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)

A 53-year-old Japanese woman suffered hypophosphatemic osteomalacia secondary to bone tumor. Her clinical symptoms did not improve for a long time following the oral administration of Alfacalcidol (vitamin D3). A bone survey using radiographs revealed a small tumor located in the proximal head of the left fibula. Hypophosphatemia and low levels of 1-alpha,25-dihydroxycholecalciferol (1-alpha,25(OH)2D3) returned towards normal levels soon after an en-bloc tumor resection, and bone pain and muscle weakness gradually disappeared. The histology, especially of the trabecular bone of the left fibula, showed typical features of osteomalacia with demineralization. The tumor comprised numerous small blood vessels, spindle shaped or oval neoplastic cells, a few multinucleated giant cells, osteoid tissue with or without calcification, chondroid tissue and hemangioma. The spindle shaped or oval cells contained a round nucleus with no mitotic figures. These clinical and histological findings coincide well with a diagnosis of benign ossifying mesenchymal tumor of the bone with vitamin D resistant hypophosphatemic osteomalacia.
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PMID:Oncogenic vitamin D resistant hypophosphatemic osteomalacia (benign ossifying mesenchymal tumor of bone): case report. 194 53

Biological activity of 24-epi-1 alpha,25-dihydroxyvitamin D-2 (24-epi-1,25(OH)2D2) and 1 alpha,25-dihydroxyvitamin D-7 (1,25(OH)2D7), the 22,23-dihydro derivative of the former compound, was investigated. Both of the vitamin D derivatives stimulated intestinal calcium transport and calcium mobilization from bones in rats; however, the effect was about 50% of that of 1 alpha,25-dihydroxyvitamin D-3 (1,25(OH)2D3). On the other hand, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 inducement of HL-60 human leukemia cell differentiation was comparable to that of 1,25(OH)2D3. Accordingly, the differentiation-inducing activity of 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 was much greater than their ability to stimulate calcium metabolism. In contrast to 1,25(OH)2D3, 24-epi-1,25(OH)2D2 and 1,25(OH)2D7 exerted little hypercalcemic activity in mice. These results suggest that both vitamin D derivatives will be useful as anti-tumor agents.
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PMID:Biological activity of 1 alpha, 25-dihydroxyvitamin D derivatives--24-epi-1 alpha, 25-dihydroxyvitamin D-2 and 1 alpha,25-dihydroxyvitamin D-7. 199 78

Effects of dietary calcium on mammary carcinogenesis in rats were investigated because of evidence that calcium counteracts the promotion of colon cancer by dietary fat and because experimental diets for rats normally contain higher amounts of calcium and vitamin D than do human diets. Our earlier experiments indicated that yields of tumors induced in young, Sprague-Dawley rats by 7,12-dimethylbenz(a)-anthracene (DMBA) were higher when dietary calcium, phosphate, and vitamin D were decreased. Results of an experiment in which dietary amounts of calcium, phosphate, and vitamin D were varied independently suggested that phosphate and vitamin D have interactive effects with calcium. Another experiment in which dietary vitamin D alone was varied provided evidence that higher amounts inhibited tumorigenesis in the presence of low amounts of calcium and phosphate but the results with a high-calcium and -phosphate diet were inconclusive. The findings suggest that low amounts of dietary calcium and vitamin D and high amounts of phosphate increase susceptibility to DMBA-induced mammary neoplasia.
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PMID:Calcium and carcinogenesis of the mammary gland. 205 63

Tubular reabsorption of calcium (Ca) is becoming recognized as a determinant of malignant hypercalcemia. However, its importance as compared to increased bone resorption has not yet been widely investigated. We determined Ca fluxes of bone resorption and tubular reabsorption in 141 rehydrated patients with hypercalcemia of malignant or benign origin, before any specific treatment. Bone resorption (BRI) was evaluated by fasting urinary Ca excretion and Ca tubular reabsorption using an index (TRCaI) calculated from a nomogram relating fasting urinary Ca excretion and calcemia. The relationship between alterations in TRCaI and in the tubular capacity to reabsorb inorganic phosphate (Pi), as judged by TmPi/GFR, was also examined for each cause of hypercalcemia. Among 101 cases with malignancy, 67% had overt bone metastases, but all displayed increased BRI. Calcemia was highest in breast cancer and lowest in prostate carcinoma. BRI was markedly increased in breast cancer, lymphoma, and multiple myeloma, whereas it was slightly elevated in lung squamous cell, renal, and liver carcinomas. TRCaI was increased in 49% of malignant hypercalcemia, particularly in epidermoid (above the upper normal limit in 71% of the cases), renal, and liver carcinomas. It was elevated in 54% of breast cancer and normal in multiple myeloma and prostate cancer. In nonmalignant hypercalcemia, BRI was markedly increased in vitamin D intoxication, sarcoidosis, and immobilization. In primary hyperparathyroidism (PHP), BRI was moderately increased. TRCaI was abnormally elevated in PHP, but normal in vitamin D intoxication, sarcoidosis, and immobilization. In malignant hypercalcemia, TmPi/GFR was low in 77% of patients and in all types of tumors, except in prostate carcinoma. The index ratio [TRCaI/(TmPi/GFR)] gave a better discrimination of PHP from other causes of nonmalignant hypercalcemia than the use of either TRCaI or TmPi/GFR taken alone. Thus, in malignant hypercalcemia, increased bone resorption is associated with an elevation in tubular Ca reabsorption in half the patients surveyed, whereas low tubular Pi reabsorption is observed in more than 75%. Increased TRCaI is restricted to some types of tumor, whereas decreased TmPi/GFR is observed in all types except prostate carcinoma. In nonmalignant hypercalcemia, a significant increase in mean TRCaI was only observed in PHP, of which individual cases can be fully discriminated from other conditions by using a new index taking into account alteration in the renal transport capacity of both Ca and Pi.
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PMID:Evaluation of bone resorption and renal tubular reabsorption of calcium and phosphate in malignant and nonmalignant hypercalcemia. 205 36

In the past, chemotherapy has had only a minor role in the treatment of retinoblastoma. There are three clinical settings in which chemotherapy may be useful, namely, in intraocular retinoblastoma, in cases of micrometastatic spread, and where there are overt extraocular metastases. Clinical trials in all three settings have been impeded by biological, statistical, and ethical limitations. Extensive review of the literature, including case reports, small retrospective series, and occasional prospective studies, does not lead to any clear conclusions. However, responsiveness of retinoblastoma to chemotherapy in each of the above categories has been documented, and cyclophosphamide is consistently the most effective single agent. For small intraocular tumors, there may be a role for a combination of nonoperative treatment modalities. Whether decreased occurrence of extraocular relapse is produced by the use of adjuvant chemotherapy for presumed micrometastatic disease remains controversial A prospective randomized study of stratified high-risk categories of patients needs to be done on an international level. The most widely accepted regimen in this setting is the combination of cyclophosphamide and vincristine. Improving the survival of patients with overt metastases is a major challenge, which is especially relevant to the less developed parts of the world. Several multiagent regimens, particularly in combination with bone marrow transplantation, offer some promise. Experimental models are being used to overcome some of the limitations of clinical studies. Evaluations of responsiveness to chemotherapy, both in cell culture and animal models, are being conducted. Other areas being investigated include pharmacologic enhancement of radiotherapy and hematoporphyrin photodynamic therapy, use of tumor cell targeting techniques, differentiating agents, vitamin D, and immunotherapy. The nude mouse intraocular xenograft model appears to confirm clinical observations for responsiveness to conventional therapeutic agents.
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PMID:Chemotherapy in retinoblastoma: current status and future directions. 206 30

Passive immunization using antisera raised against rat PTH-like peptide [PLP-(1-34)] and rat PTH-(1-84) was used to assess and compare the roles played by PLP and PTH in modulating mineral metabolism in hypercalcemic rats bearing the Rice-500 Leydig cell tumor and in normocalcemic control animals. After immunization, plasma calcium in the tumor-bearing animals rapidly normalized and remained within the normal range for several days, plasma phosphate rose, and urinary phosphate and cAMP fell. These changes were associated with increased longevity of the tumor-bearing rats. Reduction of plasma calcium was shown to be a function of early (5 h) neutralization of PLP bioactivity in the kidney, whereas the effect of immunoneutralization of PLP in bone appeared later (24-48 h) and was more prolonged. Immunization against PTH in normocalcemic animals resulted in a hypocalcemic episode of smaller magnitude and shorter duration than that achieved in hypercalcemic animals immunized against PLP and appeared to be unassociated with neutralization of distal tubular effects. Neutralization of proximal tubular and skeletal actions of PTH appeared to occur in a manner analogous to that seen for PLP in tumor-bearing animals, but were of shorter duration. These studies suggest that in normal animals the action of PTH in the skeleton and/or on vitamin D metabolism contributes considerably more than renal transport activity to the maintenance of normocalcemia and that compensatory mechanisms rapidly restore homeostasis. PTH appears to be the major modulator of calcium homeostasis in normal rats, with PLP playing a minor role, if any. In tumor-bearing rats, mechanisms to restore calcium levels to baseline are delayed after PLP immunoneutralization, and PLP appears to be both necessary and sufficient for the hypercalcemic state.
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PMID:Effects of passive immunization against parathyroid hormone (PTH)-like peptide and PTH in hypercalcemic tumor-bearing rats and normocalcemic controls. 216 15

Secreted phosphoprotein 1 (Spp-1; osteopontin) is one of the abundant noncollagenous proteins in bone matrix and is produced by osteoblasts. We examined the promoter region of the mouse Spp-1 gene and identified a sequence responsible for 1,25-dihydroxyvitamin D3 enhancement of the Spp-1 gene expression. This 24-base-pair (bp) sequence (vitamin D response element) is located 761 bp upstream of the transcription start site and consists of two direct repeats of a unique 9-bp motif, AGGTTCACG. The vitamin D response element confers responsiveness of a heterologous promoter to 1,25-dihydroxyvitamin D3 in a position- and orientation-independent and copy-number-dependent manner. The basal level of expression of the reporter constructs containing this sequence and its response to 1,25-dihydroxyvitamin D3 were not affected by cotreatment with transforming growth factor beta or the tumor promoter phorbol 12-myristate 13-acetate or by cotransfection with a JUN expression vector. The vitamin D response element forms DNA-protein complexes, as indicated by gel-retardation assays. The addition of a monoclonal antibody raised against the vitamin D receptor further retarded the mobility of the DNA-protein complex. Another antibody that recognizes the DNA binding region of the vitamin D receptor attenuated its binding to the sequence. These results indicate that this 24-bp sequence containing two 9-bp motifs binds to the vitamin D receptor and mediates the vitamin D3 enhancement of murine Spp-1 gene expression.
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PMID:Identification of a DNA sequence responsible for binding of the 1,25-dihydroxyvitamin D3 receptor and 1,25-dihydroxyvitamin D3 enhancement of mouse secreted phosphoprotein 1 (SPP-1 or osteopontin) gene expression. 217 18

We studied the effects of specific nutritional modifications on colonic epithelial cell proliferation in mice and rats. The nutritional stress diet developed for this study was based on the AIN (American Institute of Nutrition)-76A semisynthetic diet, modified to contain four suggested risk factors of the human Western-style diet: increased fat and phosphate and decreased calcium and vitamin D content. We fed diets to mice and rats for 12 weeks beginning at 3 weeks of age. Hyperplasia developed in both sigmoid and ascending colon of mice and rats with lengthening of colonic crypts. Hyperproliferation developed in the sigmoid colon of mice and rats, and in the ascending colon of rats, with increased [3H]thymidine-labeling of epithelial cells. Thus, in colonic mucosa, the nutritional stress diet, which included risk factors of a Western-style diet, induced changes that occur in carcinogen-induced rodent models and in humans who are at increased risk for colonic neoplasia.
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PMID:Colonic hyperplasia and hyperproliferation induced by a nutritional stress diet with four components of Western-style diet. 231 21

The target proteins for calcium, when it acts as a second messenger, are a group of intracellular, specific calcium-binding proteins that contain EF-hand structures. Calmodulin regulates a number of Ca2+-dependent processes and is present in all eukaryotic cells. Parvalbumin, the S-100 proteins, two vitamin D-dependent Ca2+-binding proteins, and two tumor-associated proteins are present only in a few tissues and are there in distinct cell types serving more specific functions such as Ca2+-buffering or Ca2+-transport. The properties, distribution, and possible roles of these calcium-binding proteins in muscle, brain, and tumor cells are compared.
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PMID:Intracellular calcium-binding proteins: structure and possible functions. 243 30

Hypercalcemia and leukocytosis of malignancy have been highlighted over a decade. We report a case of a gallbladder cancer with marked hypercalcemia and leukocytosis. A 54-year-old woman was admitted to the hospital because of remittent fever and left hypochondric pain. The computed tomographic scan of the abdomen revealed the cancer of the gallbladder with liver metastases. The patient's medical condition deteriorated as the tumor was rapidly growing up. Her medical course was marked by hypercalcemia and an increase in mature neutrophils. Medical therapy with normal saline, furosemide, indomethacin, prednisolone, and calcitonin failed to ameliorate hypercalcemia. On the twenty-ninth hospital day the serum calcium was elevated to 17.6 mg/dl which responded to 1000 micrograms of mithramycin while leucocytosis continued. Despite the chemotherapy with doxorubicin and tegafur, the tumor continued to grow. Leukocytosis was attributed to the elevated colony-stimulating factor activity which was two-fold of control. The parathyroid hormone and nephrogeneous cyclic AMP levels were normal with low vitamin D levels. Hypercalcemia was attributed to a parathyroid hormone-like substance because of a decrease in %TRP in the presence of normal renal function and the normal parathyroid hormone level. Autopsy revealed an undifferentiated adenocarcinoma of the gallbladder with multiple liver metastases, and bone resorption in the vertebral column and sternum without evident bone metastasis.
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PMID:A case of a gallbladder cancer with marked hypercalcemia and leukocytosis. 253 86


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