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)

Parathyroid hormone related protein (PTHrP) is a novel calcium regulating hormone that may have a significant role in the pathophysiology of breast cancer. We have previously demonstrated a relationship between immunohistochemically detectable PTHrP in primary breast tumours and the subsequent development of bone metastases and hypercalcaemia. The aim of this study was to compare the PTHrP status in the primary tumours from three groups of patients with widely varying prognosis. (1) The favourable outcome group; all patients had a favourable prognosis and minimum 3 years disease free follow up (n = 30). (2) The unfavourable outcome group; all patients presented with localized breast cancer but developed distant disease within 3 years (n = 26). (3) The unfavourable presentation group; all had distant disease at first presentation (n = 26). No differences in PTHrP status of the primary tumour amongst the three patient groups were found (66%, 65% and 61% positive respectively). The development of bone with liver metastases and hypercalcaemia was associated with increased positive PTHrP status of the primary tumor.
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PMID:Parathyroid hormone related protein in breast cancers of widely varying prognosis. 849 17

Parathyroid hormone related protein (PTHrP) is produced by several breast cancers. 1,25 dihydroxyvitamin D (1,25[OH]2D) and Dexamethasone (DEX) have been shown to decrease PTHrP mRNA expression in several cell lines. We therefore tested the in vivo effect of both steroids on PTHrP secretion and tumor development of the Walker carcinoma (WC). WC cells were injected subcutaneously in Fisher rats which were simultaneously treated with either vehicle, or 1,25(OH)2D (0.5 micrograms/kg/d) or DEX (2 mg/kg/d). After 7 days, tumor weight was significantly decreased in the 2 treated-groups as compared to the control group. Vehicle treated-rats developed hypercalcemia, which was also observed in rats treated with 1,25(OH)2D; by contrast, the plasma calcium was significantly decreased in the DEX-treated group compared to vehicle-treated rats. In a dose-effect experiment, this dose of 1,25(OH)2D induced marked hypercalcemia in rats not implanted with WC, but was required to decrease the tumor weight in implanted rats. In both 1,25(OH)2D and DEX-treated groups, plasma PTHrP levels were significantly decreased, but there was a similar correlation between PTHrP plasma level and tumor weight in the three groups. Indeed, the cytosolic PTHrP content/mg tumor was identical in the 3 groups. By contrast, the PTHrP/Actin mRNA in the tumor was significantly decreased in the 1,25(OH)2D group, comparatively to the vehicle and DEX groups. Our results show that Dexamethasone and 1,25(OH)2D decrease WC tumor development in vivo, but do not change the PTHrP secretion by the remaining tumor although steady state PTHrP mRNA content level is decreased by 1,25(OH)2D.
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PMID:1,25 dihydroxyvitamin D and dexamethasone decrease in vivo Walker carcinoma growth, but not parathyroid hormone related protein secretion. 855 38

Amphibians living partially or totally in a terrestrial environment are the first tetrapods to possess parathyroid glands. Purely aquatic amphibians and amphibian larvae lack these endocrine glands. The parathyroids develop at the time of metamorphosis. The parathyroid glands in caecilians consist of a single cell type, that of urodeles may be composed of basal (supporting) cells and suprabasal (chief) cells, and that of anurans of small and large chief cells. Parathyroid glands of caecilians and anurans lack connective tissue, blood vessels, and nerves. The parathyroid cells become activated in response to decreased blood calcium concentration and undergo changes indicating increased parathyroid hormone secretion. Increased blood calcium concentration suppresses secretory activity. Usually, parathyroidectomy elicits hypocalcemia in most amphibians. Such operations have no effect in lower urodeles. Parathyroid hormone administration provokes hypercalcemia in most amphibians. The parathyroids of caecilians have not been studied in detail. The urodeles and anurans exhibit seasonal changes in the parathyroid glands. These changes may be initiated by environmental stimuli such as light, temperature, or alterations in blood calcium levels caused by natural hibernation.
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PMID:Amphibian parathyroids: morphological and functional aspects. 858 May 12

Cells of the monocyte-macrophage lineage have been thought to play a role in bone resorption. We examined the effects of in vivo administration of parathyroid hormone and 1,25-dihydroxyvitamin D3 on the ability of monocytes to degrade bone in vitro. Administration of parathyroid hormone for 4 d resulted in sustained hypercalcemia and a transient 1-d increase in plasma 1,25-dihydroxyvitamin D3. Parathyroid hormone significantly stimulated bone degradation by monocytes 2.6 times more than that of pretreatment controls. Parathyroid hormone treatment significantly enhanced (threefold) release of superoxide anion by monocytes stimulated with phorbol 12-myristate 13-acetate and increased migration of monocytes to bone particles in vitro. Continuous 7-d infusion of 1,25-dihydroxyvitamin D3 (50 micrograms/d) elevated plasma 1,25-dihydroxyvitamin D3 until infusions were discontinued. Increased 1,25-dihydroxyvitamin D3 was associated with hypercalcemia, which continued for several days postinfusion. In vivo administration of 1,25-dihydroxyvitamin D3 did not affect in vitro ability of monocytes to degrade bone. We concluded that in vivo administration of parathyroid hormone enhanced in vitro responsiveness of isolated monocytes in a manner consistent with a role for monocytes in bone remodeling. Furthermore, these data suggested that circulating monocytes could be a useful experimental model for further studies on parathyroid hormone responsiveness and bone resorption for the cow with milk fever.
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PMID:In vivo parathyroid hormone stimulates in vitro bone resorption by bovine monocytes. 867 53

Parathyroid hormone-related peptide (PTHrP) is thought to be responsible for hypercalcemia in some patients with malignant tumors. The PTHrP gene has seven exons, giving rise to three types of PTHrP isoform through alternative splicing. We studied the expression of mRNAs in 14 human cell lines using the reverse transcription-PCR method, to examine tissue-specific expression. All the cell lines expressed at least two types of PTHrP transcript. Most cell lines expressed all four types of PTHrP mRNA isoform. However, a rhabdomyosarcoma cell line, RD, and a bladder carcinoma cell line, T24, expressed only two types. These results may suggest that PTHrP mRNA is expressed in the majority of tumor and normal tissues and that it shows less tissue- or tumor-specificity.
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PMID:Multiple alternative splice isoforms of parathyroid hormone-related peptide mRNA in human cell lines. 874 30

Parathyroid hormone-related peptide (PTHrP) was initially identified as a product of malignant tumors that mediates paraneoplastic hypercalcemia. It is now known that the parathyroid hormone (PTH) and PTHrP genes are evolutionarily related and that the products of these two genes share a common receptor, the PTH/PTHrP receptor. PTHrP and the PTH/PTHrP receptor are widely expressed in both adult and fetal tissues, and recent gene-targeting and disruption experiments have implicated PTHrP as a developmental regulatory molecule. Apparent PTHrP functions include the regulation of endochondral bone development, of hair follicle formation, and of branching morphogenesis in the breast. Herein, we report that overexpression of PTHrP in chondrocytes using the mouse type II collagen promoter induces a novel form of chondrodysplasia characterized by short-limbed dwarfism and a delay in endochondral ossification. This features a delay in chondrocyte differentiation and in bone collar formation and is sufficiently marked that the mice are born with a cartilaginous endochondral skeleton. In addition to the delay, chondrocytes in the transgenic mice initially become hypertrophic at the periphery of the developing long bones rather than in the middle, leading to a seeming reversal in the pattern of chondrocyte differentiation and ossification. By 7 weeks, the delays in chondrocyte differentiation and ossification have largely corrected, leaving foreshortened and misshapen but histologically near-normal bones. These findings confirm a role for PTHrP as an inhibitor of the program of chondrocyte differentiation. PTHrP may function in this regard to maintain the stepwise differentiation of chondrocytes that initiates endochondral ossification in the midsection of endochondral bones early in development and that also permits linear growth at the growth plate later in development.
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PMID:Targeted overexpression of parathyroid hormone-related peptide in chondrocytes causes chondrodysplasia and delayed endochondral bone formation. 881 83

Parathyroid hormone-related peptide was originally identified as a tumor-produced factor that mediated malignancy-associated hypercalcemia by binding to the common parathyroid hormone/parathyroid hormone-related peptide receptor to stimulate osteoclastic bone resorption and renal tubular resorption of calcium. Its role as a humoral factor in hypercalcemia of malignancy is well established, and recent work has demonstrated its importance as a tumor-produced factor in the pathogenesis of bone metastasis. Besides these cancer-related functions, work in the past decade has clearly established that parathyroid hormone-related peptide has many important functions in normal physiology related to growth and development, reproductive function and smooth muscle relaxation. Many other physiological functions are also being attributed to this versatile peptide. An understanding of these functions in malignancy and normal physiology should lead to innovative therapy for malignancy as well as other disorders not previously related to calcium homeostasis.
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PMID:Physiological and pathological roles of parathyroid hormone-related peptide. 882 27

Stimulation of bone resorption by local factors, the cytokines, is key to the development of hypercalcemia in multiple myeloma patients. Parathyroid hormone-related peptide, the systemic factor found in humoral hypercalcemia, has rarely been incriminated in myeloma. We report a case of myeloma with hypercalcemia and elevated serum level of parathyroid hormone-related peptide. Bisphosphonate therapy was rapidly effective in correcting serum calcium levels despite persistent high levels of the peptide. Seven other cases of myeloma with hypercalcemia and high serum parathyroid hormone-related peptide levels have been reported. Expression by myeloma plasmocytes of the messenger RNA for this peptide has also been demonstrated. These data suggest that parathyroid hormone-related peptide may contribute to the development of hypercalcemia in some myeloma patients.
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PMID:Secretion of parathyroid hormone-related peptide in patients with multiple myeloma. 889 65

Parathyroid hormone-related peptide (PTHrP) is involved in cell proliferation in both neoplastic and non-neoplastic tissues. We describe an autopsy case of gastric cancer in a patient who showed serum hypercalcemia and overexpression of PTHrP and PTH/PTHrP receptor in the metastatic tumor cells. The primary gastric tumor was poorly differentiated adenocarcinoma, and multiple metastases were present in the bone, multiple visceral organs, peritoneum, and lymph nodes. PTHrP and its mRNA were detected only in the metastatic tumor cells, but not in primary gastric tumor. PTH/PTHrP receptor was also demonstrated immunohistologically in metastatic tumor cells. This case suggests that the expression of PTHrP is related to tumor progression and the poor prognosis in tumors associated with humoral hypercalcemia.
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PMID:Gastric cancer associated with overexpression of parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor in relation to tumor progression. 921 56

The measurement of calciotropic hormones may be useful in metabolic bone disease. Assays of intact parathyroid hormone are essential to differentiate between primary hyperparathyroidism and nonparathyroid-mediated hypercalcemia. Vitamin D status is best assessed by measuring serum 25(OH)D. Concentrations of calciotropic hormones should be measured in osteoporotic patients if the degree of osteopenia does not correlate with the risk factors. The decrease in circulating parathyroid hormone in osteoporotic patients treated with vitamin D reflects the success of the vitamin D treatment. Parathyroid hormone is also a potential anabolic agent.
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PMID:Diagnostic and therapeutic aspects of calciotropic hormones. 922 85


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