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)

The present studies were carried out in 11 human renal cell carcinomas to determine the presence of a receptor specific for an active form of vitamin D, 1,25-dihydroxyvitamin D3. Saturation and Scatchard analyses of the cytosol receptor for 1,25-dihydroxyvitamin D3 showed that nine tumors had a detectable level of the receptor (two fmol/mg. protein). The equilibrium dissociation constant of these receptors ranged between 46 and 380 pM and the binding capacity also ranged between 3.5 and 12.7 femtomol/mg. protein. Sucrose density gradient analysis of the specific binders revealed that the tumors had a receptor protein appearing as a single 3.6S peak. Two tumors which had only a trace of the receptor were high grade solid tumors consisting mainly of spindle or pleomorphic cells. Nine tumors possessing 1,25-dihydroxyvitamin D3 receptor consisted of clear and/or granular cells. Thus, the absence of the receptor was only accompanied by low differentiated sarcomatoid tumors with poor prognosis. However, so far, the amount of the receptor in the receptor-positive tumor did not relate to the other clinical and pathological features of the patients.
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PMID:1,25-Dihydroxyvitamin D3 receptors and their relationship to histological features in renal cell carcinoma. 303 39

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

Hypercalcemia in patients with breast cancer is usually attributed to osteolytic bone metastases. Seventeen patients with biopsy-proved breast cancer and hypercalcemia were identified in a prospective, unselected manner. Biochemical and clinical evaluation included measurements of parathyroid hormone, nephrogenous cAMP, vitamin D metabolites, fasting calcium excretion, and maximal tubular phosphate reabsorption, and bone radionuclide scanning. Tumor histologic findings were also reviewed. Four of the 17 patients (23.5 percent) had no evidence of bone involvement by bone scanning or radiography. Two additional patients (a total of 35 percent) appeared to have a humoral component to their hypercalcemia as determined by the presence of elevated nephrogenous cAMP excretion. These observations suggest that humoral, tumor-derived products may play a more important role in the hypercalcemia of breast cancer than has been previously recognized.
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PMID:Hypercalcemia in breast cancer. Reassessment of the mechanism. 303 97

A 7-year study of a patient with tumor (hemangiopericytoma)-induced hypophosphatemic osteomalacia (TIO) is presented, and the findings are in keeping with the depressed tubular reabsorption of phosphate and low 1,25(OH)2 vitamin D levels seen in other studies. Despite normalization of 1,25(OH)2 vitamin D levels with pharmacologic doses of vitamin D2, there was no discernible effect on serum phosphorus levels. Also, despite hypercalcemia induced by pharmacologic doses of vitamin D2, serum parathyroid hormone levels were persistently elevated, and gradually returned to subnormal levels after removal of the tumor. Following removal of the tumor, there was a rapid increase of the 1,25(OH)2 vitamin D levels to supraphysiologic levels, prompt appropriate increase in tubular reabsorption of phosphate levels, and symptomatic improvement in the osteomalacia. Speculations on the physiologic and pathophysiologic role of the putative hormone(s) produced by the tumors associated with this syndrome are presented.
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PMID:Studies in a patient with tumor-induced hypophosphatemic osteomalacia. 308 59

Two patients, one with myeloma (Patient 1) and the other with probable chronic lymphocytic leukemia (Patient 2), had reduced renal tubular phosphate reabsorption in the absence of hyperparathyroidism together with other features of the Fanconi syndrome, as consequences of the nephropathy associated with light-chain proteinuria. Both patients had hypophosphatemic osteomalacia, demonstrated for the first time in this condition by iliac bone histomorphometry after in vivo double tetracycline labeling, despite absence of bone pain or Looser zones. Neither patient was vitamin D-depleted, but plasma calcitriol level was normal in Patient 1 and low in Patient 2; only the latter patient had severe muscle weakness. Complete histologic correction of osteomalacia was achieved by treatment in accordance with the biochemical defects--oral phosphate therapy alone in Patient 1 and combined with calcitriol in Patient 2. Both patients are now symptom-free, five and three years after the initial diagnosis of bone disease and hematogenous malignancy. Thirteen previous instances of the same form of osteomalacia were reviewed; in most cases, the Fanconi syndrome developed before its probable cause became apparent. The Fanconi syndrome has also been reported in two cases of osteomalacia due to mesenchymal tumor, but not in osteomalacia associated with prostatic carcinoma. Light-chain nephropathy and consequent renal tubular dysfunction appears to be a third form of oncogenous osteomalacia.
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PMID:Hypophosphatemic osteomalacia and adult Fanconi syndrome due to light-chain nephropathy. Another form of oncogenous osteomalacia. 310 97

Tumors causing humoral hypercalcemia of malignancy (HHM) were implanted to athymic nude rats. In one of these rat models transplanted with uterine cancer (UCC), a complete reproduction of human HHM syndrome was achieved: hypercalcemia, hypophosphatemia with increased urinary phosphate and cyclic AMP excretion, and suppressed serum 1,25-dihydroxy-vitamin D (1,25(OH)2D) level. In another hypercalcemic nude rat model implanted with oral cavity cancer (OCC), all the features were similar except for markedly elevated serum 1,25(OH)2D. Hypercalcemia disappeared by surgical removal of the tumors in both models, confirming the humoral mechanisms for causing these features. Furthermore, in UCC tumor-bearing rats, hypophosphatemia, increased renal phosphate excretion, and reduced serum 1,25(OH)2D concentration were already present when these rats were only marginally hypercalcemic. These results raise the possibility that the changes in renal tubular phosphate handling and vitamin D metabolism in HHM are not secondary to hypercalcemia but are due to direct effects of the humoral factor(s) that cause this syndrome. Extracts of both tumors exhibited stimulation of cyclic AMP production in osteoblastlike cells, UMR 106, which could be almost completely inhibited by parathyroid hormone (PTH) antagonist, human PTH(3-34). By comparing the nature and characteristics of humoral factor(s) from UCC and OCC models, mechanisms responsible for causing these abnormalities can be explored. Thus, these nude rat models can be useful for elucidating the underlying mechanism of the development of HHM.
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PMID:A hypercalcemic nude rat model that completely mimics human syndrome of humoral hypercalcemia of malignancy. 314 74

The potential calcium-binding protein p9Ka is related to S-100 protein and the vitamin D-dependent intestinal calcium-binding protein. p9Ka accumulates abundantly in cultured rat mammary myoepithelial-like cells but is very much less abundant in the parental cuboidal epithelial cells. p9Ka mRNA is found in normal rat mammary gland, and preliminary experiments suggest that it is found in the mammary myoepithelial cells. A 17-kilobase pair fragment of cloned normal rat DNA contains the gene for p9Ka, but it also contains the gene for two additional polypeptides of molecular mass 6 kDa that are resolved as two isoelectric focusing variants by two-dimensional gel electrophoresis. These two isoelectric focusing variants correspond to two abundant polypeptides present in the cultured myoepithelial cells and probably arise from postsynthetic modification of the product of a single gene. The mRNA for the product of this gene and the p9Ka mRNA are both found in the normal rat mammary gland, but these two mRNAs are differentially expressed in certain tumor-derived rat cell lines.
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PMID:The identification of a normal rat gene located close to the gene for the potential myoepithelial cell calcium-binding protein, p9Ka. 317 May 56

We report 2 cases of true hypocalcemia (not caused by decreased binding proteins) associated with metastatic prostate cancer and review previously reported cases. Hypocalcemia is a common but frequently unrecognized complication of prostatic cancer. Estrogen therapy often is associated with the hypocalcemia, which may be asymptomatic. The hypocalcemia is always associated with osteoblastic metastases and usually it is associated with increased serum alkaline phosphatase activity, acid phosphatase activity and serum parathyroid hormone concentration. Serum concentrations of magnesium, phosphorus and vitamin D frequently are decreased. Patients are in a positive calcium balance. The osteoblastic metastases seem to act as a calcium sink, creating a "hungry tumor phenomenon". The role of estrogens may be to stop the resorption of normal bone resulting in lower serum calcium concentrations.
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PMID:Hypocalcemia associated with estrogen therapy for metastatic adenocarcinoma of the prostate. 317 54

In 1966, Verhoeff suggested that retinoblastomas might be sensitive to vitamin D because they sometimes undergo calcification and spontaneous regression. In recent years, the antineoplastic effect of vitamin D has been established in vitro and in vivo. This study presents evidence that vitamin D2 inhibits the growth of the human retinoblastoma cell line (Y-79) grown in athymic mice. In mice treated with ergocalciferol, the subcutaneous retinoblastomas were smaller and showed increased tumor necrosis and calcification. Unfortunately, the vitamin D caused significant toxic reactions. Further studies that reduce the toxicity of vitamin D will be needed before its use in children with retinoblastomas can be advocated. To our knowledge, this is the first demonstration of the activity of ergocalciferol against a tumor in vivo and it suggests that ergocalciferol or one of its derivatives may be an effective chemotherapeutic agent against retinoblastomas in humans.
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PMID:Verhoeff's query: is vitamin D effective against retinoblastoma? 325 14

Described herein is a case of oncogenic osteomalacia that ran a course of at least 16 years before curative resection of a mixed mesenchymal tumor. Hypercalcemic hyperparathyroidism developed in the patient, and review of the literature indicated that this occurs in about 10 percent of reported cases. Changes in serum parathyroid hormone levels with and without phosphate supplement therapy and before and after tumor resection suggested that both the high intake of phosphate and the effect of the neoplasm on vitamin D bioactivation engendered the parathyroid overactivity. Despite marked hyperparathyroidism, serum 1,25-dihydroxyvitamin D levels were subnormal preoperatively but showed a sevenfold increase within 48 hours of tumor resection. Thereafter, a gradual increase in the maximal tubular reabsorption of phosphate occurred during several months. Biopsy of the iliac crest confirmed that tumor removal was followed by resolution of osteomalacia, but there was no accompanying increase in vertebral mineral density as assessed by quantitative computed tomography or in total-body bone mineral as measured with dual-photon absorptiometry. The findings presented are consistent with secretion by the tumor of a factor with a short half-life that is potent enough to inhibit renal 25-hydroxyvitamin D-1 alpha-hydroxylase despite hyperparathyroidism. The resulting subnormal circulating 1,25-dihydroxyvitamin D levels may have secondarily contributed to decreased renal tubular reabsorption of phosphate.
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PMID:Hypercalcemic hyperparathyroidism complicating oncogenic osteomalacia. Effect of successful tumor resection on mineral homeostasis. 330 28


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