Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Serum levels of procollagen type I carboxy-terminal extension peptide (PICP) reflect the synthesis of type I collagen. As PICP is produced by osteoblasts and is not incorporated into bone matrix, serum PICP levels have been suggested as a marker of bone formation. In 37 cancer patients (21 men and 16 women; age: 72.4 +/- 8.6 (mean +/- SD) years) with bone metastases and 23 women (age: 77.3 +/- 6.64 years) as controls, the following biochemical variables were measured: serum PICP, calcium (Ca), phosphorus, alkaline phosphatase (AP) and tartrate-resistant acid phosphatase (TRAP), and urinary hydroxyproline and calcium corrected for creatinine excretion. Higher serum levels of PICP were observed in cancer patients than in control (245 +/- 177 micrograms/l vs 121.7 +/- 36 micrograms/l, p < 0.01). Cancer patients also had higher AP levels than controls (704 +/- 755 U/l vs 216.5 +/- 56 U/l, p < 0.01). Abnormal PICP and AP serum concentrations (above the mean + 2SD of controls) were found in 46% and 51% of patients, respectively. Moreover, patients showed significantly lower serum calcium concentrations (p < 0.001), and higher TRAP and hydroxyproline levels although statistical significance was not reached. In the patients, PICP was correlated directly with AP (r = 0.50, p < 0.01) and TRAP (r = 0.34, p < 0.05). In conclusion, patients with bone metastases have increased bone turnover as shown by serum markers. Serum PICP may be used as an adjunctive, non-invasive index to assess bone metabolism. However, the clinical usefulness of PICP in cancer patients needs further evaluations.
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PMID:Serum levels of procollagen type I carboxyterminal extension peptide in cancer patients with bone metastases. 756 Dec 34

The effects of a third-generation bisphosphonate, YM175 (disodium dihydrogen (cycloheptylamino)-methylene-1,1-bisphosphonate), on bone resorption induced by a metastatic human melanoma cell line (A375) were investigated morphologically using an experimental model of bone metastases in nude mice. An injection of A375 in the left cardiac ventricle produced multiple osteolytic lesions. Then, 4 weeks after the cell injection, we administrated YM175 (1 mg/kg) intravenously once and sacrificed the animals 3 days later. On histochemical observation, there was a layer of stromal cells with numerous mononuclear and multinucleated tartrate-resistant acid phosphatase (TRAPase)-positive cells in the untreated control group. In contrast, this layer was extensively reduced in most areas, and only a few TRAPase-positive cells were seen around tumor nests and on the bone surface in the experimental group. Most of the TRAPase-positive cells were stained only weakly and/or homogeneously, and there was little evidence of cell polarity. Some of them were vacuolated. Ultrastructurally, they were round and devoid of ruffled borders and clear zones. The findings suggest that YM175 decreases the number and activity of osteoclasts. In addition, a few showed the morphology of cell death, which seemed to be one of the reasons leading to the decrease of osteoclasts. There was no substantial change in the morphological relationships or ultrastructure of osteoclast precursor cells, stromal cells, extracellular matrices, and tumor cells between the experimental and the control groups. In the experimental group, the distribution of extracellular matrices (heparan sulfate proteoglycan and fibronectin) was less conspicuous, but the localization of osteotropic cytokines (interleukin-6 and prostaglandin E2) was essentially similar to that of the control group. The cause leading to the decrease of osteoclast precursor cells remains to be clarified. In conclusion, YM175 inhibits bone resorption induced by tumor, by decreasing the activity of mature osteoclasts and possibly affecting the production of osteoclast precursor cells.
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PMID:Inhibitory effects of bisphosphonate (YM175) on bone resorption induced by a metastatic bone tumor. 871 29

Angiogenesis inhibitor TNP-470, 6-O-(N-chloroacetyl-carbamoyl)-fumagillol, semisynthetic analogue of fumagillin, has strong inhibitory activities against in vivo tumor growth and metastasis in a wide variety of tumors. However, it is still unknown whether this agent inhibits bone metastasis. We examined the effects of TNP-470 in a bone metastasis model in nude mice in which intracardiac injection of the human breast cancer cell line MDA-MB-231 (MDA-231) produced osteolytic bone metastasis. After inoculation of MDA-231 cells into the left heart ventricle, TNP-470 (30 mg/kg, three times a week) or PBS was s.c. administrated for 4 weeks. After this period, the TNP-470 had reduced not only the number and area of osteolytic bone metastases (approximately 60 and 70%, respectively) but also their radiolucency. Histological examination of the femurs of the untreated group revealed that most of the cancellous bone had been replaced by the metastatic cancer. Numerous active osteoclasts were present along the trabecular bone surface surrounded by the metastatic MDA-231 cancer cells aggressively invading the bone marrow. In contrast, in the bone from TNP-470-treated mice, bone destruction was markedly inhibited, and there were much fewer osteoclasts. In a murine bone marrow culture under 1,25-dihydroxyvitamin D3 in which mature functional osteoclasts formed in vitro, TNP-470 significantly inhibited the formation of tartrate-resistant acid phosphatase-positive multinucleated osteoclast-like cells. And also, TNP-470 suppressed the in vivo bone resorption in calvaria treated with interleukin-1beta, an osteoclast stimulator. These data suggested that TNP-470 inhibited bone metastasis through not only antitumor action by its angiogenesis inhibition but also by the inhibition of osteoclastic bone resorption. Our results indicate that TNP-470 should be a potentially beneficial drug to be used in the treatment of osteolytic metastasis.
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PMID:Angiogenesis inhibitor TNP-470 inhibits human breast cancer osteolytic bone metastasis in nude mice through the reduction of bone resorption. 945 90

Bone turnover is characterized both by the formation of new bone by the osteoblasts and the resorption of old tissue by the osteoclast. This process takes place only on the surface of bone and can be described in terms of spatio-temporal events that are the bone metabolic unit and the bone remodelling cycle. The former consists of a discrete group of cells (osteoblasts and osteoclasts) involved in a particular remodelling event while the latter represents the succession of resorption and formation. In a typical remodelling cycle, resorption takes 7-10 days, whereas formation requires 2-3 months. Remodelling is regulated either by local or systemic factors, including electrical and mechanical forces, hormones (e.g. parathyroid hormone, sexual steroids, calcitriol, cortisol, thyroid hormones, calcitonin), growth factors and cytokines. Recently different circulating biochemical markers have been proposed for the investigation of bone turnover. In addition to classical parameters such as serum alkaline phosphatase and urinary calcium and hydroxyproline, new markers have gained clinical attention because of their accuracy in assessing the dynamic changes in bone remodelling (bone alkaline phosphatase, osteocalcin, propeptides PICP and PINP, tartrate-resistant acid phosphatase, deoxypyridinoline, pyridinoline, telopeptide CTx and NTx). The aim of this review is to present the recent advances in this field and the clinical application of markers of bone turnover in patients with bone metastases from solid tumors. Also the cellular and molecular bases of bone remodelling are reported with details.
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PMID:Clinical utility of biochemical marker of bone remodelling in patients with bone metastases of solid tumors. 1145 78

Bone resorbing osteoclasts contain high amounts of tartrate-resistant acid phosphatase (TRACP) 5b and secrete it into the blood circulation. Circulating TRACP 5b activity is derived exclusively from osteoclasts. We have developed a TRACP 5b-specific-immunoassay using a monoclonal antibody O1A that was developed using TRACP 5b purified from human osteoclasts as antigen. Serum TRACP 5b activity has a low diurnal variability, and it does not accumulate in the circulation in renal or hepatic failure. It is elevated in 80% of patients with osteoporosis, while decreased 40-50% after antiresorptive therapy with estrogen and the bisphosphonate alendronate. Preliminary results show that serum TRACP 5b activity is normal in breast cancer patients without bone metastases, and elevated in approximately 80% of breast cancer patients with bone metastases. These results suggest that serum TRACP 5b activity may be a useful marker for the early detection of the spreading of breast cancer cells to bone.
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PMID:Tartrate-resistant acid phosphatase 5B is a specific and sensitive marker of bone resorption. 1282 Mar 42

Diagnosis and follow-up of bone metastases in breast cancer patients usually rely on symptoms and imaging studies. Tartrate-resistant acid phosphatase 5b (TRACP 5b) is a specific marker of osteoclasts and is herein proposed as a marker of bone metastasis in breast cancer patients. An immunoassay using a monoclonal antibody, 14G6, was used to measure the activity of serum TRACP 5b at pH 6.1 in 30 early breast cancer patients without bone metastasis and in 30 aged-matched breast cancer patients with bone metastasis. Another 60 normal volunteers were recruited as controls. Bone alkaline phosphatase (BAP), a traditional marker of bone turnover, was also measured in selected cases. The overall mean TRACP 5b activity in normal women was 2.83 +/- 1.1 U/l, and it increased with age. The mean TRACP 5b activity in early breast cancer patients did not differ from that of the normal group (2.93 +/- 0.64 vs. 2.83 +/- 1.1 U/l; p = 0.66), whereas it was significantly higher in breast cancer patients with bone metastasis (5.42 +/- 2.5 vs. 2.83 +/- 1.1 U/l; p < 0.0001). BAP activity was significantly higher in breast cancer patients with bone metastasis than in early breast cancer patients (p = 0.004). Serum TRACP 5b activity correlated well with BAP activity in breast cancer patients with bone metastasis (p < 0.0001), but not in normal individuals or in patients without bone metastasis. TRACP 5b activity can be considered a surrogate indicator of bone metastasis in breast cancer patients.
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PMID:Tartrate-resistant acid phosphatase 5b as a serum marker of bone metastasis in breast cancer patients. 1515 86

Our aim was to assess the diagnostic accuracy of bone markers in serum of patients with prostate cancer (PCa) for early detection of bone metastases and their usefulness as predictors of PCa-caused mortality. In sera of 117 PCa patients (pN0M0, n = 39; pN1M0, n = 34; M1, n = 44), 35 healthy men and 35 patients with benign prostatic hyperplasia, bone formation markers [total and bone-specific alkaline phosphatase (tALP, bALP), amino-terminal procollagen propeptides of type I collagen (P1NP), osteocalcin (OC)], bone resorption markers [bone sialoprotein (BSP), cross-linked C-terminal (CTX) and cross-linked N-terminal (NTX) telopeptides of type I collagen, tartrate-resistant acid phosphatase isoenzyme 5b (TRAP)] and osteoclastogenesis markers [osteoprotegerin (OPG), receptor activator of nuclear factor kappaB ligand (RANKL)] were measured. tALP, bALP, BSP, P1NP, TRAP, NTX and OPG were significantly increased in PCa patients with bone metastases compared to patients without metastases. OPG showed the best discriminatory power to differentiate between these patients. Logistic regression analysis resulted in a model with OPG and TRAP as variables that predicted bone metastasis with an overall correct classification of 93%. Patients with concentrations of OPG, P1NP, tALP, bALP, BSP, NTX, TRAP and CTX above cut-off levels showed significantly shorter survival than patients with low marker concentrations. Multivariate Cox proportional hazards regression revealed that only OPG and BSP were independent prognostic factors for PCa-related death. Thus, the importance of serum OPG in detecting bone metastatic spread, alone or in combination with other bone markers, and predicting survival in PCa patients has been clearly demonstrated.
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PMID:Comparison of 10 serum bone turnover markers in prostate carcinoma patients with bone metastatic spread: diagnostic and prognostic implications. 1525 51

Serum activity of tartrate-resistant acid phosphatase 5b (TRAP 5b) in patients with breast cancer and prostate cancer having bone metastases was much higher than in healthy donors and patients without skeletal injuries. TRAP 5b activity in patients with breast cancer and multiple bone metastases surpassed that in patients with single bone metastases. The mean activity of TRAP 5b and range of enzyme activity in women treated with bisphosphonates were significantly lower than in patients not receiving antiresorptive therapy. Diagnostic sensitivity and specificity of TRAP 5b as a marker of skeletal metastases in patients with breast cancer were 82 and 87%, respectively. In patients with prostate cancer these indexes were 71 and 83.4%, respectively. Detection of this marker in tumor patients holds much promise for early diagnostics of bone metastases, estimation of the severity of skeletal metastases, and monitoring of the efficiency of bisphosphonate therapy.
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PMID:Tartrate-resistant acid phosphatase as a marker of bone metastases in patients with breast cancer and prostate cancer. 1551 30

The pathogenesis of bone metastases may require the activation of osteoclasts by tumor-secreted factors, which promote important interactions with the bone microenvironment. We utilized an intratibial model of bone metastasis with bioluminescent imaging (BLI) to measure the effect of osteoclast inhibition on the interaction of human lung cancer cells with bone, and on tumor growth. Mice were injected with luciferase-transduced tumor cells (HARA, human pulmonary squamous carcinoma) and divided into three groups: (1) untreated, (2) twice weekly treatment with the bisphosphonate zoledronic acid (ZOL), or (3) osteoprotegerin (OPG). Histomorphometry and imaging were used to evaluate tumor burden, and parameters of osteoclast activity. Mice in the treated groups had increased bone density and decreased osteoclast numbers in nontumor-bearing tibiae. There was greater than 60% reduction in mean tumor volume in both treatment groups when evaluated by histomorphometry (P = 0.06 [OPG], P = 0.07 [ZOL]). However, bioluminescent imaging failed to show a reduction in tumor burden due to wide variability in the data. Osteoclast numbers along tumor-associated bone were significantly increased compared to tumor-free bone, and were not reduced by either treatment. Plasma calcium concentration was increased in all groups. Plasma tartrate-resistant acid phosphatase 5b was reduced in both treatment groups. Plasma PTHrP was significantly increased in the untreated tumor-bearing group, but was not significantly different in the two treatment groups compared to normal mice. OPG or ZOL did not change tumor cell proliferation, but ZOL increased HARA cell apoptosis. OPG and ZOL reduced tumor growth in the tibiae of treated mice, however, PTHrP production by HARA cells may have resulted in a high concentration in the bone microenvironment, partially overriding the antiosteoclast effects of both OPG and ZOL.
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PMID:The effect of zoledronic acid and osteoprotegerin on growth of human lung cancer in the tibias of nude mice. 1671 52

Prognostic value of a bone resorption marker, tartrate-resistant acid phosphatase isoform 5b (TRACP 5b), and two matrix metalloproteinases (MMP-2 and MMP-9) was compared with the standard clinical analyses of total alkaline phosphatase (tALP) and prostate-specific antigen (PSA), in prostate cancer (PC) patients with (BM+) or without (BM-) bone metastases. Diagnostic accuracy evaluation showed the highest area under the curve for tALP (AUC=0.98), followed by PSA (AUC=0.87), TRACP 5b (AUC=0.82), MMP-9 (AUC=0.62) and MMP-2 (AUC=0.53). Significantly shorter survival was observed for patients with tALP (p<0.001), TRACP 5b (p=0.002) and PSA (p<0.001) levels, above the determined cut-off values compared with lower marker levels. In multivariate Cox regression analysis, only tALP and PSA, in addition to Gleason score were independent prognostic factors for survival. Of the three novel markers tested, only TRACP 5b proved to be predictive of survival in PC with bone metastases. MMP-2 and -9 are thus not recommended for further studies in this context.
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PMID:Survival markers related to bone metastases in prostate cancer. 1721 55


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