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

Cultured human malignant melanoma cells, when added to normal human lymphocytes stimulated to proliferate by mitogen or antigen, were found to inhibit the uptake of 3H-thymidine (3H-T) by the lymphocytes. A heat-labile factor present in the supernatants of the melanoma cultures is responsible for inhibition. Cell viability and blastogenesis are unimpaired in the lymphocyte cultures containing the inhibitor. Inhibition of 3H-deoxyuridine uptake was also noted indicating that both salvage and de novo pathways of DNA synthesis are involved. Lymphocytes appear to be preferentially affected as cultured colon cancer cells take up 3H-T normally in the presence of the inhibitor. Normal mitotic indices and biochemical estimation of DNA content in lymphocyte cultures containing the inhibitory factor indicate that DNA synthesis does proceed normally. The mechanisms of action of the inhibitor would appear to involve alteration of exogenous nucleoside rather than a metabolic inhibition of intracellular nucleic acid synthesis.
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PMID:Characterisation of human malignant melanoma cell lines. VI. Inhibition of 3H-thymidine uptake by normal stimulated lymphocytes. 59 53

Tumorigenicity is reversibly suppressed in mouse melanoma cells grown with 5-bromodeoxyuridine (BrdU). The nontumorigenic cells are immunogenic, and preinjection of these cells can protect mice against tumors inevitably formed when the parental, untreated melanoma cells are inoculated into inbred strain C57BL/6. A mixture of highly immunogenic clone, C(3)471, with malignant cells is also nontumorigenic. These effects are related to the host immune response since they occur only in immunocompetent mice. BrdU also reversibly suppresses functions related to pigment formation and plasminogen activation. These effects require incorporation of BrdU into DNA, emphasizing the value of the thymidine analog, BrdU as a tool to relate normal regulation of gene activity to perturbations of this regulation which produce malignant cells. This research can facilitate basic understanding of the malignant state and its relationship to host response as well as a method for immunizing melanoma patients after surgery to prevent tumor recurrence.
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PMID:Reversible suppression of malignancy and differentiation of melanoma cells. 59 22

In order to compare the biological effects of different thymidine (dT) analogs, two unusual cell lines (B-4 and HAB) previously isolated from a Syrian hamster melanoma line by selection with 5-bromodeoxyuridine (BrdU) were analyzed for their response to other analogs. B-4 cells require high concentrations of BrdU for optimal growth, and it was seen that the requirement for BrdU could be satisfied partially by 5-chlorodeoxyuridine (CldU) but not by the other dT analogs tested. HAB cells are able to grow with all the dT residues in nuclear DNA replaced by BrdU, and it was found that they could also grow with essentially all the dT residues in nuclear DNA replaced by CldU but not by other analogs. New cell lines resistant to 100 micrometer concentrations of CldU, 5-iododeoxyuridine (IdU), and 5-hydroxymethyldeoxyuridine (HMdU) were isolated from the melanoma line and tested for cross-resistance to the other dT analogs. A high level of cross-resistance was observed only with BrdU and CldU. The ability of the cell lines resistant to BrdU, CldU, and IdU to incorporate these analogs into nuclear DNA also was determined. BrdU and CldU were incorporated efficiently by all of the lines tested, but the IdU-resistant cells seemed to preferentially exclude IdU.
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PMID:Effects of thymidine analogs on Syrian hamster melanoma cells: phenotypes arising from selection for analog resistance. 60 84

L-Dopa has has been shown to demonstrate enhanced toxicity toward melanoma cells in vitro. Since melanocytes arise from the neural crest embryologically, the effect of L-dopa methyl ester, a soluble analog, on the murine C1300 neuroblastoma was studied. There was significant antitumor activity against the neuroblastoma, which was enhanced by combination with a dopa decarboxylase inhibitor, Ro4-4602. In vitro studies suggested inhibition of DNA synthesis as the principal site of action. A mechanism involving sulfhydryl compound scavenging is postulated.
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PMID:L-Dopa methyl ester: prolongation of survival of neuroblastoma-bearing mice after treatment. 62 65

Twelve consecutive treatments of a human melanoma cell line (MM253) with melphalan gave a subline (MM253-12M) which was five times more resistant to melphalan with respect to survival. In contrast to mustard-resistant rodent cells, the MM253-12M line had a higher stemline number than the parent line while growth rate and cell and colony morphology were unchanged. A further melphalan treatment following attempted mutagenesis with UV did not increase resistance. In a comparison of these two lines with two melanoma lines derived from other patients and the rat XC line, resistance was correlated with lower frequency of melphalan-induced chromosome aberrations, determined 48 h after a 4-h exposure to melphalan (3 microgram/ml). In the two cell lines studied, aberration-free metaphase cells from treated culture had fewer chromosomes than untreated cells. DNA synthesis studied in the 4- to 72-h period after treatment was inhibited to the same extent in MM253 and MM253-12M cells at 4 microgram/ml but to a greater extent in the sensitive line at 0.1-1.5 microgram/ml. During the first hour of treatment at 0.1-1.5 microgram/ml, DNA synthesis in MM253 appeared to be enhanced.
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PMID:Melphalan-induced chromosome damage in sensitive and resistant human melanoma cell lines. 66 48

The addition of deoxycytidine (dCyd) to the growth medium of cultured Syrian hamster melanoma cells causes a reversal of the toxic effects of 5-bromodeoxyuridine (BrdU) and a decrease in the extent of incorporation of BrdU into nuclear DNA. These effects of dCyd can be accounted for, in part, by the intracellular conversion of the exogenously supplied dCyd to thymidine (dThd) nucleotides which can compete with BrdU nucleotides for incorporation into DNA. To some extent, the conversion of dCyd to dThd nucleotides can be inhibited by increasing the concentration of BrdU in the growth medium. The conversion of dCyd to dThd nucleotides is inhibited completely by aminopterin (Apt), and Apt also prevents dCyd from reversing BrdU toxicity and from decreasing the level of BrdU incorporation into nuclear DNA. In a clone of Syrian hamster melanoma cells, increasing the concentration of dCyd in the growth medium from 1 micron to 1000 micron resulted in a progressive increase in the percentage of dThd residues in nuclear DNA being derived from the exogenous dCyd, until more than 90% of the dThd residues came from the exogenous dCyd. However, despite the increasing amount of dThd derived from exogenous dCyd, there was a plateau in the decrease in BrdU incorporation into nuclear DNA at concentrations of dCyd above 8 micron.
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PMID:Biological and biochemical effects of bromodeoxyuridine and deoxycytidine on Syrian hamster melanoma cells. 69 30

The mouse melanoma cell line PG19 has been found to be unresponsive to the growth-stimulatory action of insulin, although it responds well to other growth factors present in serum. Insulin stimulates DNA synthesis in mouse embryo fibroblasts, and responsiveness to insulin has been found to be a dominant characteristic in mouse fibroblast x PG19 hybrids. To examine the possibility that the unresponsiveness to insulin of the melanoma cells is attributable to a lack of insulin receptors, we have measured the binding of 125I-labeled insulin to the fibroblasts, melanoma cells, and fibroblast x melanoma hybrids. Insulin binds to the surface of the melanoma cells; however, the binding affinity appears to be lower than that observed for binding to diploid fibroblasts. In addition, the dissociation of insulin from the melanoma cells is not accelerated by excess unbound insulin, a kinetic effect observed in the dissociation of insulin from the fibroblasts and fibroblast x melanoma hybrids. This suggests that the class of insulin receptors characterized by this effect is absent on the PG19 cells, and present on the fibroblasts and fibroblast x PG19 hybrids.
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PMID:Responsiveness to insulin is a dominant characteristic in somatic cell hybrids. 70 85

In human fibroblasts, cholesterol oxide induced a similar degree of chromosome damage (8.6% of metaphases) and DNA repair synthesis (8-10% of cells with lightly-labelled nuclei) as low doses of ultraviolet light (UV), but did not produce single-strand DNA breaks or DNA damage detectable by inhibition of thymidine incorporation. Chromosome aberrations were detected up to 8 weeks after treatment with cholesterol oxide and UV. Combined treatments had almost additive effects on the frequency of chromosome aberrations but not on repair synthesis. Multiple daily doses of UV did not cause more aberrations than a single dose. Attempts to transform two fibroblast strains from normal donors and three derived from melanoma patients using single and combined treatments of UV, cholesterol oxide and hyperthermia (40 degrees) were unsuccessful.
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PMID:Chromosome damage and DNA repair induced in human fibroblasts by UV and cholesterol oxide. 70 20

Xeroderma pigmentosum (XP) is a rare inherited, heterogeneous syndrome with pigment anomalies, sun sensitivity, multiple cutaneous neoplasms and abnormal self protecting systems (SPS). The transmittence is autosomal-recessive. 50 percent of XP patients gets melanoma and 15 percent have neurological abnormalities. Clinical differentiation, determination of the DNA repair rate and cell fusion studies allow the differentiation of 6 complementation groups including De Sanctis-Cacchione syndrome and the XP variant typ. Pigmented Xerodermoid is a special form. Cytogenetic studies give evidences for the model character of XP for UV carcinogenesis.
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PMID:Xeroderma pigmentosum: heterogeneous syndrome and model for UV carcinogenesis. 71 83

The resistance of a human melanoma cell line (MM96) to both ultraviolet and ionizing irradiation was compared by two different methods of cloning, on plates and in agar. A high level of resistance to both ultraviolet (D0 = 320 ergs/sq mm) and ionizing irradiation (D0 = 4300 rads) was observed when viability of cells was determined by cloning in agar. In contrast, melanoma cells were found to be as sensitive as were other cells when viability after irradiation was determined by cloning on plastic plates. The difference in sensitivity to radiation between the two methods of cloning can be explained in a model involving damage to membranes as well as to DNA. At least for ionizing radiation, this effect is not restricted to melanoma cells since a HeLa subline, HeLa-QB1, showed a similar response. In contrast, a human lymphoblastoid line (JHP) cloned in agar was sensitive under these conditions (D0 = 120 rads).
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PMID:Dependence on cloning method of survival of human melanoma cells after ultraviolet and ionizing radiation. 71 46


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