The ubiquitin-proteasome pathway and enhanced activity of NF-kappaB in gastric carcinoma.

BACKGROUND AND OBJECTIVES: NF-kappa B, ubiquitin and proteasome have been shown be important factors in oncogenesis. The aim of this study was to determine whether NF-kappa B could be a sensitive biomarker for gastric carcinoma. METHODS: Tumor and adjacent mucosal tissue specimens in 92 patients with gastric carcinoma were studied. The expression of NF-kappa B was evaluated by immunohistochemistry. The expression of I kappa B alpha, ubiquitin in cytoplasm and NF-kappa B in nucleoplasm was assayed by Western blot. DNA binding-activity of NF-kappa B was confirmed by electrophoretic mobility shift assay (EMSA). Fluorogenic technique was performed to measure the 26S proteasome activity. RESULTS: NF-kappa B positive expression in tumor tissues (82.4%) was significant higher than that in adjacent mucosal tissues (32.7%, P < 0.05). The increase of NF-kappa B activation was accompanied by the increases of ubiqutin, 26S proteasome activation and a degradation of I kappa B alpha but not the ubiquitin-conjugated I kappa B alpha/NF-kappa B complex in gastric carcinoma. NF-kappa B expression was significantly increased in patients with lymph node metastasis, TNM stage III/IV or with the habit of high intake of pickled vegetables. CONCLUSIONS: This study demonstrates that the constitutive activation of NF-kappa B is likely due to the activation of ubiquitin-proteasome pathway and NF-kappa B can be used as a prognostic biomarker.

An animal model of black pigment gallstones caused by nanobacteria.

Black pigment gallstones are often founded in gallbladder, but their pathogenesis is unclear. The present study was undertaken to study the role of nanobacteria in pigment gallstone formation in Japanese white rabbits. Nanobacteria were successfully cultured from 3 of 7 cholecystolithiasis patients gallbladder (without acute cholecystitis) bile samples and affirmed by Hoechst 33258 staining and specific immunostaining using monoclonal antibody. Nanobacteria were injected into rabbits' gallbladder. After 2 weeks follow-up, the incidence of black pigment gallstones in rabbits was significantly greater in nanobacteria-injected group (8/10) than that in DMEM-injected group (2/10) and that in hydroxyapatite-injected group (2/10). This study indicates that nanobacteria exists in gallbladder bile of cholelithiasis patients and causes the formation of black pigment gallstones in rabbits. For the first time, we successfully established an animal model of black pigment gallstones caused by nanobacteria. This will be helpful in further delineating the pathogenesis of black pigment gallstones.

Adjuvant hepatic chemotherapy after resection of solitary hepatocellular carcinoma associated with hepatitis B virus cirrhosis.

BACKGROUND: Although resection is the major treatment for patients with hepatocellular carcinoma (HCC), the high intrahepatic recurrence remains a cardinal cause of death. This study was undertaken to evaluate the effect of hepatic arterial infusion chemotherapy on the survival and recurrence of HCC patients with hepatitis B virus (HBV) cirrhosis after resection. METHODS: Twenty-eight patients who had undergone placement of a hepatic arterial pump at the time of liver wedge resection for HCC from 1998 through 2004 were reviewed retrospectively. These patients aged 23-71 years had HBV cirrhosis (Child-Pugh class A or B). They were given floxuridine (FUDR)(250 mg), doxorubicin (10 mg) and mitomycin C (4 mg) alternatively every 2 or 3 days through arterial pumps for 8 cycles each year in the first two years after resection. Meanwhile, traditional Chinese herbal medicine was prescribed to the patients. When the leukocyte count was as low as 3X10(9)/L or asparate aminotransferase (AST) level was significantly increased, the regimen of chemotherapy was delayed for the normalization of leukocyte count and AST level (below 80 U/L). RESULTS: Of the 28 patients, 23 received 8 or 16 cycles of the set regimen of chemotherapy. These patients are alive with no evidence of recurrence. Among them, 5, 7, and 11 patients are alive beyond 5 years, 3 years, and 1 year respectively. In the remaining 5 patients, 3 who had had a HCC 10 cm or more in diameter showed tumor recurrence within 1 year, in whom, 8 cycles of chemotherapy were not completed because of their low leukocyte count (<3 x 10(9)/L) and poor liver function. One patient who had received 8 cycles of chemotherapy demonstrated recurrence at 16 months after resection. One patient who had received 16 cycles of chemotherapy had intrahepatic recurrence at 58 months after surgery. No recurrence was observed in 17 patients who had received 16 cycles of chemotherapy. CONCLUSION: Adjuvant hepatic arterial chemotherapy may be feasible to improve the survival of patients after resection of solitary HCC associated with HBV cirrhosis.

[Application of sleeve anastomosis in development of cervical heart transplantation in rats].

OBJECTIVE: To simplify surgical technique and increase postoperative survival rate, sleeve anastomosis technique combined cuff technique was used in developing the model of cervical heart transplantation in rats. METHODS: In this model, the hearts from 25 male SD rats were transplanted into the neck of Wistar rats by anastomosing the donor innominate artery to the recipient right common carotid artery by use of sleeve technique, and the donor pulmonary artery to the recipient right external jugular vein by use of cuff technique. After operation, the rats were treated with cyclosporine A (1.5 mg/kg, q.d.), transplanted hearts were followed by daily inspection or palpation and the allograft survival time was more than 3 days as the standard of successful operation. RESULTS: The mean operative time was (48.7 +/- 3.4) min, with a successful rate of 88% (22/25). Complications were anastomotic hemorrhage (1 case) and thrombosis(2 cases). During the follow-up period, 6 rats died of pulmonary infection, abscess in the neck, liver or bladder tumor. The remaining 16 transplanted hearts survived more than 3 months. CONCLUSION: The modified operation have advantages of less operative procedure, shorter operation and ischemia time and easier monitoring of graft function.