Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In summary, Sarcoidosis is a rare but well-recognized cause of diffuse osteosclerosis. The differential diagnosis of osteosclerosis is limited and includes osteoblastic metastases, sclerotic myeloma, myelofibrosis, and less common infiltrative bone marrow processes such as mastocytosis and sarcoidosis. In all of these entities the sclerosis is found most often in the axial (red marrow) skeleton. In this regard, it is interesting that cases of osseous sarcoid are usually lytic and located in the peripheral skeleton. In patients with osteosclerotic sarcoidosis, the diagnosis may be suggested by a past history of the disease or ancillary signs such as hilar node enlargement and subtle skin involvement. However, the specific diagnosis usually requires bone marrow biopsy with the demonstration of extensive, noncaseating granulomas.
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PMID:Case report 705. Osteosclerotic sarcoidosis. 160 45

Bone metastases in breast cancer may be osteolytic, osteosclerotic, or a mixture of the two. Although stimulation of bone resorption by breast cancer cells has attracted some interest, the formation of osteosclerotic secondary tumours and the influence of human mammary carcinoma cells on osteoblasts (bone forming cells), both important in understanding breast cancer--bone interactions, have been largely neglected. We therefore examined the effects of conditioned medium (CM) from two cultured human breast cancer cell lines (MCF7 and ZR-75) and from primary cultures of breast carcinomas from two patients, on osteoblasts and recruitment of bone-resorbing cells (osteoclasts) in vitro. Osteoblast-like cells (BDC) were cultured from human trabecular bone explants. Osteoclast maturation was studied in fetal rat calvaria cultured on collagen gels. CM from the MCF-7 line and cells derived from one patient each inhibited BDC DNA synthesis, but stimulated osteoclast recruitment. In contrast, CM from the second patient's cells or ZR-75 enhanced DNA synthesis in BDC, but blocked osteoclast maturation. This suggests that human breast carcinomas secrete soluble factors which influence both osteoclasts and osteoblasts. A further unexpected implication is that mammary carcinoma cells may cause local osteosclerosis by directly stimulating osteoblasts, rather than through raised bone turnover in metastases.
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PMID:Breast carcinomas synthesize factors which influence osteoblast-like cells independently of osteoclasts in vitro. 200 8

Medulloblastoma is a relatively common intracranial neoplasm in childhood. Its extraneural spread was, until recently, thought to be a rare occurrence. Metastases are most commonly to bone. Five patients with medulloblastoma metastatic to bone are presented, and findings are compared to those of previous reports. Two of the five cases showed patchy extensive osteosclerosis of the pelvis and/or proximal femora. One case had concurrent lymph node involvement. In patients with past or present medulloblastoma and bone pain, metastases to bone should be excluded. Medulloblastoma metastatic to bone is a rare cause of extensive osteosclerosis.
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PMID:Metastases to bone in medulloblastoma. A report of five cases. 281 54

The radiographic manifestations of 127 skeletal metastases in 50 patients with melanoma were reviewed and correlated with the scintigraphic findings. Although the features of most of the metastases were nonspecific and appeared similar to those of other osteolytic metastases, several of them had unusual features, including expansion, subarticular location, osteosclerosis, and a thin, sclerotic rim. These features could result in some of the metastases being mistaken for other lesions. The radionuclide bone scans were more sensitive in that they detected the lesions earlier and in greater numbers than the radiographs. Prognosis was poor once skeletal metastasis was diagnosed, the mean survival time being 4.7 months.
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PMID:Skeletal metastases of melanoma: radiographic, scintigraphic, and clinical review. 678 58

We studied bone biopsies from 65 normocalcaemic women with breast cancer and predominantly osteolytic bone metastases in order to examine the pathophysiology of bone destruction in metastatic bone disease. Quantitative histomorphometric measurements were made at sites of tumour involvement, at sites adjacent to tumour tissue and at sites distant from tumour tissue. There were no significant differences in bone volume or in indices of bone resorption or formation between biopsies taken from sites distant from tumour and the controls. Bone resorption, as judged by eroded surface, increased progressively from bone distant from tumour to tumour-laden bone. The number of osteoclasts was significantly increased in bone immediately adjacent to tumour and within metastases. There was no decrease in the ratio of osteoclast to eroded surface in breast cancer compared to controls suggesting that increased resorption in breast cancer was mainly osteoclast mediated and locally activated by the tumour. Two thirds of the biopsies taken from tumour involved regions showed osteosclerosis with woven bone formation. The volume of the pre-existing lamellar trabecular bone was lower than normal in 75% of these biopsies, suggesting that bone resorption must have been increased before the onset of woven bone formation. Since all patients were receiving hormonal treatment or chemotherapy, it is likely that osteosclerosis at sites of previous resorption mainly resulted from the basic cancer treatment as a sign of response to treatment. Osteoclastic bone resorption was, however, not completely inhibited by the active cancer treatment.
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PMID:Histomorphometric evidence for osteoclast-mediated bone resorption in metastatic breast cancer. 808 33

This study of the topographic distribution of tumoral and pseudotumoral lesions of the proximal femur shows that certain lesions have a preferential site, for example osteoid osteoma affects the internal cortex of the neck and diaphysis or the intertrochanteric zone; chondroblastoma occurs in zones of epiphyseal ossification of the head; fibrous dysplasia affects the femoral neck, while sparing the epiphyseal femoral head and trochanters. The island of osteosclerosis is situated, at least partially, in the support fan; so-called physiological cysts are situated on or above the midline of the neck and below the basicapital line. Osteolytic or mixed metastases preferentially involve Ward's triangle in the femoral neck and the intertrochanteric region. The sites of these lesions therefore appears to depend on the bony architecture which, in turn, is dependent on mechanical stresses. However, this purely morphological study fails to demonstrate whether mechanical stresses influence the development of these lesions.
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PMID:[Topography of tumoral and pseudotumoral lesions of the proximal femur]. 833 97

There are three principal disturbances in bone remodelling that occur in neoplasia affecting the skeleton. The first is an increase in bone turnover that in solid tumors may be confined to sites of metastases or be a generalized phenomenon, most likely related to the secretion of parathyroid hormone-related protein. In the bone remodelling sequence, bone resorption precedes formation, so that increases in turnover result in substantial skeletal deficits more marked at cancellous than cortical bone sites. The second abnormality in bone remodelling is an imbalance between the amount resorbed and that formed at each remodelling site. This is a conspicuous feature of myelomatosis with moderate grades of plasma cell infiltration. The third phenomenon is the process of uncoupling. In osteolytic disease this is associated with the creation of erosion cavities that are never subsequently repaired. Progressive waves of bone resorption result in the destruction of skeletal elements and focal osteolysis. Osteosclerotic metastases formed by uncoupled bone formation represent the deposition of new bone either on quiescent bone surfaces or arising from stromal condensations within the marrow cavity. In solid tumors biopsy evidence suggests that uncoupled bone resorption and formation occur within the same metastases and that the radiographic expression (osteosclerosis, osteolysis) depends on the predominant component. The understanding that abnormalities of skeletal metabolism are mediated by authentic bone cells raises the possibility that skeletal specific markers of bone turnover might be utilized for the diagnosis of metastases, to assess the skeletal prognosis, or to monitor treatment. A variety of skeletal markers have been assessed. The pyridinium crosslinks currently provide the markers of greatest predictive value. Although they have high specificity, their sensitivity is low (< 30%). This indicates that many individuals with skeletal metastases would be missed. In contrast, skeletal markers have proven invaluable in the assessment of the natural history of the disease and response to intervention. They have been particularly useful in assessing the pharmacodynamics of bisphosphonate treatment. However, their day-to-day precision is sufficiently low that they are of limited value in the monitoring of individuals.
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PMID:Bone turnover and biochemical markers in malignancy. 936 20

The characteristic sclerotic appearance of bone metastases from prostate cancer is unexplained but could involve excess peritumoural activity of osteoblast mitogens such as the insulin-like growth factors (IGFs). Since prostatic metastases are distinguished by androgen-dependent secretion of prostate-specific antigen (PSA), a serine protease which cleaves extracellular IGF-binding proteins and thereby enhances the bioavailability of IGFs, the relationship was examined between tumour PSA expression and the osteoblastic phenotype. To this end, a cohort of 27 prostate cancer patients was evaluated to determine the relationship between serum PSA and radiographic bone lesion density at first presentation with metastatic disease. No linear correlation between absolute PSA levels and metastatic osteosclerosis was apparent. However, non-parametric statistical analysis revealed a highly significant link between low-PSA (<20 ng/ml) metastatic prostate cancer and osteolytic bone lesions (p<0.0001, chi(2)=21.5). This finding raises the possibility that the osteoblastic phenotype of prostate cancer derives in part from PSA-dependent proteolysis of IGF-binding proteins within bone matrix.
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PMID:Correlation of the osteoblastic phenotype with prostate-specific antigen expression in metastatic prostate cancer: implications for paracrine growth. 1041 96

In human cancers, bone is a common site for metastasis. It is well known that metastasis is the cause of morbidity and mortality in patients with cancer. Both breast and prostate carcinomas have a propensity to metastasize to bone. In general, metastatic breast cancers result in osteolytic lesions. On the other hand, prostate cancer metastases are osteoblastic and result in osteosclerosis. Thus, bone formation and bone resorption are at the crux of the cancer metastasis problem. For example, in the prostate, there is a vicious cycle of metastasis to bone (Fig. 1). Metastases to bone causes excruciating bone pain, pathological fractures, and eventually death, and therefore is a serious challenge to both bone biologists and cancer cell biologists. The stromal-epithelial interactions in breast and prostate are critical in initiation of carcinogenesis and the progression of the metastatic cascade to bone (Fig. 2). Over a hundred years ago, Stephen Paget enunciated the seed and soil hypothesis in which seeds of metastatic cancer cells of breast preferentially settle in the soil of bone matrix. Thus, the prostate/breast cancer bone interface and continuum has continuously presented challenges and opportunities and were discussed at a recent workshop.
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PMID:Mechanisms of tumor metastasis to the bone: challenges and opportunities. 1256 95

Bisphosphonates are a class of therapeutic agents originally designed to treat loss of bone density. It has been shown that the primary mechanism of action is inhibition of osteoclastic activity. Accumulating data show that these drugs are useful in diseases with propensities toward osseous metastases. In particular, they are effective in diseases in which there is clear upregulation of osteoclastic or osteolytic activity such as breast cancer and multiple myeloma. Despite the fact that osseous metastases in prostate cancer manifest as osteosclerosis rather than osteolysis, studies now show that bisphosphonates are useful in the management of this disease. In particular, they have demonstrated an impact on osteoporosis associated with hormonal therapy, bone pain from metastases, and skeleton-related events from prostatic adenocarcinoma. This review briefly summarizes the available clinical data on the utilization of bisphosphonates in the disease of prostate cancer.
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PMID:The emerging role of bisphosphonates in prostate cancer. 1470 97


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