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

We assessed the relationship between the parathyroid hormone-related protein (PTHrP) and the development of humoral hypercalcemia of malignancy (i.e., hypercalcemia due to the production by solid tumors of hypercalcemic factors) by assaying tumor extracts from hypercalcemic and normocalcemic patients with cancer for immunoreactive PTHrP contents. Immunoreactive PTHrP was demonstrated in extracts of 21 of 22 tumor tissues obtained from 22 patients with humoral hypercalcemia of malignancy. Immunoreactive PTHrP was rarely seen in tumor tissue extracts obtained from 34 normocalcemic patients with cancer and two hypercalcemic patients with cancer with severe bone metastases. Gel filtration studies of tumor extracts revealed a molecular-size heterogeneity of immunoreactive PTHrP. These radioimmunoassay data indicate a close relationship between detection of PTHrP in tumor tissues and the development of humoral hypercalcemia of malignancy.
 ...
PMID:Parathyroid hormone-related protein in tumor tissues obtained from patients with humoral hypercalcemia of malignancy. 229 55

Hypercalcemia is a frequent complication of cancer. Recently, parathyroid hormone-related protein has been isolated from tumors associated with this syndrome. In the present study, the effects of tumor-derived hypercalcemic factor and bovine parathyroid hormone (PTH) on bone were compared in an organ culture system using calvarial bones from newborn mice. Mouse calvaria were incubated for 72 h with control medium or media containing 0.15 mg/m tumor extract (TE) or 2 x 10(-9) M PTH. Bone resorption, as assessed by the amount of calcium released into the medium and the number of osteoclasts counted on light microscopy, was increased by both PTH and TE. On electron microscopy, areas for cytoplasm, ruffled border and clear zone were statistically increased in PTH- and TE-treated calvaria as compared to control. These values were not significantly different between PTH- and TE-treated calvaria. The study therefore demonstrates that the ultrastructural changes in osteoclasts induced by the hypercalcemia-producing TE are similar to those induced by PTH.
 ...
PMID:Effects of hypercalcemia-producing tumor extract and parathyroid hormone on osteoclast ultrastructure. 231 31

Tumors from patients with humoral hypercalcemia of cancer produce a parathyroid hormone-related protein (PTHRP). We have developed two region-specific immunoassays capable of measuring PTHRP in plasma: an immunoradiometric assay directed toward PTHRP amino acid sequence 1 to 74 and a radioimmunoassay directed toward PTHRP amino acid sequence 109 to 138. Sixty normal subjects had low or undetectable plasma PTHRP (1 to 74) concentrations (mean, 1.9 pmol per liter) and undetectable PTHRP (109 to 138) concentrations (less than 2.0 pmol per liter). Patients with humoral hypercalcemia of cancer (n = 30) had elevated levels of both PTHRP (1 to 74) (mean, 20.9 pmol per liter) and PTHRP (109 to 138) (mean, 23.9 pmol per liter). The plasma concentrations of immunoreactive PTHRP correlated with the levels of urinary cyclic AMP excreted; in some patients, the concentrations decreased after the tumors were resected. Patients with chronic renal failure (n = 15) had plasma PTHRP (1 to 74) concentrations similar to those in the normal subjects, but their plasma PTHRP (109 to 138) concentrations were elevated (mean, 29.6 pmol per liter). The levels of both peptides were normal in patients with hyperparathyroidism and those with hypercalcemia due to various other causes. Breast milk contained high concentrations of PTHRP. An anti-PTHRP (1 to 36) immunoaffinity column failed to extract PTHRP (109 to 138) immunoactivity from plasma, suggesting that the C-terminal region circulates as a separate peptide. We conclude that plasma PTHRP concentrations are high in the majority of patients with cancer-associated hypercalcemia and that the circulating forms of PTHRP in such patients include both a large N-terminal (1 to 74) peptide and a C-terminal (109 to 138) peptide. Measuring the concentrations of PTHRPs may be useful in the differential diagnosis of hypercalcemia.
 ...
PMID:Immunochemical characterization of circulating parathyroid hormone-related protein in patients with humoral hypercalcemia of cancer. 232 83

The presence of parathyroid hormone-related protein (PTHrP) in the apocrine adenocarcinoma tumor line (CAC-8) derived from a hypercalcemic dog was demonstrated by western and northern blot analyses. Western blots of CAC-8 tumor extracts revealed a major protein with a molecular weight of approximately 18,000 daltons that cross-reacted with antiserum to human PTHrP. Northern blots demonstrated multiple-sized messenger RNA transcripts in CAC-8 that hybridized to a full-length cDNA probe to human PTHrP. Adenocarcinomas derived from apocrine glands of the anal sac also were stained immunohistochemically for antigens that cross-react with antiserum to human PTHrP. The tumor line (CAC-8) maintained in nude mice stained positively for PTHrP in 13 of 24 tumors. Three of ten apocrine adenocarcinomas from dogs with hypercalcemia stained for PTHrP, whereas zero of ten tumors were positive from normocalcemic dogs. Normal canine epidermal keratinocytes and areas of squamous metaplasia in a perianal gland carcinoma also were positive for PTHrP. These data demonstrated that canine tissues contained a homologue to human PTHrP that likely is important in the pathogenesis of humoral hypercalcemia of malignancy.
 ...
PMID:Identification of parathyroid hormone-related protein in canine apocrine adenocarcinoma of the anal sac. 234 42

A 54-yr-old man with a left adrenal pheochromocytoma showed mild hypercalcemia and elevated nephrogenous cAMP. Serum levels of PTH and 1,25-dihydroxyvitamin D3 were not elevated. Postoperatively, serum calcium and nephrogenous cAMP declined to normal ranges. Pathologically, the tumor was a benign pheochromocytoma. The clinical findings resembled those of humoral hypercalcemia of malignancy (HHM), and PTH-related protein (PTHrP) immunoreactivity was detected in the tumor extract at a concentration of 80.7 pmol/g wet wt, which is high compared to levels in malignant tumors causing HHM. Production of PTHrP was further confirmed by the demonstration of PTHrP mRNA with Northern blot hybridization analysis. Gel filtration of the extract revealed the presence of at least two different molecules with both immunological and biological activities. One of the peaks appeared close to PTHrP-(1-34), and the other between cytochrome-c and BSA. The latter showed a higher bioactivity to immunoreactivity ratio. These data indicate the multiplicity of PTHrP molecules in pheochromocytoma and support the idea that PTHrP produced by pheochromocytoma causes hypercalcemia in a similar fashion as HHM.
 ...
PMID:A case of pheochromocytoma producing parathyroid hormone-related protein and presenting with hypercalcemia. 234 92

A cDNA complementary to the parathyroid hormone related protein (PTHrP), the humoral hypercalcemia factor in malignancy, was recently isolated and sequenced. PTHrP expression in human carcinomas was examined (determined) by Northern blot hybridization, Southern blot hybridization and radioimmunoassay (RIA). Expression of PTHrP mRNA was detected in three out of four lung squamous cell carcinomas, two out of ten breast carcinomas and the one adenosquamous carcinoma of the maxilla. No clinical hypercalcemia was found in these PTHrP mRNA positive carcinomas. No expression of PTHrP was detected in normal human or rat tissues. In Southern blot hybridization, no amplification of PTHrP gene was found in PTHrP positive cases. An insertion in one allele of promotor region of the gene was identified in one PTHrP positive lung squamous cell carcinoma. The serum level of PTHrP was examined using human PTHrP (1-34) RIA in lung carcinomas. We found no correlation between the level of PTHrP and clinical hypercalcemia or the histopathological diagnosis. We discuss some problems of the PTHrP assay as a novel tumor marker for malignancies. A new RIA assay study using recombinant human PTHrP expressed in Escherichia coli is also reported.
 ...
PMID:[A parathyroid hormone related protein (PTHrP) implicated in hypercalcemia associated with malignancy: research of the PTHrP for novel hormonal tumor marker]. 234 64

Bone resorption is increased in both humoral hypercalcemia of malignancy (HHM) and primary hyperparathyroidism. On the other hand, bone formation parameters are increased in primary hyperparathyroidism and decreased in HHM. Recently, a PTH-related protein (PTHrP) has been shown to be responsible for the hypercalcemia in the syndrome of HHM. In the present study we evaluated the effects of a neutralizing antiserum to PTHrP on bone histomorphometric parameters in hypercalcemic athymic mice bearing a human squamous cell lung cancer. These effects were compared to those of tumor resection. Similar to the effects of tumor resection, the antiserum to PTHrP resulted in a decrease in serum Ca levels, a decrease in bone resorption, and an increase in bone formation parameters. The studies, therefore, indicate that PTHrP is the major factor responsible for all of the features, including the decreased bone formation seen in HHM.
 ...
PMID:Tumor resection and antibodies to parathyroid hormone-related protein cause similar changes on bone histomorphometry in hypercalcemia of cancer. 236 75

The Rice H500 rat Leydig cell tumor is a well characterized model of humoral hypercalcemia of malignancy (HHM). Circulating concentrations of PTH-related protein (PTHRP) have not been reported in this or any other animal model of HHM. Taking advantage of the marked N-terminal amino acid homology between rodent and human PTHRPs, we have adapted a sensitive two-site immunoradiometric assay developed for measurement of human PTHRP for use in measuring rat PTHRP. Circulating calcium and PTHRP concentrations were serially measured after sc passage of the Leydig cell tumor in rats. Significant hypercalcemia and elevation of PTHRP occurred on day 9 after tumor inoculation. When grouped by tumor size, both plasma calcium and PTHRP levels were significantly elevated in animals with tumor burdens greater than 10 cc. The PTHRP concentration was strongly correlated with both serum calcium (r = 0.88) and tumor size (r = 0.80). Circulating rat PTHRP averaged 12.8 pM on day 9 and 27.5 pM on day 10 or 11. PTHRP was undetectable in the plasma of 19 control rats. In 3 rats, plasma calcium returned to normal, and PTHRP became undetectable within 24 h after tumor excision. Rat milk displayed a PTHRP concentration of 2000 pM, while acid-urea extract of the rat tumor contained 0.32 pmol/mg protein. Dilutions of rat plasma, milk, and tumor extract displayed response curves that were parallel to the human PTHRP-(1-74) standard in the assay. This two-site immunoradiometric assay is a sensitive and easily performed means of measuring rat PTHRP. It should be useful in studying this animal model of HHM and the function of PTHRP in normal tissues.
 ...
PMID:Measurement of circulating parathyroid hormone-related protein in rats with humoral hypercalcemia of malignancy using a two-site immunoradiometric assay. 238 60

Adult T cell leukemia (ATL) is associated with human T cell leukemia virus type 1 (HTLV-1) infection, and almost all ATL patients have the complication of hypercalcemia. To understand the mechanism of the high incidence of hypercalcemia in ATL, we studied the expression of a parathyroid hormone-related protein (PTHrP) gene that has been proposed as a causative factor of hypercalcemia in some solid tumors. The polymerase chain reaction coupled with reverse transcription of mRNA was applied to RNA from peripheral blood mononuclear cells. Cells from all 13 ATL patients examined showed abundant expression of the PTHrP gene, while cells from uninfected normal subjects did not. Significant expression of PTHrP gene was also detected in HTLV-1 carriers without any symptoms and in patients with HTLV-1-associated myelopathy or tropical spastic paraparesis. PTHrP mRNA levels correlated with the number of infected cells that were estimated by the integrated HTLV-1 DNA. These results suggest that HTLV-1-infected cells are expressing the PTHrP gene. This concept was further supported by the finding that the HTLV-1 trans-activator, the tax gene product, caused trans-activation of the PTHrP gene promoter linked to the CAT gene. These observations might explain the general expression of the PTHrP gene in ATL patients and the high incidence of hypercalcemia in ATL.
 ...
PMID:Constitutive expression of parathyroid hormone-related protein gene in human T cell leukemia virus type 1 (HTLV-1) carriers and adult T cell leukemia patients that can be trans-activated by HTLV-1 tax gene. 238 34

We investigated the possible involvement of parathyroid hormone-related protein (PTHrP) in 2 cases of metastatic pancreatic neuro-endocrine tumors associated with severe hypercalcemia. Both patients displayed biochemical alterations in renal tubular reabsorption of calcium and phosphate, as well as in urinary cAMP excretion, similar to those encountered in primary hyperparathyroidism, although plasma levels of parathyroid hormone were within the normal range. Tumor protein extracts stimulated cAMP production, which was inhibited by the PTH-antagonist (8,18 Nle, 34 Tyr)bPTH-(3-34)amide, in the PTH-responsive osteoblastic cell line UMR-106. Northern blot analysis of tumor extracts revealed the presence of PTHrP mRNA transcripts, while PTH mRNA was undetectable. In contrast, neither PTHrP mRNA(s) nor cAMP-stimulating activity was detectable in other neuroendocrine tumors not accompanied by hypercalcemia. These results demonstrate that certain pancreatic neuroendocrine tumors associated with hypercalcemia can synthesize and release PTHrP.
 ...
PMID:Parathyroid hormone-related protein and hypercalcemia in pancreatic neuro-endocrine tumors. 239 7


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>