Pigment Cell & Melanoma Research[JOURNAL]
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155 papers
Tyrosinase transfection produces melanin synthesis and growth retardation in glioma cells.
Singh MV, Jimbow K
Melanoma Res · 1998 Dec · PMID 9918410 · Publisher ↗
Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells. We transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned in a high expression vector. Stable transfectants were selected...
Tyrosinase is the key enzyme in melanin biosynthesis in pigmented cells. We transfected 9L rat glioma cells with human tyrosinase cDNA that had been cloned in a high expression vector. Stable transfectants were selected by their resistance to the antibiotic G418. More than a dozen G418-resistant clones were isolated and were screened for tyrosinase expression using dopa-oxidase activity. The clone with the highest tyrosinase activity was selected and expanded for further studies. Northern blot analyses of total RNA from cells showed that the transfected cells had relatively more tyrosinase transcript than SK-MEL-23 human melanotic melanoma cells. The melanin content of the transfected cells was dependent on the concentration of L-tyrosine in the culture medium. In addition, the growth of transfected cells was inhibited when grown in a medium containing high concentrations of L-tyrosine. These results suggest that tyrosinase activity is cytotoxic in a substrate-dependent manner. This may have far reaching therapeutic use for glioma tumours.
Two types of pattern modification detected on the follow-up of benign melanocytic skin lesions by digitized epiluminescence microscopy.
Braun RP, Lemonnier E, Guillod J … +3 more , Skaria A, Salomon D, Saurat JH
Melanoma Res · 1998 Oct · PMID 9835457 · Publisher ↗
Digital epiluminescence microscopy (DELM) is currently being developed for the diagnosis of pigmented skin lesions (PSL) and the early diagnosis of malignant melanoma. So far there are only few studies documenting if mod...
Digital epiluminescence microscopy (DELM) is currently being developed for the diagnosis of pigmented skin lesions (PSL) and the early diagnosis of malignant melanoma. So far there are only few studies documenting if modifications in PSL may be detected by DELM over time. Our purpose was to determine if DELM is an adequate tool for the follow-up of PSL and if any detectable modifications occur within PSL over time. We followed 150 PSL over 2 years in 67 patients using a DELM system. At the end of the follow-up period, the retrieved DELM images were analysed by two observers and evaluated for the presence and type of modifications. Modifications were observed in 69% of the PSL. These modifications were of two types. Type 1 corresponded to an increase in the pigment content of the lesion without modification of either its size or architecture, and was probably related to sun-related seasonal variation. Type 2 included an increase in the size and various variations in the architecture, corresponding to a progression of the lesion. Correlation of the type of modification with the type of PSL, as defined by its epiluminescence microscopy (ELM) patterns, indicated that type 2 modifications were associated with lesions initially showing ELM signs of 'dysplasia', whereas lesions showing only type 1 modifications did not show such patterns. We have documented the feasibility of following up PSL with DELM. The pattern of modification of a PSL over time could be correlated with its nature.
Melan A/MART-1 immunoreactivity in formalin-fixed paraffin-embedded primary and metastatic melanoma: frequency and distribution.
Hofbauer GF, Kamarashev J, Geertsen R … +2 more , Böni R, Dummer R
Melanoma Res · 1998 Aug · PMID 9764809 · Publisher ↗
Monoclonal antibody (MAb) A103 specifically detects Melan A/MART-1 protein expression. Melan A/MART-1-derived peptides are recognized by CD8+ T-cells and are used in immunotherapy. We examined formalin-fixed paraffin-emb...
Monoclonal antibody (MAb) A103 specifically detects Melan A/MART-1 protein expression. Melan A/MART-1-derived peptides are recognized by CD8+ T-cells and are used in immunotherapy. We examined formalin-fixed paraffin-embedded tissue from 57 melanomas (34 primary, 23 metastatic) and 39 control cases (junctional, dermal, compound, Spitz, Reed and balloon-cell naevi) using the alkaline phosphatase and anti-alkaline phosphatase immunochemical method after antigen retrieval. Immunoreactivity was rated as low, medium or high, and staining pattern as homogeneous or heterogeneous. Staining with MAb A103 showed a sensitivity of 88% for melanoma, with a very high specificity for melanocytic cells. Immunopositivity decreased along with clinical stage, with stage I showing 100%, stage II 88%, stage III 90% and stage IV 75% immunoreactivity. Staining changed from an exclusively homogeneous pattern in the early clinical stages to a more heterogeneous pattern in the later stages. Melanocytic control tissues consisting of naevi of different subtypes all showed weak to moderate homogeneous immunoreactivity, with polarity towards the epidermis. Analysis of short-term melanoma cell cultures using reverse transcription-polymerase chain reaction (RT-PCR) enzyme-linked immunosorbent assay (ELISA) demonstrated mRNA expression in only one third of the originally immunopositive tumours, suggesting rapid mRNA expression loss in culture. MAb A103 allows the detection of melanoma-associated Melan A/MART-1 protein expression in routine archival tissue and thus enables the profiling of melanomas suited for immunotherapy approaches involving Melan A/MART-1 derived epitopes.
An analysis of p16 protein expression in sporadic malignant melanoma.
Grover R, Chana JS, Wilson GD … +2 more , Richman PI, Sanders R
Melanoma Res · 1998 Jun · PMID 9664149 · Publisher ↗
Inactivation of p16 tumour suppressor gene has been reported frequently in melanoma cell lines, and mutations have been detected in familial melanoma kindreds. The aim of this study was to assess the role of p16 inactiva...
Inactivation of p16 tumour suppressor gene has been reported frequently in melanoma cell lines, and mutations have been detected in familial melanoma kindreds. The aim of this study was to assess the role of p16 inactivation in melanocytic progression by measuring the level of p16 protein in a range of sporadic, benign and malignant melanocytic lesions. Using dual parameter flow cytometry, p16 protein expression was measured in 30 benign melanocytic naevi, 38 primary and 51 metastatic melanomas. A high level of p16 expression was demonstrated in benign melanocytic naevi (96% median nuclear positivity), with a significant reduction in primary melanomas (69%, P < 0.001). The median nuclear positivity of primary melanomas was significantly higher (P < 0.03) than the level of expression in metastatic lesions (median positivity 37%). A progressive loss of p16 expression was demonstrated from benign melanocytic naevi through to primary and metastatic lesions. These data suggest that loss of p16 protein expression is not only associated with the early transformation of benign lesions, but also with the later stages of malignant progression.
Regression by differentiation in the Sinclair swine model of cutaneous melanoma.
Greene JF, Morgan CD, Rao A … +2 more , Amoss MS, Arguello F
Melanoma Res · 1997 Dec · PMID 9464619 · Publisher ↗
The spontaneous regression of melanoma in Sinclair miniature swine involves the replacement of tumours by pigmented cells, hitherto interpreted as pigment-laden macrophages (PLMs). We hypothesized that these residual cel...
The spontaneous regression of melanoma in Sinclair miniature swine involves the replacement of tumours by pigmented cells, hitherto interpreted as pigment-laden macrophages (PLMs). We hypothesized that these residual cells are terminally differentiated melanoma cells, not monocyte-derived macrophages. Swine melanoma explants with no regression were transplanted into severe combined immunodeficient (SCID) mice. Harvested transplant sites were examined by routine light and electron microscopy techniques. Paraffin sections were also stained with Hoeschst dye and examined by fluorescence microscopy. All but one site had completely regressed and were replaced by PLM-like cells. Hoeschst staining indicated they were of swine, not mouse, origin. The ultrastructural features of the single, partially regressed lesion demonstrated many premelanosomes in these cells. We conclude that tumour differentiation is an important mechanism of regression in the Sinclair swine melanoma model.
Cytotoxic interactions of Zn2+ in vitro: melanoma cells are more susceptible than melanocytes.
Borovanský J, Blasko M, Siracký J … +3 more , Schothorst AA, Smit NP, Pavel S
Melanoma Res · 1997 Dec · PMID 9464616 · Publisher ↗
Previous studies have shown that sensitivity to high extracellular levels of Zn2+ is a general feature of cells in vitro and that a prerequisite of the toxic action of zinc is entry into cells via channels that are share...
Previous studies have shown that sensitivity to high extracellular levels of Zn2+ is a general feature of cells in vitro and that a prerequisite of the toxic action of zinc is entry into cells via channels that are shared with iron or calcium. As the biochemical and toxicological behaviour of zinc chelate complexes could be different from that of free Zn2+, the effect of chelating agents on zinc transport into human melanoma cell lines was tested. EDTAcal and tetracycline reduced the toxic action of zinc ions in vitro, whereas phenytoin and diethyldithiocarbamate potentiated its effects. D-penicillamine, an effective chelator of zinc in vivo, also exerted a protective action in vitro. Comparison of sensitivity to Zn2+ in vitro between human melanoma lines and several lines of pigment cells from skin of various origins demonstrated that melanoma cells are killed by zinc ions at concentrations which are only partially toxic for normal pigment cells. This is consistent with the repeatedly observed high uptake of 65Zn by melanoma cells.
Statistical evaluation of epiluminescence microscopy criteria in the differential diagnosis of malignant melanoma and pigmented basal cell carcinoma.
Püspök-Schwarz M, Steiner A, Binder M … +3 more , Partsch B, Wolff K, Pehamberger H
Melanoma Res · 1997 Aug · PMID 9293480 · Publisher ↗
Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epilumi...
Pigmented basal cell carcinoma (PBCC) is a tumour with distinct clinical features which occasionally may be difficult to differentiate from malignant melanoma (MM). The purpose of this study was to re-examine the epiluminescence microscopy (ELM) criteria for PBCC and to determine their statistical significance in the differential diagnosis of MM. Fifty histologically verified pigmented skin lesions (25 PBCCs and 25 MMs) were investigated using ELM for the presence of ELM criteria; their significance was determined by calculating the odds ratios. We found that individual ELM criteria have different weights of significance in the differential diagnosis of PBCC (leaf-like distribution of diffuse pigmentation, gradual thinning at the periphery and telangiectasia) and MM (pigment network, black and grey pigmentation, radial streaming, pseudopods, brown globules and black dots). Selected patterns of ELM criteria adjusted to the distinct types of pigmented skin lesions are characteristic features for preoperative diagnosis. The prevalence of distinct ELM criteria in PBCC and MM is of critical value in differentiating between the two types of lesions.
Expression of fibroblast growth factor receptors in naevus-cell naevus and malignant melanoma.
Ahmed NU, Ueda M, Ito A … +3 more , Ohashi A, Funasaka Y, Ichihashi M
Melanoma Res · 1997 Aug · PMID 9293479 · Publisher ↗
In a previous study, we showed by immunohistochemical analysis that basic fibroblast growth factor (bFGF) is expressed strongly and homogeneously in naevus-cell naevus (NCN), while that in malignant melanoma (MM) is hete...
In a previous study, we showed by immunohistochemical analysis that basic fibroblast growth factor (bFGF) is expressed strongly and homogeneously in naevus-cell naevus (NCN), while that in malignant melanoma (MM) is heterogeneous and sometimes non-existent. In order to elucidate the role of bFGF in these pigmented tumours, the expression of its receptors must be determined. In this study, we performed an immunohistochemical analysis of FGF receptors 1, 2 and 3 (FGFR-1, FGFR-2 and FGFR-3, respectively) in NCN and MM and compared their expression and localization with those of bFGF. The expression of bFGF and its three receptors was also examined in melanoma cell lines. None of the 10 NCN that showed strong, homogeneous staining for bFGF expressed FGFR-1 or FGFR-3 proteins; six weakly expressed FGFR-2 protein. Ten primary and 10 metastatic MM showed heterogeneous expression for the three receptors, with larger populations of FGFR-3-negative cells in the primary than in the metastatic tumours. Western blot analysis showed homogeneous expression of bFGF protein in all four melanoma cell lines tested, while FGFR proteins had a heterogeneous distribution in the different cell lines. Cultured NCN and normal melanocytes showed no immunoreactive band for FGFR-1 protein, the only protein tested. Our results suggested that tumour-derived bFGF is involved in melanoma formation through an autocrine mechanism, but is involved mostly through a paracrine or other mechanisms in NCN.
Prognostic significance of nm23 protein expression in malignant melanoma. An immunohistochemical study.
van den Oord JJ, Maes A, Stas M … +3 more , Nuyts J, De Wever I, De Wolf-Peeters C
Melanoma Res · 1997 Apr · PMID 9167178 · Publisher ↗
The NM23 genes, encoding for the red blood cell nucleoside diphosphate kinases A and B, have been found to serve as metastasis-suppressor genes in experimental animal models of tumour progression, and in some, but not al...
The NM23 genes, encoding for the red blood cell nucleoside diphosphate kinases A and B, have been found to serve as metastasis-suppressor genes in experimental animal models of tumour progression, and in some, but not all cancers in man. To investigate the role of NM23 in the progression of human malignant melanoma, we studied the expression and distribution of the nm23 protein with a sensitive immunohistochemical technique and a well-characterized monoclonal antibody in 41 benign pigment cell lesions and 71 uniformly treated malignant melanomas with a long follow up-up. In benign naevi, the junctional nests frequently expressed nm23 protein, whereas the immunoreactivity tended to decrease when the lesions matured. All malignant melanomas expressed nm23 protein in their vertical and/or radial growth phases, and the immunoreactivity tended to increase towards the deeper parts of the lesion. No relation was found between nm23 expression and patient outcome. In addition, nm23 was found in activated lymphoid cells, and this feature was significantly associated with a brisk lymphocytic stroma response in malignant melanomas. Our data are at variance with previous mRNA studies on malignant melanoma, and indicate that routine immunohistochemical analysis for nm23 protein on paraffin-embedded tumour tissue cannot reliably be used as a prognostic marker for patients suffering from malignant melanoma. In contrast, our findings suggest that the nm23 protein in pigment cell lesions is related to the proliferative or activated state of pigment cells, rather than to their metastatic potential.
Melanosomal proteins as melanoma-specific immune targets.
Sakai C, Kawakami Y, Law LW … +2 more , Furumura M, Hearing VJ
Melanoma Res · 1997 Apr · PMID 9167173 · Publisher ↗
Pigmentation of our skin, hair and eyes is essential for photoprotection, embryological development, detoxification and protective/cosmetic coloration. A number of proteins important to the production of melanin within m...
Pigmentation of our skin, hair and eyes is essential for photoprotection, embryological development, detoxification and protective/cosmetic coloration. A number of proteins important to the production of melanin within melanosomes have now been identified including enzymatic and structural proteins encoded at the murine albino, brown, pinkeyed-dilution, MART1, slaty and silver loci. Interestingly, many of those melanosomal proteins (including epitopes derived from tyrosinase, TRP1/gp75, silver/gp100 and MART1/melan-A) function in vivo as targets of humoral and cellular autoimmune responses directed specifically against normal or transformed melanocytes. These findings have provided new impetus to research on immune responses to melanoma and, perhaps more importantly, examining why they are insufficient to provide protection against tumour growth and what type of immune therapy can be designed to correct that. The melanosome must now be considered beyond its function in pigmentation, and assumes the role of a valuable source for specific immune targets for malignant melanoma.
Childhood melanoma: a clinicopathological study of 22 cases.
Scalzo DA, Hida CA, Toth G … +2 more , Sober AJ, Mihm MC
Melanoma Res · 1997 Feb · PMID 9067967 · Publisher ↗
Childhood melanoma is a rare disease with an estimated incidence of one per million per year. Careful study of childhood melanoma patients is critical due to the limited data currently available pertaining to this diseas...
Childhood melanoma is a rare disease with an estimated incidence of one per million per year. Careful study of childhood melanoma patients is critical due to the limited data currently available pertaining to this disease. Twenty-two children 15 years of age or under with malignant melanoma were treated at the Pigmented Lesion Clinic of Massachusetts General Hospital over a 33-year period. The medical records of all patients were reviewed, as well as the histologic characteristics of the lesions. Patients who were initially diagnosed with malignant melanoma but on review found to have Spitz naevi were not included in our study. Ten patients were boys and 12 were girls. The median ages of the boys and girls in our study were 12.9 and 13.6 years, respectively. Among the classified primary melanomas, 10 were superficial spreading, three were borderline/minimal deviation, two were nodular and one was melanoma in situ. Four of 22 patients had a documented family history of melanoma, and two additional patients had a family history of dysplastic naevi. A majority of lesions (14/22) arose in association with a precursor lesion. Two children died of disease at 1 and at 7 years following initial diagnosis. Eight patients had documented metastases. Since the majority of melanomas arose in association with a precursor lesion, follow-up of children with congenital and/ or dysplastic naevi is recommended. An interesting finding was the sometimes paradoxical behaviour of relatively thin lesions with metastases. Thus, a high index of suspicion is needed by the clinician confronted with melanocytic lesions of childhood. We found children from age 12 to 15 to be more at risk for the development of melanoma than younger children. Melanoma presenting before the age of 10 is very unusual.
Analysis of T cell receptor AV and BV chain gene expression by infiltrating lymphocytes in Spitz naevi and in halo naevi.
Birck A, thor Straten P, Li L … +3 more , Hou-Jensen K, Sugár J, Zeuthen J
Melanoma Res · 1997 Feb · PMID 9067965 · Publisher ↗
Spitz naevi and halo naevi are benign melanocytic lesions that share many histological features with malignant melanoma. All lesions are characterized by a brisk infiltration of lymphocytes, mainly of the T cell subtype,...
Spitz naevi and halo naevi are benign melanocytic lesions that share many histological features with malignant melanoma. All lesions are characterized by a brisk infiltration of lymphocytes, mainly of the T cell subtype, and halo naevi are known to undergo spontaneous regression. Since the benign nature of Spitz naevi and halo naevi might therefore be caused by specific T cell responses against tumour-associated antigens, it was found of interest to characterize this T cell response in detail. A reverse transcriptase-polymerase chain reaction (RT-PCR)-based method adapted for analysis of paraffin-embedded material combined with Southern blot analysis has been used to analyse the T cell receptor (TCR) AV and BV repertoires of infiltrating lymphocytes in 14 different melanocytic lesions. The results have shown that only a few particular TCRAV and TCRBV regions are expressed in each lesion. To evaluate the T cell response, it is of interest to know the HLA-type of the analysed lesions, since most melanoma-specific effector lymphocytes are CD8+ cytotoxic T cells and therefore HLA class I-restricted. As blood samples were not available from any of these patients, an RT-PCR method using HLA-A2-specific primers was used to analyse for the presence of this allele. The preferentially expressed TCRAV genes were sequenced, and this analysis showed that the high expression of these TCRAV genes was due to a clonal or oligocional expansion of T cells. In summary, the expression of relatively few TCR variable regions indicates a clonal expansion of T cells.
Mel-5: a novel antibody for differential diagnosis of epidermal pigmented lesions of the skin in paraffin-embedded sections.
Bhawan J
Melanoma Res · 1997 Feb · PMID 9067964 · Publisher ↗
Histological evaluation of epidermal melanocytes on routine staining is difficult and cannot be made with accuracy. Widely known antibodies such as S-100 and HMB-45 are unreliable for normal epidermal melanocytes. Furthe...
Histological evaluation of epidermal melanocytes on routine staining is difficult and cannot be made with accuracy. Widely known antibodies such as S-100 and HMB-45 are unreliable for normal epidermal melanocytes. Furthermore, S-100 stains other cells including Langerhans' cells. Results of incubation with DOPA are inconsistent and the procedure is time-consuming. We have evaluated the use of Mel-5, an antibody that was developed against melanoma and melanocytes. This antibody is a mouse monoclonal antibody that specifically detects a 75 kDa glycoprotein usually expressed by normal melanocytes, naevi and melanoma cells in routinely fixed paraffin sections. Histological differentiation between pigmented actinic keratosis in photodamaged skin and lentigo maligna can be difficult. The atypical keratinocytes, particularly in the basal layer, can be confused with atypical melanocytes, especially if they are pigmented. Similarly, distinctions between lichen planus-like keratosis and lichenoid melanoma in situ and lentigo maligna and lentigo may be difficult. Use of Mel-5 in such cases has shown consistent results in separating melanocytic from non-melanocytic lesions. This antibody is also helpful in evaluating biopsies of patients with vitiligo, post-inflammatory pigmentary alteration and regressed or regressing melanocytic lesions. Furthermore, Mel-5 is an invaluable tool in quantification of epidermal melanocytes in research projects.
Modulation of 5-S-cysteinyldopa formation by tyrosinase activity and intracellular thiols in human melanoma cells.
Benathan M
Melanoma Res · 1996 Jun · PMID 8819121 · Publisher ↗
The catechol 5-S-cysteinyldopa (5-S-CD) is produced in large amounts in metastatic malignant melanoma. To further understand the mechanism of formation of 5-S-CD, we investigated the effects of thiol modulating agents an...
The catechol 5-S-cysteinyldopa (5-S-CD) is produced in large amounts in metastatic malignant melanoma. To further understand the mechanism of formation of 5-S-CD, we investigated the effects of thiol modulating agents and melanin precursors on human melanoma cells. Under standard culture conditions (0.1 mM cystine), the cell levels of 5-S-CD were highly correlated with the degree of melanization and the dopa oxidase activity of the four cell lines investigated (Me8, JUSO, GLL19, Swift). Inhibition of glutathione (GSH) biosynthesis with buthionine sulphoximine did not affect 5-S-CD levels in the low melanotic GL 19 cells. In contrast, the highly pigmented Swift cells showed a strong increase in the cell levels of cystine (CysH) and 5-S-CD. When the cystine concentration of the growth medium was increased to 0.2 mM, a similar situation of 5-S-CD synthesis caused by an increase in intracellular CysH levels was observed in the Swift cells. The GLL19 cells showed enhanced 5-S-CD formation in the presence of 0.1 mM L-dopa. This effect was associated with a fourfold increase in dopa oxidase activity. Our data clearly indicate that 5-S-CD is formed in human melanoma cells by a tyrosinase-dependent mechanism involving the addition of CysH to dopaquinone. Based on the enhancing effect of buthionine sulphoximine on 5-S-CD formation, it is proposed that GSH is not directly implicated in 5-S-CD formation, but regulates CysH levels via the enzyme gamma-glutamylcysteine synthetase.
c-KIT receptor expression in cutaneous malignant melanoma and benign melanotic naevi.
Ohashi A, Funasaka Y, Ueda M … +1 more , Ichihashi M
Melanoma Res · 1996 Feb · PMID 8640066 · Publisher ↗
To investigate the role of c-KIT receptor in melanocytic tumour development and progression, we analysed the expression and localization of c-KIT by immunohistochemistry and Western blotting. In contrast to the positive...
To investigate the role of c-KIT receptor in melanocytic tumour development and progression, we analysed the expression and localization of c-KIT by immunohistochemistry and Western blotting. In contrast to the positive staining shown by melanocytes and naevus cells in the epidermis of common naevi (n=20), all dysplastic naevi (n=13) were negative, as were dermal melanocytic cells of blue naevi (n = 4) and common naevi (n = 26). Three out of four superficial spreading melanomas lost c-KIT expression both in the epidermal and dermal parts, while nodular melanomas showed no expression of c-KIT except in partially positive cells, and six out of seven metastatic melanomas were negative. In acral lentiginous melanomas (n = 8), in contrast to other types of melanoma, all cases with melanoma cells growing basally in the epidermis showed strong c-KIT positivity, but melanoma cells growing at the upper layers of the epidermis and vertically into the dermis lost c-KIT expression. Using the Western blot method on cultured pigment cells, human epidermal melanocytes, junctional naevus cells and one out of three metastatic melanoma cell lines showed 125 and 145 kDa bands corresponding to c-KIT, whereas dermal naevus cells did not. These results suggest that dysplastic naevi are distinct from ordinary naevi in terms of c-KIT expression and that basally growing cells in acral lentigenous melanomas could be at an initial stage of tumour progression, before c-KIT loss occurs.
Photodynamic therapy: a 5-year study of its effectiveness in the treatment of posterior uveal melanoma, and evaluation of haematoporphyrin uptake and photocytotoxicity of melanoma cells in tissue culture.
Favilla I, Favilla ML, Gosbell AD … +4 more , Barry WR, Ellims P, Hill JS, Byrne JR
Melanoma Res · 1995 Oct · PMID 8541727 · Publisher ↗
A human melanoma cell line RVH-421 which selectively demonstrates melanin synthesis when cultured in L15 Leibowitz medium but not in RPMI medium was used as a model to examine haematoporphyrin derivative (HPD) uptake and...
A human melanoma cell line RVH-421 which selectively demonstrates melanin synthesis when cultured in L15 Leibowitz medium but not in RPMI medium was used as a model to examine haematoporphyrin derivative (HPD) uptake and the photocytotoxicity of photodynamic therapy (PDT). Confocal scanning microscopy and extraction fluorometry showed HPD uptake in both non-pigmented and pigmented melanoma cells. Phototoxicity was determined by incubating pigmented and non-pigmented monolayer cells with HPD, exposing them to variable periods of white fluorescent light and calculating the number of viable cells in the samples relative to the controls. Both the non-pigmented and pigmented melanoma cells were affected by light-dependent cytotoxicity which was greater in the non-pigmented cells. Melanin or other substances may reduce the photo-oxidative effects of PDT. Posterior uveal melanomas in 36 patients were treated with PDT with the longest duration of tumour control being 6.5 years. Kaplan-Meier survival analysis showed that 76% of melanomas were not growing at the end of the first year, declining to 62% at the end of the second year, with 38% showing no signs of growth at the end of the fifth year. No eyes were lost as a result of PDT. Cox's hazards analysis showed that the degree of tumour pigmentation and patient age at therapy significantly influence the tumour response to PDT.
Coordinated mRNA expression of c-Kit with tyrosinase and TRP-1 in melanin pigmentation of normal and malignant human melanocytes and transient activation of tyrosinase by Kit/SCF-R.
Luo D, Chen H, Searles G … +1 more , Jimbow K
Melanoma Res · 1995 Oct · PMID 8541720 · Publisher ↗
The proto-oncogene c-Kit encodes a membrane receptor protein with intrinsic tyrosine kinase activity. Activation of c-Kit induces cell proliferation, differentiation or migration among different cell types. The present s...
The proto-oncogene c-Kit encodes a membrane receptor protein with intrinsic tyrosine kinase activity. Activation of c-Kit induces cell proliferation, differentiation or migration among different cell types. The present study provides evidence that c-Kit plays an important role in the cell differentiation rather than in cell proliferation in pigment cells. We found that normal human melanocytes and a limited number of melanoma cells, e.g. WM35, WM39 and G361 cell lines, expressed the c-Kit gene together with tyrosinase and TRP-1 genes. When exposed to alpha-melanocyte stimulating hormone, these three cell lines also showed an increased tyrosinase (dopa-oxidase) activity. By incubating these cells with 20 ng/ml of stem cell factor (SCF) which is a ligand of c-Kit receptor, we found a transient increase of tyrosinase activity 2-4 h post-incubation, indicating an early response of tyrosinase activation, either by elevating tyrosinase protein expression or by tyrosinase protein modification (e.g. phosphorylation). However, Western blot analysis using anti-tyrosinase antibody suggested that there was no change of tyrosinase protein expression between SCF-treated and non-treated cells. We therefore suggest that protein modulation of tyrosinase (e.g. phosphorylation) plays an important role in c-Kit-induced melanogenesis.
6th meeting of the European Society for Pigment Cell Research. Lausanne, Switzerland, 19-21 October 1995. Abstracts.
Melanoma Res · 1995 Sep · PMID 8601080
Abstract loading — click title to view on PubMed.
The histological and immunohistochemical changes in the skin of patients with melanoma who develop changes in skin pigmentation following immunotherapy.
Salter J, MacLennan K, Bridgewater JA … +5 more , Moore J, Atkinson H, Nicolson M, Riches P, Gore ME
Melanoma Res · 1995 Aug · PMID 7496163 · Publisher ↗
The histological and immunocytochemical appearances of skin with altered pigmentation from two patients receiving chemoimmunotherapy for melanoma were examined. In both patients, there was a clinical response to treatmen...
The histological and immunocytochemical appearances of skin with altered pigmentation from two patients receiving chemoimmunotherapy for melanoma were examined. In both patients, there was a clinical response to treatment coincident with depigmentation of skin and hair. Skin biopsies showed extensive infiltration with CD8+ and CD4+ lymphocytes rather than CD57+ in the depigmented areas suggestive of a specific MHC-related cytotoxic T-cell activity against melanocytes. In keeping with this, MHCII expression was markedly up-regulated. These observations suggest the development of a simultaneous anti-tumour and anti-melanocyte immune response stimulated by chemoimmunotherapy, possibly against the same or similar antigens.
In vivo autofluorescence of an unpigmented melanoma in mice. Correlation of spectroscopic properties to microscopic structure.
Sterenborg HJ, Thomsen S, Jacques SL … +1 more , Motamedi M
Melanoma Res · 1995 Aug · PMID 7496155 · Publisher ↗
Recently, fluorescence spectroscopy and imaging have been under investigation for in vivo diagnosis of several types of superficial cancer, including primary melanomas of the skin. Here we report on a detailed investigat...
Recently, fluorescence spectroscopy and imaging have been under investigation for in vivo diagnosis of several types of superficial cancer, including primary melanomas of the skin. Here we report on a detailed investigation of the autofluorescence properties of a K1735P melanoma implanted intradermally in the ears of syngeneic C3H/HeN mice. Although this tumour can produce melanin in some cases, it appeared as an unpigmented lesion in our experiments. Excitation-emission maps in the wavelength range of 360-700 nm were recorded from tumours and normal ears. The control ears and the tumour-bearing ears showed fluorescence in a broad range of excitation and emission wavelengths. Valleys of decreased fluorescence were observed in the 385-425 nm range and could be related to absorption of the excitation light by haemoglobin, oxyhaemoglobin and a third unknown absorber. The spectroscopic differences between the malignant melanoma and the control skin could be related to either differences in blood oxygenation or the tissue dimensions. However, no spectroscopic features were detected reflecting intrinsic differences between the melanoma and normal tissue.
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