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)

Bone metastases strongly affect skeletal metabolism by both their growth and their paracrine activities. However, so far no specific laboratory marker has been found to signal the spread of neoplastic disease to bone. We performed a cross-sectional study of 153 cancer patients and an equal number of healthy controls matched for sex and age, in which we determined serum levels of calcium and total alkaline phosphatase (TAP) as well as the fasting urinary excretion of calcium (uCa) and of the collagen cross-links pyridinoline (uPYD) and deoxypyridinoline (uDPD). The aim of the study was to analyze the diagnostic validity of the biochemical parameters measured with regard to neoplastic bone involvement. In the cancer group, 98 patients had overt bone metastases, as judged from radiographic and radioisotopic bone imaging. The remaining 55 patients were also in an advanced stage of disease, but there was no evidence of malignant bone involvement. In comparison to healthy controls, patients both with and without metastatic bone disease had significantly higher levels of TAP, uPYD, and uDPD (P < 0.0001). Only in cancer patients with bone metastases was the median serum calcium level higher than in the healthy controls (P < 0.02). uCa was the same in cancer patients and the control group. Within the collective of cancer patients, individuals with skeletal metastases had higher levels of serum calcium (P < 0.05), TAP (P < 0.01), and uPYD and uDPD (both P < 0.0001), than patients without evidence of malignant bone disease. uCa did not differ between the 2 groups of cancer patients. The cancer patients were then stratified into 4 subgroups according to the serum calcium level (< or = 2.6 mmol/L >) and the absence or evidence of bone metastases. This stratification revealed that in patients with bone metastases, uPYD and uDPD levels were similar in normocalcemic and hypercalcemic subjects, whereas in hypercalcemic patients, uCa levels significantly exceeded those in normocalcemic patients. When the efficacy of TAP, uCa, uPYD, and uDPD in discriminating between patients with and without bone metastases was evaluated by use of receiver-operating characteristic curves and stepwise multivariate regression analysis, uPYD was found to have the highest diagnostic validity. Using 50 mumol PYD/mol creatinine (i.e. the upper limit of normal range) as the cut-off level, the sensitivity of uPYD was 88.7%, whereas the specificity was only 41.8% (odds ratio, 5.598; 95% confidence interval, 2.547-12.306).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The diagnostic value of urinary pyridinium cross-links of collagen, serum total alkaline phosphatase, and urinary calcium excretion in neoplastic bone disease. 782 46

The collagen crosslinks, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), were recently identified as potential markers of the rate of bone resorption. To determine whether urinary concentrations of Pyr and D-Pyr might provide an early warning of bone metastases in patients being monitored for cancer of the prostate, we compared these two newer parameters with the conventional indicators, that is, the serum concentrations of Bone Gla protein (BGP: osteocalcin) and alkaline phosphatase (ALP), in patients with prostate cancer with and without bone metastases vs. those of age-matched patients with benign prostatic hyperplasia (BPH). Urinary excretion of these compounds, expressed as a ratio to urinary creatinine (mg/dl), was determined by high performance liquid chromatography (HPLC) in 23 patients with prostate cancer (16 with bone metastases and 7 without bone metastases) and in 23 patients with BPH. The mean values of urinary Pyr and D-Pyr; 65.02 +/- 38.16 pmol/mumol of creatinine and 8.87 +/- 7.01 pmol/mumol of creatinine and 8.87 +/- 7.01 pmol/mumol of creatinine, respectively, for patients with bone metastases of prostate cancer were significantly higher than those for patients without bone metastases of prostate cancer (27.43 +/- 10.29 pmol/mumol of creatinine and 4.24 +/- 1.88 pmol/mumol of creatinine) or for patients with BPH (25.58 +/- 7.54 pmol/mumol of creatinine and 3.52 +/- 1.07 pmol/mumol of creatinine). Among these three groups of patients, there were statistically significant (Pyr: P = 0.0001, D-Pyr: P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Assay of urinary pyridinoline and deoxypyridinoline as potential markers of the rate of bone resorption: usefulness of urinary pyridinoline and deoxypyridinoline in patients with prostate cancer with bone metastases]. 799 Mar

We investigated the usefulness of serum levels of procollagen type III N-peptide (P III P) and the type IV collagen, 7S-domain, (IV-C) as markers of recurrent and metastatic breast cancer. Serum P III P and IV-C levels were found to be significantly higher in patients who showed postoperative recurrence, with 76.9% of P III P-positive cancer bearing patients and 68.0% of IV-C-positive cancer bearing patients having metastases in the bone and/or liver. Furthermore, 66.7% of all patients with metastases in the bone and/or liver were P III P-positive and 75.6% were IV-C-positive. Patients with liver metastases were either P III P- or IV-C-positive, and the levels were higher than those in patients with bone metastases. Thus, a positive correlation of serum P III P and IV-C levels was observed. These findings suggest that both serum P III P and IV-C levels are useful markers of recurrent and metastatic breast cancer, especially of disease in the bone and/or liver.
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PMID:Procollagen type III N-peptide and type IV collagen 7S-domain in the sera of breast cancer patients. 840 Jun 71

Pyridinoline (PYD) and deoxypyridinoline (DPD), two collagen-based cross-links found in bone, were measured by high-performance liquid chromatography in urine samples from 65 control subjects and 97 patients with either untreated or progressive cancer. Patients with cancer had significantly (P < 0.001) higher urine concentrations of PYD and DPD than did control subjects. Both cross-links were increased in cancer patients with and without clinically detectable bone metastases, although patients with bone and liver involvement had higher mean concentrations. The mean concentrations of both cross-links were also significantly higher in the urine samples of inpatients than in an outpatient ambulatory population. These findings suggest that the measurement of PYD and DPD in urine may be useful in assessing bone metastases and bone resorption in cancer patients.
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PMID:Increased urinary excretion of pyridinium cross-links in cancer patients. 847 54

We report on the diagnostic validity of the serum concentrations of the C-terminal propeptide of type I procollagen (a marker of bone formation) and of the urinary excretion of deoxypyridinoline (a marker of bone resorption) in a consecutive series of 89 tumour patients who were routinely examined by 99mTc-methylene bisphosphonate bone scintigraphy for detection of bone metastases. Z score analysis reveals that the discriminating power of deoxypyridinoline is superior to that of calcium excretion whereas the discriminating power of the C-terminal propeptide concentrations is inferior to that of bone alkaline phosphatase values. Accuracy (as assessed by the area under the receiver-operating characteristic curve) was 0.75 for deoxypyridinoline and 0.82 for the C-terminal propeptide. Combination of both markers did not yield an increase of accuracy (0.82) compared with the determination of the C-terminal propeptide concentrations alone. There was a correlation (r = +0.398; p < 0.0001) between C-terminal propeptide concentrations and deoxypyridinoline excretion values in the group of 89 patients examined. Further studies should be done to elucidate whether the determination of bone collagen turnover is suitable as a screening procedure for detecting bone metastases.
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PMID:Simultaneous assessment of bone collagen synthesis and degradation in patients with different malignant tumours. Comparison with the results of 99mTc-methylene bisphosphonate bone scintigraphy. 854 30

Three new collagen markers deriving from the collagenous matrix, e.g. carboxyterminal propeptide of type I procollagen (PICP), carboxy-terminal pyridinoline cross-linked telopeptide of type I collagen (ICTP), and aminoterminal propeptide of type III procollagen (PIIINP) were used for the diagnose of prostatic bone metastases. Blood samples were obtained prior to biopsy or TURP. Serum PICP, PIIINP and ICTP were measured with commercial available RIAs and PSA by IRMA. Serum PSA was increased in patients with local prostatic cancer compared with patients with hyperplasia (p < 0.05). The level of PIIINP, ICTP, and PICP did not differ between these two groups. In patients with metastatic prostatic cancer all five markers were increased compared to the level measured in patients with localized cancer (p < 0.0001). All variables showed a significant positive relationship with alkaline phosphatase. The sensitivity ranged from 0.53 to 0.62 and specificity from 0.91 to 0.95. The sensitivity for alkaline phosphatase and PSA was 0.69 and 0.66 and specificity 0.91 and 0.68, respectively.
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PMID:Collagen derived serum markers in carcinoma of the prostate. 857 75

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

Serum bone alkaline phosphatase (BALP), serum carboxy-terminal propeptide of type I procollagen (PICP) and serum bone gla protein (BGP) as markers of bone formation, serum carboxy-terminal telopeptide of type I collagen (ICTP) as a marker of collagen resorption and fasting molar ratio of urinary calcium to creatinine (CaCr) and serum parathyroid hormone (PTH) were determined in two groups of cancer patients: 48 with advanced or metastatic disease with negative bone scan and 174 with bone metastases categorised as having lytic, mixed or blastic lesions and with more or fewer than or equal to three sites involved. In patients without apparent bone involvement, bone formation markers were rarely elevated. Conversely, serum ICTP was frequently found to be supranormal, showing it to be a non-specific marker for early detection of bone metastases. As expected, values of bone formation markers progressively increased in patients with lytic, mixed and blastic lesions, but ICTP levels did not show any differences according to the types of bone appearances, confirming previous reports of elevated osteoclast activity also in patients with apparent blastic lesions. Serum PTH increased significantly in patients with lytic compared with patients with mixed and blastic appearances, paralleling the bone formation markers, but CaCr showed the opposite pattern. These data are compatible with calcium entrapment in the bone in patients with increased osteoblast activity. This so called 'bone hunger syndrome' is further confirmed by the finding that in the subgroup of blastic appearances CaCr diminished whereas both ICTP and PTH increased according to the extent of tumour load in the bone.
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PMID:Biochemical evaluation of bone turnover in cancer patients with bone metastases: relationship with radiograph appearances and disease extension. 866 34

The most abundant protein in bone is type I collagen. During type I collagen formation two extension peptides from both ends of the procollagen molecule, carboxy- and aminoterminal propeptides (PICP and PINP), are liberated in equimolar concentrations into the circulation. Type I collagen carboxyterminal telopeptide (ICTP) is formed during bone collagen breakdown and is liberated into the circulation. Serum concentration of the propeptides reflect bone formation, and the concentration of the telopeptide, bone resorption. We evaluated the usefulness of these bone remodelling markers in diagnosing and monitoring metastatic bone disease in breast cancer patients. Serum concentrations of ICTP, PICP and PINP were measured and the PICP/PINP-ratio calculated in 25 patients with bone metastases, 12 patients without metastases and their age matched healthy controls. S-ICTP and S-PINP were significantly higher in metastatic patients (p = 0.0001 and 0.02 respectively), and the S-PICP/PINP-ratio lower (p = 0.002) than in controls. S-PICP in metastatic patients did not differ significantly from that of controls. ICTP values in patients without metastases also differed from those of controls (p = 0.01). The clinical sensitivity for diagnosing metastatic bone disease was 56% for ICTP, 24% for PICP, 30% for PINP and 52% for PICP/PINP ratio. The clinical specifities were 93%, 100%, 98% and 91% respectively. During follow-up the changes in the marker values were parallel to the behaviour of the disease. We conclude that these markers alone are not sensitive enough for diagnosis, but they seem to be of use in detecting bone metastases and monitoring the activity of bone disease.
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PMID:Serum concentrations of type I collagen carboxyterminal telopeptide (ICTP) and type I procollagen carboxy-and aminoterminal propeptides (PICP, PINP) as markers of metastatic bone disease in breast cancer. 869 58

Approximately 70% of patients with prostate cancer develop bone metastases in the advanced state of the disease. In the present study, we sought to test the hypothesis that prostatic cancer cells produce factors that inhibit the mineralisation process in vitro, decreasing the content of type I collagen in rat fetal calvaria osteoblasts. We investigated the capacity of conditioned media (CM) from the human prostatic tumour cell line PC-3 to inhibit the expression of the differentiation programme on osteoblasts in culture, with a primary focus on type I collagen synthesis and degradation. Our results show that PC-3 CM inhibits collagen synthesis and stimulates the production of interstitial collagenase from osteoblasts. A consequential decrease in the content of immunoreactive type I collagen was observed. We have previously demonstrated that PC-3 CM blocks osteoblast differentiation in culture. We propose that under the effect of factors present in PC-3 CM, osteoblastic cells retain the undifferentiated phenotype.
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PMID:Soluble factors produced by PC-3 prostate cells decrease collagen content and mineralisation rate in fetal rat osteoblasts in culture. 869 58


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