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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sunlight exposure and certain host factors such as red hair and fair skin are established risk factors for non-melanoma skin cancers. Because deficient DNA repair capacity has contributed to the development of skin cancers in a rare genetic disease, xeroderma pigmentosum, we explored this deficiency as an etiologic factor in a recent population study. We used a new DNA repair assay, the host-cell reactivation, in a clinic-based case-control study to test the hypothesis that reduced DNA repair is the underlying molecular mechanism for the development of sunlight-induced basal cell carcinoma. The peripheral lymphocytes from 88 patients with primary BCC and 135 cancer-free controls were tested for their capacity to repair ultraviolet light-induced DNA damage in a reporter gene, chloramphenicol acetyl transferase. All subjects were between the ages of 20 and 60 years and were frequency matched by age (+/- 5) and sex. Among those who reported frequent sunbathing, poor tanning ability, a history of multiple sunburns, exposure to chemicals, or multiple medical irradiations, the BCC patients had significantly lower DNA repair capacity than controls (p < 0.05). DNA repair capacity was also found substantially lower in the basal cell carcinoma patients who had red hair and light skin (type I). Compared to controls, basal cell carcinoma cases with selected risk factors had a relative decrease in DNA repair capacity of 10-28%. These findings provided evidence that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.
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PMID:DNA repair capacity for ultraviolet light-induced damage is reduced in peripheral lymphocytes from patients with basal cell carcinoma. 861 26

Non-melanoma skin cancer is common and offers unrivaled opportunities to relate genetic changes to clinical and biologic behavior. Recent technical advances in molecular biology render genetic analysis of even the smallest skin cancers possible. In this review I will discuss the role of p53 gene in skin carcinogenesis, the relation between p53 immunostaining and p53 mutation, and recent evidence for the involvement of putative tumor suppressor genes both on chromosome 9 and other chromosomes in non-melanoma skin cancer.
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PMID:Genetic alterations in non-melanoma skin cancer. 779 10

Basic investigation into the nature of melanin monomer and polymer synthesis in pigment cells has revealed many of the new underlying factors involved in its regulation and control by three melanogenesis-related genes, tyrosinase, TRP-1 and TRP-2, and other non-tyrosinase glycoproteins. Pigment cells can undergo clinically and biologically recognizable progressive multi-step carcinogenesis. Generally parallel to this progressive cancerization is accentuated melanogenesis. Using this accentuated melanogenesis to develop a specific diagnosis and cure for melanoma (Mm) has long been a challenge. However, until recently, no success was achieved. As an example, attempting to utilize the fact that dopa accumulates as a melanin substrate within Mm cells, hybrid compounds of dopa and cytotoxic drugs were developed. However, these compounds were found to have severe systemic side effects and were therefore unusable. Another newer Mm treatment involves high energy radiation such as fast neutrons. But this is quite non-selective, killing both the target cancer and the normal surrounding tissue. Since 1972, I have developed the idea of coupling the high energy releasing system of thermal neutron irradiation with the non-toxic 10B-dopa analogue, 10B1-L-p-boronophenylalanine (10B1-L-BPA). Thermal neutrons are essentially harmless, but, after specific absorption by 10B, release high LET alpha-particles and 7Li-atoms with an energy of 2.33 MeV up to a distance of 14 mu, the diameter of Mm cells, thus selectively killing them without damaging surrounding normal tissue. After the synthesis of 10B1-L-BPA, exhaustive in vitro and in vivo radiological studies on its enhanced killing effect were done to develop optimal Mm Boron Neutron Capture Therapy (NCT).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Melanogenesis investigation leading to selective melanoma neutron capture therapy and diagnosis. 785 54

Microsatellite instability secondary to replication errors (RER), characterized by length changes at repetitive loci scattered throughout the genome, is a recently recognized genetic mechanism important in the development of some human cancers. Although RER has been reported in sebaceous gland tumors from patients with the Muir-Torre syndrome, the frequency of RER in human non-melanoma and melanoma skin cancers is not known. In this study, we investigated the importance of RER in human skin carcinogenesis. RER was identified in three of four actinic keratoses from a patient belonging to a kindred with documented Muir-Torre syndrome, which indicates that defective DNA replication may contribute to skin cancer development in such patients. Examination of a series of tumors from patients without Muir-Torre, including 137 skin cancers (47 basal cell carcinomas, 49 squamous cell carcinomas, and 41 primary malignant melanomas), 19 actinic keratoses, and 20 cases of Bowen's disease, using 10 or more microsatellite markers, identified repeat-sequence instability in less than 5% of the tumors studied. In six of the eight tumors, the sole change was an alteration 2 base pairs in length at a single locus. One patient with a squamous cell carcinoma showed changes at multiple loci suggesting defective mismatch repair. Although the low frequency of RER found in this study of a large series of human skin tumors suggests that this phenomenon is uncommon in patients with skin cancer, the identification of RER at multiple loci in two patients suggests that error-prone replication may be important in skin cancer development in some individuals.
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PMID:Microsatellite instability in human non-melanoma and melanoma skin cancer. 786 Sep 92

Regeneration-competent urodele Amphibia are highly resistant to spontaneous development of neoplasms, in comparison with other vertebrates which do not exhibit great regenerative power. This observation implies that at least one growth parameter of urodele cells might be subject to different developmental mechanisms than the cells of animals incapable of epimorphic regeneration. Therefore, keeping records concerning the incidence of tumors in urodeles and investigating those exceptional cases might prove invaluable in understanding the basic biological principles governing organ regeneration and carcinogenesis, and might therefore help in cancer therapy. The present report depicts a case of two spontaneous, dermal, melanoma-like tumors found in an adult newt Triturus cristatus. Both tumors were located in the pelvic region. Histological examinations and tumor transplantations were conducted. It was found that the tumors were melanomata. When allografted within the body cavity, their mass was progressively eliminated.
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PMID:Allografting of a nontransmissible, spontaneous dermal melanoma in the newt Triturus cristatus. 807 27

ras mutations have been reported as an early event in some human malignancies and in the mouse skin model of multistep carcinogenesis; early studies in human non-melanoma skin cancers have reported variable rates of ras mutations. A recent study, however, has reported a high frequency of activating mutations of the Harvey-ras proto-oncogene in non-melanoma skin cancers, and the site specificity of the mutation at the second position of codon 12 prompted us to re-examine the importance of Ha-ras codon 12 mutations as an early event in the development of these tumours, using a combination of PCR and restriction fragment polymorphism of codon 12 of the Ha-ras gene. Dilution experiments confirmed that the method was sensitive and capable of detecting mutations at this codon when only 4% of the total alleles are mutated. We were surprised to find no mutations in the 40 basal cell carcinomas, 12 squamous cell carcinomas and 12 cases of Bowen's disease studied. We conclude that Ha-ras codon 12 mutations are rare events in human non-melanoma skin cancer in the U.K. The marked differences in the frequency of codon 12 Ha-ras mutations in published studies may relate to either technical artefacts, or differences in the molecular epidemiology between areas of low and high sun exposure.
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PMID:Codon 12 Harvey-ras mutations are rare events in non-melanoma human skin cancer. 809 49

Although the precise etiology of melanoma remains unknown, much data link sunlight to melanoma. The imperfect evidence associating sun exposure (particularly UVB radiation) with melanoma emerges from human data, obviating problems inherent in extrapolation from animal and other models. However, the mechanism by which sunlight might possibly initiate or promote melanoma remains obscure. Some clarification should emerge from the potential isolation of genes that carry susceptibility to melanoma in families prone to the disease; such work could serve as a basis to distinguish genetic and environmental influences in melanoma [167]. Continued studies of faulty DNA repair in XP patients may elucidate the steps in mutagenesis and carcinogenesis. Future case-control studies must address the limits on the accuracy of recall and the limits on statistical methods to separate the cluster of phenotypic risk needed in determining biologically effective dose. Animal and in vitro studies must contribute more insight. Further research in the South American opossum models appears promising [72]. Although ozone depletion has been documented, there has been little definitive evidence of subsequent increase of UVB at the Earth's surface. Nevertheless, the threat posed by ozone depletion deserves continued environmental action and public education. The role of precursor lesions, particularly dysplastic nevi/atypical moles, must be clarified with future research. The distribution of melanoma among various work forces suggests that occupational risk factors may play an important role in the etiology of this disease [168-170]. The consistent reports of excess melanoma among accountants, clerical workers, professional workers, and teachers deserve further study. Furthermore, evidence of excesses in printing and press, petrochemical, and the telecommunications industries require follow-up. Carefully planned studies that account for nonoccupational risk factors are recommended. Research over the last four decades has brought much information about melanoma etiology. More work is needed to learn the precise cause and ultimately to prevent avoidable mortality from malignant melanoma.
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PMID:Etiology of melanoma. 810 18

The role of alkylation of the N3 position of adenine in the cytotoxicity of alkylating agents in mammalian cells is still undefined. By co-transfecting NIH3T3 murine fibroblast and murine B78 H1 melanoma cells with pSG5tag and pSV2neo, we obtained clones expressing the mRNA of the bacterial tag gene coding for N3-methyladenine-DNA glycosylase I (Gly I), which specifically repairs N3-methyladenine. The levels of Gly I were 400 times higher in NIH3T3 pSG5tag (clone 3.9.4) and 12-33 times higher in B78 H1 tag clones (2A4, 2A6, 2C3 and 2D1) than in the respective control cells. The sensitivity to alkylating agents was evaluated in tag-expressing cells in comparison with pSG5, pSV2neo co-transfected control cells. As regards the cytotoxic activity of methylating agents (N-methylnitrosourea, N-methyl-N'-nitro-N-nitrosoguanidine, dimethylsulfate and temozolomide) and other alkylators with different structure and different interactions with DNA such as CC-1065 and FCE-24517 (minor groove binders known to bind to N3 of adenine), 4-[bis(2-chloroethyl)amino]-L-phenylalanine and cis-diamminedichloroplatinum II, cytotoxicity was the same for tag-expressing and non-expressing cells. These results suggest that the increased expression of N3-methyladenine-DNA glycosylase is not necessarily a crucial mechanism for the resistance of cells to alkylating agents.
Carcinogenesis 1994 Mar
PMID:3T3 NIH murine fibroblasts and B78 murine melanoma cells expressing the Escherichia coli N3-methyladenine-DNA glycosylase I do not become resistant to alkylating agents. 811 39

Low plasma selenium levels have been linked to increased risk of non-melanoma skin cancer in humans. The present study examined the relationship between selenium level in the diet and development of skin tumors induced by ultraviolet radiation in female Skh:HR-1 hairless mice. Animals were maintained on a torula yeast-based diet containing either 0, 0.1, or 0.5 mg/kg selenium as Na2SeO3. Ultraviolet light at a dose of 90 mJ/cm2, three times weekly for 20 weeks, resulted in skin tumors in all groups. Following cessation of ultraviolet light exposure, tumors continued to increase in selenium-deficient mice and those fed only 0.1 mg/kg, but leveled off for those on 0.5 mg/kg. During the carcinogenesis process, epidermal antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were monitored. Selenium deficiency decreased glutathione peroxidase and resulted in an early increase in superoxide dismutase and catalase in response to ultraviolet light treatment. These results indicate that dietary Se may be an important chemopreventive agent for skin cancer.
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PMID:Effects of dietary selenium on UVB-induced skin carcinogenesis and epidermal antioxidant status. 817 60

Transplant recipients successively develop benign, premalignant and malignant skin lesions on sun-exposed areas. It has been suggested that UV radiations might induce mutations in ras oncogenes and p53 tumour-suppressor gene, responsible for skin cancers. With PCR and oligoprobe hybridization, we investigated c-Ha-ras gene mutations at codons 12 and 61 in 120 cutaneous lesions from grafted patients, since they could represent a marker of the evolution of benign skin lesions towards malignancy in this population; 29 similar skin biopsies from non-immunosuppressed patients were also analyzed. In transplant recipients, we detected mutations at codon 12 only in 1/42 non-melanoma skin cancers and 2/29 pre-cancerous keratoses. No mutation was detected in 11 cases of cutaneous Bowen's disease from grafted patients and in pre-malignant and malignant skin samples from control patients. Benign warts exhibited an overall incidence of 18% and 15% of mutations at codon 12 of c-Ha-ras gene in grafted and control patients respectively. We detected only one mutation at codon 61 in a plantar wart. Human papillomaviruses (HPV) are thought to be involved in the malignant evolution of cutaneous disorders in transplant recipients and cooperate with a ras oncogene to induce malignancy in vitro. The presence of HPV DNA in our series of skin samples from grafted patients showed no correlation with the occurrence of c-Ha-ras mutations. Our findings indicate that c-Ha-ras-gene activation by mutations is rare in cutaneous lesions from transplant recipients, and is unlikely to play a crucial role in transformation towards malignancy in skin carcinogenesis among grafted patients.
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PMID:Low incidence of c-Ha-ras gene mutations in benign and malignant cutaneous lesions from transplant recipients. 825 28


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