Medizinische Universität Graz - Research portal
Selected Publication:
Yarosh, D; Klein, J; O'Connor, A; Hawk, J; Rafal, E; Wolf, P.
Effect of topically applied T4 endonuclease V in liposomes on skin cancer in xeroderma pigmentosum: a randomised study. Xeroderma Pigmentosum Study Group.
Lancet. 2001; 357(9260):926-929
Doi: 10.1016/S0140-6736(00)04214-8
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- Co-authors Med Uni Graz
- Wolf Peter
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- Abstract:
- BACKGROUND: In patients with xeroderma pigmentosum the frequency of all forms of skin cancer is higher than in the general population, owing to a genetic defect in DNA repair. The bacterial DNA repair enzyme, T4 endonuclease V, delivered intracellularly, increases the rate of repair of sunlight-induced DNA damage in human cells. We tested the ability of this enzyme in a liposomal delivery vehicle applied topically (T4N5 liposome lotion) to lower the rate of new skin cancers in patients with xeroderma pigmentosum. METHODS: 30 patients were enrolled in this prospective, multicentre, double-blind study. Patients were randomly assigned T4N5 liposome lotion or a placebo liposome lotion, to be applied daily for 1 year. At 3-monthly visits, new actinic keratoses and basal-cell carcinomas were identified and removed. Analyses were by intention to treat. FINDINGS: 20 patients were assigned T4N5 liposome lotion and ten placebo lotion; one placebo-group patient withdrew before treatment and one withdrew with progressive disease at 9 months. The annualised rate of new actinic keratoses was 8.2 among the patients assigned T4N5 liposome lotion and 25.9 among those assigned placebo (difference 17.7 [95% CI 11.8-26.5]; p=0.004 by Poisson modelling). For basal-cell carcinoma, the annualised rates of new lesions were 3.8 in the treatment group and 5.4 in the placebo group (difference 1.6 [0.38-2.82]). No significant adverse effects were found among any of the patients. INTERPRETATION: DNA damage has an important role in the development of skin cancer and precancerous skin lesions. The topical application of DNA repair enzymes to sun-damaged skin of patients with xeroderma pigmentosum lowered the rate of development of two forms of these lesions during a year of treatment.
- Find related publications in this database (using NLM MeSH Indexing)
- Administration, Topical -
- Adolescent -
- Adult -
- Carcinoma, Basal Cell - epidemiology
- Child - epidemiology
- Child, Preschool - epidemiology
- DNA Repair - drug effects
- Deoxyribonuclease (Pyrimidine Dimer) - drug effects
- Double-Blind Method - drug effects
- Endodeoxyribonucleases - administration and dosage
- Europe - epidemiology
- Female - epidemiology
- Humans - epidemiology
- Keratosis - epidemiology
- Liposomes - epidemiology
- Male - epidemiology
- Middle Aged - epidemiology
- Multivariate Analysis - epidemiology
- Photosensitivity Disorders - epidemiology
- Prospective Studies - epidemiology
- Regression Analysis - epidemiology
- Skin Neoplasms - epidemiology
- United States - epidemiology
- Viral Proteins - epidemiology
- Xeroderma Pigmentosum - drug therapy