Hypercalcemia and Elevated 1,25-Dihydroxyvitamin D Levels in a Patient with End-Stage Renal Disease and Active Tuberculosis

Gkonos, Peter J.; London, Robert T.; Hendler, Ernesto D.

doi:10.1056/nejm198412273112607

Cited by 157 publications

(69 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thus, the humoral mediators in the hypercalcaemia associated with haematological malignancies include both 1,25-(OH) 2 D 3 and PTHrP. (Adams et al 1983, Gkonos et al 1984, Mason et al 1984. Similarly, a major mediator of hypercalcaemia in Hodgkin's disease, non-Hodgkin's lymphoma and other haematological malignancies appears to be an extra-renal production of 1,25-(OH) 2 D 3 (Seymour et al 1994).…”

Section: Hhm Vsmentioning

confidence: 99%

“…Vitamin D receptors within renal proximal convoluted tubule cells are involved in an autocrine negative feedback loop, whereby increased levels of 1,25-(OH) 2 D 3 will down-regulate 1,25-(OH) 2 D 3 production (Takeyama et al 1997). Other known important extra-renal sites of 1,25-(OH) 2 D 3 production are the placenta and granulomatous tissue (Barbour et al 1981, Gkonos et al 1984, Zerwekh & Breslau 1986.…”

Section: Pthmentioning

confidence: 99%

See 1 more Smart Citation

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Clines

Guise²

2005

Endocr Relat Cancer

229

211

View full text Add to dashboard Cite

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-b 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.

show abstract

Section: Hhm Vsmentioning

confidence: 99%

Section: Pthmentioning

confidence: 99%

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Clines

Guise²

2005

Endocr Relat Cancer

229

211

View full text Add to dashboard Cite

show abstract

“…Human pulmonary alveolar macrophages from patients suffering from sarcoidosis have been shown capable of la-hydroxylation, which converts 25-hydroxyvitamin D3 to calcitriol by a metabolic process distinct in its regulation from classical renal metabolism of vitamin D (6). Local production of calcitriol by macrophages may be sufficient to cause systemic effects even in the absence of renal production ofcalcitriol (7,8). Moreover, normal human monocytes and macrophages can be induced by gamma interferon (IFN-7y)' or lipopolysaccharide (LPS) to exhibit I a-hydroxylase activity (9).…”

Section: Introductionmentioning

confidence: 99%

Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA.

Rigby¹,

Denome²,

Fanger³

1987

J. Clin. Invest.

347

176

View full text Add to dashboard Cite

The steroid hormone, la,25-dihydroxyvitamin D3 (calcitriol), has been shown to inhibit T cell proliferation, primarily through inhibition of interleukin 2 (IL-2) production. In these experiments, we show that calcitriol also markedly inhibited production of the lymphokine, gamma interferon (IFN-y), by activated human T lymphocytes. Regulation of both IL-2 and IFN-y production as well as transferrin receptor (TfR) expression by calcitriol was apparent at the messenger RNA (mRNA) level as determined by Northern blotting. The decrease in IL-2 and IFN-'y mRNA that occurred with calcitriol treatment was coordinate and not apparent up to 12 h after phytohemagglutinin stimulation, whereas decreased accumulation of TfR mRNA was not present before 24-36 h. Furthermore, the effects of calcitriol on IL-2, IFN-'y, and TfR mRNA accumulation were specific; actin mRNA accumulation was comparable between control and treated cells. These data indicate that calcitriol regulated proteins associated with T cell activation at the transcriptional level and that these effects were mediated in a specific, coordinate fashion.

show abstract

“…In contrast, in sarcoidosis, tuberculosis, several granulomatoses, and rheumatoid arthritis, abnormal 1,25D homeostasis is the cause of hypercalcemia (1,18,19,34). In these patients, high levels of 1,25D in serum result from excessive 1,25D synthesis by the disease-activated macrophage (2,3,28) and loss of the capacity of 1,25D to regulate its own synthesis and degradation (16,42).…”

mentioning

confidence: 99%

Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

Vidal

Ramana

Dusso

2002

Molecular and Cellular Biology

122

View full text Add to dashboard Cite

Hypercalcemia and Elevated 1,25-Dihydroxyvitamin D Levels in a Patient with End-Stage Renal Disease and Active Tuberculosis

Cited by 157 publications

References 19 publications

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Hypercalcaemia of malignancy and basic research on mechanisms responsible for osteolytic and osteoblastic metastasis to bone

Regulation of lymphokine production and human T lymphocyte activation by 1,25-dihydroxyvitamin D3. Specific inhibition at the level of messenger RNA.

Stat1-Vitamin D Receptor Interactions Antagonize 1,25-Dihydroxyvitamin D Transcriptional Activity and Enhance Stat1-Mediated Transcription

Contact Info

Product

Resources

About