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Medline ® Abstracts for References 1,2,5,6

of '恶性肿瘤高钙血症的机制'

1
TI
Clinical practice. Hypercalcemia associated with cancer.
AU
Stewart AF
SO
N Engl J Med. 2005;352(4):373.
 
AD
Division of Endocrinology, University of Pittsburgh School of Medicine, Pittsburgh 15213, USA. stewart@dom.pitt.edu
PMID
2
TI
Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone.
AU
Clines GA, Guise TA
SO
Endocr Relat Cancer. 2005;12(3):549.
 
Calcium homeostasis is a tightly regulated process involving the co-ordinated efforts of the skeleton, kidney, parathyroid glands and intestine. Neoplasms can alter this homeostasis indirectly through the production of endocrine factors resulting in humoral hypercalcaemia of malignancy. Relatively common with breast and lung cancer, this paraneoplastic condition is most often due to tumour production of parathyroid hormone-related protein and ensuing increased osteoclastic bone resorption. Although control of hypercalcaemia is generally successful, the development of this complication is associated with a poor prognosis. The metastasis of tumour cells to bone represents another skeletal complication of malignancy. As explained in the 'seed and soil' hypothesis, bone represents a fertile ground for cancer cells to flourish. The molecular mechanisms of this mutually beneficial relationship between bone and cancer cells are beginning to be understood. In the case of osteolytic bone disease, tumour-produced parathyroid hormone-related protein stimulates osteoclasts that in turn secrete tumour-activating transforming growth factor-beta that further stimulates local cancer cells. This 'vicious cycle' of bone metastases represents reciprocal bone/cancer cellular signals that likely modulate osteoblastic bone metastatic lesions as well. The development of targeted therapies to either block initial cancer cell chemotaxis, invasion and adhesion or to break the 'vicious cycle' is dependent on a more complete understanding of bone metastases. Although bisphosphonates delay progression of skeletal metastases, it is clear that more effective therapies are needed. Cancer-associated bone morbidity remains a major public health problem, and to improve therapy and prevention it is important to understand the pathophysiology of the effects of cancer on bone. This review will detail scientific advances regarding this area.
AD
Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia, PO Box 801419, Charlottesville, Virginia 22908-1419, USA.
PMID
5
TI
Development of a sensitive two-site immunoradiometric assay for parathyroid hormone-related peptide: evidence for elevated levels in plasma from patients with adult T-cell leukemia/lymphoma and B-cell lymphoma.
AU
Ikeda K, Ohno H, Hane M, Yokoi H, Okada M, Honma T, Yamada A, Tatsumi Y, Tanaka T, Saitoh T
SO
J Clin Endocrinol Metab. 1994;79(5):1322.
 
We have developed a sensitive immunoradiometric assay for PTH-related peptide (PTHrP) using a monoclonal antibody against PTHrP(1-34) and a polyclonal antibody against PTHrP(50-83), with recombinant human PTHrP(1-87) as the standard. The detection limit of the immunoradiometric assay was 0.5 pmol/L, and plasma PTHrP(1-87) concentrations in 110 healthy subjects were 0.8 +/- 0.01 pmol/L, with the upper limit of the normal range being 1.1 pmol/L. Increased circulating PTHrP(1-87) concentrations were demonstrated in all 46 cancer patients with hypercalcemia, but not in patients with primary hyperparathyroidism, chronic renal failure, or hypoparathyroidism. Normalization of serum calcium levels after resection of tumors was shown to correlate well with that of plasma PTHrP(1-87) concentrations in 2 cancer patients. High circulating PTHrP(1-87) levels were also demonstrated in 12 out of 13 hypercalcemic patients with adult T-cell leukemia/lymphoma and in 7 out of 8 hypercalcemic patients with non-Hodgkin's lymphoma especially of B-cell type. These results suggest that PTHrP is a major humoral factor responsible for the hypercalcemia frequently associated with adult T-cell leukemia/lymphoma and also with B-cell lymphoma.
AD
Fourth Department of Internal Medicine, University of Tokyo School of Medicine, Japan.
PMID
6
TI
Direct comparison of sustained infusion of human parathyroid hormone-related protein-(1-36) [hPTHrP-(1-36)]versus hPTH-(1-34) on serum calcium, plasma 1,25-dihydroxyvitamin D concentrations, and fractional calcium excretion in healthy human volunteers.
AU
Horwitz MJ, Tedesco MB, Sereika SM, Hollis BW, Garcia-Ocaña A, Stewart AF
SO
J Clin Endocrinol Metab. 2003;88(4):1603.
 
PTH and PTH-related protein (PTHrP) cause primary hyperparathyroidism and humoral hypercalcemia of malignancy (HHM), respectively. These syndromes are similar in several important ways, but differ in several characteristic, yet unexplained, ways. Two of the unresolved questions in HHM and hyperparathyroidism involve renal physiology. 1) Why does renal proximal tubular production of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D]differ between the two syndromes? 2) Do distal tubular calcium responses to PTH and PTHrP differ in the two syndromes? To address these questions, we compared the two peptides, human PTH-(1-34) and PTHrP-(1-36), in a direct, head to head study using a continuous, steady state infusion of each peptide at the same dose in normal human volunteers for 46 h. We had previously described such methods as applied to PTHrP, but a direct multiday comparison of PTHrP to PTH has not previously been reported. In two groups (seven subjects each) of healthy young (25- to 35-yr-old) normal volunteers, PTH and PTHrP infused at 8 pmol/kg.h displayed similar calcemic effects, although PTH was slightly more potent in this regard. Both peptides also displayed similar phosphaturic effects.In addition, both peptides had similar effects on renal tubular calcium handling, yielding fractional calcium excretion values of approximately 3.5%, some 50% below the values (6.5%) observed in subjects rendered similarly hypercalcemic by the infusion of calcium. In contrast to these several quantitatively similar effects of PTH and PTHrP, PTH tended to be selectively more effective than PTHrP in stimulating renal production of 1,25-(OH)(2)D. These studies indicate that renal tubular calcium reabsorption is likely to contribute to hypercalcemia in patients with HHM. In addition, PTH may be selectively more effective than PTHrP in stimulating 1,25-(OH)(2)D production, in contrast to its phosphaturic, calcemic effects and its effects to stimulate nephrogenous cAMP excretion and renal tubular calcium reabsorption.
AD
Division of Endocrinology, University of Pittsburgh School of Medicine, Pennsylvania 15213, USA. horwitz+@pitt.edu
PMID