interleukin-8 and Precancerous-Conditions

We determined whether the proinflammatory cytokine interleukin-8 (IL-8) can serve as a predictor for the response to standard (120 mg.) and low (40 mg.) dose intravesical bacillus Calmette-Guerin (BCG) (modified Danish 1331 strain) for managing superficial bladder cancer in patients at risk for recurrence and progression.. We randomized 26 patients with superficial bladder cancer to receive a 6-week course of standard dose 120 mg. or low dose 40 mg. intravesical BCG. Voided urine samples were collected immediately before and after (2 and 4 hours) BCG instillation. Urine samples were centrifuged at 1,500 rpm for 8 minutes and stored at -80C. IL-8 was measured using a commercial enzyme-linked immunosorbent assay. Patients were monitored for recurrence, progression and side effects of BCG treatment at 3-month intervals.. At a median followup of 24 months (range 12 to 30), 5 and 6 patients who received a standard and low dose, respectively had disease recurrence and/or progression (nonresponders). At 4 hours after BCG mean Il-8 levels plus or minus SD were significantly higher in responders than in nonresponders (1,099.33 +/- 708.51 versus 261.82 +/- 182.66 pg./ml., p = 0.001). There was no difference at 4 hours in mean IL-8 levels in the standard and low dose groups (596.92 +/- 546 and 893 +/- 798.67 pg./ml., respectively, p = 0.28). In all patients who remained disease-free IL-8 levels were greater than 400 pg./ml. In 9 of the 11 patients with disease recurrence/progression IL-8 levels were less than 400 pg./ml.. IL-8 secretion after the initial intravesical BCG instillation strongly correlates with the possibility of future recurrence/progression. The quantitative IL-8 response to low and standard dose intravesical BCG (Danish 1331) is similar.

Topics: BCG Vaccine; Carcinoma in Situ; Disease Progression; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; India; Interleukin-8; Male; Neoplasm Recurrence, Local; Neoplasm Staging; Precancerous Conditions; Prospective Studies; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms

Barrett's esophagus (BE) is known to progress to esophageal adenocarcinoma in a setting of chronic inflammation. Toll-like receptor (TLR) 4 has been linked to inflammation-associated carcinogenesis. We aimed to determine the expression and functional activity of TLR4 in the esophagus and whether TLR4 activation in BE could promote carcinogenesis by inducing COX-2 expression.. TLR4 expression in esophageal adenocarcinoma, BE, duodenum, reflux esophagitis and normal squamous esophagus biopsies was assessed using real-time PCR and validated by in situ hybridization and immunohistochemistry. Ex vivo cultures of BE, duodenum and normal squamous esophagus biopsies and a BE cell line (BAR-T) were stimulated with the TLR4 agonist lipopolysaccharide (LPS). To evaluate the effect of TLR4 activation, NF-κB activation, IL8 secretion and expression and COX-2 expression were determined.. TLR4 expression was significantly increased in esophageal adenocarcinoma, BE, duodenum and reflux esophagitis compared to normal squamous esophagus. LPS stimulation resulted in NF-κB activation and a dose-dependent increase of IL8 secretion and mRNA expression. The induction of IL8 was more evident in BE compared to normal squamous esophagus. Upon LPS stimulation, COX-2 expression increased significantly in ex vivo cultured BE biopsies, which was observed in both epithelium and lamina propria cells. However, no effect was found in duodenum and normal squamous esophagus biopsies.. TLR4 activation in BE results in a strong increase in COX-2 and may contribute to malignant transformation.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biopsy; Cyclooxygenase 2; Esophageal Neoplasms; Esophagitis, Peptic; Female; Gene Expression Regulation, Neoplastic; Humans; Interleukin-8; Intracellular Signaling Peptides and Proteins; Male; Middle Aged; NF-kappa B; Precancerous Conditions; RNA, Messenger; Tissue Culture Techniques; Toll-Like Receptor 4; Up-Regulation; Young Adult

Epidemiological evidences suggested an inverse association between the use of glucosamine supplements and colorectal cancer (CRC) risk. In this study, the efficacy of glucosamine to attenuate dextran sodium sulfate (DSS)-induced colitis, a precancerous condition for CRC, was evaluated.. C57BL/6 mice were separated into three groups receiving glucosamine sulfate at concentrations of 0, 0.05, and 0.10% (w/w) of AIN-93G diet, respectively for 4 weeks. Colitis was induced by supplying two cycles (5 days per cycle) of 2% DSS in the animals' drinking water.. Glucosamine supplementation at the level of 0.10% of the diet (w/w) reduced colitis-associated symptoms as measured by disease activity index (DAI). Tumor necrosis factor-α (TNF-α), interleukin-1β, and nuclear factor-kappa B mRNA expression in the colonic mucosa was significantly lower in animals fed 0.10% glucosamine compared with those of the control group. Expression of the tight junction proteins ZO-1 and occludin was significantly higher in the 0.10% glucosamine-supplemented group compared with the other groups. Also, colonic protein expression of lipocalin 2, and serum concentrations of interleukin-8 and amyloid P component (SAP) were significantly reduced in the 0.10% glucosamine-supplemented group compared with the control group.. These results suggest that glucosamine attenuates the colitis disease activity by suppressing NF-κB activation and related inflammatory responses.

Topics: Acute-Phase Proteins; Administration, Oral; Animals; Colitis; Colon; Dextran Sulfate; Dietary Supplements; Disease Models, Animal; Gene Expression; Glucosamine; Inflammation Mediators; Interleukin-1beta; Interleukin-8; Lipocalin-2; Lipocalins; Mice, Inbred C57BL; NF-kappa B; Occludin; Oncogene Proteins; Precancerous Conditions; RNA, Messenger; Serum Amyloid P-Component; Tumor Necrosis Factor-alpha; Zonula Occludens-1 Protein

A subgroup of the transient receptor potential (TRP) channels, including vanilloid 1 (TRPV1), TRPV2, TRPV3, TRPV4, and TRP ankyrin 1 (TRPA1), is expressed in cutaneous peptidergic somatosensory neurons, and has been found in skin non-neuronal cells, such as keratinocytes. Different cancer cells express TRPs, where they may exert either pro- or antitumorigenic roles. Expression and function of TRPs in skin cancers have been, however, poorly investigated. Here, we have studied the distribution and expression of TRPs by immunohistochemistry and messenger RNA (mRNA) in human healthy skin and human keratinocytic tumors, including intraepidermal proliferative disorders (solar keratosis (SK) and Bowen's disease), and non-melanoma skin cancer (NMSC; basal cell and squamous cell carcinomas). Similar TRPV1, TRPV2, and TRPV3 staining was found in keratinocytes from healthy and tumor tissues. TRPA1 staining was increased solely in SK samples. However, the marked TRPV4 staining and TRPV4 mRNA expression, observed in healthy or inflamed skin, was abrogated both in premalignant lesions and NMSC. In a human keratinocyte cell line (HaCaT), TRPV4 stimulation released IL-8, which in turn downregulated TRPV4 expression. Selective reduction in TRPV4 expression could represent an early biomarker of skin carcinogenesis. Whether the cytokine-dependent, autocrine pathway that results in TRPV4 downregulation contributes to NMSC mechanism remains to be determined.

Topics: Adult; Aged; Aged, 80 and over; Autocrine Communication; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; HEK293 Cells; Humans; Interleukin-8; Keratinocytes; Keratosis; Male; Middle Aged; Precancerous Conditions; Skin Neoplasms; Tissue Banks; TRPV Cation Channels

To evaluate the clinical utility of salivary interleukin 8 (IL-8) in the differential diagnosis of potentially malignant lesions (PMLs) and oral squamous cell carcinoma (OSCC) in a region with high oral cancer prevalence.. Saliva and blood samples were collected from 100 participants in each group (OSCC, PMLs, and healthy controls). Serum and salivary IL-8 levels were measured by enzyme-linked immunosorbent assay. The data were subjected to appropriate statistical analysis.. A significant increase in levels of serum and salivary IL-8 was found in OSCC compared with PMLs and healthy controls. Receiver operating characteristic curve analysis found salivary IL-8 to have superior sensitivity in detecting OSCC. A significant increase in IL-8 levels based on the histologic grading of OSCC was also observed.. This study confirms that salivary IL-8 can be a potent marker that can be used as a tool in the differential diagnosis of PMLs and OSCC.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Carcinoma, Squamous Cell; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-8; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Precancerous Conditions; Risk Factors; Saliva; Sensitivity and Specificity

Interleukin 8 (IL-8) is a pro-angiogenic, pro-inflammatory mediator that belongs to the family of chemokines. Due to its pro-angiogenic characteristic, it may play a vital role in tumour angiogenesis and progression.. This study was designed to estimate the levels of salivary IL-8 in oral precancer and oral squamous cell carcinoma (OSCC) patients and compare them with healthy controls. The aim was to evaluate its efficacy as a potential biomarker for these diseases.. Each group comprised 25 individuals. The salivary IL-8 levels were determined by enzyme-linked immunosorbent assay.. The levels of salivary IL-8 were found to be significantly elevated in patients with OSCC as compared to the precancer group (p < 0.0001) and healthy controls (p < 0.0001). However, the difference in salivary IL-8 concentrations among the precancer group and controls was statistically non-significant (p = 0.738).. Our results suggested that salivary IL-8 can be utilised as a potential biomarker for OSCC. Salivary IL-8 was found to be non-conclusive for oral premalignancy in this preliminary study. Hence, its possible role in transition from premalignancy to malignancy needs further research with larger sample sizes.. Saliva as a diagnostic biofluid offers a number of advantages over blood-based testing. The role of IL-8 in oral cancer if validated further by future research can provide an easy diagnostic test as well as a prognostic indicator for patients undergoing treatment. Therefore, if it's role in tumourigenesis can be sufficiently assessed, it could open up new avenues to find out novel treatment modalities for oral cancer.

Topics: Adolescent; Adult; Aged; Angiogenesis Inducing Agents; Areca; Biomarkers, Tumor; Carcinoma, Squamous Cell; Case-Control Studies; Female; Humans; Inflammation Mediators; Interleukin-8; Leukoplakia, Oral; Male; Middle Aged; Mouth Neoplasms; Neoplasm Staging; Oral Submucous Fibrosis; Precancerous Conditions; Saliva; Salivary Proteins and Peptides; Smoking; Tobacco Use; Young Adult

Chronic infection of Helicobacter pylori in the stomach mucosa with translocation of the bacterial cytotoxin-associated gene A (CagA) effector protein via the cag-Type IV secretion system (TFSS) into host epithelial cells are major risk factors for gastritis, gastric ulcers, and cancer. The blood group antigen-binding adhesin BabA mediates the adherence of H. pylori to ABO/Lewis b (Le(b)) blood group antigens in the gastric pit region of the human stomach mucosa. Here, we show both in vitro and in vivo that BabA-mediated binding of H. pylori to Le(b) on the epithelial surface augments TFSS-dependent H. pylori pathogenicity by triggering the production of proinflammatory cytokines and precancer-related factors. We successfully generated Le(b)-positive cell lineages by transfecting Le(b)-negative cells with several glycosyltransferase genes. Using these established cell lines, we found increased mRNA levels of proinflammatory cytokines (CCL5 and IL-8) as well as precancer-related factors (CDX2 and MUC2) after the infection of Le(b)-positive cells with WT H. pylori but not with babA or TFSS deletion mutants. This increased mRNA expression was abrogated when Le(b)-negative cells were infected with WT H. pylori. Thus, H. pylori can exploit BabA-Le(b) binding to trigger TFSS-dependent host cell signaling to induce the transcription of genes that enhance inflammation, development of intestinal metaplasia, and associated precancerous transformations.

Topics: Adhesins, Bacterial; Animals; Bacterial Adhesion; Bacterial Secretion Systems; Chemokine CCL5; CHO Cells; Cricetinae; Cricetulus; Dogs; Gastric Mucosa; Gene Deletion; Helicobacter Infections; Helicobacter pylori; Homeodomain Proteins; Humans; Inflammation; Interleukin-8; Lewis Blood Group Antigens; Metaplasia; Mucin-2; Precancerous Conditions; Signal Transduction

Chitinase 3-like-1 (CHI3L1/YKL-40) is a protein secreted from restricted cell types including colonic epithelial cells (CECs) and macrophages. CHI3L1 is an inflammation-associated molecule, and its expression is enhanced in persons with colitis and colon cancer. The biological function of CHI3L1 on CECs is unclear. In this study, we investigated the role of CHI3L1 on CECs during the development of colitis-associated neoplasia. We analyzed colonic samples obtained from healthy persons and from persons with ulcerative colitis with or without premalignant or malignant changes. DNA microarray and RT-PCR analyses significantly increased CHI3L1 expression in non-dysplastic mucosa from patients with inflammatory bowel disease (IBD) who had dysplasia/adenocarcinoma compared with that in healthy persons and in patients with IBD who did not have dysplasia. As determined by IHC, CHI3L1 was expressed in specific cell types in the crypts of colonic biopsies obtained from patients with ulcerative colitis who have remote dysplasia. Purified CHI3L1 efficiently activated the NF-κB signaling pathway and enhanced the secretion of IL-8 and TNF-α in SW480 human colon cancer cells. In addition, colon cancer cell proliferation and migration were significantly promoted in response to CHI3L1 in these cells. In summary, CHI3L1 may contribute to the proliferation, migration, and neoplastic progression of CECs under inflammatory conditions and could be a useful biomarker for neoplastic changes in patients with IBD.

Topics: Adipokines; Biomarkers, Tumor; Cell Movement; Cells, Cultured; Chitinase-3-Like Protein 1; Colitis, Ulcerative; Colon; Colorectal Neoplasms; Dose-Response Relationship, Drug; Epithelial Cells; Female; Humans; Interleukin-8; Intestinal Mucosa; Irritable Bowel Syndrome; Lectins; Male; Middle Aged; NF-kappa B; Precancerous Conditions; Tumor Necrosis Factor-alpha

Oral cancer is the sixth most common malignancy worldwide with a mortality rate that is higher than many other cancers. Death usually occurs as a result of local invasion and regional lymph node metastases. Decorin is a multifunctional proteoglycan of the extracellular matrix that affects the biology of various types of cancer. Previously; we have shown that decorin is aberrantly expressed in the nucleus in human dysplastic oral keratinocytes (DOK) and malignant squamous cells carcinoma (SCC-25) and human biopsy tissues. In this study, we examined the role of nuclear decorin in oral cancer progression.. We have used a post-transcriptional gene silencing (RNA interference) approach to stably knockdown nuclear decorin gene expression in DOK and SCC-25 cells using a specific shRNA plasmid and a combination of immunological and molecular techniques to study nuclear decorin function in these oral epithelial cell lines.. More than 80% decorin silencing/knockdown was achieved as confirmed by real time PCR and western blot analysis in both DOK and SCC-25 cells. This RNA interference-mediated knockdown of nuclear decorin expression resulted in significantly reduced invasion and migration in these cell lines as measured by Matrigel™ coated and uncoated Trans well chamber assays respectively. Decorin silencing also resulted in reduced IL-8 mRNA and proteins levels in these cell lines. Culturing decorin silenced DOK and SCC-25 cells, with recombinant human IL-8 or IL-8 containing conditioned medium from respective un-transfected cells for 24 h prior to migration and invasion experiments, resulted in the salvation of reduced migration and invasion phenotype. Furthermore, we found that nuclear localized decorin interacts with EGFR in the nuclear fractions of both DOK and SCC-25 cells. Interestingly, EGFR (trans) activation has previously been shown to be involved in IL-8 production in various epithelia.. Taken together, our results indicate that nuclear localized decorin plays an important role in migration and invasion of oral cancer cells and thus may present as a novel potential target for the treatment of oral cancer.

Topics: Carcinoma, Squamous Cell; Cell Growth Processes; Cell Line, Tumor; Cell Movement; Cell Nucleus; Decorin; ErbB Receptors; Female; Gene Expression Regulation, Neoplastic; Gene Knockdown Techniques; Humans; Interleukin-8; Male; Mouth Neoplasms; Neoplasm Invasiveness; Precancerous Conditions; RNA, Small Interfering

Polymorphisms in cytokine genes may contribute to increased susceptibility to different cancers. The aim of this paper is to investigate the association of IL-8-251A/T polymorphism and Helicobacter pylori (H. pylori) infection with the risk of developing gastric cardiac adenocarcinoma (GCA) in the south of Taihang Mountain, a high-incidence area of esophageal cancer in China. The IL-8-251 A/T polymorphism was genotyped in 519 cases of GCA and 504 healthy controls. The H. pylori infection in GCA patients and controls was detected by rapid urease test (RUT), histopathology or (14)C-urea breath test ((14)C-UBT). The results showed that family history of upper gastrointestinal cancer (UGIC) and H. pylori infection significantly increased the risk of developing GCA. The overall genotype and allelotype distributions of IL-8 promoter SNPs in GCA patients were significantly different from those in healthy controls. Compared with TT genotype, AA genotype significantly elevated the risk of developing GCA. The stratification analysis revealed that, compared with the TT genotype, the AA genotype significantly elevated the risk of developing GCA in both positive family history of UGIC and H. pylori infection subgroups. This study provides evidence to support a relationship of increased susceptibility to GCA in individuals of the south Taihang Mountain region with IL-8 251 AA genotype, especially for those individuals who have family history of UGIC or H. pylori infection.

Topics: Adenocarcinoma; Aged; Base Sequence; China; Demography; Female; Genetic Predisposition to Disease; Helicobacter Infections; Helicobacter pylori; Humans; Incidence; Interleukin-8; Male; Middle Aged; Molecular Sequence Data; Polymerase Chain Reaction; Polymorphism, Single Nucleotide; Precancerous Conditions; Risk Factors; Sequence Analysis, DNA; Stomach Neoplasms

Psoriasin (S100A7) has originally been described to be expressed by psoriatic keratinocytes possibly as a result of altered differentiation and inflammation. As psoriasin was found to be overexpressed in human breast and bladder cancer suggesting a role in tumour progression, we investigated the expression of psoriasin in human epithelial skin tumours.. Realtime reverse transcription-polymerase chain reaction experiments were performed to analyse the mRNA-expression levels of psoriasin together with involucrin as a marker for epithelial differentiation and interleukin-8 (IL-8) as a marker for inflammation in skin biopsy samples from patients with precancerous skin lesions (PSL, n = 6), squamous cell carcinoma (SCC, n = 11), basal cell carcinoma (BCC, n = 17), and healthy controls (n = 10).. Unexpectedly, mRNA expression levels for Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) revealed a variation of up to 600-fold in all cDNA-samples under investigation, indicating that GAPDH is not suitable as a housekeeping gene in human skin samples. Psoriasin mRNA expression was significantly up-regulated in samples of PSL, SCC and BCC. In situ hybridisation and immunohistochemical examinations identified psoriasin mRNA and protein expression in the differentiated layers of the epidermis. IL-8 mRNA expression was significantly up-regulated in SCC, however, there was no correlation between elevated levels of psoriasin and the expression of IL-8.. Similar to the findings in breast and bladder cancer, the up-regulation of psoriasin might play a role in the progression of skin cancer. The expression of psoriasin in human skin tumours seems to be independent from differentiation and inflammation.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Calcium-Binding Proteins; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Female; Gene Expression Regulation, Neoplastic; Glyceraldehyde-3-Phosphate Dehydrogenases; Humans; Immunohistochemistry; In Situ Hybridization; Interleukin-8; Male; Middle Aged; Precancerous Conditions; Reverse Transcriptase Polymerase Chain Reaction; RNA, Neoplasm; S100 Calcium Binding Protein A7; S100 Proteins; Skin Neoplasms; Up-Regulation

To determine if immunohistochemistry (IHC) could be used to monitor nuclear factor-kappaB (NF-kappaB) activity in oesophageal adenocarcinoma and pre-malignant (Barrett's) oesophageal tissues, relative to normal oesophageal mucosa. The pro-inflammatory cytokine interleukin-8 (IL-8), a transcriptional target of NF-kappaB, was also studied to better understand NF-kappaB functionality; its RNA and protein levels were assessed in oesophageal tissues.. IHC was employed using an antibody against the nuclear localisation sequence (NLS) of the p65 subunit as well as an antibody against IL-8. To assess NF-kappaB function, changes in gene expression of NF-kappaB controlled genes (IL-8 and I-kappaB) were also assessed in the histological sequence using real-time PCR. More global expression changes were also studied using membrane arrays.. IHC was effective at monitoring overall NF-kappaB activity and IL-8 abundance. This method also allowed NF-kappaB activity and IL-8 abundance to be pinpointed in specific cell types. There were significant increases in nuclear NF-kappaB activity and IL-8 abundance across the histological series. Gene expression analysis also showed consistent up-regulation of IL-8, confirming the IHC data and showing enhanced transcriptional NF-kappaB activity. I-kappaB (another NF-kappaB target) showed down-regulation in dysplastic and adenocarcinoma tissues. Down-regulation of I-kappaB gene expression may partly explain increased NF-kappaB activity.. IHC, using antibodies against the NLS of p65, may be useful in monitoring overall NF-kappaB activity in oesophageal tissues. As IHC is amenable to high-throughput screening (whereas traditional electrophoretic mobility shift assay methods are not), this may lead to the development of a better screening tool for early cancer risk.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers, Tumor; Carrier Proteins; Disease Progression; Esophageal Neoplasms; Humans; Interleukin-8; NF-kappa B; Polymerase Chain Reaction; Precancerous Conditions; Transcription Factor RelA; Up-Regulation

The incidence of esophageal adenocarcinoma has increased significantly in the western world over the last 20 yr. Most cases arise in a background of chronic gastroesophageal reflux, and specialized intestinal metaplasia in Barrett's esophagus is frequently an antecedent phenotype or evident in association with adenocarcinoma. The molecular events that characterize the pathway from inflammation to metaplasia to dysplasia and adenocarcinoma are poorly understood.. To examine the expression of the proinflammatory cytokines IL-8 and IL-1beta along the esophagitis, metaplasia, dysplasia, and adenocarcinoma pathway, and to correlate this with histological changes and expression of the transcription factor NF-kappaB.. Fresh biopsy specimens were collected from patients with reflux esophagitis (n=15), Barrett's esophagus (n=35), Barrett's adjacent to adenocarcinoma (n=8), and esophageal adenocarcinoma (n=35). IL-8 and IL-1beta expression were measured using enzyme-linked immunosorbent assay. NF-kappaB expression was measured by electrophoretic mobility shift assay.. Elevated expression of NF-kappaB was found in 2 (13%) out of 15 patients with reflux esophagitis, 21 (60%) out of 35 patients with Barrett's esophagus, and 28 (80%) out of 35 patients with esophageal adenocarcinoma. All 5 patients with Barrett's esophagus and high-grade dysplasia showed elevated expression of NF-kappaB. IL-8 and IL-1beta were significantly increased in esophagitis, Barrett's, and adenocarcinoma compared with squamous epithelium, and in adenocarcinoma compared with all other groups. There was a stepwise increase in the expression of IL-8, IL-1beta, and NF-kappaB from normal through Barrett's epithelium to adenocarcinoma in eight cases of esophageal adenocarcinoma. The levels of both IL-8 and IL-1beta in adenocarcinoma patients correlated with stage of disease. Patients with adenocarcinoma who were NF-kappaB positive had significantly higher levels of both IL-8 (p=0.04) and IL-1beta (p=0.03) compared to adenocarcinoma patients who were NF-kappaB negative.. The proinflammatory cytokines IL-8 and IL-1beta are elevated in esophagitis and Barrett's epithelium, and markedly elevated in adenocarcinoma. NF-kappaB activation is infrequent in esophagitis, but is increased in Barrett's epithelium and adenocarcinoma. The association of NF-kappaB activation with cytokine upregulation was only evident in patients with adenocarcinoma. These patterns may play an important role in Barrett's inflammation and tumourigenesis, and inhibition of the NF-kappaB/proinflammatory cytokine pathway may be an important target for future chemoprevention strategies.

Topics: Adenocarcinoma; Barrett Esophagus; Biomarkers; Biopsy; Electrophoresis; Endoscopy, Digestive System; Enzyme-Linked Immunosorbent Assay; Esophageal Neoplasms; Esophagitis; Female; Gastroesophageal Reflux; Humans; Interleukin-1; Interleukin-8; Intestinal Mucosa; Male; Metaplasia; Middle Aged; NF-kappa B; Precancerous Conditions; Prospective Studies

We previously reported that vascular endothelial growth factor (VEGF) expression correlates with vessel density in human esophageal squamous cell carcinomas. However, tumor angiogenesis is not controlled simply by the presence of VEGF, and is likely regulated by several angiogenic factors produced by tumor and host cells. The goal of the present study was to determine the angiogenic profile of precancerous and cancerous lesions of the esophagus. Expression of mRNAs for VEGF, platelet derived endothelial cell growth factor (PD-ECGF), basic fibroblast growth factor (bFGF), and interleukin (IL)-8 was examined in six esophageal carcinoma cell lines and fresh biopsy specimens from 16 patients with invasive esophageal carcinoma by RT-PCR. Immunohistochemical analyses with antibodies against VEGF, PD-ECGF, bFGF, and IL-8 were performed on archival specimens of 60 normal esophageal mucosa, 11 dysplasias and 49 carcinomas of the esophagus. Microvessels were stained with anti-CD34 antibody and quantified by counting the number of vessels in a x200 field in the most vascularized areas of the tumor. Esophageal carcinoma cell lines and tumor tissues expressed mRNAs for one or more these angiogenic factors at various levels. An initial increase in vessel density and enhanced expression of PD-ECGF and VEGF were observed in dysplastic epithelium. Vessel density was significantly higher in more advanced lesions. bFGF and IL-8 were not expressed in dysplasias and mucosal carcinomas, but expression was increased in late stage squamous cell carcinoma. These findings suggest that the angiogenic switch is a very early event in the development of invasive carcinoma. Several different angiogenic factors produced by tumor cells and host cells may regulate angiogenesis during different steps of esophageal carcinogenesis.

Topics: Base Sequence; Carcinoma, Squamous Cell; Cell Line, Tumor; DNA Primers; Esophageal Neoplasms; Fibroblast Growth Factor 2; Humans; Interleukin-8; Neovascularization, Pathologic; Precancerous Conditions; RNA, Messenger; Thymidine Phosphorylase; Vascular Endothelial Growth Factor A

Pancreatic cancer is the most deadly of all gastrointestinal (GI) malignancies, yet relatively little is known regarding mechanisms of tumor development including the role of inflammation.. Chronic pancreatitis (CP) increases the risk of developing cancer by 10- to 20-fold; mediators of the chronic inflammatory process and the surrounding fibrotic stroma likely support a transformation to malignancy, yet the exact mechanisms remain undefined. The purpose of our present study was to determine potential inflammatory components in epithelial and stromal cells that may contribute to both CP and pancreatic cancers.. Specimens of normal pancreas, CP, and pancreatic cancer were examined using laser-capture microdissection (LCM), gene array, and immunohistochemistry.. Gene array analysis from LCM-dissected tissues demonstrated: (i) increased expression of interleukin-8 (IL-8), an activator of the inflammatory factor nuclear factor-kappaB (NF-kappaB), and (ii) decreased expression of IkappaB (an inhibitor of NF-kappaB) in CP ductal cells compared with normal ducts. Compared with CP, cancers demonstrated: (i) increased expression of tumor related genes including S100A4, cyclin E1, and epidermal growth factor (EGF) receptor, and (ii) expression of matrix metalloproteinase 2, a pro-invasive factor for tumor cells, which was not present in the CP stroma. Increased staining of both the p50 NF-kappaB subunit and IKKalpha kinase (a protein that allows activation of NF-kappaB) was noted in CP and cancers.. Our results demonstrate that similar inflammatory components and downstream effectors are present in CP and pancreatic cancers. Importantly, these findings suggest that a common pathway for pancreatic cancer development may be through a chronic inflammatory process including stroma formation. These findings may lead to novel strategies for pancreatic cancer prophylaxis based on inhibition of inflammatory mediators.

Topics: Biomarkers, Tumor; Case-Control Studies; Cell Transformation, Neoplastic; Cells, Cultured; Chronic Disease; Culture Techniques; Female; Humans; Immunohistochemistry; Inflammation Mediators; Interleukin-8; Male; NF-kappa B; Pancreatic Ducts; Pancreatic Neoplasms; Pancreatitis; Precancerous Conditions; Prognosis; Sensitivity and Specificity

To evaluate the relationship between mitochondrial DNA instability (mtMSI) and interleukin-8 (IL-8) activity in gastric mucosa of various lesions.. IL-8 level in gastric mucosa was assayed using ELISA method. The mtMSI was detected by PCR-SSCP techniques.. mtMSI was observed in 11 out of 30 (36.7%) gastric cancers, 2 of 15 (13.3%) intestinal metaplasia, 2 of 10 dysplasia and 1 of 10 chronic atrophic gastritis. IL-8 level in mtMSI+ group [(76.8 +/- 3.8) pg/mg] was significantly higher than that in mtMSI- group [(48.3 +/- 3.6) pg/mg, P < 0.05].. mtMSI closely correlates with IL-8 level in gastric mucosa and is involved in gastric carcinogenesis.

Topics: DNA, Mitochondrial; Enzyme-Linked Immunosorbent Assay; Gastric Mucosa; Gastritis, Atrophic; Genomic Instability; Humans; Interleukin-8; Metaplasia; Polymerase Chain Reaction; Polymorphism, Single-Stranded Conformational; Precancerous Conditions; Stomach Neoplasms

To explore the expression of IL-8 on laryngeal carcinoma and the edge tissues and its relationship with the character of laryngeal carcinoma.. Immunohistochemical SABC detections were carried out in 35 case of original laryngeal cancer and the edge tissues (1.0 cm near the tumor).. The positive rate was 68.6% in 24 case of carcinoma group, 42.9% in 15 case of edge group. The statistical difference between carcinoma group with edge group was very significant(P < 0.05). The expression of IL-8 had no difference in location, tumor developed degree and lymph metastases.. The expression of IL-8 may play an important role in the process of laryngeal cancer and the patients' immune stage.

Topics: Aged; Carcinoma, Squamous Cell; Female; Humans; Interleukin-8; Laryngeal Neoplasms; Male; Middle Aged; Precancerous Conditions

Although there is experimental evidence supporting the involvement of angiogenesis in the pathogenesis of breast cancer, the exact nature and effects of interaction between human breast epithelial cells (HBECs) and endothelial cells (ECs) have not been described thus far. This approach requires an assay system that permits growth and differentiation of both epithelial and endothelial cells. Here, we report the development of a three-dimensional in vitro culture system that supports growth and functional differentiation of preneoplastic HBECs and ECs and recapitulates estrogen-induced in vivo effects on angiogenesis and the proliferative potential of MCF10AT xenografts. MCF10A and MCF10AT1-EIII8 (referred to as EIII8) cell lines used in this study are normal or produce preneoplastic lesions, respectively. When MCF10A or EIII8 cells are seeded on reconstituted basement membrane (Matrigel), both lines organize into a three-dimensional tubular network of cells; however, tubes produced by EIII8 cells appear multicellular in contrast to unicellular structures formed by MCF10A cells. However, when MCF10A or EIII8 cells are cocultured with human umbilical vein endothelial cells (HUVECs) on Matrigel, rather than interacting with extracellular matrix, the ECs exhibit preferential adherence to epithelial cells. Although both MCF10A and EIII8 cells provide preferential substrate for EC attachment, only EIII8 cells facilitate sustained proliferation of ECs for prolonged periods that are visualized as "endothelial cell enriched spots," which express factor VIII-related antigen. At regions of endothelial-enriched spots, preneoplastic HBECs undergo branching ductal-alveolar morphogenesis that produce mucin, express cytokeratins, and proliferating cell nuclear antigen. The presence of actively proliferating and functional endothelial cells is essential for ductal-alveolar morphogenesis of preneoplastic HBECs because without ECs, the epithelial cells formed only tubular structures. This ability to establish functional ECs and ductal-alveolar morphogenesis is facilitated only by preneoplastic HBECs because normal MCF10A cells fail to elicit similar effects. Thus, a cause-effect relationship that is mutually beneficial exists between EC and preneoplastic HBECs that is critical for generation of functional vascular networks and local proliferative ductal alveolar outgrowths with invasive potential. Both these processes are augmented by estrogen, whereas antiestrogens inhibit

Topics: Basement Membrane; Breast; Breast Neoplasms; Cell Differentiation; Cell Division; Cells, Cultured; Coculture Techniques; Collagen; Culture Media, Conditioned; Drug Combinations; Endothelial Growth Factors; Endothelium, Vascular; Epithelial Cells; Estrogens; Female; Humans; Hyperplasia; Interleukin-8; Keratins; Laminin; Lymphokines; Matrix Metalloproteinase 2; Mucins; Precancerous Conditions; Proliferating Cell Nuclear Antigen; Proteoglycans; Receptor Protein-Tyrosine Kinases; Receptors, Growth Factor; Receptors, Vascular Endothelial Growth Factor; Umbilical Veins; Vascular Endothelial Growth Factor A; Vascular Endothelial Growth Factors

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