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)

The rapid increase in melanoma incidence and mortality has given rise to nationwide and international campaigns that encourage the public to protect themselves from solar radiation with clothing, sunscreens, and other measures. The basis of these campaigns has been challenged by proponents of the theory that vitamin D, which is generated in the skin by ultraviolet B radiation, inhibits the development of melanoma. The present investigation tests this theory by examining the relation between dietary vitamin D and melanoma risk in a case-control study. Vitamin D intake was assessed by a food-frequency questionnaire in 165 melanoma patients and 209 controls. After controlling for age, hair color, and family history of melanoma, there was no association of melanoma risk with total vitamin D intake, calorie-adjusted vitamin D intake, vitamin D intake from foods, or consumption of milk or vitamin D supplements. We find no evidence to suggest that vitamin D protects against melanoma, and therefore continue to support the ongoing public health campaigns aimed at reducing sun exposure for the prevention of melanoma.
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PMID:Case-control study of melanoma and dietary vitamin D: implications for advocacy of sun protection and sunscreen use. 156 30

Melanoma is the second most common cancer, after testicular cancer, in males in the U.S. Navy. A wide range of occupations with varying exposures to sunlight and other possible etiologic agents are present in the Navy. Person-years at risk and cases of malignant melanoma were ascertained using computerized service history and inpatient hospitalization files maintained at the Naval Health Research Center. A total of 176 confirmed cases of melanoma were identified in active-duty white male enlisted Navy personnel during 1974-1984. Risk of melanoma was determined for individual occupations and for occupations grouped by review of job descriptions into three categories of sunlight exposure: (1) indoor, (2) outdoor, or (3) indoor and outdoor. Compared with the U.S. civilian population, personnel in indoor occupations had a higher age-adjusted incidence rate of melanoma, i.e., 10.6 per 100,000 (p = .06). Persons who worked in occupations that required spending time both indoors and outdoors had the lowest rate, i.e., 7.0 per 100,000 (p = .06). Incidence rates of melanoma were higher on the trunk than on the more commonly sunlight-exposed head and arms. Two single occupations were found to have elevated rates of melanoma: (1) aircrew survival equipmentman, SIR = 6.8 (p less than .05); and (2) engineman, SIR = 2.8 (p less than .05). However, there were no cases of melanoma or no excess risk in occupations with similar job descriptions. Findings on the anatomical site of melanoma from this study suggest a protective role for brief, regular exposure to sunlight and fit with recent laboratory studies that have shown vitamin D to suppress growth of malignant melanoma cells in tissue culture. A mechanism is proposed in which vitamin D inhibits previously initiated melanomas from becoming clinically apparent.
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PMID:Occupational sunlight exposure and melanoma in the U.S. Navy. 225 10

The classic function of 1,25-dihydroxyvitamin D3, the hormonally active form of vitamin D, is the maintenance of normal levels of calcium and phosphorus in the blood. 1,25-Dihydroxyvitamin D3 binds to a specific receptor protein and exerts its biologic action by a mechanism analogous to that proposed for other steroid hormones, that is, the receptor-ligand complex acts on the chromatin to induce transcription of specific genes. Intracellular receptors that bind 1,25-dihydroxyvitamin D3 with high affinity have been found in a large number of tumor cell lines examined as melanoma, osteosarcoma, and human breast and colonic carcinoma cells. The 1,25-dihydroxyvitamin D3 receptor in these cells has characteristics similar to the receptor in bone and intestine, the known target tissues of the hormone. In fact, 1,25-dihydroxyvitamin D3 inhibits the proliferation of melanoma, osteosarcoma, and breast carcinoma cells. More recently, 1,25-dihydroxyvitamin D3 has been shown to suppress the growth and induce monocytic differentiation of murine and human myeloid leukemia cells in vitro. These results point to a previously unsuspected involvement of vitamin D in cell proliferation and differentiation and suggest that analogs of the vitamin D hormone may be of interest as possible therapeutic agents in the treatment of malignancy.
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PMID:The relationship between the vitamin D system and cancer. 303

Exposure of the skin to sunlight results in both tanning and vitamin D3 production. It has therefore been suggested that vitamin D3 or its active metabolite 1,25-dihydroxyvitamin D3 may be the mediator of UV-induced melanogenesis. To test this hypothesis, newborn foreskin-derived melanocytes were cultured in paired dishes in hormone-supplemented medium with 2% serum containing no detectable vitamin D3 or in the same medium containing 10(-8) or 10(-10) M of either provitamin D3, lumisterol, previtamin D3, vitamin D3, 25-hydroxyvitamin D3, or 1,25-dihydroxyvitamin D3. After 10 days, cell number in cultures containing vitamin D compounds was 93%-140% of unsupplemented controls and melanin content was 60%-120% of control, with no significant difference in either parameter for any compound tested. In separate experiments, human melanocytes and Cloudman S91 melanoma cells were repeatedly irradiated with physiologic doses of simulated sunlight and incubated between irradiations with provitamin D3, previtamin D3, vitamin D3, or 1,25-dihydroxyvitamin D3. Irradiated cultures had a 90%-95% inhibition of cell growth associated with a 200%-800% increase in melanin content per cell relative to controls, but there was no effect of any vitamin D compound on either cell type. Neither cultured human melanocytes nor S91 cells showed evidence of the cytosolic 1,25-dihydroxy-vitamin D3 receptor binding by sucrose density gradient analysis using radiolabeled 1,25-dihydroxyvitamin D3. The combined data strongly suggest that neither vitamin D3 nor its precursors or metabolites directly mediate melanogenesis in these cells.
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PMID:Vitamin D, its precursors, and metabolites do not affect melanization of cultured human melanocytes. 338 13

We have identified a cDNA whose sequence is preferentially expressed when quiescent fibroblasts are stimulated to proliferate. The steady-state levels of the mRNA corresponding to this clone, called 2A9, are increased by serum, platelet-derived growth factor, and epidermal growth factor, but not by insulin or platelet-poor plasma. mRNA levels of 2A9 are also increased in human acute myeloid leukemia. The 2A9 cDNA has been molecularly cloned from an Okayama-Berg library, and its complete nucleotide sequence has been determined. It has an open reading frame of 270 nucleotides, which has a 55% homology with the coding sequence of the beta-subunit of the S-100 protein, a calcium-binding protein that belongs (like calmodulin and the vitamin D-dependent intestinal calcium-binding protein) to the family of calcium-modulated proteins and is found in abundance in several human tumors, including melanoma. The S-100 protein and the deduced aminoacid sequence of 2A9 are also partially homologous to the small subunit of a protein complex that serves as a cellular substrate to tyrosine kinase. The partial homology of 2A9 (whose RNA is inducible by growth factors and is overexpressed in human acute myeloid leukemias) to the S-100 protein, other calcium-modulated proteins, and the subunit of a substrate for tyrosine kinase, is particularly interesting in view of the role attributed to calcium and tyrosine kinases in the regulation of cell proliferation.
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PMID:Molecular cloning of the cDNA for a growth factor-inducible gene with strong homology to S-100, a calcium-binding protein. 375 24

Receptors for 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] have been described in several human breast cancer cell lines and more recently in human melanoma. The presence of 1,25-(OH)2D3 receptor (1,25-DR) in two cultured breast cancer cell lines was associated with receptors for calcitonin, another hormone thought to have effects on calcium handling. Therefore, it seemed important to examine a range of established human cancer cell lines for the presence of receptors for 1,25-(OH)2D3 and calcitonin. Thirty-three cancer cell lines were examined. 1,25-DR was found to be present in 23 lines, while calcitonin receptors were not detected in any of them. The 1,25-DR from several cell lines sedimented at about 3.5S in sucrose density gradients, had the appropriate specificity for vitamin D metabolites, had Kds of 0.8 to 2.2 x 10(-11) M, and had receptor concentrations of 12 to 99 fmol/mg protein. Ten malignant melanoma and nine colonic carcinoma lines constituted the largest groups of carcinoma cell lines, and seven and eight, respectively, of these were 1,25-DR positive. The high frequency of 1,25-DR positivity in the cultured colonic carcinoma cells is quite different from the low frequency of 1,25-DR in primary colonic carcinomas. It was also interesting that both of two cell lines derived from patients who had had both bone metastases and malignant hypercalcemia were 1,25-DR positive. These various cell lines may provide useful models for the examination of 1,25-(OH)2D3 action in vitro.
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PMID:Presence of 1,25-dihydroxyvitamin D3 receptors in established human cancer cell lines in culture. 627 75

1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3. VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10(-9) M1,25-(OH)2-vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10(-6) M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3.
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PMID:Vitamin D receptors in breast cancer cells. 788 Oct 99

The authors present 3 cases of melanoma associated with a parathyroid adenoma discovered by routine measurement of blood calcium levels. The melanomas were differently located and had different histological degrees. Hypercalcaemia is an infrequent complication of melanoma. According to data found in the literature, it is most often consecutive to bone metastases. The other causes of hypercalcaemia are metastatic extension of melanoma to the parathyroid glands, secretion of parathormone-related peptide (PTH-RP) and the actions of prostaglandins, vitamin D and the osteoclast-activating factor (OAF). Primary hyperparathyroidism due to adenoma has seldom been described associated with melanoma.
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PMID:[Melanoma and primary hyperparathyroidism]. 823 59

For more than 50 years, there has been documentation in the medical literature suggesting that regular sun exposure is associated with substantial decreases in death rates from certain cancers and a decrease in overall cancer death rates. Recent research suggests that this is a causal relationship that acts through the body's vitamin D metabolic pathways. The studies reviewed here show that (a) sunlight activation is our most effective source of vitamin D; (b) regular sunlight/vitamin D "intake" inhibits growth of breast and colon cancer cells and is associated with substantial decreases in death rates from these cancers; (c) metabolites of vitamin D have induced leukemia and lymphoma cells to differentiate, prolonged survival of leukemic mice, and produced complete and partial clinical responses in lymphoma patients having high vitamin D metabolite receptor levels in tumor tissue; (d) sunlight has a paradoxical relationship with melanoma, in that severe sunburning initiates melanoma whereas long-term regular sun exposure inhibits melanoma; (e) frequent regular sun exposure acts to cause cancers that have a 0.3% death rate with 2,000 U.S. fatalities per year and acts to prevent cancers that have death rates from 20-65% with 138,000 U.S. fatalities per year; (f) there is support in the medical literature to suggest that the 17% increase in breast cancer incidence during the 1991-1992 year may be the result of the past decade of pervasive anti-sun advisories from respected authorities, coinciding with effective sunscreen availability; and (g) trends in the epidemiological literature suggest that approximately 30,000 U.S. cancer deaths yearly would be averted by the widespread public adoption of regular, moderate sunning.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Beneficial effects of sun exposure on cancer mortality. 847 9

The expression of vitamin D receptors (VDR) and growth inhibition induced by 1,25-dihydroxyvitamin D3 have been noted in certain human malignant melanoma cell lines. In this study, widely disparate levels of VDR mRNA expression were demonstrated in a panel of eight human malignant melanoma cell lines. Quantitation of receptor level by ligand binding assay showed a similar pattern. Proliferation and growth curve analysis was performed in two cell lines: RPMI 7951 (high VDR) and SK-MEL-28 (low VDR). Significant growth inhibition was noted in RPMI 7951 cells at 10(-9) M 1,25-dihydroxyvitamin D3. SK-MEL-28 cells, which express much lower levels of VDR, did not show any growth inhibition except at extremely high concentrations of 1,25-dihydroxyvitamin D3, namely 10(-5) M. These findings suggest a receptor-mediated mechanism of growth inhibition for 1,25-dihydroxyvitamin D3 and a role for this hormone in the growth of malignant melanoma cells.
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PMID:Vitamin D receptor and growth inhibition by 1,25-dihydroxyvitamin D3 in human malignant melanoma cell lines. 876 54


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