interleukin-8 and Laryngeal-Neoplasms

Chemotherapies such as 5-fluorouracil (5-FU) and cisplatin (CDDP) have been widely used to treat laryngeal squamous cell carcinoma (LSCC), the second most common head and neck squamous cell carcinoma. However, chemoresistance seriously impairs chemotherapeutic efficacy. Our present study reveals that 5-FU and CDDP treatment increase the expression of histone deacetylase 1 (HDAC1) in LSCC cells. Consistently, increased levels of HDAC1 are observed in chemoresistant cells. Knockdown of HDAC1 significantly restores the sensitivity of LSCC cells, as HDAC1 increases the expression of interleukin-8 (IL-8), which is essential for LSCC chemoresistance. Mechanistically, HDAC1 directly initiates the transcription of IL-8 though binding to its promoter. Simultaneously, si-HDAC1 increases the levels of miR-93, which binds to the 3'UTR of IL-8 mRNA to trigger its degradation. In summary, the HDAC1/IL-8 axis can confer chemotherapeutic resistance to LSCC cells.

Topics: 3' Untranslated Regions; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Cisplatin; Drug Resistance, Neoplasm; Fluorouracil; Gene Expression Regulation, Neoplastic; Histone Deacetylase 1; Humans; Interleukin-8; Laryngeal Neoplasms; Signal Transduction; Squamous Cell Carcinoma of Head and Neck

The aim of this study was to evaluate serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) as prognostic variables in patients with laryngeal squamous cell cancer. A total of 92 patients with primary diagnosis of laryngeal squamous cell cancer (LSCC), treated between 2003 and 2005, were included in this evaluation. Preoperative serum levels of IL-6 and IL-8 were measured by enzyme-linked immunosorbent assay methods. Results were compared according to clinical and pathological date criteria. Serum IL-6 and IL-8 levels were significantly higher in patients with LSCC compared to healthy controls (P < 0.0001). Serum IL-6 level was associated with lymph node metastasis (P < 0.001), T classification (P < 0.001) and clinical stage (P = 0.001). Multivariate analysis indicated that serum IL-6 was an independent predictor of LSCC-specific progression-free survival (P = 0.049) and overall survival (P = 0.040). Higher serum IL-6 level (IL-6 > 9.7 pg/ml) was associated with a shortened overall survival and progression-free survival (P < 0.05). Our data indicate that serum IL-6 is associated with the development and progression of LSCC. Serum IL-6 may serve as an independent prognostic marker for LSCC patients.

Topics: Biomarkers, Tumor; Disease-Free Survival; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Kaplan-Meier Estimate; Laryngeal Neoplasms; Male; Middle Aged; Neoplasm Staging; Neoplasms, Squamous Cell; Prognosis; Proportional Hazards Models

The aim of this study was to analyze of TLRs mRNA expression in peripheral blood mononuclear cells as potential biomarkers of neoplastic lesions progress and to evaluate their role in the possible mechanisms responsible for the secretion of cytokines in laryngeal cancer.. The analysis of TLR2, TLR4, TRAF6, IRAK1 expression in isolated PBMCs by the reverse transcription PCR (RT-PCR) analysis as well as IL-6, IL-8 and TNF-α levels in supernatants of peripheral blood mononuclear cells from 55 patients with carcinoma of the larynx was performed by ELISA. The invasiveness of carcinoma was evaluated according to tumor front grading, TFG.. We noted that tumors with a well-defined borderline were characterized by significantly higher values of the average expression of TRAF6. Our research also confirmed that more aggressive carcinomas according to TFG, with a more dispersed type of invasion were characterized by significantly lower values of the average expression of IRAK1. Moreover, we observed that tumors with the invasion of cartilage were characterized by significantly lower values of the average expression of TLR4. In addition, the relationships of TLR2 with IL-6 and TNF-α level were highlighted. Significant interconnections were also found between the TLR4 and IL-8, TNF-α, IL-6 secretion after stimulation. The relationships of TRAF6 with IL-8 production after stimulation were noted.. Our findings confirmed the implication of the TLRs pathway molecules in proinflammatory cytokine secretions and their importance as encouraging potential indicators for assessment of the degree of aggressive tumor phenotype.

Topics: Aged; Aged, 80 and over; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-6; Interleukin-8; Laryngeal Neoplasms; Leukocytes, Mononuclear; Male; Middle Aged; Reverse Transcriptase Polymerase Chain Reaction; TNF Receptor-Associated Factor 6; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptors; Tumor Necrosis Factor-alpha

Stromal cell-derived factor-1 (SDF-1) (CXCL12) has been observed to promote laryngeal and hypopharyngeal squamous cell carcinomas (LHSCCs) invasion through cooperation with its receptor CXCR4. Here, we further explore the angiogenesis mechanism induced by SDF-1/CXCR4 interaction in LHSCCs. Immunohistochemistry (IHC) reveals the significant correlation between CXCR4 and angiogenesis in tumors. After blocking the function of CXCR4 by specific inhibitor AMD3100 and neutralized antibody 12G5 or inhibiting the expression by siRNA, we were able to disrupt the HUVECs tube formation, demonstrating that SDF-1/CXCR4 indeed regulated the angiogenesis mechanism. The angiogenesis profiling from angiogenesis array and reverse transcription polymerase chain reaction indicates that IL-8 can be significantly triggered by SDF-1/CXCR4 interaction in LHSCCs. We also demonstrate that IL-8 secretion mechanism is regulated by Akt phosphorylation after SDF-1 stimulation. These results point out the importance of SDF-1/CXCR4 interaction in LHSCCs angiogenesis. The angiogenic factor IL-8 would be triggered by the cooperation of SDF-1 and CXCR4 through an Akt-dependent pathway. This provides a new targeting therapy utility, disrupting SDF-1/CXCR4 interaction combined with downstream-induced angiogenic factors in LHSCCs would be beneficial to improve clinical outcome.

Topics: Blotting, Western; Carcinoma, Squamous Cell; Cell Line, Tumor; Chemokine CXCL12; Humans; Hypopharyngeal Neoplasms; Interleukin-8; Laryngeal Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-akt; Real-Time Polymerase Chain Reaction; Receptors, CXCR4; Reverse Transcriptase Polymerase Chain Reaction

In studied analyzed role of the cytokines in pathology of neoplasms of various origin the importance of these proteins in regulation of immunocompetent cells function has been described. The aim of this study was to estimate of cho sen cytokines concentration produced by peripheral blood mononuclear cells and in whole blood in patients with laryngeal carcinoma and to analyze the connection of cytokines profile with clinicopathological features. MATERIALA AND METHODS: 55 patients with squamous cell carcinoma of the larynx treated at ENT Department Medical University of Lodz between 2003-2007 were analyzed. For estimation of cytokine secretion the cultures of isolated peripheral blood mononuclear cells (T lymphocytes) and the whole blood were established. Production of cytokines in supernatants was detected by Elisa. Connections with clinicomorphological features (pT, pN, Anneroth, Batsakis i Lunas' classification) were analyzed.. Authors reported statistical correlation between chosen cytokines concentration and clinicomorphological parameters: pT and IL-2, IL-6, IL-8, TNFalpha produced by isolated cells and IL-2, IL-6, TNFa and IFNgamma in whole blood, pN and IL-8, IL-10, IFNgamma; ABL score and IL-6, TNFalpha, IFNgamma produced by isolated cells and IL-2, IL-6, IL-10, TNFalpha, IFNgamma in whole blood.. Our studied indicated the important influence of proinflammatory and regulatory cytokines produced by immunocompetent cells for course of neoplasm disease, aggressiveness and advance in laryngeal carcinoma.

Topics: Adult; Aged; Biomarkers, Tumor; Carcinoma, Small Cell; Cytokines; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-2; Interleukin-6; Interleukin-8; Laryngeal Neoplasms; Leukocytes, Mononuclear; Male; Middle Aged; Neoplasm Staging; Poland; Retrospective Studies; Tumor Necrosis Factor-alpha

The most important mechanism of host humoral immunity in antitumor response is cytokines activity produced by T lymphocytes. The aim of this preliminary study was estimation of IL-6 and IL-8 serum concentration in patients with squamous cell laryngeal carcinoma and analysis of indirect influence of neoplasm cells to the function of T lymphocytes and modification of proinflammatory cytokines profile.. 7 patients with squamous cell carcinoma of the larynx treated at ENT Department Medical University of Lodź between 2003-2005 were analyzed. For estimation of proinflammatory cytokine secretion the cocultures of isolated peripheral blood lymphocytes, centrum and margin neoplasm cells and noncancerous cells were established. Production of cytokines in supernatants was detected by Elisa.. Authors reported that in vitro epithelial cells of the larynx is able to secrete of IL-8, but not IL-6. The presence of normal epithelial cells and carcinoma cells in lymphocyte culture may increase concentration of IL-6 and IL-8 especially with normal laryngeal epithelium cells.. Laryngeal squamous carcinoma cells could modified T lymphocytes activity and production of proinflammatory cytokines IL-6 and IL-8.

Topics: Aged; Carcinoma, Squamous Cell; Enzyme-Linked Immunosorbent Assay; Female; Humans; In Vitro Techniques; Interleukin-6; Interleukin-8; Laryngeal Neoplasms; Male; Middle Aged; T-Lymphocytes

Epithelial defensins including human beta-defensins (hBDs) and alpha-defensins (HDs) are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown.. Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP) and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR) assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p < 0.01) suggesting that they were co-inducible in papillomavirus induced lesions. Unlike hBDs, only low levels of HD5 and HD6 were detectable in papillomas and in oral mucosa.. Human beta-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.

Topics: Adult; Aged; beta-Defensins; Child; Child, Preschool; Epithelial Cells; Female; Human papillomavirus 11; Human papillomavirus 6; Humans; Interleukin-8; Laryngeal Neoplasms; Male; Middle Aged; Papilloma; Papillomavirus Infections; Polymerase Chain Reaction; RNA, Messenger

To explore the immunological mechanism of the anti-tumor function of resveratrol (Res) through in vitro or vivo experiments.. The tumor cell growth repression rate was measured by MTT colorimetry. Flow cytometry was used to analyze the cell cycle of Hep2 cells (laryngeal squamous cancer cell line). The immune function and cytokine levels in the serum of the tumor-bearing mice were determined by MTT colorimetry, hemolysis spectrophotography, improved Mayer's method and ELISA.. Res inhibited the tumor cell growth and enhanced the apoptosis of tumor cells in time-concentration-dependent manners showing the phenomenon of obvious G(0)/G(1) blocking and apoptotic peak. The maximal tumor inhibition rate came up to 42.76%. Furthermore, Res improved function of T, B lymphocytes, killing activity of NK cells, release of antibodies, and the total complement activity in serum. It also increased contents of IL-2 and TGF-beta1 but reduced that of IL-8 and VEGF.. Res can not only affect tumor cells directly but also exert anti-tumor efficiency through reinforcing cell-mediated, humoral immune response and accommodating lymphocytes to secrete cytokines.

Topics: Animals; Antibody Formation; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Flow Cytometry; Humans; Interleukin-2; Interleukin-8; Laryngeal Neoplasms; Mice; Resveratrol; Stilbenes; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A

To find a new kind of biological response modifier to anti-laryngocarcinoma through studying the efficiency of resveratrol.. To detect the growth inhibiting rate of Hep-2 exposed to resveratrol with MTT colorimetry and to analyze the apoptosis and cell cycle of Hep-2 with flow cytometry. As having formed the model of laryngocarcinoma, quite a few indicatrixes including the content changes of IL-2, IL-8,TGF-beta1 and VEGF were detected.. Resveratrol could induce apoptosis of Hep-2 in time-concentration-dependent manners showing obvious cell cycle blocking of G0/G1 and apoptotic peak. Furthermore, resveratrol improved remarkably the growth condition of mice planted with Hep-2 while enhancing their immunological function.. As a kind of biological response modifier, resveratrol could strengthen anti-tumor immunoresponse, accommodating lymphocyte to secrete cytokine, through which it exerted the efficiency of anti-laryngocarcinoma.

Topics: Animals; Antineoplastic Agents, Phytogenic; Apoptosis; Cell Cycle; Cell Line, Tumor; Humans; Interleukin-2; Interleukin-8; Laryngeal Neoplasms; Male; Mice; Mice, Inbred C57BL; Resveratrol; Stilbenes; Transforming Growth Factor beta1; Vascular Endothelial Growth Factor A

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

Respiratory syncytial virus (RSV) is an important respiratory pathogen that preferentially infects epithelial cells in the airway, and causes a local inflammatory response. Although it has been previously demonstrated that RSV-infected airway epithelial produce cytokines, including interleukin-8 (IL-8), which contributes to the inflammatory response, the regulation of this effect of RSV is unknown. To further characterize the mechanisms by which RSV infection triggers release of IL-8, we first exposed cultured A549 cells to RSV, and measured IL-8 release via enzyme-linked immunosorbent assays (ELISA), and IL-8 messenger RNA (mRNA) induction via Northern blot analysis. We observed a dose- and time-dependent release of IL-8 in response to RSV. The optimal dose of RSV was 10(4) TCID50/ml, and maximal release of IL-8 was measured at 72 to 96 h after infection. RSV induced a biphasic (early and late) increase in IL-8 mRNA. The early phase was independent of viral infection, whereas the more pronounced late phase required the presence of live virus and infection of the epithelium. Partial (< 50%) cytopathic effects were noted at 48 h and progressed to 75% at 96 h. The monolayer was still intact at 96 h. Inhibitors of nitric oxide, including NG-monomethyl-L-arginine (L-NMMA), NG-nitro-L-arginine methyl ester (L-NAME), and aminoguanidine had no effect on IL-8 release or IL-8 mRNA induction. We did, however, demonstrate a dose-dependent decrease in IL-8 release and IL-8 mRNA induction in RSV-infected epithelial treated with the antioxidants dimethyl sulfoxide (DMSO) or 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Peak effects were noted at a concentration of 2% DMSO and 50 microM DMPO. The antioxidants did not inhibit viral replication or infection. This data suggest that RSV-induced IL-8 production in airway epithelium is mediated via changes in oxidant tone. The data also suggest a potential therapeutic role for antioxidants in RSV infections.

Topics: Antioxidants; Blotting, Northern; Epithelium; Humans; Interleukin-8; Laryngeal Neoplasms; Nitric Oxide; Oxidants; Respiratory Syncytial Virus Infections; RNA, Messenger; Tumor Cells, Cultured; Virus Replication