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)

An HTLV-III/LAV antibody-positive homosexual man in whom disseminated malignant melanoma developed is described. Immunologic analysis revealed an increase in suppressor/cytotoxic phenotype (Leu-2-positive) T cells, depressed proliferative response to mitogens, decreased proportions of T cells with interleukin-2 receptors but normal production of both interleukin-2 and interleukin-1, cutaneous anergy, elevated levels of serum IgG and IgA, and presence of autoantibodies against smooth muscle and parietal cells of the stomach. This case stresses the need for reporting all types of neoplasms associated with exposure to HTLV-III/LAV so that their true incidence in the population "at risk" for the acquired immune deficiency syndrome can be determined.
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PMID:Malignant melanoma in a homosexual man with HTLV-III/LAV exposure. 364 30

Tyrosine countertransport was used to demonstrate the existence of a carrier system for neutral amino acids in the lysosomal membrane of FRTL-5 thyroid cells. In addition to tyrosine, the carrier system recognized the neutral amino acids leucine, histidine, phenylalanine, and tryptophan. Cystine and lysine, amino acids for which a lysosomal carrier system has been demonstrated, showed no competition with tyrosine for countertransport. The tyrosine system showed stereospecificity and cation independence. It did not require an acidic lysosome or the availability of free thiols. The apparent Km for tyrosine was approximately 100 microM; the energy of activation of the system was approximately 9.7 kcal/mol. This new lysosomal membrane carrier system for neutral amino acids resembles the plasma membrane L system in 3T3 Chinese hamster ovary cells and melanoma B-16 cells.
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PMID:Characteristics of a lysosomal membrane transport system for tyrosine and other neutral amino acids in rat thyroid cells. 378 56

Two newly synthesized nitrosoureido sugars have been evaluated for their antitumor activity and diabetogenic potential in a number of in vitro and in vivo preclinical tumor model systems. 2-Amino-2-deoxy-N'-methyl-N'-nitrosoureido-1,3,4,6-tetra-O-acetyl-alpha- D- mannopyranose (MAZ), a lipophilic mannosamine derivative, and ethyl-6-deoxy-3,5-di-O-methyl-6-(3-methyl-3-nitrosoureido)-alph a- D-glucofuranoside (EDOMEN or CGP 6'809), were both found to inhibit L1210 leukemia cell growth in vitro by 50% at approximately 5.0 X 10(-5) M. At these concentrations, little effect was noted immediately on L1210 cell radiolabeled precursor incorporation; however, at higher concentrations, EDOMEN inhibited [3H]leucine and [3H]mannose incorporation, while MAZ specifically decreased L1210 cell [3H]thymidine and [3H]leucine incorporation. Inhibition of Lewis lung carcinoma and B16 melanoma cell growth by 50% in vitro was achieved at higher concentrations of these agents (10(-4) to 10(-3) M). Since the currently available nitrosoureido sugars, streptozotocin and chlorozotocin, have been observed by us to be diabetogenic, EDOMEN and MAZ were evaluated for their specific toxicity to rat pancreatic beta-cells in vitro. Cytotoxicity in beta-cell cultures was monitored both by phase-contrast microscopy and the release of insulin into the culture medium. beta-Cells were found to be 10-fold more sensitive to the toxic effects of MAZ than were pancreatic fibroblasts. EDOMEN, on the other hand, did not damage beta-cells preferentially and therefore was not considered diabetogenic. Both MAZ and EDOMEN had moderate activity as antileukemic agents in mice. At 50 mg/kg/day i.p. for 5 days, MAZ increased the life span of female DBA/2J mice with L1210 leukemia by over 50%. Similarly, doses of EDOMEN at 125 to 250 mg/kg/day i.p. for 5 days increased L1210 leukemic life span by nearly 60%. At these doses, no effect of MAZ was observed on primary Lewis lung carcinoma growth or life span of tumor-bearing C57BL/6 mice. EDOMEN, however, increased life span in Lewis lung carcinoma mice by up to 33% and caused an apparent antimetastatic effect. These studies indicate that EDOMEN may have enhanced value as a cancer chemotherapeutic agent due to its therapeutic effectiveness, lack of diabetogenic potential, and other favorable formulation properties (water solubility) as compared with other clinically available nitrosoureas.
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PMID:Therapeutic and diabetogenic potential of two newly synthesized nitrosoureido sugars. 388 Nov 70

The present study characterizes the biological response of a cloned human melanotic melanoma cell line (NEL-M1) to glucocorticoid treatment. Scatchard analysis of the binding of [3H]-triamcinolone acetonide to the glucocorticoid receptor showed a binding capacity of 170 fmol/mg protein and a dissociation constant (KD) of 1.76 X 10(-9) M. When the 3H-labeled cytosol was warmed to 25 degrees C for 30 min and then incubated with DNA-cellulose at 4 degrees C for 45 min, 32% of the specific glucocorticoid-receptor complexes were bound to DNA-cellulose. Additional studies showed that when NEL-M1 cells were cultured for 72 h with 1 X 10(-7) M triamcinolone acetonide, a 36% reduction in cellular growth was observed compared to the control cultures. The calculated population doubling time for the control cells was 17.5 h compared to 20.3 h for the triamcinolone acetonide-treated cells. Analysis of the effect of triamcinolone acetonide on macromolecular synthesis revealed that, over a 24-h incubation period, triamcinolone acetonide (a) inhibited [3H]thymidine incorporation by 51%; (b) increased the incorporation of the melanin precursor, L-3,4-dihydroxy[3H]phenylalanine, by 59%; and (c) had essentially no effect on [3H]leucine or [3H]uridine incorporation. During this same incubation period, triamcinolone acetonide inhibited [3H]glucose uptake by 19%. Further studies using synchronized NEL-M1 cells clearly show that the earliest detectable action of triamcinolone acetonide was the inhibition [3H]thymidine incorporation during the S phase of the cell cycle. Thus, these findings show that the human melanoma cell line, NEL-M1, is biologically responsive to glucocorticoid treatment. Continued studies using NEL-M1 cells may eventually lead to ascertaining the exact mechanism by which glucocorticoids regulate DNA synthesis.
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PMID:Suppression of DNA synthesis in NEL-M1 human melanoma cells by triamcinolone acetonide. 391 42

A low-molecular-weight cytotoxic protein has been purified from Pyrularia pubera Michx. (Santalaceae). By comparison with the behavior of proteins of known molecular weight during Sephadex G-75 gel filtration and denaturing electrophoresis, a molecular weight of somewhat less than 6000 is indicated. Purification involves ammonium sulfate fractionation followed by either gel filtration on Sephadex G-75 or separation on a carboxymethyl cellulose CM52 column. At concentrations of 0.04 mg/ml the protein causes visible disruption of cultured mouse B16 melanoma cells. The complete amino acid sequence has been determined. The toxin contains 47 amino acids arranged as follows:Lys-Ser-Cys-Cys-Arg-Asn-Thr-Trp-Ala-Arg-Asn-C ys-Tyr-Asn-Val-Cys-Arg-Leu-Pro-Gly-Thr-Ile-Ser-Arg-Glu-Ile-Cys-Ala-Lys- Lys-Cys-Asp-Cys-Lys-Ile-Ile-Ser-Gly-Thr-Thr-Cys-Pro-Ser-Asp-Tyr-Pro-Ly s-OH. The protein is clearly a thionin, as shown by its close resemblance to the thionins from wheat and barley, to the viscotoxins from mistletoes, and to crambin.
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PMID:A toxic thionin from Pyrularia pubera: purification, properties, and amino acid sequence. 398 14

Cytotoxic immune response by autologous natural killer (NK) cells against a spontaneous in vitro transformed tumorigenic fibroblast line, VIP-F:T, was studied in a 4 h 51Cr-release microcytotoxicity assay and in a tumor cell neutralization technique in vivo in nude mice. Although highly cytotoxic against the NK prototype target K562, the autologous NK cells in their nascent state were only marginally cytotoxic against VIP-F:T and unreactive against the autologous normal fibroblasts, Pen-F2. Autologous NK activity against VIP-F:T could, however, be induced by 2-16-h treatment of the NK cells with several species of interferon and by interferon-free interleukin 2 (IL-2). In vitro co-culture (IVC) in IL-2 of autologous peripheral blood lymphocytes (PBL) against VIP-F:T was shown by fluorescence activated cell sorting and by cold target competition experiments to generate almost exclusively an effector population bearing HNK-1 and Leu-11a phenotypes which exhibited receptor specificity for VIP-F:T distinct from receptors on Pen-F2 or K562 cells. PBL, co-cultured in IL-2 against Pen-F2 or K562, or cultured in IL-2 alone, generated high levels of nonspecific killing and showed no receptor specificity. Identical IVC in IL-2 of autologous PBL against a melanoma line, VIP (PBL and the VIP line derived from the same patient from whom the VIP-F:T line was also derived), and similar IVC in IL-2 of several other autologous PBL against their corresponding target cell lines (established from surgical specimens) generated cytotoxic responses involving cytotoxic populations bearing T8 as well as HNK-1 phenotypes; but the cytotoxic activities in none of these systems showed target receptor specificity. Autologous PBL, co-cultured against VIP-F:T in IL-2, were shown to be capable of rejecting tumorigenic challenge with VIP-F:T.3 (a clone of VIP-F:T) in nude mice at effector to VIP-F:T ratio of 10:1. The protective effect of the co-culture activated PBL was abrogated if the HNK-1+ cells were depleted from the effector population. Our data, thus, demonstrate specificity of cytotoxic reactivity which, by phenotypic markers, can be characterized as HNK-1 and Leu 11a+ cells under these experimental conditions against this particular in vitro transformed VIP-F:T line. In addition, this study shows that similar studies of cytotoxic autologous reactivities against in vitro transformed target cell lines will provide valuable information on the subject of NK-mediated surveillance against human neoplasia.
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PMID:In vitro cytotoxicity and transplantation protection by autologous natural and activated killer cells against an in vitro transformed tumorigenic fibroblast line. A case study. 398 36

Human blood monocytes, separated on a continuous percoll gradient, were not cytotoxic to allogeneic A375 melanoma cells. The monocyte monolayers were activated to become tumoricidal by incubation for 24 hr with interferon (IFN)-alpha or beta at concentrations of more than 1,000 IU/ml. Significant and reproducible activation of the monocytes was achieved by incubating them with 10,000 IU/ml of IFN-alpha or IFN-beta for 24 hr. Similarly, suspended, but not plated, monocytes were activated to a tumoricidal state by interaction with IFN-alpha or IFN-beta. Monocytes that had lost tumoricidal activity during culture, were reactivated by a second exposure to IFN-alpha. Fluorescence analysis showed that the monocyte-rich adherent monolayers were contaminated with up 2.0% of natural killer (NK) cells. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibody (Leu-11b) to deplete them of NK cell activity did not inhibit the monocyte-mediated cytotoxicity. These results indicate that human monocytes are rendered tumoricidal by direct interaction with IFN-alpha or IFN-beta, although more than 1,000 IU/ml of IFN-alpha or IFN-beta is required for maximal expression of monocyte activation.
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PMID:[Induction of human monocyte-mediated tumor cell killing by alpha or beta interferon]. 399 98

Human blood monocytes, separated on a Percoll gradient, were not cytotoxic to allogeneic melanoma (A375) cells. Fluorescent analysis showed that the monocytes were contaminated with up to 2.0% natural killer (NK) cells. The monocytes became tumoricidal on incubation for 24 h with greater than or equal to 1,000 IU/ml interferon-alpha (IFN-alpha) derived from human lymphoblastic leukemia cells. Anti-IFN-alpha antibody abolished the ability of IFN-alpha to render the monocytes tumoricidal, whereas anti-IFN-beta antibody had no effect. Pretreatment of isolated monocyte preparations with anti-NK cell monoclonal antibodies (Leu-7 and Leu-11b), to inhibit NK cell activity, did not affect the cytotoxicity of IFN-alpha-activated monocytes on tumor cells. Full expression of cytotoxicity on tumor cells required the interaction of monocytes with IFN-alpha for 24 h. These results indicate that IFN-alpha directly activates human monocytes to become tumoricidal, although greater than or equal to 1,000 IU/ml IFN-alpha is required for maximal activation.
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PMID:Induction by interferon-alpha of tumoricidal activity of adherent mononuclear cells from human blood: monocytes as responder and effector cells. 399 64

A series of hybridoma clones, each producing monoclonal antibodies to human tissue-type plasminogen activator (t-PA), were prepared from mice by standard procedures. Two of these clones were selected for further study. One HI72A1, produced antibodies that bound to t-PA and strongly inhibited its activity, whereas another, LI72D1, produced antibodies that bound to t-PA but did not affect its activity. The specificity of these antibodies was assessed in immunoabsorption experiments. Both immunoprecipitated 125I-labeled t-PA, and both were specific since only t-PA was recognized in conditioned media collected from Bowes melanoma cells cultured in the presence of 3H-leucine. Neither antibody recognized urokinase. t-PA was desorbed from antibody HI72A1-Sepharose columns with 0.5 M NaCl, consistent with its relatively low association constant (Ka = 9.37 X 10(7) M-1). In contrast, a strong chaotropic agent (i.e., 2 M KI) was required to elute t-PA from antibody LI72D1 columns (Ka = 2.08 X 10(9) M-1). This latter high affinity antibody was employed to develop an immunoradiometric assay for t-PA having a sensitivity of 0.5 ng/ml.
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PMID:Characterization of two monoclonal antibodies against human tissue-type plasminogen activator. 404 Jun 58

Dormant macrophage nuclei initiate DNA synthesis 2-3 hr after fusion of macrophages with exponentially growing melanoma cells. Cycloheximide treatment (1-5 microg/ml) of heterokaryons during the preceding lag period inhibits the initiation of macrophage DNA synthesis, in a reversible fashion. Each type of cell was also treated with streptovitacin A, an irreversible inhibitor of protein synthesis. Pretreatment of the melanoma cells (0.5-2 microg/ml), 1 hr before fusion, inhibited the induction of macrophage DNA synthesis in heterokaryons, whereas pretreatment of macrophages (1-20 microg/ml) had no effect. Melanoma cell pretreatment reduced the incorporation of leucine-(3)H into the cytoplasm and nuclei of heterokaryons, whereas macrophage pretreatment had no effect. These experiments suggested that melanoma proteins played an important role in the initiation of macrophage DNA synthesis. The relationship between the melanoma cell cycle and macrophage DNA synthesis was studied with synchronous melanoma cells. If the melanoma cells were in S phase at the time of fusion, macrophage DNA synthesis occurred 2 hr later. However, the fusion of melanoma cells in G(1) delayed macrophage DNA synthesis until the melanoma nuclei had entered S. Experiments with actinomycin and cycloheximide showed that RNA and protein, essential to achieve DNA synthesis in the macrophage nucleus, were made during late G(1) as well as S. Melanoma cells and macrophages differ in their radiolabeled acid-soluble products after incubation in thymidine-(3)H. Thymidine taken up by the macrophage remained unphosphorylated, whereas it was recovered mainly as thymidine triphosphate from melanoma cells. These findings, as well as those reported previously, suggest that the melanoma cell provides the RNA, protein, and precursors which initiate macrophage DNA synthesis. In the absence of a requirement for new macrophage RNA and protein synthesis, other changes must be responsible for the 2 hr delay in DNA synthesis. These may involve physical changes in DNA, associated with swelling, as well as the transport of melanoma products into the macrophage nucleus.
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PMID:Macrophage-melanoma cell heterokaryons. 3. The activation of macrophage DNA synthesis. Studies with inhibitors of protein synthesis and with synchronized melanoma cells. 410 91


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