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)

Prostate cancer is the most common malignancy in elderly men and is often associated with bone metastases. Although bone metastases are osteosclerotic, histological and biochemical studies clearly indicate an increase of both bone formation and bone resorption, providing the rational for using bisphosphonate as a palliative treatment in these patients. The recent development of specific and sensitive biochemical markers, reflecting the overall rate of bone formation and bone resorption, has improved the non-invasive assessment of bone turnover abnormalities in patients with prostate cancer. The immunoassays for bone-specific alkaline phosphatase and type I collagen propeptides are currently the most sensitive markers to assess bone, formation. The best indices of bone resorption are the immunoassay for the pyridinoline cross-links and the related peptides that can be measured in urine and more recently in serum. A better knowledge of the biochemistry, especially of the age-related post-translational modifications of type I collagen in the abnormal bone matrix, associated with bone metastases from prostate cancer may lead to markers of increased sensitivity. A recent example is the demonstration that the isomerization and racemization of the aspartic acid residue in C-telopeptides of type I collagen is impaired in patients with prostate cancer and bone metastases, a pattern than can be detected with specific conformational antibodies. The most sensitive markers of bone formation and bone resorption are markedly increased in patients with bone metastases compared with patients with cancer but without metastases, the levels correlating with the extent of the bone involvement. However, their sensitivity remains limited, suggesting that the currently available biochemical markers cannot be used as a surrogate for bone scintigraphy in the diagnosis of bone involvement. A few studies have suggested that the measurement of bone markers may be useful in the assessment of response to anti-endocrine therapy, although available data indicate a lower sensitivity than with prostates specific antigen. Additional longitudinal studies are required to assess the potential use of bone markers, especially to identify patients who relapse during the course of the treatment and, more specifically 3 those that result from the progression in bone metastases.Clearly, the established use of bone markers is for monitoring effects of bisphosphonate treatment. Several studies have shown a rapid decrease of bone resorption markers in patients with prostate cancer and bone metastases, the magnitude of the decrease correlating with the efficacy of the treatment in reducing bone pain. Thus, bone markers are likely to become a useful and objective tool to monitor bisphosphonate treatment and individual the therapy scheme.
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PMID:Markers of bone turnover in prostate cancer. 1141 70

Breast cancer is associated frequently with skeletal metastases, which cause significant morbidity. The main mechanism is an increase in osteoclast-mediated bone resorption. We postulated that osteoblasts could be other essential target cells and previously showed that conditioned medium (CM) of breast cancer cells (BCCs) inhibits the proliferation of osteoblast-like cells. In this study, we investigated the effects of BCC-secreted products on osteoprogenitor cells using a clonal fetal human bone marrow stromal preosteoblastic cell line (FHSO-6) that expresses alkaline phosphatase (ALP) activity, type I collagen (COLI), and increased osteocalcin (OC) and osteopontin under treatment with dexamethasone (Dex), 1,25-dihydroxyvitamin D [1,25(OH)2D], or recombinant human bone morphogenetic protein 2 (rhBMP-2). Treatment with MCF-7 CM inhibited FHSO-6 cell survival in a dose-dependent and irreversible manner. Morphological investigation indicated that MCF-7 CM increased both apoptotic and necrotic cell number. MCF-7 CM increased caspases activity and a broad inhibitor of caspase activity (benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone [z-VAD-fmk]) partly reversed the CM-induced inhibition of FHSO-6 cell survival. Western blot analyses revealed an increased bax/bcl-2 ratio in MCF-7 CM-treated FHSO-6 cells. MCF-7 cells exhibit FasLigand as membrane-bound protein and as a soluble cytokine in the CM. Deprivation of MCF-7 CM from active FasLigand by saturation with a soluble Fas molecule suppressed the induction of FHSO-6 apoptosis, whereas fibroblast CM, which did not contain FasLigand, only weakly modified FHSO-6 cell survival because of increased cell necrosis. These data indicate that FasLigand secreted by BCCs induces apoptosis and necrosis of human preosteoblastic stromal cells through caspase cascade modulated by the bax and bcl-2 protein level. The induction of apoptosis in human bone marrow stromal cells by BCCs may contribute to the inappropriately low osteoblast reaction and bone formation during tumor-induced osteolysis in bone metastases.
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PMID:Breast cancer cells release factors that induced apoptosis in human bone marrow stromal cells. 1154 30

The aim of this work was to evaluate the postoperative serum markers of type I collagen synthesis (PINP,PICP) and degradation (ICTP) and their possible potential for predicting the spread of disease and survival. 373 node-positive breast cancer patients were enrolled. 120 patients (32%) developed recurrent disease in the follow-up. The mean time to recurrence was 17 months and the mean follow-up time was 45 months. The mean level of PINP was significantly elevated in the patients who developed metastatic disease in the follow-up as compared with those without metastases. PINP was statistically significantly higher in all the patients who developed bone metastases than in those without metastases. When patients with only bone metastases or patients with bone and soft tissue and/or visceral metastases and patients with only visceral or soft tissue metastases were compared with those not exhibiting metastases, PINP was significantly higher in the group with recurrence in the bone, but there were no significant differences in serum PINP, PICP or ICTP values between the patients with only bone metastases and those who developed soft or visceral metastases during the follow-up. Postoperative high PINP was also a factor for poorer survivaL Tumor size, malignancy grade and progesterone receptors were shown in multivariate analysis to be predictors of recurrence and tumor size and PINP and progesterone receptors to be predictors of survivaL
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PMID:Postoperative PINP in serum reflects metastatic potential and poor survival in node-positive breast cancer. 1171 79

The aims of the present study were to determine whether patients with painful bone metastases from primary cancer sites showed a higher level of a bone resorption marker than those with no evidence of skeletal-related events, and to clarify the efficacy of oral administration of etidronate for pain due to bone metastases and bone resorption. Thirty outpatients with cancer were recruited: 10 with pain due to bone metastasis from the primary cancer site; lung (4), prostate (3), and breast (3) (M group), and 20 with primary cancer of the stomach (11), colon (4), breast (3), lung (1), and bladder (1) with no such evidence of skeletal-related events (non-M group). None of the patients in the M group either needed morphine for pain relief or had hypercalcemia, although all of them had been taking nonsteroidal anti-inflammatory drugs (NSAIDs). During the study, they continued taking NSAIDs, as they had before the study. The level of urinary cross-linked N-telopeptides of type I collagen (NTx) at baseline was significantly higher in the M group than in the non-M group ( P < 0.01). Oral administration of etidronate (400 mg/day for 2 weeks) to patients in the M group significantly reduced bone pain 2 and 12 weeks after the start of treatment; however, the pain relief effect was diminished 12 weeks after the start of treatment, despite a significant decrease in urinary NTx level ( P < 0.05 by one-way analysis of variance [ANOVA] with repeated measurements). The present study provides evidence suggesting that patients with painful bone metastases from primary cancer sites may have a higher level of urinary NTx than those with no evidence of skeletal-related events, and that oral administration of etidronate at the dose we used may have the potential to transiently relieve their bone pain by decreasing abnormally raised bone resorption. Although the present study had a small sample size, and had no placebo controls, the results may be useful, especially as they raise additional questions that could stimulate further research in Japan.
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PMID:Transient relief of metastatic cancer bone pain by oral administration of etidronate. 1211 69

In order to ascertain whether carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) might be useful as a serum screening parameter for bone metastases from non-prostate urological malignancies as well as prostate cancers, as series of 210 patients were examined. In addition to ICTP, serum alkaline phosphatase (ALP) and also prostate specific antigen (PSA) in the prostate cancer cases were assayed using commercial kits. The areas under the receiver operating characteristic (ROC) curves were 0.7846 for ICTP (cut-off point 9.6 microg/l), 0.8304 for ALP in prostate cancer cases, and 0.8278 for ICTP (cut-off point 10.6 microg/l), and 0.7139 for ALP in non-prostate cancer cases. While significance was only observed for ICTP and PSA in prostate cancer cases, borderline significance was also evident with ICTP for non-prostate malignancies, and with ALP for prostate cancer case. The results suggest that serum ICTP may be useful in combination with ALP as a quantitative clinical marker for low cost screening for bone metastases in patients with all types of urological malignancies.
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PMID:The efficacy of a serum carboxyterminal pyridinoline cross-linked telopeptide of type I collagen as a quantitative screening marker for bone metastases in patients with urological malignancies. 1260 Apr 12

Bone metastasis is a frequent complication of cancer disease. The metastatic spread of cancer to bone is common to many different malignancies, particularly breast (ca. 73%), prostate (ca. 68%) and lung (ca. 36%) cancers. Metastases to bone cause increased bone resorption both from direct effects of the tumor itself and thought osteoclastic activation. The diagnosis and follow-up of bone metastatic cancer patients usually relies on skeletal X-ray and bone scintigraphy. However, the development of biochemical markers, used as indicators of bone metabolism, provides data useful in the clinical practice. The most important markers for bone remodeling process, bone formation and resorption, are bone-specific alkaline phosphatase (BAP) and N-telopeptide of type I collagen (NTx), respectively. In this report, we applied two solid-phase immunoassays used for the determination of BAP and NTx in serum of breast cancer (BC) post-menopausal women with bone metastasis and healthy individuals. BAP level in patients was found to be 45.72 +/- 12.92 U/l, while the normal range for healthy individuals was 14.2 - 42.7 U/l. The respective level of serum NTx was 19.20 +/- 8.87 nM bone collagen equivalents (BCE) for patients and 15.9 +/- 3.8 nM BCE for healthy women. Correlation of the obtained data showed elevated levels for both markers indicating high rate of bone degradation in breast metastatic cancer.
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PMID:Determination and biological relevance of serum cross-linked type I collagen N-telopeptide and bone-specific alkaline phosphatase in breast metastatic cancer. 1501 61

In this study, cDNA microarrays were used to characterize gene expression changes elicited in prostate cancer cells by plating them on type I collagen. The results clearly reveal changes in the expression of genes associated with cellular signaling, cellular metabolism, gene transcription and gene translation which are indicative of cells that are actively proliferating. Together these results suggest that these changes in the gene expression profiles mediated by type I collagen may influence the proliferative capacity of prostate cancer cells in the bone microenvironment and facilitate development of prostate cancer bone metastases. Additionally, the microarray approach provides an invaluable tool to determine and track changes in gene expression in numerous disease states including prostate cancer. This technology is certain to facilitate discovery of new therapeutic gene targets.
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PMID:Type I collagen-mediated changes in gene expression and function of prostate cancer cells. 1504 90

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

Metastatic bone disease is common in cancer patients and causes substantial disease-related morbidity and mortality. However, several effective treatments are available for the management of these patients. Bisphosphonates, which inhibit osteoclast-mediated resorption of bone matrix, are especially important because they decrease the incidence of skeletal-related events in many tumour types and can complement antineoplastic therapies. At present, assessment of treatment for bone metastases is hindered by a lack of effective, rapid methods to measure disease response. We discuss the difficulties of current measures of response assessment and describe the development of new radiological and biochemical markers of bone metastases. Assays that detect type I collagen telopeptides as markers of bone resorption seem to be most promising at present.
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PMID:Assessment of therapeutic response in patients with metastatic bone disease. 1546 64

BACKGROUND: Bone metastases are common in many types of cancer. As screening methods different imaging modalities are available. A new approach for the screening of osseous metastases represents the measurement of bone metabolic markers. Therefore aim of this study was to evaluate the usefulness of the determination of bone metabolic markers aminoterminal propeptide of type I procollagen (PINP, osteoblastic activity) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP, osteoclastic activity) for the detection of bone metastases associated with other malignancies. METHODS: 88 patients aged 21 - 82 years with malignant tumors were prospectively studied. The serum concentrations of PINP and ICTP were measured and compared to the results of bone scintigraphy, radiological bone series, CT, MRI and clinical follow-up. RESULTS: Osseous metastases were found in 21 patients. 19 of them were correctly identified by bone scintigraphy (sensitivity: 90%). For bone metabolic markers results were as follows: ICTP sensitivity: 71%, specificity: 42%; PINP sensitivity: 24%, specificity: 96%. CONCLUSIONS: As markers of bone metabolism PINP and ICTP showed low sensitivity and/or specificity for the detection of osseous metastases. The presented markers did not seem to be sufficient enough to identify patients with bone metastases or to replace established screening methods.
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PMID:Evaluation of the clinical value of bone metabolic parameters for the screening of osseous metastases compared to bone scintigraphy. 1557 8


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