Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043346 (xeroderma pigmentosum)
 2,924 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000-fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre-existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13-cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5-fold after the drug was discontinued (New Engl J Med 318: 1633-1637, 1988). Toxicity (cutaneous, triglyceride, liver-function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients.
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PMID:Chemoprevention of skin cancer in xeroderma pigmentosum. 129 59

A method for measuring nucleotide excision repair in response to UV irradiation and chemical-induced DNA damage has been developed, validated, and field tested in cultured human lymphocytes. The methodology is amenable to population-based screening and should facilitate future epidemiological studies seeking to investigate associations between DNA repair proficiency and cancer susceptibility. The impetus for such endeavors derives from the suggestion that the high incidence of skin cancer in the genetic disorder xeroderma pigmentosum is manifested as a result of the reduced capacity of patients' cells to repair DNA damaged by UV-mimetic agents. For the assay, damaged, nonreplicating, recombinant plasmid DNA harboring a chloramphenicol acetyltransferase (cat) reporter gene is introduced into lymphocytes by using a DEAE-dextran/DNA complex short-term transfection conditions. Excision repair of the damaged bacterial cat gene is monitored proportionately as a function of reactivated CAT enzyme activity following a 40-h repair/expression incubation period. The validity of the approach was indicated by the ability of the assay to discriminate xeroderma pigmentosum virus-transformed lymphocyte cell lines of both severe (complementation groups A and D) and moderate (complementation group C) excision repair deficiencies from repair-proficient cell lines. Similar results were observed when a mitogen-stimulated peripheral blood lymphocyte culture from an xeroderma pigmentosum A patient was assayed concurrently with mitogen-stimulated peripheral blood lymphocytes obtained from healthy individuals. Adaptation of this DNA repair assay as a field test in a pilot-tested select group of basal cell carcinoma patients and cancer-free controls led to the preliminary identification of a specific subset at risk for this disease as a consequence of significant reduction to the repair of photochemically (UV)-damaged plasmid DNA.
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PMID:Development and field-test validation of an assay for DNA repair in circulating human lymphocytes. 193 49

This study was suggested to evaluate the possible role of porphyrins and DNA, and their interaction, in some photosensitive premalignant and malignant dermatoses. Twenty-five patients with photosensitive skin diseases viz. xeroderma pigmentosum and basal cell carcinoma, were randomly selected at the outpatient clinic of Dermatology in Mansoura University Hospital. Twenty-five matched normal individuals were used as a control group. In basal cell carcinoma patients, a high increase in skin DNA and decrease in skin total porphyrin, haemoglobin and haem concentrations were observed. In xeroderma pigmentosum, a significant decrease in both skin DNA and skin total porphyrin were found, at the same time, there were elevations in urinary total porphyrin, PBG and ALA concentrations, and a high decrease in haemoglobin and haem levels.
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PMID:Porphyrins and nucleic acid in some photosensitive skin diseases. 228 Sep 99

Basal cell carcinoma in children is rare. Its occurrence has been described in association with nevoid basal cell carcinoma syndrome, preexisting organoid nevus, and xeroderma pigmentosum. We present a case of solitary basal cell carcinoma in a 13-year-old boy with nonactive damaged skin or a genetically transmitted syndrome. The contribution of this case is to alert the physician to the possibility of basal cell carcinoma in children so that appropriate treatment may be initiated immediately and any delay avoided.
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PMID:Solitary basal cell carcinoma in a child. 253 1

There is experimental evidence that vitamin A-deficiency plays a role in tumorigenesis. Therefore, vitamin A was used in the treatment of malignant tumors. Unfortunately, it was found that the compound was too toxic and therefore its clinical usefulness was limited. Chemical modifications of the vitamin A molecule lead to what is now called the retinoids, which in general show higher efficacy and better tolerance than vitamin A itself. In this article some of the retinoids like 13-retinoic acid (Roaccutan) and etretinate (Tigason) are described with regard to their antitumor activity in animals and man. In widespread malignant disease the efficacy so far is limited to patients with basal cell carcinoma and mycosis fungoides. However, in the treatment of premalignant or in the prevention of recurrent disease retinoids have found much broader application. This is demonstrated by the successful treatment of several diseases like oral leukoplakia, actinic keratosis, xeroderma pigmentosum, bronchial metaplasia and superficial bladder carcinoma.
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PMID:[Retinoids in the prevention and treatment of cancer]. 267 75

Malignant melanomas were found in 15.8% of xeroderma pigmentosum (XP) patients with skin cancer in Japan. When multiple cancers were scored separately depending on the histopathologic types, 12.1% of the skin cancers in XP patients was malignant malignant melanoma. The relative incidence of malignant melanoma in skin cancer in XP patients is similar to that in skin cancer in general (12.6%), reported previously. Most of the malignant melanoma in XP patients developed in skin exposed to sunlight, in contrast to the high incidence of malignant melanoma in general in the unexposed skin of Japanese people. A DNA repair defect of UV damage is strongly suggested to be responsible for the high incidence of skin cancer in XP patients. The onset of malignant melanoma in XP patients was about ten years old, and was as early as those of basal cell carcinoma and squamous cell carcinoma in the patients with very low DNA repair capacities. Among nine genetic complementation groups and a variant type, group A XP cells were found to be extremely hypermutable by ultraviolet light, while group C XP cells were also hypermutable, but at the same level as normal cells when adjusted for survival. Mutagenesis as a possible mechanism of carcinogenesis in XP is supported by these results, but evidence in other cancer-prone hereditary diseases is yet to be obtained.
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PMID:Melanoma and other skin cancers in xeroderma pigmentosum patients and mutation in their cells. 271 57

Quantitative frequencies of clinical abnormalities in xeroderma pigmentosum were estimated by abstracting published descriptions of 830 patients in 297 articles obtained from a survey of the medical literature from 1874 to 1982. The median patient age was 12 years with nearly equal numbers of male and female patients. Cutaneous symptoms (sun sensitivity or freckling) had a median age of onset of between 1 and 2 years. Forty-five percent of the patients described had basal cell carcinoma or squamous cell carcinoma of the skin. The median age of first nonmelanoma skin cancer among patients with xeroderma pigmentosum was 8 years, more than 50 years less than that among patients with skin cancer in the United States. Melanomas were reported in 5% of patients. Ninety-seven percent of the reported basal and squamous cell carcinomas and 65% of the melanomas in patients with xeroderma pigmentosum occurred on the face, head, or neck. Seventy percent probability of survival was attained at age 40 years, a 28-year reduction in comparison with the US general population. Ocular abnormalities were reported in 40% of the patients described and were restricted to tissues exposed to ultraviolet radiation (lid, conjunctiva, and cornea) and included ectropion, corneal opacity leading to blindness, and neoplasms. Neurologic abnormalities were found in 18% of the cases reported, consisting of progressive mental deterioration, hyporeflexia or areflexia, and progressive deafness in some patients in association with dwarfism and immature sexual development. There was scant information concerning the efficacy of any therapeutic regimen.
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PMID:Xeroderma pigmentosum. Cutaneous, ocular, and neurologic abnormalities in 830 published cases. 354 87

Thirty-two cases of xeroderma pigmentosum (XP) of the complementation groups C (7), D (12), E (3), I (2) and 8 variants are analyzed biochemically and clinically. There is some congruence of the cellular defects (UDS, CFA, SCE) and the clinical severity of the skin symptoms. Despite the large clinical variability within and between the complementation groups, several clinical features are to be attributed to one group or another. The most striking observation is the predominance of LMM in the D group and BCC in the mild E group as well as in the variants. This observation might stimulate research to find a cellular characteristic of the melanoma risk.
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PMID:Heterogeneity of xeroderma pigmentosum (XP); variability and stability within and between the complementation groups C, D, E, I and variants. 374 52

Twenty-six patients with xeroderma pigmentosum (XP), who live in the Northeast (Tohoku) District of Japan, were examined for the clinical characteristics of UV-induced DNA synthesis (unscheduled DNA synthesis, UDS) and UV sensitivity of skin fibroblasts or lymphoblastoid cells, or both. A history of consanguineous marriage within two generations was found in 19 of 26 cases (73%). Two pairs of siblings showed similar manifestations and almost the same levels of UDS and of UV sensitivity. Squamous cell carcinoma, basal cell carcinoma, or both were observed on the exposed skin in 14 patients, but no malignant melanoma was found. Cancer had developed in approximately 71% (10/14) of the cancer-bearing patients by the age of 20, and 8 of them belonged to the UDS-deficient group. Neurological manifestations were associated with nine patients, including 3 with typical de Sanctis-Cacchione syndrome (DSC), and most of the cells derived from these patients had a UDS level less than 10% of that of the normal cells. A clear correlation between the levels of UDS and UV sensitivity, on the one hand, and the severity of clinical manifestations on the other could not be detected, but it seems that the UDS-deficient group is generally much more sensitive to UV in terms of cell killing and the induction of sister chromatid exchange (SCE) than the UDS-proficient group. After a photosensitivity test, one patient with mild skin manifestations showed distinct skin tanning without preceding erythema.
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PMID:Clinical and biological studies of 26 cases of xeroderma pigmentosum in northeast district of Japan. 397 May 83

Multiple skin cancers and other cancers in patients with xeroderma pigmentosum (XP) were investigated in relation to DNA repair defects in the cells of the patients. Multiple skin cancers of the same or different histopathological types were found in many patients and six patients had cancers, one each, in organs other than the skin. The frequency of basal cell carcinoma was higher than that of squamous cell carcinoma in XP patients, while the two types were reported to be approximately equal in frequency in all skin cancers in Japanese. Defect in the excision-resynthesis type of repair presumably enhances the error-prone type of repair of DNA damage in XP patients and may lead to the development of cancer. Although a similar DNA repair defect of damage caused by ionizing radiation has been suspected in ataxia telangiectasia (AT), induction of mutation by gamma-rays in AT cells was lower than that in normal cells at the same survival levels. The high incidence of malignancy in AT patients could be due to factors not associated with DNA repair.
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PMID:DNA repair and its possible involvement in the origin of multiple cancer. 400 91


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