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)

Adrenal medullary hyperplasia and neoplasia occur both enzootically and epizootically in untreated laboratory rats. The lesions are typically chromaffin-negative and are found incidentally in animals that have died from unrelated causes or have been killed at the end of long-term toxicity/carcinogenicity tests. Urinary excretion of catecholamines is not usually increased. Environmental, particularly dietary, factors are seemingly much more important than genetic ones as determinants of the incidence of proliferative lesions. Recent observations of enhancement of adrenal medullary proliferative disease in rats by the feeding, in high dietary concentration, of certain polyols (sorbitol, mannitol, xylitol, lactitol), or of lactose, suggested that increased absorption of calcium from the gastrointestinal tract may be a risk factor. This evidence is reported and discussed in the light of other evidence linking disturbed calcium homeostasis with adrenal medullary function in the rat. In man, adrenal medullary proliferative disease is relatively rare and there is no evidence of any relation between the hypercalcaemia associated with hyperparathyroidism and increased risk of phaeochromocytoma. Adrenal medullary proliferative disease in rats is usually seen against a background of multiple endocrine neoplasia, with the pituitary gland, the pancreatic islets and the thyroid C-cells being most commonly affected in addition to the adrenal medulla. A parallel between this situation and Sipple's disease in humans has previously been suggested. We now stress the possible importance of three factors as determinants of enzootic and epizootic adrenal medullary proliferative disease in rats: excessive food intake, excessive dietary levels of calcium and phosphate and excessive intake of other food components, such as vitamin D and poorly absorbable carbohydrates, which predispose to increased calcium absorption.
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PMID:Enzootic and epizootic adrenal medullary proliferative disease of rats: influence of dietary factors which affect calcium absorption. 398 3

The field of vitamin D metabolism and mechanism of action has continued to be very active. Autoradiography has shown specific nuclear localization of 1,25-(OH)2D3 in target organs prior to initiation of mechanism of action. Specific nuclear localization has also been demonstrated in a variety of other tissues not previously appreciated as targets of vitamin D action, suggesting the possibility that vitamin D carries out subtle functions previously unappreciated. A macromolecule believed to be a receptor that specifically binds 1,35-(OH)2D3 has been found in the cells showing nuclear localization and in a number of tumor and cancer cell lines. Since 1,25-(OH)2D3 has been found to cause differentiation of certain myeloid leukemia cells, a possible relationship between the vitamin D system and cancer has appeared. Substantial evidence exists that 1,25-(OH)2D3 functions in a nuclear-mediated process, although some evidence exists that not all of the actions of 1,25-(OH)2D3 are carried out through such a mechanism. Substantial advances in our understanding of the metabolism of vitamin D have also been made. The presence of significant amounts of 1 alpha-hydroxylase has been located in the placenta in addition to the kidney. Although there have been reports of extrarenal synthesis of 1,25-(OH)2D3, these sites, if they produce 1,25-(OH)2D3, produce it in insufficient amounts for function. The renal 1 alpha-hydroxylase has been solubilized and shown to be a three-component system. The 25-hydroxylase in the liver has also been solubilized and shown to be a two-component mixed-function monooxygenase. New pathways of vitamin D metabolism include a 23-oxidation to form 23,25-(OH)2D3 or a 23-hydroxylated form of 1,25-(OH)2D3. 23,25-(OH)2D3 is further oxidized to produce a 25-(OH)2D3-26,23-lactone. Although these pathways are of significant magnitude, their roles remain unknown since the products have low biological activity. Important analogs of the vitamin D metabolites include 24,24-F2-25-OH-D3 and the 26,26,26,27,27,27-F6-25-OH-D3. These have been used to show that the 24-hydroxylation, the 26-hydroxylation, and the lactone formation do not play a significant role in the function of vitamin D. Their 1-hydroxy analogs have also been prepared and shown to be extremely biologically active, being somewhere around ten times more active than the native 1,25-dihydroxyvitamin D3, illustrating that important analogs of the vitamin D system continue to be discovered.
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PMID:Vitamin D: recent advances. 631 Oct 80

A patient with phosphaturic osteomalacia without chemical or pathological evidence of hyperparathyroidism and subnormal urinary cyclic AMP excretion was treated with vitamin D and phosphates for 9 months with partial improvement of osteomalacia, but not phosphaturia. Subsequent removal of a mesenchymal chondrosarcoma of the foot led to prompt resolution of phosphaturia and healing of the osteomalacia. Although 1,25-dihydroxyvitamin D levels were not obtained before vitamin D therapy, the levels noted during continued severe phosphaturia preoperatively were not lower than those obtained several months postoperatively during the healing phase. Studies done 1 year after tumor removal showed normalization of phosphaturia, urinary cyclic AMP, and bone histology. We suggest that the tumor elaborated products which promoted nonparathyroid mediated phosphate excretion independently from any effects on vitamin D metabolism.
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PMID:Oncogenic osteomalacia associated with a mesenchymal chondrosarcoma. 651 84

A radioreceptor assay for serum 1,25-dihydroxyvitamin D (calcitriol) was used to screen patients with hypercalcemia of malignancy. Three patients with non-Hodgkin's lymphoma and hypercalcemia (serum Ca, 12.0, 13.4, and 13.0 mg/dL, respectively) had increased serum calcitriol levels (56, 72, and 77 pg/mL, respectively; normal, less than 50 pg/mL). Elevated levels of calcitriol, an active vitamin D metabolite, occurred in the presence of significant renal impairment (creatinine clearance, 8 to 19 mL/min) and relative parathyroid suppression (serum immunoreactive parathyroid hormone, 17 to 39 microL-eq/mL; mean value in end-stage renal disease, 182 +/- 39 microL-eq/mL). Hypercalcemia and excessive serum calcitriol levels responded to glucocorticosteroid therapy. In two patients, the hypercalcemia and increased serum calcitriol level were related to a tumor, but not to the serum immunoreactive parathyroid hormone level. Fractional intestinal 47Ca absorption, measured in one patient, was increased (0.94; normal, less than 0.61) and varied directly with the serum calcitriol level. No patient had evidence of sarcoidosis. Hypercalcemia associated with certain lymphomas may be caused by the increased synthesis of calcitriol by lymphoma cells.
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PMID:Hypercalcemia associated with increased serum calcitriol levels in three patients with lymphoma. 654 27

The clinical and biochemical data in 42 reported cases of oncogenous osteomalacia are reviewed, and data in two previously unreported cases are recorded. It is likely that the syndrome is more common than suggested by the paucity of reports and may account for a substantial fraction of nonfamilial, adult-onset "idiopathic" osteomalacia. Tumors associated with the syndrome are characteristically benign, of mesenchymal origin, highly vascular, and composed principally of giant and spindle cells. Complete excision of tumors results in cure of the osteomalacia in the majority of patients. The syndrome presumably represents an instance of humor-induced phosphaturia but supporting experimental data are scanty. Plasma levels of 1,25-dihydroxycholecalciferol are uniformly low, and treatment with this metabolite is generally very effective; however, abnormal vitamin D metabolism cannot by itself account for the syndrome.
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PMID:Oncogenous osteomalacia. Review of the world literature of 42 cases and report of two new cases. 654 80

Neonatal inbred Wistar albino rats were given either 5 or 10 microCi radioiodine (131I) within 24 hours of birth. After weaning, animals were placed on diets high, normal, or deficient in vitamin D3 (cholecalciferol) for periods up to 2 years. In animals aged 12 months and older, adenomas were found in 0 of 67 unirradiated controls, in 22 of 67 given 5 microCi 131I, and in 25 of 67 given to microCi 131I. The incidence of tumors in irradiated animals was highest (55%) in those on a low-vitamin D diet and lowest (20%) in those on a high-vitamin D diet. Plasma calcium levels were significantly increased by the high-vitamin D diet, but the low-vitamin D diet did not lead to any significant decrease as compared to the calcium levels of the normal vitamin D diet group. Small but significant calcium increases were found in tumor-bearing animals. These findings indicate that parathyroid tumors in the rat can be induced by radiation and that their incidence is strongly influenced by dietary vitamin D content. The possibility that metabolites of vitamin D3 may influence parathyroid growth and tumor formation directly is discussed.
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PMID:Experimental induction of parathyroid adenomas in the rat. 657 10

Although the primary cell type in human osteosarcoma is usually a neoplastic osteoblast, numerous other mesenchymal cell types may coexist in the same tumor. Previously described cloned, long-term osteosarcoma cell lines have had an osteoblastic phenotype. In this report, we describe a nonosteoblastic, long-term cell line derived from an osteosarcoma in a patient with Paget's disease. The cell line (FM-2) is nontransformed in having a low saturation density and anchorage-dependent growth, and it is nontumorigenic in nude mice. Important features of its fine structure include numerous elongated mitochondria, abundant Golgi and lysosomes, and a poorly developed rough endoplasmic reticulum. The line has high levels of lysosomal enzymes (acid phosphatase and N-acetylglucosaminidase) and low levels of alkaline phosphatase. It lacks numerous macrophage markers (lysozyme, C3, Fc receptors, and M1 antigen). The FM-2 line had a dose-dependent cyclic AMP response (7-fold increase) following treatment with calcitonin but not with parathormone. In 125I-calcitonin-binding experiments, we calculated approximately 5.3 +/- 0.2 X 10(3) receptor sites/cell with a kd of 1.8 +/- 0.1 X 10(-9) M. Conditioned medium from the FM-2 line was a potent stimulator of calcium release as assayed in a 45Ca-labeled fetal rat bone organ culture. This activity was not prostaglandin, vitamin D, parathormone, or epidermal growth factor, which are known stimulators of bone resorption. The FM-2 line does not appear to be derived from an osteoblast, macrophage, or fibroblast and may represent a calcitonin-responsive bone stem cell.
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PMID:Characteristics of a calcitonin-responsive cell line derived from a human osteosarcoma. 657 18

The FM-2 cell line is a cloned, immortalized cell line derived from a human osteosarcoma. Conditioned medium from FM-2 cultures contains a factor which stimulates calcium mobilization from fetal rat bone organ cultures. Treated bones contain increased numbers of osteoclasts and decreased bone matrix. This factor has a molecular weight of approximately 29,000 as determined by gel filtration. Its biological activity is dependent on a protein moiety and is completely inhibited by calcitonin. Its synthesis by the FM-2 line is dependent on cell density and replenishment of fresh medium. This factor is not parathyroid hormone, a vitamin D metabolite, prostaglandin E, epidermal growth factor, or osteoclast-activating factor, all of which have bone-resorbing activities. Also, FM-2-conditioned medium inhibits collagen synthesis in fetal rat calvaria cells and decreases alkaline phosphatase levels in an osteoblastic cell line, and these two properties coelute with the calcium-mobilizing factor from a hydroxylapatite column. These biological products, synthesized by a cell line derived from a tumor, may represent physiological factors normally synthesized by a subpopulation of bone cells.
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PMID:New bone resorption stimulation factor elaborated by a human osteosarcoma cell line. 660 87

Biochemical and other parameters in VX-2 carcinoma in rabbits were evaluated. VX-2 carcinoma not only produced hypercalcemia but also hypophosphatemia and 25-OH-vitamin D deficiency. An increased turnover of 25-OH-vitamin D seems likely. Serum parathyroid hormone and urinary cyclic AMP did not increase. Hypokalemia occurred in association with hypophosphatemia and lowered blood glucose within 1 week after tumor transplantation. At the end of the experiment glucose and insulin were both below the control range. It is concluded that VX-2 carcinoma in rabbits yields much more complex biochemical alterations than reported before on calcium metabolism.
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PMID:Electrolyte and glucose metabolism in VX-2 carcinoma of the rabbit. 668 51

Humoral hypercalcemia associated with malignancy has rarely been reported in exocrine pancreatic cancer. We report a patient with cancer of the exocrine pancreas who presented with hypercalcemia which did not respond to indomethacin. Her serum levels of parathyroid hormone and vitamin D derivatives were low. Technetium diphosphonate bone scan revealed no evidence of bone metastasis, a finding which was confirmed at autopsy. On light microscopy, histological classification of the tumor was moderately differentiated tubular adenocarcinoma. The electron microscopic study, however, revealed a few zymogen-like granules containing cancer cells lying between ductal-type cancer cells. A review of humoral hypercalcemia in cancer of the exocrine pancreas is presented. A humoral factor(s) other than parathyroid hormone, prostaglandin E, and vitamin D derivatives is considered responsible for hypercalcemia in this patient.
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PMID:Exocrine pancreatic cancer with humoral hypercalcemia. 669 85


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