Ulinastai reverses experimental hepatofibrosis in rats / 中华普通外科杂志

Objective To explore if Ulinastai reverses hepatofibrosis in rats.Method Rat hepatofibrosis models were induced by TAA subcutaneously injection.18 rats with hepatofibrosis were divided into 2 groups,Ulinastai treatment group (9 rats),normal saline control group (9 rats).AST,ALT,HA,SOD,MDA,LN level were measured and compared between the 2 groups and that of healthy rats (3 rats).Rats liver morphology was observed using HE,Masson stain and type-B ultrasonic.TGF-β1、caspase-3 were detected by immunohistochemistry.Result After 3 weeks Ulinastai treatment,elastic index and SSS score in Ulinastai group decreased significantly compared to pretreatment (t =2.472,P ＜0.05).ALT,AST,SOD,MDA,HA and LN level significantly improved (F =3.862,5.774,3.442,4.157,4.173,3.674,P ＜ 0.05).Compared with NS treatment group HE and Masson staining showed fewer inflammatory cells infiltration in central vein,ballooning degeneration of liver cells,collagen proliferated,hepatic lobules degradation and pseudolobule arise after 3 weeks intervenion.Also in Ulinastai group,TGF-β1、caspase-3 positive cells were much less than that in NS treatment group.Conclusions Ulinastai can reverse rat hepatic fibrosis and alleviate fibrosis degree and collagen fiber deposit.

Recombined adeno-associated viral vector-mediated systemic delivery of caveolin-1 inhibits angiogenesis of implanted hepatocellular tumor in vivo / 中华普通外科杂志

Objective To investigate the antitumor effect of the recombined adeno-associated virus encoding caveolin-1 regulated by progression-elevated gene (PEG) promotor on the angiogenesis of implanted human hepatocellular carcinoma(HCC) cell lines in a nude mouse model. Methods HepG2 cells were inoculated subcutaneously into NOD/SCID mice, and animals were treated with rAAV-PEG-caveolin-1 after tumor cell innoculation. The fluorescence ratio of Evans blue to FITC-dextran was used to assess the changes of microvasculature permeability of the tumor. Western blot and immunohistochemical analyses were employed to detect PECAM-1 expression in tumor microvascular endothelium and microvessel density(MVD), respectively; NOS activity was assessed by citrulline generation. Tumor growth was observed and tumor cell apoptosis in tumor tissues were measured by TUNEL. Results Tumor growth was significantly inhibited in mice injected with rAAV-PEG-caveolin-1. The administration of rAAV-PEG-caveolin-1 significantly blocked vascular leakage in the tumor microcirculation. The levels of PECAM-1 protein detected by Western blot were markedly reduced in rAAV-PEG-caveolin-1-treated mice, and there were fewer MVD in tumors from caveolin-1-treated mice, while NOS catalytic activity was much lower in rAAV-PEG-caveolin-1-treated mice compared to the control and empty vector-treated animals. TUNEL demonstrated significant induction of tumor cell specific apoptosis. Conclusions rAAV-PEG-caveolin-1 can reduce tumor progression through blocking microvascular formation by inhibiting eNOS.

Application of MSCT in the diagnosis of solid pseudopapillary tumor of the pancreas / 中华内分泌外科杂志

Objective To investigate the application of multi-slice spiral computed tomography(MSCT) in the diagnosis of solid pseudopapollary tumor of the pancreas (SPTP). Methods Clinical data and CT films of 12 patients with SPTP were retrospectively analyzed from January 2003 to December 2008. Results SPTP presented a typical cystic lesion with well-limited silhouette and no intensification in the cyst on enhanced CT scan. However, a slight to moderate enhancement in the solid components and a markedly enhanced envelope could be seen. Three dimensional images of MSCT can reveal clearly an anatomic relationship of the lesions with surrounding organs and blood vessels. Of 12 cases, there was one case showed that the envelope was incomplete, 3 with duodenal invasion, 2 with superior mesenteric vein involvement, and 1 with closed adhesion with spleen. All 12 patients underwent surgery and had only one tumor, tumor diameter ranged from 4 cm to 18 cm. The location of tumor in pancreas, the relation with surrounding tissue and the pathological presentation were helpful to make peroperative diagnosis. Three dimensional imaging technology of MSCT can offer important referrence for the preroperative evaluation and increase the diagnosis accuracy.

Hyperproliferation of human colon cancer cells in co-cultures of rat regenerating hepatocytes / 国际外科学杂志

Objective To investigate the stimulated proliferation of colon cancer cells in co-cultures of regenerating hepatocytes. Methods Regenerating hepatocytes(24 hours after partial hepatectomy)were obtained by collagenase perfusion of models of rats undergoing 70% liver resection. To determine whether the ratio of human colon cell line SW480 cells to hepatocytes in co-cultures has influence on their interaction,these cells were cultured in ratios of 1: 101:1, or 10: 1. Proliferation capacity was assessed by the percentage of 3 H-TdR incorporation. Expression of epidermal growth factor receptor(EGFR), insulin-like growth factor1 receptor(IGF-1R)and hepatocyte growth factor receptor(c-met) were analyzed by western blot. Results For co-cultured SW480 and hepatocytes in the ratios of 1: 1 and 1: 10, an increase of disintegrations per minute(dpm) occurred after 72 hours' culture, and lasted at 120 hours' culture(P < 0.05). No difference was found between the group with ratio of 10:1 and control group. Protein levels of EGFR and IGF-1R, but not c-met, were significantly increased between culture of 24 hours and 120 hours; however, no change of these receptors was found in the ratio of 10: 1. Conclusions These results imply that co-culturing human colon cancer cells with regenerating hepatocytes leads to increased expression of EGFR and IGF-1R. We conclude that this effect is probably dependent on paracrine stimulation, by which numerous signals from the hepatocytes contribute to the hyperproliferative state of colon cancer cells via up-regulating the responding receptors.

Effects of short hairpin RNA expression plasmid targeting vascular endothelial growth factor-C on the proliferation and invasion of HepG2 cells / 中华消化外科杂志

Objective To investigate the effects of short hairpin RNA (shRNA) expression plasmid targeting vascular endothelial growth factor-C (VEGF-C) on the proliferation and invasion of HepG2 cells. Methods The VEGF-C shRNA plasmid vector labeled with green fluorescent protein was constructed and stably transfected into HepG2 cells. The transfected cells were sorted by G418 and visualized by fluorescent microscope and assayed by flow cytometry. Expression of VEGF-C in transfected cells was determined by RT-PCR and Western blot. The inhibition rates of the cell proliferation and invasion were determined by MTT assay and reconstituted basement membrane invasion assay, respectively. Results VEGF-C shRNA effectively downregulated VEGF-C mRNA and protein expression in HepG2 cells, and it also effectively inhibited the proliferation of HepG2 cells in a time-dependent manner. The invasion capacity of HepG2 cells was inhibited by VEGF-C shRNA, and the inhibition rate was 51.54%. Conclusions VEGF-C plays an important role in tumor proliferation, invasion and metastasis. RNA interfering technology that targets VEGF-C may serve as a potential therapeutic intervention in the treatment of human hepatic cancer.

Diagnosis and surgical treatment of hepatic inflammatory myofibroblastic tumor / 国际外科学杂志

Objective To analyze the clinical features and image manifestations of hepatic inflammatory myofibro-blastie tumor( HIMT), and to investigate the optimal management of this disease. Methods From January 2000 to January 2007, clinical data with HIMT verified by pathology were retrospectively analyzed. Results Eight patients 5 men, 3 women were included in the analysis. The mean age was 41.3 years. All eases did not have a history of previous hepatitis and liver cirrhosis, and 6 with no typical clinical symptoms. Hepatic functions, serum levels of AFP, CEA, CA199 in these patients were all within the normal ranges. Preoperative imaging by ultrasonography and computed tomography(CT) were not indicative of HIMT. Morphologic features by CT scan were summarized: at nonenhanced CT, the masses appeared as low density lesions. At contrast enhanced CT, the masses exhibited mod-erate intensification in the solitary areas, and the intensification peak appeared during the period of artery. During the period of portal vein and delayed scan, the masses showed low to moderate intensification in the solitary areas, in which the degree of intensification was a little lower than that in peripheral liver parenchyma. Gross specimens showed single solid masses, 3～12 cm, without classic envelope. All the patients underwent surgery whereas no incidence of perioperative death. Diagnosis of HIMT was confirmed by pathology of surgical specimens. Condusion Although typical presentation and the diagnostic workup are still lacking for HIMT, CT is helpful in diagnosing HIMT as well as combined with clinical findings. Surgical management would be likely the optimal treatment of this disease.

Raav-PIEG-MDA-7 inhibits the growth of hepatocellular carcinoma in vivo / 中华普通外科杂志

Objective To investigate the anti-tumor effect of the recombined adeno-associated virus encoding melanoma differentiation -associated gene-7 (MDA-7) regulated by progression-elevated gene (PEG) promotor on human hepatocellular carcinoma (HCC) in nude mice. Methods A nude mouse model of subcutaneously implanted HCC cell line HepG2 tumor was established. AAV-PEG-MDA-7 was injected from the tail vain after tumor cell innoculation. RT-PCR, Western blot and immunohistochemical analysis were employed to detect MDA-7 expression in mice; MDA-7 plasma concentration was detected by ELISA assay. Tumor growth was observed, tumor cell apoptosis and angiogenesis in tumor tissues were measured by TUNEL and immunohistochemical analysis. Results Seven days after tumor cell innoculation RT-PCR, Western blot, and immunohistochemistry showed that MDA-7 was only expressed in the liver. ELISA assay showed that the concentration of MDA-7 in plasma was gradually increased to reach the plateau (200 ng/ml). Tumor growth was significantly inhibited in mice injected with rAAV-PEG-MDA-7, and the tumor growth-inhibiting rate was 62%. TUNEL and immunohistochemical analysis demonstrated significant induction of tumor cell specific apoptosis and reduction of vascular formation in tumor tissues. Conclusions rAAV-PEG-MDA-7 exhibits tumor-specific cytotoxicity and liver tendency, inhibiting tumor growth possibly by tumor cell apoptosis-induciug effect and antiangiogenesis.

Emergency hand-assisted laparoscopic hepatectomy for spontaneous rupture of primary hepatocellular carcinoma / 国际外科学杂志

Objective To assess the efficacy of emergency hand-assisted laparoscopic hepatectomy for spontaneous rupture of primary hepatocellular carcinoma.Methods A total of 15 eases who underwent emergency hand-assisted laparoscopic hepatectomy for spontaneous rupture of primary hepatocellular carcinoma were retrospectively reviewed.Results All operations were successful.The postoperative mortality rate was.Thirteen cases were followed-up from 11 months to 56 months.The overall 1-,3-year survival rate was 84.6%(11/13),53.8%(7/13)respectively.Conclusion Emergency hand-assisted laparoscopic hepatectomy is a safe and feasible approach for pontaneous rupture of primary hepatocellular carcinoma in clinically selected patients.If the patients condition permits it,emergency hand-assisted laparoscopic hepatectomy should be the treatment of choice.

Ultrasound microbubble contrast agent enhances TRAIL gene transfection into hepatocellular carcino-ma cells / 国际肿瘤学杂志

Objective To evaluate the impact of the recombined plasmid vector with enhanced green fluorescent protein (EGFP) encoding soluble tumor necrosis factor related apoptesis inducing ligand (pIRES-EGFP-sTRAIL) on proliferation and apoptosis of human hepatocellular carcinoma cell line HepG2, and investi-gate the feasibility and efficiency of the transfection of pIRES- EGFP- sTRAIL into HepG2 by ultrasound micro-bubble contrast agent. Methods pIRES-EGFP-sTRAIL was constructed and transfected into HepG2 cells by using different types of mediated methods: microbubble echocontrast agent combining appropriate dose of ultra-sound irradiation, liposome method, microbubble echocontrast agent only or blank medium treatment. Transfec-tion efficiency was evaluated by EGFP-expressed cell count; proliferation-lnhibiting rate and the apoptosis rate of HepG2 cells were determined by MTT method and flow cytometry analysis; changes of cell morphology were examined by microscopy with Hoechst33258 dyeing; expression of caspase-8 and caspase-3 was detected by Western blot. Results Ultrasound microbubbh enhanced pIKES-EGFP-sTRAIL uptake by HepG2 cells, and the transfection efficiency was significantly higher in ultrasound microlmbble group than that in other groups( P<0.05 ) ; pIRES- EGFP- sTBAIL effectively inhibited HepG2 cell proliferation and induced cell apoptosis by triggering caspase cascade. Both the inhibiting rate and apoptosis rate were significantly higher in ultrasound microbubble group than those in other groups(P<0.05). Conclusion pIRES-EGFP-sTRAIL expresses ef-fectively in HepG2 cells, sTRAIL has a potential role on the inhibiting proliferation and inducing apoptosis of HepG2 cells by triggering caspase cascade, and this role can be enhanced by the administration of low-intensity ultrasound and microbubble echecontrast agent.