Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The aim of the present study was to establish a cytofluorometric method for the simultaneous determination of protein-bound sulfhydryl-groups (PSH) and DNA in isolated cell nuclei. DNA was stained with ethidiumbromide and PSH with N-iodoacetyl-N(5-sulfo-1-naphthyl) ethylendiamine (AEDANS). Disulfide groups of nuclear proteins were determined by the same method after reduction with sodium borohydride or thioglycollic acid. The method was established by using nuclei of human lymphocytes, which then served as a biological standard for further investigations of the nuclei of different mammalian cell types: nuclei from mouse liver cells and nuclei from the cells of two human melanoma cell lines. For non-proliferating lymphocytes distinct DNA- and PSH-values could be measured. The PSH-values detected in the nuclei of the other cell types were higher by comparison and varied within the cell cycle; i.e., PSH increased during the S-phase and was almost doubled during the cell generation cycle from G1- to G2-phase. Cell line and cell cycle-dependent variations of nuclear disulfides could also be detected. These results are discussed with respect to their radiobiological implications. In conclusion, thiol groups may represent one factor determining the radiosensitivity of cells, but they are not the only decisive one.
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PMID:Cytofluorometric determination of protein-bound thiols and DNA in cell nuclei. 234 Jul 70

Neuroglandular antigen (NGA) was identified as a human melanoma-associated antigen by a panel of murine monoclonal antibodies of both IgG2a (LS62, LS76, LS159) and IgG1 (LS113, LS140, LS152) subclasses, developed in this laboratory (L. Sikora, A. Pinto, D. Demetrick, W. Dixon, S. Urbanski, and L. M. Jerry, Int. J. Cancer, 39: 138-145, 1987). Monoclonal antibody LS62 was used to immunoprecipitate NGA from radiolabeled cultured melanoma cells, and it behaved as a heterogeneous glycoprotein "smear" on sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis (Mr 29,000-70,000). Radioactive pulse-chase time course experiments using human melanoma cells cultured in the presence or absence of inhibitors of protein glycosylation showed that the antigen consisted of a core protein with a molecular weight of 22,000 on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. This molecule was modified by the addition of at least three N-linked oligosaccharide side chains (as revealed by limited N-glycanase digestion) to give a precursor form with a molecular weight of approximately 34,000. Subsequent processing steps yielded a heterogeneous family of glycoproteins with varying amounts of covalently attached carbohydrate. Much of this heterogeneity in both molecular weight and pI (as revealed by two-dimensional electrophoresis) could be removed by treatment of the antigen with neuraminidase, suggesting heavy sialylation of the glycoprotein. NGA could be detected on the surface of melanoma cells by fluorescence-activated cell sorter analysis, surface radioiodination, and, as previously shown, immunoperoxidase staining. However, there was a larger intracellular pool of the molecule and the antigen was rapidly released into the culture supernatant. The function of NGA remains unknown but its elevated expression in transformed melanocytes have prompted this characterization to understand its biochemical nature and relation to other melanoma-associated antigens.
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PMID:Biosynthesis, glycosylation and intracellular processing of the neuroglandular antigen, a human melanoma-associated antigen. 236 31

In previous studies, we have found that combined treatment with BCNU and sodium cyanate could have a greater effect on the survival of mice bearing B16 melanoma than treatment with either agent alone. With rat hepatoma and human colon cancer cells in culture, we have obtained evidence that the inhibition of cell proliferation by sodium cyanate is greater at pH 6.6 than at pH 7.4. In the present work, the effects of combination treatments on the proliferation of cancer cells were studied with cyanate, pH, BCNU, and hyperthermia. With HT29 human colon cancer cells, the inhibitory effect of BCNU (50-100 micrograms/ml) was greater when the cells were treated at pH 6.6 than at pH 7.4. The influence of pH appeared to be absent or minimal at lower or higher concentrations of BCNU. We confirmed our previous observation that the inhibition of proliferation of LS174T human colon cancer cells is greater at pH 6.6 than at pH 7.4, and we observed an inhibitory effect of BCNU (50 or 200 micrograms/ml). However, no more than additive effects were seen with combination treatment. An inhibitory effect of hyperthermia was seen for the incorporation of [3H]-leucine into protein of rat hepatoma cells (HTC) and for that of [3H]-thymidine into DNA of human colon cancer (HT29) cells. In neither case was the effect of hyperthermia significantly enhanced by treatment with sodium cyanate beyond that seen with one of the treatments alone. The data confirmed that the inhibitory effect of sodium cyanate on cell proliferation can be enhanced by a low pH but did not provide evidence for synergistic effects in combination with BCNU or hyperthermia.
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PMID:Combined effect of pH and sodium cyanate on the inhibition of tumor cell proliferation and metabolism by BCNU and hyperthermia. 236 91

Phase II trials of flavone acetic acid have been performed in a total of 87 patients including 17 with advanced breast cancer, 23 with advanced colorectal cancer, 25 with advanced malignant melanoma and 22 with advanced head and neck cancer. Patients with colorectal cancer and melanoma had received no prior chemotherapy; in breast and head and neck cancer patients prior chemotherapy had been given with a median of 5 and 2 drugs respectively. The schedule used was a once-weekly regime, with a dose of 4.8 gms/m2 given as a 1 hour infusion, together with alkalinization (with i.v. sodium bicarbonate) given before and after FAA. Reassessment was performed after 6 weekly doses, although in 23 patients fewer than 6 doses were given, because of early disease progression in 15, and undue toxicity in 5. An additional 3 patients died within 72 hours of having received FAA and, although the precise cause of death in each case was not established, FAA toxicity could not be excluded. Treatment was generally manageable, the major manifestations of toxicity comprising uncomfortable warmth and flushes, nausea, diarrhoea, and visual complaints. Hypotension was also documented in 8 patients. No objective responses were seen in any of the patient sub-groups, although disease-stabilization was seen in 3 patients with breast cancer, 1 patient with advanced colorectal cancer, 2 patients with advanced melanoma and 4 patients with head and neck cancer. Further Phase II studies, using a higher dose of 8.6 gm/m2 over 6 hours once weekly, are currently in progress in Europe.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trials with flavone acetic acid (NCS. 347512, LM975) in patients with advanced carcinoma of the breast, colon, head and neck and melanoma. 238 21

The pattern of melanoma-associated antigens (MAAs) expressed on the surface of melanoma cells in 23 metastases, 15 obtained from different patients and 8 from different metastases in two patients, was studied by immunoprecipitation and sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis using monoclonal and polyclonal melanoma antisera. Though there were differences in the MAAs expressed by each melanoma, there were marked similarities as well. No more than two melanomas had a similar pattern of MAAs. However, all melanomas expressed some MAAs, and most MAAs were commonly expressed by several melanomas. Two of the MAAs studied, with molecular weights of approximately 75,000 and 95,000 to 97,000, were particularly well represented, and at least one of these two antigens was expressed by all melanoma cells. These results suggest that complete absence of tumor-associated antigens on metastatic melanoma cells is a rare phenomenon. All melanoma lines we studied expressed at least one of a restricted number of antigens. Thus despite antigenic heterogeneity, sufficient similarity remains between different melanomas to permit specific immunotherapy to be targeted to a limited number of tumor antigens.
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PMID:Immunophenotype of human melanoma cells in different metastases. 241 93

In previous studies we showed that human sarcoma and melanoma cell lines synthesize and secrete into culture medium a glycoprotein, migrating in urea sodium dodecyl sulfate-polyacrylamide gel electrophoresis at Mr 140,000. It is not detected in cultures of the corresponding normal cells. Conditioned medium of the melanoma cell line HMB-2, producing among the cell lines tested the largest amounts of this glycoprotein, has now been used as a source for purification of the protein. NH2-terminal amino-acid sequence determination of the purified glycoprotein showed that it is identical to human alpha 2-macroglobulin (alpha 2M). Rabbit antibodies raised against the glycoprotein specifically reacted in immunoblotting and immunodiffusion tests with alpha 2M present in human plasma. Likewise, these antibodies immunoprecipitated from the conditioned media of 35S-methionine-labelled melanoma and osteosarcoma cell lines the protein which had a molecular weight corresponding to alpha 2M. alpha 2M was also synthesized and secreted by 2 strains of fetal lung fibroblasts but not by fetal skin fibroblasts or adult skin fibroblasts autologous to the osteosarcoma cell line.
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PMID:Human tumor cells synthesize and secrete alpha-2-macroglobulin in vitro. 241

Supernatants from human mixed leukocyte cultures or lectin-depleted supernatants from cultures of PHA-activated human peripheral blood leukocytes were depleted of IL 2 by passage over an anti-human rIL2 immunoadsorbent column. The column eluates were concentrated, dialyzed, and tested for their ability to synergize with human rIL 2 in facilitating human cytolytic T lymphocyte (CTL) responses to allogeneic, uv-irradiated HT144 melanoma cells in vitro. CTL were generated in the presence of 1 X 10(-4) M hydrocortisone sodium succinate in order to minimize the generation of nonspecific lymphokine-activated killer (LAK) cells. IL 2-depleted lymphokine-containing supernatant (LKS), alone or in the presence of less than or equal to U/ml rIL 2 did not stimulate significant CTL responses. Recombinant IL 2 at greater than 2 U/ml stimulated weak CTL responses in the absence of LKS. However, strong synergistic CTL responses were observed when both IL 2-depleted LKS and greater than 2 U/ml rIL 2 were added to the cultures. CTL generated in these cultures could be distinguished from nonspecific LAK cells on the basis of their i) specificity, ii) T3 phenotype, and iii) kinetics of generation. Nevertheless, rIL 2 and IL 2-depleted LKS were sometimes observed to synergize in facilitating the generation of nonspecific LAK cells as well as the generation of specific CTL. When the times at which rIL 2 and IL 2-depleted LKS were added to the cultures were varied, IL 2 was found to be required early in CTL responses, whereas the synergistic factor(s) in LKS seemed to act later. Recombinant human interferon-gamma was unable to replace LKS in synergizing with rIL 2 to elicit CTL responses. In summary, these experiments suggest that LKS contains a late-acting factor(s), antigenically distinct from IL 2, which synergizes with IL 2 in facilitating human CTL responses.
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PMID:Synergy between recombinant interleukin 2 (rIL 2) and IL 2-depleted lymphokine-containing supernatants in facilitating allogeneic human cytolytic T lymphocyte responses in vitro. 241 10

The relationship of antigenic heterogeneity to the epitope recognized by an antibody was examined with monoclonal antibodies to human melanoma-associated antigens. Expression of the human melanoma-associated antigens, 250-Kd glycoprotein/proteoglycan and p97, was examined quantitatively by flow cytometry on fresh cell suspensions of human melanoma. Percent positive cells and mean fluorescence intensity were consistently higher with antibody 9.2.27 to the 250-Kd glycoprotein/proteoglycan than with antibody to p97. In addition, assessment of percent positive cells in multiple skin lesions biopsied from individual patients indicated that in 26 of 30 lesions, greater than 90% of the cells stained positively with 9.2.27. This relative lack of antigenic heterogeneity with antibody 9.2.27 contrasted with previous reports which showed considerable antigenic heterogeneity with other antibodies to the 250-Kd glycoprotein/proteoglycan. The explanation for this distinction was sought by quantitative flow cytometric and sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) techniques. Comparison by flow cytometry and immunoperoxidase of three antibodies, which recognized distinct epitopes of the 250-Kd glycoprotein/proteoglycan, indicated that 9.2.27 reacted more intensely with cultured cells and tissue sections than other antibodies to the same antigen. Examination by SDS-PAGE indicated that 9.2.27 could immunoprecipitate a larger proportion of 250-Kd glycoprotein molecules than other antibodies. In addition, immunodepletion experiments in gels indicated that the 9.2.27 determinant was present on a higher proportion of 250-Kd glycoprotein molecules than PG-2 antibody to a separate determinant. It is likely that 9.2.27 antibody displays less antigenic heterogeneity because its epitope is represented on a higher proportion of the antigen molecules. Thus, not only the nature of the antigen but also the epitope recognized by an antibody influences the degree of antigenic heterogeneity.
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PMID:Human melanoma-associated antigens: analysis of antigenic heterogeneity by molecular, serologic and flow-cytometric approaches. 242 45

Surface macromolecules shed into culture medium by radioiodinated human melanoma cells were fractionated on Sepharose 6B and by sequential lectin-affinity chromatography. Radioactivity associated with melanoma-associated antigens (MAAs) was assayed by indirect immunoprecipitation with anti-melanoma serum. Two MAAs were separated and highly purified. Both antigens were single-chain glycoproteins expressed on many, but not all, melanoma cells but undetectable on normal melanocytes and a variety of unrelated normal, fetal, and malignant cells. One MAA, with a molecular mass of approximately 115 kd, eluted on Sepharose 6B in a lower molecular mass peak and had a high affinity for ricin lectin. The carbohydrate side chain of this antigen contained D-galactose. The other MAA, with a molecular mass of approximately 125 kd, eluted on Sepharose 6B in a peak of higher molecular mass and had a high affinity for wheat germ lectin. The carbohydrate side chain of this antigen contained sialic acid. Both antigens were highly purified. By sodium dodecyl sulfate-poly-acrylamide gel electrophoresis analysis, no contaminating proteins were present in the purified 115-kd MAA fraction, and only a single minor contaminant was present in the fraction containing the purified 125-kd MAA. These two antigens differed in their biochemical or immunological properties from other MAAs of similar size that have been previously described.
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PMID:Identification and purification of 115- and 125-kilodalton cell surface human melanoma-associated antigens. 242 67

The cell-surface antigen detected by the monoclonal antibody JONES is expressed in the retina and a number of other central nervous system regions of the rat during the latter part of embryonic development and the early postnatal period. In addition to the expression on certain neuroblast populations it is found on some but not all axons and is also expressed at high levels on the end feet of radial glia in regions through which axons actively grow. In the perinatal rat retina, almost all the antigenic activity was carried on a ganglioside migrating between GM1 and GM2. The epitope recognized by antibody JONES was base labile and treatment with 0.1 M sodium carbonate or ammonia vapor converted the antigen into GD3. Resistance to oxidation by sodium periodate and reformation of the epitope by chemical acetylation of base-treated gangliosides with N-acetylimidazole identify the antigen as 9-O-acetyl GD3. The acetylation of GD3 seems to be regulated independently from GD3 expression itself since acetylated and nonacetylated GD3 do not have identical immunocytochemical distributions in the developing central nervous system. In addition, five independent human melanoma cell lines varied substantially in their expression of 9-O-acetyl GD3, even though they all expressed high levels of GD3. Acetylation of ganglioside-linked sialic acid provides a mechanism for generating unique patterns of surface carbohydrates, which may influence cell interactions in development.
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PMID:O-acetylation of a cell-surface carbohydrate creates discrete molecular patterns during neural development. 244 30


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