Expression of nitric oxide synthase in gastric cancer

Doi, Chiharu; Noguchi, Yoshikazu; Marat, Doulet; Saito, Aya; Fukuzawa, Kuniyasu; Yoshikawa, Takaki; Tsuburaya, Akira; Ito, Takaaki

doi:10.1016/s0304-3835(99)00222-0

Cited by 30 publications

(17 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This fact suggests that the high production of these proteins may contribute to the process. In fact, the concentration of the inducible enzyme is clearly related to the intensity of metastasis, therefore a role in tumor extension is arrogated to this enzyme [166]. Nevertheless, it has not been possible to prove that iNOS expression might be induced by inflammatory cytokines like TNFα or IL-1.…”

Section: Implications Of Nitric Oxide In Physiological An Pathophysiomentioning

confidence: 98%

New Issues about Nitric Oxide and its Effects on the Gastrointestinal Tract

Martín

Jiménez²,

Motilva³

2001

CPD

111

View full text Add to dashboard Cite

Over the last years the important role of nitric oxide (NO) as endogenous modulator of numerous physiological functions has been shown. NO is involved in the regulation of blood flow, maintenance of vascular tone, control of platelet aggregation, and modulation of the activity of the mastocytes. It also plays a key role as neurotransmitter in the central and peripheric nervous system (non adrenergic non colinergic, NANC, neurons), in the nervous control of the cerebral blood flow and in the neuroendocrine regulation or synaptic plasticity. However, NO shows a dual behavior: at physiological concentrations, released through the constitutive synthase (cNOS), it regulates house-keeping functions, whereas its overproduction by the inducible isoenzyme (iNOS) exhibits cytotoxic activity because interacting with reactive species producing peroxinitrites (ONOO) and other compounds, which are highly damaging for the tissues. In the gastrointestinal tract (GIT) NO participates in the modulation of the smooth musculature tone, such as the regulation of intestinal peristaltism, gastric emptying and antral motor activity. It also regulates acid and gastric mucus secretion, alkaline production, and is involved in the maintenance of mucosal blood flow. In physiological conditions, NO acts as an endogenous mediator modulating both, the repairing and integrity of the tissues, and exhibits gastroprotective properties against different types of aggressive agents. However, high concentrations of NO are related to numerous pathological processes of GIT including peptic ulcer, chronic gastritis, gastrointestinal cancer, bacterial gastroenteritis, celiac or chronic inflammatory bowel diseases. Recently, this hypothesis that cNOS is always beneficial and iNOS is always deleterious, has been questioned, since that a series of data suggest that the increase of cNOS activity could be responsible for the derived pathological changes and, by contrast, NO liberated by the inducible isoenzyme might play a repairing effect in certain pathological disorders. The pharmaceutical industry is really interested in proving the clinical benefits of the mediator. Numerous NO-donor drugs, nitrate derivatives, have been frequently used in the cardiovascular diseases due to their vasodilating properties, which allow an enhancement of coronary blood flow. More recently, the protective effect of NO against non steroidal antiinflammatory drugs (NSAID)-gastroenteropathy has been shown, because its vasodilating and antioxidant properties render it a potentially useful agent. Different NSAID, including acetyl salicylic acid, diclofenac or naproxen, have been formulated by attaching a NO releasing-moiety. These NO-NSAID, antiinflammatories combined with precursors of the mediator, or with inhibitors of the inducible synthase, are currently being evaluated. However, although the pharmacotherapeutical possibilities of NO are considerable, it is necessary to elucidate the exact mechanisms derived from stimulation/inhibition of the isoenzymes in order to determine th...

show abstract

Section: Implications Of Nitric Oxide In Physiological An Pathophysiomentioning

confidence: 98%

New Issues about Nitric Oxide and its Effects on the Gastrointestinal Tract

Martín

Jiménez²,

Motilva³

2001

CPD

111

View full text Add to dashboard Cite

show abstract

“…We previously reported a novel bioactive antigen (SAA) that induces NO synthesis by murine peritoneal exudate cells (PEC) from a culture supernatant of S. anginosus (Sasaki et al , 2001). Furthermore, SAA induced cyclooxygenase‐2 (COX‐2) mRNA expression by PEC (Sasaki et al , 1995b), the overexpression of which has also been observed in cancer tissues (Zang et al , 1998; Doi et al , 1999; Marrogi et al , 2000). It has also been reported that upregulation of the inducible species of both NOS and COX‐2 could be associated with a risk of cancer (Giardiello et al , 1993; Iwasaki et al , 1997; Ambs et al , 1999; Jadeski and Lala, 1999).…”

Section: Introductionmentioning

confidence: 99%

Streptococcus anginosus infection in oral cancer and its infection route

Sasaki¹,

Yamaura²,

Ohara‐Nemoto³

et al. 2005

Oral Diseases

111

View full text Add to dashboard Cite

show abstract

“…In several human tumors overexpression of NOS, NOS activity, and nitrite/nitrate serum levels have been correlated with tumor carcinogenesis and progression, [8][9][10][11][12][13][14] angiogenesis, 8,[15][16][17] tumor cell apoptosis, 18 clinical outcome, [19][20][21][22] and lymph node and systemic metastasis. 23,24 Sarcomas are a heterogeneous group of mesenchymal tumors with variable clinical behavior and histologic presentation. 25 Tumor size, histologic grade, depth, and status of surgical margins have been identified as prognostic factors.…”

mentioning

confidence: 99%

Sarcomas Often Express Constitutive Nitric Oxide Synthases (NOS) But Infrequently Inducible NOS

Cunha¹,

Lopes²,

Falzoni³

et al. 2006

Applied Immunohistochemistry &Amp; Molecular Morphology

View full text Add to dashboard Cite

Nitric oxide (NO) has a dual action in tumors, with both pro-tumor and anti-tumor activities. NO is produced by nitric oxide synthases (NOS). There are three enzyme isoforms: two of them are constitutively produced (neuronal or brain NOS and endothelial NOS), and one is an inducible form (iNOS). NOS expression has been shown in several epithelial tumors, but there is no report addressing NOS expression in sarcomas. The authors evaluated the expression of NOS in 97 cases of various sarcomas spotted in duplicate in a tissue array paraffin block. Eighty-four of the 97 tumor specimens (86.6%) expressed nNOS, and most of them showed a strong expression of the isoenzyme. Only chondrosarcomas and liposarcomas had significant numbers of negative cases, and all pleomorphic sarcomas, alveolar soft part sarcomas, angiosarcomas, gastrointestinal stromal tumors, and synovial sarcomas showed some degree of positivity. Forty-three cases (44.4%) showed eNOS immunostaining, but only 15.5% showed a strong signal, with emphasis on angiosarcomas, chondrosarcomas, alveolar soft part sarcomas, and synovial sarcoma. Strong expression of iNOS was observed in only 9 cases (9.3%), with weak expression in another 26 cases (26.8%). Strong expression of iNOS was found in malignant peripheral nerve sheet tumors, liposarcomas, pleomorphic sarcomas, fibrosarcomas, chondrosarcomas, and synovial sarcomas. Apparently alveolar soft part sarcomas are unusual in their capacity of expression of NOS isoforms, and in a very peculiar pattern. In conclusion, sarcomas in general commonly express constitutive NOS, and only a few types of sarcomas can express iNOS, the isoenzymes capable of releasing large amounts of NO. More comprehensive studies should be performed to better understand the clinical importance of NOS expression and NO production in sarcomas.

show abstract

Expression of nitric oxide synthase in gastric cancer

Cited by 30 publications

References 13 publications

New Issues about Nitric Oxide and its Effects on the Gastrointestinal Tract

New Issues about Nitric Oxide and its Effects on the Gastrointestinal Tract

Streptococcus anginosus infection in oral cancer and its infection route

Sarcomas Often Express Constitutive Nitric Oxide Synthases (NOS) But Infrequently Inducible NOS

Contact Info

Product

Resources

About