High microvascular density is correlated with high VEGF, iNOS and COX‐2 expression in penetrating growth‐type early gastric carcinomas

Ichinoe, Masaaki; Mikami, Taisei; Shiraishi, Hiroaki; Okayasu, Isao

doi:10.1111/j.1365-2559.2004.02031.x

Cited by 27 publications

(22 citation statements)

References 15 publications

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“…Increased levels of COX-2 have been reported in carcinomas of the colon, stomach, breast, esophagus lung liver, and pancreas. 8,10,[11][12][13][14][15] Cyclooxygenase 2 is important for tumorigenesis because prostaglandins, especially prostaglandin E 2 , affect cell proliferation, differentiation, apoptosis, angiogenesis, and metastasis. 10 Nitric oxide produced by iNOS has been reported to enhance the activity of COX-2.…”

Section: Discussionmentioning

confidence: 99%

“…10 Expression of the genes for COX-2 and iNOS is correlated in human lung, colon, prostate, pancreas, and gastric cancers. [11][12][13][14][15] In an animal model of ESCC, Chen et al 16,17 also reported a correlation between COX-2 and iNOS. However, to our knowledge, there have been no detailed reports mentioning the correlation between COX-2 and iNOS in early-stage human ESCC.…”

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confidence: 99%

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Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Kumagai

Sobajima

Higashi

et al. 2015

International Surgery

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Using immunohistochemical staining, the present study was conducted to examine whether cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) affect angiogenesis in early-stage esophageal squamous cell carcinoma (ESCC). We also analyzed the correlation between these two factors. Cyclooxygenase 2, iNOS, and angiogenesis in early-stage ESCC are unclear. Using 10 samples of normal squamous epithelium, 7 samples of low-grade intraepithelial neoplasia (LGIN), and 45 samples of superficial esophageal cancer, we observed the expression of COX-2 and iNOS. We then investigated the COX-2 and iNOS immunoreactivity scores and the correlation between COX-2 or iNOS scores and microvessel density (MVD) using CD34 or CD105. The intensity of COX-2 or iNOS expression differed significantly according to histological type (P , 0.001). The scores of COX-2 and iNOS were lowest for normal squamous epithelium, followed in ascending order by LGIN, carcinoma in situ and tumor invading the lamina propria mucosae (M1-M2 cancer); and tumor invading the muscularis mucosa (M3) or deeper cancer. The differences were significant (P , 0.001). Cancers classified M1-M2 (P , 0.01 and P , 0.05, respectively); M3; or deeper cancer (P , 0.01) had significantly higher COX-2 and iNOS scores than normal squamous epithelium. There was a significant correlation between COX-2 and iNOS scores (P , 0.001, r s ¼ 0.51). Correlations between COX-2 score and CD34-positive MVD or CD105-positive MVD were significant (r s ¼ 0.53, P , 0.001; r s ¼ 0.62, P , 0.001, respectively). Inducible nitric oxide synthase score was also significantly correlated with CD34 MVD and CD105 MVD (r s ¼ 0.45, P , 0.001; r s ¼ 0.60, P , 0.001, respectively). Chemoprevention of COX-2 or iNOS activity may blunt the development of ESCC from precancerous lesions.Key words: COX-2 -iNOS -CD34 -CD105 -Esophageal cancer -Angiogenesis T he depth of invasion of superficial esophageal carcinoma is expressed in accordance with the sub-classification criteria of the Japan Esophageal Society (Guidelines for clinical and pathologic studies on carcinoma of the esophagus). 1Angiogenesis is essential for cancer progression in order to supply nutrients and oxygen, and remove metabolic waste. Understanding the mechanism of angiogenesis, especially during the early stage of cancer progression, may uncover new targets for treatment or prevention.We have previously reported in detail the use of microvessel density (MVD) as a feature of earlystage esophageal squamous cell carcinoma (ESCC) revealed by immunostaining using CD34 and CD105.2 In that report, we mentioned that MVD based on CD34 and CD105 immunostaining increased according to the grade of atypia or depth of ESCC progression, and also that these findings were correlated with the morphological features of microvessels at the surface of superficial ESCC observed by magnifying endoscopy.As a subsequent step, we examined the angiogenic factors that induced these newly recruited capillaries at the early stage of ESCC progression. Based on a revie...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Kumagai

Sobajima

Higashi

et al. 2015

International Surgery

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“…VEGF increases cancer cell growth by promoting the cleavage and proliferation of tumor cells by binding to the tyrosinase receptor (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Function of inducible nitric oxide synthase in the regulation of cervical cancer cell proliferation and the expression of vascular endothelial growth factor

Dong

Cheng

Sun

2013

Molecular Medicine Reports

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“…8c). Both VEGF and iNOS have been linked to promoting tumor cell growth and poor survival in human studies [57,58]. The release of Table 7.…”

Section: Skov·3 Csa Expressing Tumor Cells Have Significantly Reducedmentioning

confidence: 99%

“…Tumor promoting mechanisms of iNOS are likely mediated through the production and activity of NO promoting increased growth of tumor and stromal cells, as well as increasing VEGF and vascular activity [57,58]. iNOS levels present in SKOV-3 CV and WT tumors potentially promote tumor vascularization through induction of VEGF expression in the tumor.…”

Section: C5a Enhancement Of Recruitment and Anti-tumor Effects On Macmentioning

confidence: 99%

Effect of complement C5a in tumor progression and the local tumor microenvironment.

Gunn¹

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High microvascular density is correlated with high VEGF, iNOS and COX‐2 expression in penetrating growth‐type early gastric carcinomas

Abstract: Increased MVD in PEN type has an intimate causal relationship to angiogenic factors, high VEGF and iNOS expression. The SUP type, in contrast, has characteristics of low angiogenesis.

Cited by 27 publications

References 15 publications

Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Coexpression of COX-2 and iNOS in Angiogenesis of Superficial Esophageal Squamous Cell Carcinoma

Function of inducible nitric oxide synthase in the regulation of cervical cancer cell proliferation and the expression of vascular endothelial growth factor

Effect of complement C5a in tumor progression and the local tumor microenvironment.

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