ABSTRACT
Objective To investigate the expressions of Hedgehog sisnaling pathway genes in hepatocellular carcinoma tissues(HCC),and the effect of specific Hedgehog pathway inhibitor(KAADcyclopamine)on the growth of HCC cells and the expressions of Hedgehog genes. Methods The expression of Hedgehog signaling pathway components(Ihh,Ptch,Smo and Gli)was investigated in 14 HCC tissue slices,4 HCC cell lines and a normal hepatic cell line by using immunochemistry.The expression of Ihh,Ptch,Smo and Gli proteins was investigated in 9 HCC tissue specimens and 6 normal hepatic tissue specimens by using Western blotting.The expression of Ihh、Ptch、Smo、Gli and Hip genes was investigated by RT-PCR.Results The positive ratio of Gli,Ptch,Ihh and Smo were 42.9%,71.4%,71.4% and 85.7% in 14 HCC tissue slices,respectively.The expressions of Gli protein and Gii gene were up regulated while the expression of Hip gene was down regulated in HCC specimens compared with normal hepatic tissue specimens.Hedgehog signaling pathways in HCC cell lines HepG2,Bel-7402 and QGY-7701 were activated;KAAD-cyclopamine,a specific inhibitor of the Hedgehog signaling pathway,down regulated cell growth and the expressions of Ptch and Gli genes in the 3 HCC cell lines(Ptch gene:tHepG2=3.78,tBel-7402=9.03,tQGY-7701=5.63;Gli gene:tHepG2=9.61,tBel-7402=4.15,tQGY-7701=20.30,P＜0.05 in each group).The expression of Hip gene was up regulated in QGY-7701 after treated with KAAD-cyclopamine(t=4.70,P＜0.05).Conclusion The expression of main Hedgehog signaling pathway components were detected in HCC,KAAD-cyclopamine specifically inhibited the Hedgehog signaling pathway.
ABSTRACT
Objective To investigate the surgical measures for relieving biliary malignancies that occur in bile duct cysts (BDCs). Methods Twenty four cases of biliary carcinoma occurring in BDCs treated in our Department from October 1965 to June 1999 were reviewed. Results Of the patients, 5 were male and 19 female. The average age at the time of being diagnosed was 38. Nine patients had undergone cystoenterostomy before. The mean duration between operation of drainage and detection of carcinoma was 10 years. Operations included excision of the extrahepatic bile duct plus pancreatoduodenectomy in 5, excision of extrahepatic bile duct in 6, and various palliative procedures because of extensive spread of tumor in 13. Follow up data were obtained in all but 2 patients who died in hospital. The mean survival time for the 16 death cases after discharge was 11 months. Four patients have been alive and free from disease for 12, 7, 6.5 and 0.5 years, respectively. Conclusions 1) Early diagnosis and curative resection for the biliary carcinoma in BDCs are the key points to achieve better outcomes. 2) Prophylactic excision of cyst in adults with BDCs, especially those previously treated with cystoenterostomy, can effectively reduce the risk of malignant changes.
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Objective To investigate the correlation between VEGF-C and COX-2 expression in human rectal cancers and its significance in cancer metastasis. Methods VEGF-C expression was detected with Western blot in LOVO cells treated with NS-398 or PGE2. VEGF-C and COX-2 expression in 45 rectal adenocarcinomas was tested with immunohistochemistry. Results NS-398 inhibited the VEGF-C expression, and PGE2 up-regulated the expression of VEGF-C in a dosage-dependent way in LOVO cells. VEGF-C expression was significantly higher in adenocarcinomas with lymph node metastasis, and was related with the expression of COX-2 in 45 rectal adenocarcinomas. Conclusion COX-2 up-regulates VEGF-C and VEGF-C plays an important role in lymphatic metastasis of rectal cancers.