scholarly journals Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocarcinoma

2020 ◽  
Author(s):  
Zhenyang Shen ◽  
Jingbo Xiao ◽  
Junjun Wang ◽  
Lungen Lu ◽  
Xinjian Wan ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Intrahepatic Cholangiocarcinoma ◽  
Smooth Muscle Actin ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Nuclear Antigen ◽  
Cytokeratin 19 ◽  
High Recurrence Rate ◽  
Local Inflammation ◽  
Ductular Reaction

Abstract Background: Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods: Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.Results: A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037-0.557; P = 0.008 and r = 0.742, 95% CI, 0.580-0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43±0.29 vs 0.28±0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001).Conclusions: Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.

scholarly journals Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocarcinoma

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Zhenyang Shen ◽  
Jingbo Xiao ◽  
Junjun Wang ◽  
Lungen Lu ◽  
Xinjian Wan ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Intrahepatic Cholangiocarcinoma ◽  
Smooth Muscle Actin ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Nuclear Antigen ◽  
Cytokeratin 19 ◽  
High Recurrence Rate ◽  
Local Inflammation ◽  
Ductular Reaction

Abstract Background Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues. Results A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037–0.557; P = 0.008 and r = 0.742, 95% CI, 0.580–0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43 ± 0.29 vs 0.28 ± 0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001). Conclusions Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.

scholarly journals Peritumoral ductular reaction can be a prognostic factor for intrahepaticcholangiocellular carcinoma

2020 ◽  
Author(s):  
Zhenyang Shen ◽  
Jingbo Xiao ◽  
Junjun Wang ◽  
Lungen Lu ◽  
Xinjian Wan ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Smooth Muscle Actin ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Nuclear Antigen ◽  
Cytokeratin 19 ◽  
High Recurrence Rate ◽  
Local Inflammation ◽  
Ductular Reaction ◽  
Small Bile Duct

Abstract Background: Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods: Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.Results: A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037-0.557; P = 0.008 and r = 0.742, 95% CI, 0.580-0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43±0.29 vs 0.28±0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001).Conclusions: Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.

scholarly journals Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocellular carcinoma

2020 ◽  
Author(s):  
Zhenyang Shen ◽  
Jingbo Xiao ◽  
Junjun Wang ◽  
Lungen Lu ◽  
Xinjian Wan ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Smooth Muscle Actin ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Nuclear Antigen ◽  
Cytokeratin 19 ◽  
High Recurrence Rate ◽  
Local Inflammation ◽  
Ductular Reaction ◽  
Small Bile Duct

Abstract Background: Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocarcinoma (ICC) which may be derived from small bile duct cells or liver progenitor cells (LPCs) was known to us. However, whether peritumoral DR is also related to non-mucin-producing ICCs remains to be investigated. Methods: Forty-seven patients with non-mucin-producing ICC were eventually included in the study and clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.Results: A significant correlation existed between peritumoral DR and local inflammation and fibrosis. (r = 0.357, 95% CI, 0.037-0.557; P = 0.008 and r = 0.742, 95% CI, 0.580-0.849; P < 0.001, respectively). Patients with obvious peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively) comparing with mild peritumoral DR. Compared with the mild peritumoral DR group, the proliferation activity of LPCs/ cholangiocytes was higher in obvious peritumoral DR, which, however, was not statistically significant. (0.43±0.29 vs 0.28±0.31, P = 0.172). Furthermore, the correlation analysis showed that the DR grade was positively related to the portal/septalα-SMA level (r = 0.359, P = 0.001).Conclusions: Peritumoral DR was associated with local inflammation and fibrosis. Patients with non-mucin-producing ICC having obvious peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC. However, the mechanism should be further investigated.

scholarly journals Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocellular carcinoma

2020 ◽  
Author(s):  
Zhenyang Shen ◽  
Jingbo Xiao ◽  
Junjun Wang ◽  
Lungen Lu ◽  
Xinjian Wan ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Smooth Muscle Actin ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Cholangiocellular Carcinoma ◽  
Nuclear Antigen ◽  
Cytokeratin 19 ◽  
High Recurrence Rate ◽  
Ductular Reaction ◽  
Intrahepatic Cholangiocellular Carcinoma

Abstract Background: Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocellular carcinoma (ICC), may be derived from small bile duct cells or liver progenitor cells (LPCs). However, whether peritumoral DR is also related to non-mucin-producing ICCs needs to be investigated. Methods: Forty-seven patients with non-mucin-producing ICC were eventually included in the study. Clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues.Results: Peritumoral DR is significantly correlated with local inflammation and fibrosis. Patients with significant peritumoral DR had high recurrence rate(81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time ( P = 0.01 and P = 0.03, respectively). Significant peritumoral DR showed high proliferation activity of LPC/cholangiocytes and abundant background extracellular matrix. Conclusions: Patients with non-mucin-producing ICC having significant peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC; however, the mechanism should be further investigated. Keywords: Intrahepatic cholangiocellular carcinoma, non-mucin producing, ductular reaction, prognostic factor

scholarly journals Peritumoral ductular reaction can be a prognostic factor for intrahepatic cholangiocellular carcinoma

2020 ◽  
Author(s):  
Zhenyang Shen ◽  
Jingbo Xiao ◽  
Junjun Wang ◽  
Lungen Lu ◽  
Xinjian Wan ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Smooth Muscle Actin ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Cholangiocellular Carcinoma ◽  
Nuclear Antigen ◽  
Cytokeratin 19 ◽  
High Recurrence Rate ◽  
Ductular Reaction ◽  
Intrahepatic Cholangiocellular Carcinoma

Abstract Background Peritumoral ductular reaction (DR) was reported to be related to the prognosis of combined hepatocellular-cholangiocarcinoma and hepatocellular carcinoma. Non-mucin-producing intrahepatic cholangiocellular carcinoma (ICC), may be derived from small bile duct cells or liver progenitor cells (LPCs). However, whether peritumoral DR is also related to non-mucin-producing ICCs needs to be investigated. Methods Forty-seven patients with non-mucin-producing ICC were eventually included in the study. Clinicopathological variables were collected. Immunohistochemical analysis and immunofluorescence staining for cytokeratin 19, proliferating cell nuclear antigen, and α-smooth muscle actin were performed in tumor and peritumor liver tissues. Results Peritumoral DR is significantly correlated with local inflammation and fibrosis. Patients with significant peritumoral DR had high recurrence rate (81.8% vs 56.0%, P = 0.058) and poor overall and disease-free survival time (P = 0.01 and P = 0.03, respectively). Significant peritumoral DR showed high proliferation activity of LPC/cholangiocytes and abundant background extracellular matrix. Conclusions Patients with non-mucin-producing ICC having significant peritumoral DR had a poor prognosis. Peritumoral DR could be a prognostic factor for ICC; however, the mechanism should be further investigated.

scholarly journals PASS-Predicted Hepatoprotective Activity ofCaesalpinia sappanin Thioacetamide-Induced Liver Fibrosis in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Farkaad A. Kadir ◽  
Normadiah M. Kassim ◽  
Mahmood Ameen Abdulla ◽  
Behnam Kamalidehghan ◽  
Fatemeh Ahmadipour ◽  
...  
Keyword(s):  
Liver Fibrosis ◽  
Transforming Growth Factor ◽  
Antioxidant Activities ◽  
Smooth Muscle Actin ◽  
Immunohistochemical Analysis ◽  
Hepatoprotective Activity ◽  
Nuclear Antigen ◽  
Sprague Dawley ◽  
Liver Fibrogenesis

The antifibrotic effects of traditional medicinal herbCaesalpinia sappan(CS) extract on liver fibrosis induced by thioacetamide (TAA) and the expression of transforming growth factorβ1 (TGF-β1),α-smooth muscle actin (αSMA), and proliferating cell nuclear antigen (PCNA) in rats were studied. A computer-aided prediction of antioxidant and hepatoprotective activities was primarily performed with the Prediction Activity Spectra of the Substance (PASS) Program. Liver fibrosis was induced in male Sprague Dawley rats by TAA administration (0.03% w/v) in drinking water for a period of 12 weeks. Rats were divided into seven groups: control, TAA, Silymarin (SY), and CS 300 mg/kg body weight and 100 mg/kg groups. The effect of CS on liver fibrogenesis was determined by Masson’s trichrome staining, immunohistochemical analysis, and western blotting.In vivodetermination of hepatic antioxidant activities, cytochrome P450 2E1 (CYP2E1), and matrix metalloproteinases (MPPS) was employed. CS treatment had significantly increased hepatic antioxidant enzymes activity in the TAA-treated rats. Liver fibrosis was greatly alleviated in rats when treated with CS extract. CS treatment was noted to normalize the expression of TGF-β1,αSMA, PCNA, MMPs, and TIMP1 proteins. PASS-predicted plant activity could efficiently guide in selecting a promising pharmaceutical lead with high accuracy and required antioxidant and hepatoprotective properties.

Serum Cytokeratin 19 Fragment (CYFRA21-1) as a Prognostic Factor in Intrahepatic Cholangiocarcinoma

2007 ◽  
Vol 15 (2) ◽  
pp. 583-589 ◽  
Author(s):  
Takahiro Uenishi ◽  
Osamu Yamazaki ◽  
Hiromu Tanaka ◽  
Shigekazu Takemura ◽  
Takatsugu Yamamoto ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Intrahepatic Cholangiocarcinoma ◽  
Cytokeratin 19 ◽  
Cytokeratin 19 Fragment

scholarly journals Autophagy Plays a Role in the CUL4A-Related Poor Prognosis of Intrahepatic Cholangiocarcinoma

2021 ◽  
Vol 27 ◽  
Author(s):  
Shao-Wen Weng ◽  
Ting-Ting Liu ◽  
Hock-Liew Eng ◽  
Huey-Ling You ◽  
Wan-Ting Huang
Keyword(s):  
Intrahepatic Cholangiocarcinoma ◽  
Poor Prognosis ◽  
Disease Free Survival ◽  
Immunohistochemical Analysis ◽  
Cell Types ◽  
Tumor Stage ◽  
Autophagic Flux ◽  
Bafilomycin A1 ◽  
The Relationship

CUL4A regulate the termination of autophagy in a physical process. However, the relationship between CUL4A and autophagy in cancer is unclear. We retrospectively investigated 99 intrahepatic cholangiocarcinoma (iCCA) cases. Whole sections were used for immunohistochemical analysis for p62, and LC3B expression. Q-score was defined as the sum of the labeling intensity and proportion. The cut-off point for immunoreactivity was set. CUL4A was overexpressed in cell lines and autophagy reflux was compared after manipulation. The iCCA cases with CUL4A overexpression had significantly higher prevalence of intact activated autophagy (42.4 vs. 15.2%; p = 0.003), which was significantly associated with advance tumor stage (34.1% vs. 15.4%; p = 0.032), less extensive necrosis (8.3 vs. 49.3%; p &lt; 0.001), and shortened disease-free survival (mean, 19.6 vs. 65.5 months, p = 0.015). In vitro, iCCA cells with CUL4A overexpression significantly increased LC3II level as compared to the cells under basal condition. Although both cell types showed intact autophagy with increased LC3II expression after bafilomycin A1 treatment, the accumulation of LC3II was higher in CUL4A-overexpressing cells. CUL4A overexpression increased the proliferation of cells as compared with control cells. After treatment with bafilomycin A1, proliferation was inhibited in both cell types, but the effects were more prominent in the cells overexpressing CUL4A. CUL4A promotes autophagy, and exhibits significantly higher autophagic flux which affects the proliferation of iCCA cells; these effects correlated with advance tumor stage and poor prognosis. Thus, targeting autophagy may be potentially therapeutic in iCCA.

Loss of ARID1A induces a stemness gene ALDH1A1 expression with histone acetylation in the malignant subtype of cholangiocarcinoma

2019 ◽  
Vol 41 (6) ◽  
pp. 734-742 ◽  
Author(s):  
Jun Yoshino ◽  
Yoshimitsu Akiyama ◽  
Shu Shimada ◽  
Toshiro Ogura ◽  
Kosuke Ogawa ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Intrahepatic Cholangiocarcinoma ◽  
Promoter Region ◽  
Inverse Correlation ◽  
Immunohistochemical Analysis ◽  
Independent Prognostic Factor ◽  
Histone Deacetylase 1 ◽  
Histone H3k27 ◽  
Cholangiocarcinoma Cell ◽  
Frequent Mutations

Abstract Genomic analyses have recently discovered the malignant subtype of human intrahepatic cholangiocarcinoma (ICC) characterized by frequent mutations of chromatin remodeling gene ARID1A; however, the biological and molecular functions still remain obscure. We here examined the clinical and biological significances of ARID1A deficiency in human ICC. Immunohistochemical analysis demonstrated that the loss of ARID1A was an independent prognostic factor for overall survival of ICC patients (P = 0.023). We established ARID1A-knockout (KO) cells by using the CRISPR/Cas9 system from two human cholangiocarcinoma cell lines. ARID1A-KO cells exhibited significantly enhanced migration, invasion, and sphere formation activity. Microarray analysis revealed that ALDH1A1, a stemness gene, was the most significantly elevated genes in ARID1A-KO cells. In addition, ALDH enzymatic activity as a hallmark of cancer stem cells was markedly high in the KO cells. ARID1A and histone deacetylase 1 were directly recruited to the ALDH1A1 promoter region in cholangiocarcinoma cells with undetectable ALDH1A1 expression by chromatin immunoprecipitation assay. The histone H3K27 acetylation level at the ALDH1A1 promoter region was increased in cells when ARID1A was disrupted (P &lt; 0.01). Clinically, inverse correlation between ARID1A and ALDH1A1 expression was also identified in primary ICC (P = 0.018), and ARID1A-negative and ALDH1A1-positve ICCs showed worse prognosis than only ARID1A-negative cases (P = 0.002). In conclusion, ARID1A may function as a tumor suppressor in ICC through transcriptional downregulation of ALDH1A1 expression with decreasing histone H3K27 acetylation. Our studies provide the basis for the development of new epigenetic approaches to ARID1A-negative ICC. Immunohistochemical loss of ARID1A is an independent prognostic factor in intrahepatic cholangiocarcinoma patients. ARID1A recruits HDAC1 to the promoter region of ALDH1A1, a stemness gene, and epigenetically suppresses ALDH1A1 expression with decreasing histone H3K27 acetylation in cholangiocarcinoma cells.

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