Zink- und Vitamin-A-Mangel bei Mundschleimhauterkrankungen

Kleier, C.; Werkmeister, R.; Joos, Ulrich

doi:10.1007/s100060050080

Cited by 13 publications

(2 citation statements)

References 25 publications

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“…[5][6][7][8][9] In 2005, Abnet et al 10 provided the strongest evidence of an association between ZD and esophageal cancer in humans, by establishing an inverse relationship between zinc concentration in biopsy samples from a high esophageal SCC incidence area and subsequent risk of developing cancer.…”

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confidence: 99%

Prevention of upper aerodigestive tract cancer in zinc‐deficient rodents: Inefficacy of genetic or pharmacological disruption of COX‐2

Fong¹,

Jiang²,

Riley³

et al. 2007

Intl Journal of Cancer

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Zinc deficiency in humans is associated with an increased risk of upper aerodigestive tract (UADT) cancer. In rodents, zinc deficiency predisposes to carcinogenesis by causing proliferation and alterations in gene expression. We examined whether in zinc-deficient rodents, targeted disruption of the cyclooxygenase (COX)-2 pathway by the COX-2 selective inhibitor celecoxib or by genetic deletion prevent UADT carcinogenesis. Tongue cancer prevention studies were conducted in zinc-deficient rats previously exposed to a tongue carcinogen by celecoxib treatment with or without zinc replenishment, or by zinc replenishment alone. The ability of genetic COX-2 deletion to protect against chemically-induced forestomach tumorigenesis was examined in mice on zinc-deficient versus zinc-sufficient diet. The expression of 3 predictive biomarkers COX-2, nuclear factor (NF)-j B p65 and leukotriene A 4 hydrolase (LTA 4 H) was examined by immunohistochemistry. In zinc-deficient rats, celecoxib without zinc replenishment reduced lingual tumor multiplicity but not progression to malignancy. Celecoxib with zinc replenishment or zinc replenishment alone significantly lowered lingual squamous cell carcinoma incidence, as well as tumor multiplicity. Celecoxib alone reduced overexpression of the 3 biomarkers in tumors slightly, compared with intervention with zinc replenishment. Instead of being protected, zinc-deficient COX-2 null mice developed significantly greater tumor multiplicity and forestomach carcinoma incidence than wild-type controls. Additionally, zinc-deficient COX-22/2 forestomachs displayed strong LTA 4 H immunostaining, indicating activation of an alternative pathway under zinc deficiency when the COX-2 pathway is blocked. Thus, targeting only the COX-2 pathway in zinc-deficient animals did not prevent UADT carcinogenesis. Our data suggest zinc supplementation should be more thoroughly explored in human prevention clinical trials for UADT cancer. ' 2007 Wiley-Liss, Inc.Key words: zinc deficiency; upper aerodigestive tract cancer; chemoprevention; COX-2; COX-2 null mice Upper aerodigestive tract (UADT) cancer, including esophageal and oral cancer, is an important cause of morbidity and mortality worldwide. 1 With a 5-year survival of 10%, esophageal cancers are deadly. The prognosis of oral cancer, the major site being the tongue, is equally dismal, with an increasing incidence worldwide, particularly in young adults. 2 Patients with oral cancer have a high mortality rate, because of field cancerization effects that result in second primary tumors, particularly in the esophagus. 3,4 Thus, new chemopreventive and therapeutic approaches are much needed to prevent and treat these deadly cancers.While chronic alcohol consumption and tobacco use are the major risk factors for UADT cancer, epidemiologic and clinical studies have implicated dietary zinc deficiency (ZD) in the etiology of esophageal squamous cell carcinoma (SCC) and head and neck SCC. [5][6][7][8][9] In 2005, Abnet et al. 10 provided the strongest evidence of an a...

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