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高钙血症和恶性病变患者血浆中的甲状旁腺激素相关肽

Parathyroid hormone-related peptide in plasma of patients with hypercalcemia and malignant lesions.

作者信息

Kao P C, Klee G G, Taylor R L, Heath H

机构信息

Section of Clinical Chemistry, Mayo Clinic, Rochester, MN 55905.

出版信息

Mayo Clin Proc. 1990 Nov;65(11):1399-407. doi: 10.1016/s0025-6196(12)62163-6.

DOI:10.1016/s0025-6196(12)62163-6
PMID:1700240
Abstract

We developed and validated a radioimmunoassay for circulating human parathyroid hormone-related peptide (PTHrP), based on a commercial antiserum to the synthetic 1-34 fragment of PTHrP, 125I-Tyr degrees-PTHrP(1-34) as radioligand, and prior extraction of the native peptide from plasma with C-2 cartridges. We determined immunoreactive PTHrP concentrations in plasma samples from 48 healthy persons (mean +/- SD, 3.1 +/- 1.0 pmol/liter; range, less than 2 to 5 pmol/liter), 8 patients with primary hyperparathyroidism, 36 patients with hypercalcemia and a concurrent malignant lesion, and 9 normocalcemic patients with cancer and increased serum levels of carcinoembryonic antigen or prostate-specific antigen. PTHrP was normal in samples from patients with primary hyperparathyroidism (3.2 +/- 1.1 pmol/liter), secondary hyperparathyroidism (2.5 +/- 1.3 pmol/liter), and cancer without hypercalcemia (2.4 +/- 1.0 pmol/liter). In contrast, plasma immunoreactive PTHrP levels were increased (6.0 to 85.0 pmol/liter) in 47% of patients with hypercalcemia and cancer of various types, with or without bone metastatic lesions. Large amounts of PTHrP were also found in conditioned medium from cultured human prostatic carcinoma cells. Thus, PTHrP may be a causative factor for hypercalcemia associated with a malignant lesion in at least half of the cases. Measurement of circulating PTHrP may be of differential diagnostic help in hypercalcemic states.

摘要

我们基于针对甲状旁腺激素相关肽(PTHrP)合成的1 - 34片段的商业抗血清、以125I - Tyr0 - PTHrP(1 - 34)作为放射性配体,并先用C - 2柱从血浆中提取天然肽,开发并验证了一种用于检测循环中人甲状旁腺激素相关肽(PTHrP)的放射免疫分析方法。我们测定了48名健康人(均值±标准差,3.1±1.0 pmol/升;范围,小于2至5 pmol/升)、8名原发性甲状旁腺功能亢进患者、36名高钙血症并发恶性病变患者以及9名血钙正常但癌胚抗原或前列腺特异性抗原血清水平升高的癌症患者血浆样本中的免疫反应性PTHrP浓度。原发性甲状旁腺功能亢进患者(3.2±1.1 pmol/升)、继发性甲状旁腺功能亢进患者(2.5±1.3 pmol/升)以及无高钙血症的癌症患者(2.4±1.0 pmol/升)样本中的PTHrP水平正常。相比之下,47%的各类高钙血症合并癌症患者,无论有无骨转移病变,其血浆免疫反应性PTHrP水平升高(6.0至85.0 pmol/升)。在培养的人前列腺癌细胞的条件培养基中也发现了大量PTHrP。因此,PTHrP可能是至少一半病例中与恶性病变相关的高钙血症的致病因素。检测循环中的PTHrP可能有助于高钙血症状态的鉴别诊断。

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