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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Esthesioneuroblastoma (ESTH) is a neuroepithelial-cell-derived neoplasm of the olfactory mucosa composed of homogeneous small round cells which contain neurosecretory granules. Melanin has been detected in such tumours only occasionally. Here we describe a new case of ESTH with divergent differentiation. The primary neoplasm was found in a 67 year-old female, involving the left nasal and maxillary sinus; she died of cerebral metastasis ten months after diagnosis. Histologically only small round cells were seen, with S-100 and NSE positivity. Electron microscopy revealed neurosecretory granules and filaments, as well as the occasional presence of melanosomes. A nude mice xenograft line has been established, and is presently in its ninth transfer. Two cell types are present: small round-to-spindle shaped cells with neural features, and large epithelial-like ones. Both immunohistochemistry and electron microscopy confirm this dual differentiation, with the presence of membrane-bound dense-core neural secretion, as well as melanosomes of neuroectodermal origin. Additionally, an in vitro cell line has been established. Cytogenetic analysis confirmed the presence of both malignant human melanoma patterns; non-random abnormalities in chromosomes 1 and 6, extra copies of chromosome 7. Duplication of the long arm of chromosome 14, as seen in olfactory neuroblastoma, is also seen.
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PMID:Pigmented esthesioneuroblastoma showing dual differentiation following transplantation in nude mice. An immunohistochemical, electron microscopical, and cytogenetic analysis. 249

A distinguishing characteristic of cells of the melanocyte lineage is the expression of the melanosomal enzyme tyrosinase that catalyzes the synthesis of the pigment melanin. A tyrosinase cDNA clone, designated BBTY-1, was isolated from a library constructed from the pigmented TA99+/CF21+ melanoma cell line SK-MEL-19. Expression of BBTY-1 in mouse L929 fibroblasts led to synthesis and expression of active tyrosinase, and, unexpectedly, to stable production of melanin. Melanin was synthesized and stored within membrane-bound vesicles in the cytoplasm of transfected fibroblasts. BBTY-1 detected a 2.4-kb mRNA transcript in nine of nine pigmented, tyrosinase-positive melanoma cell lines. Tyrosinase transcripts of the same size and abundance were detected in a subset (three of eight) of nonpigmented, tyrosinase-negative melanoma cell lines, suggesting that post-transcriptional events are important in regulating tyrosinase activity. Two melanocyte antigens, recognized by mAbs TA99 and CF21, that are specifically located within melanosomes and are coexpressed with tyrosinase activity, did not react with transfected mouse fibroblasts expressing human tyrosinase, supporting the conclusion that these antigenic determinants are distinct from the tyrosinase molecule coded for by BBTY-1.
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PMID:Induction of pigmentation in mouse fibroblasts by expression of human tyrosinase cDNA. 249 55

The histogenesis of clear cell sarcoma was investigated by immunohistochemical examination of five tumors (two melanotic and three amelanotic) and electron microscopic examination of two of these tumors (one melanotic and one amelanotic). Melanin production was observed histologically in two of the tumors. The cytoplasm of cells in both types of tumor contained various numbers of melanosomes. Melanoma-specific antibody (HMB-45), anti-S-100 protein, and anti-vimentin antibodies gave positive reactions in four tumors, while all tumors showed Leu-7 immunoreactivity. No cytokeratin or epithelial membrane antigen (EMA) was detected immunohistochemically in any tumor. The immunoreactivity of this type of tumor with HMB-45 antibody strongly suggests melanocytic differentiation rather than schwannian or synovial differentiation. The reaction of the cells of one tumor with only Leu-7 indicates the existence of undifferentiated clear cell sarcoma of neuroectodermal origin that does not show definite melanocytic differentiation.
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PMID:Clear cell sarcoma. An immunohistochemical and ultrastructural study. 260 58

Forty-five tumors exhibiting the histological features of desmoplastic malignant melanoma or its variant, neurotropic melanoma, were found among approximately 4,500 soft-tissue tumors referred in consultation from Australia and New Zealand. All patients were Caucasians. Tumors fell into three groups: (a) desmoplastic melanoma with an atypical intra-epidermal melanocytic component (classical desmoplastic melanoma) (12 cases); (b) desmoplastic melanoma without an atypical intra-epidermal melanocytic component (de novo desmoplastic melanoma) (21 cases); (c) predominantly nerve-centered superficial malignant tumors with or without an atypical intra-epidermal melanocytic component (12 cases). Three of the nerve-centered tumors were associated with pigmentary abnormalities in the overlying skin. The patients' ages ranged from 42 to 91 years, with a peak in the seventh decade; 31 patients were male and 14 were female. Lesions were located in the head and neck (35 cases), shoulder and arm (four), back and chest (three), abdomen (one), thigh (one), and leg (one). Three tumors arose in irradiated areas, and one occurred on the face of a radiotherapist. Melanin was found in only four tumors, but the S-100 protein stain was positive in 19 tumors and negative in three. Follow-up details of 42 patients were available. In follow-up times from 4 months to 15 years (mean, 4.6 years), 15 patients (36%) had died of the disease or were terminally ill; 24 (57%) were alive with no apparent residual tumor; and three (7%) had died of other causes. Twenty-three patients (55%) developed one or more local recurrences; 17 (40%) developed distant spread, including extension into the cranial cavity along nerves; and 14 (33%) had both local recurrence and distal spread. Nine (82%) of 11 patients with nerve-centered tumors died or were terminally ill. The usual treatment was surgical. Most uncontrolled recurrences were resistant to chemotherapy and radiotherapy; however, two patients responded well, one to chemotherapy and one to radiotherapy. Our observation support Reed and Leonard's metaplastic explanation for the varied differentiation seen in desmoplastic melanomas.
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PMID:Desmoplastic malignant melanoma and its variants. A study of 45 cases. 271 88

Melanin synthesis of B16 mouse melanoma cells was found to be stimulated dose and time dependently by 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3], the hormonal form of vitamin D3. The stimulation of melanogenesis resulted from an increase in the activity of tyrosinase, a key enzyme in melanin synthesis. The minimum dose required for this stimulation was as low as 0.05 ng/ml, or 0.12 nM, a physiological level of plasma 1 alpha,25(OH)2D3. The stimulation by 1 alpha,25(OH)2D3 was specific; other derivatives of vitamin D3 caused no stimulation at a concentration of 500 ng/ml. When the cells were plated on agar plates, the proportion of dark or black colonies was not increased by the exposure to 1 alpha,25(OH)2D3. Furthermore, this compound did not induce melanin synthesis of an amelanotic variant. Thus, its stimulatory effect seemed to be due to stimulation of melanin synthesis of melanotic cells, rather than to conversion of amelanotic clones to melanotic ones. 1 alpha,25(OH)2D3 did not induce intracellular cyclic adenosine 3':5'-monophosphate, while cholera toxin induced cyclic adenosine 3':5'-monophosphate and stimulated melanin synthesis and tyrosinase activity much more than did 1 alpha,25(OH)2D3, suggesting that 1 alpha,25(OH)2D3 stimulates melanin synthesis by a cyclic adenosine 3':5'-monophosphate-independent mechanism. B16 melanoma cells contained specific receptors for 1 alpha,25(OH)2D3. Scatchard plot analysis revealed two types of receptor; the high-affinity receptor had a Kd of 18.3 pM and an Nmax of 10.6 fmol/mg of protein. The specificity of receptor binding was demonstrated by studies showing that, for 50% displacement of 1 alpha,alpha,25(OH)2D3 binding, other derivatives were required at 500 times higher concentrations or more. In contrast to 1 alpha,25(OH)2D3, retinoic acid inhibited melanin synthesis and tyrosinase activity of B16 melanoma cells dose and time dependently. On simultaneous treatment, 1 alpha,25(OH)2D3 and retinoic acid caused mutual interference, and a balance between their respective stimulating and inhibitory effects was obtained at a molar ratio of 10:1; i.e., with 10 nM 1 alpha,25(OH)2D3 and 1 nM retinoic acid.
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PMID:Regulation of melanin synthesis of B16 mouse melanoma cells by 1 alpha, 25-dihydroxyvitamin D3 and retinoic acid. 298 83

Melanin formation from 3,4-dihydroxyphenylalanine (dopa) was studied in the presence of estradiol and 2-hydroxyestradiol by use of a tyrosinase isolated from B16-F10 melanoma cells grown in C57 black female mice. Both steroids were found incorporated into melanin, but the 2-hydroxy compound was incorporated to a higher extent. The melanin was also able to bind substantial amounts of the two steroids, and the more highly oxidized compound showed higher binding. Melanin isolated from incubates of dopa with mushroom tyrosinase has the ability to bind the steroids and to incorporate small amounts into its structure. It is suggested that melanin in mammalian tissues may function as a depository for estrogens, particularly for those which are more highly oxidized.
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PMID:Role of estradiol and 2-hydroxyestradiol in melanin formation in vitro. 313 36

We describe results demonstrating the positive regulation of melanogenesis by two substrates of the melanogenic pathway. We have found that L-tyrosine and L-dihydroxyphenylalanine (L-dopa), whose metabolic fates are affected by the activity of that pathway, can also act as its regulators. In living pigment cells, tyrosinase (EC 1.14.18.1), a crucial and rate-limiting enzyme of melanogenesis, acts in subcellular organelles known as melanosomes. Melanin is laid down only in these organelles. We demonstrate that supplementing Ham's F-10 medium with additional L-tyrosine or L-dopa during the culture of amelanotic Bomirski hamster melanoma cells results in a rapid increase in melanin formation, which is not simply due to greater availability of substrate. There is a rapid increase in tyrosinase activity and a large scale synthesis of melanosomes. The effects of L-tyrosine and L-dopa are prevented by the addition of cycloheximide. The actions of L-tyrosine and L-dopa are specific in that under similar conditions D-tyrosine, D-dopa, N-acetyl-L-tyrosine, L-phenylalanine, L-tryptophan and L-valine have little or no effect. The two substrates, L-tyrosine and L-dopa, appear to act through related but distinct mechanisms. Our findings provide an example of a little-known phenomenon: regulation of a differentiated eukaryotic phenotype through positive control by substrates in the pathway.
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PMID:Positive regulation of melanin pigmentation by two key substrates of the melanogenic pathway, L-tyrosine and L-dopa. 314 38

Treatment of exponentially proliferating melanogenic Harding-Passey melanoma cells in monolayer culture (HPM-73 line) with a single dose of X-irradiation (up to 8 Gy) or continuously (for several weeks) with L-3,4-dihydroxyphenylalanine (L-Dopa) up to 5 X 10(-4) M resulted in a dose-dependent inhibition of cell proliferation, but not in death of all cells. Actually, 8 Gy-irradiated or L-Dopa (2 X 10(-4) M)-treated cultures finally reached the cell number and cell density of controls. However, a combination of a single dose of radiation (8 Gy) followed by L-Dopa (2 X 10(-4) M)-treatment resulted in destruction of all cells. Melanin formation was stimulated by L-dopa-treatment or X-irradiation, and was further elevated by the combined application of radiation and L-Dopa-exposure. Whether the effects of exogenously applied L-Dopa, an intermediary metabolite of melanin synthesis, are due to the conversion to growth-inhibitory metabolites (quinones, radicals, etc.) inside or outside the cell, was discussed. The latter might result from release (due to membrane damage or cell disintegration) of tyrosinase or/and melanosomes into the culture medium with the consequence of extracellular synthesis of potentially cytotoxic metabolites from medium substrates. Further, endocytosis of exogenous melanosomes and tyrosinase with potentially harmful effects is feasible. An application of such a combination therapy of melanoma to clinical medicine should be considered.
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PMID:Augmentation by L-dopa of growth inhibition and melanin formation of X-irradiated Harding-Passey melanoma cells in culture. 340 51

Synthetic eumelanin prepared by autooxidation of D,L-DOPA causes DNA strand breaks, as determined by alkaline elution after cell lysis with detergent and proteolysis, in B16CL4 mouse melanoma cells. The melanin is toxic to the cells in the range of doses that causes strand breaks. When the melanin was incubated with the cells at 37 degrees C in tissue culture medium, it was maximally effective after 15 to 20 min at causing strand breaks in the DNA. The extent of damage is concentration dependent, but the effect plateaus at 1 mg/ml. The nature of the interaction of the cellular DNA with melanin is consistent with strand breaks, not DNA-DNA crosslinks. The strand break damage is repaired, even in the continued presence of melanin, but repair is more rapid if the cells are washed and the melanin is removed. The form of the melanin is important for obtaining the effect. Sonication for 3 min abrogates the effect to a considerable extent, and repeated cycles of sonication can completely destroy the activity. Lost activity returns slowly with storage at 4 degrees C. Melanin is more effective at damaging DNA in a protein-free medium. It is also DNA-damaging at 4 degrees C, but less so than at 37 degrees C. Preliminary studies indicate that the strand breaks caused by melanin are additive with those caused by ionizing radiation. The extent of DNA strand breaks and alkali-labile sites caused by several other melanins was also determined. Some melanins did not cause frank strand breaks, but were active in causing alkali-labile sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Eumelanin causes DNA strand breaks and kills cells. 350 74

A B16 mouse melanoma cell line resistant to doxorubicin was obtained by continuous in vitro exposure to the drug. The ID50 for this line was 200 times higher than that for the parental cell line. The resistant cell line had some biological characteristics similar to those of the sensitive parental cell line, like saturation density and protein content. Differences were found in doubling time which was longer, cloning efficiency which was lower and DNA content which was higher in the resistant as compared to the parental line. Intracellular distribution of doxorubicin was also different having a nuclear-cytoplasmic ratio higher in sensitive than in resistant cells. Melanin content was an unstable feature in the sensitive cell line, whereas melanin was always present in resistant cells. Resistance to doxorubicin was maintained during 50 in vitro passages in the absence of the drug. Cross-resistance was found with vincristine and other anthracyclines, like daunorubicin and 4'-epi-doxorubicin but not with cis-platinum, and a new doxorubicin derivative, 4'-deoxy-4'-iodio-doxorubicin. The B16 line showed a lower resistance index to 4'-deoxy-doxorubicin and 4-demethoxy-daunorubicin (30 and 3 respectively), as compared to doxorubicin. Doxorubicin-resistance was partially circumvented by pretreatment of resistant cells with verapamil, a calcium chelating agent, and by trifluoperazine, a calmodulin-antagonist.
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PMID:Characterization of a doxorubicin-resistant murine melanoma line: studies on cross-resistance and its circumvention. 373 Feb 55


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