Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10145 (IL-8)
 23,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To evaluate the role of chronic inflammation in the development of gallstones and biliary tract cancer, we examined the risk associated with 62 single nucleotide polymorphisms (SNPs), in 22 inflammation-related genes, in a population-based case-control study conducted in Shanghai, China, where the incidence of biliary tract cancer has been increasing in recent decades. The study included 411 cases with biliary tract cancer (237 gallbladder, 127 extrahepatic bile duct, and 47 ampulla of Vater), 895 with biliary stones, and 786 controls randomly selected from the population. Unconditional logistic regression was used to calculate odds ratios and 95% confidence intervals for the association of individual SNPs and haplotypes with biliary stones and biliary tract cancer. Of the 62 SNPs examined, 14 were related to the risk of biliary cancer and stones. Specifically, variants in the IL8, IL8RB, RNASEL, and NOS2 genes were associated with biliary stones, whereas VEGF variants were associated with gallbladder cancer. Of the 10 genes with multiple SNPs from which we inferred haplotypes, only one IL8RB haplotype, consisting of 3 SNPs (rs2230054, rs1126579, and rs1126580), was associated with the risk of bile duct cancer (P = 0.003) and biliary stones (P = 0.02), relative to the most frequent haplotype. In summary, common variants in genes that influence inflammatory responses may predispose to gallstones and biliary tract cancer, suggesting the need for future studies into the immunologic and inflammatory pathways that contribute to biliary diseases, including cancer.
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PMID:Variants in inflammation genes and the risk of biliary tract cancers and stones: a population-based study in China. 1867 70

Most gallbladder cancer (GBC) cases arise in the context of gallstones, which cause inflammation, but few gallstone patients develop GBC. We explored inflammation/immune-related markers measured in bile and serum in GBC cases compared to gallstone patients to better understand how inflammatory patterns in these two conditions differ. We measured 65 immune-related markers in serum and bile from 41 GBC cases and 127 gallstone patients from Shanghai, China, and calculated age- and sex-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for GBC versus gallstones. We then focused on the markers that were significantly elevated in bile and serum to replicate the findings in serum from 35 GBC cases and 31 gallstone controls from Chile. Comparing the highest versus lowest quantile, 15 markers (23%) were elevated in both serum and bile from GBC versus gallstone patients in the Shanghai study (p<0.05). The strongest OR was for CXCL8 (interleukin-8) in serum (96.8, 95% CI: 11.9-790.2). Of these 15 markers, 6 were also significantly elevated in serum from Chile (CCL20, C-reactive protein, CXCL8, CXCL10, resistin, serum amyloid A). Pooled ORs from Shanghai and Chile for these 6 markers ranged from 7.2 (95% CI: 2.8-18.4) for CXCL10 to 58.2 (95% CI: 12.4-273.0) for CXCL8. GBC is associated with inflammation above and beyond that generated by gallstones alone. This local inflammatory process is reflected systemically. Future longitudinal studies are needed to identify the key players in cancer development, which may guide translational efforts to identify individuals at high risk of developing GBC.
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PMID:Association of inflammatory and other immune markers with gallbladder cancer: Results from two independent case-control studies. 2717 14

We previously demonstrated that cancer-associated fibroblasts (CAFs) promoted the proliferation of gallbladder cancer (GBC) cells, but the mechanism is not clear. Neuropilin-1 (NRP-1) plays an important role in various malignancies as transmembrane glycoprotein. Our goal was to reveal the relationship between CAFs and NRP-1 and their potential functions in GBC. In this study, we found NRP-1 was overexpressed in GBC tissue, associated with poor survival and was up-regulated by CAFs. The cytokine array cluster analysis revealed IL-8 secreted by CAFs facilitated the up-regulation of NRP-1 in tumour cells. NRP-1 knockdown suppressed tumour growth in vivo. Gene expression microarray analysis showed 581 differentially regulated genes under NRP-1 knockdown conditions. Ingenuity pathway analysis demonstrated that NRP-1 knockdown may inhibit tumour progression by affecting cell proliferation. We then confirmed that NRP-1 knockdown in NOZ and GBC-SD cells significantly inhibited cell proliferation. Additionally, the IL-8 mediated MDM2 and CCNA2 expression were affected by NRP-1 knockdown. Our findings suggested that NRP-1 was up-regulated by CAF-secreted IL-8, which subsequently promoted GBC cell proliferation, and these molecules may serve as useful prognostic biomarkers and therapeutic targets for GBC.
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PMID:Neuropilin-1 is up-regulated by cancer-associated fibroblast-secreted IL-8 and associated with cell proliferation of gallbladder cancer. 3295 27