Circulating levels of midregional parathyroid hormone‐related protein in hypercalcaemia of malignancy

Blind, E.; Raue, Friedhelm; Götzmann, Joachim; Schmidt-Gayk, H; Kohl, B.; Ziegler, Reinhard

doi:10.1111/j.1365-2265.1992.tb02324.x

Cited by 34 publications

(13 citation statements)

References 29 publications

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“…In contrast to the present findings, others also using assays which recognize epitopes within the 1-74 region found that PTHrP was unstable in EDTA plasma and that addition of protease inhibitors was necessary to prevent progressive degradation.v" In a recent study using a RIA directed at residues 53-84, PTHrP was found to be stable in serum and plasma for several days. 8 There is evidence from cell culture studies that PTHrP produced in vitro is processed within the amino-terminus at residues 20 and 37. 10 Proteolysis at these sites could explain the apparent instability of amino-terminal PTHrP in unseparated blood.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast endogenous PTHrP53-84 activity is reported to be stable in serum and plasma for up to 3 days at 4°C. 8 Here we describe a systematic comparison of the effects of different anticoagulants and protease inhibitors on the in vitro stability of endogenous PTHrPI-86 from patients with HM as measured by a sensitive, specific immunoradiometric assay (IRMA).2…”

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confidence: 99%

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In vitro Stability of Endogenous Parathyroid Hormone-Related Protein in Blood and Plasma

et al. 1994

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SUMMARY. We describe a systematic comparison of the effects of anticoagulants, protease inhibitors and conditions of sample handling on the in vitro stability of endogenous parathyroid hormone-related protein (PTHrP) in blood from patients with hypercalcaemia of malignancy (HM). When blood was separated within 15 min of collection, PTHrPI-861eve1s measured by two-site immunoradiometric assay in serum and heparinized plasma were significantly lower than in ethylenediarninetetraacetic acid (EDTA) plasma (P<0·02). PTHrP was unstable in blood kept at 20°C for 4 h and inclusion of protease inhibitors reduced, but failed to abolish, this instability. In blood collected in the presence of EDTA, inclusion of leupeptin either alone or in combination with pepstatin and aprotinin increased the mean half-time of disappearance from 3·9 to 10'1 and 11· 2 h, respectively (P< 0,05). In contrast, when blood containing EDTA was separated within 15 min, PTHrP was stable in plasma at 20°C for at least 4 h. As a result of the instability of PTHrPI-86 immunoreactivity in whole blood at ambient temperatures we advise that for our immunoradiometric assay (IRMA) blood collected in EDTA should be separated within 15 min, and the plasma frozen until assay.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

In vitro Stability of Endogenous Parathyroid Hormone-Related Protein in Blood and Plasma

et al. 1994

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“…Normal values were obtained for white blood count, platelet count, prothrombin, and partial thromboplastin time, albumin, creatinine, BUN, calcium, phosphate, sodium, potassium, AST, ALT, LDH, total protein, C-reactive protein, and serum protein. Levels for parathyroid hormone (pTH, measured as Nterminal pTH and total pTH), 1.25 (OH)2 vitamin D, and 25 OH vitamin D (determined with commercial radioimmunoassays) were within normal limits, pTH-related activity was not detectable in the serum [1]. Arterial blood pH, pO2, pCO2, bicarbonate, base excess were normal.…”

Section: Case Reportmentioning

confidence: 94%

Reversible metastatic pulmonary calcification in a patient with multiple myeloma

et al. 1996

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A-52-year-old patient presented with a 2-year history of multiple myeloma, recurrent episodes of hypercalcemia, and extensive bone involvement. She developed pulmonary infiltrates, initially misdiagnosed as interstitial pneumonia. High-resolution computed tomography and bone scintiscanning indicated pulmonary calcification, which was confirmed by a transbronchial biopsy. Cytostatic treatment of multiple myeloma in combination with repetitive i.v. administration of bisphosphonates over a period of 6 months led to a significant improvement of clinical symptoms. Regression of pulmonary infiltrates was demonstrated by chest radiograph and computed tomography. There are only a few reports on pulmonary calcification in patients with multiple myeloma; the condition was associated mostly with progressive disease, kidney failure, adult respiratory distress syndrome and bad prognosis. In our patient isolated calcification of the lungs without involvement of other organ systems was successfully treated. These findings suggest that interstitial pulmonary calcinosis in multiple myeloma can be reversed by normalization of serum calcium levels using bisphosphonates combined with cytostatic treatment.

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“…For this assay, 100 l goat antiserum (1:8000), raised against amino acids 53 -84 (Blind et al, 1992), and 100 l reconstituted CM were incubated under non-equilibrium conditions. Synthetic human PTHrP (1 -86) (Bissendorf Biochem., Hannover, Germany) was used as standard and for tracer preparation (Schilling et al, 1996).…”

Section: Midregional Ipthrp Radioimmunoassay (Ria)mentioning

confidence: 99%

Regulation of PTHrP and PTH/PTHrP Receptor by Extracellular Ca2+Concentration and Hormones in the Breast Cancer Cell Line 8701-BC

Luparello

Santamaria²,

Schilling³

2000

Biological Chemistry

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It was previously reported that 8701-BC breast tumour cells express the gene for parathyroid hormone-related peptide (PTHrP) and PTH/PTHrP receptor (PTHrP-R) and release immunoreactive PTHrP (iPTHrP) into the extracellular medium. Since the regulation of PTHrP and PTHrP-R by breast cancer cells has been poorly investigated so far, we have chosen the 8701-BC cell line as a model system to investigate whether alterations in the extracellular Ca2+ concentration ([Ca2+]e) and treatment with some well-known differentiation agents for breast cells, such as dimethyl sulfoxide, hydrocortisone, progesterone, prolactin, all-trans retinoic acid and transforming growth factor-beta1 might (i) modulate quantitatively the release of iPTHrP, (ii) affect the PTHrP promoter usage and mRNA splicing patterns, and (iii) modify the expression of PTHrP-R. The data obtained indicate that 8701-BC cells are potentially able to utilise different start sites and mRNA splicing patterns for PTHrP transcription, and respond to variations of [Ca2+]e and to the addition of two hormones, hydrocortisone and progesterone, with modifications in the extracellular amount of iPTHrP. Moreover, expression of PTHrP-R is also modulated by changes of [Ca2+]e or treatment with hydrocortisone. This indicates that the 8701 -BC cell line is a suitable in vitro model for further studies on the complex molecular regulation of the PTHrP/PTHrP-R pair in breast cancer.

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Circulating levels of midregional parathyroid hormone‐related protein in hypercalcaemia of malignancy

Abstract: This radioimmunoassay of midregional PTHrP provides high diagnostic sensitivity in the identification of humoral hypercalcaemia of malignancy caused by solid tumours. The assay should therefore be useful in the differential diagnosis of hypercalcaemia.

Cited by 34 publications

References 29 publications

In vitro Stability of Endogenous Parathyroid Hormone-Related Protein in Blood and Plasma

In vitro Stability of Endogenous Parathyroid Hormone-Related Protein in Blood and Plasma

Reversible metastatic pulmonary calcification in a patient with multiple myeloma

Regulation of PTHrP and PTH/PTHrP Receptor by Extracellular Ca2+Concentration and Hormones in the Breast Cancer Cell Line 8701-BC

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