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

In the 1970s a considerable amount of work was carried out in an attempt to identify an anti-tumor serological response in cancer patients. These analyses have not been very informative due to the complexity and heterogeneity of the response. More recently, the availability of recombinant molecules, synthetic peptides and analytic and semi-quantitative assays has enabled a better dissection of humoral immunity. Antibodies against intracellular antigens (c-myb, c-myc, p53 and p21 ras) have been found in a significant, albeit varying, proportion of patients bearing various tumors. Association with a poor prognosis is documented for anti-p53 antibodies in breast carcinoma patients. A number of cell surface antigens, including mucins, oncoproteins and carbohydrate antigens have been found to elicit a humoral immune response and, in some instances, circulating immune complexes were observed. A protective role for or, on the other hand, masking effects of such antibodies is still controversial. An indication that a serological response can be beneficial comes from vaccination studies. A significant association between the development of an anti-tumor antigen antibody response and prolonged survival was observed following vaccination of melanoma patients with GM2 or anti-idiotypic antibodies which molecularly mimic tumor-associated antigens. It is to be hoped that in the near future the numerous ongoing immunization trials and prognostic studies demonstrate whether antibody response can exert a protective role in vivo.
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PMID:1975-1995 revised anti-cancer serological response: biological significance and clinical implications. 874 Jul 84

Expression of mutant p53 detected by immunohistochemistry has been described in human malignant melanoma, but there are few reports of molecular analyses. To investigate the genetic basis for p53 expression in malignant melanoma, we examined 58 primary tumors and 5 cutaneous metastases. The entire coding sequence of the p53 gene was screened by single-strand conformation polymorphism analysis and direct genomic sequencing of polymerase chain reaction products. p53 and mdm-2 expression were studied by immunohistochemistry. Two p53 gene mutations could be found in 1/63 samples examined, both having occurred in the same specimen from a patient with a nodular melanoma. p53 and mdm-2 expression were found immunohistochemically to increase with tumor progression both in frequency and in the mean proportion of positive cells, with the same cases staining positively for both antibodies. Our results suggest that a) p53 gene mutations are a rare event in human melanoma; b) accumulation and thus immunohistochemically detectable expression of p53 may result from posttranslational mechanisms affecting the p53 gene product; and c) p53 and mdm-2 are more important in late events in melanoma carcinogenesis.
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PMID:Immunohistochemical detection of p53 in melanomas with rare p53 gene mutations is associated with mdm-2 overexpression. 874 96

Many human tumours are hyperdiploid, particularly in advanced stages of growth. The purpose of the present work was to investigate whether exposure to hypoxia followed by reoxygenation might induce hyperploidisation of diploid human tumour cells in vitro. The investigation was performed by using the diploid melanoma cell line BEX-c (median chromosome number, 46; DNA index, 1.10 +/- 0.04) as test line and the hyperdiploid melanoma cell line SAX-c (median chromosome number, 61; DNA index, 1.42 +/- 0.03) as control line. Cell cultures kept in glass dishes in air-tight steel chambers were exposed to hypoxia (O2 concentrations < 10 p.p.m. or < 100 p.p.m.) at 37 degrees C for 24 h. DNA content was measured by flow cytometry. Metaphase spreads banded with trypsin-Versene-Giemsa were examined to determine the number of chromosomes per cell. An electronic particle counter was used to measure cell volume. The expression of p53 and pRb was studied by Western blot analysis. Transient exposure to hypoxia was found to induce a doubling of the number of chromosomes in BEX-c but not in SAX-c. The fraction of the BEX-c metaphase spreads with 92 chromosomes was approximately 10% at 18 h after reoxygenation, decreased to approximately 2% at 7 days after reoxygenation and then increased gradually with time. The whole cell population became tetraploid within 25 weeks. BEX-c and SAX-c behaved differently during the 24 h hypoxia exposure. Cell volume and fraction of cells in G2 + M increased with time in BEX-c but remained essentially unchanged in SAX-c. On the other hand, the expression of p53 and pRb was similar for the two lines; hypoxia induced increased expression of p53 and hypophosphorylation of pRb.
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PMID:Hypoxia-induced tetraploidisation of a diploid human melanoma cell line in vitro. 876 66

In this study we analysed snap-frozen surgical resections of 16 superficial spreading melanomas, 13 nodular malignant melanomas, 2 lentigo maligna melanomas, 1 dysplastic nevus, 1 congenital nevus and 5 normal nevi from 38 patients for point mutations in the human p53 gene at exons 5-8 by polymerase chain reaction/single-strand conformation polymorphism as well as for loss of heterozygosity of p53 by restriction-fragment-length polymorphism/polymerase chain reaction in order to determine whether p53 aberrations are associated with melanoma subtypes. In addition, we analysed six melanoma cell lines for point mutations in p53. Our results revealed the absence of point mutations and loss of heterozygosity in all fresh resected lesions. However, a TAC (Tyr) to TGC (Cys) transition at codon 163 in exon 5 was found in one cell line.
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PMID:Lack of p53 mutations and loss of heterozygosity in non-cultured human melanocytic lesions. 878 68

p53 immunoreactivity was examined in 132 cutaneous non-melanoma tumours from renal transplant recipients and in 114 histologically matched specimens from immunocompetent individuals. Skin lesions examined included 52 viral warts, 50 dysplastic keratoses, 51 intraepidermal carcinomas (IEC), 50 invasive squamous cell carcinomas (SCC) and 43 basal cell carcinomas (BCC). Overall, 51% (51/101) pre-malignant skin lesions and 45% (42/93) non-melanoma skin cancers (NMSC) showed p53 immunoreactivity, with extensive (> 50% cells positive) p53 staining in 27% (27/101) of pre-malignant and 20% (19/93) of malignant lesions. 17% (9/52) viral warts showed p53 immunoreactivity, but this was limited to focal or basal p53 staining. p53 immunoreactivity in all tumours was less in transplant than in non-transplant patients and this reached statistical significance for SCCs (p = 0.03).
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PMID:p53 immunoreactivity in non-melanoma skin cancer from immunosuppressed and immunocompetent individuals: a comparative study of 246 tumours. 879 57

Cancer is a disease characterized by defects in growth control, and tumor cells often display abnormal patterns of cellular differentiation. The combination of recombinant human fibroblast interferon and the antileukemic agent mezerein corrects these abnormalities in cultured human melanoma cells resulting in irreversible growth arrest and terminal differentiation. Subtraction hybridization identifies a melanoma differentiation associated gene (mda-7) with elevated expression in growth arrested and terminally differentiated human melanoma cells. Colony formation decreases when mda-7 is transfected into human tumor cells of diverse origin and with multiple genetic defects. In contrast, the effects of mda-7 on growth and colony formation in transient transfection assays with normal cells, including human mammary epithelial, human skin fibroblast, and rat embryo fibroblast, is quantitatively less than that found with cancer cells. Tumor cells expressing elevated mda-7 display suppression in monolayer growth and anchorage independence. Infection with a recombinant type 5 adenovirus expressing antisense mda-7 eliminates mda-7 suppression of the in vitro growth and transformed phenotype. The ability of mda-7 to suppress growth in cancer cells not expressing or containing defects in both the retinoblastoma (RB) and p53 genes indicates a lack of involvement of these critical tumor suppressor elements in mediating mda-7-induced growth inhibition. The lack of protein homology of mda-7 with previously described growth suppressing genes and the differential effect of this gene on normal versus cancer cells suggests that mda-7 may represent a new class of cancer growth suppressing genes with antitumor activity.
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PMID:The melanoma differentiation associated gene mda-7 suppresses cancer cell growth. 879 71

Cancer is a multi-stage process in which the accumulation of genetic changes allows clonal expansion of abnormal cells that will eventually form a tumor. Skin cancer is the most common malignancy affecting human beings. Mutations of the tumor suppressor gene p53 are often found in non-melanoma skin cancer and pre-invasive lesions, like actinic keratosis. The type of mutations detected in the p53 gene strongly indicate UV light as the initiating and promoting agent in skin cancer development. Chromosome instability is also an early event in skin tumor formation. However, despite the huge amount of information available in the literature on molecular markers of skin cancers, much remains to be uncovered about the progression of genetic events that separate normal sun-exposed epidermis from skin cancer. In this paper the following issue will be addressed: how far are we from being able to define a human model for multistage skin carcinogenesis in humans?
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PMID:Genetic alterations in skin cancer. 880 85

p53, A tumor suppressor gene, has been documented as the most frequently mutated gene in human cancers including non-melanoma skin tumors. It has been controversial whether the p53 gene mutation plays a major role for melanoma genesis. To examine the role of p53 in human malignant melanoma carcinogenesis, we performed immunohistochemical analysis using anti-p53 antibodies (CM-1 and DO-7) in microwaved paraffin sections. When cases having more than 1% reactive cells were regarded as positive, immunohistochemical analysis revealed that in primary melanomas 14 of 51 (27%) were positive with CM-1 or 15 of 51 (29%) were positive with DO-7. Tumor thickness of primary melanomas in p53 positive cases was significantly thicker than that in p53 negative cases. In metastatic melanomas, 35 of 41 (85%) lymph node metastases were positive with either antibody and in skin metastases 16 of 28 (57%) lesions with CM-1 or 18 of 28 (64%) lesions with DO-7 were positive. The mean percentages of reactive cells were 2.3% in primary lesions and 4.9% in metastases. The incidence of positivity was significantly higher in metastases than primary lesions. In 10 cases examined, with both primary and metastatic melanoma, 3 cases were negative in both lesions and 1 case was positive in both lesions, while 6 cases were negative in the primary lesions and positive only in metastatic lesions. Four Spitz nevi, 6 dysplastic nevi and 11 common nevi were all negative. These data suggest that the expression of p53 protein may be a late event in melanoma progression.
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PMID:Expression of p53 protein in melanoma progression. 881 40

Differentially regulated expression of activators and inhibitors of cyclin-dependent kinases (cdks) modulate cell cycle progression. In normal fibroblasts, these complexes consist of the cdk inhibitor p21WAF1/PCNA/G1 cyclin/cdk. We now show that bromodeoxyuridine (BrdUrd), a thymidine analogue and radiation sensitizer, inhibits growth and activity of cyclin A-cdk2 kinase in metastatic C8161 and nonmetastatic neo 6.3/C8161 human melanoma cells. Inhibition is not due to altered levels of cyclin D or catalytic cdk2 but involves a decrease in cyclin A and proliferating cell nuclear antigen, paralleled by higher levels of p21WAF1 without increases in p53. In contrast to serum starvation, which prevents accumulation of cyclins A and D in normal fibroblasts, such treatment did not down-regulate either cyclin in these melanoma cells, implying an aberrant control for G1 cyclins in these tumor cells. However, cyclin A was decreased by BrdUrd, suggesting that this pyrimidine analogue arrests melanoma cells at a G1 transition point, unlike that of serum starvation. This is the first report indicating that the antitumor therapeutic action of BrdUrd may be mediated by a p53-independent reciprocal effect on activators and inhibitors of cdk kinases.
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PMID:p53-independent increase in p21WAF1 and reciprocal down-regulation of cyclin A and proliferating cell nuclear antigen in bromodeoxyuridine-mediated growth arrest of human melanoma cells. 882 3

A common characteristic of cancer cells is unrestrained cell division. This may be caused by mutational changes in genes coding for components of cell cycle-controlling networks. Alterations in genes involved in G1 checkpoint control have been registered in many human tumours, and investigations from several laboratories show that such alterations, taken together, are the most frequent changes detected in cancer cells. The present paper describes mutational analysis by polymerase chain reaction-single-strand conformation polymorphism (PCR/SSCP) and nucleotide sequence analysis of the genes coding for the p15, p53 and N-ras proteins in 26 metastases from 25 melanoma patients. The registered mutation frequencies add together with previously registered mutations in p16 in the same patient samples to a substantial total frequency of 44% of patients with mutation in at least one of the investigated genes. These results show the occurrence of heterogeneous defects among components of the cell cycle controlling machinery in a human melanoma tumour sample collection and demonstrate that the total frequency of detected alterations increases with the number of cell cycle controlling genes included in the screening panel.
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PMID:Genes involved in cell cycle G1 checkpoint control are frequently mutated in human melanoma metastases. 882 61


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