Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

According to recent cancer epidemiology reports malignant melanoma in both sexes and lung carcinoma in females, are the only cancers of which the incidence continuously increases. In Australia, Northern Europe and Canada the incidence doubling time of malignant melanoma has been 10 to 20 years only. The highest incidence has been found in the State of Queensland, Australia, with an incidence of 32/100,000 inhabitants per year in males and 33.4/100,000 in females. Moreover 1 of 3 persons is likely to develop skin cancer during life span in Queensland. The new habit of Whites to sun-bath in sunny regions of the world seems to be in close relationship with the increased incidence of malignant melanoma. In addition, the hazard of skin cancer is higher in the south of U.S.A. as compared with the north, where the UVB radiations is lower. Genetic factors seem to play a role in malignant melanoma. Patients having this tumour report sunburn and freckling in a 4 fold higher frequency than non melanoma patients. Chemicals such as psoralens; used as photosensitizers, synthetic steroids and probably some cosmetics, may act as error prone carcinogenic agents in the presence of hv from UV light. This field of skin toxicology and carcinogenesis leads into to the way of new developments in cosmetics, including the design of efficient skin protectors. Therefore, future efforts in preventing further increase of malignant melanoma incidence should take into account the following: UV irradiation is a causative factor of malignant melanoma; the evidence of genetic propensity at developing malignant melanoma.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Epidemiology and etiology of malignant melanoma. 352 90

This review is designed to inform the clinician of current concepts regarding the pathogenesis of chemically induced skin cancer. Chemicals induce cutaneous cancers in a wide variety of experimental animals and in humans. The most common benign experimental tumors are papillomas and keratoacanthomas, whereas common malignancies are squamous cell carcinomas and melanomas. Carcinoma development is a multistage process that involves at least three mechanistically distinct steps. Initiation is the earliest change in an epidermal cell exposed to carcinogens such as polycyclic aromatic hydrocarbons, alkylating agents, or nitrosamines. This stage appears to result from carcinogen-induced deoxyribonucleic acid damage leading to a mutation-like genetic change. Only a limited number of epidermal genes may be changed to yield the initiated cell, and one has been identified as the Harvey ras gene, a gene involved in epidermal proliferation. Initiated epidermal cells are not malignant but are insensitive to the normal signals for terminal differentiation in the epidermis. The second stage, tumor promotion, results from repeated exposure of initiated skin to one of a variety of noncarcinogenic promoting agents such as phorbol esters, benzoyl peroxide, anthralin, or certain halogenated aromatic hydrocarbons. Some promoters require specific cellular receptors and produce transient changes in the growth or differentiation of the epidermis. Collectively these agents produce a tissue environment that is conducive to the selective clonal outgrowth of the initiated cell population, resulting in a clinically apparent premalignant tumor. During the third stage of carcinogenesis, premalignant cells are converted to malignancy. This step may occur spontaneously, but the frequency is greatly enhanced by exposure to mutagens, including several initiating agents. Thus malignant conversion is likely due to additional mutations in a benign tumor cell. The Harvey ras gene may also be a potential target in the conversion step. Several agents, such as corticosteroids and retinoids, have been identified as anticarcinogens for skin. They appear to be primarily antipromoting agents and could important clinical applications. Melanomas can be induced in several species by repeated exposure to initiators or by exposure to an initiator and a tumor promoter. the experimental pathogenesis of this tumor is unclear. It is proposed that intermediates in the synthesis of melanin pigment could act as endogenous carcinogens or promoters in melanoma development. Increased awareness of the mechanisms of chemical carcinogenesis in skin will enhance cancer prevention in this tissue. Furthermore, astute
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PMID:Cutaneous chemical carcinogenesis. 353 25

The present study describes two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000, which are associated with the transformed phenotype of melanocytes. The monoclonal antibodies (MoAb) MUC18 and MUC54, raised against human malignant melanoma, were selected for differential reactivity with normal and neoplastic cells of melanocyte lineage. The antigen defined by MoAb MUC18 is a membrane bound monomeric sialylated glycoprotein with an apparent molecular weight of 113,000. In contrast to the broad reactivity with melanomas, isolated nevus nests were stained in only 1 of 55 nevi investigated. No staining of MoAb MUC18 was observed in a large variety of surgically removed normal and tumor tissues except for smooth muscle cells of the blood vessel wall and hair follicles. MoAb MUC54 immunoprecipitated a cytoplasmic monomeric protein with an apparent molecular weight of 76,000. By immunoperoxidase staining, the antigen was demonstrated on a large number of melanomas and in addition on 1 of 36 nevocellular, 3 of 4 Spitz, and 5 of 14 dysplastic nevi. The Mr 76,000 protein was found in a number of epithelial tissues and various types of neoplasms. Both antibodies presented in this study define structural changes in the antigenic profile of melanocytes occurring during carcinogenesis.
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PMID:Discrimination between benign and malignant cells of melanocytic lineage by two novel antigens, a glycoprotein with a molecular weight of 113,000 and a protein with a molecular weight of 76,000. 354 95

The effects of hyperoxia on lung tumor development were examined in mice and rats. In mice, exposure to 70% O2 prevented the development of urethan- or 3-methylcholanthrene-induced lung tumors. Dietary antioxidants [butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA)] were unable to prevent the inhibition of tumor development by oxygen, although BHT retained its capability to enhance tumor development in mouse lung. In visible-size tumors, oxygen did not depress DNA synthesis. Oxygen also reduced the number of pulmonary metastatic nodules after i.v. injection of mammary gland-derived carcinoma cells, but failed to inhibit growth of murine lung carcinoma or murine melanoma-derived cell lines. Rats treated with one single intratracheal instillation of 3-methylcholanthrene developed multiple lung lesions; their growth could be prevented by exposure of the animals to 40 or 70% O2. It is concluded that hyperoxia prevents development of transformed cells in vivo in the lung and may affect adversely the growth of selected cell lines metastatic to the lung.
Carcinogenesis 1986 Sep
PMID:Modification of lung tumor growth by hyperoxia. 374 30

Mouse skin melanomas were induced in two stage skin carcinogenesis with 7,12-dimethylbenz[a]anthracene as initiator and croton oil as promoter. After approximately 25 weeks of promotion, small black macules of the skin were observed in C57BL, CDF1 and BDF1 mice, and progressively grew with time. Macules less than 2 mm in diameter were localized mostly in the lower portion of the dermis and, histologically, these lesions were consistent with the diagnosis of melanocytoma and were composed of polygonal to round cells loaded with large numbers of melanin granules. The cells were closely packed forming well-demarcated cell-nests with occasional columnar arrangement. In the macules over 2 mm in diameter, the cells were closely packed to form irregularly bordered cell-nests, showing invasive growth into the surrounding tissues. The lesions were diagnosed as malignant melanomas. The incidence of benign and/or malignant melanoma differed among strains: 80% in BDF1, 70% in CDF1, 30% in C57BL/6 and 0% in DBA/2 mice. One example of tumor induced in a CDF1 mouse was transplantable to homologous CDF1 mice.
Carcinogenesis 1985 Jun
PMID:Mouse skin melanoma induced in two stage chemical carcinogenesis with 7,12-dimethylbenz[a]anthracene and croton oil. 392 35

The cytotoxic and mutagenic effects of 1-nitropyrene (1-NP) and its reduced metabolite 1-nitrosopyrene (1-NOP) were determined in diploid human fibroblasts. Conditions for the metabolic activation of the parent compound (1-NP) by human cells in culture were developed. The cytotoxic effect of 1-NP in normal cells was compared with that for repair-deficient xeroderma pigmentosum (XP) cells, and cells from a patient with hereditary cutaneous malignant melanoma (HCMM), which we have shown earlier are abnormally sensitive to 4-nitroquinoline-1-oxide. The slope of the survival curve for XP cells was 2.5 times steeper than that of normal cells; that of HCMM cells was intermediate. When these cells were exposed to 1-NOP, the slope of the survival curve for the XP cells was also 2.5 times steeper than normal but the HCMM cells showed a normal response, suggesting that their defect is not in repair of DNA adducts, but in activation. 1-NP and 1-NOP also proved to be mutagenic in the human cell assay. When compared on the basis of concentration, 1-NOP was much more mutagenic than 1-NP. But when the compounds were compared on the basis of equal cell killing or equal number of DNA adducts initially bound to DNA, they were very similar. An equal number of residues covalently bound to DNA caused approximately the same amount of cell killing for either compound. XP cells were killed by a 7-fold lower number of bound adducts, suggesting that the increased survival and decreased mutation induction in the normal cells reflects their ability to remove potentially cytotoxic and mutagenic lesions.
Carcinogenesis 1986 Jan
PMID:Cytotoxic and mutagenic effects of 1-nitropyrene and 1-nitrosopyrene in diploid human fibroblasts. 394 46

Ascorbate-Cu2+ shows considerable cytotoxicity for human melanoma cells at a dose which has very little effect on human fibroblasts. Ascorbate itself inhibits DNA synthesis in melanoma cells but does not fragment the parental DNA. However, the combined action of ascorbate-Cu2+ generates fragmentation of the parental DNA due to the induction of alkali-labile bonds in the DNA. In contrast, if DNA polymerase alpha is inhibited by aphidicolin prior to treatment with ascorbate-Cu2+ one cannot detect the fragmentation of the DNA. The generated fragments show a discrete appearance in agarose gel electrophoresis with a single-stranded size of approximately 5 kb. When fibroblasts were analyzed using the same experimental protocol it was not possible to detect the fragmentation of the DNA.
Carcinogenesis 1983
PMID:Ascorbate-Cu2+ fragments melanoma DNA but not fibroblast DNA into a discrete DNA population. 640 86

In previous studies we found that, when added to primary normal human epidermal cultures, 12-O-tetradecanoyl phorbol 13-acetate (TPA) (10 ng/ml) selectively suppresses the growth of the otherwise predominant keratinocyte cell population and that this is associated with the outgrowth of normal melanocytes. The present study indicates that these melanocytes can be subsequently grown for at least 30 passages if the medium contains TPA, but if the compound is removed the cells cease to divide. The ability of a series of phorbol esters to support the growth of normal human melanocytes correlates, in general, with their tumor promoting activity on mouse skin. Two structurally unrelated types of compounds which have recently been shown to have tumor promoting activity on mouse skin, teleocidin and aplysiatoxin, also support melanocyte growth. On the other hand, several polypeptide growth factors could not substitute for TPA. Since human melanoma cell lines grow vigorously in the absence of tumor promoters our results suggest that the malignant transformation of melanocytes is associated with the acquisition of autonomy from certain unidentified endogenus growth factors.
Carcinogenesis 1983
PMID:Stimulation of growth of human melanocytes by tumor promoters. 640 74

The dysplastic nevus syndrome (DNS) is a preneoplastic melanocyte abnormality which occurs in families affected by hereditary cutaneous malignant melanoma (HCMM). A putative role of host-environmental interactions in the etiology of hereditary melanoma has been strengthened by the recent finding that fibroblasts derived from HCMM/DNS patients demonstrated enhanced sensitivity to u.v.-irradiation in vitro. We report here an extension of these studies in which we have examined the in vitro responses to a model environmental carcinogen, 4-nitroquinoline 1-oxide (4NQO), of six non-tumor skin fibroblast strains from HCMM/DNS patients representing five families. Three of the six HCMM/DNS strains showed enhanced cell killing with sensitivities greater than that of a xeroderma pigmentosum (XP) variant strain but less than those of ataxia telangiectasia and XP Group D cell strains. The inhibition and recovery of de novo DNA synthesis, together with the expression of repair synthesis, following 4NQO exposure appeared to be normal in HCMM/DNS strains, irrespective of their subsequent clonogenic potential. Our data point to a metabolic anomaly which may contribute to the carcinogenic risk of the melanoma prone preneoplastic state presented by some DNS patients.
Carcinogenesis 1983
PMID:Abnormal responses to the carcinogen 4-nitroquinoline 1-oxide of cultured fibroblasts from patients with dysplastic nevus syndrome and hereditary cutaneous malignant melanoma. 640 40

Because of a possible etiologic link between mutations and carcinogenesis, we compared fibroblasts derived from skin biopsies of several patients with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome for sensitivity to the mutagenic and/or cytotoxic effect of broad-spectrum simulated sunlight and of a UV mimetic carcinogen, 4-nitroquinoline 1-oxide (4NQO). The genetic marker was resistance to 6-thioguanine; loss of colony-forming ability was the assay for cytotoxicity. All five strains tested were more sensitive than normal to the killing effect of 4NQO (slopes of survival curves were 2- to 3-fold steeper), but only one strain was hypersensitive to killing by Sun Lamp radiation. Two strains were tested for mutagenicity. The response of each to the mutagenic action of these agents corresponded to its response to cell killing. Both strains were hypermutable after exposure to 4NQO, but only one showed a higher than normal frequency of mutants induced by simulated sunlight. The finding that nonmalignant fibroblasts from patients with a hereditary variant of malignant melanoma are abnormally susceptible to carcinogen-induced mutations suggests that hypersensitivity to mutagens contributes to risk of melanoma in patients. It also supports the somatic cell mutation hypothesis for the origin of cancer.
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PMID:Fibroblasts from patients with hereditary cutaneous malignant melanoma are abnormally sensitive to the mutagenic effect of simulated sunlight and 4-nitroquinoline 1-oxide. 642 69


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