Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0025202 (melanoma)
 69,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chlorozotocin is a glucose-substituted chloroethyl nitrosourea with pharmacologic properties suggesting it is a relatively nonmyelosuppressive cancer chemotherapy drug. Preclinical studies have shown that this drug possesses approximately twice the in vitro alkylating activity of the chloroethyl nitrosoureas BCNU and CCNU. In the L1210 leukemia system, chlorozotocin has curative activity at doses that result in minimal bone marrow toxicity. In vitro studies of human bond marrow stem cells have shown that chlorozotocin is relatively sparing of these cells compared to BCNU. Phase I and phase II trials in man have been performed that show that chlorozotocin's dose-limiting toxicity is thrombocytopenia at doses greater than 120 mg/m2. In the phase II trial, 16% of patients with colon cancer and 20% of patients with malignant melanoma evidenced objective regression of disease. Chlorozotocin is now undergoing phase II evaluation in combination chemotherapy trials in colon and stomach cancer.
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PMID:Preclinical and clinical studies on chlorozotocin, a new nitrosourea with decreased bone marrow toxicity. 644 66

Matched pairs of malignant and non-malignant hybrid cells were compared in their response to glucose deprivation and to tunicamycin. Glucose deprivation induced an increase in the maximum velocity in the malignant cells, but not in the non-malignant cells. The Michaelis constant of hexose uptake was largely unchanged by glucose deprivation except in the case of one melanoma derivative, PG19 G-, which showed a large increase in Michaelis constant when deprived of glucose. Tunicamycin increased the Michaelis constant of hexose uptake in both malignant and non-malignant cell lines. It is therefore possible that the Michaelis constant of hexose uptake is affected by the extent of glycosylation of one or more of the cell membrane glycoproteins.
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PMID:Alterations induced by glucose deprivation and tunicamycin in the kinetic parameters of hexose transport in hybrid cells. 649 Jul 36

Three types of murine tumors, B-16 melanoma, A-10 carcinoma, and S-180 sarcoma, were shown to contain elevated glycosaminoglycan (GAG) concentrations in vivo as compared to normal muscle or subcutaneous tissue. Hyaluronate was especially concentrated in the A-10 carcinoma, which contained approximately six times more hyaluronate than subcutaneous tissue and 18 times more than muscle. In all three tumors, chondroitin sulfates, especially chondroitin-4-sulfate, were present in higher concentrations than in the normal tissues. In culture, however, all three tumor cell lines produced less than 5% as much GAG as mouse fibroblasts, when measured by incorporation of [3H] acetate or by chemical analysis. Varying the culture passage number or the medium composition, ie, glucose, serum, and insulin concentrations, had little effect on GAG synthesis by the tumor cells. The low GAG levels in the tumor cell cultures were not due to hyaluronidase activity in their media. In an attempt to mimic possible host-tumor cell interactions that could account for the elevated GAG levels in vivo, tumor cells were cocultured with fibroblasts, but no stimulation above the amount made by the tumor cells alone plus that by the fibroblasts alone was observed. Conditioned media from the tumor cells, either dialyzed or not against fresh complete medium, had no effect on fibroblast GAG synthesis. Tumor extracts, however, were found to stimulate synthesis of hyaluronate by fibroblasts. Stimulation by extracts of A-10 carcinoma was greater than and additive to that of serum. The above results strongly suggest that GAG production in these tumors is in part regulated by host-tumor interactions.
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PMID:Stimulation of glycosaminoglycan production in murine tumors. 651 22

To study its specificity for hyperglycemia, stable HbA1 was determined with ion-exchange chromatography in 240 patients consecutively hospitalized in the department of internal medicine and in a non-diabetic reference population. Reference values were found to increase significantly with age in the age groups less than 30, 30-60, and greater than 60 years. 41 patients had stable HbA1 more than 2 SD above the mean of the reference group and random blood glucose less than 7 mmol/l, and 21 of these were classified as non-diabetics according to data in medical records. Four non-diabetic patients had stable HbA1 higher than + 4 SD. One of them had haemoglobinopathia, one severe anaemia under cortisone treatment, one cortisone treated myelomatosis with renal insufficiency and severe anaemia, and one patient had lymphoma and renal insufficiency. Nine patients had stable HbA1 between + 3 and 4 SD and diagnoses of coronary heart disease (4), rheumatoid arthritis (2), asthma (1), chronic renal failure (1) and malignant melanoma (1). Five of them were treated with cortisone or diuretics. Four patients had stable HbA1 slightly below the reference range. In summary marked elevation of stable HbA1 due to factors other than diabetes occurred in a few patients with haematological disorders.
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PMID:Abnormal concentration of stable HbA1 in non-diabetic patients. 653 2

5-Fluorouracil (5FU) metabolism was studied in intact cancer cells kept in suspension by incubation with tritiated 5FU. Metabolites were analyzed using various chromatographic procedures, including a one-directional separation on PEI-cellulose sheets, which separated 5FU from the mono-, di- and triphosphate forms and from nucleotide sugars. The monophosphate ester was present as FdUMP, as could be demonstrated with another chromatographic procedure. In the human melanoma cell lines IGR3 and M5 the main metabolite of 5FU was 5-fluorouridine, while in the murine B16 melanoma only a small amount of 5-fluorouridine was formed. In B16 cells more 5FU label was present as the triphosphate ester while in M5 cells more FdUMP was formed. With all three cell lines 5FU was incorporated into RNA; this incorporation was stimulated by 1 mM N-(phosphonacetyl)-L-aspartate (PALA). PALA did not significantly affect the conversion of 5FU into other metabolites, nor did it affect the incorporation of 5FU into DNA. A 5FU-nucleotide sugar, present as the diphosphate-glucose, was a predominant 5FU-metabolite in M5 cells but not in the other cell lines. Its identity was confirmed by thin-layer chromatography and high-performance liquid chromatography. Its possible function is discussed.
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PMID:Separation of several 5-fluorouracil metabolites in various melanoma cell lines. Evidence for the synthesis of 5-fluorouracil-nucleotide sugars. 654 12

The in vitro growth characteristics of a human malignant melanoma cell line cultured in 0.5 mM pyridoxal supplemented medium were studied. Experimentation revealed that the high-dose pyridoxal supplemented medium severely inhibited the growth of melanoma cells over a 72-hour growth period. Additional experimentation showed that cells cultured for 6 hours in the pyridoxal supplemented medium took up 25% less and incorporated 20% less [3H]uridine than control cultures. [3H]Glucose uptake was reduced by 23% at this time point. [3H]Thymidine uptake was inhibited by 12%, but no inhibition was detected in [3H]thymidine incorporation. When the vitamin B6 antagonist 4-deoxypyridoxine (which competes with pyridoxal for pyridoxal kinase) was added to the pyridoxal supplemented medium, the inhibition in [3H]uridine incorporation was reduced from 19% to 6%. However, 4-deoxypyridoxine did not reverse the inhibition of [3H]uridine uptake. These results indicate that pyridoxal and its metabolite, pyridoxal 5'-phosphate, may be involved in the growth regulation of a human malignant melanoma cell line.
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PMID:High-dose pyridoxal supplemented culture medium inhibits the growth of a human malignant melanoma cell line. 663 29

The tyrosinase (EC 1.14.18.1) activity of cultured B-16 mouse melanoma cells (C2M) in the stationary phase depends greatly on whether the culture medium contains glucose or galactose. The activity in medium containing galactose was about ten times that in medium containing glucose at pH 7.2. This difference in tyrosinase activity was concluded to be due to a shift of balance between synthesis and degradation of the enzyme. Experiments were conducted with stationary phase cultures in the presence of cycloheximide. The melanoma cells did not synthesize tyrosinase in medium containing glucose in the stationary phase. But when they were cultured under identical conditions, except that glucose was replaced by galactose, they continued to synthesize tyrosinase. The rate of synthesis in medium containing galactose at pH 6.3 was one third of that in the same medium at about pH 7, in which the increase in specific activity of tyrosinase per day was about 30 nmoles/mg cell protein per hr. The rate of degradation of the enzyme was practically the same in medium containing glucose as in medium containing galactose, and largely depended on the pH of the culture medium. At pH 6.3, the half-life was about one third of that at pH 7.2, where it was about 1.8 days. The degradation at acidic pH values was much reduced by ammonium salt and was strongly inhibited by the protease inhibitor, leupeptin.
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PMID:Synthesis and degradation of tyrosinase in cultured melanoma cells. 677 69

The human malignant melanoma cell line, NEL, was found to contain glucocorticoid receptors. When the binding data were analyzed according to the method of Scatchard, results indicated a ligand binding capacity of 247 fmol/mg protein and a Kd of 1 X 10(-9) M. Additional studies show that the continuous incubation of NEL cells with triamcinolone acetonide (TA) for 72 hr results in a 30% inhibition in cell growth. To ascertain the mechanism by which glucocorticoids inhibit the growth of NEL cells, uptake and incorporation studies were carried out using various 3H precursors. Results indicate that, after 4 hr of TA treatment, a modest inhibition in [3H]thymidine uptake was observed, while stimulation of [3H]thymidine incorporation was noted at all steroid concentrations tested. However, cells incubated for 18 hr with TA (concentration, greater than or equal to 10(-8) M) showed a 30% decrease in the amount of [3H]thymidine incorporated into DNA. TA had no effect on [3H]leucine or [3H]glucose uptake after 4 hr of treatment but did inhibit [3H]glucose (42%) uptake after 18 hr of treatment. A slight stimulation (9%) in [3H]leucine incorporation was observed at this time point. When NEL cells were incubated with TA and the antiglucocorticoid, progesterone, the inhibition in [3H]thymidine incorporation was negated. These findings indicate that glucocorticoids exert some influence on the growth of human melanoma cells, and this effect is mediated through the glucocorticoid receptor.
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PMID:In vitro growth inhibition of human malignant melanoma cells by glucocorticoids. 685 May 83

It has been reported previously that malignancy in hybrid cells is associated with changes in two glycoproteins of molecular mass 90,000 and 100,000. In the current paper the characteristics of a clonal derivation of a murine melanoma cell line (PG19G-), selected for growth in low levels of glucose, are described. The cells had considerably reduced amounts of the 90 K and 100 K glycoproteins as judged by lectin affinity-labelling. When the level of glucose in the medium is raised the two glycoproteins become detectable after a few hours. This inducibility is specific for D-glucose and D-mannose at concentrations in excess of 300 mg/l and is inhibited by cytochalasin B but not by cytochalasin A. The 90 K glycoprotein differs from the 100 K in that its level varies with the glucose concentration even in the parent cell line PG19 and in other tumour lines. This is not the case for the 100 K glycoprotein, the synthesis and/or glycosylation of these two glycoproteins are, therefore, governed by separate control mechanisms. The relationship of the glucose-sensitive proteins to the glucose transporter is discussed.
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PMID:The apparent inducibility of tumour marker glycoproteins in a melanoma cell line selected for growth in low levels of glucose. 707 25

An immuno-modulator fraction (Alva) extracted from an endemic plant, in the south of Madagascar, the Aloe vahombe, significantly protects mice against bacterial, parasitic and fungal infections. Wishing to verify whether the fraction Alva was active in tumour reduction, we studied its effect on the development of experimental fibrosarcoma and melanoma in mice by intravenous and intracutaneous injections and injections directly into the tumour of the immunostimulant fraction. We have observed cures, only in the case of the McC3-1 tumour but it is encouraging to note that under different experimental conditions the rate of growth of tumours in animals which were treated is slower than in those not treated. The Alva fraction is a substance which is hydrosoluble, thermostabile, having a molecular weight exceeding 30 000 and is a polysaccharide. The predominant sugars are glucose and mannose in 3:1 ratio. Preliminary studies of its action seem to indicate that the Alva fraction acts upon non-specific response and could possibly stimulate the phagocyte activity of the peritoneal macrophagus.
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PMID:[Immunomodulating properties of an extract isolated and partially purified from Aloe vahombe. 3. Study of antitumoral properties and contribution to the chemical nature and active principle]. 718 35


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