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)

We report that human leukocyte interferon preparations increase the expression of beta 2-microglobulin by 100-200% on the surface of normal fibroblast and melanoma cell lines sensitive to interferon. This increase in expression can be correlated with an increase in HLA synthesis as measured by incorporation of [35S]methionine in these antigens. This enhanced HLA synthesis, which is 5- to 17-fold, is time dependent and dose related. Synchronized cells in the G0/G1 phase of the cell cycle appear to be more sensitive to this interferon action. Neither an increase in surface expression nor in HLA synthesis is observed in a melanoma cell line resistant to the antiviral and antigrowth effects of interferon. Furthermore, there appears to be a stronger correlation between this increased HLA synthesis and the antiviral function than between it and the antiproliferative action of interferon.
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PMID:Interferon increases HLA synthesis in melanoma cells: interferon-resistant and -sensitive cell lines. 617 79

Murine tumors contain low molecular weight factors that inhibit macrophage accumulation at inflammatory foci. Certain oncogenic murine leukemia viruses contain similar inhibitory activity and the active component of the retroviruses was shown to be the envelope protein P15E. A number of murine malignant and nonmalignant cell lines, as well as primary tumors, have now been examined to determine whether production of retroviral P15E or a related protein is characteristic of neoplastic cells. Tumor lines examined included the Hep 129 hepatocarcinoma, BP8 fibrosarcoma, RL1 lymphoma, and three variants of the B16 melanoma. Tumor lines were virus negative by electron microscopy. Nonmalignant cells examined included ST0, 3T3/BALB, and 3T3/L1 fibroblasts and unstimulated, as well as mitogen-stimulated murine splenocytes. Cells were pulse-labeled with [35S]methionine, proteins immunoprecipitated with two monoclonal antibodies to P15E and analyzed by SDS-PAGE and gel fluorography. All tumor lines synthesized a approximately 19,000-dalton protein that co-migrated with retroviral P15E on SDS-PAGE. None of the nonmalignant cells synthesized this protein. Two-dimensional gel electrophoresis of the proteins precipitated from two B16 melanoma lines by monoclonal anti-P15E showed them to be physicochemically similar to P15E from Rauscher leukemia virus. A competition ELISA assay for P15E was developed and confirmed the results obtained by metabolic labeling and demonstrated P15E-related antigens in the tumor cell lines and also in the ascites fluid of mice injected with Hep 129 cells. More importantly, P15E antigens were expressed in both a spontaneous mammary adenocarcinoma and in a primary methylcholanthrene-induced fibrosarcoma. Nonmalignant tissues from animals bearing these tumors contained no detectable P15E antigen. Extracts from the primary fibrosarcomas, when injected into the thighs of mice, inhibited the intraperitoneal accumulation of inflammatory macrophages. The inhibitory activity was specifically removed by absorption with monoclonal antibody to P15E. These results suggest that synthesis of the immunosuppressive retroviral protein P15E, or a very similar protein, routinely occurs during the growth of murine neoplastic cells. This P15E-related protein is present in spontaneous murine primary tumors as well as in all murine tumor cell lines tested. The expression of such proteins by transformed cells in vivo could confer a selective advantage for their sustained growth since they would be more likely to escape immune surveillance.
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PMID:Murine malignant cells synthesize a 19,000-dalton protein that is physicochemically and antigenically related to the immunosuppressive retroviral protein, P15E. 619 38

alpha-Melanocyte-stimulating hormone (alpha-melanotropin; alpha-MSH) is a linear tridecapeptide (Ac-Ser-Tyr-Ser-Met-Glu-His-Phe-Arg-Trp-Gly-Lys-Pro-Val-NH2) that reversibly darkens amphibian skins by stimulating melanomsome (pigment granule) dispersion within melanophores. By using a number of in vitro melanocyte assays, we have examined the conformational requirements for alpha-MSH activity. Synthesis of [half-Cys4,half-Cys10]-alpha-MSH, a cyclic, conformationally restricted, "isosteric" analogue of alpha-MSH, provided a melanotropin with a potency greater than 10,000 times that of the native hormone in stimulating frog (Rana pipiens) skin darkening. The cyclic analogue also showed substantially prolonged activity relative to the native hormone. [half-Cys4,half-Cys10]-alpha-MSH was approximately 30 times more potent than alpha-MSH in stimulating lizard (Anolis carolinensis) skin melanophores in vitro. By using a cell-free Cloudman S-91 mouse melanoma plasma membrane preparation, we found the cyclic analogue to be approximately 3 times as potent as the native hormone in stimulating adenylate cyclase activity. These results provide insight into the conformational requirements for biological activity of alpha-MSH, and the comparative conformational requirements of alpha-MSH at a number of pigment cell receptors.
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PMID:[half-Cys4,half-Cys10]-alpha-Melanocyte-stimulating hormone: a cyclic alpha-melanotropin exhibiting superagonist biological activity. 628 85

The antiviral and antiproliferative effects of highly purified Escherichia coli-derived human interferons (IFNs) were examined in human melanoma cells (Hs294T). Antiproliferative activity was monitored by measuring inhibition of cell multiplication, and antiviral activity was determined by inhibition of herpes simplex virus type 1 replication. Treatment of cells with IFN-gamma in combination with IFN-alpha A or IFN-beta 1 resulted in potentiation of both antiproliferative and antiviral activities. In contrast, combination treatments composed of IFN-alpha A and IFN beta 1 yielded inconsistent results. Some combinations reflected additive responses, whereas others were antagonistic. To examine correlations between IFN-induced biological activities and interactions of the different IFNs with cell surface receptors, in vivo [35S]methionine-labeled IFN-alpha A was prepared. Binding studies indicated the presence of 2,980 +/- 170 receptors per cell, each with an apparent Kd of (8.4 +/- 1.3) X 10(-11) M. Results from competitive binding studies suggested that Hs294T cells possess at least two types of IFN receptors: one which binds IFN-alpha A and IFN-beta 1 and another to which IFN-gamma binds.
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PMID:Synergistic antiviral and antiproliferative activities of Escherichia coli-derived human alpha, beta, and gamma interferons. 631 48

We have prepared several alpha-melanotropin (alpha-MSH) analogues with tyrosine substituted for methionine at the 4-position and determined their melanotropic activities on the frog (Rana pipiens), lizard (Anolis carolinensis) and S-91 (Cloudman) mouse melanoma adenylate cyclase bioassays. The potencies of Ac-[Tyr4]-alpha-MSH4-10-NH2 and Ac-[Tyr4]-alpha-MSH4-11-NH2 were compared with alpha-MSH and with their corresponding methionine and norleucine substituted analogues. The Tyr-4 analogues were found to be less active than the Nle-4 analogues on both the frog and lizard assays. Ac-[Tyr4]-alpha-MSH4-10-NH2 was found to be less active than Ac-[Tyr4]-alpha-MSH4-11-NH2 on the lizard bioassay, but more active than the longer fragment on the frog skin assay. Ac-[Tyr4]-alpha-MSH4-10-NH2 exhibited extremely prolonged biological activity on frog skin, but not on lizard skin, while the melanotropic activity of Ac-[Tyr4]-alpha-MSH4-11-NH2 was rapidly reversed on both assay systems. The increased potency of Ac-[Tyr4]-alpha-MSH4-10-NH2 over Ac-[Tyr4]-alpha-MSH4-11-NH2 on frog melanocytes may be related to the fact that the shorter 4-10 analogue exhibits prolonged biological activity. Interestingly, it was found that both Tyr-4 analogues were partial agonists on the mouse melanoma adenylate cyclase bioassay, and stimulated the enzyme to only about 50% of the maximal activity of alpha-MSH. We reported previously that replacement of L-Phe-7 by its D-enantiomer in [Nle4]-alpha-MSH and its Nle-4 containing analogues resulted in peptides with increased potency and in some instances prolonged activity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Comparative biological activities of potent active-site analogues of alpha-melanotropin. Effect of tyrosine substitution at position-4. 633 85

To demonstrate antigens in cultured human tumor cells recognized by antibodies in human sera, extracts of cultured malignant melanoma cells were separated by SDS-PAGE, and electrophoretically transferred to nitrocellulose paper (NCP). The resulting electroblots were incubated with human serum, and bound immunoglobulin (Ig) was visualized with rabbit antibodies specific for human IgG, IgA or IgM, followed by peroxidase-conjugated goat anti-rabbit IgG. Antigen-antibody reactions in the nitrocellulose paper were also detected using 125I-labeled anti-rabbit IgG. As little as 125 pg of bound antibody per band were detectable. The numbers of proteins recognized by antibodies in human sera depended both on the quantity of protein transferred and the concentration of Ig applied to the NCP. Whole serum could not be used at dilutions less than or equal to 1:20 without an unacceptable increase in background staining. Binding of Ig to tumor cell proteins transferred to NCP depended on interactions with the Fab', not the Fc region of the Ig molecule. To determine the efficiency of transfer as a function of both time and molecular weight, tumor cell proteins were intrinsically labeled with 75Se-labeled methionine and transferred for up to 4 h after fractionation in gels containing acrylamide concentrations of 5%, 7.5%, 10% or 12%. Proteins less than 150 kDa were transferred with particularly high efficiency in greater than or equal to 2 h. Different antigens were recognized by the IgA, the IgG and the IgM molecules from the same sera. The methods outlined herein are proving to be useful in monitoring the purification of specific antigens from whole tumor cell extracts.
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PMID:Use of human antibodies to identify antigens in cultured human tumor cells: detection of discrete antigen molecules using electroblotting and enzyme-linked antibody probes. 635 16

An IgM monoclonal antibody, D6.1, has been obtained by fusion of P3 X 63Ag8.653 with spleen cells from congenitally athymic nu/nu mice immunized with partially purified human melanoma TAA bound to insolubilized lens culinaris lectin. The D6.1-defined antigen is present on the cell membrane of melanoma cells maintained in tissue culture but is not detected in spent culture media. Eighteen of twenty-three melanoma cell lines tested were found to react with D6.1, in contrast to only 17% of nonmelanoma tumor cell lines. Among those reactive nonmelanoma tumor lines were 3/3 colon adenocarcinomas tested. Melanoma cells, in general, express greater quantities of this antigen than do reactive nonmelanomas. Similar data were obtained using immunoperoxidase techniques on frozen sections of fresh tumor. All melanomas tested (8/8) stained intensely, although there was tumor cell heterogeneity. D6.1 reacted, but generally less intensely, with 42% (18/42) of the nonmelanoma tumors tested, including 7/8 colon carcinomas, but with smaller percentages of all other tumor types. D6.1 lightly stained normal stroma in many tissues and reacted strongly with macrophages but not with epithelial tissues. By HPLC filtration, the D6.1-defined TAA from detergent-solubilized melanoma cell membranes was determined to have an apparent molecular weight of 150,000 to 280,000 daltons. D6.1 does not precipitate TAA from exogenously (125I) or endogenously (35S-methionine, 33H-leucine, 33H-glucosamine) labeled melanoma cells.
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PMID:D6.1, a murine antimelanoma monoclonal antibody from congenitally athymic nude mice immunized with purified melanoma tumor-associated antigen. 639 96

Retinoic acid inhibits the proliferation of the murine melanoma clone S91-C-2 cells, enhances the glycosylation of specific cell surface sialoglycoproteins, and stimulates sialytransferase activity. Mutant clones, selected from the S91-C-2 cells for resistance to the growth-inhibitory effect of retinoic acid, were used to explore whether cell surface modulation by retinoic acid is related to growth inhibition. Glycoprotein synthesis was assessed by analysis of [3H]glucosamine incorporation into glycoconjugates, and cell surface sialo- and galactoglycoproteins were analyzed after radiolabeling by the NaIO4:NaB3H4 and the neuraminidase plus galactose oxidase:NaB3H4 methods, respectively. The cells were solubilized and the labeled molecules were separated by polyacrylamide gel electrophoresis and identified by fluorography. Sialytransferase activity was measured in detergent-solubilized cells, using cytidine 5' -monophosphate-[14C]sialic acid as a sugar donor and asialofetuin as an exogenous acceptor. The results demonstrated that retinoic acid enhanced [3H]glucosamine incorporation into a Mr 160,000 glycoprotein in the S91-C-2 cells but not in any of the resistant mutant clones, while the pattern of [35S]methionine-labeled proteins was not modified in either the sensitive or the resistant clones. Radiolabeling of a Mr 160,000 sialoglycoprotein on the surface of S91-C-2 and of several retinoic acid-sensitive subclones of S91-C-2 was augmented by retinoic acid. A considerably smaller effect was observed on the labeling of Mr 160,000 sialoglycoprotein on one of the resistant clones, and no significant effect could be detected on the other resistant mutant clones. Sialytransferase activity was increased 2- to 3-fold by retinoic acid in the S91-C-2 cells and in several sensitive subclones, but not in any of the resistant mutant clones. Tetradecanoylphorbol acetate, which inhibits the proliferation of both retinoic acid-sensitive and retinoic acid-resistant cells, failed to increase either sialyltransferase activity or cell surface labeling of sialoglycoproteins. These findings suggest that the ability of retinoic acid to stimulate sialyltransferase activity and glycosylation of cell surface glycoproteins is related to the growth-inhibitory effect of this compound.
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PMID:Correlation of retinoic acid-enhanced sialyltransferase activity and glycosylation of specific cell surface sialoglycoproteins with growth inhibition in a murine melanoma cell system. 649 40

Two human melanoma cell lines, extremely different in their thermal sensitivity, were pulse-labelled with (35S)-methionine after 60 min of exposure at 42 degrees C. For both cell lines, fractionation of the intrinsically labelled proteins by polyacrylamide gel electrophoresis (PAGE) showed increased labelling of a polypeptide band of Mr 72,000, along with a slight reduction of overall protein synthesis. By two-dimensional electrophoresis, the Mr 72,000 band resolved into multiple pattern components of the same size but differing in isoelectric points. The absence of qualitative and quantitative differences between the two melanoma cell lines indicates that the different thermal sensitivities are unrelated to their ability to express the heat-shock proteins.
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PMID:Heat-shock proteins produced by two human melanoma cell lines: absence of correlation with thermosensitivity. 650 Jul 44

Two human melanoma cell lines, largely different from one another in their intrinsic thermosensitivity, were exposed to supranormal temperatures and labeled with 35S-methionine. The protein patterns resolved by SDS-polyacrylamide gel electrophoresis showed in both cell lines an increased synthesis of a unique set of heat shock proteins (HSP) of 72 Kdalton (KD). Already evident after 15 min at 42 degrees C, the relative rate of synthesis of these HSP increased progressively for up to 3 h of continuous heat treatment. The cells exposed for 1 h at 42 degrees C and then returned to 37 degrees C maintained a high relative rate of HSP synthesis for more than 6 h. The rate of decay of the neosynthesized HSP did not differ from that of the overall cell proteins. Since in both cell lines all the parameters concerning HSP induction were identical, no correlation can be established between their intrinsic sensitivity towards the conditioning treatment and the capacity to respond to heat treatment with an increased synthesis of these proteins.
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PMID:Modulation of heat shock protein synthesis in two human melanoma cell lines. 650 23


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