Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The strain of Walker carcinosarcoma 256 described induces hypercalcaemia, hyperphosphataemia and hyperuraemia in tumour bearing rats. Changes in calcium and phosphorus excretion are observed as well as accompanying calcification of soft tissue organs and loss of bone calcium. These changes in calcium metabolism disappear after removal of the tumour, so that long-range action of the tumour can be stated. The results are discussed in comparison with three other animal models of tumour dependent hypercalcaemia.
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PMID:The hypercalcaemic syndrome in rats bearing the Walker carcinosarcoma 256. 117 20

High calcium leads to the secretion of calcitonin, and the administration of 1,25-dihydroxyvitamin D3 leads to a decreased transcription of the calcitonin gene. We now report the effect of chronic hypercalcemia, hypocalcemia, and vitamin D deficiency on calcitonin gene expression in vivo in the rat. Hypercalcemia was created by calcium infusions for 6 h, a high-calcium diet given to weanling rats for 3 weeks, and the transplantation of the Walker carcinosarcoma 256 cell line. Despite serum calcium as high as 22 mg/dl, there was no difference in calcitonin mRNA levels among these rats. The control genes studied, actin and somatostatin, which is specific for C cells in the thyroparathyroid tissue, also did not differ among the different groups of rats. Injected 1,25-(OH)2D3 decreased calcitonin mRNA levels at 6 h, as previously reported. Hypocalcemia, created by feeding diets deficient in calcium and vitamin D to weanling rats for 3 weeks, had no effect on calcitonin mRNA levels, in contrast to the large increases in PTH mRNA levels. These results demonstrate that calcitonin gene expression in vivo in the rat is regulated by administered 1,25-(OH)2D3 but not by changes in serum calcium.
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PMID:Regulation of calcitonin gene expression by hypocalcemia, hypercalcemia, and vitamin D in the rat. 136 Jul 44

The hypercalcaemic Walker carcinosarcoma 256 is a rat model for humoral hypercalcaemia of malignancy (HHM). Tumour products such as parathyroid hormone-related proteins (PTHRP) and various growth factors appear to be responsible for this syndrome. Recently, PTHRP immunoreactivity has been detected in the conditioned medium of Walker tumour cells. The present report describes the isolation of a 18,000-Da molecular weight form of PTHRP from Walker tumour homogenates, by using a relatively simple immunoaffinity purification method. Our results suggest that this PTHRP form is similar to that purified from other HHM-related tumours.
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PMID:Isolation of a 18,000-Da molecular weight form of parathyroid hormone-related protein from the rat Walker carcinosarcoma 256. 145 Nov 1

One of the strains of the Walker 256 carcinosarcoma induces in the rat a humoral hypercalcaemia of malignancy (HHM) syndrome which is similar to that reported in human patients. We have isolated from this tumour a chromatographic fraction which displays an adenylate cyclase stimulating activity in dog kidney cortical membranes, similar to that of a parathormone (PTH) related protein isolated from various HHM related tumours. In addition, this fraction stimulated initial calcium (Ca) uptake in confluent Madin-Darby canine kidney (MDCK) cell monolayers in a dose-dependent manner. Maximal stimulation of Ca uptake was associated with an enhanced Ca efflux from MDCK cells preloaded with the cation, and with an increased DNA synthesis in these cells. These activities might be involved in development of increased tubular calcium reabsorption in Walker 256 tumour-bearing rats.
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PMID:Co-purification of calcium transport-stimulating and DNA synthesis-stimulating agents with parathormone-like activity isolated from the hypercalcaemic strain of the Walker 256 tumour. 183 87

The rat Walker carcinosarcoma 256 is an animal model for humoral hypercalcaemia of malignancy (HHM). In this model, the relative contribution of bone and kidney in the hypercalcaemia of tumour-bearing rats was investigated. Daily administration of pamidronate, a bone resorption inhibitor, for 2 days prevented the increased fasting Ca2+ excretion observed in the hypercalcaemic rats, although serum Ca2+ remained high. However, the high serum Ca2+ normalised after the acute injection of ethiofos, an inhibitor of renal Ca2+ reabsorption, which was associated with a marked increase of Ca2+ excretion. Changes in Ca2+ were accompanied by similar changes in Mg2+. The results indicate that altered renal Ca2+ handling has a key role in the hypercalcaemia associated with this HHM model.
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PMID:Relative role of bone and kidney in the hypercalcaemia associated with the rat Walker carcinosarcoma 256. 184 15

Bisphosphonates are compounds with a high affinity for bone and other calcified tissues. They inhibit tumor-induced bone destruction and the associated hypercalcemia by hindering the activity of the osteoclasts. Owing to a long biological half-life of bisphosphonates in the bone, a treatment using a prophylactic regimen seems possible. This paper summarizes preclinical studies with the bisphosphonate 3-amino-1-hydroxypropylidene-1,1-diphosphonic acid and two methyl derivatives; 3-N,N-dimethylamino-1-hydroxypropylidene-1,1-diphosphonic acid and 4-N,N-dimetyhlamino-1-hydroxybutylidene-1,1-diphosphonic acid with respect to their bone-protecting activity in therapy as well as in prophylaxis. To find substances that are useful for the treatment of primary tumor, as well as bone metastasis, we synthesized and tested cis-diammine[nitrilotris(methylphosphonato)(2-)-O1,N1]platin um(II) and cis-diammine[( bis-(phosphonatomethyl)amino]acetato(2-)-O1,N1)platinum(II), which contain both an osteotropic and an antineoplastic moiety. Experiments were carried out: (a) in the intratibial transplanted Walker carcinosarcoma 256B of the rat, which mimics osteolytic bone metastasis, and (b) in the transplantable osteosarcoma of the rat, which shows a histology and metastatic pattern similar to that found in man. These investigations indicate that it is possible to effect adjuvant therapy of bone metastases by combination of two compounds with different properties into one structure without losing the therapeutic characteristics of the parent compounds. They thus provide evidence that it may be possible to design compounds well suited for the therapeutic or prophylactic treatment of bone-related malignancies.
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PMID:Anticancer-agent-linked phosphonates with antiosteolytic and antineoplastic properties: a promising perspective in the treatment of bone-related malignancies? 215 96

We tested the existence of 25-hydroxyvitamin D-1 alpha-hydroxylase activity in the Walker carcinosarcoma 256 implanted in rats. This tumour has been shown to induce hypercalcaemia in the host animal. We found this enzyme activity in tumour homogenates, which was in the same range as that in the kidney of tumour-bearing rats. Our results suggest that 1,25-dihydroxyvitamin D synthesized by the Walker tumour might be involved in the mechanism responsible for the hypercalcaemia in the host rat.
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PMID:Evidence of 1,25-dihydroxyvitamin D synthesis by the rat Walker carcinosarcoma 256. 239 82

Neoplasms of the parathyroid glands are uncommon in all species of laboratory and domestic animals, but occur in low incidence in rats, Syrian hamsters, and dogs and rarely in mice. Proliferative lesions of the parathyroid gland include hyperplasia (diffuse and focal), adenomas, and carcinomas. The tumors may be functional or nonfunctional. Trophic atrophy of remaining parathyroid tissue is present around functional tumors. Humoral hypercalcemia of malignancy (HHM) is a syndrome that occurs in human and animal patients with certain malignant neoplasms and is characterized by hypercalcemia, hypophosphatemia, and increased osteoclastic bone resorption. The syndrome is thought to be due to the release of parathyroid hormone (PTH)-like factors by the tumor cells which bind to PTH receptors in bone and kidney and result in the clinical manifestations of HHM. Parathyroid hormone-related protein (PTHrP) is a newly purified and sequenced protein which originated from human tumors associated with HHM. PTHrP has been shown to stimulate in vitro and in vivo effects similar to PTH-like proteins isolated from tumors associated with HHM. Well characterized animal models of HHM include a rat Leydig cell tumor line (Rice-500), the rat Walker mammary carcinosarcoma, and the canine apocrine adenocarcinoma. All 3 models have been found to contain 3 biologic activities which are thought to be important in the pathogenesis of HHM, viz., in vitro bone resorbing activity, adenylate cyclase-stimulating activity of bone and kidney cells, and transforming growth factor activity. The first 2 activities are due to PTH-like proteins which are able to compete for binding to the PTH receptor. The complete spectrum of functional disturbances in patients with HHM may be the result of the combined effects of a PTH-like protein (i.e., PTHrP) and transforming growth factors.
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PMID:Tumors of the parathyroid gland and circulating parathyroid hormone-related protein associated with persistent hypercalcemia. 267 85

The effects of WR-2721 [S-2-(3-aminopropylaminoethyl)phosphorothioic acid] in two in vivo and in vitro models of experimental hypercalcemia in the rat were examined. Chronic WR-2721 administration by osmotic minipump (250 mg/kg/24 hr) reduced serum calcium from 12.0 +/- 0.1 to 9.5 +/- 1.0 mg/dl (P less than .01) in rats receiving 1,25-(OH)2 Vitamin D3. Control rats receiving Vitamin D without WR-2721 had a rise in serum calcium to 13.4 +/- 0.2 mg/dl over the same 5-day period. In an experimental form of humoral hypercalcemia of malignancy, the Walker carcinosarcoma tumor-implanted rat, WR-2721 reduced serum calcium from 13.6 +/- 0.3 to 8.4 +/- 0.6 mg/dl by 5 to 6 days (P less than .001). In vitro bone resorption assays utilizing fetal rat long bones in organ culture showed complementary results. WR-2721 (10(-4) M) blocked bone resorption (assayed as percentage of 45Ca release) induced by both conditioned medium derived from cell lines of Walker carcinosarcoma (7.6 +/- 1.4 vs. 24.0 +/- 1.8%, P less than .01) and by addition of 1,25-(OH)2 Vitamin D3 (10(-8) M) (9.8 +/- 0.8 vs. 17.3 +/- 1.0%, P less than .01). These results suggest that WR-2721 may be effective in controlling clinical hypercalcemia due to excess bone resorption.
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PMID:In vivo and in vitro effects of WR-2721 in experimental hypercalcemia in the rat. 301 29

This study was designed to assess the capacity of etidronate disodium (etidronate) to affect neoplastic involvement of bone by murine tumors. Using sublines of the Walker 256 carcinoma, differing in the pattern of bone involvement, etidronate was found to inhibit hypercalcemia caused by systemically acting humoral factors, to inhibit bone metastasis following inoculation of tumor cells into the abdominal aorta, and to reduce the invasion of bone adjacent to tumors. Etidronate was also found to prevent bone metastasis in syngeneic rat mammary carcinoma. Etidronate was found devoid of direct antineoplastic activity, whether administered intramuscularly, subcutaneously, or intravenously, in a series of murine tumors of different histologic varieties. At the same time, it was shown that etidronate did not modify the antineoplastic activity of any of the major chemotherapeutic agents used in these studies, nor did it demonstrate any degree of immunosuppression. The experimental models used for this study should prove useful in evaluating agents that may affect the various types of bone involvement seen in neoplastic disease. The drug's apparent lack of interference with the antineoplastic activity of standard cytotoxic agents and its lack of immunosuppressive activity suggest that it may be readily adaptable to combination chemotherapy regimens.
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PMID:Effect of etidronate disodium on the interactions between malignancy and bone. 310 35


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