tretinoin and Xeroderma-Pigmentosum

Topics: Adult; Benzoates; Bowen's Disease; Carcinoma, Basal Cell; Child; Etretinate; Female; Humans; Isotretinoin; Male; Precancerous Conditions; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Topics: Biological Evolution; Carcinogens; Chronic Disease; DNA Repair; Environmental Pollutants; Genetic Diseases, Inborn; Humans; Mutation; Neoplasms; Tretinoin; Xeroderma Pigmentosum

To confirm reports that skin cancer can be prevented with retinoids, we conducted a three-year controlled prospective study of oral isotretinoin (also called 13-cis retinoic acid) in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal-cell or squamous-cell carcinomas. Patients were treated with isotretinoin at a dosage of 2 mg per kilogram of body weight per day for two years and then followed for an additional year, without the drug. Before, during, and after treatment, biopsies of all suspicious lesions were performed, and skin cancers were surgically removed. The patients had a total of 121 tumors (mean, 24; range, 8 to 43) in the two-year interval before treatment. During two years of treatment with isotretinoin, there were 25 tumors (mean, 5; range, 3 to 9), with an average reduction in skin cancers of 63 percent (P = 0.019). After the drug was discontinued, the tumor frequency increased a mean of 8.5-fold (range, 2- to 19-fold) over the frequency during treatment (P = 0.007). Although all patients experienced mucocutaneous toxic effects, and triglyceride, liver-function, or skeletal abnormalities developed in some, high-dose oral isotretinoin was effective in the chemoprophylaxis of skin cancers in patients with xeroderma pigmentosum.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Clinical Trials as Topic; Female; Humans; Isotretinoin; Male; Prospective Studies; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare autosomal recessive dermatosis that is often complicated by multiple skin tumours at exposed locations, which are difficult to treat. We report a case of a 12-year-old girl with XP treated with oral retinoic acid and photodynamic therapy (PDT) with good clinical results. She had an 8-year history of multiple skin lesions that first appeared on her nasal dorsum, but gradually increased in size and spread to her entire face, neck, and upper limbs. Notably, the lesions became evidently aggravated after sun exposure. When she was 6 years old, sesame-seed-sized papules and plaques appeared, which were fragile and irregular in shape and would self-rupture, accompanied with slight itchiness and bloody exudate. Examination revealed multiple basal cell carcinomas. The tumours were treated with local carbon dioxide laser therapy combined with PDT. On the follow-up visit 2 months after the surgery, most of the skin lesions on her face had subsided. In cases of multiple tumours, PDT can be the treatment method of choice because it is less invasive, has less side effects, and does not damage the surrounding normal tissues.

Topics: Carcinoma, Basal Cell; Child; Drug Therapy, Combination; Face; Female; Hematoporphyrins; Humans; Lasers, Gas; Photochemotherapy; Photosensitizing Agents; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Topics: DNA Helicases; DNA Repair; Gene Expression Regulation; Humans; Transcription Factor TFIIH; Transcription Factors, TFII; Tretinoin; Xeroderma Pigmentosum

New tumor formation was suppressed by retinoic acid (RA) administration in xeroderma pigmentosum (XP) patients who have a defect in nuclear excision repair. However, the inhibition is not due to enhanced removal of UV-damaged DNA. These results prompted us to investigate whether or not RA metabolism is abnormal in XP fibroblasts and what the underlying mechanism is. Compared with wild type fibroblasts, low activities of RA synthesis were determined on HPLC in mouse fibroblasts lacking XP group A (XPA) gene and UV-induced XPA deficient cancer cells. Moreover, we observed an impaired expression of cytochrome P450 1a1 in XPA deficient fibroblasts by RT-PCR and a decreased expression of retinoic acid receptor gamma in XPA deficient cancer cells by Western blotting. Finally, pre-treatment of RA isoforms significantly protected the XPA deficient fibroblasts from UV-induced death. These results suggest that decreased structure activity of RA synthesis, resulting from impaired mRNA expression of cytochrome P450 1a1 may, at least together with UV irradiation, involve in skin carcinogenesis in XP patients.

Topics: Alitretinoin; Animals; Cell Line; Cell Survival; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System; DNA-Binding Proteins; Fibroblasts; Mice; Oxygenases; Receptors, Retinoic Acid; Retinal Dehydrogenase; Retinol-Binding Proteins; Tretinoin; Ultraviolet Rays; Xeroderma Pigmentosum; Xeroderma Pigmentosum Group A Protein

Topics: Child; Consanguinity; Humans; Keratolytic Agents; Male; Tretinoin; Xeroderma Pigmentosum

Fifteen middle aged or elderly patients with chronic solar damage of the skin, eight patients with melasma and three patients with xeroderma pigmentosum were treated with topical tretinoin for 6 months. There was a significant improvement in fine surface lines in periorbital region, but no significant improvement was observed in deep furrows. No significant change was induced in melasma despite the improvement in smoothness of the skin surface. Global improvement was also seen in one patient with xeroderma pigmentosum. With regard to the functions of the stratum corneum that was assessed on the flexor surface of the forearms, values of water content as well as transepidermal water loss were found to increase one month after start of the application of tretinoin cream. On the other hand, there was no significant change in the amino acid content of the stratum corneum when measured after 4 months of the treatment. It is concluded that tretinoin cream is capable of partly reversing fine surface lines in photodamaged facial skin of the Japanese. However the irritation induced by 0.1% tretinoin cream was unexpectedly severe in the Japanese as compared to that reported in Caucasians.

Topics: Administration, Topical; Adolescent; Adult; Aged; Aging; Amino Acids; Female; Humans; Japan; Male; Melanosis; Middle Aged; Photosensitivity Disorders; Skin; Sunlight; Tretinoin; Water Loss, Insensible; Xeroderma Pigmentosum

To confirm reports that skin cancer can be prevented with retinoid treatment, a three-year controlled prospective study was conducted of oral isotretinoin in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal cell or squamous cell carcinomas. Patients were treated with isotretinoin, 2 mg/kg per day for two years, and then evaluated for an additional year without using the drug. Before, during, and after treatment, biopsy specimens of all suspicious lesions were examined, and skin cancers were removed surgically. The patients had a total of 121 tumors in the two years before treatment. During two years of treatment with isotretinoin, there were twenty-five tumors, with an average reduction in skin cancers of 63 percent (p = 0.019). After use of the drug was discontinued, the tumor frequency increased a mean of 8.5 times over the frequency during treatment (p = 0.007). Although all patients experienced mucocutaneous toxic effects, and abnormalities in triglyceride levels, results of liver function tests, or skeletal findings occurred in some, high-dosage oral isotretinoin was effective in the chemoprophylaxis of skin cancers in patients with xeroderma pigmentosum.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Female; Follow-Up Studies; Humans; Male; Prospective Studies; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Topics: Cells, Cultured; DNA Repair; Fibroblasts; Humans; In Vitro Techniques; Tretinoin; Ultraviolet Rays; Xeroderma Pigmentosum

Topics: Adult; beta Carotene; Canthaxanthin; Carotenoids; Cell Transformation, Neoplastic; Child; Child, Preschool; Electrosurgery; Eye Diseases; Female; Humans; Infant; Male; Neurologic Manifestations; Skin Diseases; Tretinoin; Xeroderma Pigmentosum

Topics: Child; Etretinate; Female; Humans; Skin Neoplasms; Time Factors; Tretinoin; Xeroderma Pigmentosum

Aromatic retinoid Ro 10-9359 1 mg/kg body weight was given to an 11-year-old girl with xeroderma pigmentosum. Therapy resulted in disappearance of actinic keratoses and basal cell carcinomas. The occurrence of new tumors could be prevented in this patient while she participated in this preventive therapy for 7 months. The reduction of the aromatic retinoid to 0.4 mg/kg body weight every other day resulted in the reappearance of four basal cell carcinomas an one keratoacanthoma within 6 weeks.

Topics: Child; Etretinate; Female; Humans; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

Beneficial effects of oral retinoids in prophylaxis of epithelial neoplasias have been demonstrated by experimental works. In this study oral retinoid (RO 10-9359) was used in human dermatosis with high frequency of cutaneous malignancies: xeroderma pigmentosum with or without malignant neoplasias, Mibelli's porokeratosis with multifocal malignant degeneration, basal cell naevus syndrome with basal cell carcinomas, familial epithelioma of Ferguson-Smith and actinic keratosis. This work started in december 1977. Visible epitheliomas have been treated before trial. Initial dose of retinoid was 1 mg/kg daily, decreased depending on individual tolerance. Results were appreciated by comparising number of epitheliomas observed in years preceding retinoid therapy and number of them appearing during treatment; in two familial cases (basal cell naevus syndrom in twins and xeroderma pigmentosum in two brothers) comparison was made between treated and untreated patients. First results are very promising: an excellent response on solar keratosis is noted; epitheliomas occurrence seems actually to be prevented or delayed by oral retinoid therapy. Of course more numerous cases, a longer time, periods without treatment are necessary to confirm these interesting first results. On the other hand drug is not with this dose active on already constituted carcinomas.

Topics: Adolescent; Basal Cell Nevus Syndrome; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Etretinate; Female; Humans; Keratosis; Male; Precancerous Conditions; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum