ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Reversible oxidation sensitivity of N-Oct-3 DNA binding activity was seen when melanoma extracts and recombinant Brn-2 protein were treated with a variety of metals, hydrogen peroxide and the cysteine disulphide bond forming agent diamide. Western blot analysis of diamideoxidized N-Oct-3 protein indicated that this was likely to be due to intramolecular disulphide bonding. The potential role of oxidative loss of N-Oct-3 DNA binding activity is discussed in relation to redox changes that may occur during the early phase of apoptosis in neuronal cell lines and tissues. Brn-2 C-terminal antibody Western blot analysis of melanoma cell line nuclear extracts prepared using a combination of sodium dodecyl sulphate and NP-40 detergent cell lysis procedures demonstrated the formation of NOct- 5 DNA binding activity via N-terminal proteolytic clipping of Brn-2/N-Oct-3. © 1998 Rapid Science Ltd

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

In order to determine the possible use of uveal melanoma cell lines as stimulators in immunotherapy, we evaluated the expression of the human genes for MAGE-1, -2 and -3, gp100 and tyrosinase in uveal melanoma cell lines. mRNA expression of the MAGE-1, -2 and -3, gp100 and tyrosinase genes and the HLA class I specificity were determined in five primary and three metastatic uveal melanoma cell lines. Expression of the examined genes was heterogeneous in the primary and metastatic cell lines. The cell lines OCM-1 and OMM-1 expressed MAGE-1, -2 and -3, whereas EOM-3, MEL202, 92-1 and OMM-3 were negative for these antigens. gp100 was expressed in all cell lines, and tyrosinase in all but three (EOM-29, OMM-2 and OMM-3). Except for EOM-3, the HLA-A type of all the cell lines could be determined by complement-dependent microlymphocytotoxicity assay. Since at least two melanoma-associated antigens can be found in uveal melanoma cell lines, as well as the HLA class I molecules, these cell lines may be applicable as immunogens for specific immunotherapy against metastatic uveal melanoma. © 1998 Rapid Science Ltd

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Metastatic melanomas are often resistant to chemotherapy. To study whether the p53 mutational status affects chemosensitivity, we compared the responses to chemotherapy of four melanoma cell lines containing the wild-type p53 and four cell lines carrying the mutant p53. Cisplatin, at 10,µM, virtually killed all the cells in the wildtype p53 cell lines, while 57-95% of the cells in the mutant p53 cell lines survived (P=0.005). After treatment with 100 nM of vincristine, on average 18% of the wildtype p53 melanoma cells survived compared with 55% of the mutant p53 cells (P=0.04). After treatment with 40 nM, 200 nM or 1 µM of camptothecin the survival rates were, on average, 16%, 8% and 4% for the wild-type p53 melanoma cells, compared with 89%, 67% and 38% for the mutant p53 cells, respectively (P=0.00004, P=0.003 and P=0.04, respectively). The anticancer agents were not toxic to normal melanocytes at doses inducing cytotoxicity in wild-type p53 melanoma cells. The main mechanism of cytotoxicity appears to be drug-induced apoptosis. Cisplatin, camptothecin and vincristine all induced apoptosis in wild-type p53 melanoma cells, but not in mutant p53 cells. Our results suggest that chemotherapy- induced apoptosis in melanoma cells is p53 dependent, and mutation of the p53 gene is an indicator of drug resistance in melanoma. © 1998 Rapid Science Ltd

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Interferon regulatory factor-1 (IRF-1) is a cell growth inhibitor, induced by cytokines, which transactivates downstream effector genes. The role of IRF-1 in the antiproliferative effect of interleukin-6 (IL-6) was investigated using the A375 human melanoma cell line. IL-6 is a stronger inhibitor of A375 proliferation compared with interferon-γ(IFNγ). However, in contrast to IFNγ, IL-6 triggered lower IRF-1 DNA binding activity and induced barely detectable IRF-1- dependent transactivation activity. Furthermore, although IFNγ induces only activation of signal transducer and activator of transcription (STAT) 1, IL-6 activates mainly STAT3. These data suggest that IRF-1 plays a minor role in the antiproliterative effect of IL-6, which uses alternative signalling events to induce growth inhibition in A375 melanoma cells. © 1998 Rapid Science Ltd

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

We assessed the antiproliferative effects of human recombinant interferon-α 2a (IFNα 2a) and 13-c/s-retinoic acid (13c/s-RA) on two human melanoma cell lines (JR8 and M14). Both cell lines showed a very modest sensitivity to IFNα 2a and 13c/s-RA as single agents. In JR8 cells, the combination of the two compounds consistently produced simple additive effects. In contrast, different effects of the combination were recorded in the M14 cell line depending on the treatment schedule. Specifically, an additive interaction was observed when IFNα 2a and 13c/s-RA were given in sequence, independently of the order of drug administration, whereas a supra-additive antiproliferative effect was seen when cells were simultaneously exposed to the two drugs. Exposure to 1000 IU/ml IFNα 2a markedly increased the nuclear expression of signal transducers and activators of transcription (STAT) proteins in both cell lines. By itself 10 µM 13c/s-RA did not affect STAT protein expression or modify the extent of activation of such proteins by IFNα 2a. Results from our study showed an enhancement of the antiproliferative activity of IFNα 2a and 13c/s-RA when given in combination and suggest that such an enhancement is not mediated by a concomitant effect of 13c/s-RA on STAT protein activation. © 1998 Rapid Science Ltd.

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The total serum activity of γ-glutamyl transpeptidase (GGT) was shown to increase with the growth of transplantable B16 and S91 melanomas in inbred mice. In an effort to define the source of the GGT shed into the bloodstream the physicochemical characteristics of the partially purified GGT isoforms from liver, serum and B16 melanoma were compared. The molecular weights of the serum and melanoma isoforms were identical (86 kDa) and differed from that of the liver isoform (69 kDa). In polyacrylamide gel electrophoresis the serum and melanoma isoforms had a similar mobility which exceeded that of the liver enzyme. Treatment of the enzyme preparations with neuraminidase removed the differences in the electrophoretic mobility of the three GGT isoforms studied. On ion exchange chromatography on a DEAE-Spheron 300 LC column the melanoma and serum isoforms had an affinity to the sorbent unlike the liver isoform. Our observations suggest that melanoma cells express a sialoform of GGT which is responsible for an increase in the total GGT serum activity. Biochemical and histochemical analyses did not reveal any increase in liver GGT production associated with melanoma development. Detection of the GGT isoform of tumour origin in sera ranks GGT among the specific melanoma markers. © 1998 Rapid Science Ltd.

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

Although some cases of dysplastic naevi (DN) and familial melanoma have been linked to anonymous markers on chromosome 1p36, the gene has not been identified. A candidate gene, RPA2, which codes for the 32 kDa subunit of replication protein A, is located in the 1p35-36 region. We examined the RPA2 gene in seven lymphoblastoid cell lines from members of melanoma-prone families linked to chromosome 1p36. Southern and Northern blot analyses showed the DNA and RNA bands were of normal size and intensity. DNA sequencing demonstrated no nucleotide alterations in the RPA2cDNA. Western blot analysis exhibited normal electrophoretic migration and intensity of the RPA2 protein. These results indicate that alterations do not occur in the RPA2 gene in these DN/familial melanoma families linked to chromosome 1p36. © 1998 Rapid Science Ltd

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

It is now generally agreed that solar exposure is a major external factor in the causation of cutaneous melanoma in light skinned populations with red hair and a marked susceptibility to the acute effects of ultraviolet (UV) radiation. In the present study, we investigated the existence of a possible relationship between hair melanin composition and minimal erythema dose (MED), as an indicator of UV sensitivity, in a group of 15 healthy red-haired subjects aged 20-46 years. In spite of comparable skin and hair colour, marked variations were observed in the MED values as well as in the hair melanin composition. Phaeomelanin levels varied in the range 0.026-0.53% w/w and were generally comparable to or higher than eumelanin levels (0.042-0.17% w/w). No significant relationship was found between MED values and phaeomelanin, eumelanin or total melanin (eumelanin plus phaeomelanin) content. Notably, however, a gross positive correlation was found between the eumelanin/phaeomelanin ratio and the MED values. These results would suggest that a high UV sensitivity is associated with high phaeomelanin and low eumelanin levels, and point to the eumelanin/phaeomelanin ratio as a novel chemical parameter that could be used for predicting individuals at high risk for skin cancer and melanoma. © 1998 Rapid Science Ltd.

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID

摘要:

The correct staging of potentially metastatic melanoma is essential for an appropriate therapeutic attitude. Current methods include computed tomography, magnetic resonance imaging, ultrasonography and scintigraphy. Another tool is whole-body positron tomography using the radiopharmaceutical 2-fluorine-18-fluoro-2-deoxy-D-glucose as an emitter because it accumulates inside neoplasms, especially melanoma. We report two cases of malignant melanoma in which computed tomography and magnetic resonance imaging suggested visceral metastatic spread. In contrast, whole-body positron emission tomography indicated the absence of metastases, and this was confirmed by histological examination of the organs where metastases were suspected. Whole-body positron emission tomography appears to have high specificity and sensitivity for clinical melanoma staging. © 1998 Rapid Science Ltd

ISSN:0960-8931    

出版商:OVID    

年代:1998

数据来源: OVID