What are cyclooxygenases and lipoxygenases doing in the driver's seat of carcinogenesis?

Fürstenberger, Gerhard; Krieg, Peter; Müller‐Decker, Karin; Habenicht, Andreas J. R.

doi:10.1002/ijc.22153

Cited by 154 publications

(139 citation statements)

References 91 publications

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“…Despite the progress achieved in cancer therapy in the last decades, the prognosis of oral SCC has not been drastically improved and the 5 years survival rate does not exceed 50% (3,4). Epidemiological data, in vitro studies in cell cultures, as well as in vivo animal studies and controlled clinical trials have demonstrated that nonsteroidal anti-inflammatory drugs (NSAIDs) exert antineoplastic effects in various types of cancer, such as colon, lung, breast, prostate, and head and neck cancer (5)(6)(7)(8)(9)(10). NSAID sulindac has shown growth inhibitory and proapoptotic effects on various cancer cell lines in vitro, including colon and breast cancer cell lines (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model

Katoumas

Nikitakis

Perrea

et al. 2015

Cancer Prevention Research

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The antineoplastic properties of the NSAID sulindac have long been studied. The purpose of this study was to explore sulindac's in vivo effects on oral squamous cell carcinoma (SCC) oncogenesis using the hamster cheek pouch oral carcinogenesis model (HOCM). Thirty Syrian golden hamsters were divided into three experimental and two control groups (n ¼ 6 each). The animals' right buccal pouches were treated with carcinogen for 9 weeks in one experimental and one control group and for 14 weeks in all other three groups. The animals of two experimental groups received sulindac from the 1st week and those of the third experimental group from the 10th week. After the end of carcinogenesis, treated buccal pouches were removed and examined. In animals treated with carcinogen for 14 weeks, development of oral SCC and tumor volume were significantly lower in animals that received sulindac from the first week of the experiment. Oral SCC developing in animals that received sulindac were more frequently well differentiated compared with the control group. In animals treated with carcinogen for 9 weeks, the animals that received sulindac developed lower grade of epithelial dysplasia. Proliferation index Ki-67 and positivity for the antiapoptotic molecule survivin were lower in the animals that received sulindac. Treatment with sulindac appears to delays the progression of oral premalignant lesions to oral SCC in the HOCM, also resulting in smaller and better differentiated tumors. These in vivo antineoplastic effects may be related to sulindac's ability to decrease cell proliferation and to prevent survivin expression.

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Section: Introductionmentioning

confidence: 99%

In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model

Katoumas

Nikitakis

Perrea

et al. 2015

Cancer Prevention Research

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“…[12][13][14] Cyclooxygenase 2 (COX2) is a key enzyme in the arachidonic acid metabolism involved in the biosynthesis of prostagladins, which contribute to a pro-angiogenic microenvironment in tumors. 15 Expression of COX2 is upregulated in squamous cell carcinoma and treatment with COX2 selective inhibitors results in reduced tumor growth. 16,17 Furthermore, a large body of evidence demonstrates that inhibition of COX2 enzymatic reaction results in substantial changes in the tumor-associated neo-vasculature, suggesting that COX2 could have a key role in regulating tumor-associated neoangiogenesis.…”

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confidence: 99%

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

et al. 2012

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Prostate-specific membrane antigen (PSMA) is a transmembrane protein expressed in prostate cancer as well as in the neo-vasculature of nonprostatic solid tumors. Here, we determined the expression pattern of PSMA in the vasculature of oral squamous cell carcinoma. Using a previously validated antibody, PSMA staining distribution and cyclooxygenase 2 (COX2) expression status was evaluated in a cohort of patients with squamous cell carcinoma of the oral cavity (n ¼ 96) using immunohistochemistry and was correlated with clinicopathological features as well as outcome. Twenty-four (25%) cases showed no detectable PSMA staining, 48 (50%) demonstrated positive immunoreactivity for PSMA in less than 50% of microvessels and 24 (25%) cases showed strong endothelial PSMA expression in more than 50% of tumor-associated microvessels. High endothelial PSMA expression was associated with greatly reduced survival (18.2 vs 77.3 months; P ¼ 0.0001) and maintained prognostic significance after adjusting for grade and stage in multivariate analysis (hazard ratio ¼ 2.19, P ¼ 0.007). Furthermore, we observed a strong association between endothelial PSMA and cancer cell-specific COX2 expression. In conclusion, we provide the first evidence for the prognostic significance of endothelial PSMA expression in oral squamous cell carcinoma and, suggest a potential interaction between arachidonic acid metabolites and endothelial PSMA expression in the tumor neo-vasculature.

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“…L eukotrienes (LTs) are biologically active lipid mediators that play important roles in inflammation and are involved in pathological states with an inflammatory component, such as asthma, cardiovascular disease, or cancer (1)(2)(3)(4)(5). They derive from arachidonic acid (AA) through the action of 5-lipoxygenase (5LO) (6), an enzyme expressed in a limited number of cells, including neutrophils, eosinophils, monocytes, macrophages, mast cells, and basophils (7,8).…”

mentioning

confidence: 99%

Transcellular biosynthesis of cysteinyl leukotrienes in vivo during mouse peritoneal inflammation

Zarini

Gijón

Ransome

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Leukotrienes (LTs) are lipid mediators of inflammation formed by enzymatic oxidation of arachidonic acid. One intriguing aspect of LT production is transcellular biosynthesis: cells expressing 5-lipoxygenase (5LO) form LTA4 and transfer it to cells expressing LTA4 hydrolase (LTA4H) or LTC4 synthase (LTC4S) to produce LTB4 or LTC4. This process has been demonstrated in vivo for LTB4, but not for cysteinyl LTs (cysLTs). We examined transcellular cysLT synthesis during zymosan-induced peritonitis, using bone marrow transplants with transgenic mice deficient in key enzymes of LT synthesis and analyzing all eicosanoids by liquid chromatography/ tandem mass spectrometry. WT mice time-dependently produced LTB4 and cysLTs (LTC4, LTD4, and LTE4). 5LO ؊/؊ mice were incapable of producing LTs. WT bone marrow cells restored this biosynthetic ability, but 5LO ؊/؊ bone marrow did not rescue LT synthesis in irradiated WT mice, demonstrating that bone marrow-derived cells are the ultimate source of all LTs in this model. Total levels of 5LO-derived products were comparable in LTA4H ؊/؊ and WT mice, but were reduced in LTC4S ؊/؊ animals. No differences in prostaglandin production were observed between these transgenic or chimeric mice. Bone marrow cells from LTA 4H ؊/؊ or LTC4S ؊/؊ mice injected into 5LO ؊/؊ mice restored the ability to synthesize LTB4 and cysLTs, providing unequivocal evidence of efficient transcellular biosynthesis of cysLTs. These results highlight the potential relevance of transcellular exchange of LTA 4 for the synthesis of LTs mediating biological activities during inflammatory events in vivo. chimeric mice ͉ leukotriene B4 ͉ mass spectrometry ͉ leukotriene E4 ͉ 5-lipoxygenase

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What are cyclooxygenases and lipoxygenases doing in the driver's seat of carcinogenesis?

Cited by 154 publications

References 91 publications

In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model

In VivoAntineoplastic Effects of the NSAID Sulindac in an Oral Carcinogenesis Model

High expression of prostate-specific membrane antigen in the tumor-associated neo-vasculature is associated with worse prognosis in squamous cell carcinoma of the oral cavity

Transcellular biosynthesis of cysteinyl leukotrienes in vivo during mouse peritoneal inflammation

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