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

Two series of examinations were carried out in two voluntary test groups for the purpose of elucidating the correlation between ultraviolet light load and oxidative stress as well as the way it is influenced by nutritive radical scavengers. After a 6 to 7-hour impact of sunshine on the whole body (sunbathing beach) at n = 8 a continuous progredient increase of thiobarbituric acid reactive substances could be identified in the serum (from 5.56 +/- 0.98 to 8.91 +/- 0.99 mumol/l, p < 0.001), which after new exposure to sunshine reached 11.3 +/- 2.4 mumol/l. Likewise, a 15-minute exposure to ultraviolet light at n = 24 induced increases of TBRS concentrations lasting from 1-2 days. After 14-day supplementation with beta-carotene (n = 6), D-alpha-tocopherol (n = 6), selenium (n = 6), and ginkgo biloba extract (n = 6) the extent of the oxidative stress could be inhibited during a second exposure to ultraviolet light up to the following efficiency: Se > Ginkgo > beta-carotene > vitamin E. The clastogenous effect of sunshine and ultraviolet light must be regarded as a factor for initiating and promoting cancerogenesis in the total organism. Concerning the aetiopathogenesis of malignant melanoma the paramagnetic properties of free radicals with their nonenergetic effects of the magnetic field have to be considered more carefully in scientific examinations.
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PMID:[Protection from uv-light-induced oxidative stress by nutritional radical scavengers]. 146 77

This study compares the toxic effects of the carotenoids, beta-carotene and canthaxanthin, and alpha-tocopherol (vitamin E) on human tumor cells and their normal counterparts in vitro. Seven different malignant cell lines were examined: oral carcinoma (two cell lines), breast (two cell lines), lung carcinoma (two cell lines), and malignant melanoma. The in vitro cell culture assays showed a consistent morphologic change in the affected tumor cells following treatment with carotenoid or vitamin E. A rounding of the tumor cells and eventual lifting off the tissue culture plate were observed. These changes were apparent after 1 to 5 hours of treatment depending on the tumor cell line. Associated with these observable cellular changes were quantitative reductions in proliferation (3H-thymidine proliferation) and succinic dehydrogenase activity (MTT assay). In addition, there was a noticeable change in protein expression, with an increased expression of a 70-kD protein following treatment with beta-carotene. This protein was associated with tumor cells showing a decrease in proliferation (oral carcinoma, malignant melanoma) but not with normal keratinocytes or melanocytes. These studies substantiate a selective cytotoxic effect on human tumor cell growth by carotenoids and alpha-tocopherol in vitro, and may provide an explanation of the therapeutic activity of these agents and their possible use in the treatment of premalignancy or early oral carcinoma.
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PMID:The selective cytotoxic effect of carotenoids and alpha-tocopherol on human cancer cell lines in vitro. 154 92

The rate of oxidation by purified mushroom tyrosinase of 30 compounds was measured by oximetry, and the tyrosinase-dependent cytotoxicity of each estimated in an in vitro assay using exposure of non-melanogenic cells to the agents in the presence and absence of tyrosinase. Cytotoxicity was estimated by immediate inhibition of DNA synthesis; 4-hydroxyanisole was used as the reference material. Compounds that were not oxidized by tyrosinase were found to be non-toxic but there was no direct relationship between the rate of oxidation and the relative cytotoxicity of those materials that acted as substrates for the enzyme. Thioethers were found to be more cytotoxic than the corresponding phenoxyethers. This was partly due to their greater rate of oxidation by tyrosinase and, in the case of propylthiophenol, the consequence of higher effective toxicity of the lipophilic species. The optimum chain length for the side chain of the oxyethers was three saturated carbon atoms and the toxicity appeared to be influenced by the lipophilicity of the compounds, possibly reflecting the relative lipid solubility of the putative toxic ortho-quinones generated from them. The maximum tyrosinase-dependent toxicity observed was in the range 5-6 times the relative toxicity of 4-hydroxyanisole. Sulphinyl and sulphonyl derivatives were inactive. In addition to oxyethers and thioethers, esters and glycosides of oxyethers were also examined and were found to be toxic in the presence of tyrosinase when hydrolysed. The succinates were found to be oxidized and toxic in our test system, suggesting that they rapidly underwent spontaneous hydrolysis. Oximetry data suggest that slight spontaneous hydrolysis of the other compounds occurs but they were not toxic in our assay. Ring-methylated phenoxyethers were oxidized relatively slowly and were non-toxic. Fluorine-substituted phenoxyethers were oxidized slightly more rapidly and exhibited clear toxicity in our system. Sesamol was oxidized to a black pigment but was non-toxic in our assay. A water-soluble vitamin E derivative was not oxidized and was non-toxic. Allyl hydroquinone was not oxidized but exhibited significant direct toxicity.
Melanoma Res
PMID:In vitro assessment of the structure-activity relationship of tyrosinase-dependent cytotoxicity of a series of substituted phenols. 182 34

Patients (n = 15) with metastatic malignant melanoma, hypernephroma, and colon carcinoma received a three-phase adoptive immunotherapy protocol: phase 1, 10(5) units (high-dose) interleukin-2 (IL-2) iv every 8 h or 1 mg/m2 continuous intravenous infusion; phase 2, 6.5 d rest + leukapheresis; phase 3, 4 d of high-dose IL-2 plus three infusions of autologous lymphokine-activated killer cells. Toxicities of treatment included fever, chills, tachycardia, hypotension, vomiting, diarrhea, and fluid retention. Patients entering the trial were not malnourished, and mean plasma ascorbic acid concentrations before therapy were normal (36.3 +/- 14.2 mumol/L). Mean concentrations dropped by 80% after the first phase of treatment with high-dose IL-2 alone (to 7.4 +/- 4.5 mumol/L). Mean plasma ascorbic acid concentrations remained severely depleted (between 4.5 and 7.4 mumol/L) throughout the remainder of the 15-d treatment. Ascorbic acid concentrations became undetectable (less than 2.8 mumol/L) in 12/15 patients during this time. Blood pantothenate and plasma vitamin E concentrations remained within normal limits in all patients tested throughout the phases of therapy.
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PMID:Hypovitaminosis C in patients treated with high-dose interleukin 2 and lymphokine-activated killer cells. 196 85

In 1974 and 1975, serum specimens were collected from 25,802 volunteers in Washington County, Maryland. The serum was kept frozen at -73 degrees C until the time of assay. Prediagnostic samples from 436 cancer cases and 765 matched control subjects have been assayed. Nine sites have been studied: colon, rectum, pancreas, lung, melanoma, basal cell of skin, breast, prostate, and bladder. Serum beta-carotene levels showed a strong protective association with lung cancer, suggestive protective associations with melanoma and bladder cancer, and a suggestive but nonprotective association with rectal cancer. Serum vitamin E levels had a protective association with lung cancer; none of the other sites showed impressive associations. Low levels of serum lycopene were strongly associated with pancreatic cancer and less strongly associated with cancer of the bladder and rectum.
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PMID:Prediagnostic serum levels of carotenoids and vitamin E as related to subsequent cancer in Washington County, Maryland. 198 96

Novel or modified serum-free media were developed for the anchorage-dependent growth of nontransformed murine mammary epithelial cells (MMEC) and Balb/MK murine keratinocytes respectively. Growth rates for both cell lines were similar in serum-containing and serum-free media. The serum-free media were used to evaluate potential mechanisms of epithelial cell growth regulation by type 1 transforming growth factor beta (TGF-beta 1). The growth of MMEC and Balb/MK cells was reversibly inhibited 40-65% in a time- and dose-dependent fashion by TGF-beta 1 under both serum-containing and serum-free conditions. Constitutive over-expression of a transfected c-myc oncogene in MMEC did not result in loss of sensitivity to growth inhibition by TGF-beta 1. In addition, Balb/MK and MMEC growth inhibition by TGF-beta 1 was not potentiated by polyunsaturated fatty acids or reversed by vitamin E. Exogenous type V collagen was able to mimic the inhibitory effects of TGF-beta 1 on the serum-free growth of Balb/MK and MMEC. In contrast, collagen types I and IV, fibronectin and laminin did not inhibit the growth of these cells. The type V collagen used was not contaminated with TGF-beta, and subsaturating, but not saturating concentrations of type V collagen and TGF-beta 1 were additive with respect to Balb/MK and MMEC growth inhibition. These results demonstrate that nontransformed epithelial cell growth inhibition by TGF-beta 1 is mediated by mechanisms distinct from those observed with certain carcinoma and melanoma cells. Our results also suggest the possible involvement of type V collagen in Balb/MK and MMEC growth inhibition by TGF-beta 1.
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PMID:Evaluation of the role of extracellular matrix proteins, polyunsaturated fatty acids and c-myc expression in the inhibition of the serum-free growth of epithelial cells by TGF-beta 1. 207 65

Treatment of B-16 melanoma cells in culture with d-alpha-tocopheryl succinate (vitamin E succinate) at concentrations of 11.3 and 15.1 microM inhibited growth and induced cell differentiation in culture. Vitamin E succinate treatment decreased the levels of c-myc and H-ras specific mRNAs in melanoma cells. Similar results were obtained by the vitamin retinoic acid and the nonvitamin agents R020-1724 (4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone), an inhibitor of cyclic nucleotide phosphodiesterase (0.72 mM), and sodium butyrate (1 mM), which induced differentiation and (or) inhibited growth of melanoma cells in culture. The extent of inhibition of c-myc mRNA was greater than that of H-ras mRNA. These results indicate that vitamin E succinate induced reduction of the levels of c-myc and H-ras mRNAs is related to growth inhibition of melanoma cells in culture.
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PMID:Decreased expressions of c-myc and H-ras oncogenes in vitamin E succinate induced morphologically differentiated murine B-16 melanoma cells in culture. 217 40

It has been estimated that of all new cancers diagnosed annually in the USA almost one third originate in the skin such as basal cell carcinoma, squamous cell carcinoma, and melanoma. Much progress has been achieved in our understanding of the pathogenesis and it became clear primarily by studies of chemical carcinogenesis in murine skin that this is a stepwise process comprising at least three distinct stages: initiation, promotion, and malignant conversion or progression. This knowledge of the pathogenesis prompted to the development of chemoprevention of cancer in humans. Large clinical chemoprevention intervention studies with vitamin A, -carotene, vitamin E, and selenium are on the way. The metabolism of chemical carcinogens by cytochrome P-450 isozymes and other xenobiotica metabolizing enzymes has been proven essential in chemocarcinogenesis but it plays also a crucial role in the biotransformation of cancer themotherapeutic agents and may be of importance in influencing the efficacy as well as the side effects of these drugs in the target organ. Although our current knowledge is limited, studies of the xenobiotic metabolizing enzymes in extrahepatic tissues such as the skin demonstrate that they are possible. They may be of special importance in the near future in order to design individual therapies that will avoid unwanted toxicities and enhance therapeutic effectiveness.
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PMID:[The skin as a signal organ in the development of recent cytostatic drugs and anti-tumor strategies]. 218 7

Dietary intake and the plasma levels of retinol, alpha-tocopherol, lycopene, alpha-carotene, and beta-carotene for 204 cases with malignant melanoma were compared with those of 248 controls. Cases and controls were patients 18 years of age or older making their first visit to a dermatology subspecialty clinic for pigmented lesions from July 1, 1982 to September 1, 1985. Intakes of nutrients were estimated using a semiquantitative food frequency questionnaire. No significant associations with malignant melanoma were observed for higher plasma levels of lycopene, retinol, or alpha-carotene in logistic regression analyses after controlling for age, sex, plasma lipids, and known constitutional risk factors (hair color and ability to tan). In similar models, the odds ratio comparing the highest with the lowest quintile was 0.9 (95% confidence interval (CI) 0.5-1.5) for plasma beta-carotene, 0.7 (95% CI 0.5-1.3) for plasma alpha-tocopherol, 0.7 (95% CI 0.4-1.2) for carotene intake, and 0.7 (95% CI 0.4-1.3) for total vitamin E intake. A trend toward reduced risk of melanoma was observed for increasing intake of iron (not including supplements); this was related to the more frequent consumption of baked goods, such as cake, among controls. Alcohol consumption was positively associated with risk of melanoma (chi for trend = 2.1, p = 0.03); the odds ratio for consumption of over 10 g/day compared with persons with no alcohol intake was 1.8 (95% CI 1.0-3.3).
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PMID:Diet, plasma levels of beta-carotene and alpha-tocopherol, and risk of malignant melanoma. 231 93

Improved serum-free media were developed for the anchorage-dependent growth of A549 human lung carcinoma and B16 mouse melanoma cell lines in vitro. Type 1 transforming growth factor beta (TGF-beta 1) inhibited the growth of A549 or B16 cells under serum-free conditions or in the presence of 10% serum by 15-33%. In contrast, in the presence of micrograms/ml concentrations of polyunsaturated fatty acids (PUFAs), picomolar concentrations of TGF-beta 1 irreversibly inhibited the serum-free growth of A549 or B16 cells by 90-100%. The PUFAs alone had little effect on cell growth. Cell growth inhibition by TGF-beta 1 was not potentiated by saturated fatty acids, monounsaturated fatty acids, or prostaglandins. Inhibition of A549 or B16 cell growth by TGF-beta 1 in the presence of PUFAs was almost completely reversed by the antioxidant vitamin E, suggesting a role for lipid peroxidation in this process. Inhibition of A549 or B16 cell growth by TGF-beta 1 in the presence of 5% fetal calf serum was also potentiated by PUFAs and partially reversed by antioxidants. The presence of retinoic acid was required for maximal PUFA-dependent growth inhibition of A549 or B16 cells by TGF-beta 1 under some, but not all, conditions. These results suggest that inhibition of carcinoma and melanoma cell growth by TGF-beta 1 is mediated, in large part, by PUFAs.
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PMID:Inhibition of carcinoma and melanoma cell growth by type 1 transforming growth factor beta is dependent on the presence of polyunsaturated fatty acids. 237 Dec 87


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