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

Four melanin pigment-containing intracranial tumors were found in three Long-Evans rats in the course of experimental oncogenesis by transplacental ethylnitrosourea (ENU). One of them was a leptomeningeal melanoma. Aside from the presence of scattered melanin-pigmented cells, the other three had the typical histological features of ENU-induced malignant nerve sheath tumors. Two of the three tumors were studied by electron microscopy and in tissue and organ culture systems. One of them demonstrated progressive melanogenesis in vitro; the other failed to produce more melanin and showed increasing differentiation, with a Schwannoma-like pattern by light microscopy. Melanosomes and premelanosomes were identified in both tumors by electron microscopy; the other fine structural features were those of malignant Schwannomas. These observations are relevant to the controversy on the histogenesis of pigmented nerve sheath tumors occasionally encountered in man and on the relationship of these tumors to pigmented nevi. The findings in the present study support the view of Masson that neoplastic nerve sheath cells are capable of melanogenesis.
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PMID:Studies on experimental malignant nerve sheath tumors maintained in tissue and organ culture systems. III. Melanin pigment and melanogenesis in experimental neurogenic tumors: a reappraisal of the histogenesis of pigmented nerve sheath tumors. 127 30

The melanoma determining Tu locus of the teleost Xiphophorus contains an accessory gene, x-erbB*a, which is closely related to the EGF receptor gene family, and is probably oncogenic. x-erbB*a exists in allelic forms that are specific for distinct Tu-loci, and shows high homology to a non-allelic non-oncogenic counterpart x-erbB*i which is transcribed into mRNA of 4.6 kb in non-tumorous and tumorous tissues of fish harboring and lacking Tu. Expression of a 4.0-kb mRNA in tumors (melanoma and fibrosarcoma) of different etiology is strictly correlated with the inheritance of X. maculatus x-erbB*a alleles; transcripts of 8.0 kb were detected in melanoma and carcinoma of fish harboring a certain x-erbB*a of X. variatus. The expression of the putative x-erbB*a transcripts parallels the stage of malignancy of the tumor. The expression of the xiphophorine EGF receptor gene (x-erbB) was detected in almost all tumors, is strongly enhanced in carcinoma, and is positively correlated with the degree of malignancy of melanoma and fibrosarcoma. Some tumors show expression of erbA-related genes. The PDGF receptor mRNA is expressed in all tumors analyzed and shows enhanced expression in malignant tumors of neurogenic, epithelial and mesenchymal origin. Expression of x-pdgf was observed in several cases of melanoma, but more frequently in carcinoma and fibrosarcoma. We conclude that x-erbB*a might be involved in initiation of tumors of different cellular origin and etiology in fish harboring Tu, as well as in the determination of the malignancy of the tumor. Furthermore, we assume that x-erbB*i, x-erbB, x-pdgf and x-pdgf-r play a role in secondary events in tumorigenesis by, e.g., conferring a selective growth advantage to the tumor cells.
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PMID:Expression of genes related to the human erbB, erbA, pdgf and pdgf-r in tumors of different etiology in Xiphophorus. 132 41

Tyr-SV40E transgenic mice are susceptible to melanoma due to simian virus 40 oncogenic sequences specifically expressed in pigment cells. Skin melanomas form relatively late. Therefore, melanocyte cell lines have been established from very young transgenic animals, when they showed no skin lesions, so that the spontaneous and gradual progress of the cells toward tumorigenesis could be characterized under culture conditions in which wild-type cells of the same inbred strain remain untransformed. Melanocytes of an in vitro transgenic line were irradiated with very low intensities of ultraviolet B (UVB) (280- to 320-nm wavelength) light at culture passages when the cells had not achieved anchorage independence. After a single exposure to 0.7 mJ/cm2 of UVB radiation, the cells became anchorage independent and formed foci at confluence; however, cells propagated from the foci were not tumorigenic. After one exposure to 1.75 mJ/cm2, more numerous and larger foci resulted, and the cells grown from them yielded malignant melanomas in graft hosts. Wild-type melanocytes were not transformed at these UVB doses. At least two genetic changes contributing to malignant conversion--in addition to the initiating effect of the transgene--are likely to have occurred, one change leading to anchorage independence and another to further progress toward malignancy. Cells at these stages provide an opportunity to isolate the relevant genes and identify any molecular defects attributable to UVB. Tumorigenesis after a very low UVB dose in cells where an initiating stimulus is already present suggests that some other stimulus, such as a gene or a carcinogen, might lead to melanoma in conjunction with exposure to relatively little UVB.
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PMID:Genetic predisposition of transgenic mouse melanocytes to melanoma results in malignant melanoma after exposure to a low ultraviolet B intensity nontumorigenic for normal melanocytes. 132

Elevated levels of pp60c-src tyrosine kinase activity have been implicated in both tumorigenesis and cell differentiation. We have found a 2- to 4-fold elevation in pp60c-src specific activity in certain human melanoma cell lines compared to human foreskin fibroblasts. This activation of pp60c-src did not appear to be related to melanoma tumor progression, because when normal human epidermal melanocytes were examined, it was found that they contained pp60c-src having a 7-fold elevation in specific activity compared to pp60c-src from human fibroblasts. It was determined that pp60c-src from melanocytes was not the neuronal form, pp60c-src+. Melanocyte pp60c-src exhibited a reduced level of phosphorylation on its carboxyl-terminal regulatory site, tyrosine 530, which might be responsible for its elevated specific activity. These results suggest that, in melanocytes, regulation of tyrosine 530 phosphorylation-dephosphorylation favors activation of pp60c-src. This activation may be involved in the growth, differentiation, or function of human melanocytes.
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PMID:pp60c-src in human melanocytes and melanoma cells exhibits elevated specific activity and reduced tyrosine 530 phosphorylation compared to human fibroblast pp60c-src. 138 53

The protooncogene c-kit encodes a tyrosine kinase with a molecular weight of 145,000, highly related to the platelet derived growth factor/colony stimulating factor receptors. Mutations of the murine gene result in impairment of hematopoiesis, gametogenesis, and of the melanocyte cell lineage. In order to elucidate c-kit functions in development and oncogenesis we have analyzed immunohistochemically its expression in human normal and transformed nonlymphoid tissues. The receptor has been detected in spermatogonia, melanocytes, and unexpectedly, in astrocytes, renal tubules, parotid cells, thyrocytes, and breast epithelium. While the gene product is expressed in seminoma, lung tumors, and melanoma of low invasiveness, no detectable levels have been detected in thyroid and breast carcinomas, astrocytomas, and invasive melanomas. In breast tumors these findings were confirmed by paired, Northern blot analysis of RNA preparations from normal and transformed tissue. The present results demonstrate that the c-kit receptor plays a role in the development of a larger spectrum of cell lineages. Furthermore, on the basis of the transformation associated changes, we speculate that, while in some cell types, c-kit expression positively regulates mitogenesis and is selected for in neoplastic transformation, in other tissues the c-kit pathway is involved in morphogenesis and differentiation and is, therefore, negatively selected in the course of tumor progression.
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PMID:Expression of c-kit receptor in normal and transformed human nonlymphoid tissues. 138 54

The purpose of this study was to determine the carcinogenic effect in male rats of a single i.v. injection of N-methyl-N-nitrosourea (MNU) after sequential treatment with cyproterone acetate (for 21 days) and testosterone propionate (for 3 days). This treatment has previously been shown to induce carcinomas of the prostate and other male accessory sex glands. A wide spectrum of non-melanoma skin tumors was found in 38-48% of Wistar (Cpb:WU) rats given this sequential treatment, but only in 5% of rats that received only MNU. Castration long and, particularly, early after MNU markedly reduced this skin tumor response to a 10-13% incidence. The skin tumorigenic efficacy of MNU was dependent on the time between the start of the testosterone propionate treatment and carcinogen administration: MNU injection after 48-50 or 60-63 h induced skin tumors in 17-21% of Wistar rats, whereas injection after 72-74 h induced a 48% incidence. The Fischer F344 and Sprague-Dawley strains were not very sensitive to induction of skin tumors by this approach. Thyroid follicular cell tumors were also induced by MNU only after the hormonal pretreatment, and their induction was influenced by the time of MNU injection as well. The time of MNU injection and rat strain used did not significantly influence the induction of sebaceous-squamous neoplasms of the ear-duct/Zymbal's glands or other tumors. These data indicate that endogenous androgens are critically involved in the later stages of rat skin tumorigenesis and suggest that androgen-induced cell proliferation influences the initiation stage of this process and, possibly, of thyroid tumorigenesis.
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PMID:Induction of skin and thyroid tumors in male rats by N-methyl-N-nitrosourea after sequential treatment with cyproterone acetate and testosterone propionate: effects of castration, rat strain and time of carcinogen injection. 153 74

Cellular adhesion receptors termed integrins play an important role in the interaction of cells with extracellular matrix (ECM) during wound healing, development and tumorigenesis. During such events, ECM may become modified or damaged which could alter the types of adhesive signals presented to cells. In this study, cell adhesion and affinity chromatography experiments were performed to determine whether different integrins interact with denatured versus native ECM molecules. Human melanoma cells were found to adhere to denatured versus native type I collagen through different integrins. The cells adhere to denatured collagen through the alpha v beta 3 integrin and this interaction is inhibited by an RGD containing peptide but not by a control peptide. In contrast, adhesion to native type I collagen appears to be mediated by several beta 1 integrins and thus, is not inhibited by either alpha v beta 3 antibodies or the RGD peptide. Affinity chromatography reveals a marked increase in the quantity of alpha v beta 3 isolated on denatured collagen versus native collagen-sepharose. These results suggest that RGD sites in type I collagen may be masked and that they become exposed upon denaturation of the molecule. Wounding of extracellular matrix may, thus, expose RGD sites in collagens that facilitate the interaction of cells with damaged extracellular matrix through RGD binding integrins.
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PMID:Affinity of integrins for damaged extracellular matrix: alpha v beta 3 binds to denatured collagen type I through RGD sites. 154 Jan 51

Cytogenetic analysis of 10 primary and 18 metastatic malignant melanomas revealed that structural abnormalities of chromosome 11 were present in 50% of metastatic lesions and were not found in primary tumors. Our findings suggest that chromosome 11 aberrations represent secondary changes in malignant melanoma tumorigenesis.
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PMID:Absence of structural rearrangements of chromosome 11 in human primary malignant melanoma. 155 Oct 88

The discovery and characterization of growth regulatory genes, in the form of oncogenes, and their counterparts, tumor suppressor (TS) or antioncogenes, has vastly expanded the basic understanding of tumorigenesis. Human solid tumors, such as colorectal cancer, for which the molecular genetics have been most clearly defined, display progressive evolution from cellular dysplasia to anaplasia and metastasis through the stepwise accumulation of genetic defects, involving the regulation and expression of both oncogenes and TS genes. The study of basic genetic abnormalities in melanoma and the identification of the most fundamental of these is critical both to the understanding of abnormal melanocyte proliferation and its potential pharmacologic or immunologic regulation, and also to the identification and screening of patients at high risk for the development of melanoma. The search for such genetic abnormalities has included an analysis of melanomas for defects in known characterized oncogenes and TS genes, and, more importantly, the use of families with hereditary melanoma (HM) and dysplastic nevi in an endeavor to find the melanoma gene. The importance of HM is fundamental, since in the case of other hereditary cancer syndromes for which the genetic basis has been identified, the same or similar genetic abnormalities underlie sporadic tumors of the same tissue type. Thus HM is likely to be the major signpost to the melanomagenic defect.
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PMID:Hereditary melanoma and the search for the melanoma gene. 156 6

Mutations in ras genes have been found in the DNA of numerous cancer types including melanomas, but the expression of these mutations in melanomas has not yet been addressed. We have used the polymerase chain reaction (PCR) and allele-specific restriction analysis (ASRA) to determine the frequency of expressed N-ras mutations on 25 short-term melanoma tissue culture samples. N-ras cDNA generated using reverse transcriptase from whole cells was used as the PCR template. 14 secondary melanoma cultures that varied in differentiation patterns were analysed. Only 2 were found to express N-ras mutations; in both, the mutation was localised to one of the first two positions of the 61st codon of N-ras. These tumour lines, KMI-M8412a and KMI-M8412b, were established from separate tumour deposits in the same patient. Codons 12 and 13 were found to be free of mutations in all of the lines studied. 8 primary melanomas and 3 unclassified skin lesions were also analysed and found free of N-ras mutations. These results suggest that N-ras may not play such an important role in melanoma tumorigenesis as is speculated by others.
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PMID:Analysis of expressed N-ras mutations in human melanoma short-term cell lines with allele specific restriction analysis induced by the polymerase chain reaction. 156 99


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