Article

Expressions of nuclear factor kappa B, inducible nitric oxide synthase, and vascular endothelial growth factor in adenoid cystic carcinoma of salivary glands: Correlations with the angiogenesis and clinical outcome

Key Lab for Oral Biomedical Engineering, Ministry of Education, School of Stomatology, Wuhan University, Wuhan, PR China.
Clinical Cancer Research (Impact Factor: 8.19). 10/2005; 11(20):7334-43. DOI: 10.1158/1078-0432.CCR-05-0241
Source: PubMed

ABSTRACT To evaluate the expressions of nuclear factor kappaB (NF-kappaB p65), inducible nitric oxide synthase enzyme (iNOS), and vascular endothelial growth factor (VEGF) in relation to angiogenesis (microvessel density, MVD) and clinical outcomes in adenoid cystic carcinoma (ACC) of salivary glands.
Immunohistochemical staining was used to quantify the protein expression levels of NF-kappaB p65, iNOS, and VEGF in 80 surgically resected ACCs and 20 normal salivary tissues. In all cases of ACCs, MVD was evaluated by counting CD34-reactive endothelial cells or endothelial cell clusters.
The nuclear localization of NF-kappaB p65 was only detected in ACC cells. Both iNOS and VEGF staining activities in ACCs were more significant than those in normal gland tissues (P < 0.01). MVD had significant correlations with NF-kappaB p65, iNOS, and VEGF expressions (P < 0.01). In three histologic types of ACCs, the NF-kappaB, iNOS, VEGF expressions, and MVD were significantly higher in solid type than in cribriform and tubular types (P < 0.01). The NF-kappaB, iNOS, VEGF expressions, and MVD were significantly correlated with clinical stage, tumor size, vascular invasion, recurrence, and metastasis (P < 0.05). Multivariate analysis showed NF-kappaB, iNOS and VEGF expression, MVD, solid histotype, and perineural invasion had an independent prognostic effect on overall survival.
The expressions of NF-kappaB p65, iNOS, and VEGF were related with MVD. Clinical outcomes raised the possibility that the overexpression of these cytokines might contribute to tumor angiogenesis and have prognostic value in ACCs.

0 Bookmarks
 · 
56 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The adenoid cystic carcinoma (ACC) is a neurotropic salivary gland tumor with a high blood-borne metastasis tendency. The treatment of choice for localized disease consists of radical surgical resection and, depending on resection status, adjuvant radiotherapy. Due to the high recurrence rate with limited local therapeutic options and frequent occurrence of distant metastases, one is confronted inevitably with the search for an adequate systemic therapy. ACC shows little response to a variety of chemotherapeutic agents, partial or complete remissions are extremely rare. Beside classical chemotherapies, immunotherapeutics and targeted therapies with more favorable side effect profiles were tested in trials, but due to the small number of patients, a definitive statement on the effectiveness can be hardly made. This results in the need for prospective multicenter studies that allow clear recommendations for systemic therapy of the tumor. The present paper gives an overview of the sub-cellular and genetic characteristics of ACC, which represent possible targets for systemic therapies and have partly already been included in running clinical trials.
    Laryngo-Rhino-Otologie 10/2014; 93(10):657-64. DOI:10.1055/s-0034-1382024 · 0.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: Adenoid cystic carcinoma (ACC) is a rare tumor of secretory glands. Recent advances in molecular characterization and in therapeutics are reviewed.Design: A search of articles in Pubmed and of abstracts from national meetings was performed.Results: Recent genetic analyses find that recurrent chromosome 6:9 translocations in ACC generate a MYB:NFIB fusion resulting in overexpression of the MYB oncoprotein. Several other frequent mutations are recently published which may be relevant for drug development. Several trials of targeted drugs are reviewed. Some agents delay tumor progression, but tumor responses remain rare.Conclusions: Adenoid cystic carcinomas have a characteristic chromosomal translocation, but also frequently pick up additional mutations. Clinical research is limited by the rarity of ACC and slow growth of ACC. Several ongoing trials are testing agents that inhibit fibroblast growth factor receptor signaling or other signaling pathways. Novel treatments based on the recently sequenced tumor genome are under development. This article is protected by copyright. All rights reserved.
    Head & Neck 12/2014; DOI:10.1002/hed.23925 · 2.83 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, we aimed to explore the effect of inducible nitric oxide synthase (iNOS) on vascular endothelial growth factor (VEGF) expression in salivary gland adenoid cystic carcinoma (SACC). Using RNAi, we transfected chemically synthesised iNOS siRNA into ACC-M cells (a highly metastatic adenoid cystic carcinoma cell line) and detected the change in the gene and protein expression levels of iNOS and VEGF by qRT-PCR and Western blotting. A transwell invasiveness assay was used to examine the changes in invasive ability of ACC-M cells. Cell growth was determined using a CCK-8 assay. Apoptosis and cell-cycle phases were detected by flow cytometry. We found that silencing iNOS down-regulated the expression of VEGF and then inhibited cell growth and invasiveness of SACC cells, while it increased apoptosis. Therefore, we concluded that iNOS can regulate VEGF expression and iNOS may be a therapeutic target.
    Journal of Oral Pathology and Medicine 07/2014; DOI:10.1111/jop.12217 · 1.87 Impact Factor