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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and forty-seven patients with hypercalcaemia and advanced breast cancer have been reviewed. One hundred and twenty-five (85%) had definite bone metastases but in 22 (15%) there was no radiographic evidence of skeletal involvement. Sixty-eight (46%) patients also had liver metastases. These were present in 15/22 (68%) without definite skeletal involvement and 53/125 (42%) with bone metastases (P = less than 0.05). In a series of 498 patients with first relapse in bone after primary treatment hypercalcaemia was more common after the development of liver metastases than in patients with disease remaining confined to the skeleton (31% v 15%; P = less than 0.001). A subsequent prospective biochemical study of 35 patients with hypercalcaemia suggested that a humoral factor was more pronounced in 18 with liver metastases. In this group renal tubular reabsorption of calcium was higher, serum phosphate and tubular reabsorption of phosphate lower, and cyclic AMP excretion was increased. The data suggest that there is an association between the presence of liver metastases and the development of hypercalcaemia in patients with breast cancer. The mechanisms by which liver involvement may contribute to the pathogenesis of hypercalcaemia are not known but could arise from either increased production or decreased clearance of a humoral factor.
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PMID:Hypercalcaemia and breast cancer--an increased humoral component in patients with liver metastases. 284 66

In an attempt to analyze the pathological processes which lead to hypercalcemia in patients with multiple bone metastases, 23 advanced breast cancer patients with multiple bone metastases, three hypercalcemic patients with other malignancies and seven early breast cancer patients without any distant metastasis were studied. Of the 23 patients with advanced breast cancer, nine showed serum calcium levels higher than 10 mg/dl. In five of the nine hypercalcemic patients with advanced breast cancer, urinary cyclic AMP excretion was lower than 4 nmol/100 ml of glomerular filtrate (GF), indicating that the secretion of parathyroid hormone was suppressed. However, urinary cyclic AMP excretion was higher than 4 nmol/100 ml of GF in the other four hypercalcemic patients with advanced breast cancer and three hypercalcemic patients with other malignancies. In patients with higher urinary cyclic AMP excretion, fractional excretion of calcium (FECa) showed a negative correlation (r = 0.83, P less than 0.05) with urinary cyclic AMP. Parathyroid hormone immunoreactivity was not detected in any of six patients showing serum calcium levels higher than 11 mg/dl. These results suggest that in about a half of hypercalcemic patients with advanced breast cancer and multiple bone metastasis, there is a factor which increases urinary cyclic AMP and enhances calcium reabsorption in the kidney, but which is different from parathyroid hormone. This factor may facilitate retention of calcium mobilized into the circulation by bone metastases, and lead to hypercalcemia.
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PMID:Stimulation of calcium reabsorption observed in advanced breast cancer patients with hypercalcemia and multiple bone metastases. 298 61

The relation between circulating 1,25-dihydroxyvitamin D (1,25(OH)2D) levels and intestinal calcium absorption--as determined by an oral calcium load test--was studied in 16 patients with hypercalcaemia of malignancy (HM) and 16 with hypercalcaemic primary parathyroidism (HPT). In the HPT group serum calcium rose significantly after the oral calcium load and the increment correlated significantly with 1,25(OH)2D levels. While 1,25(OH)2D levels were raised to within the hyperparathyroid range in a number of HM patients, there was no correlation between change in serum calcium and 1,25(OH)2D level in the HM group and serum calcium did not rise significantly after the oral calcium load. HM patients with detectable or raised 1,25(OH)2D levels typically had few, or no, bone metastases in association with squamous lung cancers. A high proportion of these patients exhibited other aspects of hyperparathyroid-like activity such as increased renal tubular calcium reabsorption, depressed renal tubular phosphate reabsorption and elevated urinary cyclic AMP excretion. Conversely, HM patients with undetectable 1,25(OH)2D levels typically had extensive metastatic bone disease in association with breast carcinoma and were less likely to exhibit other hyperparathyroid-like features. It is postulated that in the former, the 'inappropriately' detectable or raised 1,25(OH)2D levels may have been due to enhanced renal 1 alpha-hydroxylase activity stimulated by the parathyroid hormone (PTH)-like effect of a non-PTH ectopic humoral mediator. In the latter the suppressed 1,25(OH)2D levels would be the predicted result of a non-humorally mediated hypercalcaemia. It is currently unclear why intestinal calcium absorption was depressed in all HM patients when 1,25(OH)2D levels were normal or raised in some cases. It is possible, however, that in HM there is 'end organ' resistance to the effects of 1,25(OH)2D due to a generalized malabsorptive process.
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PMID:Comparison of intestinal calcium absorption and circulating 1,25-dihydroxyvitamin D levels in malignancy-associated hypercalcaemia and primary hyperparathyroidism. 365 75

Postmortem bone and parathyroid gland histology in nine hypercalcemic cancer patients without bone metastases was compared to bone and parathyroid histology in ten normocalcemia patients. Parameters of parathyroid function, including serum immunoreactive parathyroid hormone, acid base status, serum phosphate, and nephrogenous cyclic AMP were measured in the hypercalcemic group and compared to normals and to patients with primary hyperparathyroidism. Bone histology in all nine hypercalcemic cancer patients showed increased osteoclastic bone resorption and increased fibrous connective tissue in the bone marrow. Parathyroid glands were of normal size in all nine patients but contained little or no fat, one criterion of parathyroid hyperplasia. In the normocalcemic cancer patients only 2/10 had minimally increased bone resorption while 7/10 had decreased or absent stromal fat in the parathyroid glands. Despite the hyperplastic appearance of the parathyroid glands, serum biochemical parameters in the hypercalcemic cancer patients indicate a state of suppressed parathyroid function suggesting that the osteoclastic bone resorption is related to a humoral substance elaborated by the tumors which is distinct from parathyroid hormone.
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PMID:Abnormal bone and parathyroid histology in carcinoma patients with pseudohyperparathyroidism. 627 64

Elevated plasma calcitonin was detected by radioimmunoassay in 19 of 99 unselected cancer patients (19%). The frequency of hypercalcitoninaemia in patients with tumours of lung, uterus, gastrointestinal tract, and urinary bladder was about 40%, in carcinoma of the breast 18%, and in carcinoma of the skin 4%. In 8 patients with bone metastases, 4 were hypercalcitoninaemic. None of 19 patients with non-malignant disorders had elevated plasma calcitonin. The highest plasma calcitonin level in cancer patients was 8200 ng/l. Urinary cyclic AMP was elevated in patients with hypercalcitoninaemia as compared with patients with normal plasma calcitonin. All 6 patients with medullary carcinoma of the thyroid had very high plasma calcitonin levels: more than 50000 ng/l in five and 30000 ng/l in one patient. Of the family members of these patients, raised plasma calcitonin was detected after stimulation with oral alcohol in 6 of 12. It is concluded that plasma calcitonin levels in excess of 10000 ng/l suggest the presence of medullary carcinoma of the thyroid, while levels below 10000 ng/l have a poor diagnostic value but should alert the clinician to look for a possible malignancy.
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PMID:Hypercalcitoninaemia in medullary carcinoma of the thyroid and other malignancies: value of calcitonin as tumour marker. 628 27

A case of humoral non-parathyroid hypercalcemia in a breast cancer patient is discussed. Bone metastases developed 23 months after the first clinical evidence of increased serum calcium levels and did not appear to be etiologically involved in this case of hypercalcemia. Serum levels of I-PTH and PGE2 were normal, as were urinary c-AMP levels. Furthermore, no significant response to corticosteroid therapy was observed. However, the correlation between the activity of metastatic disease and calcemia suggests that this cancer produced humoral factor(s) with calcium-mobilizing activity.
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PMID:Humoral nonparathyroid hypercalcemia without evidence of bone involvement. 630 87

Although small cell carcinoma of the lung has a high incidence of skeletal metastasis and is frequently associated with paraneoplastic syndromes, it is only rarely associated with hypercalcemia. Similarly, the more unusual small cell carcinoma of the pancreas has not been associated with hypercalcemia. The authors describe the first such patient with small cell carcinoma of the pancreas and hypercalcemia. Comprehensive metabolic measurements (fasting calcium excretion, renal phosphorus threshold, 1,25 dihydroxyvitamin D, 25 hydroxyvitamin D levels, nephrogenous cyclic AMP and immunoreactive PTH levels) suggest that although bone metastases were present, the hypercalcemia may have been caused in part by humoral mechanisms.
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PMID:Hypercalcemia in small cell carcinoma of the pancreas. 632 Oct 9

To find out if the concentration of parathyroid hormone-related protein (PTHrP) predicts the response of tumour-inducing hypercalcaemia (TIH) to pamidronate, we studied 44 patients. Pretreatment measurements of serum PTHrP, calcium and phosphate, nephrogenous cyclic AMP, tubular threshold for calcium and phosphate (TmP), and the presence of bone metastases were correlated with response to pamidronate. Response was considered good (normal calcium concentration corrected for albumin [CCa] for > 14 days), or poor (failure of CCa to fall, or a rise above normal < or = 14 days). PTHrP correlated significantly with response (good vs poor, p = 0.02). Undetectable PTHrP (< 2 pmol/L) was associated with a good response in all seven treatments, PTHrP in the range 2-12 pmol/L was associated with good response in 10 of 14 treatments, while PTHrP > or = 12 pmol/L was associated with a poor response in all 11 treatments. Tubular threshold for calcium correlated with the fall in CCa by day 6 after treatment (p = 0.02). Urinary clearance estimations in poor responders suggested that there was an incomplete reversal of the renal tubular component of hypercalcaemia. Serum PTHrP correlates with response to pamidronate in the treatment of TIH; which may be associated with a renal tubular mechanism not significantly affected by currently available treatment. Drugs that inhibit tubular reabsorption of calcium or PTHrP secretion may help in patients who do not respond to pamidronate.
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PMID:Parathyroid hormone-related protein and response to pamidronate in tumour-induced hypercalcaemia. 810 20

Bisphosphonates are potent inhibitors of osteoclast function widely used to treat excessive bone resorption associated, e.g., with bone metastases. They have also antitumor activity. However, it is unclear whether this reflects an indirect effect via inhibition of bone resorption or a direct antitumor effect. Nitrogen-containing bisphosphonates (N-BPs), including zoledronic acid (ZOL), act by inhibiting farnesyl pyrophosphate synthase (FPPS). The mevalonate pathway is blocked and the accumulation of isopentenyl pyrophosphate (IPP) consequently occurs. IPP is conjugated to AMP to form a novel ATP analog (ApppI). The present study was undertaken to clarify whether IPP and/or ApppI has a direct involvement in apoptosis caused by ZOL in different cancer cell lines. There are marked differences in ZOL-induced ApppI formation between different cancer cell lines. On this basis, we selected three cancer cell lines that differ significantly from each other in their ZOL-induced IPP and ApppI accumulation: human estrogen-dependent (MCF7) and estrogen-independent (MDA-MB 436) breast cancer cell lines and a human myeloma cell line (RPMI 8226). The amount of IPP/ApppI correlated with the capacity of cells to undergo apoptosis. Geranylgeraniol (GGOH), an intermediate of mevalonate metabolism, blocks both IPP and ApppI formation and to some degree ZOL-induced apoptosis in a cell line-dependent manner. In addition, lovastatin (LOV), an inhibitor of the enzyme HMGCoA reductase, completely blocks IPP/ApppI formation as determined by mass spectrometry analysis, but enhances apoptosis. In conclusion, the current data suggest that ZOL-induced IPP/ApppI formation can contribute to ZOL-induced apoptosis. This mechanism and the inhibition of protein prenylation, both outcomes of FPPS inhibition in mevalonate pathway, seem to act in concert in ZOL-induced apoptosis in cancer cells.
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PMID:The level of ATP analog and isopentenyl pyrophosphate correlates with zoledronic acid-induced apoptosis in cancer cells in vitro. 1969 19

We report two cases of adult T-cell leukemia/lymphoma(ATLL)having their main lesions in the stomach. Case 1 was a 74-year-old man, complaining of left upper abdominal mass and pain. Upper gastrointestinal endoscopy revealed an ulcerous lesion in the stomach. Histological analysis and southern blotting for HTLV-1 pro-viral DNA led us to our diagnosis of ATLL. There were no apparent lesions in the bone marrow and other organs. He died of tumor lysis and multi-organ failure shortly after treatment with the VCAP-AMP-VECP regimen. Case 2 was a 68-year-old man complaining of abdominal bloating and pain. Upper gastrointestinal endoscopy disclosed an irregularity of the gastric mucosa. A biopsy sample was diagnosed pathohistologically as non-Hodgkin's lymphoma. We conducted total gastrectomy. Based on the results from the histological study and southern blotting for HTLV-1 p ro-viral DNA in the resected specimen, a diagnosis of ATLL was made. We treated him with a VCAP-AMP-VECP regimen, but multiple bone metastases and pathologic fracture occurred, proving that the disease was progressive. ATLL having a main lesion in the stomach is rare, and requires an accumulation of cases analyzed with careful diagnostic approach to establish a standard therapy for it.
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PMID:[Two cases of adult T-Cell leukemia/lymphoma with main lesion in stomach treated by VCAP-AMP-VECP regimen]. 2315 32


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