Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A RIA for PTH-related protein (PTHrP) is described, using a polyclonal goat antiserum against synthetic PTHrP-(1-40) and recombinant PTHrP-(1-84) as standard. The detection limit is 2 pmol/L, and intra- and interassay coefficients of variation are 4.8% and 13.6%, respectively. This assay does not detect PTH even at concentrations of up to 2000 pmol/L. Cross-reactivity studies using various synthetic PTHrP peptides localize the antibody-binding epitope between residues 20 and 29. Hypercalcemic patients with a range of solid tumors and no evidence of bone metastases on radionuclide scanning (n = 27) all had detectable PTHrP levels (range, 2.8-51.2 pmol/L). Of 17 patients with solid tumors (other than breast) and bone metastases, 11 (64%) also had detectable PTHrP levels (range, 4.9-47.5 pmol/L). Twenty samples from breast cancer patients with hypercalcemia, 19 with evidence of bone metastases, and 1 with a negative bone scan were assayed, and detectable PTHrP levels were found in 13 (65%; range, 3.8-61.6 pmol/L). Patients with squamous cell carcinomata and normal serum calcium levels (n = 11) had no detectable PTHrP or levels close to the detection limit of the assay (range, less than 2 to 3.7 pmol/L). Plasma levels in normal volunteers were below the detection limit of the assay in all but 1 of 38 normal subjects. Patients with chronic renal failure on hemodialysis (n = 18) and patients with primary hyperparathyroidism (n = 14) all had undetectable PTHrP in this assay. This assay allows positive identification of patients with PTHrP-mediated hypercalcemia and, therefore, should be useful in the clinical investigation of the hypercalcemic patient. Furthermore, it has allowed detection of circulating PTHrP in hypercalcemic breast cancer patients with bone metastases, indicating a significant role for PTHrP in this disease.
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PMID:Parathyroid hormone-related protein: elevated levels in both humoral hypercalcemia of malignancy and hypercalcemia complicating metastatic breast cancer. 195 13

The mechanisms of hypercalcaemia were assessed in 20 hypercalcaemic patients with breast cancer. Abnormalities suggestive of a PTH-related peptide (PTHrP) mechanism were observed in up to 60% of cases; urinary cyclic adenosine monophosphate (UcAMP) was elevated in nine patients (45%), renal tubular reabsorption of calcium (RTRCa) was elevated in nine (45%) and the renal tubular threshold for phosphate reabsorption (TmPO4) depressed in 12 (60%). While TmPO4 was lower in patients with high UcAMP, there was no consistent relationship between RTRCa and UcAMP or UcAMP and the extent of bone metastases. In a control group of nine normocalcaemic breast cancer patients, bone resorption as assessed by urinary calcium/creatinine ratio was slightly increased but UcAMP, RTRCa and TmPO4 were generally normal. These observations indicate that a PTHrP-mediated mechanism of hypercalcaemia may be operative in up to 60% of patients with breast cancer, irrespective of the presence or extent of bone metastases.
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PMID:Breast cancer-associated hypercalcaemia: a reassessment of renal calcium and phosphate handling. 196 70

In a consecutive series of 771 patients with pathologically verified squamous cell carcinoma of the head and neck, 28 patients (3.6%) had hypercalcemia (greater than 11.0 mg/dl) during the course of their disease. The buccal mucosa (16/205, 7.8%) and tongue (8/148, 5.4%) were the most frequent primary sites. Most of the patients were stage IV patients with recurrence and advanced disease. The prognosis was poor with a median survival of only 6 weeks. The possible etiology of their hypercalcemia included humoral factors, bone metastases and independent primary lung cancer. The treatment of hypercalcemia was evaluated in 22 patients. Success was noted in all patients initially receiving chemotherapy (10 cases) or radiotherapy (3 cases) with or without saline hydration plus furosemide diuretics. However, the response rate in patients (9 cases) initially receiving hydration plus furosemide diuretics alone was 22% (2/9), with 4 of 7 failure cases later responding to chemotherapy. It is suggested that hypercalcemia be treated with chemotherapy or radiotherapy quickly, along with hydration plus diuretics. Also, the serum calcium level must be checked in patients with advanced buccal or tongue cancer.
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PMID:Hypercalcemia in squamous cell carcinoma of the head and neck. 197 96

Tubular reabsorption of calcium (Ca) is becoming recognized as a determinant of malignant hypercalcemia. However, its importance as compared to increased bone resorption has not yet been widely investigated. We determined Ca fluxes of bone resorption and tubular reabsorption in 141 rehydrated patients with hypercalcemia of malignant or benign origin, before any specific treatment. Bone resorption (BRI) was evaluated by fasting urinary Ca excretion and Ca tubular reabsorption using an index (TRCaI) calculated from a nomogram relating fasting urinary Ca excretion and calcemia. The relationship between alterations in TRCaI and in the tubular capacity to reabsorb inorganic phosphate (Pi), as judged by TmPi/GFR, was also examined for each cause of hypercalcemia. Among 101 cases with malignancy, 67% had overt bone metastases, but all displayed increased BRI. Calcemia was highest in breast cancer and lowest in prostate carcinoma. BRI was markedly increased in breast cancer, lymphoma, and multiple myeloma, whereas it was slightly elevated in lung squamous cell, renal, and liver carcinomas. TRCaI was increased in 49% of malignant hypercalcemia, particularly in epidermoid (above the upper normal limit in 71% of the cases), renal, and liver carcinomas. It was elevated in 54% of breast cancer and normal in multiple myeloma and prostate cancer. In nonmalignant hypercalcemia, BRI was markedly increased in vitamin D intoxication, sarcoidosis, and immobilization. In primary hyperparathyroidism (PHP), BRI was moderately increased. TRCaI was abnormally elevated in PHP, but normal in vitamin D intoxication, sarcoidosis, and immobilization. In malignant hypercalcemia, TmPi/GFR was low in 77% of patients and in all types of tumors, except in prostate carcinoma. The index ratio [TRCaI/(TmPi/GFR)] gave a better discrimination of PHP from other causes of nonmalignant hypercalcemia than the use of either TRCaI or TmPi/GFR taken alone. Thus, in malignant hypercalcemia, increased bone resorption is associated with an elevation in tubular Ca reabsorption in half the patients surveyed, whereas low tubular Pi reabsorption is observed in more than 75%. Increased TRCaI is restricted to some types of tumor, whereas decreased TmPi/GFR is observed in all types except prostate carcinoma. In nonmalignant hypercalcemia, a significant increase in mean TRCaI was only observed in PHP, of which individual cases can be fully discriminated from other conditions by using a new index taking into account alteration in the renal transport capacity of both Ca and Pi.
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PMID:Evaluation of bone resorption and renal tubular reabsorption of calcium and phosphate in malignant and nonmalignant hypercalcemia. 205 36

Hypocalcemia based on total calcium measurement is frequent in certain cancers (especially prostate) in association with osteosclerotic bone metastases. In a majority of these patients hypocalcemia is related to the low serum albumin and/or renal failure. True ionized hypocalcemia may be seen as a toxic effect of certain chemotherapeutic agents or as a consequence of hyperphosphatemia due to rapid tumor lysis. In addition, tumors may produce osteoblast-stimulating factor(s) which cause massive accretion of calcium by the skeleton. Isolation and purification of these factors may provide us with unique osteoblast-stimulating factors which may have therapeutic applications.
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PMID:Hypocalcemia in cancer. 222 3

The bisphosphonate pamidronate (3 amino-1, 1-hydroxypropylidene bisphosphonate (APD), Ciba-Geigy) is a powerful inhibitor of osteoclast function and has been shown to significantly reduce osteolysis associated with bone metastases in breast cancer. Until recently, however, only an intravenous preparation has been readily available. We have evaluated the toxicity and effect on urinary calcium excretion of an enteric-coated oral preparation of pamidronate in a phase I/II trial in patients with bone metastases from breast cancer. Sixteen women with progressive disease and evidence of active bone resorption with an elevated calcium excretion (fasting urine calcium/creatinine ratio greater than 0.4 (mmol mmol-1) on two occasions prior to treatment) were studied. Four were given 150 mg daily; four 300 mg daily; four 450 mg daily and four 600 mg daily. Urinary calcium/creatinine (Ca2+/Cr) ratios were measured on all patients after an overnight fast. In patients on 150 mg daily the mean ratio fell from 0.65 (range 0.57-0.72) before treatment to 0.13 (0.02-0.19) after three weeks treatment. Mean values at entry for patients on 300, 450 and 600 mg were 1.18 (0.72-2.1), 0.76 (0.42-1.5) and 0.63 (0.52-0.82) respectively and after treatment these fell to 0.11 (0.05-0.18), 0.37 (0.14-0.68) and 0.17 (0.06-0.25). There were no significant differences in efficacy between treatment groups. Oral, enteric-coated disodium pamidronate is non-toxic and effectively reduces calcium excretion, raised in association with metastatic bone disease at doses of 150 mg or above. At the doses used to date it is as effective as weekly treatments with 30 mg of the intravenous preparation. Further studies are required in order to determine its value for preventing complications of bone disease and possibly as an adjuvant to surgery for breast cancer.
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PMID:Reduction in calcium excretion in women with breast cancer and bone metastases using the oral bisphosphonate pamidronate. 229 83

Secondary hyperparathyroidism can develop as a result of bone metastases from prostatic cancer, but this has not been studied from the multiple aspects of biochemistry, hormonal status and histomorphometry. In 20 patients with stage-D prostatic cancer, a transiliac bone biopsy was performed for histomorphometric study. In all of them, molecular parathormone (PTH-M) and osteocalcin were determined by radioimmunoassay together with other parameters considered to be biological markers of bone remodelling. Of these 20 patients, only 2 (10%) had elevated PTH-M (240 +/- 20.6 pmol/l), differing significantly from the other 18 (58.6 +/- 11.7 pmol/l) and from controls (60.4 +/- 7.2 pmol/l). In the high PTH-M patients, corrected calcium was low (7.8 +/- 0.4 mg/dl) as compared to normal PTH-M patients (9.2 +/- 0.5 mg/dl, p less than 0.001), and this was also the case for serum phosphorus (2.2 +/- 0.6 vs. 3.2 +/- 0.3 and 3.4 +/- 0.4 mg/dl, respectively p less than 0.001). Alkaline phosphatase was raised in the patient groups as compared to controls (p less than 0.001) and was higher in the high PTH-M group (362 +/- 58 vs. 224 +/- 62 U/l, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperparathyroidism in metastases of prostatic carcinoma: a biochemical, hormonal and histomorphometric study. 231 37

Serum bone GLA-protein, a modern and sensitive marker of bone turnover, was measured in 15 patients with primary hyperparathyroidism, 18 patients with hypercalcemia of malignancy, 41 patients with bone metastasis without hypercalcemia, and 29 healthy subjects. Serum bone GLA-protein was increased in primary hyperparathyroidism (17.6 +/- 3.9 ng/ml) and normal in hypercalcemia of malignancy (5.2 +/- 2.8 ng/ml; p less than 0.001 vs hyperparathyroidism) and in normocalcemic patients with bone metastases. In primary hyperparathyroidism parathyroid hormone correlated positively with urinary calcium excretion (p less than 0.05) and with urinary hydroxyproline excretion (p less than 0.001). The sensitivity of serum bone GLA-protein measurements in differentiating between primary hyperparathyroidism and hypercalcemia of malignancy was 91% and the specificity 84%. Thus this marker appears to be a useful tool for the differential diagnosis of hypercalcemias.
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PMID:Serum bone GLA-protein in hypercalcemia of primary hyperparathyroidism and malignancy. 232 Dec 72

Malignancy-related hypocalcaemia has received less attention in the literature than the opposite perturbation, hypercalcaemia. Only, scarce and contradictory data exist about hypocalcaemia associated with bone metastases (BMH). We have reviewed the clinical records of 155 patients with bone metastases of solid tumours, 122 of which were followed during the whole course of the disease until death. The frequency of hypocalcaemia ranged from 5 to 13%, depending on the formula used to correct calcium values for protein concentration. BMH was almost exclusively limited to patients with osteoblastic metastases. The frequency of BMH among patients with prostate carcinoma was 13-27%, depending on the formula used. Only two of 60 patients with lytic bone lesions presented hypocalcaemia, and in both cases it was rather mild. The development of hypocalcaemia did not seem to imply a worse prognosis, at least in patients with carcinoma of the prostate. Thus, the prevalence of BMH appears to be higher than is usually considered. Adequate attention should be given to this disorder because of the potentially deleterious effects on several organ systems.
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PMID:The clinical spectrum of hypocalcaemia associated with bone metastases. 248 31

Atypical carcinoid tumors of the bronchial tree are uncommon. Their tendency to metastasize is well recognized, characteristically producing osteoblastic bone deposits without disturbance of calcium homeostasis. We report two patients who presented with hypercalcemia and osteolytic bone metastases following surgical removal of atypical bronchial carcinoid tumors. In one of the patients, chemotherapy induced remission and controlled the hypercalcemia.
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PMID:Hypercalcemia in atypical bronchial carcinoid tumors. 255 47


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