| Autor: |
Mawer, E B, Walls, J, Howell, A, Davies, M, Ratcliffe, W A, Bundred, N J |
| Jazyk: |
angličtina |
| Rok vydání: |
1997 |
| Předmět: |
|
| Zdroj: |
Mawer, E B, Walls, J, Howell, A, Davies, M, Ratcliffe, W A & Bundred, N J 1997, ' Serum 1,25-dihydroxyvitamin D may be related inversely to disease activity in breast cancer patients with bone metastases ', The Journal of Clinical Endocrinology and Metabolism, vol. 82, no. 1, pp. 118-22 . https://doi.org/10.1210/jcem.82.1.3642 |
| DOI: |
10.1210/jcem.82.1.3642 |
| Popis: |
1,25-dihydroxyvitamin D (1,25-(OH)2D) stimulates differentiation and controls proliferation in breast cancer cells. The role of endogenous 1,25-(OH)2D and its relation to PTH related protein (PTHrP) during the progression of breast cancer is not known; we therefore investigated these hormones in two studies. In a cross-sectional study of patients with breast cancer at different stages of disease, serum 1,25-(OH)2D levels (mean +/- SE) were highest in early disease (102 +/- 3.7 pmol/L), fell in normocalemic patients with bone metastases (52 +/- 5.3 pmol/L; P < 0.01), and were lowest in hypercalcemic patients (33 +/- 5.6 pmol/L; P < 0.001). PTHrP was detectable in the serum of only one normocalcemic patient with progressive metastases but was present in 11 of the 12 hypercalcemic patients, thus PTHrP did not stimulate 1,25-(OH)2D synthesis. In a 6-month longitudinal study of normocalcemic patients with bone metastases undergoing hormonal therapy, serum 1,25-(OH)2D concentrations fell in patients whose disease progressed (P = 0.0056), but remained constant in those who were stable or responded to treatment. These changes in 1,25-(OH)2D preceded clinical signs of progression and predicted disease response. In the progressive group, five of whom died during the study, 1,25-(OH)2D decreased between the initial and final samples, PTH fell significantly from 24.8 to 13.5 ng/L (P = 0.025), serum calcium rose from 2.27 to 2.39 mmol/L (P = 0.017), and the urinary calcium/creatinine ratio rose from 0.37 to 0.68 (P = 0.046). PTH and 1,25-(OH)2D were significantly correlated in the final samples from this group, Spearman's rank correlation = 0.80, P = 0.022. The results indicate that normocalcemia in these patients is maintained, at the expense of suppressing PTH and 1,25-(OH)2D, in the face of increased calcium released from lytic lesions in bone. Loss of the antiproliferative effects of 1,25-(OH)2D may then permit more rapid secondary growth of the tumor. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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