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)

Cytokines produced in the tumour microenvironment have an important role in cancer pathogenesis. Altered cytokine expression may result in increased susceptibility to and/or poor prognosis in certain cancers. Therefore, the aim of this study was to investigate the influence of interleukin (IL)-8 and IL-10 on sporadic colon cancer development and progression. In our study, a statistically significant increase in IL-8 messenger RNA (mRNA) expression and decrease in IL-10 mRNA expression in tumour tissue compared with normal mucous tissue was observed (P = 0.003; P = 1.3 x 10(-9)). No association was found between IL-8 -251 A/T genotypes and IL-8 mRNA expression in tumour and corresponding normal mucous tissue, as well as susceptibility to sporadic colon cancer. Positive immunohistochemical IL-8 staining was more frequent in moderately and poorly differentiated tumours compared with well-differentiated tumours (P = 0.024). Finally, IL-8 significantly stimulated invasion of HT-29 cells in vitro (P = 0.000172). Significant association of IL-10 -1082 A/G, -819 T/C and -592 A/C genotypes and IL-10 mRNA expression in tumour tissue was observed (P = 0.022; P = 0.013; P = 0.02). Significant association of -819 T/C and -592 A/C genotypes and IL-10 mRNA expression in corresponding normal mucous tissue was observed (P = 0.01; P = 0.04) as well. IL-10 single-nucleotide polymorphism (SNP) promoter genotypes associated with low IL-10 mRNA expression (-819 TT; -592 AA) were also associated with increased risk of sporadic colon cancer compared with high-expression genotypes [odds ratio, 5.53; 95% confidence interval (CI), 1.53-20.1; odds ratio, 4.07; 95% CI, 1.28-12.96]. Positive IL-10 immunohistochemical reaction was more frequent in well-differentiated and moderately differentiated tumours compared with poorly differentiated tumours (P = 0.036). In Dukes' C tumours, positive IL-10 immunohistochemical reaction was less frequent compared with Dukes' A and B tumours (P = 0.023). Taken together, our results point to possible tumour promoting role of IL-8 and potential protective role of IL-10 in sporadic colon cancer.
Carcinogenesis 2008 Aug
PMID:Influence of interleukin-8 and interleukin-10 on sporadic colon cancer development and progression. 1862 51

Nitropyrene (1-NP) is classified as Group 2B carcinogen and is one of the main components of diesel exhaust particles (DEP), which are generated from incomplete combustion of automobile engines to cause human cancer or inflammatory diseases. Although many reports on the mutagenesis or carcinogenesis of 1-NP have been released, non-carcinogenic toxicities of 1-NP have not been widely studied. In this study, induction of pro-inflammatory signals by 1-NP was investigated using cultured human bronchial epithelial cells, BEAS-2B. By using microarray analysis and RT-PCR technique, it was found that 1-NP induced the expression of genes related to the pro-inflammatory responses such as pentaxin, IL-1beta, IL-6, IL-8, C-X-C motif ligand 2 (CXCL2), and TNF-alpha. 1-NP was also found to induce ROS generation and intracellular GSH decrease. It suggested that 1-NP may be a pivotal component of DEP to cause inflammatory diseases.
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PMID:Induction of pro-inflammatory signals by 1-nitropyrene in cultured BEAS-2B cells. 1904 80

IL-8 or CXCL8 has been associated with tumor angiogenesis, metastasis, and poor prognosis in breast cancer. Estrogen is crucial in breast carcinogenesis and tumor progression. Whether sex steroids affect IL-8 secretion of normal breast tissue or breast cancer is not known. Several cell types in a tissue secrete IL-8. Hence, regulatory mechanisms of IL-8 need to be investigated in whole tissue. We used microdialysis to sample IL-8 in normal human breast tissue in situ in pre- and postmenopausal women, preoperatively in breast cancers of women, and in experimental breast cancer in mice. We found a significant positive correlation between IL-8 and estradiol in normal breast tissue and hormone-dependent breast cancer in vivo. Ex vivo, estradiol exposure increased the IL-8 secretion of normal whole breast tissue in culture. In experimental breast cancer, estradiol increased IL-8 whereas the anti-estrogen tamoxifen inhibited the secretion of IL-8 both in vitro and extracellularly in vivo in tumors of nude mice. An anti-IL-8 Ab inhibited endothelial cell proliferation induced by cancer cell produced IL-8 and tumors with low IL-8 levels exhibited decreased angiogenesis. Our results strongly suggest that estradiol has a critical role in the regulation of IL-8 in normal human breast tissue and human breast cancer. IL-8 may present a novel therapeutic target for estrogen driven breast carcinogenesis and tumor progression.
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PMID:Estradiol increases IL-8 secretion of normal human breast tissue and breast cancer in vivo. 1910 68

Stimulation of epidermal growth factor receptor (EGFR) results in the activation of signal transducer and activator of transcription-3 (STAT3), a transcriptional factor associated with carcinogenesis. Proinflammatory cytokines are capable of activating a tumor cell death program by reducing EGFR tyrosine phosphorylation. This study aimed to identify EGFR expression in laryngeal carcinoma and determine the relationship with STAT3 and proinflammatory/regulatory cytokine secretion. An analysis of EGFR expression (membranous EGFR-m and cytoplasmic EGFR-c) was performed in tumor tissues by immunohistochemical (IHC) staining in 45 medical cases of laryngeal carcinoma. STAT3 expression in freshly isolated tumor and non-cancerous normal epithelial cells by RT-PCR was analyzed in 24 patients after total larynx resection. The concentrations of TNFalpha, IL-2, IL-6, IL-8 and IFNgamma secreted by purified peripheral blood mononuclear cells (PBMCs) or contained in whole blood samples were measured by ELISA. The relationship between EGFR and mRNA STAT3 expression as well as the level of secreted cytokines was investigated. In our study, 93.3% tumors expressed EGFR-m and 37.8% EGFR-c. It also revealed a statistically significant dependence of the EGFR status on STAT3 expression in neoplastic tissues. Tumors with IHC EGFR-m positive staining >50% of the total number of cells, as well as with EGFR-c positive staining, were characterized by the most frequent presence of STAT3 expression. Our data demonstrate a significant negative relationship between EGFR-m expression and TNFalpha concentration, and a positive connection between membranous EGFR and IL-8 or IFNgamma levels recorded in isolated PBMCs. Furthermore, this study revealed a significant relationship between EGFR-c immunoexpression and IL-8 or IFNgamma concentration. Our findings have confirmed a key role of EGFR in determining the proliferative and malignant potential of laryngeal carcinoma.
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PMID:Impact of EGFR immunoexpression on STAT3 activation and association with proinflammatory/regulatory cytokine pattern in laryngeal squamous cell carcinoma. 1914 33

Systemic inflammation plays an important role in the initiation, promotion, and progression of lung carcinogenesis. The effects of interventions to lower inflammation have not been explored. Accordingly, we conducted a pilot study to explore the effects of exercise training on changes in biomarkers of systemic inflammation among patients with malignant lung lesions. Using a single-group design, 12 patients with suspected operable lung cancer were provided with structured exercise training until surgical resection. Participants underwent cardiopulmonary exercise testing, 6 min walk testing, pulmonary function testing, and blood collection at baseline and immediately prior to surgical resection. Systemic inflammatory markers included intracellular adhesion molecule (ICAM)-1, macrophage inflammatory protein-1alpha, interleukin (IL)-6, IL-8, monocyte chemotactic protein-1, C-reactive protein, and tumor necrosis factor-alpha. The overall exercise adherence rate was 78%, with patients completing a mean of 30 +/- 25 sessions. Mean peak oxygen consumption increased 2.9 mL.kg-1.min-1 from baseline to presurgery (p = 0.016). Results indicate that exercise training resulted in a significant reduction in ICAM-1 (p = 0.041). Changes in other inflammatory markers did not reach statistical significance. Change in cardiorespiratory fitness was not associated with change in systemic inflammatory markers. This exploratory study provides an initial step for future studies to elucidate the potential role of exercise, as well as identify the underlying mechanisms of action, as a means of modulating the relationship between inflammation and cancer pathogenesis.
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PMID:Effects of presurgical exercise training on systemic inflammatory markers among patients with malignant lung lesions. 1937 50

Prostate cancer (PCa) is one of the most common cancers in the world. Inflammation has been described as a risk factor for PCa and depends on the production of cytokines in response to tissue damage or the presence of stimuli that induces cellular stress. Interindividual variation in cytokine production is partially controlled by single-nucleotide polymorphisms (SNPs) that have been associated with differential production of cytokines. We have recently showed that SNP-SNP interactions of cytokine genes are associated with PCa risk. However, little is known about the association of cytokine SNPs and PCa aggressiveness. In this study, we evaluated the association of 15 SNPs in five cytokine genes and aggressiveness of PCa in African- and Caucasian-American individuals. Caucasian Americans with the genotypes IL10-1082GG or IL1B+3954TT had 2.31-fold [95% confidence interval (CI) = 1.13-4.72] and 3.11 (95% CI = 1.20-8.06)-fold risk, respectively, of developing aggressive PCa, as compared with individuals without those genotypes. We did not find any associations in the African-American group. Using Multivariate Adaptive Regression Splines modeling for exploratory SNP-SNP interactions, our results showed that more aggressive PCa in Caucasians Americans is associated with the CT genotype at IL8-47 [odds ratios (OR) = 3.50; 95% CI = 1.13-10.88] or combined genotypes of IL1B-511CC and IL10-1082GG (OR = 3.38; 95% CI = 1.70-6.71). Unfortunately, the same analysis could not be performed in the African-Americans due to limited number of individuals. With limited sample size, the results from this study suggest that SNPs in cytokine genes may be associated with PCa aggressiveness. More extensive studies are warranted to validate our findings.
Carcinogenesis 2009 Aug
PMID:Cytokine genetic polymorphisms and prostate cancer aggressiveness. 1947 90

Recently, lipoxins (LXs) and resolvins (Rvs) have become the topic of intense interest because of expanding views of their action, particularly in chronic disorders where unresolved inflammation is a key factor leading to colon carcinogenesis. Rvs are biosynthesized from omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) via cyclooxygenase-2/lipoxygenase (COX-2/LOX) pathways; Rvs are shown to dramatically reduce dermal inflammation, peritonitis, dendritic cell migration, and interleukin production. This explains that dietary supplementation of omega-3 fatty acids generates potent local endogenous mediators that control inflammation. LXs are biosynthesized from COX-2/LOX pathways. Metabolites of 15-LOX-1 and 2 are anti-tumorigenic; similarly, 15-epi-LXA(4) synthesized during COX-2 acetylation by low doses of aspirin too possesses anti-tumorigenic effects. Acetylating nonsteroidal anti-inflammatory drugs (NSAIDs), like aspirin, switches COX-2 from forming PGE(2) (promoting tumorigenesis) to 15-epi-LXA(4) (antitumorigenesis). LXs and Rvs are endogenously generated during the spontaneous resolution phase. These newly identified LXs and Rvs have proved to be potent regulators of both leukocytes and cytokine productions, thereby regulating the events of interest in inflammation and resolution. In light of existing knowledge on interconnected pathways of pro-inflammatory mediators (leukotrienes, chemokines (IL8, SDF-1 alpha, MIP-1 alpha, MCP-1,2 etc), and cytokines (IL3, IL6, IL12, IL-1 beta, GM-CSF, B94, TNF-alpha etc)), the anti-inflammatory properties of pro-resolving mediators in preventing chronic inflammation which leads to carcinogenesis needs further understanding. In this review, we explore the mechanisms that trigger formation of LXs and Rvs, to highlight the relative importance of LXs and Rvs in carcinogenesis in relation to pro-inflammatory mediators.
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PMID:Role of lipoxins and resolvins as anti-inflammatory and proresolving mediators in colon cancer. 1960 7

Nuclear factor-kappaB (NF-kappaB) plays a major role in host inflammatory responses and carcinogenesis and as such is an important drug target for adjuvant therapy. In this study, we examined the effect of caffeic acid phenethyl ester (CAPE), an NF-kappaB inhibitor, on Helicobacter pylori (H. pylori)-induced NF-kappaB activation in cell culture and chronic gastritis in Mongolian gerbils. In AGS gastric cancer cells, CAPE significantly inhibited H. pylori-stimulated NF-kappaB activation and mRNA expression of several inflammatory factors in a dose-dependent manner, and prevented degradation of IkappaB-alpha and phosphorylation of p65 subunit. To evaluate the effects of CAPE on H. pylori-induced gastritis, specific pathogen-free male, 6-week-old Mongolian gerbils were intragastrically inoculated with H. pylori, fed diets containing CAPE (0-0.1%) and sacrificed after 12 weeks. Infiltration of neutrophils and mononuclear cells and expression of NF-kappaB p50 subunit and phospho-IkappaB-alpha were significantly suppressed by 0.1% CAPE treatment in the antrum of H. pylori-infected gerbils. Labeling indices for 5'-bromo-2'-deoxyuridine both in the antrum and corpus and lengths of isolated pyloric glands were also markedly reduced at the highest dose, suggesting a preventive effect of CAPE on epithelial proliferation. Furthermore, in the pyloric mucosa, mRNA expression of inflammatory mediators including tumor necrosis factor-alpha, interferon-gamma, interleukin (IL)-2, IL-6, KC (IL-8 homologue), and inducible nitric oxide synthase was significantly reduced. These results suggest that CAPE has inhibitory effects on H. pylori-induced gastritis in Mongolian gerbils through the suppression of NF-kappaB activation, and may thus have potential for prevention and therapy of H. pylori-associated gastric disorders.
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PMID:Anti-inflammatory effects of caffeic acid phenethyl ester (CAPE), a nuclear factor-kappaB inhibitor, on Helicobacter pylori-induced gastritis in Mongolian gerbils. 1961 61

Chemokines are important in inflammation and in carcinogenesis. We hypothesized that besides oro-laryngeal cancer, oral inflammatory states, such as periodontitis, may also influence the chemokine profile of oral fluid. The aim of this study was to characterize the chemokine isoforms in the oral fluid of patients with periodontitis and in the oral fluid of patients with head and neck cancer. Using enzyme-linked immunosorbent assays (ELISA), it was found that the concentrations of CXCL8, CXCL10, and CCL14 were significantly elevated in the oral fluids of the cancer patients. However, periodontitis did not significantly alter the chemokine levels in oral fluid. Identification of chemokine isoforms by a proteomic approach using a newly developed three-step purification procedure was applied on the oral fluid of head and neck cancer and periodontitis patients and on the conditioned medium from carcinoma cells. Carcinoma cells produced predominantly intact CXCL1, CXCL2, CXCL8, and CCL2, whereas CXCL8 also appeared in a truncated, more active, form. Unfortunately, the chemokine concentrations in oral fluids were too low to allow full biochemical identification of the modified isoforms. However, the chemokine profile of head and neck cancer significantly changed after therapy, indicating that it is a useful parameter in clinical practice.
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PMID:Carcinoma cell-derived chemokines and their presence in oral fluid. 1962 45

The small GTPase Ras is mutated to remain in the active oncogenic state in one-third of human cancers, thereby promoting tumorigenesis. It has recently come to light that one consequence of oncogenic Ras signaling is secretion of cytokines vascular endothelial growth factor (VEGF), interleukin 6 (IL6), hCXCL1 (Gro-alpha) and hCXCL8 (IL8). As the latter two belong to the ELR+ Cys-X-Cys (CXC) chemokine family, we investigated whether the entire family of ELR+ CXC chemokines plays a role in oncogenic Ras-mediated tumorigenesis. We now demonstrate that oncogenic Ras induced the expression and secretion of the ELR+ CXC chemokine family in different tumorigenic human cells and that these chemokines are elevated in tumor specimens. Moreover, genetic ablation of the common receptor for these chemokines, mCXCR2, reduced oncogenic Ras-driven tumorigenesis in mice. Taken together, we suggest that oncogenic Ras induces the secretion of the ELR+ CXC chemokine family to promote tumorigenesis. This chemokine signature may identify the presence of Ras activation in cancer and perhaps even serve as targets for oncogenic Ras-driven tumor cells.
Carcinogenesis 2009 Nov
PMID:ELR+ CXC chemokines and oncogenic Ras-mediated tumorigenesis. 1980 74


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