Frequent expression of inducible nitric oxide synthase in esophageal squamous cell carcinomas.

Tanaka, Hikaru; Kijima, Hiroshi; Tokunaga, Tetsuji; Tajima, T.; Himeno, Shinji; Kenmochi, Takahiro; Oshiba, G; Kise, Yoshifumi; Nishi, Takayuki; Chino, Osamu; Sasaki, Hideo; Machimura, Takao; Tanaka, Makiko; Makuuchi, Hiroyasu

doi:10.3892/ijo.14.6.1069

Cited by 40 publications

(44 citation statements)

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“…Oxidative stress contributes to the formation of peroxynitrite, which can damage DNA, and can be catalyzed by tissue peroxidases to products that induce COX-2. iNOS is overly expressed in many human cancers including esophageal SCC [34]. Dietary 5% BRBs significantly down-regulated iNOS mRNA with a reduction in nitrite levels in esophageal tissues [30].…”

Section: Effects Of Berries On Gene Expression In the Esophagusmentioning

confidence: 99%

Cancer prevention with freeze-dried berries and berry components

Stoner

Wang

Zikri

et al. 2007

Seminars in Cancer Biology

150

119

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Our laboratory is developing a food-based approach to the prevention of esophageal and colon cancer utilizing freeze-dried berries and berry extracts. Dietary freeze-dried berries were shown to inhibit chemically-induced cancer of the rodent esophagus by 30-60% and of the colon by up-to 80%. The berries are effective at both the initiation and promotion/progression stages of tumor development. Berries inhibit tumor initiation events by influencing carcinogen metabolism, resulting in reduced levels of carcinogen-induced DNA damage. They inhibit promotion/progression events by reducing the growth rate of premalignant cells, promoting apoptosis, reducing parameters of tissue inflammation and inhibiting angiogenesis. On a molecular level, berries modulate the expression of genes involved with proliferation, apoptosis, inflammation and angiogenesis. We have recently initiated clinical trials; results from a toxicity study indicated that freeze-dried black raspberries are well tolerated in humans when administered orally for 7 days at a dose of 45 grams per day. Several Phase IIa clinical trials are underway in patients at high risk for esophagus and colon cancer; i.e., Barrett's esophagus, esophageal dysplasia and colonic polyps, to determine if berries will modulate various histological and molecular biomarkers of development of these diseases.

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Section: Effects Of Berries On Gene Expression In the Esophagusmentioning

confidence: 99%

Cancer prevention with freeze-dried berries and berry components

Stoner

Wang

Zikri

et al. 2007

Seminars in Cancer Biology

150

119

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“…iNOS expression is highly associated with esophageal squamous cell carcinoma [57][58][59][60][61] . Barrett's esophageal is a premalignant condition arising from chronic reflux esophagitis and high levels of iNOS as well as COX-2 have been observed in this condition 58,[60][61][62] .…”

Section: Studies Demonstrating Importance Of Inos and No In Cancermentioning

confidence: 99%

Nitric Oxide and Cancer Development

et al. 2007

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Abstract:The role of nitric oxide (NO) in cancer development has become a very active research area. This review presents an overview of many studies that implicate an important role of NO in the development of cancer. These include results in experimental models as well as many observations made on NO and inducible nitric oxide synthase (iNOS) in human cancers. Our survey of the literature has allowed us to conclude that in general large levels of NO will kill cancer cells but paradoxically at intermediate to lower levels NO prevents cancer cell apoptosis and enhances tumor growth. This basic tenet has been demonstrated in many experimental models. The mechanistic basis of how intermediate levels of NO mediate tumor development is an active area of research and is the subject of this review. NO mediated S-nitrosylation of key enzymes and regulatory proteins plays a critical role. Key proteins S-nitrosylated which enhance tumor development include several caspases involved in apoptosis, PTEN the tumor suppressor protein, Bcl-2 the mitochondrial protein which protects from apoptosis, OGG1 the DNA repair protein and methionine adenosyl transferase the liver protein which synthesizes adenosylmethionine. The S-nitrosylation of these proteins enhances DNA mutations, prevents cancer cell apoptosis and enhances oncogenic cell growth. (J Toxicol Pathol 2007; 20: 77-92)

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“…The level of NOS protein and/or NOS activity has been positively correlated with the degree of malignancy in human gynaecological cancers (Thomsen et al, 1994), central nervous system tumours (Cobbs et al, 1995), breast cancer (Thomsen et al, 1995), squamous-cell carcinomas of the head and neck (Gallo et al, 1998), lung cancer (Fujimoto et al, 1997) and oesophageal squamous cell carcinoma (Tanaka et al, 1999). Obviously, NO plays an ambivalent role in tumorigenesis depending on NOS activity and resulting NO concentrations.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide of human colorectal adenocarcinoma cell lines promotes tumour cell invasion

et al. 2002

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The present study investigates the role of nitric oxide and the involvement of nitric oxide synthase II isoform on the invasion of human colorectal adenocarcinoma cell lines HRT-18 and HT-29. HRT-18 cells, which constitutively express nitric oxide synthase II mRNA were three-fold more invasive in a Matrigel 1 invasion assay than nitric oxide synthase II mRNA negative HT-29 cells. Treatment of HT-29 cells with the nitric oxide donor Deta NONOate (50 nM) as well as induction of nitric oxide synthase II mRNA and production of endogenous nitric oxide by inflammatory cytokines (IFN-g and IL-1a) increased the invasiveness of HT-29 cells by approximately 40% and 75%, respectively. In HT-29 cells nitric oxide synthase II mRNA was also induced in co-culture with human monocytes. The invasiveness of HRT-18 cells and stimulated HT-29 cells was partly inhibited by the nitric oxide synthase II inhibitor 1400 W. These results show that nitric oxide increases the invasion of human colorectal adenocarcinoma cell lines HRT-18 and HT-29, and the involvement of nitric oxide synthase II isoform in tumour cell invasion. Therefore, the production of nitric oxide and secretion of pro-inflammatory cytokines by tumour-associated macrophages, which in turn induce nitric oxide synthase II isoform in tumour cells, promotes tumour cell invasiveness. British Journal of Cancer (2002) There is no doubt that tumour-associated macrophages (TAM) are an important component of the tumour stroma. They affect the behaviour of tumour cells by a variety of mediators. One of these mediators is nitric oxide (NO). NO is produced by three isoforms of the nitric oxide synthase (NOS I-III) using L-arginine as substrate. In macrophages NOS II is generally inducible by inflammatory stimuli and mediates a high-output long-lasting release of NO. Because NO is the source of reactive nitrogen intermediates (RNI), the NOS II induction is one part of macrophage cytotoxicity against tumour cells. On the other hand, NO favours neoangiogenesis, if NO concentrations do not reach a cytotoxic level (Wink et al, 1998). In human malignant tumours high NO concentrations have been measured in vivo. Although the main source of NO probably are tumour-associated macrophages, there are some reports that the synthesis of NO is inducible by cytokines in some human carcinoma cell lines like DLD-1, HT-29, A-172 and NIH:OVCAR-3 (Thomsen and Miles, 1998). The biological significance of NO in malignant tumours is not clear, but a recent study suggest that a high expression of NOS II and NOS III is associated with aggressive behaviour of colorectal adenocarcinomas (Yagihashi et al, 2000). The aim of the present study was to investigate if NO is able to modulate tumour cell invasiveness of human colorectal adenocarcinoma cell lines , and whether NO can be induced by cytokines produced by stromal macrophages. MATERIALS AND METHODS Monocyte isolationMonocytes were isolated from buffy coats with Ficoll-Paque (Pharmacia, Freiburg, Germany) followed by hypotonic density gradient centrifugatio...

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Frequent expression of inducible nitric oxide synthase in esophageal squamous cell carcinomas.

Cited by 40 publications

References 0 publications

Cancer prevention with freeze-dried berries and berry components

Cancer prevention with freeze-dried berries and berry components

Nitric Oxide and Cancer Development

Nitric oxide of human colorectal adenocarcinoma cell lines promotes tumour cell invasion

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