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ABSTRACT: Abstract Objectives. Recent epidemiological studies suggest that metformin treatment may reduce the risks of cancer and overall cancer mortality among patients with diabetes mellitus (DM). However, data on hepatocellular carcinoma (HCC) are very limited and inconsistent. This meta-analysis was designed to pool data currently available to determine the association between metformin use and HCC among diabetic patients. Methods. The Medline and Embase databases were searched to identify the relevant studies between January 1966 and December 2011. The overall analysis was derived using a random-effects meta-analysis model (DerSimonian and Laird method). Subgroup analysis was performed to explore the source of heterogeneity and validate the results from overall analysis. The Newcastle-Ottawa Quality assessment scales were adopted for quality assessment; Begg's funnel plot and Egger's regression asymmetry test were used to detect the publication bias. Results. A total of seven studies were identified, including three cohort studies and four case-control studies. Based on the available data, the overall prevalence of HCC was 3.40% (562/16,549) in DM patients. The overall analysis showed a significantly reduced risk of HCC in metformin users versus nonusers in diabetic patients (relative risk (RR) 0.24, 95% confidence interval (CI) 0.13-0.46, p < 0.001). Fifteen subgroup analyses were performed, and most of them (12/15 = 80%) provided supporting evidence for the results of overall analysis. Begg's (Z = -0.15, p = 0.8819) and Egger's test (t = -0.79, p = 0.468) showed no significant risk of having a publication bias. Conclusion. Metformin treatment was associated with reduced risk of HCC in diabetic patients. To clarify this relationship, more high-quality studies are required.
Scandinavian journal of gastroenterology 11/2012; · 2.08 Impact Factor
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Bu-Shan Xie, Hong-Chuan Zhao,
Shu-Kun Yao,
De-Xiang Zhuo,
Bo Jin,
Dui-Cai Lv,
Cheng-Lin Wu,
Dai-Long Ma,
Chun Gao,
Xiao-Ming Shu,
Zheng-Lin Ai
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ABSTRACT: Induction of autophagy usually acts as a survival mechanism of cancer cells in response to chemotherapy. However, the function and molecular mechanism of autophagy in human hepatoma cells under drug treatment is still not clear. To address this issue, we established an experimental model in which HepG2 cells were treated with etoposide, a widely used anticancer agent. We demonstrate the etoposide-induced accumulation of GFP-LC3 dots by fluorescent microscopy, the up-regulation of LC3-II protein expression by Western blotting and the increased number of autophagic vacuoles by electron microscopy, confirming the activation of autophagy by etoposide in HepG2 cells. Inhibition of autophagy by either 3-methyladenine (3MA) or beclin-1 small interfering RNA enhanced etoposide-induced cell death. Furthermore, activation of p53 and AMPK was detected in etoposide-treated cells and inhibition of AMPK triggered apoptosis through suppression of autophagy. On the other hand, inactivation of p53 promoted cell survival through augmentation of autophagy. Collectively, these findings indicate that etoposide-induced autophagy promotes hepatoma cell adaptation and survival, and that autophagy inhibition improves the chemotherapeutic effect of etoposide. Moreover, AMPK activation is clearly associated with etoposide-induced autophagy. We conclude that manipulation of AMPK may be a promising approach of adjuvant chemotherapy for hepatocellular carcinoma.
International Journal of Molecular Medicine 01/2011; 27(4):599-606. · 1.98 Impact Factor
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ABSTRACT: To determine the role of diabetes mellitus (DM) and other associated factors in Chinese hepatocellular carcinoma (HCC) patients with cirrhosis, compared with those HCC patients without cirrhosis, in the single setting of hepatitis B virus (HBV) infection, after other known concomitant diseases were excluded.
A total of 482 patients, treated at the China-Japan Friendship Hospital, Ministry of Health (Beijing, China), in the period January 2003 to June 2009, and with a hospital discharge diagnosis of HCC, were included. Demographic, clinical, laboratory, metabolic and instrumental features were analyzed.
Of the total, 310 patients were diagnosed with HBV infection and, following the inclusion and exclusion criteria, 224 were analyzed, including 122 patients (54.5%) with cirrhosis (the case group) and 102 patients without cirrhosis (the control group). Twenty-seven patients (12.1%) were diabetic, including 19 in the case group and 8 in the control group (19/122 = 15.6% vs 8/102 = 7.8%, P = 0.077). Thirty-one possible relevant parameters were compared by univariate analysis, and 9 variables were selected for multivariable analysis, including DM (P = 0.077), past history of HBV infection (P = 0.005), total bilirubin (P < 0.001), albumin level (P < 0.001), international normalized ratio (INR) (P < 0.001), alanine aminotransferase (P = 0.050), platelet (P < 0.001), total cholesterol (P = 0.047), and LDL cholesterol (P = 0.002) levels. Diabetes showed a statistical difference by multivariable analysis [odds ratio (OR) 4.88, 95% confidence interval (CI): 1.08-21.99, P = 0.039], although no significant difference was found in univariate analysis. In addition, three cirrhosis-related parameters remained statistically different, including INR (OR 117.14, 95% CI: 4.19-3272.28, P = 0.005), albumin (OR 0.89, 95% CI: 0.80-0.99, P = 0.027), and platelet count (OR 0.992, 95% CI: 0.987-0.999, P = 0.002).
Besides the three cirrhosis-related parameters, DM was found to be the sole independent factor associated with HCC in patients with HBV-related cirrhosis, compared with those without cirrhosis.
World Journal of Gastroenterology 09/2010; 16(35):4467-75. · 2.47 Impact Factor
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ABSTRACT: To investigate the efficacy and safety of compound azintamide on dyspepsia symptoms.
One hundred and eighty dyspepsia patients were divided into two groups according to dyspepsia symptom related with gastrointestinal disease (group A) or biliary system disease (group B), whose dyspepsia symptom were not improved by the Domperidone 10 mg tid for 2 weeks. Two tablets of compound azintamide were administered orally following a meal, tid for 2 weeks. The changes of symptoms score of upper abdominal distention, upper abdominal pain or discomfort anorexia and effective rate as well as adverse events were recorded.
Compound azintamide greatly improved the symptoms of upper abdominal distention, upper abdominal pain or discomfort and anorexia. All symptoms scores were significantly decreased after 2 weeks of compound azintamide (P < 0.01). The effective rate of each symptom and total symptoms score were more than 84.9% and 92.5%. One patient reported mild rash at the fourteenth days, which disappeared 3 days later.
Compound azintamide showed effective and safety in treatment of patient with dyspepsia symptoms when Domperidone therapy is not satisfactory.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 11/2008; 47(11):910-3.
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ABSTRACT: To develop a conditionally replicative gene-viral vector system called CNHK500-p53, which contains dual promoters within the E1 region, and combines the advantages of oncolytic virus and gene therapies for hepatocellular carcinoma (HCC).
CNHK500-p53 was constructed by using human telomerase reverse transcriptase (hTERT) promoter to drive adenovirus E1a gene and hypoxia response element (HRE) promoter to drive adenovirus E1b gene. p53 gene expressing cassette was inserted into the genome of replicative virus. Viral replication experiments, cytopathic effect (CPE) and methyl thiazolyl tetrazolium (MTT) assay were performed to test the selective replication and oncolytic efficacy of CNHK500-p53.
Immunohistochemistry verified that infection with CNHK500-p53 was associated with selective replication of adenovirus and production of p53 protein in telomerase-positive and hypoxia-inducible factor-dependent HCC cells. p53 protein secreted from HepG2, infected with CNHK500-p53 was significantly higher than that infected with nonreplicative adenovirus Ad-p53 in vitro (388 +/- 34.6 microg/L vs 76.3 +/- 13.17 microg/L). Viral replication experiments showed that replication of CNHK500-p53 and CNHK500 or WtAd5, was much stronger than that of Ad-p53 in tested HCC cell lines. CPE and MTT assay indicated that CNHK500-p53 selectively replicated in and killed HCC cells while leaving normal cells unaffected.
A more efficient gene-viral system is developed by combining selective oncolysis with exogenous expression of p53 against HCC cells.
World Journal of Gastroenterology 03/2007; 13(5):683-91. · 2.47 Impact Factor
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ABSTRACT: To investigate whether microvessel density (MVD) is related with prognosis in gastric cancer patients, and the expression of cyclooxygenase-2 (COX-2) and vessel endothelial growth factor (VEGF) so as to determine the possible role of COX-2 and VEGF in gastric cancer angiogenesis.
Forty-seven formalin-fixed paraffin-embedded tissue samples of gastric cancer were evaluated for COX-2, VEGF by immunohitochemical staining. To assess tumor angiogenesis, MVD was determined by immunohitochemical staining of endothelial protein factor VIII-related antigen. The relationship among COX-2 and VEGF expression, MVD, and clinicopathologic parameters was analyzed.
Among the 67 samples, high MVD was significantly associated with lymph node metastasis and poor survival. Multivariate survival analysis showed that MVD value and lymph node metastasis were independent prognostic factors. The expression rate of COX-2 and VEGF was significantly higher than that of the adjacent tissues. COX-2 and VEGF expression in gastric cancer was significantly correlated with tumor differentiation and depth of invasion, but not with survival. The mean MVD value of COX-2 or VEGF positive tumors was higher than that of COX-2 or VEGF negative tumors. A significant correlation was found between the expressions of COX-2 and VEGF.
MVD may be one of the important prognostic factors for gastric cancer patients. COX-2 and VEGF may play an important role in tumor progression by stimulating angiogenesis. VEGF might play a main role in the COX-2 angiogenic pathway. The inhibition of angiogenesis or COX-2, VEGF activity may have an important therapeutic benefit in the control of gastric cancer.
World Journal of Gastroenterology 01/2007; 12(47):7598-603. · 2.47 Impact Factor
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ABSTRACT: Over-dose glucocorticoid was frequently used in patients with severe acute respiratory syndrome (SARS), the aim of the present study is to investigate the frequency and risk factors of corticosteroid-induced diabetes in this situation.
One hundred thirty-three cases of SARS admitted from May to June 2003 in our hospital were included in the study. Maximal dose, average daily dose, treatment course and fasting plasma glucose level (FPG) were recorded. Corticosteroid-induced diabetes was diagnosed if FPG was equal to or higher than 7 mmol/L twice or more after the administration of glucocorticoids.
Ninety five patients (71.9%) were prescribed with glucocorticoid among the 132 patients. Thirty-three patients (36.3%) were diagnosed as corticosteroid-induced diabetes according to the FPG. Significant differences were found in daily maximal dosage, duration of treatment and average dosage of methylprednisolone between the patients with and without corticosteroid-induced diabetes (275 mg/d vs 136 mg/d, 24 d vs 16 d, 139 mg/d vs 91 mg/d, P < 0.01). As compared with the lowest tertile, the frequency of diabetes in SARS patients treated with highest tertile of maximal daily dosage, treatment duration, average dosage or total dosage were significantly higher (64.7% vs 13.0, 61.9% vs 17.4%, 62.5% vs 21.7%, and 59.2% vs 13.6%, P < 0.05 for all comparisons). If the patients were treated with an average dose less than 90 mg/d and treatment duration shorter than 15 days, the diabetes incidence was 10.5%. After adjusting age and sex, the daily maximal dosage of methylprednisolone was the only factor that might predict the occurrence of diabetes.
Over-dose administration of methylprednisolone in SARS patients leads to a high frequency of diabetes. Decreasing the daily maximal dosage may be beneficial to the reduction of corticosteroid-induced of diabetes.
Zhonghua nei ke za zhi [Chinese journal of internal medicine] 03/2004; 43(3):179-82.
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 07/2003; 11(6):373-4.
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Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology 03/2003; 11(2):116.
