ABSTRACT
Objective To investigate the effects of sorafenib combined with dendritic cells and cytokine induced killer (DC-CIK) cells on the growth,invasion and metastasis of hepatocellular carcinoma.Methods CIK cells and dendritic cells from healthy adults were cultured in vitro.Mice models with H22 hepatic cancer were established,and randomly divided into the normal saline group,sorafenib group,DC-CIK group and the sorafenib + DC-CIK group according to the random number table.There were 40 rats in each group.All the mice received intragastric gavage with sorafenib of 100 μg/g once a day.DC-CIK cells were intraperitoneally injected into the mice every 3 days with 1 × 107 cells each time.Twenty mice bearing tumors in each group were sacrificed after treatment for 3 weeks,and the peripheral venous blood and hepatic tumor tissues were harvested.The levels of alphafetoprotein (AFP) were detected by ELISA,and the necrotic degree of tumor tissues was evaluated by hematoxylin and eosin staining.The protein expressions of Ki-67 and CD34 in the tumor tissues were determined by immunohistochemical method.The survival time of the other 20 mice bearing the tumor in each group were detected.All data were analyzed using the analysis of variance or LSD test.Results CIK cells and dendritic cells were successfully cultured.The levels of AFP in the peripheral venous blood of the normal saline group,sorafenib group,DC-CIK group and sorafenib + DC-CIK group were (0.675 ± 0.177) rg/L,(0.379 ± 0.052) ng/L,(0.415 ± 0.028) ng/L,(0.288 ± 0.012) ng/L,with significant difference between the 4 groups (F =0.415,P ＜ 0.05).The numbers of intrahepatic and peritoneal metastasis of the normal saline group,sorafenib group,DC-CIK group and sorafenib + DC-CIK group were 21.2 ± 1.3 and 29.7 ± 7.6,16.4 ± 1.6 and 17.4 ± 1.8,20.2 ± 1.7 and 26.4 ± 1.7,15.2 ± 1.3 and 15.2 ± 1.3,with significant difference between the 4 groups (F =2.137,3.271,P ＜0.05).The tumor inhibition rate of the normal saline group,sorafenib group,DC-CIK group and sorafenib + DC-CIK group were 0,21％ ± 3％,9％ ± 3％ and 24％ ± 5％,with significant difference between the 4 groups (F =3.715,P ＜0.05).The survival time of mice in the normal saline group,sorafenib group,DC-CIK group and sorafenib ± DC-CIK group were (18.2 ± 2.5) days,(21.6 ± 2.1) days,(24.3 ± 2.8) days and (25.4 ± 1.4) days,with significant difference between the 4 groups (F =6.247,P ＜ 0.05).Conclusions Sorafenib combined with immunotherapy can significantly increase the therapeutic effects of molecular targeted drug on hepatocellular carcinoma.
ABSTRACT
Objective To investigate the auxiliary effects of huaier granule on hepatoeellular carcinoma (HCC)patients after liver transplantation.Methods Sixty HCC patients who had undergone liver transplantation from Julv 2004 to June 2006 and met the standard of UCSF were involved in this study.All patients were divided into huaier granule group(n=20),chemotherapy group(n=15),huaier granule+chemotherapy group (n=15)and control group(n=10).The white blood cell count,liver function,cell immunity and immunologieal reiection were detected.The 1-year tumor recurrence rate wag calculated.Results The white blood cell counts in chemotherapy group 1,3,and 6 months after treatment were significantly lower than that before treatment (F=62.053,58.472,49.807,P＜0.05).The changes of white blood cell counts of the other 3 groups before and aftertreatment were small.The difference on the white blood cell counts of the 4 groups had no statistical 8ignincanee(F=102.361,113.412,87.572,P＜0.05).The NK activity,CD4+/CD8+ ratio,IL-2 level in huaier granule group and huaier granule+chemotherapy group 1,3,6 months after treatment were significantly higher than those before treatment,and were significantly higher than those in chemotherapy group and control group(P＜0.05).No immunological rejection occurred in all the groups.Two patients in each group had recurrence and metastasis of HCC within 1 year after the treatment.and the incidence in control group was higher than the other 3 groups(P＜0.05). Conclusions Humer granule can increase the white blood cell count which is decreased after chemotherapy,impmve cellular immunity,and effectively suppress the recurrence and metastasis of HCC at the first year after operation.
ABSTRACT
AIM: To investigate whether ?-tyrosol could induce expression of DT-diaphorase (NQO 1) gene and inhibit proliferation of hepatoma cells and their relationship.METHODS: The DT-diaphorase activity, mRNA expression and cell proliferation were examined using direct measurement of DT-diaphorase from cells cultured in microtiter wells, semi-quantitative reverse transcription-PCR (RT-PCR) technique and crystal violet assay after treatment of SMMC-7721 cells with ?-tyrosol for 24 h. RESULTS: Treatment of SMMC-7721 cells with ?-tyrosol caused an increase in DT-diaphorase activity and DT-diaphorase mRNA expression in a dose-dependent manner. A statistically significant correlation between DT-diaphorase mRNA levels and enzyme activities was evident. In almost the same concentration range of 70 mg/L to 100 mg/L, ?-tyrosol resulted in a dose-dependent inhibition of cell proliferation which well inversely correlated with DT-diaphorase activity.CONCLUSION: ?-tyrosol can induce DT-diaphorase activity and enhance expression of its gene, which may contribute to antiproliferation of hepatoma cells caused by the same chemical.