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)

Mice bearing the B16 melanoma or treated with Corynebacterium parvum develop elevated levels of plasma neutral proteinase activity. Similar experiments carried out with C57BL/6-bg/bg (beige) mice, which are genetically deficient in polymorphonuclear neutrophil (PMN) proteinases, revealed that such mice develop significantly diminished elevation in plasma proteinase activity compared to C57BL/6-bg/+ mice. Lysates of C. parvum elicited PMN from beige mice contained approximately 80% less neutral proteinase activity as did lysates of PMN from bg/+ mice. These results indicate that host cells, such as PMN, may become activated during the tumor progression, or following C. parvum treatment, causing degranulation and a subsequent elevation in plasma proteinase levels. If such an interpretation is correct, then this phenomenon may be the murine corollary to what has been observed in patients with certain inflammatory diseases or tumors.
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PMID:Differences between beige and bg/+ mice in the disruption of plasma proteinase regulation in the tumor-bearing state or following Corynebacterium parvum treatment. Evidence for the involvement of polymorphonuclear leukocyte proteinases. 305 56

The antigenic profile of melanocytic cells in the course of local and systemic tumor progression of human malignant melanoma was investigated by the reactivity of a panel of monoclonal antibodies (MAbs) in frozen sections of histologically defined melanocytic lesions. Specific antigenic phenotypes made it possible to distinguish 5 groups of lesions which could be ranked in relation to each other due to the sequential acquisition or loss of progression markers. On this basis, a scheme of antigenic changes which accompany the stepwise transformation of normal skin melanocytes into highly malignant metastatic melanoma cells is proposed. The steps of tumor progression identified solely by phenotyping with MAbs were in complete concordance with the concept of melanoma progression derived from histological, statistical and clinical analyses. Furthermore, our finding that the expression of gp89 as well as HLA-DR antigens can be induced by interferon-gamma in vitro provides evidence that immune interferon may play a role in the regulation of genes leading to phenotypic changes in progressing melanoma cells.
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PMID:Tumor progression in human malignant melanoma: five stages defined by their antigenic phenotypes. 310 15

To examine the potential regulatory role of interferon-gamma in the cellular immune response to melanoma and its precursor lesions, we have tested the capacity of this lymphokine to enhance HLA class II antigen-dependent T lymphocyte blastogenesis, its in vitro production by autologous T cells stimulated by melanoma, and its presence in melanocytic lesions in situ. Cell lines derived from a dysplastic nevus, a radial growth phase primary tumor, a vertical growth phase primary, and metastatic lesions were induced by recombinant interferon-gamma to express increased amounts of HLA class II antigens. Such cells were then examined in radioimmunoassay for expression of HLA-DR antigens and in co-culture for their ability to stimulate proliferation of autologous T cells. Interferon-gamma treatment of melanocytic cells increased their expression of HLA-DR antigens threefold to sixfold. In parallel with these findings, co-culture of T cells with interferon-treated cells of a dysplastic nevus and a radial phase melanoma led to augmented T cell incorporation of tritiated thymidine, and this stimulation was inhibited with a monoclonal antibody to HLA-DR antigens. Despite augmented expression of HLA class II antigens (HLA-DR, -DQ, and -DP), vertical growth phase and metastatic melanoma cells failed to stimulate autologous T cells. When T cells were co-cultured with stimulating melanoma cells, culture supernatants contained significantly increased amounts of interferon-gamma (12 U/ml) in comparison with supernatants of T cells alone (4 U/ml). No interferon was detectable in cultures of melanoma cells alone. To link these in vitro phenomena to in situ events, we used murine monoclonal antibodies to interferon-gamma, the interleukin 2 receptor, and HLA-DR antigens in an immunoperoxidase system to detect interferon production and lymphocyte activation in frozen sections of lesions representative of melanocytic tumor progression. In these studies, precursor dysplastic nevi and radial phase melanomas contained the highest numbers of activated lymphocytes and stained positively for interferon-gamma. These results suggest that interferon-gamma plays a central role in the regulation of the cellular immune response to melanoma. It is produced by T cells, likely activated by tumor antigens seen in the context of HLA class II antigens. In turn, interferon-gamma production enhances expression of HLA class II antigens by melanoma and precursor cells, and such enhancement is associated with additional T cell activation in a positive feed-back loop.
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PMID:Interferon-gamma regulates the T cell response to precursor nevi and biologically early melanoma. 310 2

We have established nonmetastatic mouse B16 melanoma clone, C1-2, and metastatic variant, C4-1, by subcloning the 30th passage of nonmetastatic W1-4 cells. We have investigated oncogene expression and chromosomal abnormalities to see whether there is some correlation with tumor progression and phenotypic diversification in melanoma cells. Not only metastatic C4-1 but also nonmetastatic C1-2 showed similarly high expression of c-Ha-ras and c-myc oncogenes by Northern blotting method. The chromosome numbers of both clones were distributed mainly within the range of 48-52. C1-2 had about 20 biarmed chromosomes and C4-1 had 13 or 14, which made real ploidy of C1-2 and C4-1, hypotetraploidy and triploidy, respectively. 21 marker chromosomes were commonly observed, while 9 marker chromosomes peculiar to C1-2 and 4 peculiar to C4-1 were constantly recognized. In partial accordance with a previous report, chromosomes 4, 5, 6, 8, 10, 13, 18, 19, and X were additionally observed in nonmetastatic C1-2 cells, compared with metastatic C4-1 cells. Furthermore, in our study, the increase of chromosomes 1, 15, and 16 was found to be greater in metastatic C4-1.
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PMID:Comparative analysis of oncogene expression and chromosome abnormalities between metastatic and nonmetastatic B16 melanoma clones. 314 2

Three mouse monoclonal antibodies (mAbs) recognizing antigens of human melanocytic cells were used to study a large panel of cultured normal and tumor cells and fresh tissues. Two of the monoclonal antibodies (designated TA99 and CF21) detect melanosomal antigens, whereas mAbC350 recognizes a cell surface antigen. Among cultured cells the three mAbs reacted exclusively with normal melanocytes and pigmented melanomas, but not with nonpigmented melanomas or cells of other lineage. Immunohistochemical assays using mAbTA99 and mAbCF21 on fresh-frozen sections from a large panel of normal tissues revealed a characteristic pattern of reactivity restricted to pigmented cells. mAbC350 did not react with any normal tissues. All nevi and primary melanoma specimens and 93% of metastatic melanomas were reactive with at least one of these three monoclonal antibodies. No reactivity was found with 62 nonmelanoma tumors. An inverse correlation was observed between TA99 expression and stage of tumor progression. These markers are useful for studies of melanocyte differentiation and malignant transformation, subsetting of melanocytic lesions, and identification of tumors of melanocytic origin.
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PMID:Differentiation antigens of melanocytes and melanoma: analysis of melanosome and cell surface markers of human pigmented cells with monoclonal antibodies. 328 Jun 98

The effects of tuftsin and steroids (methyl prednisolone) on the induction of disrupted plasma proteinase regulation in mice bearing the B16 melanoma or treated with Corynebacterium parvum was investigated. Tuftsin treatment inhibited tumor progression only if treatment was started at the time of tumor transplantation. However, tuftsin inhibited the development of splenomegaly in mice with established tumors. In contrast, tuftsin did not influence either the induction of elevated plasma proteinase activity or the activity in plasma from animals with established tumors. Treatment of mice with high, anti-inflammatory, doses of steroid (20 mg/kg/day) partially inhibited tumor progression, inhibited the induction of splenomegaly, but did not inhibit the induction of disrupted plasma proteinase regulation. Likewise, steroid treatment did not suppress the induction of elevated plasma proteinase activity following treatment of mice with C. parvum. Thus the induction of elevated plasma proteinase activity, previously demonstrated to be a host regulated phenomenon, is resistant to regulation by this anti-inflammatory drug and likely not a component of the anti-tumor response. These findings raise the possibility that this phenomenon results from the interaction of activated RES elements with components of the plasma proteinase cascades.
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PMID:Steroids and tuftsin fail to prevent the induction of altered plasma proteinase homeostasis in mice bearing the B16 melanoma or treated with C. parvum. 331 18

Spontaneous wheat germ agglutinin (WGA)-resistant mutants of the MeWo human malignant melanoma line were isolated after sequential selection in increasingly toxic concentrations of WGA, without prior mutagenesis. They were isolated in an attempt to obtain "membrane glycosylation mutants" having significantly altered metastatic properties when grown in nude mice, and to characterize the biochemical (oligosaccharide) changes associated with altered metastatic behavior. The lines were assessed for their sensitivity to other lectins, membrane glycoprotein profiles, ploidy levels, and their ability to produce "artificial" metastases in nude mice after i.v. inoculation. One mutant, called 70-W, manifested a 3- to 4-fold resistance to WGA compared with wild-type cells. When inoculated into NIH Swiss nude mice, 70-W cells not only produced extensive lung colony formation but also showed an extraordinary ability to disseminate widely and extensively in a clinical fashion to many extrapulmonary sites such as the subcutis, mesentery, muscle, and brain. Moreover the majority of these metastases were deeply pigmented facilitating visual identification of very small visceral metastases. A second mutant called 3S5 was isolated and found to be highly resistant to WGA (greater than 20-fold resistance). This line was virtually devoid of metastatic ability and was found by biochemical analysis to be phenotypically similar to the class I WGA resistant non-metastatic mutants previously isolated from the highly metastatic murine tumor MDAY-D2 which are known to be deficient in sialic acid and galactose. The similarity between these and earlier results using lectin resistant mutant rodent cell lines strongly suggests that sialylated glycoconjugates contribute to the metastasis of both animal and human tumors of different tissue origin. These new spontaneously derived WGA resistant MeWo mutants should be valuable new tools for the study of human tumor progression in vivo and factors involved in metastasis, especially the contribution of oligosaccharide moieties of cell surface glycoconjugates.
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PMID:Isolation and characterization of spontaneous wheat germ agglutinin-resistant human melanoma mutants displaying remarkably different metastatic profiles in nude mice. 333 29

The melanoma-associated antigen ME491 is expressed strongly during the early stages of tumor progression. The ME491 gene was molecularly cloned by means of DNA-mediated gene transfer followed by screening a lambda genomic library with human repetitive Alu sequences as a probe. The cloned DNA, after transfection into mouse L-cells, generated a protein with characteristics that were indistinguishable in Western blot analysis from the ME491 antigen expressed by human melanoma cells. Repeat-free subfragments of the cloned DNA were used for further studies. By Northern blot analysis, the subfragments detected a single 1.2-kilobase mRNA in the transformants and various human melanoma cell lines. ME491 complementary DNA clones were then obtained by probing a melanoma complementary DNA library with the genomic subfragments. Nucleotide sequence analysis of the cloned complementary DNA indicated that the ME491 antigen consists of 237 amino acids (Mr 25,475) with four transmembrane regions and three putative N-glycosylation sites. No significant structural homology was observed with other proteins thus far reported. We observed that the amounts of mRNA varied greatly with different melanoma cell lines. Southern blot analysis revealed no amplification or rearrangement of the ME491 gene in the human melanoma cell lines tested, including both high and low expressors of this antigen. The ME491 gene has been mapped to chromosome region 12p12----12q13 by somatic cell hybrid analysis and more narrowly localized to 12q12----12q14 by in situ hybridization.
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PMID:Molecular cloning and characterization of an antigen associated with early stages of melanoma tumor progression. 336 86

In Xiphophorus the causative, primary cellular oncogene for melanoma formation has been assigned by classical genetics to a sex-chromosomal locus, designated Tu. Activation of Tu was proposed to be the result of the elimination of Tu-specific regulatory genes which normally suppress the transforming function in the non-tumorous state. In order to understand the role which known proto-oncogenes might play in this process, we have analysed the expression of src, erb A, erb B, ras, abl, sis and mil related genes from Xiphophorus during embryogenesis, in non-tumorous organs and in melanoma cells. For src, ras, erb B and sis a differential expression during embryogenesis and/or in normal organs was detected, with preferential expression of src in neural tissues, a high abundance of sis transcripts in an embryonal epitheloid cell line and of erbB transcripts in the head nephros. In melanoma cells ras, src and a v-erb B related gene were found to be expressed. The src gene most likely is more involved in secondary processes during tumor progression, while the expression of the v-erb B related gene might be transformation-specific because recently such a sequence was found to map to the close vicinity of the Tu-locus.
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PMID:Expression of proto-oncogenes in embryonic, adult, and transformed tissue of Xiphophorus (Teleostei: Poeciliidae). 337 60

Radioimmunoscintigraphy is presented as a new imaging modality in nuclear medicine, using specific antigen-antibody interactions. Monoclonal antibodies to tumor-associated antigens facilitate the characterization of molecular differences between tumors and normal cells. Labelled with gamma-emitting radioisotopes like I-131, I-123, In-111, and Tc99M, these antibodies can be used for in-vivo imaging. Radioimmunoscintigraphy does not compete with morphological modalities like CT and ultrasound, but provides additional information based on its functional principle. Hidden lesions may be detected. Target-to-background ratios, however, are still rather low hampering scintigraphic imaging. The use of Single Photon Emissions Computed Tomography (SPECT) in addition to planar scintigraphy resolves background activities thus providing better visualization and localization of tumors, and increasing sensitivity. The high cost of these time-consuming studies is still a limiting factor to its wider use. Its preliminary indication is founded on the suspicion of tumor progression, based on clinical findings and/or increasing serum tumor markers (CEA, CA 19-9, CA 12-5). This paper provides an overview over possible applications of radioimmunoscintigraphy. Its clinical use is demonstrated by studies of malignant melanoma, colorectal cancer and ovarian cancer.
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PMID:[Radioimmunoscintigraphy with monoclonal antibodies]. 350 11


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