Pigment Cell & Melanoma Research[JOURNAL]
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155 papers
Metastatic variants of the B16 melanoma: metastasis is related to environmental conditions. Phenotypic changes in vitro and metastatic colonization potential in nude mice.
Aubert C
Melanoma Res · 1995 Jun · PMID 7640514
Variants of B16 melanoma exhibit strikingly different metastatic potential in AY/a (YB16 tumours) and a/a C57BL/6J (MB16 tumours) syngeneic mice. This study focused on relative pigmentation and metastatic potential in ei...
Variants of B16 melanoma exhibit strikingly different metastatic potential in AY/a (YB16 tumours) and a/a C57BL/6J (MB16 tumours) syngeneic mice. This study focused on relative pigmentation and metastatic potential in eight subline cultures initiated from B16 control and YB16 and MB16 tumours. During 6 months of in vitro growth in minimal essential medium, cells displayed a continuous decrease in their ability to form spontaneous lung colonies in 140 syngeneic mice with only persistence of enhanced metastasis-related characteristics depending on genetic change in yellow AY/a mice. Conversely, in a parallel experiment in 101 syngeneic mice in vitro, cells had a greater capacity to generate experimental metastases; this might be related to successive different environmental factors. In order to compare these prior results obtained in syngeneic mice, the above eight secondary cell lines were inoculated subcutaneously into Swiss nude mice. The primary tumours thus obtained were then serially transplanted monthly during 4 months. The new results obtained in a total of 277 mice showed that metastatic properties of cells were enhanced or restored in nude mice. Various tumour cell environments seem to be responsible for selective pressures that determine the melanoma metastatic potential. New, enhanced, heritable, metastasis-related characteristics can occur in melanoma cells as a result of genetic and metabolic changes and immunologic deficiency of the host. Apparent tumour-host relationship should not be neglected, since it has a clear influence on neoplastic diversity and malignant behaviour.
Ganglioside profiles of experimental melanomas and of their melanosomal fractions.
Vedralová E, Borovanský J, Hach P
Melanoma Res · 1995 Apr · PMID 7620344 · Publisher ↗
We compared ganglioside profiles of animal tumours (B16 and Cloudman S91 murine melanomas, Bomirski Syrian hamster melanoma), which are widely used as models of human melanoma, and of their melanosomal fractions. A gangl...
We compared ganglioside profiles of animal tumours (B16 and Cloudman S91 murine melanomas, Bomirski Syrian hamster melanoma), which are widely used as models of human melanoma, and of their melanosomal fractions. A ganglioside fraction was extracted and purified and the amount of each component ganglioside was assessed by thin-layer chromatography. GM3 was the dominant ganglioside species in the murine melanomas studied. Unlike human melanomas, the GD3 expression in mouse melanomas was low. GD3 and GM3 were major gangliosides in Bomirski hamster melanoma. Alkali-labile O-acetyl-GD3, a melanoma-specific ganglioside, was detected only in Bomirski melanoma. GD2, which in human melanoma is seen as a distinct signal of tumour progression, was not found in the animal melanomas studied. Melanosomes isolated from B16 and Bomirski melanomas contained GM3 and GD3 as their major ganglioside components. These data extend the group of common antigenic determinants shared by melanosomes and cell surface of pigment cells.
Detection of a human DNA sequence correlated with melanocyte-like differentiation and tumour suppression after transfection into murine melanoma cells.
Wakeling WF, Souberbielle BE, Bennett DC
Melanoma Res · 1995 Feb · PMID 7734953 · Publisher ↗
Since there is much indirect evidence for dominant suppressor genes for melanoma, we sought to isolate such a gene. Metastatic B16-F10 murine melanoma cells were lipofected with a normal human genomic library in a cosmid...
Since there is much indirect evidence for dominant suppressor genes for melanoma, we sought to isolate such a gene. Metastatic B16-F10 murine melanoma cells were lipofected with a normal human genomic library in a cosmid vector that also confers resistance to the drug G418. A few of the G418-resistant colonies acquired combinations of properties resembling those of normal melanocytes, including differentiated features (pigmentation, dendricity), slower growth, flat shape, monolayered colony form, stimulation of proliferation by a phorbol ester, and anchorage dependence. Four out of eight also showed reduced tumorigenicity in mice. Southern blotting indicated the presence of numerous cosmids in the melanocyte-like transfectants. DNA from one such line was used for secondary transfection. One secondary G418-resistant line showed pronounced melanocytic properties and marked tumour suppression in syngeneic and nude mice. A human repetitive sequence detected in this line was used in the polymerase chain reaction (PCR) to isolate intervening unique DNA sequences. One unique human sequence was attenuated in all tumors arising from both primary and secondary transfectants, suggesting close linkage with the sequence responsible for tumour suppression.
Impairment of the melanogenic pathway in B16 melanoma cells transfected with class I H-2 genes.
Prezioso JA, Hearing VJ, Muller J … +3 more , Urabe K, Wang N, Gorelik E
Melanoma Res · 1995 Feb · PMID 7734952 · Publisher ↗
Transfection of class I H-2Kb or H-2Kd into cells of a pigmented subclone of B16-F10 BL6 (termed BL6-8) results in the loss of melanin production. In contrast, transfected BL6-8 cells expressing H-2Dd, H-2Ld, class I H-2...
Transfection of class I H-2Kb or H-2Kd into cells of a pigmented subclone of B16-F10 BL6 (termed BL6-8) results in the loss of melanin production. In contrast, transfected BL6-8 cells expressing H-2Dd, H-2Ld, class I H-21Ak and/or the neor genes maintained their pigmented phenotype. Melanogenesis was also inhibited in cells which expressed the endogenous H-2Kb, but not the endogenous H-2Db, gene. In order to identify the specific defects in the melanogenic pathway responsible for the absence of melanin production, factors known to be related to the regulation of pigment formation were evaluated in H-2K-expressing cells. These studies showed that: (1) transfection of BL6-8 cells with the H-2Kb or H-2Kd, but not with the H-2Dd, H-2Ld or H-21Ak, genes was associated with complete inhibition of tyrosinase activity; (2) alpha-melanocyte-stimulating hormone (MSH) and theophylline (an inhibitor of cAMP phosphodiesterase) failed to stimulate tyrosinase activity in H-2K-positive cells, whereas tyrosinase activities in untransfected, or H-2DdH-2Ld, neor or H-21Ak-transfected cells were dramatically increased by those agents; (3) treatment with MSH had no effect on cAMP levels in H-2K-positive cells but stimulated cAMP levels more than 100-fold in H-2K-negative cells; (4) in contrast to MSH, forskolin, a stimulator of adenylate cyclase, was able to stimulate cAMP levels in all cell lines tested, but in H-2Kb-positive cells the levels of forskolin-induced cAMP were significantly less than those elicited in H-2Kb-negative cells; (5) electron microscopy showed that H-2K-positive cells lacked mature melanosomes; (6) Northern blot analyses showed that H-2K-positive cells lacked mRNA for tyrosinase or for the MSH receptor. Taken together, expression of the endogenous or transfected H-2K gene in BL6 melanoma cells results in down-regulation of the entire melanogenic pathway, including the inhibition of tyrosinase and MSH receptor gene expression, cAMP responses and melanosomal biogenesis.
Melphalan uptake, hyperthermic synergism and drug resistance in a human cell culture model for the isolated limb perfusion of melanoma.
Clark J, Grabs AJ, Parsons PG … +3 more , Smithers BM, Addison RS, Roberts MS
Melanoma Res · 1994 Dec · PMID 7703715 · Publisher ↗
Isolated limb perfusion with melphalan is a long-standing treatment for melanoma but the clinical conditions have not been subjected to a systematic evaluation. In order to establish optimal conditions for perfusion, thr...
Isolated limb perfusion with melphalan is a long-standing treatment for melanoma but the clinical conditions have not been subjected to a systematic evaluation. In order to establish optimal conditions for perfusion, three human melanoma cell lines were cultured with melphalan in vitro under conditions comparable to in vivo therapy. The most important findings were that: (a) 41.5 degrees C was synergistic for melphalan killing of three human melanoma cell lines; (b) prolonging the treatment time beyond 1 h had little additional toxicity; and (c) varying the initial pH of the culture medium had no effect. After 1 h of treatment, cells accumulated more melphalan at 41.5 degrees C than at 37 degrees C, relative to the extracellular concentration. A cell line (MM418) derived from a primary tumour was the most resistant of the three lines; pigmented or non-pigmented sublines were equally resistant. The A2058 line showed the lowest level of synergism with hyperthermia, and displayed a marked plateau at 10% of controls in the dose-response for survival, yet no melphalan-resistant subpopulation could be isolated. The implications of this work are that (a) enhanced cellular uptake of melphalan may account for hyperthermic synergism of melphalan; (b) varying conditions other than treatment time will be necessary to deal with the variation in resistance between tumours; and (c) repeated cycles of treatment may be needed for phenotypes such as A2058 where melphalan resistance appears to be based on an epigenetic mechanism.
Alteration of tyrosinase activity in human melanocytes and melanoma cells by histamine H2 and H3 ligands.
Le Gros G, Zhang XM, Parsons PG
Melanoma Res · 1994 Dec · PMID 7535606 · Publisher ↗
Nontoxic doses of the histamine H2 antagonists ranitidine, cimetidine, lamtidine and mifentidine rapidly and reversibly increased tyrosinase activity in an amelanotic human melanoma cell line (MM96L) with low constitutiv...
Nontoxic doses of the histamine H2 antagonists ranitidine, cimetidine, lamtidine and mifentidine rapidly and reversibly increased tyrosinase activity in an amelanotic human melanoma cell line (MM96L) with low constitutive activity. The H2 antagonists, famotidine and MGTI, and the imidazol(in)e receptor ligand clonidine had no effect either alone or in competition with ranitidine, whilst metiamide decreased tyrosinase activity. Lysosomotropic amines had a similar effect to ranitidine, except that induction reached a plateau at 6 h and was insensitive to amiloride. Human melanocytes and pigmented human melanoma cell lines exhibited minimal levels of tyrosinase induction, which was dependent on protein synthesis but not on RNA or DNA synthesis. Constitutive tyrosinase activity in MM96L cells was much less stable than in melanocytes and pigmented melanoma cells. No change was observed in expression of gp75, neural specific octamer binding proteins, or in mRNA levels of tyrosinase, Pmel-17 and gp75 (TRP-1). Tyrosinase was inhibited by the H3 agonist imetit but not by alpha-methylhistamine or the H3 antagonist thioperamide. Overall, this work showed that certain H2 antagonists activate an unstable form of tyrosinase in amelanotic melanoma cells by a post-transcriptional mechanism dependent on protein synthesis. An imidazoline/guanidinium receptor site rather than the H2 receptor appeared to be involved.
Thymidine kinase in malignant melanoma.
Borovanský J, Stríbrná J, Elleder M … +1 more , Netíková I
Melanoma Res · 1994 Oct · PMID 7858409
Thymidine kinase (EC 2.7.1.21) is an enzyme supporting DNA synthesis under conditions of increased cell proliferation. Although it has proved to be a useful marker for various malignant diseases, it has not been tested i...
Thymidine kinase (EC 2.7.1.21) is an enzyme supporting DNA synthesis under conditions of increased cell proliferation. Although it has proved to be a useful marker for various malignant diseases, it has not been tested in malignant melanoma. Thymidine kinase activity was measured by means of a radioenzymic assay in two classical animal models of melanoma disease--B16 and Cloudman S91 melanoma-bearing mice. Tumour cell proliferation was assessed histochemically by measuring the expression of proliferating cell nuclear antigen (PCNA). Tumour cytosolic specific thymidine kinase activity was found to be higher in less pigmented Cloudman S91 melanoma than in differentiated, ie pigmented B16 melanoma, relative to the proliferative activity of the two tumours. Serum thymidine kinase levels were increased in melanoma-bearing animals of both types compared with healthy mice; this also reflected the efficacy of the therapy: cyclophosphamide-treated B16 melanoma-bearing mice in which the tumour development was slowed down had significantly lower serum enzyme levels in comparison with the non-treated group and the same levels compared with control, healthy mice. Our results suggest that serum thymidine kinase levels might be used as a marker to follow the effect of melanoma therapy.
5th meeting of the European Society for Pigment Cell Research. Vienna, Austria, 19-22 October 1994. Program and abstracts.
Melanoma Res · 1994 Sep · PMID 7812159
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Metastatic variants of the B16 melanoma: metastasis is related to environmental conditions. Genetic and metabolic effects.
Aubert C
Melanoma Res · 1994 Aug · PMID 7950358 · Publisher ↗
Using variant B16 metastatic melanomas, attempts were made to explore the effects of both genetic and metabolic environmental factors in vivo as well as in vitro, on specific steps in the metastatic process. Metastases o...
Using variant B16 metastatic melanomas, attempts were made to explore the effects of both genetic and metabolic environmental factors in vivo as well as in vitro, on specific steps in the metastatic process. Metastases of the progenitor tumour in black C57BL/6J mice arose from a stable, heritable, non-random, pre-existing subpopulation of metastatic cells. In vitro, the environment influenced both pigmentary and metastatic phenotypes of variant B16 metastatic melanomas. The possibility that cells from different strains may express a phenotype following reinoculation into syngeneic mice was also explored. The experimental results suggested that new, enhanced, heritable, metastasis-related characteristics can develop as a result of genetic changes in yellow Ay/a and C57BL/6J mice that are accompanied by pigmentary changes. Such genetic changes can determine unstable non-random and random epigenetic metastatic effects with enhancement in vivo or disappearance in vitro of spontaneous metastatic ability and of the number of metastases, as monitored by serial transfers of tumour cells in vivo.
Cellular pathways leading to melanoma differentiation: therapeutic implications.
Soballe PW, Herlyn M
Melanoma Res · 1994 Aug · PMID 7950357 · Publisher ↗
The induction of differentiation, as evidenced by benign growth characteristics, dendritic morphology, pigmentation capability, and a mature antigenic phenotype, is an attractive theoretical basis for therapy in human me...
The induction of differentiation, as evidenced by benign growth characteristics, dendritic morphology, pigmentation capability, and a mature antigenic phenotype, is an attractive theoretical basis for therapy in human melanoma. Melanoma differentiation can be experimentally induced by modulating intracellular pathways involving protein kinase C, tyrosine kinases, and protein kinase A, or by modulating nuclear transcription with retinoids, DNA-damaging agents, and chemotherapeutic drugs. Other experimental differentiating agents include the amino acid tyrosine, histamine receptor antagonists, polyamine antagonists, dimethylsulphoxide, caffeic acid ester, and butyrate. The mechanisms involved in the actions of many of these agents are beginning to be understood and the pathways are often intersecting; cross-talk in the form of negative and positive feedback loops is extensive. Uncoupling of pathways is also seen, with some agents leading to simultaneous increases in both differentiated and transformed characteristics. While clinical benefits of this approach have so far been sparse, greater understanding of the cellular pathways of differentiation may open new therapeutic options in melanoma.
A low NM23.H1 gene expression identifying high malignancy human melanomas.
Caligo MA, Grammatico P, Cipollini G … +3 more , Varesco L, Del Porto G, Bevilacqua G
Melanoma Res · 1994 Jun · PMID 7919963 · Publisher ↗
The NM23 gene has been proposed as a metastasis-suppressor gene, and its use has been suggested as prognostic factor. NM23 was identified in a system of murine melanoma cell lines, in which an inverse relationship was fo...
The NM23 gene has been proposed as a metastasis-suppressor gene, and its use has been suggested as prognostic factor. NM23 was identified in a system of murine melanoma cell lines, in which an inverse relationship was found between NM23 expression and metastatic ability. In a human malignant melanoma study NM23 expression was found to be significantly lower in metastases that developed less than 24 months after diagnosis of the primary tumours. The present paper studies the expression of the NM23.H1 gene in cell lines which derive from primary or metastatic human malignant melanomas in relation to staging, infiltration degree, lymphocytic infiltration, cell morphology, cell pigmentation, karyotype, and disease-free survival. The level of mRNA expression of the NM23 gene is significantly lower in cell lines that derive from more infiltrating primary melanomas than in cell lines obtained from less infiltrating tumours. Moreover, cell lines derived from tumours of patients with a disease-free survival of more than 24 months (24-58 months) express the NM23 gene at higher levels than cell lines obtained from melanomas of patients with a disease-free survival of less than 24 months (6-15 months).
No high affinity melatonin binding sites are detected in murine melanoma cells and in normal human melanocytes cultured in vitro.
Mengeaud V, Skene D, Pevet P … +1 more , Ortonne JP
Melanoma Res · 1994 Apr · PMID 8069101 · Publisher ↗
Saturation studies of 2-(125I)-iodomelatonin binding to membranes from normal human melanocytes, mouse melanoma cells B16F10 and amelanotic S91 revealed no specific binding. Using 2-(125I)-iodomelatonin in the concentrat...
Saturation studies of 2-(125I)-iodomelatonin binding to membranes from normal human melanocytes, mouse melanoma cells B16F10 and amelanotic S91 revealed no specific binding. Using 2-(125I)-iodomelatonin in the concentration range of 6 to 566 pM, no high affinity melatonin binding sites were detectable in any of the cell types. Even when the concentration of radioligand was increased up to 2000 pM, specific binding was either low or absent and not reproducible. These results suggest that in the culture conditions used in this study, no high affinity melatonin binding sites are detected in pigmented cells.
Recreational exposure to sunlight and lack of information as risk factors for cutaneous malignant melanoma. Results of an European Organization for Research and Treatment of Cancer (EORTC) case-control study in Belgium, France and Germany. The EORTC Malignant Melanoma Cooperative Group.
Autier P, Doré JF, Lejeune F … +7 more , Koelmel KF, Geffeler O, Hille P, Cesarini JP, Liénard D, Liabeuf A, Joarlette M
Melanoma Res · 1994 Apr · PMID 8069100 · Publisher ↗
This study addressed the impact of exposure to ultraviolet radiation on the risk of cutaneous malignant melanoma (CMM), as well as the behavioral components at stake in its occurrence. We performed a one-to-one unmatched...
This study addressed the impact of exposure to ultraviolet radiation on the risk of cutaneous malignant melanoma (CMM), as well as the behavioral components at stake in its occurrence. We performed a one-to-one unmatched case-control study among subjects aged 20 years or more with naturally non-pigmented skin in Germany, France and Belgium. Four-hundred and twenty consecutive patients with CMM diagnosed from 1 January 1991 on were derived from hospital registries; 447 controls were chosen randomly in the same municipality as cases. Subjects unaware of the dangers of exaggerated exposure to sunlight display an estimated CMM risk of 3.72% (95% confidence interval 2.63-5.26). The number of holiday weeks spent annually in sunny resorts and sunbathing during the hot hours of the day are strong risk factors in the three countries, but not the number of years spent outdoors, as farmers or building workers. Multiple logistic adjustments on the host characteristics increases the CMM risk associated with recreational exposure to sunlight, as well as the adjustment on the unawareness of the dangers of exaggerated exposure to sunlight. Recreational exposure to sunlight and sunburn early in life seem capable of fostering the proliferation of pigmented lesions of the skin. Our data support the hypothesis that most CMM develop from pigmented lesions of the skin containing initiated melanocytes, and that the cell proliferation due to brutal, intermittent exposures to solar radiation amplifies the likelihood of a melanocyte entering into a malignant process.(ABSTRACT TRUNCATED AT 250 WORDS)
Immunocytochemical diagnosis of amelanotic metastatic melanoma using monoclonal antibodies HMB-45 and Ep1-3.
Mottolese M, Venturo I, Benevolo M … +4 more , Di Filippo F, Lopez M, Bigotti A, Natali PG
Melanoma Res · 1994 Feb · PMID 8032219 · Publisher ↗
The analysis of fine-needle aspirates and effusions has proved to be a valuable tool for the cytological identification of metastatic melanoma. Nevertheless, while malignant pigmented cells can be easily detected on cyto...
The analysis of fine-needle aspirates and effusions has proved to be a valuable tool for the cytological identification of metastatic melanoma. Nevertheless, while malignant pigmented cells can be easily detected on cytological specimens, their identification may be very difficult in patients bearing amelanotic lesions. In the present study we have evaluated whether this limitation can be overcome using two monoclonal antibodies (mAbs) HMB45 and Ep1-3, which are highly specific for the melanocyte lineage. These reagents were assayed in immunocytochemical tests performed on cytological material obtained from 50 patients with a past history of melanoma and 463 bearing metastases from a cryptic primary tumour. These mAbs, employed in combination with a panel of monoclonal reagents with well-defined tumour specificity, may improve the accuracy of the conventional cytopathological diagnosis of melanoma metastases in the two groups of patients.
Development and characterization of a murine monoclonal antibody against phaeomelanin and its precursor 5-S-cysteinyldopa.
Liu J, Jimbow K
Melanoma Res · 1993 Dec · PMID 8161885 · Publisher ↗
This study reports our success in developing a murine monoclonal antibody (mAb) against phaeomelanin and its major precursor, 5-S-cysteinyldopa (5-S-CD). A competitive enzyme-linked immunosorbent assay was developed and...
This study reports our success in developing a murine monoclonal antibody (mAb) against phaeomelanin and its major precursor, 5-S-cysteinyldopa (5-S-CD). A competitive enzyme-linked immunosorbent assay was developed and demonstrated that the new mAb, designated as 6D4 (IgG1, kappa), reacted with both 5-S-CD and phaeomelanin, but not with eumelanin. The concentrations required for 50% inhibition of 5-S-CD and phaeomelanin were 65 ng/ml and 95 ng/ml respectively. The minimal amount of 5-S-CD and phaeomelanin which could be detected by mAb 6D4 was approximately 5 and 6 ng/ml, respectively. The immunohistochemical assay indicated that the antigenic epitope(s) recognized by mAb 6D4 was localized in the cytoplasm of certain types of melanocytic tumours, such as superficial spreading melanoma.
In vivo depigmentation by hydroxybenzene derivatives.
Menter JM, Etemadi AA, Chapman W … +2 more , Hollins TD, Willis I
Melanoma Res · 1993 Dec · PMID 8161883 · Publisher ↗
Certain mono- and dihydroxybenzene derivatives are selectively cytotoxic for melanocytes in vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxicity/hair depigmentation in C57Bl mice...
Certain mono- and dihydroxybenzene derivatives are selectively cytotoxic for melanocytes in vivo, and can cause depigmentation of skin and hair. We produced selective melanocytotoxicity/hair depigmentation in C57Bl mice by injection of 0.032-1.0% p-t-butylcatechol (tBC) or p-hydroxyanisole (MMEH) in physiological saline. No depigmentation occurred on injection of 3,4-dihydroxyphenylalanine (DOPA) or 3,4-dihydroxyphenylacetic acid (DOPAC). Light- and electron-microscopic examination of biopsy specimens taken from depigmented areas indicates selective melanocyte damage as early as 2 h post-injection. Melanocytes from anagen hair are most susceptible to depigmentation. All four compounds are substrates for tyrosinase, but only tBC and MMEH generate their respective isolable 1,2-benzoquinones, tBCQ and MMEHQ. These caused depigmentation in C57Bl mice to a comparable degree to the parent compounds. DOPA- and DOPAC-quinones (DOPAQ and DOPACQ) are not spectroscopically detectable in solution, suggesting extremely low steady-state levels of these compounds. The net observed rate of reaction of the respective 1,2-quinone with 300 microM bovine serum albumin (BSA) in vitro varies widely, with tBCQ >> MMEHQ = DOPACQ >> DOPAQ. The results are consistent with a mechanism involving attack of -SH on melanosomal proteins and/or enzymes by tyrosinase-generated 1,2-quinones. This mechanism evidently differs from that involved in in vitro hydroxybenzene melanocytotoxicity of melanoma cells, in which active oxygen intermediates generated by hydroxybenzene autoxidation play a significant role. The most reliable prognosticator of in vivo depigmentation appears to be the ability of the depigmenter to form a spectroscopically stable 1,2-quinone which is capable of reacting with protein -SH.
Characterization of melanosome-associated proteins by establishment of monoclonal antibodies and immunoscreening of a melanoma cDNA library through an anti-melanosome antibody.
Dakour J, Jimbow K, Vinayagamoorthy T … +2 more , Luo D, Chen H
Melanoma Res · 1993 Oct · PMID 8292889 · Publisher ↗
Monoclonal antibodies against melanosomal components (human melanosome specific antigens; HMSAs) have been developed in our laboratory. HMSA-1-4 recognizes structural matrix proteins of melanosomes. HMSA-5 is identical t...
Monoclonal antibodies against melanosomal components (human melanosome specific antigens; HMSAs) have been developed in our laboratory. HMSA-1-4 recognizes structural matrix proteins of melanosomes. HMSA-5 is identical to TRP-1, equivalent to the b (brown) locus of murine melanocytes and expressed in early stages of melanosomal maturation. HMSA-6 is a protein associated with melanosomes but its role is still unclarified, and HMSA-7 is identical to the lysosomal protein CD63. We have also recently identified p90 calnexin-like, Ca(2+)-binding protein p97 melanotransferrin, and p64 beta-D-galactosidase-like protein associated with melanosomes through immunological screening of our melanocytes (melanoma cells) cDNA library. Approximately 150 genes and 60 loci are known to influence eye, skin and hair colour in mammals. Tyrosinase is a rate-limiting enzyme responsible for melanin synthesis. In addition, tyrosine-related proteins (TRPs) and their genes have been identified and cloned. Tyrosinase and TRPS (e.g., TRP-1; b-locus protein identical to HMSA-5 and TRP-2; dopachrome tautomerase) are synthesized according to underlying genetic programmes, and are up- and/or down-regulated to create various forms of abnormal melanin pigmentation. We herein propose the importance of investigating the role of non-tyrosinase related proteins such as those which we have recently identified.
Proliferative activity in Spitz's naevi compared with other melanocytic skin lesions.
Hofmann-Wellenhof R, Rieger E, Smolle J … +1 more , Kerl H
Melanoma Res · 1993 Oct · PMID 7904841 · Publisher ↗
Proliferative activity has been shown to correlate with the degree of malignancy in various human neoplasms. Immunostaining with the monoclonal antibody PC10 binding to proliferating cell nuclear antigen (PCNA) facilitat...
Proliferative activity has been shown to correlate with the degree of malignancy in various human neoplasms. Immunostaining with the monoclonal antibody PC10 binding to proliferating cell nuclear antigen (PCNA) facilitates the assessment of proliferation in routinely fixed, paraffin-embedded tissue sections. In this study we investigated the expression of PCNA in 29 Spitz's naevi in comparison with 43 primary malignant melanomas (MM), 18 cutaneous metastases of malignant melanoma (MMM) and 16 benign melanocytic naevi (BMN). After selection of the microscopic field with the highest number of PCNA-positive nuclei, the nuclear density (NDmax) of PCNA-stained nuclei in this field was assessed using interactive image analysis. The mean value of NDmax (given as 1000 nuclei/mm3 tissue) of SN was 27.9 (+/- 16.7) and differed significantly from that of MM (48.1 +/- 40.5; U-test: p < 0.05) and that of MMM (114.4 +/- 56.3; p < 0.01). Comparing NDmax of the subgroups of MM according to their maximal vertical tumour thickness with NDmax of SN we found significant differences only between SN and MM > 1.5 mm thick (n = 14; NDmax = 67.8 +/- 36.1) but not between SN and MM < or = 1.5 mm thick (n = 29; NDmax = 38.8 +/- 39.3). PCNA expression in SN did not differ from that of BMN (NDmax 23.8 +/- 28.5). Proliferative activity as assessed by measurement of PCNA expression therefore showed significant differences between BMN, SN and thin primary melanomas on one hand and thick primary melanomas and cutaneous metastases of malignant melanomas on the other hand.
Early recognition and prognostic markers of melanoma.
Pehamberger H, Binder M, Steiner A … +1 more , Wolff K
Melanoma Res · 1993 Aug · PMID 8219761
Malignant melanoma can be cured if the tumour is recognized at an early phase. Therefore, early recognition is of critical importance and cannot be overemphasized. Epiluminescence microscopy is a non-invasive technique t...
Malignant melanoma can be cured if the tumour is recognized at an early phase. Therefore, early recognition is of critical importance and cannot be overemphasized. Epiluminescence microscopy is a non-invasive technique that makes sub-surface structures of skin accessible for in vivo microscopic examination and thus provides additional criteria for the diagnosis of pigmented skin lesions. Thereby preoperative clinical diagnosis can be improved. In order to assess the prognosis of a melanoma patient and to predict the outcome of the disease a number of morphological and immunological parameters these will be reviewed, are helpful.
Ocular melanoma: an experimental model in New Zealand white rabbits.
Rodriguez Vicente J, Vicente Ortega V, Garcia Serrano F … +1 more , Garcia Rojo B
Melanoma Res · 1993 Jun · PMID 8400856
An experimental model is suggested for reproducing ocular melanoma in New Zealand white rabbits using B16 melanoma cells and protocols differing with respect to either tumour origin (subcutaneous fragments of melanoma B1...
An experimental model is suggested for reproducing ocular melanoma in New Zealand white rabbits using B16 melanoma cells and protocols differing with respect to either tumour origin (subcutaneous fragments of melanoma B16 or B16-F10 tumour cell cultures) or implant site (the anterior chamber or subchoroidal). In 20 animals, 20 mg of methylprednisolone acetate was injected subconjunctivally as a local immunosuppressant. The only protocol resulting in tumour was inoculation of 4 x 10(6) B16-F10 melanocytes into the anterior chamber of the eye. Trans-scleral injections of cell suspensions produced tumour growth in 43% (13/30) of animals so treated. Thirteen animals developed non-neoplastic pigmented lesions formed of numerous melanophages. Another 19 animals showed non-pigmented lesions caused by reaction to the surgical procedures. Subconjunctivally injected methylprednisolone acetate did not increase the incidence of tumour growth.
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