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)

Melanogenesis in mammalian pigment cells is regulated by changes in the activity of tyrosinase, the rate-limiting enzyme for melanin synthesis. Because recent evidence suggests that this enzyme may exist in pigment cells in both active and inactive stages, a competitive enzyme-linked immunoadsorbent assay (ELISA) was developed to compare tyrosinase levels in amelanotic and melanotic melanoma cell clones. The melanotic cell line used for this study, MEL-11A, had basal tyrosinase levels approximately 40 times that of the amelanotic cell line, AM-7. Both cell lines responded to melanocyte-stimulating hormone by demonstrating large increases in tyrosinase activity. For competitive ELISA analysis of tyrosinase levels in these two clones, microtiter plates were coated with purified tyrosinase, and trypsinized cell extracts were tested for their ability to compete with bound tyrosinase for antibody binding. Although tyrosinase activity in the amelanotic clone was 1/40 that of the melanotic clone, immunoreactive tyrosinase levels in AM-7 cells were found to be approximately one-half that present in the melanotic clone. Additional evidence for the presence of an inactive (or at least, catalytically less active) enzyme in AM-7 cells was obtained from immunotitration analysis of tyrosinase in cell extracts from both cell lines. These results suggest that at least some amelanotic melanoma cells may contain significant levels of catalytically inactive tyrosinase molecules and that the level of pigmentation in mammalian melanocytes may be regulated by a tyrosinase activation process.
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PMID:Comparison of tyrosinase levels in amelanotic and melanotic melanoma cell cultures by a competitive enzyme-linked immunoadsorbent assay and by immunotitration analysis. 312 44

Effects of combination treatment with human recombinant alpha-2b interferon (IFN-alpha 2b) and gamma interferon (IFN-gamma) and sequencing of the combination on colony formation of human tumor cells were studied in a human tumor clonogenic assay (HTCA) with or without ascites-associated macrophages (AAM). Five different human tumor cell lines were studied. Three of the five cell lines (ovarian cancer cell line BG-1, cervical cancer cell line ME-180, and melanoma cell line SK-MEL 28) were sensitive to both IFNs. Cervical cancer cell line CaSki was sensitive to IFN-alpha 2b but resistant to IFN-gamma. Endometrial cancer cell line HEC-1A was resistant to both IFNs. Synergistic interaction was observed in BG-1 and SK-MEL 28 with a combination of the IFNs. ME-180 did not exhibit a positive interaction, in spite of its sensitivity to each IFN. CaSki and HEC-1A also did not exhibit a positive combined interaction at clinically achievable concentrations. One sequential combination method (method 1: IFN-alpha 2b----IFN gamma with a 24-h interval) resulted in a similar antitumor effect as the simultaneous combination. A reversed sequential method (method 2: IFN-gamma----IFN-alpha 2b with a 24-h interval) was less effective in three of the five cell lines. In BG-1, AAM enclosed in the lower layer markedly enhanced the antitumor effect of combined IFNs as well as each IFN alone. The antitumor effect with method 1 was significantly greater than that achieved with simultaneous combination or combination according to method 2 in the presence of AAM (P less than 0.01). These results suggest that (1) a synergistic antitumor effect of IFN-alpha 2b and IFN gamma is demonstrable in selected types of tumors, depending upon the sensitivity of each tumor cell line to both IFNs; (2) optimal scheduling for the direct antitumor effect of combined IFNs seems to be long-term exposure of cells to the IFN, the cells being treated with both IFNs either simultaneously or sequentially (IFN-alpha 2b preceding IFN-gamma); and (3) AAM potentiate the antitumor effect of IFNs either alone or in combination. Finally, IFN-alpha 2b may have some priming effects for the indirect effect of IFN gamma mediated through AAM in certain tumor cells.
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PMID:Effects of scheduling and ascites-associated macrophages on combined antiproliferative activity of alpha-2b interferon and gamma-interferon in a clonogenic assay. 313 42

Physiochemical properties of an estrogen binding protein were characterized in three human melanoma cell lines, UISO-MEL-1, UISO-MEL-2, and UISO-MEL-4. Estrogen binding to melanoma cytosol was saturable, specific for estrogens, and represented by a single class of high-affinity, limited-capacity binding sites (Kd 5.5 x 10(-10) M, 2.7 +/- 0.5 fmol/mg of cytosol protein, UISO-MEL-2; 2.2 x 10(-10) M, 7.8 +/- 3.3, UISO-MEL-4) (SEM). UISO-MEL-1 cytosols did not bind estradiol. The binding protein in UISO-MEL-2 and -4 sedimented at 8.5S and 9.2S, respectively, in the presence of 10 mM sodium molybdate. Solid-phase radioimmunoassay with a monoclonal antibody specific for human estrogen receptor (H222 sp lambda) showed good correlation (r = 0.84) with a hydroxyapatite biochemical assay of identical melanoma cytosols. Exposure of UISO-MEL-2 to estradiol produced a time- and temperature-dependent increase in total nuclear receptor for estrogen in vitro. Estradiol treatment of athymic mice also significantly increased cytosol progesterone receptor content in UISO-MEL-2 and UISO-MEL-4 xenografts. Estradiol had no effect on the plating efficiency or growth of any melanoma cell line or normal melanocytes in vitro. Tamoxifen also had no effect on melanoma growth in vitro. In contrast, chronic exposure of athymic mice carrying estrogen receptor-positive UISO-MEL-2 to estradiol resulted in a sex-dependent increase in tumor latency and overall inhibition of tumor growth. Taken together, these observations suggest that a subset of human melanomas contains limited amounts of an estrogen binding protein similar to that observed in other estrogen-responsive tissues. The lack of effect of estradiol on melanocyte and melanoma growth in vitro, coupled with a decrease in tumor growth in athymic mice, suggests that, while inhibition may be receptor mediated, possible indirect actions of estradiol must also be considered.
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PMID:Effect of 17 beta-estradiol on the growth of estrogen receptor-positive human melanoma in vitro and in athymic mice. 319 86

Natural killer cell cytotoxic factor (NKCF), a cytotoxic factor contributing to human natural killer cell-mediated cytotoxicity, was generated from lymphocyte-conditioned medium using various stimuli. Crude NKCF activity was concentrated, and partially purified by ammonium sulfate precipitation and gel filtration. NKCF activities eluted as two molecular weight peaks, corresponding to Mr 33,000-43,000 (pool I) and approximately Mr 5,000 (pool II). The cytotoxic activity and target specificity of the partially purified NKCFs were found to be different from both recombinant human TNF and recombinant human lymphotoxin. In the NKCF assay, up to 10(6) units/ml of TNF and lymphotoxin had virtually no effect, whereas both NKCFs lysed 22% (range 17-33%) of the NK-sensitive target K562. In contrast, TNF and lymphotoxin were active in a standard assay against the sensitive murine L929 fibroblast cell line in all concentrations tested (10(-1)-10(6) units/ml). In addition, the effect of these cytotoxic factors in a short-term (4-h) chromium-release assay using peripheral blood mononuclear cells as effector cells was tested: only NKCF (pool I), but not TNF, lymphotoxin, or low molecular weight NKCF (pool II), enhanced NK and lymphokine-activated killer cell cytolysis, both against the NK-sensitive target K562 and the NK-resistant melanoma cell line SK-MEL 30. Results were not affected in the presence of neutralizing antibodies against TNF. NKCF could, therefore, be distinguished from TNF and lymphotoxin with respect to their biological activities.
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PMID:Distinction of partially purified human natural killer cytotoxic factor from recombinant human tumor necrosis factor and recombinant human lymphotoxin. 325 13

Involvement of Ia-positive nylon wool adherent cells (AC) for the expression of cytotoxic T-lymphocyte (CTL) activity specific to melanocyte-associated antigens (MAA) was studied. Although unseparated peripheral blood lymphocytes (PBL) from several patients with Vogt-Koyanagi-Harada's (VKH) disease showed significant cytotoxic activity against SK-MEL-28 (P-36) human melanoma cells which carried cross-reactive surface antigens with normal melanocytes, the cytotoxic activity of nylon wool column passed nonadherent cells (NAC) against the same target cells markedly decreased in the absence of Ia-positive nylon wool AC. The reduced cytotoxic activity of the NAC was reconstituted not only by the addition of Ia-positive AC from the same VKH patient, but also by the addition of allogeneic IA-positive AC mismatched with human leukocyte antigen (HLA) complex-DR region haplotype. Moreover, the cytotoxic activity of nylon wool NAC was augmented by the addition of interleukins instead of DR-positive AC. The data indicate that the primed CTL in patients with VKH would be stimulated nonspecifically by factors from Ia-positive cells, presumably to differentiate the precursor CTL (CTL in memory state) into mature CTL (effector cells).
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PMID:Requirement of Ia-positive nylon wool adherent cells for activation of cytotoxic T-lymphocytes specific to melanocyte-associated antigens in patients with Vogt-Koyanage-Harada's disease. 326 67

The mechanism of the cytostatic and cytocidal activities of TNF was studied in human tumour cells. BT-20 breast and ME-180 cervical cancer cells were significantly growth-inhibited by TNF, but other cells were not. When protein synthesis was inhibited by cycloheximide, however, TNF was cytotoxic for all cells except BT-20 cells. This suggests that different mechanisms are responsible for the cytostatic and cytocidal activities of TNF. The sensitivity of different cell lines could not be correlated with the number or affinity of TNF receptors. Some protease inhibitors completely protected human and murine cells from TNF cytotoxicity. Inhibitors of chymotrypsin-like proteases were more effective than inhibitors of trypsin-like proteases. Reversible and irreversible inhibitors (such as alkylating compounds) were both protective. The cells were best protected when pretreated with inhibitors before the addition of TNF. When the protease inhibitors were removed the cells gradually lost their resistance to TNF cytotoxicity. The inhibitors did not interfere with the functioning of TNF-receptor complexes, since SK-MEL-109 melanoma cells treated with a protease inhibitor synthesized TNF-induced proteins. These findings suggest that a protease is involved in the cytocidal activity of TNF.
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PMID:Cytocidal activity of tumour necrosis factor: protection by protease inhibitors. 333 13

Four monoclonal antibodies (MoAbs) (35, 115, 17-1A, and B72.3) directed towards human carcinoma surface antigens have been studied in athymic nude mice with LS174T, CO112, or SW948 colon carcinoma xenografts or negative control melanoma (MEL-1), lymphoma (Namalwa), and breast (MCF-7) carcinoma xenografts to evaluate the effects of antigenic heterogeneity and time after administration on localization and imaging. 125I-labeled 115 showed the highest uptake of any antibody in LS174T tumors. MoAbs 35 and B72.3 showed similar but lower levels of uptake in LS174T and CO112 tumors, but B72.3 concentrated less in SW948 tumors. 17-1A showed the highest degree of accumulation in SW948 tumor xenografts. No specific uptake of the four anti-carcinoma MoAbs was observed in MEL-1, Namalwa, or MCF-7 xenografts. The specificity of the in vivo tumor localization of the four anti-carcinoma MoAbs was confirmed by the low degree of accumulation of a control MoAb against influenza virus in LS174T tumors. Imaging studies with 131I-labeled colorectal cancer MoAbs showed specific uptake and retention in LS174T tumors, with progressive clearance from the whole body. The colorectal cancer MoAbs were compared for immunohistochemical binding against biopsies from patients with colorectal cancer and adjacent normal colonic tissue. Most colorectal cancer specimens showed moderate to strong staining with the four MoAbs. The percentage of positive cells varied within and between tumors demonstrating antigenic heterogeneity. Absent to slight focal staining was seen with normal colon tissue. B72.3 showed the highest degree of staining specificity. This study indicates a difference in the immunohistochemical binding of a panel of MoAbs against biopsies of colon adenocarcinoma and a dependence of in vivo localization on the human colon cancer cell line used as target. This has important implications for future clinical diagnostic and therapeutic studies.
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PMID:Localization and imaging of radiolabeled monoclonal antibodies against colorectal carcinoma in tumor-bearing nude mice. 339 Aug 28

A cell line, MEL #26, was established from a metastatic solid tumor specimen obtained from a patient with malignant melanoma. Cytogenetic analyses were performed on both the fresh biopsy specimen (using short-term culture; 2 days) and an established cell line at three different passages. The chromosome number of the fresh biopsy specimen was in the near-triploid range and the chromosome number of the cell line was tetraploid. Three stable marker chromosomes involving #1, #6, and #7 were observed both in the original tumor and cell line. The marker chromosomes involving #1 and #7 were consistently present in all passages of this line, whereas, i(6p) was not present in every metaphase; a 15p+ marker completely disappeared after passage 20. Based on the results of the present study, we conclude that exclusive of one marker chromosome, the nonrandom chromosome changes seen in the original tumor were retained by the cell line and no particular additional clonal changes occurred during in vitro growth and establishment of this cell line. These considerations are of importance in the interpretation of results of various other studies that have been (or could be) performed with this cell line.
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PMID:Cytogenetic findings in a malignant melanoma and its derived cell line. 346 80

We conducted a trial of a murine monoclonal antimelanoma antibody-ricin A chain immunotoxin (XOMAZYME-MEL) in 22 patients with metastatic malignant melanoma. The dose of immunotoxin administered ranged from 0.01 mg/kg daily for 5 days to 1 mg/kg daily for 4 days (total dose: 3.2 to 300 mg). Side effects observed in most patients were a transient fall in serum albumin with an associated fall in serum protein, weight gain, and fluid shifts resulting in edema. In addition, patients experienced mild to moderate malaise, fatigue, myalgia, decrease in appetite, and fevers. There was a transient decrease in voltage on electrocardiograms without clinical symptoms, change in serial echocardiograms or elevation of creatine phosphokinase MB isozyme levels. Symptoms consistent with mild allergic reactions were observed in three patients. The side effects were related to the dose of immunotoxin administered and were generally transient and reversible. Encouraging clinical results were observed, even after a single course of a low dose of immunotoxin. In addition, localization of antibody and A chain to sites of metastatic disease was demonstrated by immunoperoxidase staining of biopsy specimens. Additional studies are being conducted to continue the evaluation of safety and efficacy of immunotoxin therapy for malignancy.
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PMID:Therapy of patients with malignant melanoma using a monoclonal antimelanoma antibody-ricin A chain immunotoxin. 349 66

Natural killer activity against K562 targets and recombinant interleukin-2 induced cytotoxicity to NK resistant targets (MEL-4 and T24) was investigated in 15 melanoma patients. Before elective surgery no differences in cytotoxic activities were demonstrated when compared with patients with colorectal adenocarcinoma and controls. No correlation with the depth of the melanoma lesion was observed. Numbers of precursors of IL-2 induced killers in melanoma patients were in normal range. In conclusion, no defects in non-specific NK and IL-2 induced behavior in peripheral blood of melanoma patients were found. Other factors, specific, non-specific, related or unrelated to the tumor side should be thus considered.
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PMID:Effect of human recombinant interleukin-2 on cytotoxic response of peripheral blood mononuclear cells in melanoma patients before surgery. 350 Jun 90


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