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Abstract Background Liver cancr is a heterogeneous disease in terms of etiology, biologic and clinical behavior. Very little is known about how many genes concur at the molecular level of tumor development, progression and aggressiveness. To explore the key genes involved in the development of liver cancer, we established a rat model induced by diethylnitrosamine to investigate the gene expression profiles of liver tissues during the transition to cirrhosis and carcinoma. Methods A rat model of liver cancer induced by diethylnitrosamine was established. The cirrhotic tissue, the dysplasia nodules, the early cancerous nodules and the cancerous nodules from the rats with lung metastasis were chosen to compare with liver tissue of normal rats to investigate the differential expression genes between them. Affymetrix GeneChip Rat 230 2.0 arrays were used throughout. The real-time quantity PCR was used to verify the expression of some differential expression genes in tissues. Results The pathological changes that occurred in the livers of diethylnitrosamine-treated rats included non-specific injury, fibrosis and cirrhosis, dysplastic nodules, early cancerous nodules and metastasis. There are 349 upregulated and 345 downregulated genes sharing among the above chosen tissues when compared with liver tissue of normal rats. The deregulated genes play various roles in diverse processes such as metabolism, transport, cell proliferation, apoptosis, cell adhesion, angiogenesis and so on. Among which, 41 upregulated and 27 downregulated genes are associated with inflammatory response, immune response and oxidative stress. Twenty-four genes associated with glutathione metabolism majorly participating oxidative stress were deregulated in the development of liver cancer. There were 19 members belong to CYP450 family downregulated, except CYP2C40 upregulated. Conclusion In this study, we provide the global gene expression profiles during the development and progression of liver cancer in rats. The data obtained from the gene expression profiles will allow us to acquire insights into the molecular mechanisms of hepatocarcinogenesis and identify specific genes (or gene products) that can be used for early molecular diagnosis, risk analysis, prognosis prediction, and development of new therapies.

Abstract Background The non-human primate (NHP) research community has been intensely interested in obtaining whole-genome expression arrays for their work. Recently, novel approaches were used to generate the DNA sequence information for a rhesus GeneChip. To test the reliability of the rhesus GeneChip across different centers, RNA was isolated from five sources: cerebral cortex, pancreas, thymus, testis, and an immortalized fibroblast cell line. Aliquots of this RNA were sent to each of three centers: Yerkes National Primate Research Center, Oregon National Primate Research Center and the University of Nebraska Medical Center. Each center labeled the samples and hybridized them with two rhesus macaque GeneChips. In addition, rhesus samples were hybridzed with human GeneChips to compare with samples hybridized with the rhesus GeneChip. Results The results indicate that center effects were minimal and the rhesus GeneChip appears highly reliable. To test the validity of the rhesus GeneChip, five of the most differentially expressed genes among tissues identified in the reliability experiments were chosen for analysis with Quantitative PCR. For all 5 genes, the qPCR and GeneChip results were in agreement with regard to differential expression between tissues. Significantly more probesets were called present when rhesus samples were hybridized with the rhesus GeneChip than when these same samples were hybridized with a human GeneChip. Conclusion The rhesus GeneChip is both a reliable and a valid tool for examining gene expression and represents a significant improvement over the use of the human GeneChip for rhesus macaque gene expression studies.

Rationale and Objectives: Transjugular intrahepatic portosystemic shunt (TIPS) is an established method for portal hypertension. This study was to investigate the long-term safety, technical success, and patency of TIPS, and to determine the risk factors and clinical impacts of shunt dysfunction.Materials and Methods: A total of 154 consecutive patients undergoing embolotherapy of gastric coronary vein and/or short gastric vein and TIPS creation were prospectively studied. Follow-up data included technical success, patency and revision of TIPS, and overall survival of patients.Results: During the study, the primary and secondary technical success rates were 98.7% and 100%, respectively. Sixty-three patients developed shunt dysfunction, 30 with shunt stenosis and 33 with shunt occlusion. The cumulative 60-month primary, primary assisted, and secondary patency rates were 19.6%, 43.0%, and 93.4%, respectively. The cumulative 60-month overall survival rates were similar between the TIPS dysfunction group and the TIPS non-dysfunction group (68.6% vs. 58.6%, P = .096). Baseline portal vein thrombosis (P < .001), use of bare stents (P = .018), and portal pressure gradient (PPG) (P = .020) were independent predictors for shunt dysfunction, hepatocellular carcinoma (P < .001), and ascites (P = .003) for overall survival. The accuracy of PPG for shunt dysfunction was statistically significant (P < .001), and a cutoff value of 8.5 had 77.8% sensitivity and 64.8% specificity.Conclusions: The long-term safety, technical success, and patency of TIPS were good; baseline portal vein thrombosis, use of bare stents, and PPG were significantly associated with shunt dysfunction; shunt dysfunction has little impact on patients' long-term survival because of high secondary patency rates. [ABSTRACT FROM AUTHOR]

Background: The outcome of patients with intermediate stage hepatocellular carcinoma (HCC) treated by transarterial chemoembolization (TACE) remains poor. Search for a more effective therapy is still necessary. Objective: This study aimed to investigate the effect of combining TACE with Kang’ai (KA) injection for treating patients with intermediate stage HCC. Methods: A total of 89 patients with intermediate stage HCC were enrolled and divided into TACE +KA group (n = 48) receiving repeated TACE plus KA injection, and TACE group (n = 41) receiving repeated TACE alone. All patients were prospectively studied. Primary endpoints were overall survival (OS) and time to radiologic progression (TTP). Results: The TACE + KA group had significantly longer median OS (27.0 vs 21.0 months, P = .038) and TTP (12.0 vs 10.0 months, P = .028) than TACE group. The 1-, 2-, and 3-year OS rates in the TACE + KA group were markedly higher than in TACE group (88.5%, 58.8%, and 20.8% vs 81.3%, 44.9%, and 6.7%, respectively, P = .038), while the 1- and 2-year TTP rates in the TACE + KA group were significantly lower than in TACE group (49.3% and 86.9% vs 75.3% and 100%, P = .028). TACE + KA group displayed significantly lower incidences of intrahepatic and extrahepatic metastases, as well as postembolization syndrome than TACE group (P < .05). Multivariate analyses revealed group (P = .023), maximum tumor size (P = .019), and tumor number (P = .034) as significant predictors for OS, and group (P = .046), maximum tumor size (P = .002) and α-fetoprotein level (P = .020) as significant predictors for TTP. Both TACE and KA injection were well tolerated. Conclusion: TACE plus KA injection is more effective than TACE alone for treating patients with intermediate stage HCC in this nonrandomized study. Further research is warranted. [ABSTRACT FROM AUTHOR]

Portal vein thrombosis (PVT) is a common complication in cirrhosis. The aim of this study was to determine risk factors for PVT, assess the efficacy of anticoagulant therapy, and evaluate the effects of PVT on patients with cirrhosis undergoing elective transjugular intrahepatic portosystemic shunt (TIPSS). A total of 101 patients with cirrhosis undergoing elective TIPSS were prospectively studied. After TIPSS, all patients received preventive therapy for PVT and were followed up at 3, 6, 12, and 24 months. Clinical outcomes were compared between patients who developed PVT after TIPSS and those who did not. Multivariate analysis showed that white blood cell count (relative risk [RR]: 0.377; 95% confidence interval [CI]: 0.132-0.579; P = .001), Child-Turcotte-Pugh score (RR: 1.547; 95% CI: 1.029-2.365; P = .032), and ascites (RR: 1.264; 95% CI: 1.019-1.742; P = .040) were independent predictors for PVT. Warfarin treatment within 12 months achieved significantly higher rates of complete recanalization than aspirin or clopidogrel in patients with PVT (54.5% vs 31.3%; P = .013), although adverse events were similar between the 2 groups (P > .05). Patients without PVT had significantly lower 2-year cumulative rates of variceal rebleeding (15.9% vs 36.6%; P = .023), shunt dysfunction (27.0% vs 46.8%; P = .039), hepatic encephalopathy (24.1% vs 42.6%; P = .045), and hepatocellular carcinoma (11.4% vs 31.2%; P = .024) and markedly higher 2-year cumulative survival rates (89.8% vs 72.9%; P = .041) than those with PVT. The PVT is associated with poorer clinical outcomes in TIPSS-treated patients, and warfarin is both safe and more effective in recanalizing PVT than aspirin or clopidogrel. [ABSTRACT FROM AUTHOR]