Hongmei Zheng

Association of IL-1beta gene polymorphism with cachexia from locally advanced gastric cancer

BackgroundIL-1beta has been implicated in inflammatory episode. In view of the inflammatory nature of cancer cachexia, we determined the predictive value of IL-1B-31 T/C, -511 C/T, +3954 C/T and IL-1RN VNTR gene polymorphisms on the occurrence of cachexia associated with locally advanced gastric cancer.MethodsThe study included 214 patients and 230 healthy volunteers. Genomic DNA was prepared from peripheral blood leukocytes. Genotypes and allele frequencies were determined in patients and healthy controls using restriction fragment length polymorphism analysis of polymerase chain reaction products.ResultsThe overall frequencies of IL-1B-31 T, -511 T, +3954 T and IL-1RN VNTR alleles in patients with locally advanced gastric cancer were all comparable with those in controls. No significant differences were found in the distribution of IL-1B-31 T, -511 T and IL-1RN VNTR between patients with cachexia and without. Patients with cachexia showed a significantly higher prevalence of IL-1B+3954 T allele than those without (P = 0.018). In a logistic regression analysis adjusted for actual weight, carcinoma location and stage, the IL-1B+3954 CT genotype was associated with an odds ratio of 2.512 (95% CI, 1.180 – 5.347) for cachexia.ConclusionThe IL-1B+3954 T allele is a major risk for cachexia from locally gastric cancer. Genetic factors studied are not likely to play an important role in the determination of susceptibility to locally advanced gastric cancer.

Association of Interleukin-8 with Cachexia from Patients with Low-Third Gastric Cancer

Background. Interleukin (IL)-8 has been implicated in the development of cancer cachexia. The polymorphism of IL-8 gene, which may affect the production level of IL-8, may be associated with cancer cachexia. Methods. The serum IL-8 level in our study was examined by radioimmunoassay. We also analyzed single nucleotide polymorphisms (SNPs) −251 A/T and +781 C/T of IL-8 gene, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results. The serum levels of IL-8 were significantly elevated in patients with low-third gastric cancer compared with controls, and were further up-regulated in patients with cachexia than those without (Z = −3.134, P = .002). A significantly increased frequency of +781 T allele was noted in patients with cachexia (OR = 2.247, 95% CI: 1.351–3.737, P = .002). The +781 TT genotype was observed to be associated with a significantly increased risk of cachexia (OR = 3.167, 95% CI: 1.265–7.929, P = .011), and with odds ratio of 3.033 (95% CI: 1.065–8.639, P = .038) for cachexia after adjusting for potential confounding factors. Meanwhile, haplotype analysis indicated a borderline positive association between T251T781 haplotype and cachexia as compared with the T251C781 haplotype (OR = 4.92, 95% CI: 1.00–24.28;, P = .053). Conclusions. IL-8 appears to be associated with cachexia from patients with low-third gastric cancer.

Interleukin-10 Gene Polymorphisms Influence Susceptibility to Cachexia in Patients with Low-Third Gastric Cancer in a Chinese Population

AbstractBackground and Objective: Interleukin (IL)-10 is a pleiotropic cytokine that can both stimulate and suppress the immune response. Previous studies have reported that IL-10 production was significantly elevated in cachectic patients, and it has been confirmed that polymorphisms of the IL10 gene could influence its expression. Therefore, we designed this study to investigate whether polymorphisms of the IL10 gene were associated with cachexia in patients with low-third gastric cancer in a Chinese population. Methods: 190 patients with low-third gastric cancer were included in this study. The serum levels of IL-10 were measured by radioimmunoassay. The single nucleotide polymorphisms (SNPs) at positions -1082A/G, -819T/C, and -592A/C in the IL10 gene promoter were analyzed using polymerase chain reaction (PCR) restriction fragment length polymorphism (PCR-RFLP). Results: The serum levels of IL-10 were significantly higher in patients with cachexia than in those without (Z = −10.66, p<0.001). Single SNP analysis showed that the frequency of the IL10 -1082G allele was increased in patients with cachexia (p = 0.02). The -1082AG and -819CC genotypes were observed to be associated with an increased risk of cachexia. In a logistic regression analysis adjusted for actual weight and carcinoma stage, the -1082AG genotype was associated with an odds ratio (OR) of 2.45 (95% CI 1.21, 4.96; p = 0.01), and the -819CC genotype was associated with an OR of 3.70 (95% CI 1.20, 11.39; p = 0.02) for cachexia. Furthermore, haplotype analysis of the -1082A/G, -819T/C, and -592A/C SNPs revealed that at least five haplotypes (ATA, ACC, GCC, ACA, and ATC) were present in this Chinese population, and the -1082G/-819C/-592C (GCC) haplotype was associated with a significantly increased risk of cachexia as compared with the ATA haplotype (OR = 2.42; 95% CI 1.17, 5.00; p = 0.02). Conclusion: Our results indicate that genetic polymorphisms of IL-10 may influence susceptibility to cachexia in patients with low-third gastric cancer in this Chinese population.

Arpin contributes to bacterial translocation and development of severe acute pancreatitis

AIM To assess the impact of Arpin protein and tight junction (TJ) proteins in the intestinal mucosa on bacterial translocation in patients with severe acute pancreatitis (SAP). METHODS Fifty SAP patients were identified as study objects and then classified into two groups according to the presence of bacterial translocation (BT) in the blood [i.e., BT(+) and BT(-)]. Twenty healthy individuals were included in the control group. BT was analyzed by polymerase chain reaction, colonic mucosal tissue was obtained by endoscopy and the expression of TJ proteins and Arpin protein was determined using immunofluorescence and western blotting. RESULTS Bacterial DNA was detected in the peripheral blood of 62.0% of patients (31/50) with SAP. The expression of TJ proteins in SAP patients was lower than that in healthy controls. In contrast, Arpin protein expression in SAP patients was higher than in healthy controls (0.38 ± 0.19 vs 0.28 ± 0.16, P < 0.05). Among SAP patients, those positive for BT showed a higher level of claudin-2 expression (0.64 ± 0.27 vs 0.32 ± 0.21, P < 0.05) and a lower level of occludin (OC) (0.61 ± 0.28 vs 0.73 ± 0.32, P < 0.05) and zonula occludens-1 (0.42 ± 0.26 vs 0.58 ± 0.17, P = 0.038) expression in comparison with BT (-) patients. Moreover, the level of Arpin expression in BT (+) patients was higher than in BT (-) patients (0.61 ± 0.28 vs 0.31 ± 0.24, P < 0.05). CONCLUSION Arpin protein affects the expression of tight junction proteins and may have an impact on BT. These results contribute to a better understanding of the factors involved in bacterial translocation during acute pancreatitis.

TLR and MBL Gene Polymorphisms in Severe Acute Pancreatitis

AbstractBackground and objective: Mannose-binding lectin (MBL) and toll-like receptor (TLR)-4 gene polymorphisms have been implicated in inflammatory episodes in a number of studies. In view of the inflammatory nature of acute pancreatitis, we aimed to determine the predictive value of two point mutations in the promoter region at position −550 (H/L variants) and −221 (X/Y variants) of the MBL2 gene, and the Asp299Gly and 119C>A polymorphisms of the TLR4 gene on the occurrence of severe acute pancreatitis (SAP). Methods: The study included 132 patients with SAP, 106 with mild acute pancreatitis (MAP), and 121 healthy volunteers. Genotypes were determined using restriction fragment length polymorphism analysis of PCR products and by allele-specific PCR. Results: No significant difference in genotype frequency was noted between the patients with acute pancreatitis and controls for any of the gene loci studied. The distributions of the HY/HY, HY/LY, LY/LY, and LY/LX genotypes of MBL2 gene promoter and 119C>A genotype of the TLR4 gene were similar in patients with mild or severe acute pancreatitis. HY/LX genotype frequency was significantly higher in patients with SAP compared with MAP (26% vs 14%; p = 0.028). Conclusion: Results indicate that the MBL2 HY/LX genotype plays an important role in the determination of disease severity to acute pancreatitis.

Effect of intestinal epithelial autophagy on bacterial translocation in severe acute pancreatitis

BACKGROUND AND OBJECTIVE We examined the impact of autophagy activation on bacterial translocation (BT) and tight junction (TJ) proteins in the intestinal mucosa of patients with severe acute pancreatitis (SAP). METHODS Thirty-one SAP patients were divided into two groups, BT(+) and BT(-), according to the presence of BT in the blood, as detected by 16S rDNA sequencing. Eight healthy individuals were included in the control group. Serum endotoxin levels were measured by ELISA. Colonic mucosal tissue was obtained by endoscopy, and the TJ proteins and phosphatidylethanolamine-conjugated microtubule-associated protein light chain 3 (LC3-II) were analyzed using immunofluorescence and Western blotting. RESULTS The expression of LC3II in patients with SAP was higher than that observed in healthy controls. Patients who tested positive for the presence of BT had a higher level of claudins-2 (CL-2) and a lower level of occludin and Zonula occluden-1 (ZO-1) than BT(-) patients. Moreover, the levels of LC3II in BT(-) patients was higher than that found in BT(+) patients, and occludin and ZO-1 were positively correlated with LC3II. CONCLUSIONS Autophagy activation in the intestinal epithelial cells of patients with SAP and its effects on BT may act through enhancing para-cellular TJs.

Clinicopathological and prognostic significance of aberrant Arpin expression in gastric cancer

AIM To detect the expression of Arpin, and determine its correlation with clinicopathological characteristics and the prognosis of gastric cancer (GC) patients. METHODS A total of 176 GC patients were enrolled as study subjects and classified into groups according to different clinicopathological variables. GC mucosal tissues were obtained via surgery. Another 43 paraffin-embedded tissue blocks of normal gastric epithelium (> 5 cm away from the edge of the tumor) were included in the control group. Immunohistochemistry (IHC) for the Arpin and Arp3 proteins was performed on the formalin-fixed, paraffin-embedded GC tissues. Additionally, expression of the Arpin protein in 43 normal gastric tissues was also determined using IHC. RESULTS Expression of the Arpin protein in GC was lower than that in normal gastric mucosa (30.68% vs 60.47%, P < 0.001). A χ2 test of the 176 GC samples used for IHC showed that decreased Arpin expression was associated with advanced TNM stage (P < 0.01) and the presence or absence of lymph node metastasis (80.92% vs 35.56%, P < 0.001). Additionally, a significant correlation was observed between the expression of Arpin and the presence of the Arp2/3 complex in GC tissues (χ2 = 30.535, P < 0.001). Moreover, a multivariate Cox regression analysis revealed that Arpin expression [hazard ratio (HR) = 0.551, P = 0.029] and TNM stage (HR = 5.344, P = 0.001) were independent prognostic markers for overall survival of GC patients. Regarding the 3-year disease-free survival (DFS), the recurrence rate of GC patients with low Arpin expression levels (median DFS 19 mo) was higher than that in the high-Arpin-expression group (median DFS 34 mo, P = 0.022). CONCLUSION Low Arpin levels are associated with clinicopathological variables and a poor prognosis in GC patients. Arpin may be regarded as a potential prognostic indicator in GC.