UMLS:C0376358 - FACTA Search

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Query: UMLS:C0376358 (prostate cancer)
59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We compared clodronate with placebo administration in 42 primarily or secondarily hormone-refractory prostate cancer patients with skeletal metastases and persisting pain. Serum total alkaline phosphatase (ALP), bone ALP isoforms, osteocalcin, cross-linked carboxy-terminal telopeptide of type I collagen, and prostate-specific antigen were analyzed before and after 1 month of treatment. Six ALP isoforms were quantified by HPLC: one bone/intestinal, two bone (B1, B2), and three liver ALP isoforms. The most apparent difference compared with healthy males was observed for the bone ALP isoform B2. Patients and healthy males had a B2 activity corresponding to 75% and 35% of the total ALP activity, respectively (P <0.0001). We propose that the different bone ALP isoforms reflect different stages of osteoblast differentiation during the extracellular matrix maturation phase of osteogenesis. All bone markers except osteocalcin increased after 1 month of clodronate administration. These increases were associated with pain only in the upper part of the body. We suggest that the uptake of clodronate by the skeleton was not uniform during our treatment period.
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PMID:Differences of bone alkaline phosphatase isoforms in metastatic bone disease and discrepant effects of clodronate on different skeletal sites indicated by the location of pain. 970 48

The aim of this work was to evaluate the usefulness of serum aminoterminal propeptide of type I collagen (PINP) in the early detection of bone metastases associated with prostatic carcinoma. The results were compared with those of bone isoenzyme of alkaline phosphatase (bAP). Levels of total alkaline phosphatase (TAP) and prostatic specific antigen (PSA), related to the existence of bone metastases, are also evaluated. Fifty-five male patients aged 70-80 years were studied. Nine presented a benign prostatic hyperplasia (BPH) and the rest clinically confirmed prostatic cancer. Cancer patients were classified in accordance with the staging grouping of the International Union Against Cancer/American Joint Committee on Cancer TNM 1992 Revision: stage 0 or BPH (n=9), I (n=6), II (n=12), III (n=18) and IV (n=10). According to this classification, patients of groups BPH, I, II and III have no evidence of metastases. Those of stage IV present any type of metastases. In the case of this work, all patients of group IV presented bone metastases. Some patients of group BPH, I and II were untreated. The rest of the patients were under treatment (radical prostatectomy, telecobaltotherapy or hormonal therapy) for a period of between 6 months and 15 years. Serum PSA (Quimioluminiscence, IMMULITE), PINP (RIA, Orion Diagnostica), bAP (IRMA, Tamdem R-Ostase, Hybritech), and TAP (autoanalyzer) were determined. We found the following sensitivities and specificities (relating the presence of bone metastases to values higher than the upper limit of normality and, in the case of PSA, to values higher than 100 microg/L): (1) PINP: 100% (10/10) and 87% (39/45), (2) bAP: 90% (9/10) and 82% (37/45), (3) TAP: 60% (6/10) and 93% (42/45), (4) PSA: 40% (4/10) and 100% (45/45). These results suggest that PINP and bAP are adequate biochemical markers of bone formation to be used in the detection of bone metastases in prostatic carcinoma, improving the sensitivity and specificity of TAP and PSA. With respect to PINP, bAP presents the disadvantage of its cross-reactivity with liver isoenzyme.
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PMID:Aminoterminal propeptide of type I collagen and bone alkaline phosphatase in the study of bone metastases associated with prostatic carcinoma. 1035 26

Carboxyterminal propeptide of type I collagen (P1CP) and cross-linked carboxyterminal telopeptide of type I collagen (1CTP) are known as parameters of bone metastasis in patients with prostate cancer (PCa). We measured the serum P1CP and 1CTP levels in 52 PCa patients and evaluated the clinical usefulness of these serum markers. Both serum levels of P1CP and 1CTP were significantly higher in patients with extent of disease (EOD) grade 2 or 3 bone metastases than in patients without bone metastasis. Thus, P1CP and 1CTP are not as useful at first detection of bone metastases as bone scintigram. On the other hand, in the patients who indicated high serum levels of P1CP or 1CTP before initial treatment, the changes in the concentrations of these markers may be helpful in evaluating the response to treatment or the progression of disease. Our results suggest that P1CP and 1CTP are useful markers for monitoring the metastatic burden in the bone of PCa patients, but the efficacy is limited in high EOD grade cases.
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PMID:[Measurements and clinical usefulness of carboxyterminal propeptide of type I collagen and cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer]. 1036 41

The usefulness of a new biochemical marker of bone resorption, N-telopeptide of type I collagen (NTx), in the diagnosis of bone metastasis was assessed in 69 prostate cancer patients. Based on the bone scintigraphy findings, the patients were divided into a bone metastasis (+) group (n = 36) and a bone metastasis (-) group (n = 33). The urinary NTx level was significantly higher in the bone metastasis (+) group than in the bone metastasis (-) group (95.5 +/- 18.5 nM BCE/mM Cr vs. 63.3 +/- 7.9 nM BCE/mM Cr). There was a tendency for greater variability in urinary NTx levels during a 2 month-period in the bone metastasis (+) group than in the bone metastasis (-) group. The urinary NTx level of the 6 patients who were clinically staged as (4+) according to the extent of disease (EOD) grading system was 211.4 +/- 96.9 nM BCE/mM Cr, and was significantly higher (p < 0.05) than in the (-) group. However, there was not a significant difference in urinary NTx levels between the (1+) to (3+) groups and the (-) group. In conclusion, measuring urinary NTx levels in useful in diagnosing bone metastasis in view of the fact that it is a simple and noninvasive procedure. While it is not as sensitive as bone scintigraphy, it may be used to supplement bone scintigraphy.
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PMID:[Diagnostic value of urinary N-telopeptide of type I collagen in prostate cancer: comparison with bone scintigraphy]. 1039 Sep 56

Bone metastases are often associated with osteolysis and subsequent pathological fractures. To determine if metastatic human cancer cells can directly degrade non-mineralized and mineralized bone, we used prostate PC3 adenocarcinoma cell lines, which were originally established from skeletal metastases. We show that PC3 cells and their conditioned medium degraded non-mineralized, osteoid-like radiolabelled extracellular matrices from human Saos2 and U2OS osteoblast-like cells. These cells also directly degraded mineralized bone by inducing (45)Ca release from rat fetal calvariae and forming resorption pits on bone slices, an effect increased by transforming growth factor-beta(1). A role for matrix metalloproteinases in degradation was shown by: (1) stimulation by the phorbol ester TPA of PC3-induced matrix degradation and release of matrix metalloproteinase activity; (2) abrogation of matrix degradation by 1,10-phenanthroline, a metalloproteinase inhibitor, and (3) degradation of purified type I collagen by PC3 cells and their conditioned medium. We demonstrate that human prostate cancer cells can directly degrade bone-related matrices and that matrix metalloproteinases have a role in this process.
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PMID:Human metastatic prostate PC3 cell lines degrade bone using matrix metalloproteinases. 1072 74

Although increased bone formation is a prominent feature of patients with osteosclerotic metastases from prostate cancer, there is also some evidence for increased bone resorption. The aim of this study was to compare the clinical utility of new bone resorption markers to that of bone formation in patients with bone metastases from prostate cancer before and after bisphosphonate treatment. Thirty-nine patients with prostate cancer and bone metastasis, nine patients with prostate cancer without bone metastases, nine patients with benign prostatic hyperplasia and 355 healthy age-matched men were included. Urinary non-isomerized (alpha CTX) and beta isomerized (beta CTX) type I collagen C-telopeptides (CTX) and a new assay for serum CTX were used to assess bone resorption. Bone formation was determined by serum osteocalcin, serum total (T-ALP) and bone (BAP) alkaline phosphatase and serum type I collagen C-terminal propeptide (PICP). Fourteen patients with bone metastases were also evaluated 15 days after a single injection of the bisphosphonate pamidronate (120 mg). Levels of all bone formation and bone resorption markers were significantly (P < 0.006-0.0001) higher in patients with prostate cancer and bone metastasis than in patients with benign prostatic hyperplasia, patients with prostate cancer without bone metastases and healthy controls. In patients with bone metastases the median was increased by 67% for serum osteocalcin, 128% for T-ALP, 138% for BAP, 79% for PICP, 220% for urinary alpha CTX, 149% for urinary beta CTX and 214% for serum CTX. After bisphosphonate treatment all three resorption markers significantly decreased by an average of 65% (P = 0.001), 71% (P = 0.0010) and 61% (P = 0.0015) for urinary alpha CTX, urinary beta CTX and serum CTX, respectively, whereas no significant change was observed for any bone formation markers. Patients with prostate cancer and bone metastases exhibit a marked increase in bone resorption, which decreases within a few days of treatment with pamidronate. These findings suggest that these new resorption markers may be useful for the management of these patients.
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PMID:Markers of bone turnover for the management of patients with bone metastases from prostate cancer. 1073 59

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(-)HT(-)) and 34 patients without bone metastasis on hormonal therapy (BM(-)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procoIlagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(-)HT(+) group, the BM(-) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(-)HT(-) and BM(-)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(-)HT(-) groups with regard to bone formation and resorption. respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(-)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation.
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PMID:Biochemical markers for the detection of bone metastasis in patients with prostate cancer: diagnostic efficacy and the effect of hormonal therapy. 1115 73

The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on cell growth were studied in three human osteosarcoma cell lines, NOS-1, HuO9, and HuO-3N1; one human prostate cancer cell line, PC-3; and one human breast cancer cell line, OCUB-1M. The growth of these cell lines was not promoted by rhBMP-2 at concentrations of 50, 100, 250, and 500 ng/ml, as evaluated by colorimetric 3 (4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay. Furthermore, the protein induced osteogenic differentiation, characterized by increased alkaline phosphatase activity, and increased production of type I collagen and gamma-carboxylated osteocalcin in NOS-1 cells. The results of this study may suggest the feasibility of using rhBMP-2 for the reconstruction of bone defects caused by malignant tumors, although the data are still preliminary and require further investigation.
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PMID:Effects of bone morphogenetic protein-2 on human tumor cell growth and differentiation: a preliminary report. 1118 Sep 25

Type I collagen cross-linked N-telopeptide (NTx) in urine, the degraded form of type I collagen cross-linked in bone, has been evaluated as a marker of bone resorption. In this study, the clinical usefulness of NTx as a marker of bone metastasis of prostate cancer was compared with that the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type I procollagen (PINP), and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in serum. We assessed 37 cases of prostatic cancer in which the diagnosis had been confirmed pathologically. The patients were 15 patients with prostatic cancer with bone metastasis (before treatment or during a relapse) (Group 1); 11 patients, with bone metastasis, but for whom treatment was effective and condition had stabilized (Group 2); and 11 patients, with localized prostatic cancer and no evidence of bone metastasis (Group 3). The serum PICP, PINP, and ICTP levels and concentration of NTx in urine were compared among the three groups with the Mann-Whitney U test, with p values less than 0.05 considered significant. Urine NTx concentrations in Groups 1, 2 and 3 were 539.3 +/- 202.9, 160.6 +/- 97.6 and 48.6 +/- 7.6 nMBCE/mMCr, respectively. The differences between the Group 1 and Group 2 and between Group 1 and Group 3 were significant (p < 0.01 and p < 0.001). The differences between Group 1 and Group 3 and between Group 2 and Group 3 were significant for serum PICP, PINP and ICTP concentrations (p < 0.05). The correlation coefficient between urine NTx and each serum bone metabolic marker was 0.8 for PICP, 0.4 for PINP and 0.5 for ICTP. These bone metabolic markers are promising clinical markers of bone metastatic and may be useful for prediction of therapeutic efficacy and recurrence in bone and quantification of the extent of bone metastates.
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PMID:[Clinical usefulness of cross-linked N-telopeptide of type I collagen (NTx) as a bone metastatic marker in patients with prostate cancer--comparison with serum PICP, PINP and ICTP]. 1121 2

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

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