.Histopathological features displayed a follicular type of ameloblastoma with an accumulation of granular cells residing within the tumor follicles.After treatment by partial mandibulectomy,the patient showed a good prognosis without recurrence in a 2-year follow-up.To characterize the granular cells in ameloblastoma,we examined the expression of basement membrane(BM) proteins,including collagen type IV,laminins 1 and 5 and fibronectin using immunohistochemistry.Except for the granular cells,the tumor cells demonstrated a similar expression of BM proteins compared to follicular and plexiform ameloblastomas in our previous study,whereas the granular cells showed strong positivity to laminins 1 and 5 and fibronectin.The increased fibronectin expression in granular cells suggests a possibility of age-related transformation of granular cells in ameloblastoma.
文摘A randomized, monocentric, double-blind, intra-individual excipient-controlled comparative study was performed to evaluate the efficacy and tolerance of an active peptide (laminin 5 fragment [LN-5]) formulated in cosmetic balm, versus excipient in inter-toe cracks. Two products were tested on 10 healthy volunteers. Each of them suffered from this particular superficial wound characterized by a peeling off a skin tab between at least two inter-toe spaces. The duration of this study belonged of 28 days with an intermediate visit to D14. Initial and outcome evaluation was performed using a 4-grade-scale depending on the severity of the inter-toe cracks. Tolerance and healing were assessed using macrophotographs. At D14 and D 28, the difference of cure between the 2 treatments was in favor of the peptide active product. The clinical score showed a best efficiency of the active compared with the excipient;indeed a significant difference between D28 and D0 was observed for the active ingredient. Active product repairs more quickly inter-toes cracks than the excipient and we noted the complete disappearance of the “severe” and “moderate” stages from the 14th day. This study showed clearly a fast (in 14 days) and beneficial effect of the application of LN-5 compared with the excipient, on the cutaneous repair of inter-toes cracks. Since LN-5 fragment is capable of producing immediate biological activity and reinforcing the dermal-epidermal junction, it can accelerate tissue repair.
