Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although osteosclerotic bone metastases are characteristic of prostate cancer, mixed metastases with a lytic component are not uncommon. Type I collagen is synthesised by osteoblasts and accounts for about 90% of the organic matrix of bone. We have used new specific immunoassays for PICP (carboxy-terminal propeptide of type I procollagen) and ICTP (cross-linked carboxy-terminal telopeptide of type I collagen) which allow simultaneous assessment of the synthesis and degradation of type I collagen respectively. Forty patients with bone metastases due to prostate cancer at the time of diagnosis were investigated with these methods. Twenty-three of them had sclerotic (S) and 17 had mixed metastases with sclerotic and lytic components (S + L) as assessed by radiographs. The concentrations of PICP and ICTP in serum as well as the activity of alkaline phosphatase (AP) were increased in all patients of the S + L group, who had more aggressive bone disease and a shorter survival than the S group (P < 0.017). The ICTP level was above the reference range in half of the patients in the S group, whereas the PICP and AP levels were elevated in 35%. Of the bone markers, only ICTP was of prognostic significance (P < .05). We conclude that ICTP and PICP give information about the type and activity of the skeletal metastases. In addition, ICTP predicts prognosis.
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PMID:Type I collagen degradation product (ICTP) gives information about the nature of bone metastases and has prognostic value in prostate cancer. 773

We developed a three-dimensional type I collagen gel cell culture system that allows coculturing of human MG-63 osteoblast-like cells and various human cancer cells. Inoculation of human PC-3 metastatic prostate cancer cells into this type I collagen gel containing human MG-63 osteoblast-like cells produced an osteoblastic-like reaction that presented as an increased number of MG-63 cells and increased density of type I collagen around MG-63 cells adjacent to inoculated PC-3 cells by microscope analysis. Under identical experimental conditions, inoculation of cell-free medium, human KLE endometrial adenocarcinoma cells, and Calu-1 lung cancer cells did not produce this blastic-like reaction. In situ hybridization documented the uniform expression of insulin-like growth factor I (IGF-I) and of urokinase-type plasminogen activator (uPA) mRNA in MG-63 and PC-3 cells separately cultured in this substrata. The uniform expression of uPA was also documented by immunocytochemistry using a monoclonal and a polyclonal antihuman uPA antibody. The relative expression of uPA was higher in PC-3 cells than in MG-63, KLE, and Calu-1 cancer cells. We conclude that this novel cell culture system may become a useful model to study the pathophysiology of the osteoblastic reaction in vitro.
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PMID:Three-dimensional type I collagen gel system for the study of osteoblastic metastases produced by metastatic prostate cancer. 786 32

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

A study was undertaken to evaluate the clinical usefulness of measurements of serum concentrations of the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as parameters of bone metastasis in patients with prostate cancer. Serum PICP, ICTP, prostate-specific antigen (PSA), and alkaline phosphatase (ALP) were evaluated in 82 patients with prostate cancer and 26 patients with benign prostatic hyperplasia (BPH). These markers were measured serially in 16 prostate cancer patients during treatment. The serum levels of PICP, ICTP, ALP, and PSA were significantly higher in prostate cancer patients with bone metastasis than in patients with either BPH or prostate cancer without bone metastasis. Although the rate of detection of bone metastasis with PICP and ICTP was slightly lower than that with PSA determined by the receiver operating characteristic curve, the correlation between both PICP and ICTP and the extent of disease was much higher than that of PSA. PICP and ICTP levels varied with ALP and PSA levels, the patient's clinical course after the start of endocrine therapy and the progression of bone metastasis. The levels of PICP and ICTP did not change substantially in patients who developed local regrowth or lymph node metastasis, and decreased as bone metastases responded to radiotherapy. PICP and ICTP thus reflect the metastatic burden in bone and are useful for monitoring the response of bone metastasis to therapy.
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PMID:Clinical usefulness of serum carboxyterminal propeptide of type I procollagen and pyridinoline cross-linked carboxyterminal telopeptide of type I collagen in patients with prostate cancer. 865 56

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

Recently discovered bone metabolic markers are expected to play an additional role in the diagnosis of bone metastasis. We measured bone metabolic markers, serum pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of human type I procollagen (PICP) in 224 patients with breast cancer (106 with bone metastases), 61 patients with prostatic cancer (30 with bone metastases), 45 patients with lung cancer (17 with bone metastases) and 13 patients with miscellaneous cancers (7 with bone metastasis) and compared the values in the presence and absence of bone metastasis. ICTP and PICP increased significantly in patients with bone metastases. By the analysis of sensitivity and specificity, the cut-off levels were considered to be 5.0 ng/ml for ICTP and 140 ng/ml for PICP. In lung cancer (bone metastases are mostly of osteolytic), ICTP was excellent marker in detecting bone metastasis. In breast cancer (bone metastases are mostly of mixed type), ICTP was good in detecting bone metastases. In prostatic cancer (bone metastases are mostly of osteoblastic), ICTP and PICP were good markers in detecting high grade of bone metastases. Over all, ICTP was more sensitive in the diagnosis of bone metastases than PICP. However, both markers were not effective in detecting low grade bone metastases. ICTP and PICP should play a supportive role to imaging modalities in the diagnosis of bone metastases.
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PMID:[Serum concentration of pyridinoline cross-linked carboxy-terminal telopeptide of type-I collagen (ICTP) and carboxyterminal propeptide of human type I procollagen (PICP) in the diagnosis of bone metastases]. 881 18

We inoculated the KLE human endometrial cancer, MCF-7 and ZR-75 human breast cancer, and PC-3 human prostate cancer cells into three-dimensional type I collagen gel system that contained uniformy dispersed MG-63 osteoblast-like cells. Then, we analyzed the morphological evidence of osteoblasts reaction, local invasion around the inoculated cancer cells and expression of the cathepsin D and urokinase-type plasminogen activator (uPA) around the sites of inoculation using immunocytochemistry. The prostate cancer cells produced morphological evidence of blastic reaction presented as an increased number of MG-63 osteoblasts and increase density of type I collagen around the sites of inoculation with PC-3 cells. The inoculated MCF-7 and ZR-75 cells decreased the density of type I collagen and number of osteoblasts and invaded the collagen gel around the sites of inoculation. The KLE endometrial cancer cells and cell-free media produced no reaction at the inoculation sites suggestive of cancer cell-specific interactions with osteoblasts in this system. The expression of uPA was remarkably higher at the inoculation sites of PC-3 cells as compared with those of the other cancer cells. Cathepsin D expression was higher at the sites of inoculation with KLE, MCF-7 and PC-3 cancer cells. MG-63 osteoblasts contained relatively low expression of uPA and cathepsin D. We conclude that this collagen gel system is a useful model for studying the morphological evidence of local invasion and osteoblasts reaction produced in response to local growth of metastatic cancer cell in vitro.
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PMID:Three-dimensional type I collagen gel system containing MG-63 osteoblasts-like cells as a model for studying local bone reaction caused by metastatic cancer cells. 891 85

Prostate cancer frequently metastasizes to bone, and we propose that this process may be facilitated by the adhesion of metastatic cells to bone-derived type I collagen. We examined collagen receptor function and regulation in osteotropic PC-3 human prostatic carcinoma cells. PC-3 cell adhesion to immobilized human type I collagen was promoted by Mn2+ and Mg2+ ions and was RGD-independent. Antibodies directed against beta1 or alpha2 integrin subunits inhibited adhesion to collagen by 90% and 53%, respectively, suggesting involvement of the alpha2 beta1 receptor. Anti-alpha1 or anti-alpha3 antibodies had no effect on adhesion. Flow cytometry and immunoprecipitation of [35S]methionine-labeled cells demonstrated that alpha2 beta1 was the major collagen receptor expressed by PC-3 cells. The pretreatment of PC-3 cells with transforming growth factor-beta1 (TGF-beta1), a major bone-derived growth factor, caused a rapid (2 h) 2-fold increase in the de novo synthesis of alpha2 and beta1 integrin subunits, and also increased by 2- to 3-fold the adhesion and spreading of PC-3 cells on collagen. We conclude that alpha2 beta1 is the major collagen receptor employed by PC-3 cells, and that alpha2 beta1 upregulation by TGF-beta is associated with an increased adhesion and spreading on collagen. The data suggest that exposure of metastatic PC-3 cells to the high levels of TGF-beta in bone may promote their ability to adhere to bone-derived collagen, which may thereby facilitate the localization of metastatic cells in the skeleton.
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PMID:Transforming growth factor beta upregulates the integrin-mediated adhesion of human prostatic carcinoma cells to type I collagen. 900 5

We investigated the usefulness of two biochemical markers of bone formation (PICP, the carboxy-terminal propeptide of type I procollagen, and bone ALP, bone-derived alkaline phosphatase) and a marker of bone resorption (ICTP, the carboxy-terminal telopeptide of type I collagen), to determine whether the presence of bone metastasis in prostate cancer could be evaluated and the extent of bone metastasis could be stratified by the serum levels of these markers, compared to total alkaline phosphatase (T-ALP) and prostate-specific antigen (PSA). The serum levels of PICP, bone ALP, ICTP, T-ALP and PSA were significantly higher in patients with both prostate cancer and bone metastasis (n=49) than in patients with benign prostatic hyperplasia (n=35) and patients with prostate cancer without bone metastasis (n=70). The superiority of a marker in the rate of detection of bone metastasis was evaluated with receiver operating characteristic curves. The serum marker levels were compared as a function of metastatic burden in bone (i.e., the extent of disease, EOD grade). We found that bone ALP is the most suitable marker for evaluating bone metastasis, especially for stratifying the degree of bone metastasis. Both PICP and ICTP were useful in this respect, but rather inferior to bone ALP. T-ALP had the lowest ability for detecting bone metastasis, but its correlation with the EOD grade was excellent, second to that of bone ALP. PSA showed limited reliability for stratifying the extent of bone metastasis.
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PMID:Comparison of markers of bone formation and resorption in prostate cancer patients to predict bone metastasis. 962 52

To determine the relationship between the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) and those of bone formation and resorption markers in prostate cancer patients, we measured the serum levels of the cytokines and examined their relationship to biochemical markers of bone turnover in 46 untreated patients with prostate cancer. The carboxy-terminal propeptide of type I procollagen (PICP) levels were used as a parameter of bone formation, and the carboxy-terminal telopeptide of type I collagen (ICTP) levels were used as a marker of bone resorption. The relationship of these markers to the degree of bone metastasis was also examined. The serum levels of IL-6, PICP, ICTP, and prostate-specific antigen (PSA) were significantly higher in the patients with prostate cancer with bone metastasis (n = 23) than in the patients without bone metastasis (n = 23). The serum levels of TNF-alpha in approximately 85% of the patients were under the detectable limit (5 pg/ml). The serum levels of IL-6 were not correlated with those of PICP or ICTP, but were related to the extent of bone metastasis. These results indicate that among patients with prostate cancer, IL-6 and TNF-alpha may not play major roles in the increased bone resorption in the patients with metastatic spread to bone. Our study thus demonstrated that the serum levels of IL-6 are closely related to the metastatic burden to osseous tissue in prostate cancer patients.
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PMID:Relationship between serum levels of interleukin-6, tumor necrosis factor-alpha and bone turnover markers in prostate cancer patients. 970 Apr 71


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