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)

Clear cell chondrosarcoma is a rare mesenchymal neoplasm of unclear differentiation. Besides having a chondrogenic nature, an osteogenic differentiation was also proposed. In this study, expression analysis of extracellular matrix genes, which are specific for different mesenchymal cell differentiation pathways, were used to get a better understanding of origin and differentiation pattern of the clear cell chondrosarcoma tumor cells. Our in situ analysis of two cases shows that (1) chondrocytic cell differentiation as marked by the expression of cartilage collagen type II and proteoglycans is a characteristic feature within the development of the neoplasm, (2) multifocal chondrocyte hypertrophy as shown by the expression of type X collagen does occur, and (3) no significant expression of collagen type I, the main gene product of osteoblastic cells, is found by the neoplastic cells. Thus, our study indicates that clear cell chondrosarcoma shows a chondrogenic, but not osteogenic, differentiation and represents a true chondrosarcoma. The unusual scarcity of its extracellular and the multifocal expression of type X collagen marks clear cell chondrosarcoma as a chondrosarcoma tumor entity of a particular cell differentiation pattern. The expression of cartilage type collagens represents a distinct marker from bone metastases of clear cell neoplasms of other origins.
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PMID:Chondrocytic cell differentiation in clear cell chondrosarcoma. 895 2

The understanding of the pathophysiology and the monitoring of metastatic bone disease remains unsatisfactory. We compared several new markers of bone turnover in normocalcaemic patients with breast cancer-induced osteolysis before and after a single infusion of the bisphosphonate pamidronate. We studied 19 ambulatory patients with advanced breast cancer and extensive bone metastases who did not receive any systemic antineoplastic therapy. Pamidronate was administered at doses of 30, 60, 90 or 120 mg and the patients were followed weekly during a mean of 8 (range 4-10) weeks. Compared with healthy premenopausal women, the percentage of elevated values at baseline was 47% for fasting urinary calcium (uCa), 74% for hydroxyproline, 83% for CrossLaps (a new marker of type I collagen degradation) and 100% for the collagen cross-links (measured by high performance liquid chromatography), namely pyridinoline (Pyr) and deoxyPyr (D-Pyr). Pretreatment levels of uCa did not correlate significantly with any of the four markers of bone matrix resorption, whereas the correlations between these four markers were generally significant (r(s)=0.43-0.71). Alkaline phosphatase correlated significantly with markers of bone matrix resorption (r(s)=0.54-0.74). All parameters, except phosphaturia (uPi) and the bone formation markers (osteocalcin and alkaline phosphatase), fell significantly after pamidronate therapy, up to day 42 for hydroxyproline, D-Pyr and CrossLaps and day 56 for uCa. This longer lasting effect was probably due to the parathyroid hormone (PTH) surge following the decrease in serum calcium, implying that the decrease in uCa can overestimate the effects of bisphophonates on bone resorption. The decrease in bone turnover parameters was most marked for CrossLaps, indicating the potential of this new marker for monitoring therapy. Sequential determinations of markers of bone matrix resorption should be useful in delineating the optimal therapeutic schemes of bisphosphonates and for evaluating treatment effects on bone in cancer patients.
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PMID:Comparative evaluation of markers of bone resorption in patients with breast cancer-induced osteolysis before and after bisphosphonate therapy. 902 Apr 87

Assessing the response of bone metastases to systemic therapy remains a difficult clinical problem. The currently available markers of bone disease are limited by the length of time before the changes that accompany regression or progression become evident. The pyridinium crosslinks, pyridinoline (Pyr) and deoxypyridinoline (dPyr), are a recently described group of compounds formed by collagen breakdown. Elevated urinary crosslinks were demonstrated in patients with bone metastases when compared with controls (P<0.0001). Improvements in the sensitivity of the high performance liquid chromatography technique have enabled us to measure these compounds in serum for the first time; Pyr and dPyr were also significantly elevated when compared with controls (P<0.001). We found significant correlations between Pyr and dPyr in serum (p = 0.88; P<0.0001) as well as in urine (p = 0.94; P<0.0001). In addition, a significant relationship existed between serum Pyr and the percentage of bone involved (p = 0.78; P<0.0001). Here we describe or preliminary results using this new assay and consider the role of these markers in the clinical assessment of metastatic bone disease from breast cancer.
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PMID:Pyridinium crosslinks in the monitoring of patients with bone metastases from carcinoma of the breast. 903 11

Bone metastases in cancer of the prostate are diagnosed routinely by isotope bone scintigraphy and the measurement of alkaline phosphatase in serum and the calcium excretion in urine. The specificity of these examinations is in general not satisfactory. We therefore investigated the diagnostic value of five new markers of bone formation and bone resorption for the detection of the metastatic process. In a group of 43 patients with carcinoma of the prostate the carboxyterminal propeptide, the carboxyterminal cross-linked telopeptide, the aminoterminal cross-linked telopeptide, and the deoxypyridinoline cross-links of type 1 collagen were measured as well as the specific bone alkaline phosphatase isoenzyme. A group of 34 patients with benign prostatic hyperplasia served as a control. A receiver-operating characteristic analysis was performed. It appeared that the sensitivity of carboxyterminal cross-linked telopeptide of type I collagen was the greatest (89%), while the best specificity was obtained for the deoxypyridinoline cross-links assay (92%). The diagnostic values of the new markers were generally comparable with those of alkaline phosphatase although carboxyterminal cross-linked telopeptide of type I collagen yielded better results, but those with carboxyterminal propeptide of type I procollagen were less satisfactory. Calcium excretion in urine had no added value at all.
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PMID:Diagnostic value of some biochemical bone markers for the detection of bone metastases in prostate cancer. 905 49

We examined the osteolytic ability of metastatic cells and the role of tumour matrix metalloproteinases (MMPs) in bone degradation. The histomorphometry of experimental bone metastases of B16/F1 melanoma cells showed that osteolysis was associated with a 90% decrease in osteoclast number and predominance of cancer cells overlaying resorption pits. In vitro, B16/F1 cells and their conditioned medium (CM) degraded 3H-proline-labelled extracellular matrices from osteoblast-like cells and 45Ca-labelled calvariae. Using bone slices, we observed morphological evidence of degradation by B16/F1 cells. A role for tumour MMPs in bone degradation was supported by inhibition of degradation by 1,10-phenanthroline, collagen I degradation by tumour cells and the presence of TPA-inducible M(r) 90,000, 84,000 and 64,000 gelatinolytic, and 54,000 caseinolytic bands in B16/F1-CM. These studies indicate that metastatic cancer cells degrade bone matrix directly and that this is partially mediated by MMPs.
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PMID:Direct osteolysis induced by metastatic murine melanoma cells: role of matrix metalloproteinases. 929 16

Gallium nitrate was originally developed as an antineoplastic agent; however, further studies have revealed that this drug has extremely potent effects on turnover of bone, and that low doses can be used to reduce bone resorption. Like the bisphosphonates, gallium nitrate has been studied in both malignant and in nonmalignant conditions. The results of randomized double blind studies have suggested that this drug has superior clinical efficacy relative to etidronate, calcitonin, and pamidronate for the acute control of cancer-related hypercalcemia. In patients with Paget's disease, low doses of gallium nitrate reduce biochemical parameters of accelerated bone turnover, including urinary excretion of calcium, hydroxyproline, and urinary collagen cross-linked N-telopeptides. Preliminary studies showed similar effects in patients with bone involvement from a wide variety of tumor types. Based on this high degree of clinical potency revealed in clinical studies, two randomized Phase III studies have been initiated in patients with bone metastases from breast carcinoma and bone involvement due to multiple myeloma. Both studies employ cyclic therapy with low dose gallium nitrate (i.e., 40 mg administered as a subcutaneous injection once daily for 2 weeks, followed by 2 weeks off treatment, recycled monthly). The endpoints of both studies are to document reductions in time to "morbid skeletal events," such as palliative skeletal radiotherapy, stabilizing orthopedic surgery, or pathologic fractures, as well as decreases in pain and analgesic requirements and improvements in mobility and other aspects of quality of life. These trials should provide definitive evidence of whether this agent is safe and effective as a treatment for bone metastases.
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PMID:Gallium nitrate for the treatment of bone metastases. 936 36

Eighty-six patients with heavily pretreated progressive bone metastases (52 with breast carcinoma, 17 with prostate carcinoma, and 17 others) were included in 2 studies designed to assess the clinical and biochemical effects of a single 120 mg, 2-hour infusion of pamidronate. No other systemic anticancer treatment or radiotherapy were administered. Pamidronate had a significant beneficial effect, with a reduction in a symptom score measuring pain, World Health Organization performance status, and analgesic consumption and improvement in quality of life when compared with a placebo infusion. Symptomatic improvement corresponded with changes in the rate of bone resorption as indicated by the concentrations of pyridinoline crosslinks in the urine. In patients with the highest rates of bone resorption (N-terminal peptide-bound portion of the collagen crosslink or crosslaps excretion > or = twice that of normal) clinical response or normalization of the rate of bone resorption were rarely observed, with all clinical responses occuring in those patients with bone resorption rates of < twice that of normal. Intriguingly, symptomatic response also correlated with a modest (> 10%) fall in tumor marker levels, suggesting a possible effect of bisphosphonates on tumor activity.
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PMID:High dose pamidronate: clinical and biochemical effects in metastatic bone disease. 936 37

The role of biochemical markers of bone metabolism in the diagnosis and monitoring of bone metastases in solid tumors is reviewed. Emphasis is on the recently developed markers, which may provide a more accurate quantitation of bone metabolism. In metastatic bone disease, bone formation and resorption become uncoupled processes, leading to predominantly osteoblastic or osteolytic metastases. In osteolytic metastases, bone resorption is enhanced without appropriate acceleration of bone formation. In osteolytic metastases the resorption markers are indicated for the detection of bone metastases. Urinary pyridinium cross-links and serum collagen telopeptides are sensitive and specific markers of bone resorption. These markers, can often identify bone metastases before visualization by imaging techniques. When osteolytic lesions are responding to treatment the physiologic coupling between bone resorption and formation is partly restored. An increase in formation markers, bone specific isoenzyme of alkaline phosphatase (BSAP), osteocalcin (OC) and carboxyterminal propeptide of collagen type I (PICP), will then closely reflect restoration of coupling. In osteoblastic metastases, bone formation markers can accurately indicate early and advanced bone involvement. Bone resorption markers are less sensitive in these osteoblastic lesions. The collagen telopeptides however, are resorption markers with the ability to detect early bone metastases. Osteoblastic lesions responding to therapy are indicated by declining values of formation as well as resorption markers. The precise role of the recently developed markers of bone metabolism in early diagnosis and monitoring of bone metastases needs further evaluation in longitudinal studies. Since the delicate derangements in bone metabolism may be obscured in mixed patient groups, these studies should address uniform patient groups with respect to the primary tumor type.
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PMID:Biochemical parameters of bone metabolism in bone metastases of solid tumors (review). 945 86

Two patients with carotid body paraganglioma developed bone metastases 3 and 6 years respectively after surgical excision of the primary tumors. Plain radiographs showed ill-defined metastatic lesions. Scintigram using radiolabeled metaiodobenzylguanidine, an analogue of noradrenaline that is taken up by neurosecretary granules, showed an abnormal accumulation in the corresponding metastatic lesion. Histologically, nests of epithelioid cells with clear cytoplasm and pyknotic nuclei and abundant collagen fibers were observed within destroyed trabeculae. Treatment including external radiation and surgery provided pain relief and early local disease control.
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PMID:Carotid body paraganglioma metastatic to bone: report of two cases. 952 77

One-third of women with breast cancer will develop bone metastases and eventually die from disease progression at these sites. Therefore, we analyzed the ability of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 conditioned media (MG-63 CM), insulin-like growth factor I (IGF-I), and transforming growth factor beta 1 (TGF-beta1) to alter the effects of adriamycin on cell cycle and apoptosis of estrogen receptor negative (ER-) MDA-MB-231 and positive (ER+) MCF-7 breast cancer cells, using cell count, trypan blue exclusion, flow cytometry, detection of DNA fragmentation by simple agarose gel, and the terminal deoxynucleotidyl transferase (TdT)-mediated nick end-labeling method for apoptosis (TUNEL assay). Adriamycin arrested MCF-7 and MDA-MB-231 cells at G2/M phase in the cell cycle and inhibited cell growth. In addition, adriamycin arrested the MCF-7 cells at G1/G0 phase and induced apoptosis of MDA-MB-231 cells. Exogenous IGF-I partially neutralized the adriamycin cytotoxicity/cytostasis of cancer cells. MG-63 CM and TGF-beta1 partially neutralized the adriamycin cytotoxicity of MDA-MB-231 cells but enhanced adriamycin blockade of MCF-7 cells at G1/G0 phase. MG-63 osteoblast-like cells inhibited growth of MCF-7 cells while promoting growth and rescued MDA-MB-231 cells from adriamycin apoptosis in a collagen co-culture system. These data suggest that osteoblast-derived growth factors can alter the chemotherapy response of breast cancer cells. Conceivably, host tissue (bone)-tumor cell interactions can modify the clinical response to chemotherapy in patients with advanced breast cancer.
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PMID:Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by osteoblast-derived growth factors. 1020 74


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