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)

3-aminobenzamide (3-ABA) is an inhibitor of poly-(ADP-ribose)-polymerase, an enzyme involved in numerous subcellular processes, including cell death. Recently, a target effect of the drug on some cytoskeletal elements has also been described (Malorni et al., Biochem. Biophys. Res. Commun. 202: 915-922, 1994). In this study we evaluated the ability of 3-ABA to interfere with UV-B ray-induced apoptosis in cells selected for their cytoskeletal features and their different capability to adhere to the substrate. Human melanoma (M14) and epithelial (A431) cell lines and murine primary fibroblastic cultures (MFC) were studied. Our results indicate that cytoskeleton is indeed an important cellular target of 3-ABA, which can prevent apoptotic cell death by UV-B through a specific effect on the adhesion properties of the cells. Indeed, an inverse correlation was observed between sensitivity to UV-B-induced apoptosis (M14 > A431 > MFC) and substrate adhesion (MFC > A431 > M14). The potential relevance of these observations to understand the possible relationships among apoptosis, cytoskeletal functions and substrate adhesion is discussed.
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PMID:3-Aminobenzamide protects cells from UV-B-induced apoptosis by acting on cytoskeleton and substrate adhesion. 786 64

The intracellular distribution of the anthracyclinic antibiotic adriamycin in living cultured cells has been investigated by confocal microscopy. In human melanoma cells (M14), adriamycin was localized inside the nuclei. When adriamycin-treated M14 cells were allowed to recover in drug-free medium, a complete efflux of the drug from the nucleus was revealed. In recovered cells, a weakly fluorescent signal was observed in the perinuclear region. When M14 cells were recovered in a medium containing colcemid, a microtubule depolymerizing agent, the drug transport from the nucleus to the cell periphery appeared to be inhibited, suggesting that the microtubule network is strongly involved in drug transport mechanisms. In multidrug-resistant (MDR) cells the intracellular location of adriamycin was shown to be noticeably different from that of the parental wild-type cells. In particular, in resistant human breast carcinoma cells (MCF-7), adriamycin appeared to be exclusively located within the cytoplasm whereas the nuclei were shown to be completely negative. When adriamycin treatment was performed in association with MDR revertants, such as Lonidamine (inhibitor of the energy metabolism) or verapamil (inhibitor of the P-glycoprotein efflux pump), a marked enhancement of the cytoplasmic signal was observed in resistant cells. Under these conditions, adriamycin appeared concentrated in the perinuclear region, but the nuclei were still negative. Confocal microscopy proved to be a very useful method for the study of the intracellular transport of fluorescent substances, such as anthracyclinic antibiotics, and for the investigation of the multidrug resistance phenomenon in tumour cells.
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PMID:Intracellular localization of the antitumour drug adriamycin in living cultured cells: a confocal microscopy study. 786 63

The radiation-induced genotoxic damage in three established cell lines and 15 primary cultures of human malignant melanoma and ovarian carcinoma showing different radiosensitivity was tested by the cytokinesis-block micronucleus assay. A dose-related increase in micronucleus frequency was observed in all the cell systems. The mean number of micronuclei per Gy of ionising radiation per binucleated cell was respectively 0.44 +/- 0.0075 and 0.43 +/- 0.04 for M14 and JR8 malignant melanoma cell lines and 0.19 +/- 0.013 for the A2780 ovarian cancer cell line. The number of micronuclei did not rank the cell lines in the same order of radiosensitivity as clonogenic cell survival, which showed a surviving fraction at 2 Gy of 0.38 +/- 0.02 for JR8, 0.34 +/- 0.05 for M14 and 0.22 +/- 0.007 for A2780. As regards primary tumour cultures, no correlation was observed between micronucleus induction and surviving fraction at 2 Gy. In conclusion, the discrepancy we observed between micronucleus formation and cell death raises doubts about the potential of the micronucleus assay as a preclinical means to predict radiosensitivity.
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PMID:Lack of a correlation between micronucleus formation and radiosensitivity in established and primary cultures of human tumours. 798 Oct 62

The human monoclonal antibody (HuMAb) L92 reacts to an M(r) 43,000 protein associated with human melanoma. To identify the gene encoding its antigenic epitope, a complementary DNA expression library constructed from the human melanoma cell line UCLASO M14 was screened with HuMAb L92. DNA sequence analysis of the isolated clone revealed that the immunoreactive peptide was composed of 10 amino acids (QDLT-MKYQIF). The peptide was expressed in Escherichia coli with beta-galactosidase as a fused protein. There is no homology between the cloned sequence and other reported DNA sequences. Western blot analysis showed that the fused protein had specific binding to HuMAb L92. An antigen-encoding peptide with 10 amino acids was synthesized and tested for its immunoreactivity in vitro. HuMAb L92 reacted specifically to the 10-amino acid peptide in both an antibody-binding inhibition to the M(r) 43,000 protein and a solid-phase enzyme-linked immunosorbent assay. Using several truncated fusion proteins, we found the minimum number of amino acids required for the antibody binding to be 4 (KYQI). These results suggest that the identified peptide sequence encodes the antigenic epitope of the M(r) 43,000 protein.
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PMID:Human monoclonal antibody identified an immunoreactive tetrapeptide sequence (Lys-Tyr-Gln-Ile) in M(r) 43,000 protein of human melanoma. 801 74

3-aminobenzamide (3-ABA) is an inhibitor of poly-ADP-ribose-polymerase, an enzyme involved in numerous subcellular processes including cell death. With the aim of contributing to clarify the mode of action of the drug, which is still poorly understood, its effects on cultured melanoma cells M14 have been assessed. In particular, an impairment of cell growth accompanied by the formation of long and numerous dendritic-like protrusions has been detected. This finding appears to be due to a specific effect of the drug on some cytoskeletal elements and could be associated with its differentiating capability. This finding, together with previous data from our group--Biochem. Biophys. Res. Commun., (1994) 199, 525-530 and 1250-1255--suggests that cytoskeleton is an important target of 3-ABA.
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PMID:3-Aminobenzamide induces cytoskeleton rearrangement in M14 melanoma cells. 804 65

The modulatory activity of the polar solvent N-methylformamide (NMF) on the effects of hyperhermic treatment was investigated on a human melanoma cell line (M14). Cells treated with NMF alone (1% for 20 h), hyperthermia (Hyp) alone (42.5 degrees C for 2 h) and with the two different sequences of treatment (NMF-->Hyp and Hyp-->NMF) were analysed by scanning electron microscopy and fluorescence microscopy. Moreover, their clonogenic efficiency and adherence properties were assessed. The results obtained can be summarized as follows. (a) The sequence Hyp-->NMF appeared to be more cytotoxic than the reverse sequence or NMF and Hyp given alone. (b) Heat induced cell swelling and detachment from the substrate. The pretreatment with the polar solvent was capable of preventing such alterations. (c) Fluorescence microscopy revealed remarkable changes induced by hyperthermia on actin network, vimentin distribution and vinculin expression. NMF administration proved to be capable of modulating these changes. In particular, the actin and vimentin networks showed a quite normal arrangement in NMF-->Hyp treated cells and very altered patterns in cells treated with the reverse sequence. Concerning the effects on the adhesion plaques, revealed by vinculin labeling, a considerable increase in the expression of these structures was observed after NMF treatment. (d) A remarkable increase of the attachment to collagen I and laminin molecules was revealed in NMF treated cells, whereas heat exposure reduced the number of adherent cells. Considered all together, the results obtained indicate that the administration of NMF after hyperthermia enhances the cytotoxic effect and modifies cell adherence properties, responsible for dissemination and metastasis.
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PMID:Modulation of the effects of the hyperthermic treatment by N-methylformamide on a human melanoma cell line. 807 92

Catechols may interfere in melanogenesis by causing increased levels of toxic quinones. Several catechols and known inhibitors of the enzyme catechol-O-methyltransferase (COMT) were therefore tested for their toxicity towards a pigmented melanoma cell line, UCLA-SO-(M14). The inhibition of thymidine incorporation as a result of exposure to the compounds was measured. All agents were compared to 4-hydroxyanisole (4HA), a depigmenting agent extensively studied as an antimelanoma drug. The compounds were also tested on the epithelial cell line, CNCM-I-(221) in the presence and absence of tyrosinase. All the compounds were more effective than 4HA towards the M14-cells at either 10(-4) M or 10(-5) M. The toxicity of 4HA towards the 221-cells was shown to be completely dependent on the presence of tyrosinase. Effects of the test agents on the 221-cells were also observed in the absence of tyrosinase. Although some of them were shown to be good substrates for tyrosinase only small changes in toxicity were observed as a result of the presence of the enzyme in comparison with 4HA. No direct correlation of the toxicity of the agents and COMT inhibition was observed. The possible mode of action of the compounds through inhibition of COMT and interference in melanogenesis is discussed together with other possibilities and factors involved.
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PMID:Catechol-O-methyltransferase as a target for melanoma destruction? 808 Apr 47

Interleukin 2 (IL2) is an important regulator of the immune system. In this report, we have analysed five human melanoma cell lines expressing the IL2R for their ability to secrete IL2. In the M14 melanoma cell line, we observed the appearance of the 0.9 kb transcript specific for the IL2 gene, 72 h after subculture, and the secretion of a biologically active IL2 which specifically sustains the proliferation of the IL2 dependent murine lymphoid cell line CTLL2. In M14 cells, IL2 gene activation is transient as in lymphoid cells but is not inhibited by the immunosuppressive drugs cyclosporine-A and FK506 which are effective on PHA-blasts. In M14 cells, recombinant IL2 (36 pM) induces the down modulation of ICAM-1 expression at the surface of M14 cells. Overnight incubation of these cells with polyclonal anti-IL2 antibodies leads to an increased expression of ICAM-1 and a decreased membrane detection of the IL2R alpha, suggesting the existence of an autocrine/paracrine loop involved in the surface expression of these antigens. A decreased expression of the ICAM-1 protein could help some melanoma cells to escape from cytolytic recognition and therefore favour their metastasis.
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PMID:Human melanoma cell line M14 secretes a functional interleukin 2. 809 24

A melanoma cell line (M14) was used in order to investigate the effect of hyperthermia on the mechanisms of interaction between liposomes and cultured cells. The treatment was performed by adding different concentrations of multilamellar liposomes (L-alpha-dipalmitoylphosphatidylcholine, stearylamine and cholesterol in the ratio 7:2:1) to cell cultures which were then incubated at 37.0 or 41.5 degrees C for 2 h. The damage induced by liposome treatment in normothermia or hyperthermia was evaluated by determining cell survival and by electron microscopy. When different concentrations of liposomes were used, a dose-dependent impairment of cell survival was observed. An enhancement of the cytotoxic effect was observed when the treatment was performed at 41.5 degrees C. This effect went on even after 24 h from the end of the treatment, but the difference between cells treated in normothermia and hyperthermia was remarkably reduced. The mechanism of the liposome-plasma membrane interaction has been investigated by electron microscopy. Our observations demonstrated that the outer bilayer of the multilamellar liposomes was capable of fusing with the plasma membrane, inducing changes in its fluidity and molecular organization. Following this process the inner liposomal bilayers entered the cell. These effects seemed to be favoured when the treatment was performed under mild hyperthermic conditions, accounting for the synergic cytotoxic action displayed by the liposome-hyperthermia association.
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PMID:Effects of incubation with liposomes at different temperatures on cultured melanoma cells (M14). 814 82

The effects of sequential combinations of N-methylformamide (NMF) with adriamycin (ADM) on a human melanoma cell line (M14) were investigated. The results obtained can be summarized as follows: (i) When NMF was administered before ADM (NMF-->ADM), a decrease of ADM-induced cytotoxicity and intracellular ADM content was revealed. Conversely, the reverse combination (ADM-->NMF) produced a remarkable reduction of cell survival accompanied by a significant intracellular drug retention. (ii) The fluorescence microscopy revealed that in NMF- and in NMF-->ADM-treated cells the actin microfilament distribution appeared to be very similar to that in control cells. On the contrary, a disorganization of the microfilament architecture was observed in ADM-->NMF-treated cells. (iii) The microtubule organization was significantly altered by NMF. This effect appeared to be even more evident in M14 cells treated with the combination ADM-->NMF. (iv) Confocal microscopy observations showed an intracytoplasmic retention of ADM in ADM-->NMF-treated cells. These findings suggest that the cytoskeletal changes induced by NMF might interfere with the ADM efflux mechanisms, accounting for the high drug level and low survival detected in ADM-->NMF-treated cells.
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PMID:Effects of sequential combinations of N-methylformamide with adriamycin on cultured melanoma cells (M14). 816 67


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