Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report about one case of spontaneous healing of metastases of kidney cancer (hypernephroma). The subcutaneous and abdominal metastases appeared 3 years after the discovery of the initial neoplasm and subsequent nephrectomy. Meanwhile the patient developed an adenoma of the prostate, while the neoplasm was in a metastasizing stage. After prostatectomy, he was treated with Ephynal for mild transient incontinence. From then on, we witnessed progressive disappearance of the metastases, until they were completely eradicated. This case is very well documented, with irrefutable histological evidence of the nature of the lesions and of their healing. It adds to the 21 similar cases published worldwide until then. In recent cases, the beneficial role of vitamin D in the treatment of metastases of kidney cancer has been predicted. We have probably demonstrated accidentally that vitamin E, which has some similarities with vitamin D, is a least as effective. In addition, it is a particularly innocuous and cheap medication. This may be an interesting therapeutic improvement, considering that there is no really effective treatment of metastasized kidney cancer, except very heavy Interleukin-based therapies that are both very expensive and hard to bear for the patient.
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PMID:[Spontaneous recovery from metastatic cancer of the kidney. Favourable role of Vitamin E?]. 816 3

Compounds that induce cancer cells to differentiate are clinically effective for several types of malignancies. The 1,25-dihydroxyvitamin D3[1,25(OH)2D3(C)] induces leukemic cells, including HL-60, to differentiate and/or no longer proliferate, but it causes hypercalcemia. Development of vitamin D analogs that are more potent in their abilities to affect leukemic cells without causing greater hypercalcemia, may be useful therapeutically. A novel analog [1,25(OH)2-16ene-D3(HM)] has a double bond between C-16 and C-17; it appears to be an extremely effective antileukemic agent with the same or fewer effects on serum calciums. We define the potency of this compound and compare it with seven, previously reported, potent analogs of 1,25(OH)2D3. HM inhibited clonal growth of HL-60 cells by 50% at 1.5 x 10(-11) M. This was about equipotent to 1,25(OH)2-16ene-23yne-D3(V), about 100-fold more potent than many of the other analogs, and 1000-fold more potent than 1,25(OH)2D3. The rank order of leukemic inhibitory activity was: 1,25(OH)2-16ene-D3(HM) > or = 1,25(OH)2- 16ene-23yne-D3(V) > 1,25(OH)2-23ene-D3(EX) = 1,24(OH)2-22ene-24-cyclopropyl-D3(BT) = 22-oxa- 1,25(OH)2D3(EU) = 1,25(OH)2-24-homo-D3(ER) > 1,25(OH)2D3(C) > 1,25(OH)2-24- dihomo-D3(ES). The rank order of their effects on induction of differentiation of HL-60 cells, as measured by superoxide production and nonspecific esterase activity, was similar to their antiproliferative activities. In contrast, each analog slightly stimulated proliferation of normal human myeloid clonal growth. Serum calcium levels were the same or slightly less when either 1,25(OH)2-16ene-D3(HM) or 1,25(OH)2D3 (0.0625, 0.125, or 0.25 microgram) was given intraperitoneally to mice for 5 weeks. HM bound to 1,25(OH)2D3 receptors about 1.5-fold more avidly than 1,25(OH)2D3. In fact, this vitamin D3 appears to be the most avid binder to 1,25(OH)2D3 receptors that has been identified to date. In contrast, HM had a greater than 50-fold lower affinity for the D-binding proteins as compared with 1,25(OH)2D3, thus increasing the availability of the compound for target tissues. Further differentiation experiments showed that HM was more potent than 1,25(OH)2D3 in the presence of serum, but was equipotent in serum-free conditions. Taken together, our experiments suggest that 1,25(OH)2-16ene-D3(HM) may be more potent than 1,25(OH)2D3(C) because of its higher affinity to the 1,25(OH)2D3 receptors and its low affinity to the D-binding protein present in serum. HM is an ideal compound for clinical studies including patients with preleukemia and other neoplasia, as well as several skin disorders, such as psoriasis.
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PMID:1,25(OH)2-16ene-vitamin D3 is a potent antileukemic agent with low potential to cause hypercalcemia. 820 63

A 36-year-old Russian man presented with neck and low back pain in September 1990. He was of normal stature, and there were no stigmata of rickets. The family history was negative for bone disease. He was found to have hypophosphatemia (2.3 mg/dl), impaired phosphate reabsorption (TmP/GFR 2.08), hyperphosphatasemia (254 IU/l), normocalcemia, normal vitamin D metabolite levels, and secondary hyperparathyroidism. Clinically, his spinal movements were quite impaired and there was moderate proximal muscle weakness. On skeletal radiographs, there was generalized osteosclerosis and multiple ligamentous calcifications. Transiliac biopsy was diagnostic for severe osteomalacia. He was treated with oral phosphate (240 mEq daily) and calcitriol (4 micrograms daily) with resultant very slow clinical, biochemical, and histomorphologic improvement. The patient had hypophosphatemic osteomalacia with some features of X-linked hypophosphatemia, but sporadic and of relatively late onset. The osteopenia, height loss, incapacitating weakness, and glycinuria that are characteristics of sporadic adult onset nonfamilial hypophosphatemia, with or without an associated tumor, and the low serum calcitriol levels that may be an additional characteristic of tumor-induced osteomalacia were absent. Other known causes of acquired renal tubular dysfunction were ruled out. The etiology, pathogenesis, and nosology of the disorder remain obscure, but treatment based on experience with other forms of hypophosphatemic osteomalacia was ultimately effective.
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PMID:A unique case of adult hypophosphatemic osteomalacia. 826 43

This study examined the effect of increasing dietary vitamin D on chemically induced colon carcinogenesis. Male Fischer 344 rats were first injected with 1,2-dimethylhydrazine (200 mg/kg) and then fed one of five dietary levels of vitamin D as cholecalciferol (250, 1,000, 2,000, 4,000, and 10,000 IU/kg diet) for nine months. Dietary vitamin D3 had no effect on weight gain. Plasma 25-hydroxyvitamin D3 levels were similar for the 1,000 and 2,000 IU/kg groups but varied in a dose-related manner for the other groups. Vitamin D did not significantly alter the tumor incidence in either the distal or the proximal colon. No significant differences in the labeling index were found in either the proximal or the distal colon. Within the distal colon, the proliferative zone increased in a dose-related manner. Distribution of labeled cells within the crypt compartments was not affected by dietary vitamin D. Bone and serum minerals in general were unaffected by dietary vitamin D. This study shows that, at this level of dietary calcium, vitamin D did not affect 1,2-dimethylhydrazine-induced colon carcinogenesis.
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PMID:Effect of dietary vitamin D3 (cholecalciferol) on colon carcinogenesis induced by 1,2-dimethylhydrazine in male Fischer 344 rats. 838 42

Although several hypotheses for human carcinogenesis have been proposed, the specific genetic changes that cause normal cells to become cancer cells have not been identified. In spite of uncertainties regarding the mechanisms of carcinogenesis, several vitamins such as beta-carotene and vitamins A, C, and E, which can reduce the risk of cancer, have been identified, using animal and in vitro models of carcinogenesis. These studies have led to a hypothesis that the supplemental intake of these vitamins may reduce the risk of cancer. This hypothesis in humans can be tested only by intervention trials that are in progress. Prospective and retrospective case-controlled experimental designs are not suitable for testing the above hypothesis. The fact that some vitamins induce cell differentiation and/or growth inhibition in tumor cells in culture suggests that the use of these vitamins in cancer prevention has a cellular basis. In addition to having a direct effect on tumor cells, vitamins such as alpha-tocopheryl succinate and beta-carotene enhance the effect of other agents that induce differentiation in tumor cells. Some vitamins like beta-carotene, retinoic acid, alpha-tocopheryl succinate, and vitamin D also regulate the expressions of certain oncogenes and cellular genes. These are exciting new functions of vitamins that nobody could have predicted only a few years ago.
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PMID:Vitamins regulate gene expression and induce differentiation and growth inhibition in cancer cells. Their relevance in cancer prevention. 839 65

We investigated whether increased levels of dietary calcium and vitamin D could inhibit colon carcinogenesis in rats injected with a single dose of 1,2-dimethylhydrazine. Rats were given a single subcutaneous injection (200 mg/kg body wt) 2 wk before they were fed purified diets containing 20% fat for 32 wk. Diets contained one of three levels of calcium (5, 10 or 15 g/kg diet) as calcium gluconate and one of three levels of vitamin D (0.025, 0.05 or 0.1 mg/kg diet) as cholecalciferol in a 3 x 3 factorial design. Rats receiving the highest level of vitamin D had greater plasma concentrations of 25-hydroxy-vitamin D. Autoradiographic examination of [3H]thymidine-treated rats demonstrated that a higher dietary level of calcium as well as higher levels of vitamin D significantly affected cellular kinetic indices. The total tumor incidence and tumor incidence in the distal colon was 45% lower in rats fed the highest level of both calcium and vitamin D compared with the other eight groups, although this decrease was not statistically significant (P = 0.12). The possible importance of these observations is discussed.
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PMID:Influence of dietary calcium and vitamin D on colon epithelial cell proliferation and 1,2-dimethylhydrazine-induced colon carcinogenesis in rats fed high fat diets. 842 Dec 25

The bone-specific osteocalcin (OC) gene is transcribed only after completion of proliferation in normal diploid calvarial-derived osteoblasts during extracellular matrix mineralization. In contrast, the OC gene is expressed constitutively in both proliferating and nonproliferating ROS 17/2.8 osteosarcoma cells. To address molecular mechanisms associated with these tumor-related modifications in transcriptional control, we examined sequence-specific interactions of transactivation factors at key basal and hormone-responsive elements in the OC gene promoter. In ROS 17/2.8 cells compared to normal diploid osteoblasts, the absence of a stringent requirement for cessation of proliferation to support both induction of OC transcription and steroid hormone-mediated transcriptional modulation is reflected by modifications in transcription factor binding at (i) the two primary basal regulatory elements, the OC box (which contains a CCAAT motif as a central core) and the TATA/glucocorticoid-responsive element domain, and (ii) the vitamin D-responsive element. Particularly striking are two forms of the vitamin D receptor complex that are present in proliferating osteoblasts and osteosarcoma cells. Both forms of the complex are sensitive to vitamin D receptor antibody and retinoic X receptor antibody. After the down-regulation of proliferation, only the lower molecular weight complex is found in normal diploid osteoblasts. Both forms of the complex are present in nonproliferating ROS 17/2.8 cells with increased representation of the complex exhibiting reduced electrophoretic mobility that is phosphorylation-dependent.
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PMID:Constitutive transcription of the osteocalcin gene in osteosarcoma cells is reflected by altered protein-DNA interactions at promoter regulatory elements. 846 Jan 37

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

We have examined the effects of 1,25 dihydroxyvitamin D3 (1,25[OH]2D3) and a low calcemic analogue EB1089 on parathyroid hormone-related peptide (PTHRP) production and on the development of hypercalcemia in Fischer rats implanted with the Leydig cell tumor H-500. Leydig cell tumors were implanted subcutaneously into male Fischer rats, which received constant infusions intraperitoneally of either 1,25(OH)2D3 (50-200 pmol/24 h), EB1089 (50-400 pmol/24 h), or vehicle for up to 4 wk. A control group of animals received similar infusions without tumor implantation. Plasma calcium, plasma levels of immunoreactive iPTHRP, and tumor PTHRP mRNA levels were determined as well as tumor size, animal body weight, and animal survival time. Non-tumor-bearing animals receiving > 50 pmol/24 h of 1,25(OH)2D3 became hypercalcemic, whereas no significant change in plasma calcium was observed in animals receiving < or = 200 pmol/24 h of EB1089. Tumor-bearing animals receiving vehicle alone or > 50 pmol/24 h of 1,25(OH)2D3 became severely hypercalcemic within 15 d. However, animals treated with low dose 1,25(OH)2D3 and all doses of EB1089 maintained near-normal or normal levels of plasma calcium for up to 4 wk. Additionally, reduced levels of tumor PTHRP mRNA and of plasma iPTHRP were observed compared with controls in both vitamin D- and EB1089-treated rats. Infusion of 50 pmol/24 h of 1,25(OH)2D3 and 200 pmol/24 h of EB1089 significantly reduced tumor volume by the end of experiment. The analogue but not 1,25(OH)2D3 substantially prolonged survival time in tumor-bearing animals with longer survival achieved at the highest dose, 400 pmol/24 h, of EB1089. These studies demonstrate that 1,25(OH)2D3 and a low calcemic vitamin D analogue are potent inhibitors of PTHRP production in vivo. Low calcemic analogues may therefore represent important alternative therapy for malignancy-associated hypercalcemia.
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PMID:A vitamin D analogue (EB1089) inhibits parathyroid hormone-related peptide production and prevents the development of malignancy-associated hypercalcemia in vivo. 851 54

Tumor-induced (oncogenic) osteomalacia is a rare clinicopathologic entity in which the clinical signs and symptoms of osteomalacia and the specific laboratory abnormalities of hypophosphatemia, hyperphosphaturia, and low serum levels of 1,25(OH)2 vitamin D are associated with the finding of a neoplastic process in the patient. To date, less than 100 cases of oncogenic osteomalacia have been described. We report a new case of adult-onset hypophosphatemic osteomalacia leading to the discovery of an asymptomatic phosphaturic mesenchymal lung tumor. Complete resection of the pulmonary neoplasia was followed by rapid normalization of the laboratory findings and clinical remission. The clinical, laboratory, and histopathologic spectrum of tumor-induced osteomalacia is presented, and the postulated mechanism of this condition is discussed in light of the relevant literature. The presence of occult neoplasms should be considered in cases of unexplained adult osteomalacia, with the physician's efforts being rewarded by the dramatic cure that follows excision of the tumor.
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PMID:Tumor-induced osteomalacia. 852 89


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