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  • 1
    Electronic Resource
    Electronic Resource
    Expression Studies of Pigmentation and POU-Domain Genes in Human Melanoma Cells (1994)
    Oxford, UK : Blackwell Publishing Ltd
    Periodontology 2000 7 (1994), S. 0 
    Details
    ISSN: 1600-0757
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Human melanoma cell lines have been used to examine the regulation of the tyrosinase (TYR) and tyrosinase-related protein genes TRP-1 and TRP-2 in response to differentiating chemicals and UV irradiation. TRP-1 mRNA levels can be repressed by treatment with the differentiating chemicals DMSO and HMBA. There is little effect of UV irradiation on pigment synthesis by human melanoma cell lines or tyrosinase activity, with variable effects on the levels of the TYR, TRP-1, and TRP-2 gene transcripts. The human TRP-1 gene promoter has been isolated and its activity tested by transient cell transfection to begin an examination of signal transduction mechanisms operating in response to pigmenting and differentiating agents. To identify transcription factors that may be involved in melanocytic gene expression, we studied the N-Oct-3 and N-Oct-5 octamer-binding activities normally expressed in the neuroectodermal cell lineage and which are expressed at high levels in melanoma cells. POU-domain-containing cDNA have been isolated from the A2058 human melanoma cell line that are homologous to the brn-2 gene that encodes N-Oct-3 and N-Oct-5.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0749.1994.tb00055.x
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  • 2
    Electronic Resource
    Electronic Resource
    In Vitro Phenotypic Alteration of Human Melanoma Cells Induced by Differentiating Agents: Heterogeneous Effects on Cellular Growth and Morphology, Enzymatic Activity, and Antigenic Expression (1990)
    Oxford, UK : Blackwell Publishing Ltd
    Periodontology 2000 3 (1990), S. 0 
    Details
    ISSN: 1600-0757
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Sodium butyrate (butyrate), 5-azacytidine (5Aza-C), dimethyl sulfoxide (DMSO), and dimethyl formamide (DMF) were applied to a human melanoma cell line for the purpose of inducing pigmentation and terminal differentiation. The results are summarized as follows: 1) butyrate, DMSO, and DMF had a strong cytostatic effect, arresting cells in the G1 phase of the cycle; 2) butyrate caused a morphological change to spindle shape whereas DMSO and DMF produced rounded cells, without affecting the levels of vimentin and intermediate filaments; 3) tyrosinase activity and melanization were stimulated by DMSO and DMF but not by butyrate; 4) butyrate induced several membrane-bound enzyme activities (alkaline phosphatase and -γ-glutamyl transpeptidase); 5) changes in the expression of antigens related to tyrosinase activity (2B7 and 5C12) only partly corresponded to the changes in enzyme activity; 6) expression of the melanosomal B863 antigen was decreased by butyrate, DMSO, and DMF; and 7) the action of DMF resembled that of DMSO whereas 5Aza-C had little effect. The results indicate that these differentiating agents activate different sets of genes, the melanogenic pathway being activated independently of -γ-glutamyltranspeptidase. The down regulation of B8G3 antigen by these agents may provide a common focus for understanding the essential action of differentiation inducers in melanoma cells.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0749.1990.tb00294.x
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  • 3
    Electronic Resource
    Electronic Resource
    Monoclonal Antibody Against a Melanosomal Protein in Melanotic and Amelanotic Human Melanoma Cells (1989)
    Oxford, UK : Blackwell Publishing Ltd
    Periodontology 2000 2 (1989), S. 0 
    Details
    ISSN: 1600-0757
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: BALB/c mice were immunized with tyrosinase, partially purified in two stages from a human melanoma cell line. A hybridoma was obtained which produced monoclonal antibody (MoAb 1C11) reactive with 8/10 melanoma cell lines and 10/10 primary cultures of human melanocytes, neval cells, and melanomas. Immunoreactivity correlated to a certain extent with tyrosinase activity but not with melanin content. No crossreactivity was obtained with neuroblastoma, medulloblastoma, fibroblasts, keratinocytes, lymphoid cells, or murine melanomas. Purification of the antigen directly from cell lysates with a MoAb 1C11 CNBr-Sepharose affinity column gave a green-brown protein of 56 kDa with no detectable tyrosinase activity. This protein was therefore different from 60 kDa active tyrosinase, identified by enzyme activity and Western blotting with a MoAb derived previously (MoAb 5C12). Unlike 5C12, 1C11 reactivity was not destroyed by pretreatment of the antigen with periodate. Immunogold labelling showed that the 1C11-reactive antigen was associated with melanosomes, and there was close correlation between 5C12 and 1C11 reactivity in resistance to trypsin and in staining various melanocytic cell populations. MoAb 1C11 may therefore recognise a polypeptide epitope in a molecule closely linked to melanin biosynthesis.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0749.1989.tb00150.x
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  • 4
    Electronic Resource
    Electronic Resource
    In Vivo and In Vitro Expression of Octamer Binding Proteins in Human Melanoma Metastases, Brain Tissue, and Fibroblasts (1993)
    Oxford, UK : Blackwell Publishing Ltd
    Periodontology 2000 6 (1993), S. 0 
    Details
    ISSN: 1600-0757
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The pattern of octamer sequence-specific DNA binding proteins expressed in human melanoma was examined in nuclear extracts of seven surgically-isolated tumors, short-term cultures of these tumors, and 25 human melanoma cell lines to determine the in vivo and in vitro distribution of the melanocytic-associated Oct-M1 and Oct-M2 octamer binding activities. In the biopsy tissue and cultured melanoma cells of a metastasis from the cerebellum, two other binding activities (N-Oct-2 and N-Oct-6) in addition to the Oct-M1, Oct-M2 and the generally expressed Oct-1 protein were detected; this profile was consistent with that seen in normal human and mouse brain tissue. Melanoma tissue removed from lymph nodes and cell lines established from them also showed Oct-1, Oct-M1, Oct-M2, and N-Oct-2. N-Oct-2 was distinguished from the comigrating Oct-2A activity by failure to react with Oct-2A-specific antibody. All but one of the 25 melanoma cell lines exhibited Oct-1, Oct-M1, and Oct-M2 and/or N-Oct-2 activity, whereas cultured normal melanocytes expressed only Oct-1 and Oct-M1. In contrast to murine fibroblasts, which express only Oct-1, human fibroblast strains also expressed Oct-2A binding activity, which was confirmed by reactivity with Oct-2A antibody and the presence of Oct-2A mRNA and indicated that Oct-2A has a more general role than that of a lymphoid-specific transcription factor. Overall, the results indicate that expression of neural-specific Oct factors in human melanoma is (1) aberrant compared with normal melanocytes, (2) can be modulated by the surrounding tissue in a brain metastasis, and (3) may be part of the altered program of differentiation accompanying transformation.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1111/j.1600-0749.1993.tb00576.x
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  • 5
    Electronic Resource
    Electronic Resource
    Complementary expression of melanosomal antigens and constant expression of pigment-independent antigen during the evolution of melanocytic tumours (1990)
    Springer
    Virchows Archiv 416 (1990), S. 513-519 
    Details
    ISSN: 1432-2307
    Keywords: Monoclonal antibody ; Tyrosinase ; Malignant melanoma ; Metastasis ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We have generated monoclonal antibodies (MoAbs) against melanosomal proteins (MoAb 1C11 and MoAb HMSA-1) and a cytoplasmic protein strongly synthesized in neoplastic melanocytes but not associated with melanogenesis (MoAb 7H11). An immunohistochemical study of paraffin sections showed that nearly 90% of epidermal neoplastic melanocytes, including melanomas, expressed 1C11 antigen, whereas this antigen was poorly preserved in dermal melanocytic cells except melanomas. HMSA-1 antigen was expressed in a complementary manner to 1C11 antigen, being found in dermal naevus cells but not generally in the epidermal regions, except for dysplastic naevi and melanomas. In contrast, 7H11 antigen was distributed in nearly 90% of melanocytic tumours except solar lentigo and lentigo maligna lesions. The failure of MoAb 1C11 to react with dermal melanocytes may reflect a subtle alteration in melanogenesis during tumour evolution. Overall, the combined use of MoAbs serves as an accurate diagnosis of melanocytic tumours, the pigment-independent MoAb 7H11 being particularly useful for amelanotic and metastatic lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01600302
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  • 6
    Electronic Resource
    Electronic Resource
    A case report: Immune responses and clinical course of the first human use of granulocyte/macrophage-colony-stimulating-factor-transduced autologous melanoma cells for immunotherapy (1997)
    Springer
    Cancer immunology immunotherapy 44 (1997), S. 10-20 
    Details
    ISSN: 1432-0851
    Keywords: Key words GM-CSF-transduced autologous melanoma vaccine ; Cerebral metastases-acute cerebral oedema ; Tumour-reactive cytotoxic T lymphocytes ; Eosinophilia ; C-reactive protein
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The first use of granulocyte/macrophage-colony-stimulating-factor-transduced, lethally irradiated, autologous melanoma cells as a therapeutic vaccine in a patient with rapidly progressive, widely disseminated malignant melanoma resulted in the generation of a novel antitumour immune response associated with partial, albeit temporary, clinical benefit. An initially negative reaction to non-transduced, autologous melanoma cells was converted to a delayed-type hypersensitivity (DTH) reaction of increasing magnitude following successive vaccinations. While intradermal vaccine sites showed prominent dendritic cell accrual, DTH sites revealed a striking influx of eosinophils in addition to activated/memory T lymphocytes and macrophages, recalling the histology of challenge tumour cell rejection in immune mice. Cytotoxic T lymphocytes (CTL) reactive with autologous melanoma cells were detectable at high frequency after vaccination, not only in limiting-dilution analysis, but also in bulk culture without added cytokines. Clonal analysis of CTL showed a conversion from a purely CD8+ response to a high proportion of CD4+ clones following vaccination. A prominent acute-phase response manifested by a five- to tenfold increase in C-reactive protein was observed, as was a systemic eosinophilia. Vaccination resulted in the regression of axillary lymphatic metastases, stabilisation of pulmonary metastases, and a dramatic, reversible increase in cerebral oedema associated with multiple central nervous system metastases; however, lesions in the adrenal glands, pancreas and spleen proved refractory. The antitumour effects and immune response were not detectable 2 months following the last vaccination. Irradiation of the extensive cerebral metastases resulted in rapid deterioration and death of the patient.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002620050349
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  • 7
    Electronic Resource
    Electronic Resource
    Determinants of melanocyte density in adult human skin (1999)
    Springer
    Archives of dermatological research 291 (1999), S. 511-516 
    Details
    ISSN: 1432-069X
    Keywords: Key words Melanocyte ; Naevus ; Melanoma ; Immunohistochemistry ; Monoclonal antibody
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The distribution of melanocytes in human skin has been observed to vary within and among individuals, yet little is known of the factors that determine the density of these pigment cells. These factors were explored in a molecular epidemiological study conducted among a population-based sample of 97 male subjects aged over 50 years in Queensland, Australia. Information relating to environmental and phenotypic factors was collected through face-to-face interviews and physical examination of all participants. In addition, 2-mm biopsies of representative skin were taken from the dorsum of the hand and another anatomical site. Melanocytes were identified by cytoplasmic staining with the B8G3 (anti-TRP1) monoclonal antibody using standard immunohistochemical techniques. Melanocyte counts were performed blind by two observers. On crude analysis, melanocyte density decreased with advancing age (P = 0.0002), and increased with increasing number of naevi (P = 0.01). Other pigmentary characteristics (such as hair and eye colour and depth of tan) were not associated with epidermal melanocyte density. Melanocyte density varied significantly by anatomical site (P = 0.02), with highest densities observed on the back/shoulders (n = 50, 17.1 ± 8.8 cells/mm, mean ± SD) followed by the upper limbs (n = 11, 12.6 ± 8.8 cells/mm) and lower limbs (n = 14, 14.4 ± 5.9 cells/mm). Lowest melanocyte densities were recorded on the anterior trunk (n = 3, 3.2 ± 2.4 cells/mm). These findings confirm the results of earlier studies in which site-specific differences in melanocyte density have been found. We speculate that the unequal distribution of melanocytes may partially explain the site-specific incidence of melanoma, offering fresh perspectives on the aetiology of this cancer.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004030050446
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  • 8
    Electronic Resource
    Electronic Resource
    The in vitro Antitumour Activity of Substituted Dibutyl-1,3,2-dioxastannolanes (1997)
    New York, NY [u.a.] : Wiley-Blackwell
    Applied Organometallic Chemistry 11 (1997), S. 577-581 
    Details
    ISSN: 0268-2605
    Keywords: dioxastannolanes ; antitumour ; human cell lines ; Chemistry ; Industrial Chemistry and Chemical Engineering
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Six dibutyl-1,3,2-dioxastannolanes, including two enantiomeric pairs, exhibited greater in vitro antitumour activity towards a variety of human tumour cell lines than cisplatin but with little discrimination, suggesting hydrolysis to a common cytotoxic intermediate. A cell line hypersensitive to mitochondrial inhibitors (CI80-13S) was not sensitive to any of the test compounds, suggesting that cell mechanisms other than, or in addition to, mitochondrial function are targeted by tin antitumour agents. A pigmented melanoma cell line (MM418c5) was resistant to the test compounds, which were found to be sequestered by melanin. This resistance was not observed with triphenyltin hydroxide. © 1997 John Wiley & Sons, Ltd.
    Additional Material: 2 Ill.
    Type of Medium: Electronic Resource
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