Purpose: Persistent interleukin-8 (IL-8) production contributes to chronic inflammation of the stomach. The proinflammatory IL-1h polymorphisms, which enhance the cytokine production, are associated with increased risk of gastric cancer. The À251A/T polymorphism of the IL-8 promoter is involved in several human diseases. Particularly, the À251A is associated with decreased risk of colorectal cancer. We aimed to determine whether the À251 allele resulting in high IL-8 expression was associated with increased risk of gastric carcinoma. Experimental Design: The À251A/T promoters were cloned and analyzed by luciferase assay. Binding of nuclear proteins to the À251A/T promoters was analyzed by electrophoretic mobility shift assay.The À251A/T promoters were differentiated by PCR-RFLP. Comparison of gastric cancer risk between the À251A/T promoters was done by a case-control study. Results:The À251Tallele possessed transcriptional activity 2-to 5-fold stronger than the À251A counterpart. Electrophoretic mobility shift assay showed that the À251A promoter had strong ability to bind to an unknown protein or multiprotein complex. The À251T allele was associated with increased risk of noncardia (P trend = 0.012) and cardia (P trend = 0.029) carcinomas. Gastric carcinoma patients with the low-risk AA genotype had a tendency to sustain intestinal-type carcinomas (m 2 = 6.816; P = 0.033); however, the high-risk À251Tallele was associated with >2-fold increased risk of diffuse-type (AA versus AT + TT: odds ratio, 2.52; 95% confidence interval,1.16-5.49; P = 0.017) and mixed-type (AA versus AT + TT: odds ratio, 2.22; 95% confidence interval, 1.12-4.40; P = 0.019) carcinomas. Conclusions:The IL-8 À251Tallele is significantly associated with increased risk of gastric carcinoma, particularly the diffuse and mixed types in Chinese population.
AIM:To investigate whether vascular endothelial growth factor (VEGF) and basic fibroblastic growth factor (bFGF) are associated with spider angiomas in patients with liver cirrhosis.
METHODS:Eighty-six patients with liver cirrhosis were enrolled and the number and size of the spider angiomas were recorded. Fifty-three healthy subjects were selected as controls. Plasma levels of VEGF and bFGF were measured in both the cirrhotics and the controls.
RESULTS:Plasma VEGF and bFGF were increased in cirrhotics compared with controls (122±13 vs. 71±11 pg/mL, P=0.003 for VEGF; 5.1±0.5 vs. 3.4±0.5 pg/mL, P=0.022 for bFGF). In cirrhotics, plasma VEGF and bFGF were also higher in patients with spider angiomas compared with patients without spider angiomas (185±28 vs. 90±10 pg/mL, P=0.003 for VEGF; 6.8±1.0 vs. 4.1±0.5 pg/mL, P=0.017 for bFGF). Multivariate logistic regression showed that young age and increased plasma levels of VEGF and bFGF were the most significant predictors for the presence of spider angiomas in cirrhotic patients (odds ratio [OR]=6.64, 95 % confidence interval [CI]=2. P=0.002; OR=4.35, P=0.014; OR=5.66, P=0.004, respectively).
CONCLUSION:Plasma VEGF and bFGF are elevated in patients with liver cirrhosis. Age as well as plasma levels of VEGF and bFGF are significant predictors for spider angiomas in cirrhotic patients.
Honokiol inhibits HCV infection by targeting cell entry and replication and, only at a concentration >30 μM, IRES-mediated translation of HCV life cycle. Based on its high therapeutic index (LD(50) /EC(90) = 5.4), honokiol may be a promising drug for the treatment of HCV infection.
SummaryChronic infections with hepatitis B and C viruses (HBV and HCV) are etiologically linked to hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC). Both viruses may induce activation of nuclear factor-kappa B (NF-jB) in hepatocytes that plays a crucial role in the regulation of cell growth and apoptosis. Functional proteomics analysis of proteins associated with NF-jB signaling complexes in both viruses-related HCC tumor and non-tumor tissues may disclose possible common mechanisms in hepatocarcinogenesis. By functional proteomics, we analyzed proteins associated with NF-jB-signaling complexes in four-paired human HCC tumor and non-tumor tissues from HBV-and HCV-infected patients, respectively, and in onepaired tissue with dual viral infection. The quantity of NF-jB-associated proteins was semi-quantitatively measured by protein spot intensity on the gels of two-dimensional polyacrylamide gel electrophoresis. The results showed that overexpression of NF-jB-associated Wnt-1 protein in tumor part was detected in the majority of HBV-and HCV-infected HCC samples. These data suggest that enhanced expression of NF-jB-associated Wnt-1 protein might be a mechanism of hepatocarcinogenesis common to HBV-and HCV-infected patients. NF-jB signaling pathway and Wnt-1 protein could be potential targets for designing highly effective therapeutic agents in treating HCC and for chemoprevention of hepatocarcinogenesis.Abbreviations: m/z -mass-to-charge ratio; 2-DE -two-dimensional polyacrylamide gel electrophoresis; EMSA -electrophoretic mobility shift assay; HBV -hepatitis B virus; HCC -hepatocellular carcinoma; HCV -hepatitis C virus; HSP -heat shock protein; MALDI-Q-TOF -matrix-assisted laser desorption/ ionization-quadrupole-time-of-flight; MS -mass spectrometry; NF-jB -nuclear factor-kappa B
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