Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum osteocalcin (BGP) is an osteoblast product that probably reflects the rate of bone formation. It is a potential marker of skeletal metastases and, to investigate this, BGP was measured by radioimmunoassay in the serum of normal subjects and patients with breast or prostate cancer. Significantly higher levels were found in patients with metastatic bone disease in comparison to both normal subjects (P less than 0.001) and patients with non-metastatic cancer (P less than 0.05 for breast cancer and less than 0.001 for prostate cancer). The range of values was wide. Levels were higher in sclerotic than lytic bone metastases (P less than 0.01) and lower in patients with hypercalcaemia (P less than 0.001). Serial measurements of BGP were made in 53 patients with skeletal metastases from breast cancer receiving systemic therapy. At 1 month BGP rose by greater than 0.5 ng/ml in 15/16 responding patients compared with 7/23 patients with progressive disease (P less than 0.01). Responding patients also showed a rise in the bone isoenzyme of alkaline phosphatase and a paradoxical deterioration in the bone scan appearance, both reflecting a flare in osteoblast activity. The early increase in responding patients was followed by a gradual decrease over subsequent months as the osteoblast reaction induced by systemic therapy subsided. We conclude that BGP measurements reflect a wide variability of bone formation rates in metastatic bone disease. Bone formation was usually increased, particularly when metastases were sclerotic in appearance, but in patients with hypercalcaemia the low BGP levels suggest uncoupling of bone resorption and formation. Serial measurements of BGP may be useful in monitoring response to treatment.
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PMID:Osteocalcin: a potential marker of metastatic bone disease and response to treatment. 326 63

Assessment of response of skeletal metastases to systemic therapy is currently dependent on radiological evidence of bone healing. We have performed a prospective study of additional response criteria in patients with progressive bone metastases from breast cancer. Changes in these potential markers of response were correlated with the radiological response and the time to treatment failure (TTF). Successful systemic therapy typically led to a transient increase in osteoblast activity ('flare'), a reduction in osteoclast activity and symptomatic improvement. After 1 month a greater than 10% rise in serum osteocalcin (BGP) and alkaline phosphatase bone isoenzyme (ALP-BI) and a greater than 10% fall in urinary calcium excretion were seen in 14/16 patients with radiographic evidence of bone healing (UICC partial responders). In comparison similar biochemical changes at 1 month were seen in only 4/20 patients with progressive disease (P less than 0.001). The predictive value and diagnostic efficiency (DE) of changes at 1 month in biochemical measurements and symptom score has been calculated. The combination of a greater than 10% rise in ALPBI and BGP and a greater than 10% fall in urinary calcium excretion had a DE of 89% for discriminating response from progression, 88% for response from non-response (progressing + no change patients), and 76% for TTF of greater than 6 months from TTF of less than 6 months. Serum calcium, tartrate resistant acid phosphatase (TRP), urinary hydroxyproline excretion and bone scan changes were unhelpful in discriminating between patient groups. Independent confirmation is needed, but our results suggest there are reliable alternatives to plain radiography in the early assessment of response of bone metastases to treatment.
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PMID:Biochemical prediction of response of bone metastases to treatment. 326 66

Fifty-four subjects were studied: 36 advanced prostatic adenocarcinoma patients in stage D and 18 normal age-matched male controls. Serum alkaline phosphatase, serum acid phosphatase, plasma osteocalcin, 24-h urinary hydroxyproline excretion, and 24-h whole-body retention of [99mTc]-methylene diphosphonate were measured in all subjects before and 3, 6, and 9 weeks after the start of treatment. Skeletal metastases were identified by radiography and/or [99mTc]-methylene diphosphonate bone scan. The results confirm that acid phosphatase is a significant marker in prostatic cancer; serum alkaline phosphatase may be useful in the evaluation and monitoring of bone metastases but it is not always specific; urinary excretion of hydroxyproline is an index of osteoclastic activity; serum osteocalcin may be considered more specific in the evaluation and monitoring of osteoblastic bone metastases in prostatic cancer.
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PMID:Serum osteocalcin concentration in patients with prostatic cancer. 326 42

Serum osteocalcin (BGP) is a new marker of bone turnover that reportedly evaluates bone formation. Thus, its measurement could assess the bone formation rate in tumor-associated hypercalcemia. We measured concentrations of BGP and other parameters of bone metabolism in 54 untreated hypercalcemic cancer patients as compared to 109 healthy subjects. Primary tumor sites were breast (19), lung (11), head and neck (6), multiple myeloma (3), kidney (2), and various (11) or multiple (2). Mean BGP levels were higher in the hypercalcemic subjects, 4.6 +/- 0.4 (SEM) ng/ml, than in the normal subjects, 3.6 +/- 0.1 ng/ml (p less than .05), and were normalized in the 22 patients who could be reevaluated after successful treatment of hypercalcemia with intravenous aminohydroxypropylidene diphosphonate (APD). There was no correlation of BGP levels with age, sex, or renal function. Compared with the Gaussian distribution in the normal subjects, there was a considerable scatter of the data in hypercalcemic patients, suggesting the existence of defined subgroups with abnormally low or abnormally high values. However, we found no significant relationship of BGP concentrations with tumor site or histology or with bone metastatic involvement. We found also no significant correlation between concentrations of serum BGP and total or ionized calcium, alkaline phosphatase, parameters of bone resorption, and indices of parathyroid function. In summary, serum BGP levels were slightly elevated in tumor-associated hypercalcemia and were normalized after successful treatment of hypercalcemia. More importantly, BGP concentrations varied widely even in the subgroups of patients with hypercalcemia accompanying massive bone metastatic involvement or in the patients without detectable skeletal metastases.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Serum osteocalcin (BGP) in tumor-associated hypercalcemia. 350 43

Osteocalcin is synthesized by osteoblasts and its concentration in serum is increased when bone metabolism is raised. Radioimmunoassay of serum from 88 healthy adults gave a mean osteocalcin value for the whole group of 4.11 +/- 1.43 ng/ml. The level rose with age. In seven patients with primary hyperparathyroidism the mean value was markedly raised to 19.37 +/- 9.2 ng/ml, in 23 with metastasizing carcinoma of the breast it was elevated to 6.57 +/- 2.98 ng/ml. Serial measurements in 14 female patients over seven months revealed different changes in osteocalcin and alkaline phosphatase in some of them. In patients with breast cancer and soft-tissue metastases or without metastases both osteocalcin and alkaline phosphatase levels were normal. Three of 17 patients with multiple myeloma had increased osteocalcin levels. These results indicate that it is clinically helpful to know osteocalcin levels in primary hyperparathyroidism. Determination of osteocalcin concentration, in addition to that of alkaline phosphatase, can be of value in the postmastectomy management of patients with breast cancer, especially in the early recognition of bone metastases. The diagnostic value of osteocalcin levels in multiple myeloma remains undecided.
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PMID:[Osteocalcin, a marker in diseases with elevated bone metabolism]. 387 69

Radioimmunological determinations of the tumour markers CEA, TPA, CA 19-9, ferritin and also osteocalcin were carried out in 250 patients with ablatio mammae for breast cancer over a follow-up period of at least 1 year. Metastases were detected in 49 of the 250 patients. The normal control group comprised 193 healthy persons. CEA proved to be the most valuable tumour marker, but TPA and ferritin were also significantly elevated in metastatic breast cancer. Combined determination of all 3 parameters gave the best results. Additional measurement of CA 19-9 was helpful in only one of the 49 patients with metastases in whom the 3 other parameter were negative throughout. Hence, determination of CA 19-9 appears unnecessary in breast cancer. In progressive disease the markers generally increased and fell again following successful therapy. In a few cases the opposite was found or no changes were observed. Cases with small local recurrence or an additional carcinoma at an early stage did not exhibit increased marker values as compared to patients without metastases. Not infrequently the increase in markers preceded the manifestation of metastases by several months. Very high concentrations of tumour markers signify a poor prognosis. Osteocalcin was elevated in patients with bone metastases, but not soft tissue metastases. In general, however, it paralleled the serum alkaline phosphatase level.
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PMID:[The tumor markers CEA, TPA and CA 19-9 and ferritin and osteocalcin in follow-up studies in breast cancer]. 387 42

Although bone formation traditionally has been difficult to study in vitro, recent improvements in cell culture techniques have made it possible to study primary cultures of fetal rat calvarial osteoblasts, and to examine specific gene events associated with osteoblast proliferation, differentiation, and mineralization of extracellular matrix to form bone nodules. Results of studies show that extracellular matrix proteins such as Type I collagen and osteocalcin are expressed. Also expressed are growth regulatory factors such as the bone morphogenetic proteins, which are presumably secreted and stored in the bone matrix or involved in additional osteoblast differentiation in an autocrine/paracrine role. The bone matrix is 1 source of these growth regulatory factors for bone formation; another is those animal and human tumors associated with osteoblastic metastases. In some of these tumors, an extended form of basic fibroblast growth factor has been identified, and various bone morphogenetic proteins have been found in others.
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PMID:Local control of bone formation by osteoblasts. 764 79

The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement using lectin precipitation in confirming metastatic bone lesions was compared with total ALP and osteocalcin assay in serum. Sixty-five patients with cancer and metastases to bone (n = 44), liver (n = 15) or lymph nodes (n = 6) as well as 33 healthy adults were studied. Assay of bone ALP is as sensitive but more specific than assay of total ALP in the identification of bone metastases. On the other hand, bone ALP did not correlate with osteocalcin, as is the case in other bone diseases. In the serial monitoring of nine patients with skeletal metastases, bone ALP correlated well with the presence of pain and the progression or regression of metastatic spread.
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PMID:Monitoring skeletal cancer metastases with the bone isoenzyme of tissue unspecific alkaline phosphatase. 792 10

The efficacy of bone alkaline phosphatase (ALP) isoenzyme measurement, using a lectin precipitation method, in confirming metastatic sites was assessed in 65 patients with cancer and skeletal (n = 44), hepatic (n = 15) or lymph node (n = 6) metastases; the control group consisted of 33 healthy adults. In all subjects, total ALP activity and osteocalcin were also assayed. Our results confirm that isoenzyme analysis is more specific than total enzymatic activity measurement in the identification of bone metastases: the mean for total ALP values was increased in all patients, while significantly high mean values of bone fraction (p < 0.05 by ANOVA) were observed only in patients with bone secondaries. In the serial monitoring of 9 patients with skeletal metastases, bone ALP values correlate with pain symptomatology: a progressive decrease in bone isoenzyme activity was observed in patients with a complete remission of pain after radiotherapy, while a progressive increase in activity was observed in the presence of increased bone pain. The measurement of bone isoenzyme activity is useful in screening for skeletal metastases; levels appear to correlate with the course of bone symptomatology, thus providing useful objective evidence of response to treatment.
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PMID:Serum bone alkaline phosphatase in the follow-up of skeletal metastases. 857 29

Thirty-six patients with bone metastases included in a trial of supportive calcitonin on the treatment response to systemic therapy were monitored by conventional radiography, conventional indicators of bone metabolism [alkaline phosphatase (AP), osteocalcin (gla), urinary hydroxyproline excretion (OHP), urinary calcium (uCa), serum calcium (sCa)] and collagen metabolites (ICTP, the pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen; PICP, the carboxy-terminal propeptide of type I procollagen; and PIIINP the amino-terminal propeptide of type III procollagen). All patients had been on the same systemic treatment for at least 3 months at the start of the trial. There was a positive correlation between the concentrations of ICTP and PICP at baseline (Spearman's rank-order correlation coefficient rs = 0.62). Both ICTP and PICP showed statistically significant correlations to the other markers of bone metabolism (except sCa and uCa) as well as to the number of bone metastases on bone scans. Reduction in ICTP correlated significantly with the treatment response at three months (rs = - 0.57). while PICP showed a borderline negative correlation to therapy response (rs = - 0.37). Of all the biochemical parameters studied the changes in ICTP showed the best correlation with the treatment response. PICP and ICTP changes in patients with progressive disease differed significantly from those in patients with responding and stable metastases, whereas no difference was found between responders and stable patients.
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PMID:Markers of type I collagen degradation and synthesis in the monitoring of treatment response in bone metastases from breast carcinoma. 862 66


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