Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic cancer

Franco, L.; Doria, Denise; Bertazzoni, E. Minelli; Benini, Anna; Bassi, Claudio

doi:10.1016/j.prostaglandins.2003.12.001

Cited by 35 publications

(23 citation statements)

References 22 publications

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“…The 6 month survival is about 50% and the five-year survival after diagnosis is less than 5% 66 . It has been known for several years that pancreatic cancer is associated with increased expression levels of iNOS and COX-2 when compared to normal pancreatic tissue [67][68][69][70][71] . The most insightful study of the importance of iNOS and NO production on pancreatic carcinoma growth and their resistance to anti-cancer drugs was recently reported 72 .…”

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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Section: Studies Demonstrating Importance Of Inos and No In Cancermentioning

confidence: 99%

Nitric Oxide and Cancer Development

et al. 2007

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“…However, high levels of NO have been demonstrated to have a pro-apoptotic role on tumour cells [116,117] and induces G1 arrest [118] , whereas low levels of iNOS and NO may enhance tumour progression and metastasis [119] . Western blot analysis and immunohistochemistry have shown an increased expression of iNOS in human pancreatic cancer tissue when compared to surrounding normal tissue [120,121] . Immunohistochemical analysis has also shown increased iNOS expression in human pancreatic tissue, which correlated to an increased apoptotic index but not to prognosis [73,122] .…”

Section: Inducible Nitric Oxidementioning

confidence: 99%

Role of inflammation in pancreatic carcinogenesis and the implications for future therapy

et al. 2005

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“…Because marked cyclooxygenase-2 expression was observed in pancreatic cancer tissue (76), other agents being investigated in combination with gemcitabine included the cyclooxygenase-2 inhibitor celecoxib. Indeed, experimental data suggest that cyclooxygenase-2 may play an important role in pancreatic tumorigenesis and metastasis and may be a promising target for treatment (77).…”

Section: Novel Cancer Therapeutics Based On Genetic Abnormalitiesmentioning

confidence: 99%

Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer

Giovannetti

Mey

Nannizzi

et al. 2006

Molecular Cancer Therapeutics

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Chemotherapy has produced unsatisfactory results in pancreas cancer and novel approaches, including treatment tailoring by pharmacogenetic analysis and new molecular-targeted drugs, are required. The scarcity of effective therapies may reflect the lack of knowledge about the influence of tumor-related molecular abnormalities on responsiveness to drugs. Advances in the understanding of pancreas cancer biology have been made over the past decade, including the discovery of critical mutations in oncogenes (i.e., K-Ras) as well as the loss of tumor suppressor genes, such as TP53 and p16 INK4 . Other studies showed the dysregulation of the expression of proteins involved in the control of cell cycle, proliferation, apoptosis, and invasiveness, such as Bcl-2, Akt, mdm2, and epidermal growth factor receptor. These characteristics might contribute to the aggressive behavior of pancreatic cancer and influence response to treatment.

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Increased expression of inducible nitric oxide synthase and cyclooxygenase-2 in pancreatic cancer

Cited by 35 publications

References 22 publications

Nitric Oxide and Cancer Development

Nitric Oxide and Cancer Development

Role of inflammation in pancreatic carcinogenesis and the implications for future therapy

Pharmacogenetics of anticancer drug sensitivity in pancreatic cancer

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