ObjectiveTo investigate the expressions of Patched-1 (Ptch1) and glioma-associated oncogene homologl (Gli1) protein of sonic hedgehog signaling pathway in cholangiocarcinoma tissues, and explore their correlations to the occurrence and development of cholangiocarcinoma. MethodsThe expressions of Ptch1 and Gli1 protein in 62 specimens of cholangiocarcinoma and its bile duct tissues adjacent to cancer were detected by immunohistochemistry, and their positive rate correlated with patients, age, tumor size, differentiation grade, tumor location, lymph node metastasis, TNM stage, operation mode, and postoperative survival time were investigated by statistical analysis. ResultsThe positive rates of Ptch1 and Gli1 protein were significantly higher in cholangiocarcinoma than in tissues adjacent to cancer (74.2% vs. 14.5%, 88.7% vs. 9.7%, P < 0.05). The expressions of Ptch1 and Gli1 protein in cholangiocarcinoma had no correlation to patients age, tumor size, and tumor location (P > 0.05), but were correlated to the operation mode, differentiation grade, lymph node metastasis, TNM stage, and postoperative survival time of patients (P < 0.05). ConclusionsThe elevated expressions of Ptch1 and Gli1 protein of Hh signaling pathway participated in the occurrence and development of cholangiocarcinoma. They may be ideal targets for therapy against cholangiocarcinoma.
ObjectiveTo explore the clinical significance of promoter hypermethylation of O6-methylguanine-DNA methyltransferase (MGMT) in cholangiocarcinoma. MethodsPromoter methylation status of MGMT gene and expression of MGMT protein were detected in cholangiocarcinoma by methylationspecific PCR and immunohistochemical staining, respectively. ResultsAberrant methylation of MGMT gene was detected in 17 patients (47.2%). Twentyone cases showed negative immunoreactivities. Of 21 patients with negative MGMT expression, 14 patients had aberrant methylation of MGMT gene. In 15 patients with positive MGMT expression, aberrant methylation of MGMT gene was only found in three cases. There was a negative correlation between promoter methylation status of MGMT gene and the expression of MGMT protein (rs=-0.816, Plt;0.05). Promoter methylation status of MGMT gene was related to depth of invasion, degree of differentiation, and TNM stage (Plt;0.05), but not to age of patient, gender, pathological type, and lymph node metastasis (Pgt;0.05). ConclusionsHypermethylation of MGMT promoter is a frequency molecular event in cholangiocarcinoma and may be involved in carcinogenesis. Methylation status of MGMT gene may be used to evaluate malignant degree of cholangiocarcinoma.
Partial or complete blockage of the bile outflow tract by extrahepatic cholangiocarcinoma often leads to jaundice, which not only causes skin itching in patients, but also destroys the body environment through a series of pathophysiological processes, reduces the surgical tolerance of patients with resectable tumors, and affects the prognosis. Preoperative jaundice reduction can reduce jaundice and relieve biliary obstruction, but the various complications that follow will also adversely affect the treatment. This article elaborates on the disadvantages of different methods for jaundice reduction, the indications for preoperative jaundice reduction, the jaundice reduction options for different types of extrahepatic cholangiocarcinoma, the complications and treatment methods of preoperative jaundice reduction for extrahepatic cholangiocarcinoma, aiming to provide a reference for clinicians, so that patients can better benefit from preoperative jaundice reduction.
In this series of 34 cases, 2 patients performed hepatic dect-jejunal anatomosis, 9 were PTCD external drainage, 8 were installation of internal drainage tubes through the PTCD, 9 were laparotories, 3 were cheemotherapeutic perfusison through artery and 3 were untreated. According to the follow-up results, the authors recommend that the internal drainage through PTCD is the better method to treat unresectable carcinoma of bile duct for proper patients.
ObjectiveRecent advancements in the researches on cholangiocarcinoma (CC) related genes methylation in CC were reviewed and the clinical significances of aberrant DNA methylation for the diagnosis and treatment of CC were discussed. MethodsRelevant literatures about the relation between CC-related genes methylation and CC published recently were collected and reviewed. ResultsThe genesis of CC resulted from abnormal expressions of many genes. Many researches had shown that the abnormal methylation of CC-related genes had a close relation with CC. Epigenetic alteration had been acknowledged as an important mechanism contributing to early CC carcinogenesis. ConclusionsAbnormal methylation of CC-related genes is related with CC. The detection of CC-related genes methylation might provide new specific biomarkers for early noninvasive diagnosis of this disease. Using epigenetic agents such as azacytidine to modulate the activities of DNA methyltransferase and reverse the methylation status of CC-related gene might be an attractive strategy for future treatment of CC, which could be combined with conventional therapies.
Objective To investigate the roles of NF-κB and EGFR in hepatolithiasis associated with intrahepatic cholangiocarcinoma. Methods Ninety cases of liver tissue specimens from hepatectomies performed in the 2nd Affiliated Hospital of Sun Yat-sen University between August 1989 and June 2009 were enrolled in the study. Among them, 33 cases of hepatolithiasis associated with intrahepatic cholangiocarcinoma were considered as observing group, 32 cases of hepatolithiasis as control group, and 25 cases of normal bile duct tissues as normal control group. The SP method of immunohistochemical staining was applied to detect the expressions of NF-κB and EGFR in intrahepatic biliary ducts epithelial cells, and their relations with clinicopathologic factors and the accumulated survival rate of hepatolithiasis associated with intrahepatic cholangiocarcinoma were analyzed. Results Expression rates of NF-κB and EGFR were gradually raised from normal control group, control group to observing group (Plt;0.01). Expression of EGFR in tumor patients was related to histopathologic differentiation grading and the depth of tumor invasion (Plt;0.05), but not to gender, age, or lymph node metastasis (Pgt;0.05)； there were no significant relationships between the expression of NF-κB and factors described above (Pgt;0.05). The survival rate of patients with tumor expressed EGFR was significantly lower than that of patients with tumor non-expressed EGFR (Plt;0.01). Conclusions NF-κB expression is in the early stage during intrahepatic cholangiocarcinoma genesis. NF-κB and EGFR play cooperating roles during hepatolithiasis carcinogenesis process. Over expression of EGFR is related with poor differentiation and prognosis of tumor.
Nucleus plasma ratio was measured and silver-binding nucleolar organizer (AgNORs) were counted in 31 cases of cholangiocarinoma (11 cases were well-differentiated, 10 case moderately differentiated and 10 cases poorly differentiated) and in 17 cases of atypical epithelial hyperplasia related to hepatolithiasis (9 cases were simple hyperplasia, 8 cases atypical epithelial hyperplasia) by AgNORs techique and image analysis.The results showed that mucleus plasma ratio and AgNORs counts increased significantly from well-differentiated to poorly differentiated cholangiocarcinoma (Ｐ＜0.01). No statistically significant differance was shown between nucleus plasma ratio of atypical hyperplasia and well-differentiated cholangiocarinoma.The data imply that chronic proliferative cholngitis in the presence of hepatolithiasis can progress to atypical epithelial hyperplasia which may be an important precursor of cholangiocarcinoma.
ObjectiveTo understand the research advance of photodynamic therapy (PDT) on cholangiocarcinoma. MethodDomestic and international publications online which involving the research of PDT on cholangiocarcinoma in recent years were reviewed. Results①PDT was a new therapy on tumor from the tissue and cell level, which could destroy the target tissue and cell under the photochemical reaction and kill the tumor cell according to the characteristics of the selective intake of tumor tissue on particular photosensitizer. It could mainly induce tumor cell apoptosis and necrosis, destroy the tumor microvascular, stimulate the immune and inflammatory response.②PDT on the research level of the treatment of cholangiocarcinoma had achieved fairly good curative effects, which could make the tumor shrinkage, reduce the harm to normal bile duct cell, and prolong the survival, improve the survival rate and the quality of life.③Proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor-C (VEGF-C), and cyclooxygenase-2 (COX-2) played important roles in the development of cholangiocarcinoma. PDT could inhibit the expressions of PCNA, VEGF-C, and COX-2, and then could promote cell apoptosis, and then inhibit cell proliferation. ConclusionsPDT is a new technology in treatment of malignant tumor, which whether used alone or combined with other methods has less adverse reaction and could obviously improve the local symptoms in treatment of cholangiocarcinoma. But many problems about PDT need to be solved at present, in the base areas, such as research and development of new photosensitizer and precise mechanism of killing tumor, in the clinical applications, such as selection and application of photosensitizer, ways and parameters of the laser, formulation of treatment plans and the reduction of the complications.
Objective To validate the different expressions of human fxyd6 gene between normal bile duct tissues and malignant tumor tissues, and to observe the subcellular localization of human fxyd6 gene in human cholangiocarcinoma cells. MethodsThe different expressions between normal bile duct tissues and malignant tumor tissues were identified by RT-PCR. In situ polymerase chain reaction （IS-RT-PCR） was applied to detect the subcellular localization of fxyd6 gene in paraffin sections of human cholangiocarcinoma cells. Image analysis software was used to semiquantitatively determine the difference between normal and malignant tissues. ResultsHuman fxyd6 gene was highly expressed in cholangiocarcinoma tissues and lowly expressed in normal ones. There was a significant difference between the expressions of carcinoma cells and normal cells （P＜0.05）. IS-RT-PCR showed that fxyd6 gene localized in the kytoplasma of epithelial cells of human cholangiocarcinoma. ConclusionHuman fxyd6 gene may act as an essential component of the malignant transformation process in human cholangiocarcinoma.
ObjectiveTo study the relationship between the expression of sialyl Lewisx (SLeX) antigen and CD44v6 products and biological behaviors in cholangiocarcinomas. MethodsThe expression of SLeX and CD44v6 in 43 cases of cholangiocarcinoma tissue was respectively investigated by catalyzed signal amplification immunohistochemical technique.The relationship between expression of SLeX and CD44v6 and the clinicopathological factors of cholangiocarcinoma was analyzed.ResultsThe positive expression rate of SLeX and CD44v6 in cholangiocarcinoma was 67.4% and 62.8% respectively,which was significantly higher than that in control group (20.0%,P＜0.05).The high level expression of SLeX and CD44v6 were correlated with the TNM phase, differentiation degree,metastasis to lymph nodes and viscera in cholangiocarcinoma (P＜0.05). Moreover,there was a positive correlation between the SLeX and CD44v6 expression in cholangiocarcinoma (r=0.49,P＜0.001).Conclusion Expression of SLeX and CD44v6 could be helpful in predicting the biological behavior and prognosis of cholangiocarcinoma.