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)

A new cell line, designated EC-GI, was established from a 65-year-old patient with esophageal carcinoma who developed humoral hypercalcemia. The original tumor as well as the cell line caused marked hypercalcemia in tumor-bearing nude mice, in which a marked increase in osteoclastic bone resorption was demonstrated. The conditioned medium of EC-GI cells contained potent bone resorbing activity which stimulated cyclic AMP production in parathyroid hormone (PTH)-responsive osteoblast-like cells (ROS 17/2.8). EC-GI cells will be useful for characterization and purification of the PTH-like factor responsible for humoral hypercalcemia of malignancy.
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PMID:Establishment of a parathyroid hormone-like factor-producing esophageal carcinoma cell line (EC-GI). 282 16

Studies on the pathogenesis of hypercalcemia in canine lymphosarcoma have led to conflicting results. The biochemical and bone histomorphometric findings in canine lymphosarcoma were examined in 19 hypercalcemic and 17 nonhypercalcemic dogs with lymphosarcoma. Compared to the nonhypercalcemic group, the hypercalcemic dogs demonstrated an increase in fasting and 24-h calcium excretion, an increase in fractional phosphorus excretion, and a significant increase in nephrogenous AMP excretion. Plasma 1,25-dihydroxyvitamin D and immunoreactive PTH levels were equivalent in the two groups. Quantitative bone histomorphometry performed on iliac crest biopsies revealed increased parameters of bone resorption in those hypercalcemic dogs with no evidence of tumor at the biopsy site, without a compensatory increase in bone formation. Acid-urea tumor tissue extracts from eight hypercalcemic and six nonhypercalcemic dogs were examined for adenylate cyclase-stimulating activity (ACSA). All tumors from hypercalcemic dogs contained ACSA, whereas none of the tumors from nonhypercalcemic dogs had ACSA. Further purification of one tumor extract yielded an adenylate cyclase-stimulating protein which appeared to interact specifically with the PTH receptor. We conclude that in some cases, hypercalcemia in canine lymphosarcoma is mediated by a tumor-derived circulating bone-resorbing factor which is distinct from PTH. ACSA detected in tumor tissue appears to be a reliable marker for the syndrome in vivo. The role of this activity in the pathogenesis of the syndrome remains to be determined.
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PMID:Humoral hypercalcemia of malignancy in canine lymphosarcoma. 282 6

To evaluate the cause of hypercalciuria, we carried out the oral calcium tolerance test before and after parathyroidectomy in a patient with primary hyperparathyroidism who had recurrent and multiple nephrolithiasis. Preoperative laboratory examination showed hypercalcemia, hypophosphetamia, hypercalciuria, decrease in % tubular reabsorption of phosphorus and strikingly elevated urinary cyclic AMP excretion. The oral calcium tolerance test indicated a significantly greater increase in serum calcium (delta serum calcium: 1.4 mg/dl vs 0.8 mg/dl) and a significantly greater suppression of urinary cyclic AMP excretion (delta U-cyclic AMP:-3.56 moles/gCre vs-1.17 moles/gCre) before parathyroidectomy than after. These results showed that hypercalciuria in this case was induced not only by the significant increase in the filtrated load of calcium but by the reduction in the resorption of calcium in the distal tubule caused by the significantly suppressed parathyroid hormone effect.
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PMID:[A case report: primary hyperparathyroidism--comparison before and after parathyroidectomy by oral calcium tolerance test]. 283 26

Carbetimer (carbethimer, N-137, NED-137, carboxyimamidate) is a low molecular weight polyelectrolyte with antitumor activity in a variety of tumor models. This phase I trial evaluated a single dose of carbetimer infused over 1-2 h every 28 days. Forty-three patients received 71 courses of the drug at doses ranging from 180 to 8500 mg/m2. The dose-limiting toxicity was hypercalcemia (serum calcium greater than 12.5 mg/dl) noted in two of three patients at a dose of 8500 mg/m2. Serum calcium levels between 10.5 and 12.5 mg/dl were noted in an additional three patients treated at doses greater than or equal to 1600 mg/m2. Calcium balance studies in three patients treated at 6500 mg/m2 revealed an increase in urinary cyclic AMP and phosphate excretion after treatment accompanied by a mild elevation of serum parathyroid hormone. Immunological studies in these patients revealed a statistically significant increase in the percentage of peripheral T-helper cells. An increase in the T-helper/suppressor cell ratio was observed in two of the three patients studied. Interleukin 2 production by phytohemagglutinin-stimulated peripheral mononuclear cells was increased in two of three patients. One patient with a renal cell carcinoma showed a mixed response. The recommended dose for phase II trials as assessed from this study is 6500 mg/m2 as a single dose every 28 days.
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PMID:Phase I clinical trial of carbetimer. 284 47

One hundred and forty-seven patients with hypercalcaemia and advanced breast cancer have been reviewed. One hundred and twenty-five (85%) had definite bone metastases but in 22 (15%) there was no radiographic evidence of skeletal involvement. Sixty-eight (46%) patients also had liver metastases. These were present in 15/22 (68%) without definite skeletal involvement and 53/125 (42%) with bone metastases (P = less than 0.05). In a series of 498 patients with first relapse in bone after primary treatment hypercalcaemia was more common after the development of liver metastases than in patients with disease remaining confined to the skeleton (31% v 15%; P = less than 0.001). A subsequent prospective biochemical study of 35 patients with hypercalcaemia suggested that a humoral factor was more pronounced in 18 with liver metastases. In this group renal tubular reabsorption of calcium was higher, serum phosphate and tubular reabsorption of phosphate lower, and cyclic AMP excretion was increased. The data suggest that there is an association between the presence of liver metastases and the development of hypercalcaemia in patients with breast cancer. The mechanisms by which liver involvement may contribute to the pathogenesis of hypercalcaemia are not known but could arise from either increased production or decreased clearance of a humoral factor.
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PMID:Hypercalcaemia and breast cancer--an increased humoral component in patients with liver metastases. 284 66

The characteristics of PTH secretion, which have been extensively studied in vitro with dispersed cells of normal and abnormal parathyroid glands, remain poorly studied in vivo. We performed ethylenediamine tetraacetate (EDTA) intravenous infusions in 12 normal subjects and 5 patients with hypercalcemia (serum ionized calcium between 2.72 and 2.89 mEq/l) and surgically proven primary hyperparathyroidism (PHPT) to establish the relationship between nephrogenous cyclic AMP (NcAMP) used as an index of PTH secretion and serum ionized calcium. We determined the maximal NcAMP taken as an index of maximal secretory rate for PTH, the set point and sensitivity of parathyroid cells for calcium. In normal subjects, mean values (+/- SD) were 4.04 +/- 0.47 nmol/dl glomerular filtrate (GF) for maximal NcAMP, 2.23 +/- 0.04 mEq/l for set point, and -250 +/- 58 for sensitivity when NcAMP was expressed in percent of maximal value and serum calcium in mEq/l. In patients with PHPT, the differences between maximal and basal values of NcAMP represented 50% or more of maximal NcAMP, indicating that PTH secretion was suppressible. Sensitivity values were within normal limits in all patients. Calculated set point values were abnormally elevated (between 2.64 and 2.83 mEq/l) in all patients. Maximal NcAMP values ranged from low to normal (2.77 nmol/dl GF) to abnormally high (6.64 nmol/dl GF), and a positive linear correlation was observed with parathyroid cell mass. Basal serum calcium concentrations were not correlated with either parathyroid cell mass or maximal NcAMP values, and were close to calculated set point values for each patient.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Maximal PTH secretory rate and set point for calcium in normal subjects and patients with primary hyperparathyroidism. In vivo studies. 285 Apr 60

The syndrome of humoral hypercalcaemia of malignancy (HHM) is characterised by end-organ manifestations of parathyroid-hormone (PTH)-like effects such as abnormalities of renal tubular calcium and phosphate transport, increased nephrogenous cyclic AMP and 1,25 dihydroxyvitamin D production, and increased osteoclastic bone resorption. Despite this, true ectopic PTH production has seldom been documented in HHM. A number of bone-resorbing factors, including prostaglandins, prostaglandin-stimulating factors, lymphokines, growth factors, and vitamin-D-like sterols, have been implicated as causes of HHM, but none can reproduce the PTH-like biochemical features characteristic of the syndrome. PTH-related peptides have recently been isolated from tumours associated with HHM. These substances are the most likely putative humoral mediators of HHM, since they are structurally similar to PTH in the aminoterminal region and interact with the PTH receptor in vitro. However, the remainder of the molecule is quite distinct from PTH, which accounts for the absence of PTH immunoreactivity in serum and tumour extracts from HHM patients. Since these factors seem to act by binding to the PTH receptor, synthetic PTH antagonists may in the future be a means of treating HHM.
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PMID:The pathogenesis of humoral hypercalcaemia of malignancy. 289 2

Availability of immunoassays for specific regions of the parathyroid hormone (PTH) molecule allows discrimination with a high level of surety between primary hyperparathyroidism and tumoral hypercalcemic states associated with circulating PTH-like substances. Assay for intact, N-terminal PTH currently has the highest discriminant function. Prostaglandin-dependent and osteoclast-activating factor-mediated hypercalcemic states associated with neoplasia have suppressed serum PTH levels. PTH-like substances are detected by immunoassays, but in the intact, N-terminal system they are seen as normal-range or low values. The frequency with which any tumor produces only authentic PTH is very low. The serum chloride:phosphate ratio has limited clinical utility in distinguishing tumoral hypercalcemia from hyperparathyroid hypercalcemia, and measurements of nephrogenous cyclic AMP do not distinguish between the effects of circulating authentic PTH and PTH-like substances elaborated by tumors. Additional measures that, in the future, may help to distinguish between parathyroid and tumoral hypercalcemias include quantitative bone biopsy histomorphometry and in vitro bioassays for PTH activity in the separate plasma fractions, obtained by gel filtration, in which PTH and PTH-like substances are found.
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PMID:Diagnosis of hyperparathyroidism. 298 31

In an attempt to analyze the pathological processes which lead to hypercalcemia in patients with multiple bone metastases, 23 advanced breast cancer patients with multiple bone metastases, three hypercalcemic patients with other malignancies and seven early breast cancer patients without any distant metastasis were studied. Of the 23 patients with advanced breast cancer, nine showed serum calcium levels higher than 10 mg/dl. In five of the nine hypercalcemic patients with advanced breast cancer, urinary cyclic AMP excretion was lower than 4 nmol/100 ml of glomerular filtrate (GF), indicating that the secretion of parathyroid hormone was suppressed. However, urinary cyclic AMP excretion was higher than 4 nmol/100 ml of GF in the other four hypercalcemic patients with advanced breast cancer and three hypercalcemic patients with other malignancies. In patients with higher urinary cyclic AMP excretion, fractional excretion of calcium (FECa) showed a negative correlation (r = 0.83, P less than 0.05) with urinary cyclic AMP. Parathyroid hormone immunoreactivity was not detected in any of six patients showing serum calcium levels higher than 11 mg/dl. These results suggest that in about a half of hypercalcemic patients with advanced breast cancer and multiple bone metastasis, there is a factor which increases urinary cyclic AMP and enhances calcium reabsorption in the kidney, but which is different from parathyroid hormone. This factor may facilitate retention of calcium mobilized into the circulation by bone metastases, and lead to hypercalcemia.
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PMID:Stimulation of calcium reabsorption observed in advanced breast cancer patients with hypercalcemia and multiple bone metastases. 298 61

Secretion by tumor cells of circulating bone-resorbing factors may frequently underlie the hypercalcemia that occurs in patients with malignancy. Efforts to identify the responsible mediators have been hampered by a lack of available human tumor cell systems suitable for study of the pathogenesis of the humoral hypercalcemia syndrome. We have established a transitional-cell carcinoma (TCC) line in vitro from a patient with humoral hypercalcemia. These cells are tumorigenic and cause hypercalcemia in athymic nude mice. Culture medium conditioned by TCC cells contains potent bone-resorbing activity in vitro, the physical and biological properties of which are similar to those of bone-resorbing activity present in the original patient's urine. The bone-resorbing activity of the TCC factor is accompanied by increased prostaglandin release from bone and is blocked by indomethacin and calcitonin. The TCC-derived bone-resorbing activity coelutes with prostaglandin-stimulating activity during gel filtration with an approximate molecular weight of 15,000. This activity is nondialyzable, stable to concentrated urea and reducing agents, and destroyed by boiling. The TCC factor does not increase cyclic AMP production in bone or kidney bioassays and does not exhibit transforming growth factor activity. We conclude that a unique macromolecular factor released by TCC cells causes bone resorption by a mechanism dependent upon stimulation of bone cell cyclooxygenase, and that this factor is the probable cause of the hypercalcemia in vivo. The TCC cell line provides a new model for study of the human humoral hypercalcemia syndrome.
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PMID:Humoral hypercalcemia of malignancy. Release of a prostaglandin-stimulating bone-resorbing factor in vitro by human transitional-cell carcinoma cells. 300 59


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