Objective To explore the effect of Tie-2 small interference RNA (siRNA) treatment in human hepatoma transplanted subcutaneously in nude mice. Methods Tumor cells were implanted in the hind flank of male nude mice of 6 weeks. Tumor-bearing mice were divided into two groups (gene therapy group and control group) and injected intra-tumorally with Tie-2-siRNA/Lipofectamine and saline/Lipofectamine respectively. The tumor volume and weight, serum AFP and microvessel density (MVD) and the histological change of the tumor were tested after gene therapy. Results The growth inhibitory rates in gene therapy group were 26.94%, 53.01% and 68.91% on day 4, 7 and 10 after gene therapy respectively. The tumor volumes of gene therapy group (118.47, 111.57 and 104.59 mm3) were smaller than those of the control group (162.17, 237.46 and 336.41 mm3) respectively (P<0.01), and the weight of tumor in gene therapy group was lighter than that of the control group 〔(0.89±0.09) g vs (1.24±0.03), P<0.01〕. The AFP value in gene therapy group was obviously lower than that of the control group 〔(107.66±24.13) ng/ml vs (266.08±50.96) ng/ml, P<0.01〕. There was significant diference of MVD between the gene therapy group (34.63±4.07) and the control group (81.01±9.44) with the method of immunohistochemitry (P<0.01). Histopathology in the control group showed that the tumor volumes were bigger, and a high atypic of tumor cells were seen. The main pathological changes in tumor tissue of gene therapy group were necrosis, there were massive necrosis. The apoptosis cells were seen in the both of necrosis and non-necrosis areas in only 2 mice of gene therapy group. Conclusion Tie-2-siRNA inhibits the tumor growth and tumor angiogenesis, and is a possible new approach for liver neoplasm gene therapy.
肝门部胆管癌(hilar cholangiocarcinoma),又称Klaskin癌,是指起源于左右肝管、分叉部和肝总管上段胆管上皮的恶性肿瘤,约占胆管癌的60%~70%[1]。由于其临床表现隐匿,早期难以被发现。目前根治性手术是最有效的提高其生存率的治疗方式,随着肝门部胆管癌R0切除率的不断升高,5年生存率不断提高[2,3],但仍有不少问题有待于解决……
Objective To investigate whether protease inhibitor (ulinastatin, UTI) can protect liver from ischemiareperfusion injury in hepatocellular carcinoma (HCC) patients undergoing hepatectomy after hepatic inflow occlusion. Methods A prospective randomized control study was designed. Thirtyone HCC patients undergoing hepatectomy after hepatic inflow blood occlusion were randomly divided into the following two groups. UTI group (n=16), 1×105 units of ulinastatin was given intravenously in operation, then the dosage was continuously used twice a day up to 5 days postoperatively. Control group (n=15), the patients received other liver protective drugs. Liver function, plasma C-reactive protein (CRP) and cortisol level were compared between these two groups. Results The postoperative liver function of the UTI group was significantly improved compared with the control group. For example, on the third postoperative day the aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin level in the UTI group were significantly lower than those in the control group, respectively (P<0.05). On the first postoperative day, the plasma CRP concentration in the UTI group was significantly lower than that in the control group(P<0.01). The plasma cortisol level in the control group markedly increased compared with the level before operation(P=0.046). However, there was no significant difference in the UTI group between before and after operation. Conclusion Ulinastatin can effectively protect liver from ischemia/reperfusion injury in HCC patients undergoing hepatectomy performed after hepatic inflow occlusion. Also, it can relieve the surgical stress for patients.
【Abstract】ObjectiveTo evaluate the efficacy of whole body hyperthermia (WBH) in the treatment of advanced hepatic carcinoma and its effect on liver function. MethodsFrom 2001 to 2004, 39 cases of advanced hepatic carcinoma were treated with WBH. The effect of WBH on liver function was assessed by liver function test before and after treatment. Results①The effective rate of WBH was 61.5%(24/39) in the treatment of advanced hepatic carcinoma with declined AFP in 60.0%(9/15) of patient and 100% of patients had pain relieve. The survival rates of 6 months, 1 year and 2 years were 76.9%(30/39), 59.0%(23/39) and 12.8%(5/39), respectively. ②Alanine aminotransferase (ALT) elevated obviously in 1-3 d after treatment (Plt;0.05), and then approached to its baseline in 7 d. Aspartate aminotransferase (AST) increased significantly 1 d after treatment (Plt;0.05),and then back to its baseline in 3-7 d. Albumin (ALB) appeared dropped 1 d after treatment (Plt;0.05), and restored normally in 3 d. The levels of total bilirubin (TBIL) and gamma glutamyl transpeptidase (GGT) had no evident significant change with the WBH treatment in abnormal liver function group, but TBIL increased 1-3 d after treatment in normal liver function group (Plt;0.05). ConclusionIn the treatment of advanced hepatic carcinoma, WBH can improve the patients’ life quality and prolong their life expectancy. Meanwhile, it could also result in reversible impairment of liver function.
Objective To probe into the roles of inositol 1, 4, 5-trisphosphate (IP3) and bcl-2 gene expression in inhabiting hepatocellular carcinoma of nude mice by quercetin. Methods Animals with hepatocellular carcinoma in quercetin group were treated with injection peritoneum of quercetin 50 mg/(kg·d ) for 3 weeks, while which in control group were treated with 0.4% DMSO of RPMI 1640 0.05 ml/(g·d). Then the volume and the weight of tumors were measured, IP3, bcl-2 mRNA and bcl-2 protein were assayed by IP3-[3H] Birtrak Assay, RT-PCR and Western blot respectively. Results The volume and weight of tumors in quercetin group were lower than those in control group 〔(15.8±10.1) mm3 vs. (52.3±26.5) mm3 in volume, (44.8±10.4) mg vs.(91.3±31.4) mg in weight, P<0.01〕. Content of IP3 in quercetin group was lower than that in control group 〔(13.4±1.4) pmol/mg prot vs. (35.3±6.6) pmol/mg prot, P<0.01〕. There was no significant difference in bcl-2 mRNA expression between quercetin group and control group 〔RI (the gray degree multiply area of bcl-2 /the gray degree multiply area of β-actin): 0.55±0.05 vs. 0.79±0.19, P>0.05〕, but the expression of bcl-2 protein in quercetin group was lower than that in control group (RI: 1.07±0.12 vs. 6.69±1.80, P<0.01). Conclusion Quercetin can inhabit the growth of hepatocellular carcinoma tansplanted into liver of nude mice by reducing IP3 production and down-regulating bcl-2 gene expression.