Inducible nitric oxide synthase expression in various laryngeal lesions in relation to carcinogenesis, angiogenesis, and patients' prognosis.

The inducible nitric oxide synthase (iNOS) expression leading to vascular endothelial growth factor (VEGF) overexpression may be useful as a factor for predicting recurrence after initial treatment and prognosis in laryngeal squamous cell carcinoma (SCC). We analyzed expression of iNOS, p53, and VEGF in various laryngeal lesions. The study samples consisted of 63 SCC, 20 dysplasia, 7 polyp, and 5 normal epithelium of the larynx. The expression of iNOS, p53, and VEGF was identified by immunohistological methods. No positive immunostaining for iNOS, p53, and VEGF was observed in normal epithelium and polyps. In contrast, with the progression from mild/moderate dysplasia to severe dysplasia to carcinoma, their expression levels increased. In dysplasia, there was a significant positive correlation among expression of iNOS, p53, and VEGF. In SCC, iNOS expression correlated with VEGF overexpression and microvessel density, but not with p53 overexpression. In SCC, the expression of iNOS and VEGF significantly increased in patients who developed local recurrence and/or metastases after initial treatments. Kaplan-Meier analysis showed that disease-free survival was significantly shorter in patients with iNOS or VEGF expression. Multivariate analysis showed expression of iNOS and VEGF as independent indicators for poor disease-free survival.

Shigyo H ，Nonaka S ，Katada A ，Bandoh N ，Ogino T ，Katayama A ，Takahara M ，Hayashi T ，Harabuchi Y ... -  《ACTA OTO-LARYNGOLOGICA》

VEGF and bFGF expression and microvessel density of maxillary sinus squamous cell carcinoma in relation to p53 status, spontaneous apoptosis and prognosis.

Bandoh N ，Hayashi T ，Takahara M ，Kishibe K ，Ogino T ，Katayama A ，Imada M ，Nonaka S ，Harabuchi Y ... -  《CANCER LETTERS》

Expression of endothelial nitric oxide synthase and vascular endothelial growth factor in oral squamous cell carcinoma: its correlation with angiogenesis and disease progression.

Angiogenesis is a crucial step in the successful growth, invasion, and metastasis of a tumor. It has been popularly accepted that vascular endothelial growth factor (VEGF) is the most potent angiogenic factor in tumor angiogenesis. As another possible star molecule responsible for tumor angiogenesis, the role of nitric oxide (NO) in tumor biology has gained much attention in recent years. The aim of this study was to investigate whether the expression of endothelial nitric oxide synthase (eNOS) and VEGF in oral squamous cell carcinoma (OSCC) is associated with angiogenesis. The present study also made a preliminary exploration of the possible cross-talking existing between eNOS and VEGF during tumor angiogenesis. In this study, expression of eNOS and VEGF were studied immunohistochemically in tissue sections from 40 patients with OSCC and 20 normal controls. To exclude eNOS antibody cross-reactivity with inducible or neuronal nitric oxide (iNOS or nNOS), eNOS expression was confirmed by using an eNOS mRNA in situ hybridization kit. The intratumoral microvessels were highlighted by immunostaining with anti-factor VIII-related antigen monoclonal antibody and counted as well-established methods. Then, chi-square test or Student's t-test was performed to study the correlations between the expression of eNOS and VEGF, microvessel density (MVD), and various clinicopathologic factors. Both eNOS and VEGF expression significantly increased in OSCC tissues, with a positive rate of 47.5% and 50%, respectively. The average MVD in OSCC tissues was 23.45 per high-power field (HPF), showing an obvious association with lymph node metastasis and clinical stages of patients with OSCC. Either eNOS or VEGF positivity was correlated with vessel involvement and OSCC progression. The mean MVD was significantly higher in eNOS- or VEGF-positive tumors than in eNOS- or VEGF-negative tumors. An obvious, correlation was also seen between eNOS and VEGF expression in OSCC tissues in this study. Overexpression of eNOS and VEGF might make an important contribution to the tumor angiogenesis in OSCC. NO generation by eNOS might be implicated in the VEGF-associated angiogenic process. Further investigation of the possible cross-talking between eNOS and VEGF with respect to tumor angiogenesis is necessary.

Shang ZJ ，Li JR 《JOURNAL OF ORAL PATHOLOGY & MEDICINE》

[The correlation of vascular endothelial growth factor with angiogenesis and p53 gene in laryngeal squamous cell carcinoma].

Yaylaci A ，Cakir S ，Güneş P ，Akkaynak AC ，Naiboğlu B ，Gökçeer T ... -  《-》

Stromelysin 3, Ets-1, and vascular endothelial growth factor expression in oral precancerous and cancerous lesions: correlation with microvessel density, progression, and prognosis.

Arora S ，Kaur J ，Sharma C ，Mathur M ，Bahadur S ，Shukla NK ，Deo SV ，Ralhan R ... -  《CLINICAL CANCER RESEARCH》