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.
【Abstract】ObjectiveTo investigate the effects of nimesulide, a selective cyclooxygenase-2 (COX-2) inhibitor, on human cholangiocarcinoma QBC939 cell line in vitro. MethodsThe effects of nimesulide on QBC939 cells were observed with the following techniques: the influence of nimesulide on the proliferation of QBC939 cells was determined by MTT assay; the apoptosis of QBC939 cells was viewed and measured by transmission electron microscopy and flow cytometry, respectively; the expressions of proliferation cell nuclear antigen (PCNA) and COX-2 of cholangiocarcinoma cells were detected by immunocytochemistry. ResultsNimesulide inhibited the expressions of PCNA and COX-2 and the proliferation of cholangiocarcinoma QBC939 cells, whose effects intensified as the dose increased and time elongated. Flow cytometry showed that the apoptotic rates of QBC939 cells increased significantly as the dose of nimesulide increased. The typical morphologic features of apoptosis were also observed by transmission electron microscopy. ConclusionNimesulide significantly inhibits the proliferation of QBC939 cells in vitro by inducting cell apoptosis, which may be associated with the downregulation of COX-2 expression, and it also presents the features of dose and time dependents.
【Abstract】Objective To study the antitumor activity of HSVtk/CD combinative gene toward human cholangiocarcinoma in vivo. Methods Nude mouse models with transplanted subcutaneous cholangiocarcinoma were constructed and divided into 4 groups randomly, each group had 8 mice. Adenovirus solution free from suicide gene was injected in subcutaneous tumors of each mouse of control group. Adenovirus solution containing cytosine deaminase (CD), thymidine kinase (tk) and HSVtk/CD fusional gene were injected into single suicide gene either HSVtk or CD was transinfected into the tumor cells by injecting viras into subcutaneous tumor of mice of CD gene,tk gene and fused CD and tk gene group respectively. 24 hours after the injection, 5fluorocytosine (5FC) and ganciclovir (GCV) were injected introabdominally in each mouse. Growth of the tumors were monitored.Results Tumor growth of the genetransfection groups was suppressed in different degrees. Compared with the control group, the suppressing rates of the genetransfection groups were 41.2%, 55.7% and 70.0% respectively (P＜0.05). Histological examination showed good tumor growth in the control group, and tumor necrosis in the other 3 groups, particularly obvious in the group transfected with pAd(HSVtk/CD).Conclusion Combinative gene system has a b antitumor effect on cholangiocarcinoma in vivo. But it’s not powerful enough to eliminate tumor thoroughly because of insufficient “Bystander effect”.
Objective To investigate the expression of caspase-3 in xenograft that was treated with targeted therapy with magnetic nanoparticles in nude mice. Methods QBC939 cell lines were injected into nude mice subcutaneously to establish the model of human cholangiocarcinoma xenograft. After two weeks of tumor inoculation, the animal models were divided randomly into 4 groups: group A received placebo (sodium chloride), group B were treated with magnetic nanoparticles (250 mg/kg), group C were treated with magnetic nanoparticles (150 mg /kg) combined with inner-stent, group D with magnetic nanoparticles (250 mg /kg) combined with inner-stent (the inner-stent was used to generate the magnetic targeting effect). The 21th day after treatment, expression of caspase-3 in tumor cells of each groups were measured with histochemical method and RT-PCR. Results The quantity of caspase-3 in tumor cells that were treated with magnetic nanoparticles (250 mg/kg) combined with inner-stent was the most (P＜0.05), and the quantity of caspase-3 in cells of group C was significantly more than that of the other two groups (P＜0.05). While the quantity of caspase-3 in group B was more than that of the control group(P＜0.05). Conclusion The use of magnetic nanoparticles combined with inner-stent may increase the expression of caspase-3, and the expression is dose-dependent with magnetic nanoparticles.
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.
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.
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.
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.
ObjectiveTo establish a predictive model for survival and study it’s clinical value by reviewing the information of patients with hilar cholangiocarcinoma. MethodsMedical record of 196 patients with hilar cholangiocarcinoma were analyzed retrospectively. Seventeen possible clinicopathologic factors were selected. Cox model was used for univariate and multivariate analysis. Prognostic index (PI) was calculated based on the results of multivariate analysis. Patients with different PI were divided into three different risk level groups in order to compare the survival rate. Individual expected survival rate was calculated based on the median PI. Log cumulative hazards function plot was used to test Cox model proportional hazards assumption (PH assumption). ResultsThe significant prognostic factors influencing the survival rate were surgical procedure, surgical margin, and preoperative total bilirubin level (Plt;0.05). The predictive formula was PI=0.815×preoperative total bilirubin level+0.580×surgical margin－0.713×surgical procedure. According to the value of PI, all patients were divided into 3 groups, low risk group (PI≤－0.642), middle risk group (－0.642lt;PIlt;1.364), high risk group (PI≥1.364), and survival rate declined between groups and in groups with statistically significant difference (Plt;0.05). ConclusionThis model for survival can predict the prognosis of patients with hilar cholangiocarcinoma individually and help to conduct individual clinical therapy.
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.