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

Immunoglobulins were isolated by affinity chromatography from sera of two patients with melanoma, one with sarcoma, and one with carcinoma. The affinity columns were prepared by covalently linking the membrane-rich fraction of biopsied melanoma cells to cyanogen bromide-activated agarose beads. The membrane-rich fractions were prepared by two methods: (a) hypotonic cell lysis, and (b) homogenization and differential centrifugation. Melanoma sera were autologous to melanoma membrane preparations. The isolated immunoglobulins showed immunoreactivity against antigens prepared from melanoma, sarcoma, and carcinoma cells by complement fixation but not against antigens prepared from normal human liver and lung tissues. Absorption of the isolated immunoglobulins with rabbit anti-human immunoglobulin immunobeads resulted in complete elimination of the complement-fixing antibody titer in one instance, whereas reduction occurred in other samples. Similar absorption with rabbit anti-human immunoglobulin M immunobeads resulted in reduction, but not complete elimination, of the antibody titers against target tumor cell preparations. These results suggest the presence of immunoreactive immunoglobulin G in all immunoglobulins and immunoglobulin M in some. Absorption of the isolated immunoglobulins with cultured sarcoma cells reduced but did not completely abolish antibody activity against autologous or allogeneic melanoma target antigen, whereas it did completely abolish activity against sarcoma target antigen. However, absorption with cultured allogeneic melanoma cells abolished the antibody activity against melanoma as well as sarcoma target antigens. The antibody titers of the isolated immunoglobulins were not affected by absorption with cultured lymphoblastoid cells. Since cultured melanoma and sarcoma cells were known to contain oncofetal antigen(s), these results suggest that the isolated immunoglobulins from cancer sera by melanoma membrane affinity chromatography were of at least two specificities: (a) antioncofetal; and (b) antitumor associated. The former group may be comprised of antibody to cross-reactive antigens associated with different histological types of tumors. However, it was apparent that a portion of the antibody activity was against common tumor-associated antigen(s). These results provide further evidence for the presence of common antigen(s) associated with biopsy specimens of human malignant melanoma.
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PMID:Isolation and immunochemical characterization of antibodies from the sera of cancer patients which are reactive against human melanoma cell membranes by affinity chromatography. 42 6

Abnormal proteins in neoplastic cells are present in a variety of animal tumor systems. Our laboratory has isolated several of these abnormal proteins from murine malignant melanoma by preparative gel electrophoresis; these proteins are similar in many respects to analogous proteins found in normal tissues. Examination of these proteins by polyacrylamide gel electrophoresis, amino acid analysis, carboxy and amino terminal analysis and peptide mapping after cyanogen bromide cleavage, supports the theory that these abnormal proteins are the result of deleted sequences in the peptide chain during the attempted synthesis of normal proteins in neoplastic tissue.
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PMID:Abnormal protein synthesis in malignant melanoma cells. 55 7

The treatment of a B16 melanoma cell line with 2.45-GHz pulsed microwaves (10 mW/cm2, 10-microseconds pulses at 100 pps, 1-h exposure; SAR, 0.2 W/kg) resulted in changes of membrane ordering as measured by EPR (electron paramagnetic resonance) reporter techniques. The changes reflected a shift from a more fluid-like phase to a more solid (ordered) state of the cell membrane. Exposure of artificially prepared liposomes that were reconstituted with melanin produced similar results. In contrast, neither B16 melanoma cells treated with 5-Bromo-2-Deoxyuridine (3 micrograms/day x 7 days) to render them amelanotic, nor liposomes prepared without melanin, exhibited the microwave-facilitated increase of ordering. Inhibition of the ordering was achieved by the use of superoxide dismutase (SOD), which strongly implicates oxygen radicals as a cause of the membrane changes. The data indicate that a significant, specific alteration of cell-membrane ordering followed microwave exposure. This alteration was unique to melanotic membranes and was due, at least in part, to the generation of oxygen radicals.
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PMID:Modification of membrane fluidity in melanin-containing cells by low-level microwave radiation. 131 76

A model system for testing the efficacy of chemotherapy protocols for metastatic melanoma was established using cell cultures from two brain and three lymph node metastases of melanoma from five different patients. Continuously growing cultures which were positive for tyrosinase activity were analysed regarding their proliferation rate by continuous bromodeoxyuridine (BrdU) labelling and subsequent Hoechst-33258/ethidium bromide flow cytometry. Melanoma cell cultures exhibit a strong sensitivity to BrdU: at 5% oxygen, 50% growth inhibition is attained with 360 +/- 130 microM BrdU (range: 130-520; n = 11) vs 650 +/- 50 microM BrdU (n = 3) for diploid human fibroblasts and 570 +/- 20 microM BrdU (n = 6) for human lymphoid cell lines. Moreover, BrdU sensitivity of melanoma cells is clearly oxygen dependent: 50% growth inhibition at 200 +/- 55 microM (range: 65-400 microM) for 20% oxygen vs 360 +/- 130 microM BrdU for 5% oxygen. The cell cycle kinetic mechanism of BrdU-induced growth inhibition is accumulation of cells in the first cycle G2 phase. On the basis of these results we suggest testing BrdU in chemotherapy protocols for the treatment of metastatic melanoma.
Melanoma Res 1992 Nov
PMID:Bromodeoxyuridine hypersensitivity of metastatic melanoma cells. 149 Jan 11

Clinical and experimental observations suggest that tumor-induced endothelial cell injury may be one of several initial events in the establishment of tumor metastases. To test this hypothesis, the authors have analyzed the interaction of malignant melanoma (ST-ML-12) multicenter tumor spheroids with endothelial cell monolayers in a three-dimensional coculture system. After 1.5 hours of interaction, the authors observed a toxic effect on endothelial cells in the perispheroid region. The latter was demonstrated by testing membrane integrity with the fluorescent probes acridine orange/ethidium bromide and resulted in sensitivity to shear stress of the damaged cells. The endothelium then underwent a regenerative cycle to replace the denuded halo. Addition of the oxygen radical-scavenging enzyme superoxide dismutase to the culture medium prevented this endothelial cell damage in a dose-dependent manner for up to 12 hours. By contrast, catalase, deferoxamine mesylate, allopurinol, and the proteinase inhibitors soybean trypsin inhibitor and aprotinin were not protective under the same conditions. The endothelial damage was dependent on the attachment of the spheroids. Medium conditioned by ST-ML-12-spheroids proved to be ineffective. A similar, but less prominent, deleterious effect was seen when human peritoneal mesothelial cells were used in place of the human umbilical vein endothelial cells. Spheroids of the uroepithelial cell line HU-609 were used as control. No toxicity was observed in these cocultures. Melanin biosynthesis is associated with the production of oxygen-derived free radicals. The results suggest a possible implication of these free radicals in metastasis formation of malignant melanoma.
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PMID:Interaction of human malignant melanoma (ST-ML-12) tumor spheroids with endothelial cell monolayers. Damage to endothelium by oxygen-derived free radicals. 151 67

Autotaxin (ATX) is a potent human motility-stimulating protein that has been identified in the conditioned medium from A2058 melanoma cells. This protein has been purified to homogeneity utilizing a strategy involving five column steps. Homogeneity of ATX was verified by two-dimensional gel electrophoresis. The molecular size of ATX is 125 kDa, and it has an isoelectric point of 7.7 +/- 0.2. Purified ATX was digested with cyanogen bromide and trypsin, and the resulting ATX peptides were purified by reverse-phase high performance liquid chromatography. Eleven peptides were subjected to amino acid sequence analysis, and 114 residues were identified. The partial amino acid sequences and the amino acid composition obtained for ATX show that it does not exhibit any significant homology to known growth factors or previously described motility factors. At picomolar concentrations, ATX stimulates both random and directed migration of human A2058 melanoma cells. Pretreatment of the melanoma cells with pertussis toxin abolishes the response to purified ATX, indicating that ATX stimulates motility through a receptor acting via a pertussis toxin-sensitive G protein.
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PMID:Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. 173 49

To investigate the possibility that anticancer drugs combined with cytokines may show increased activity, human tumor cells were treated with combinations of human recombinant interleukin 1 alpha (rIL-1 alpha) and etoposide (VP-16). The cytotoxicity of these combinations was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay using rIL-1 alpha-sensitive A375-C6 melanoma cells and A375-C5 cells, a clonal variant line that is resistant to IL-1 alpha. Data were analyzed for synergism by the median effect principle of T-C. Chou and P. Talalay (J. Biol. Chem., 252: 6438-6442, 1977). At a dose ratio of VP-16 to rIL-1 alpha of 12 nM:1 unit/ml in either simultaneous or sequential exposure (VP-16 first), the calculated combination index values indicated synergistic cytotoxicity toward both A375-C6 cells and A375-C5 cells. IL-1 alpha treatment 24 h prior to VP-16 exposure had no advantage over simultaneous treatment. Surface IL-1 alpha receptors on both A375-C6 and A375-C5 cells were measured using 125I-radiolabeled rIL-1 alpha binding; A375-C6 cells had 701 +/- 128 (SD) receptor molecules/cell and A375-C5 cells only had 58 +/- 33 receptor molecules/cell. The dissociation constants for IL-1 alpha were similar in both cell types (19 +/- 6 pM for A375-C6 and 17 +/- 2 pM for A375-C5). The specific binding of rIL-1 alpha to the surface IL-1 alpha receptors of both sensitive and resistant cells was significantly increased in a dose-dependent fashion by the prior treatment with VP-16 (1.75-fold on A375-C6 cells and 3.5-fold on A375-C5 cells). VP-16 also enhanced the internalization of receptor-bound rIL-1 alpha, suggesting that a possible mechanism of the synergistic cytotoxicity of rIL-1 alpha and VP-16 might be related to the modulation of rIL-1 alpha receptors by VP-16, resulting in increased internalization of rIL-1 alpha.
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PMID:A role for the interleukin 1 receptor in the synergistic antitumor effects of human interleukin 1 alpha and etoposide against human melanoma cells. 182 25

Topsentin, a bis(indolyl)imidazole marine natural product, inhibited the proliferation of cultured human and murine tumor cells at micromolar concentrations (IC50 values ranged from 4 to 40 microM) and was active against in vivo P388 leukemia (%T/C = 137, 150 mg/kg, QD1-5) and B16 melanoma (%T/C = 144, 37.5 mg/kg, QD1-9) tumors. Effects of 30 microM topsentin (1-hr exposures) on incorporation of radiolabeled precursors by P388 cells indicated inhibition of DNA synthesis (91%) and to a lesser extent RNA synthesis (57%), whereas synthesis of protein was unaffected (0%). Fluorescence spectral changes and competitive binding experiments with ethidium bromide indicated that topsentin interacted with DNA. No evidence for intercalation was observed in DNA unwinding studies, but competitive binding experiments with Hoechst 33342 and CC-1065 indicated that topsentin bound to DNA in the minor groove.
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PMID:Antitumor activity and biochemical effects of topsentin. 186 31

In medium containing low concentrations of serum, rat 13762NF mammary adenocarcinoma cell lines and clones (MTPa and MTC; isolated from the locally growing tumor) of low metastatic potential to lung did not exhibit a growth response to lung-conditioned medium, whereas a highly metastatic cell clone isolated from a spontaneous lung metastasis (MTLn3) did. The major growth-promoting factor for MTLn3 cells from porcine and rat lung-conditioned media was isolated by using a five-step procedure (anion exchange chromatography, Affi-gel blue affinity chromatography, chromatofocusing, size exclusion chromatography, and preparative native gel electrophoresis). The lung-derived factor that stimulated the growth of highly metastatic MTLn3 cells was a glycoprotein of Mr approximately 66,000 (non-reduced) or Mr approximately 72,000 (reduced) and possessed a pI of 6.9-7.0. It preferentially promoted the growth of lung-metastasizing tumor lines over their poorly lung-metastasizing counterparts in three tumor systems: rat 13762NF mammary adenocarcinoma, murine B16 melanoma, and murine RAW117 large-cell lymphoma. The factor's growth-stimulatory affect was inactivated by reduction or exposure to high temperature (95 degrees C). Although the growth factor appears to be glycosylated, its molecular weight was not altered by treatment with the protein-deglycosylating agent, trifluoromethane sulfonic acid. Cleavage of the protein by cyanogen bromide resulted in the formation of five fragments. Malignant cell response to this lung-derived paracrine growth factor may be important in the successful formation of lung metastases.
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PMID:Purification and characterization of a Mr approximately 66,000 lung-derived (paracrine) growth factor that preferentially stimulates the in vitro proliferation of lung-metastasizing tumor cells. 216 61

HO-221, N-[4-(5-Bromo-2-pyrimidinyloxy)-3-chlorophenyl]-N'-(2-nitrobenzoyl ) urea is a novel benzoylphenylurea derivative. We had interested in various pharmacological actions of benzoylphenylurea compounds. Therefore, many compounds were synthetized and tested in various screening systems. In the process with these tests, we found HO-221 which showed an excellent antitumor activity. The antitumor activity of HO-221 was judged from the survival time and the tumor weight of experimented tumor-bearing animals. HO-221 preparation was orally administered. The compound exhibited significant effects against various animal tumors (P388, L1210, M5076, LLC, C38, S180, W256), and especially effective against the solid tumors. HO-221 was also markedly effective to MX-1 and LX-1 implanted into nude mice. However, the effect against mouse B16 melanoma was moderate. In addition, HO-221 showed a schedule dependency and once every 4 or 7 days treatments were most effective. The antitumor activities of the compound against advanced L1210 and Lewis lung tumors were examined. Tegafur and ara-C were used as reference drug for the study. Three agents showed the antitumor activities against L1210. Against Lewis lung carcinoma, HO-221 showed both the increase of life span and the tumor growth inhibition. On the other hand, tegafur and ara-C were ineffective for the increase of life span.
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PMID:[Antitumor effect of a benzoylphenylurea derivative HO-221]. 226 Aug 71


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