Silencing of CXCR4 Inhibits Tumor Cell Proliferation and Neural Invasion in Human Hilar Cholangiocarcinoma

BACKGROUND/AIMS: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. METHODS: An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. RESULTS: The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. CONCLUSIONS: CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.

A Disintegrin and Metalloprotease with Thrombospondin Motif 2 May Contribute to Cirrhosis in Humans through the Transforming Growth Factor-beta/SMAD Pathway

BACKGROUND/AIMS: We aimed to investigate the correlation between a disintegrin and metalloprotease with thrombospondin motif 2 (ADAMTS-2) and transforming growth factor-beta1 (TGF-beta1) in clinical human cirrhotic tissues. METHODS: The liver tissues of 24 patients (16 cases with cirrhotic portal hypertension as the cirrhosis group and eight cases with healthy livers as the normal group) were collected. Immunohistochemistry and Western blots were performed to evaluate the protein expression levels of ADAMTS-2 and TGF-beta1. Western blots for other key mediators of cirrhotic progression, including SMAD2, SMAD3, TGF-beta receptor II (TGFbetaRII), matrix metalloproteinases 2 (MMP2), and tissue inhibitor of matrix metalloproteinases 2 (TIMP2), were also performed. RESULTS: Cirrhotic tissues showed higher percentages of collagen. The protein expression levels of ADAMTS-2 and TGF-beta1 were significantly higher in the cirrhotic group as compared to the matched normal group (p<0.05), and there was a positive correlation between these two proteins (r=0.862, p<0.01). The protein expressions of MMP2, TIMP2, and TGFbetaRII, as well as the phosphorylated forms of SMAD2 and SMAD3, were significant higher in the cirrhotic group (p<0.01 or p<0.05). CONCLUSIONS: These findings suggested that ADAMTS-2 and TGF-beta1 may play important roles in the pathogenesis of human cirrhosis; specifically, TGF-beta1 may induce the expression of ADAMTS-2 through the TGFbeta/SMAD pathway.

Expression of Ang2 and Tie2 and their relation with the angiogenesis of hepatocellular carcinoma in rats / 中南大学学报(医学版)

OBJECTIVE@#To investigate the relationship between the expression of Ang2, Tie2 and the angiogenesis of hepatocellular carcinoma in rats.@*METHODS@#Thirty-eight healthy male rats were randomly divided into 3 groups: 5 rats in the control group; 25 rats in the experimental group were equally divided into 5-day, 10-day, 15-day, 20-day, and 25-day groups; the other 8 rats were used as the supplement of the experimental group. An allogenic transplanted rat model of CBRH-7919 hepatocellular carcinoma in situ was established by immunosuppression. The expressions of Ang2 and Tie2 were detected by immunohistochemical staining in cancerous tissues of different developmental stages and liver tissues of the control group. At the same time, microvessel density was determined by anti-CD31 immunohistochemical staining.@*RESULTS@#CBRH-7919 hepatocellular carcinoma models were successfully set up in 24 rats. The expression level of Ang2 and Tie2 in cancerous tissues was much higher than that of liver tissues of the control group (P <0.05). The overexpression of Ang2 was pristine and continuous in different developmental stages. The expressions of Ang2 and Tie2 positively correlated with microvessal density in hepatocellular carcinoma (P<0.05).@*CONCLUSION@#The up-regulation of Ang2 and Tie2 may play important roles in the angiogenesis of hepatocellular carcinoma. Ang2 may participate in the start of angiogenesis of hepatocellular carcinoma.

Surgical treatment of 2465 primary hepatolithiasis cases / 中华外科杂志

<p><b>OBJECTIVE</b>To summarize the experience of surgical treatment of primary hepatolithiasis.</p><p><b>METHODS</b>To analyze the clinical data, operation choice, postoperative complications of 2465 cases of primary hepatolithiasis retrospectively.</p><p><b>RESULTS</b>Of the patients, 2034 received external drainage (82.5%) and 431 received internal drainage (17.5%) and 586 were performed adjunctive partial hepatectomy (23.8%). The postoperative complications were found in 211 cases (8.6%) and 17 cases (0.7%) died after the operation. One thousand seven hundred and sixty-seven cases (71.7%) have been followed up for 2 to 25 years, among them therapeutic effect of 1518 cases (85.9%) was excellent or good, 315 cases (17.8%) had residual stone and 115 cases (6.5%) recurred.</p><p><b>CONCLUSIONS</b>It could decrease the incidence rate of complications, residual stone and recurrence in the patients with hepatolithiasis after surgical therapy to pinpoint the situs of the lithiasis and biliary stricture and managed properly before the surgery.</p>

Effect of Bcl-2 antisense phosphorothioate oligodeoxynucleotides on bile duct carcinoma cell line QBC939 / 中南大学学报(医学版)

OBJECTIVE@#To investigate the effect of Bcl-2 antisense oligodeoxynucleotides (ASODN) on the cell proliferation and Bcl-2 expression in bile duct carcinoma cell line QBC939.@*METHODS@#Bcl-2 ASODN and control sequence were transfected into cell line QBC939 by Lipofectamine 2000. The changes of Bcl-2 protein were detected by Western blot. The survival rate and colony formation rate of QBC939 cells incubating with Bcl-2 ASODN were evaluated by trypan blue staining assay and colony forming test.@*RESULTS@#The densitometric analysis of Gel-photograph showed that the level of Bcl-2 protein expression in the ASODN transfected group was significantly lower than that in the controls (P < 0.01). Both trypan blue staining assay and colony forming test demonstrated that Bcl-2 ASODN could partially inhibit the growth of QBC939 cells. After incubating with Bcl-2 ASODN, the survival rate and colony formation rate of QBC939 cells were significantly lower than those of the controls (P < 0.05).@*CONCLUSION@#Bcl-2 ASODN inhibits the cell proliferation in bile duct carcinoma cell line QBC939 by blocking the expression of bcl-2 gene.