interleukin-8 and Adenoma

To study the role of host immune surveillance in the initiation and progression of colorectal cancer (CRC), a set of protumor immunological factors was determined by quantitative real-time PCR (q-PCR) between the primary tumor and the adjacent tumor-free site tissues in 63 patients with colorectal neoplasms. Results showed that expression levels of interleukin (IL)-1β, IL-6, IL-8, IL-17A, IL-23, and cyclooxygenase 2 (COX2) mRNAs, except transforming growth factor beta (TGFβ), in adenoma tissues were significantly higher than that in relative adjacent tissues. Difference of immunological factor levels between adenoma and adjacent tissues (Δ values) was in an order of ΔIL-8 > ΔIL-6 > ΔIL-17A > ΔIL-1β > ΔCOX2 > ΔIL-23; Analysis showed that the value of ΔCOX2 correlated to the grade of dysplastic degree in patients with adenoma. Notably, levels of all these immunological factors in CRC tissues were continuously increased, the order of values of Δ immunological factors was ΔIL-8 > ΔCOX2 > ΔIL-6 > ΔIL-1β > ΔIL-17A > ΔIL-23 > ΔTGFβ. Further analysis revealed that increased value of Δ IL-1β was associated with advanced TNM stage, a higher value of Δ COX2 tended to predicate a deeper degree of tumor invasion; and higher values of Δ IL-1β, IL-6 and COX2 closely correlated to lymph node metastasis in patients with CRC. In addition, the ratio of ΔIL-8/ΔTGFβ was most obvious changed factor and associated with node metastasis in patients with CRC. Therefore, we concluded that the difference of protumor immunological factor levels between the primary tumor site and tumor-free site along the adenoma-carcinoma sequence reflects the change of protumor/antitumor force balance, which is associated with CRC initiation and invasion.

Topics: Adenoma; Colorectal Neoplasms; Cyclooxygenase 2; Humans; Interleukin-6; Interleukin-8

Accumulative evidence suggests that the biological behavior of cancer stem-like cells (CSCs) is regulated by their surrounding niche, in which cytokines function as one of the main mediators for the interaction between CSCs and their microenvironment in the colorectal cancer (CRC).. We characterized the presentation of CSCs and the interleukin (IL)- 8 network in the adenoma/CRC epithelium using quantitative real-time PCR (q-PCR), immunohistochemistry (IHC) and double immunofluorescence. In addition, the capacity of IL-1β to stimulate epithelial IL-8 production in colon cancer Caco-2 cells was examined in vitro and the IL-8 product was measured by enzyme-linked immunosorbent assay (ELISA).. IHC observation showed increased expression of both CSCs and IL-8 in the adenoma and CRC epithelium, and q-PCR results revealed that increased expression of IL-1β transcript was strongly correlated with increased IL-8 transcript levels in both adenoma and CRC tissues. Double immunofluorescence images demonstrated the coexpression of the IL-8 receptors IL-8RA and IL-8RB with LGR5 labeled CSCs in CRC tissue sections. Consistently, in vitro experiments showed that coculture of Caco-2 cells with IL-1β at concentrations of 1, 5, 10 and 20 ng/ml resulted in a dose-dependent release of IL-8, which could be specifically inhibited by cotreatment with the IL-1β receptor antagonist.. These results demonstrate activation of the IL-8 network in the niche of CSCs from the precancerous adenoma stage to the CRC stage, which is potentially stimulated by IL-1β in CRC cells.

Topics: Adenoma; Caco-2 Cells; Colorectal Neoplasms; Humans; Immunohistochemistry; Interleukin-8; Tumor Microenvironment

Cytokine gene polymorphisms modify expression and their circulating protein levels reflect inflammatory response. Chronic inflammation plays a key role in the pathogenesis of colorectal neoplasia (CRN) associated with inflammatory bowel disease, but it is not clear whether inflammation is a cause or an effect of tumours in sporadic CRN. We therefore investigated the association of cytokine gene polymorphisms and circulating cytokine levels on the risk of CRN in Northeast Scotland, which has a high incidence of CRN. We recruited two groups of patients from a screening colonoscopy cohort, either preprocedure or 3-24 months postprocedure. Participants with CRN were compared with participants with no evidence of CRN (controls). Blood-derived DNA was used to genotype polymorphisms in IL1B, IL1-RN, IL6, IL8, IL10, PTGS2 and TNFA genes. Circulating levels of high-sensitivity C-reactive protein and six cytokines [interleukin-1β (IL-1β), IL-4, IL-6, IL-8, IL-10 and tumour necrosis factor-α (TNF-α)] were measured. To examine the effect of CRN resection on marker levels, we used propensity score matching. A total of 884 patients were eligible for analysis, including 388 CRN cases and 496 controls. Cases were older (mean age 64 vs. 62 years, P<0.01) and more likely to be men (67 vs. 55%, P<0.001). Controls were more likely to be regular users of NSAID (P<0.0001). Compared with homozygous carriage of respective common alleles, proinflammatory CC genotypes of IL1B-31C>T [odds ratio (OR) (95% confidence interval (CI) 1.68 (1.03-2.73)] and PTGS2-765 C>G [OR (95% CI) 2.97 (1.05-8.46)] were each associated with an increased risk of CRN. Conversely, carriage of the A allele of IL8-251A>T was associated with a lower risk of CRN compared with the TT genotype [ORs (95% CI) 0.60 (0.41-0.86) for heterozygous, 0.88 (0.57-1.37) for homozygous, and 0.68 (0.48-0.95) for heterozygous and homozygous combined]. Compared with postprocedure cases, IL8, TNF-α and C-reactive protein levels were significantly higher in preprocedure cases, but IL4 and IL10 protein levels were significantly lower. Proinflammatory cytokine gene polymorphisms in IL1B-31 and PTGS2-765 increase the risk of developing CRN. Levels of proinflammatory IL8, TNF-α and C-reactive protein markers are significantly higher while CRN is in situ. Along with the NSAID findings, these data point to inflammation as an underlying pathogenetic mechanism in CRN.

Topics: Adenoma; Aged; C-Reactive Protein; Carcinoma; Case-Control Studies; Cohort Studies; Colonoscopy; Colorectal Neoplasms; Cyclooxygenase 2; Cytokines; Early Detection of Cancer; Female; Gene Frequency; Genetic Predisposition to Disease; Humans; Interleukin 1 Receptor Antagonist Protein; Interleukin-10; Interleukin-1beta; Interleukin-4; Interleukin-6; Interleukin-8; Male; Middle Aged; Occult Blood; Polymorphism, Genetic; Scotland; Tumor Necrosis Factor-alpha

To evaluate the concentrations of eight cytokines in order to identify potential biomarkers for assisting in the detection of colorectal cancer.. The concentrations of IFN-γ, IL-10, IL-6, IL-8, TNF-α, MMP-2, MMP-7 and MMP-9 were detected in the sera of 69 healthy controls, 93 colorectal adenoma patients and 149 colorectal cancer (CRC) patients.. Multivariate logistic regression analyses, which included CEA, CA199, IL-8, TNF-α and MMP-7, were used to evaluate the diagnostic value for differentiating between colorectal adenoma and CRC. The area under the curve was 0.945 (95% CI: 0.909-0.981). The sensitivity and specificity were 85.86 and 96.78%, respectively. Compared with the conventional biomarkers CEA and CA199, multivariate logistic regression showed significant improvement.. Our data demonstrated that testing using a panel of three serum cytokines, CEA and CA199 may have strong potential to assist in the detection of CRC.

Topics: Adenoma; Adult; Aged; Antigens, Tumor-Associated, Carbohydrate; Area Under Curve; Biomarkers, Tumor; Carcinoembryonic Antigen; Case-Control Studies; Colorectal Neoplasms; Cytokines; Female; Humans; Interleukin-8; Logistic Models; Male; Matrix Metalloproteinase 7; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Tumor Necrosis Factor-alpha; Young Adult

Pituitary adenomas are common intracranial neoplasms that generate symptoms as a result of either mass effect or the increased production of pituitary hormones. Although mostly benign, these tumours can be associated with considerable morbidity. We investigated a panel of immunohistochemical preparations to identify potential therapeutic targets and surrogate markers of clinical outcome.. Tumour tissue from 25 patients was evaluated for immunohistochemical expression of somatostatin receptors 1‒5, von Willebrand-factor (vWF), interleukin-8 (IL-8), vascular endothelial growth factor receptor 2 (VEGFR-2), kinesin spindle protein (Eg5) and MIB-1 (Ki-67), and its relationship with clinical features was analysed.. The proliferation marker MIB-1 (Ki-67) was the only marker predictive of adenoma recurrence. Of note, 67% of all relapses were associated with tumours showing luteinising hormone expression. All pituitary adenomas showed variable somatostatin receptor, IL-8, Eg5, vWF and VEGFR-2 expression; a relationship between these parameters and clinical outcome could not be demonstrated in this cohort.. This study validates MIB-1 (Ki-67) as a reliable marker of tumour recurrence in pituitary adenomas. Considering the consistently increased expression of Eg5, IL-8, VEGFR-2, somatostatin receptors and vWF in these tumours, further investigation as potential therapeutic targets is warranted.

Topics: Adenoma; Adult; Aged; Biomarkers, Tumor; Cell Proliferation; Female; Humans; Immunohistochemistry; Interleukin-8; Ki-67 Antigen; Kinesins; Male; Middle Aged; Neoplasm Recurrence, Local; Neovascularization, Pathologic; Pituitary Neoplasms; Prognosis; Receptors, Somatostatin; Retrospective Studies; Treatment Outcome; Vascular Endothelial Growth Factor Receptor-2; von Willebrand Factor; Young Adult

Inflammatory reactions, known to promote tumor growth and invasion, have been found associated with colorectal carcinoma (CRC). Macrophages are the chief component of the inflammatory infiltration that occurs early in the progression from non-invasive to malignant tumor, with a switch from the pro-inflammatory phenotype to the tumor-promoting phenotype. Tumor and stroma are additional sources of inflammation-related molecules. The study aimed to evaluate, during colorectal carcinogenesis from benign to malignant phases: i) the trend of serum levels of IL-8, IL-6, TGFβ1, VEGF and MMPs; ii) the parallel trend of CRP serum levels; iii) derangement of the principal TGFβ1 receptors (TGFβ1RI/RII) in tumor tissues.. 96 patients with colon adenomas or CRC at different stages of progression, and 17 controls, were recruited. Serum IL-8, IL-6, TGFβ1, VEGF, MMPs and CRP levels were analyzed before endoscopy or surgery. TGFβ1 receptors were evaluated in adenoma biopsies and surgically-removed colorectal adenocarcinomas. Serum levels of IL-8 in adenocarcinoma patients were increased from stage II, when also the enzymatic activity of MMP-9 increased. Of note, the increasing trend of the two serum markers was found significantly correlated. Trend of serum CRP was also very similar to that of IL-8 and MMP-9, but just below statistical significance. TGFβ1 levels were lower at stage III CRC, while IL-6 and VEGF levels had no significant variations. In tissue specimens, TGFβ1 receptors were already absent in about 50% of adenomas, and this percentage of missing receptors markedly increased in CRC stages III and IV.. Combined quantification of serum IL-8, MMP-9 and CRP, appears a reliable and advanced index of inflammation-related processes during malignant phase of colorectal carcinogenesis, since these molecules remain within normal range in colorectal adenoma bearing patients, while consistently increase in the blood of CRC patients, even if from stage II only.

Topics: Adenocarcinoma; Adenoma; Aged; Aged, 80 and over; C-Reactive Protein; Colorectal Neoplasms; Disease Progression; Female; Humans; Interleukin-6; Interleukin-8; Male; Matrix Metalloproteinase 9; Middle Aged; Neoplasm Staging; Receptors, Transforming Growth Factor beta; Time Factors; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A

More than 1.2 million new cases of colorectal cancer are reported each year worldwide. Despite actual screening programs, about 50% of the patients are diagnosed at advanced tumor stages presenting poor prognosis. Innovative screening tools could aid the detection at early stages and allow curative treatment interventions.. A nine target multiplex serum protein biochip was generated and evaluated using a training- and validation-set of 317 highly standardized, liquid nitrogen preserved serum samples comprising controls, adenomas, and colon cancers.. Serum levels of CEA, IL-8, VEGF, S100A11, MCSF, C3adesArg, CD26, and CRP showed significant differences between cases and controls. The largest areas under the receiver operating characteristics curve were observed for CEA, IL-8, and CRP. At threshold levels yielding 90% specificity, sensitivities for CEA, IL-8 and CRP were 26%, 22%, and 17%, respectively. The most promising marker combinations were CEA + IL-8 reaching 37% sensitivity at 83% specificity and CEA + CRP with 35% sensitivity at 81% specificity. In an independent validation set CEA + IL-8 reached 47% sensitivity at 86% specificity while CEA + CRP obtained 39% sensitivity at 86% specificity. Early carcinomas were detected with 33% sensitivity for CEA + IL-8 and 28% for CEA + CRP.. Apart from CEA, IL-8, and CRP, the screening value of additional blood markers and the potential advantage of combining serum biochip testing with fecal occult blood testing needs to be studied. Multiplex biochip array technology utilizing serum samples offers an innovative approach to colorectal cancer screening.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Algorithms; Biomarkers, Tumor; C-Reactive Protein; Carcinoembryonic Antigen; Case-Control Studies; Colonic Neoplasms; Computational Biology; Female; High-Throughput Screening Assays; Humans; Interleukin-8; Male; Middle Aged; Molecular Diagnostic Techniques; Protein Array Analysis; ROC Curve

Pituitary adenomas cause morbidity and mortality due to their localization and influence on pituitary hormone secretion. Although the pathogenesis of pituitary adenomas is unclear, studies have indicated that cytokines are involved. We investigated the role of cytokines, in particular interleukin (IL)-8, in the pathogenesis of growth hormone (GH) producing tumours.. Human somatotroph adenoma tissue was obtained from patients undergoing surgery for acromegaly. The tissue underwent mechanical and enzymatic digestion, was washed, suspended and cultured in 24-chamber plates. After stimulation/inhibition supernatants were harvested. As control of growth hormone producing properties of the cultured cells, GH releasing hormone (GHRH) stimulated and somatostatin inhibited the GH response.. The cultured adenoma cells released both IL-6 and IL-8 and the secretion was inhibited by GHRH and somatostatin. IL-1β dose-dependently stimulated GH, IL-6 and IL-8 secretion.. Using cultured primary somatotroph adenoma cells as a dynamic method, we found a consistent release not only of IL-6 as described previously, but also of IL-8. This finding could be important for reassessing a role of these cytokines in the pathogenesis of pituitary tumour growth and function, and thus form a basis for targeted therapy. In line with previous studies, our results further indicated a common physiological or pathophysiological reaction of endocrine cells to cytokine stimulation.

Topics: Adenoma; Adult; Female; Growth Hormone-Releasing Hormone; Growth Hormone-Secreting Pituitary Adenoma; Hormones; Humans; Interleukin-1beta; Interleukin-8; Male; Pituitary Gland; Somatostatin

The interleukin-8 (IL-8) network is involved in the colorectal cancer (CRC) progression. However, its role during the adenoma-carcinoma transition to date has not been fully investigated. To evaluate the dynamic changes of IL-8 network along the colorectal adenoma-carcinoma sequence, we examined the tissue IL-8 mRNA level in colorectal biopsies from 53 colorectal adenomas, 44 CRCs and 18 controls by quantitative real-time PCR (Q-PCR), and the expressions of IL-8 and its receptors (IL-8RA and IL-8RB) in the tumor microenvironment by immunohistochemistry (IHC) and double IHCs. The results showed that the tissue IL-8 mRNA level began to increase in the precancerous lesions (adenomas) as compared with the controls and became even higher in the CRCs. Significantly, the increase of IL-8 mRNA levels was associated with the increase of dysplastic grades in the adenomas, and also paralleled to the increase of Duke's stages in the CRCs. IHC results revealed that IL-8 and its receptors, IL-8RA and IL-8RB, were observed both in the stroma and in the adenomatous/cancerous cells. By double IHCs, the IL-8 expression was characterized in macrophages, lymphocytes and myofibroblasts in the tumor stroma. Further double IHC identified the co-expression of IL-8 receptors (IL-8RA and IL-8RB) with CD34 positive tumor-associated microvessels in both the adenomas and CRCs. We, therefore, conclude that activated IL-8 network in the tumor microenvironment may function as a significant regulatory factor for the adenoma progression and the adenoma-carcinoma transition.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Carcinoma; Colorectal Neoplasms; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Middle Aged; RNA, Messenger

The seroprevalence of IgG antibodies of Streptococcus gallolyticus subspecies gallolyticus, CIP 105428, was evaluated to investigate the controversial association of S. gallolyticus with colorectal carcinoma and adenoma in attempt to investigate the nature of such association if any, by exploring the mRNA expression of NF-kappaB and IL-8. Moreover, the serological behavior of S. gallolyticus IgG antibodies was compared to that of an indicator bacterium of bowel, Bacteroides fragilis.. ELISA was used to measure IgG antibodies of S. gallolyticus and B. fragilis in sera of 50 colorectal cancer, 14 colorectal adenoma patients, 30 age- and sex- matched apparently healthy volunteers (HV) and 30 age- and sex- matched colonoscopically-proven tumor-free control subjects. NF-kappaB and IL-8 mRNA expression was evaluated in tumorous and non-tumorous tissue sections of carcinoma and adenoma patients in comparison with that of control subjects by using in situ hybridization assay.. Colorectal cancer and adenoma patients were associated with higher levels of serum S. gallolyticus IgG antibodies in comparison with HV and control subjects (P < 0.05) while no similar association was found with serum IgG antibodies of B. fragilis (P > 0.05). ELISA cutoff value for the seropositivity of S. gallolyticus IgG was calculated from tumor-free control group. The expression of NF-kappaB mRNA was higher in tumorous than non-tumorous tissue sections of adenoma and carcinoma, higher in carcinoma/adenoma sections than in control subjects, higher in tumorous sections of carcinoma than in adenoma patients, and higher in S. gallolyticus IgG seropositive than in seronegative groups in both tumorous and non-tumorous sections (P < 0.05). IL-8 mRNA expression in tumorous sections of adenoma and carcinoma was higher than in non-tumorous sections, higher in carcinoma/adenoma than in control subjects, and higher in S. gallolyticus IgG seropositive than in seronegative groups in tumorous rather than non-tumorous sections (P < 0.05).. S. gallolyticus most likely plays an essential role in the oncogenic progression of normal colorectal mucosa to adenoma and to CRC. This promoting/propagating role of S. gallolyticus might take place by utilizing certain inflammatory, anti-apoptotic, and angiogenic factors of transformation including NF-kappaB and IL-8.

Topics: Adenocarcinoma; Adenoma; Adult; Aged; Antibodies, Bacterial; Colorectal Neoplasms; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G; In Situ Hybridization; Interleukin-8; Male; Middle Aged; NF-kappa B; RNA, Messenger; Seroepidemiologic Studies; Streptococcal Infections

Oncogene-induced cellular senescence (OIS) is emerging as a potent cancer-protective response to oncogenic events, serving to eliminate early neoplastic cells from the proliferative pool. Using combined genetic and bioinformatic analysis, we find that OIS is linked specifically to the activation of an inflammatory transcriptome. Induced genes included the pleiotropic cytokine interleukin-6 (IL-6), which upon secretion by senescent cells acted mitogenically in a paracrine fashion. Unexpectedly, IL-6 was also required for the execution of OIS, but in a cell-autonomous mode. Its depletion caused the inflammatory network to collapse and abolished senescence entry and maintenance. Furthermore, we demonstrate that the transcription factor C/EBPbeta cooperates with IL-6 to amplify the activation of the inflammatory network, including IL-8. In human colon adenomas, IL-8 specifically colocalized with arrested, p16(INK4A)-positive epithelium. We propose a model in which the context-dependent cytostatic and promitogenic functions of specific interleukins contribute to connect senescence with an inflammatory phenotype and cancer.

Topics: Adenoma; CCAAT-Enhancer-Binding Protein-beta; Cell Proliferation; Cellular Senescence; Colonic Neoplasms; Cyclin-Dependent Kinase Inhibitor p15; Cyclin-Dependent Kinase Inhibitor p16; Gene Expression Profiling; Heterochromatin; Humans; Inflammation; Interleukin-6; Interleukin-8; RNA Interference; Up-Regulation

To investigate the expression profile of IL-8 in inflammatory and malignant colorectal diseases to evaluate its potential role in the regulation of colorectal cancer (CRC) and the development of colorectal liver metastases (CRLM).. IL-8 expression was assessed by quantitative real-time PCR (Q-RT-PCR) and the enzyme-linked immunosorbent assay (ELISA) in resected specimens from patients with ulcerative colitis (UC, n = 6) colorectal adenomas (CRA, n = 8), different stages of colorectal cancer (n = 48) as well as synchronous and metachronous CRLM along with their corresponding primary colorectal tumors (n = 16).. IL-8 mRNA and protein expression was significantly up-regulated in all pathological colorectal entities investigated compared with the corresponding neighboring tissues. However, in the CRC specimens IL-8 revealed a significantly more pronounced overexpression in relation to the CRA and UC tissues with an average 30-fold IL-8 protein up-regulation in the CRC specimens in comparison to the CRA tissues. Moreover, IL-8 expression revealed a close correlation with tumor grading. Most interestingly, IL-8 up-regulation was most enhanced in synchronous and metachronous CRLM, if compared with the corresponding primary CRC tissues. Herein, an up to 80-fold IL-8 overexpression in individual metachronous metastases compared to normal tumor neighbor tissues was found.. Our results strongly suggest an association between IL-8 expression, induction and progression of colorectal carcinoma and the development of colorectal liver metastases.

Topics: Adenoma; Adult; Aged; Biomarkers, Tumor; Colorectal Neoplasms; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging

A patient with adrenocortical carcinoma presented with fever, leukocytosis, and increased acute phase reactants. The tumor was infiltrated with neutrophils. Immunohistochemical staining of the tumor showed positive signal for epithelial neutrophil-activating protein-78, an angiogenic and chemotactic CXC chemokine. Conditioned medium from tumor-derived cells (RL-251) showed high concentration of IL-8, epithelial neutrophil-activating protein-78, Gro alpha, and Gro gamma, angiogenic CXC chemokines with a potential role in tumorigenesis. An adrenal cancer/severe combined immunodeficiency mouse chimera was developed. Mice grew tumors rapidly, and circulating levels of IL-8 and epithelial neutrophil-activating protein-78 were detected. In contrast, animals transplanted with NCI-H295 cells, a nonchemokine-secreting cell line, grew tumors more slowly and did not have detectable chemokine levels. Similar to the patient, mice with RL-251 tumors developed marked leukocytosis and neutrophilia, and their tumors were infiltrated with neutrophils. Mice were passively immunized with epithelial neutrophil-activating protein-78 antisera. A marked decrease in tumor growth was observed. Potential for chemokine production by other adrenocortical tumors was investigated by RT-PCR in archival material. Six of seven adrenal carcinomas and one of three adenomas had cDNA for IL-8; six of seven carcinomas and the three adenomas had cDNA for epithelial neutrophil-activating protein-78. We concluded that the clinical presentation of this case resulted from increased tumor production of chemotactic chemokines. Through their angiogenic and chemotactic properties these chemokines may play an important role in adrenal tumorigenesis.

Topics: 17-Hydroxycorticosteroids; 17-Ketosteroids; Adenoma; Adrenal Cortex Neoplasms; Adrenocorticotropic Hormone; Aged; Chemokine CXCL5; Chemokines, CXC; Circadian Rhythm; Fever; Humans; Hydrocortisone; Immunohistochemistry; Interleukin-8; Leukocytosis; Male; Neutrophil Activation; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction; Syndrome; Tumor Cells, Cultured

The involvement of Streptococcus bovis, an member of the human gut flora, in colorectal neoplastic diseases is an object of controversy. The aim of this study was to determine the effects of S.bovis and of antigens extracted from the bacterial cell wall on early preneoplastic changes in the intestinal tract. Adult rats received i. p. injections of azoxymethane (15 mg/kg body weight) once per week for 2 weeks. Fifteen days (week 4) after the last injection of the carcinogen, the rats received, by gavage twice per week during 5 weeks, either S.bovis (10(10) bacteria) or wall-extracted antigens (100 microg). One week after the last gavage (week 10), we found that administration of either S.bovis or of antigens from this bacterium promoted the progression of preneoplastic lesions through the increased formation of hyperproliferative aberrant colonic crypts, enhanced the expression of proliferation markers and increased the production of IL-8 in the colonic mucosa. Our study suggests that S.bovis acts as a promoter of early preneoplastic lesions in the colon of rats. The fact that bacterial wall proteins are more potent inducers of neoplastic transformation than the intact bacteria may have important implications in colon cancer prevention.

Topics: Adenoma; Animals; Azoxymethane; Biogenic Polyamines; Cell Division; Cocarcinogenesis; Colon; Interleukin-8; Intestinal Neoplasms; Male; Precancerous Conditions; Rats; Rats, Wistar; Streptococcus bovis

Several cytokines have been shown to be expressed in normal and adenomatous pituitary tissue. Recently, interleukin-8 (IL-8) mRNA was identified by reverse transcription (RT)-PCR in each of a series of 17 pituitary tumours examined. We have investigated further the presence of IL-8 mRNA, using in situ hybridisation in two normal human anterior pituitary specimens and 25 human pituitary adenomas. IL-8 mRNA was not identified in either of the two normal pituitary specimens. Only three of the 25 adenomas were positive for IL-8 mRNA. In these three tumours, which included two null cell adenomas and one gonadotrophinoma, the majority of tumour cells (>90%) were positive for IL-8 mRNA. The remaining 22 adenomas were completely negative. There was no difference in tumour size or type between the IL-8 positive and the IL-8 negative tumours, and immunocytochemistry for von Willebrandt factor showed that the two groups were also similar in their degree of vascularisation. In conclusion, IL-8 mRNA was found in 12% of pituitary adenomas studied and was histologically identified within the tumour cells. In situ hybridisation is a more appropriate technique for assessing cytokine mRNA production by human pituitary tumours because RT-PCR may be too sensitive, identifying very small, possibly pathologically insignificant, quantities of mRNA that could be produced by supporting cells such as fibroblasts, endothelial cells or macrophages.

Topics: Adenoma; Adult; Aged; Aged, 80 and over; Female; Humans; Immunohistochemistry; In Situ Hybridization; Interleukin-8; Male; Middle Aged; Pituitary Gland; Pituitary Neoplasms; Reference Values; RNA, Messenger; von Willebrand Factor

There is increasing evidence for the role of cytokines in pituitary differentiated function and tumorigenesis, but the spectrum of cytokines found in the pituitary is unknown. Therefore profiles of cytokine expression were determined in different human anterior pituitary adenoma sub-types.. The reverse transcriptase-linked polymerase chain reaction (PCR) was used to identify the presence of cytokine mRNA within human pituitary adenomas.. Seventeen pituitary adenoma biopsies removed at transsphenoidal surgery were examined: 4 somatotrophinomas, 7 non-functional adenomas, 4 prolactinomas, one case of Cushing's disease and one case of Nelson's syndrome.. RNA was extracted from each adenoma biopsy and reverse transcribed into cDNA. This was specifically amplified in a PCR using oligonucleotide primers complementary to each cytokine. The cytokines investigated were interleukin (IL)-I alpha, IL-I beta, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, tumour necrosis factor (TNF)-alpha, TNF-beta and transforming growth factor (TGF)-beta 1, beta 2 and beta 3. The products of each PCR were visualized using agarose gel electrophoresis.. All 17 adenomas expressed IL-8 transcripts, but no expression of IL-2, IL-5 or IL-7 was found. IL-6 was expressed in all 4 somatotrophinomas, 3 of 7 non-functional tumours, 2 of 4 prolactinomas and in the single case of Nelson's syndrome. At least one of the 3 isoforms of TGF-beta was found in all but 2 tumours; one prolactinoma and one non-functional adenoma. IL-1 alpha, IL-beta, IL-4, TNF-alpha and TNF-beta were expressed sporadically by individual adenomas.. These data suggest that whilst IL-8 may be important, the local expression of the cytokines IL-2, IL-5 and IL-7 is not important in human anterior pituitary tumorigenesis.

Topics: Adenoma; Adult; Aged; Base Sequence; Cushing Syndrome; Cytokines; DNA Primers; Female; Growth Hormone; Humans; Interleukin-6; Interleukin-8; Male; Middle Aged; Molecular Sequence Data; Nelson Syndrome; Pituitary Gland, Anterior; Pituitary Neoplasms; Polymerase Chain Reaction; Prolactinoma; RNA, Messenger; Transforming Growth Factor beta