ABSTRACT
Objective To investigate the clinicopathological characteristics and prognostic factors of hepatolithiasis associated with intrahepatic cholangiocarcinoma (HLAIHCC).Method A ret rospective study was conducted on 36 patients who suffered from histopathologically confirmed HLAIHCC.These patients received surgical resection of the tumor from June 2006 to September 2009.Results The overall 1,3,5 year survival rates for patients with HLAIHCC were not significantly better than those patients with ICC (63.6％,36.4％,and 30.3i％ vs.65.4％,34.3％,and 28.6％,P=0.57).For the patients who received curative resection,the 1-,3-,and 5-year survival rates (81.4 ％,61.7 ％,and 58.6 ％) were significantly better than those who received palliative resections (x2 =20.426,P＜0.001).The white blood cell count was significantly higher in the HLAIHCC group than in the ICC group (x2 =19.70,P＜0.001) and tumor size was significantly smaller in the ICC group than in the HLAIHCC group (P=0.04).Serum CA19-9 level (P=0.049) and resection margin (P=0.019) were independent risk factors of prognosis.Conclusions This study showed HLAIHCC to have different clinicopathological characteristics from ICC.Curative resection was the optimal surgical treatment for HLAIHCC.Serum CA19-9 level and resection margin were independent risk factors of prognosis.
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Objective To investigate the role and mechanism of low-dose aspirin concurrent with IFN-a in inducing hepatocellular carcinoma apoptosis in BEL-7402 cells. Methods BEL-7402 cells were cultured and treated with IFN-α,or low dose aspirin or both.MTT and flow cytometry were used to measure the cell proliferation and apoptosis after treatment with a singular drug or the combined regiment.The expressions of the apoptosis-related proteins were detected by Western blot.Results MTT assay revealed after IFN α administration alone or combined with aspirin treatment for 48 h,the proliferation ratio of the IFN-α or aspirin group were 82.45％ ± 1.71％ and 83.22％ ±2.26 ％,compared with the control group.The group which received the combined therapy had a proliferation ratio of 69.84 ％ ±1.18 ％,which was significantly lower than the single groups (P＜0.05).The flow cytometry revealed that the apoptosis ratio in IFN-α group and aspirin group were 14.78 ％ ±1.93％ and 14.00％±0.61％,respectively,while the IFN-α + aspirin group was 21.68％±1.28％,which was also significantly higher than that of the single groups (P＜0.05).Western blot detected that IFN-α and aspirin (1 mmol/L) could promote caspase-3 and caspase-9 protein expressions,and when the two drugs were combined,caspase-3 and caspase-9 were also significantly activated.IFN-α alone or combined with aspirin can promote the expression of pro-apoptotic protein Bax (P＜0.05),while the anti-apoptotic proteins expression of Bcl-2 and Bcl-xl did not change significantly (P＞0.05).Conclusions Low-dose aspirin can cooperate with IFN-α in inhibiting the BEL-7402 cell growth and inducing the cell apoptosis by activating and increasing caspase-3 and caspase-9 levels,which may be related to the increased expression of pro-apoptotic protein Bax.
ABSTRACT
ObjectiveTo study the role and mechanism of low-dose aspirin with IFN-α in inhibiting growth and metastasis of hepatocellular carcinoma (HCC).MethodsMHCC97L cells were cultured and a metastatic model of human HCC was established by orthotopic implantation of histologically intact human HCC tissue into the liver of nude (nu/nu) mice.After administration of different doses of Aspirin and IFN-α for 40 days,the mice bearing xenografts in liver were killed,and the tumor volume and lung metastasis were evaluated.Cell proliferation and MMP-2 activity were measured by MTT and gelatin zymography,respectively.The expressions of VEGF and MMP-2 were measured by western blot and ELISA.ResultsCompared to the control group,there were no significant differences in the high-dose Aspirin [45 mg/(kg · d)] treated group regarding tumor volume [(1.89 ±0.88) cm3 vs (3.12±0.85) cm3,P＞0.05] and incidence of lung metastases (58.3％ vs 66.7％,P＞0.05),but the tumor volume and incidence of lung metastasis were significantly inhibited in the highdose IFN-α group [1.5 × 107/(kg · d)],the high-dose IFN-α combined with high-dose Aspirin group,and the low-dose IFN-α [7.5 × 106 / (kg · d) ] combined with low-dose Aspirin [15 mg/(kg · d] group (P＜0.05).2 mmol/L Aspirin did not inhibit the proliferation of MHCC97 cells (P＞0.05),but inhibited the activities and expressions of MMP-2 and VEGF.Low-dose IFN-α combined with low-dose Aspirin significantly decreased the expressions of MMP-2 and VEGF in nude mice (P＜0.05).ConclusionLow-dose Aspirin combined with low-dose IFN-α significantly inhibited the growth and metastasis of HCC through suppressing the expressions of MMP-2 and VEGF.