AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular ca...AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively). Predictors of outcome after the surgery of pri展开更多
AIM： To elucidate the role of neuropilin-1 （Nrp-1） and semaphorin 3A （Sema3A） in sinusoidal remodeling dur- ing liver regeneration in rats. METHODS： Male Wistar/ST rats at 7 wk of age, weigh- ing about 200 g, we...AIM： To elucidate the role of neuropilin-1 （Nrp-1） and semaphorin 3A （Sema3A） in sinusoidal remodeling dur- ing liver regeneration in rats. METHODS： Male Wistar/ST rats at 7 wk of age, weigh- ing about 200 g, were used for all animal experiments. In vivo, at 24, 48, 72, 96, 144 and 192 h after two- thirds partial hepatectomy （PHx）, the remnant livers were removed. Liver tissues were immunohistochemi- cally stained for Nrp-1, Sema3A and SE-1, a liver sinu- soidal endothelial cell （SEC） marker. Total RNA of the liver tissue was extracted and reversely transcribed into cDNA. The mRNA expression of Sema3A was ana- lyzed by quantitative real-time polymerase chain reac- tion and normalized to that of ribosomal protein $18. In vitro, SECs were isolated from rat liver and cultured in endothelial growth medium containing 20 ng/mL vascular endothelial cell growth factor. Migration of SECs in primary culture was assessed by cell transwell assay with or without recombinant Sema3A. Apoptotic cells were determined by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method. RESULTS： In vitro, immunohistochemistry study re- vealed that Sema3A and Nrp-1 were constitutively ex- pressed in hepatocytes and SECs, respectively, in normal rat liver tissues. Nrp-1 expression in SECs was quantified by the percentage of immunostained area with anti- Nrp-1 antibody in relation to the area stained with SE-1. Between 24 h and 96 h following resection of liver, Nrp-1 expression in SECs was transiently increased. Compared with the baseline （5.2% ± 0.1%）, Nrp-1 expression in SECs significantly increased at 24 h （17.3% ± 0.7%, P 〈 0.05）, 48 h （39.1% ± 0.6%, P 〈 0.01）, 72 h （46.9% ± 4.5%, P 〈 0.01） and 96 h （29.9% ±3.8%, P 〈 0.01） after PHx, then returned to the basal level at termination of liver regeneration. Interestingly, the expression of Sema3A was inversely associated with that of Nrp-1 in liver after PHx. Sema3A mRNA expres- sion was signifi展开更多
文摘AIM:To investigate whether expressing biliary phenotype predicted poor outcome after the surgical treatment in primary liver cancers. METHODS:Out of 204 patients that underwent liver resection due to hepatocellular carcinoma (HCC), liver specimens of 70 patients with HCC were evaluated for biliary components by cytokeratin (CK) 19 immunostain (CK19 - HCC and CK19 + HCC). CK19 positivity was defined as membranous and/or cytoplasmic expression in ≥ 5% of tumor cells with moderate or strong intensity. Patients with other primary liver cancers, such as com- bined HCC and cholangiocarcinoma (cHCC-CC), intrahe- patic cholangiocarcinoma (ICC) who received curative liver resection, were also included in the study. Clinical characteristics of CK19-HCC and CK19 + HCC patients, including survival outcome after curative liver resection, were compared with that of cHCC-CC and ICC patients. RESULTS: The overall survival (OS) rate of CK19 - HCC(n = 49) after the curative surgical treatment was 90.7%, and 80.4% at 1 and 5 years after the resection. OS rate of CK19 + HCC (n = 21) was 74.3%, 28.9% and OS rate of cHCC-CC (n = 22) was 66.7%, 32.2% at 1 and 5 years after the surgery. For ICC (n = 19), 1 and 5-year-OS rate was 50.2% and 14.3% after the cura-tive resection. The OS rates of CK19 + HCC and cHCC-CC were significantly lower than that of CK19-HCC, but higher than the OS rate of ICC (P = 0.000). There was no statistically significant difference in OS rate between CK19 + HCC and cHCC-CC. The disease free survival (DFS) rate of CK19-HCC was 72.0% and 54.5% at 1 and 3 years after the surgical treatment. DFS rate of CK19 + HCC was 53.3%, 34.3% and DFS rate of cHCC- CC was 51.5%, 39.2% at 1 and 3 years after the resection. For ICC, 1 and 3-year-DFS rate was 28.0% and 14.0% after the curative resection. DFS rate of CK19-HCC was significantly higher than that of ICC (P = 0.017), but marginally higher than DFS rate of either CK19 + HCC or cHCC-CC (P = 0.097, P = 0.089, respec-tively). Predictors of outcome after the surgery of pri
基金Supported by A Grant-in-aid for Young Scientists from Japan Society for the Promotion of Science,No.22790671
文摘AIM： To elucidate the role of neuropilin-1 （Nrp-1） and semaphorin 3A （Sema3A） in sinusoidal remodeling dur- ing liver regeneration in rats. METHODS： Male Wistar/ST rats at 7 wk of age, weigh- ing about 200 g, were used for all animal experiments. In vivo, at 24, 48, 72, 96, 144 and 192 h after two- thirds partial hepatectomy （PHx）, the remnant livers were removed. Liver tissues were immunohistochemi- cally stained for Nrp-1, Sema3A and SE-1, a liver sinu- soidal endothelial cell （SEC） marker. Total RNA of the liver tissue was extracted and reversely transcribed into cDNA. The mRNA expression of Sema3A was ana- lyzed by quantitative real-time polymerase chain reac- tion and normalized to that of ribosomal protein $18. In vitro, SECs were isolated from rat liver and cultured in endothelial growth medium containing 20 ng/mL vascular endothelial cell growth factor. Migration of SECs in primary culture was assessed by cell transwell assay with or without recombinant Sema3A. Apoptotic cells were determined by a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling method. RESULTS： In vitro, immunohistochemistry study re- vealed that Sema3A and Nrp-1 were constitutively ex- pressed in hepatocytes and SECs, respectively, in normal rat liver tissues. Nrp-1 expression in SECs was quantified by the percentage of immunostained area with anti- Nrp-1 antibody in relation to the area stained with SE-1. Between 24 h and 96 h following resection of liver, Nrp-1 expression in SECs was transiently increased. Compared with the baseline （5.2% ± 0.1%）, Nrp-1 expression in SECs significantly increased at 24 h （17.3% ± 0.7%, P 〈 0.05）, 48 h （39.1% ± 0.6%, P 〈 0.01）, 72 h （46.9% ± 4.5%, P 〈 0.01） and 96 h （29.9% ±3.8%, P 〈 0.01） after PHx, then returned to the basal level at termination of liver regeneration. Interestingly, the expression of Sema3A was inversely associated with that of Nrp-1 in liver after PHx. Sema3A mRNA expres- sion was signifi
