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.
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.
【Abstract】ObjectiveTo study the effect of transfection with antisense DNMT3b gene eukaryotic expression vector on the expression of DNMT3b gene in human cholangiocarcinoma cell line QBC-939. MethodsThe constructed antisense DNMT3b gene eukaryotic expression vector was transfected into the human cholangiocarcinoma cell line QBC-939 by using lipofectamine transfection reagents, and positive cell clones were obtained by using G418 selection after transfection. Whether the constructed recombinant vector was transfected into QBC-939 cells successfully was confirmed by amplifying the exogenous neoR gene with PCR method. The expression of DNMT3b gene mRNA and protein were detected by semi-quantitative RT-PCR and FCM methods respectively. ResultsFollowing the transfection of antisense DNMT3b gene eukaryotic expression vector, the mRNA level of DNMT3b gene in QBC-939 cells of human cholangiocarcinoma decreased from 0.956±0.053 to 0.209±0.023, and the protein level of DNMT3b gene also decreased from (75.38±3.22)% to (29.87±3.46)%. There were very significant differences on the expression levels of DNMT3b gene between non-tranfections group and the antisense DNMT3b gene eukaryotic expression vector transfection group (P＜0.01). ConclusionTransfection with antisense DNMT3b gene eukaryotic expression vector significantly reduces the expression level of DNMT3b gene in human cholangiocarcinoma cell line QBC-939, and this study may provide a valid tool and method to investigate the function of DNMT3b gene and its role in cholangiocarcinoma.
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.
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.
Objective To evaluate the expression of γ-synuclein protein （SNCG） in carcinoma of bile duct andnormal bile duct tissues， and its clinical significance. Methods The expressions of SNCG were detected by SP immuno-histochemical in 60 cases of cholangiocarcinoma and 34 cases of normal bile duct tissues， and to analysis its relationship with the clinical pathological characteristics of cholangiocarcinoma. Results The positive expression rate of SNCG in carcinoma of bile duct tissues was 73.33% （44/60）， which was higher than that in normal bile duct tissues （P＜0.01）. The positive expression of SNCG in carcinoma of bile duct tissues was correlated with the depth of tumor invasion and lymph node metastasis （P＜0.01）， but not related to patients’ age， gender， and the degree of tumor differentiation （P＞0.05）. Conclusions The expression of SNCG is correlated with the cholangiocarcinoma occurrence， development， invasion， and metastasis. SNCG plays an important role in the infiltration and metastasis of carcinoma of bile duct. SNCG is expected to become a new cancer tumor marker， which can provide a basis to prognosize and to formulate the corres-ponding therapy plan.
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.
Objective To obtain the full-length gene and functional domains of FXYD6 gene which is a cholangiocarcinoma related gene. Methods A new strategy with the integration of bioinformatics and molecular biology was used. Bioinformatical methods were used to analyze the full-length sequence, and to predict the functional domains of its protein. And the full-length sequence of FXYD6 was isolated by polymerase chain reaction from fetal hepatic, brain and spleen cDNA libraries, and then cloned in pGEM-T vector for sequence analyzing. Goldkey Sequence Analyzing Software was used to analyze the sequence of candidate domain without signal peptide.Results The full-length sequence of FXYD6 was isolated by Touch-down PCR from fetal hepatic and brain cDNA library, but was not from spleen cDNA library. The open reading frame Finder software was used in the National Center for Biotechnology Information website to find the most probable encoding regions of FXYD6 gene. And the +1 phase was selected as the template sequence, from 67 bp to 354 bp, to predict the functional domains by Goldkey Sequence Analyzing Software. The signal peptide was located from 1 amino acid (aa) to 17 aa， and the main domain was composed from 18 aa to 34 aa. The region between 35 aa and 57 aa was the transmembrane region. The FHYD peptide chain was highly conserved amino acids. Conclusion The study of full-length cDNA cloning of FXYD6 gene and its functional domains provides the basis for understanding the relationship between the structure and function of FXYD6. More work shall be performed on FXYD6 protein and its influence on the mechanism of 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.