Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0153690 (bone metastases)
 6,382 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is a long-standing clinical observation that the bone corresponds to the prevalent site for metastatic growth of prostate cancer. In addition, bone metastases of this malignancy produce a potent blastic reaction, in contrast to the overwhelming majority of other osteotropic neoplasms, whose metastases are generally associated with an osteolytic reaction. Osteoblastic metastases represent almost always the first and, frequently, the exclusive site of disease progression to hormone refractory stage, stage D3. Moreover, the number of skeletal metastatic foci is the most powerful independent prognostic factor associated with a limited response to hormone ablation therapy and poor survival of advanced prostate cancer. It is noteworthy that disease progression to hormone refractory stage occurs almost always in osteoblastic metastases. These clinical observations suggested that the osteoblastic reaction is possibly not an innocent bystander of the metastatic prostate tumour growth, simply suffering its consequences, but it may in fact facilitate the efforts of metastatic cells to expand their population. An extensive line of research in the pathophysiology of osteoblastic metastases has established that the local blastic reaction involves the uPA/plasmin/IGF/IGFBP-3/TGFbs bioregulation system which can stimulate both the growth of osteoblasts and prostate cancer cells. Furthermore, we were the first to characterize osteoblast-derived 'survival factors' able to rescue metastatic prostate cancer cells from chemotherapy-induced apoptosis. These data resulted in the development of a novel concept of an anti-survival factor therapy, namely an anti-IGF-1 therapy, which has provided encouraging preliminary data in a phase II clinical trial with terminally-ill hormone/chemotherapy-resistant prostate cancer patients.
 ...
PMID:Cancer and bone repair mechanism: clinical applications for hormone refractory prostate cancer. 1575 19

Our objective was to elucidate phenotypic differences between prostate cancer (PCa) liver, lymph node, and bone metastases. PCa metastases were obtained through a rapid tissue acquisition necropsy protocol. We grossly dissected metastatic foci from frozen samples and performed expression analyses using cDNA microarrays. Immunohistochemical analyses using a tissue microarray from thirty individuals with PCa metastases to lymph nodes, liver, and bone was used to confirm the gene expression changes associated with each metastatic site. Transcript alterations statistically-associated with bone metastases included increased expression of IBSP (Bone sialoprotein), F13A1 (factor XIII), and decreased expression of EFNA1 (ephrin-A1) and ANGPT2 (angiopoietin-2) when compared to liver and lymph node metastases. The metastasis-associated changes in proteins involved in coagulation and angiogenesis prompted further analysis of additional factors known to participate in the clotting cascade and blood vessel formation (angiopoitein-1, PAI-1, uPA, PAI-RBP-1 and hepsin). We also assessed tumor-associated microvessel density and distribution in liver, lymph node, and bone metastasis. Intense fibrin(ogen) and fibulin-1 staining was localized to epithelial cells at the periphery of metastatic tumors possibly to facilitate angiogenesis. The expression of hepsin, uPA, PAI-RBP1, PAI-1, and factor XIII may influence fibrinolysis and are regulated by the tumor microenvironment. The expression of angiopoietin-2 and apparent silencing of angiopoietin-1 in PCa bone, liver, and lymph node metastases may be critical for angiogenesis in this tumor type. In addition, the resulting tumor-associated microvessel density and distribution was significantly different between liver and bone metastasis possibly in response to the protein expression changes detailed above.
 ...
PMID:Differential expression of angiogenesis associated genes in prostate cancer bone, liver and lymph node metastases. 1797 46

When renal cell carcinoma (RCC) metastasizes to bone (a frequent site of systemic spread of this cancer) it becomes highly resistant to radiation therapy and chemotherapy. A better understanding of the biology of bone metastasis in RCC may permit to identify biomarkers for early detection of subclinical disease and better stratification of patients prior to treatment. We therefore investigated in this study, using a multiplex real-time RT-PCR assay, the expression of a panel of 16 biomarkers involved in angiogenesis and tumor invasion; the panel was applied to primary tumors and normal tissues obtained from clear-cell RCC patients with and without bone metastases. We identified a novel combination of biomarkers associated with the risk of bone metastasis. Among the transcripts of the genes studied, VEGFR-1, VEGFR-2, HIF-1alpha, uPA , and PA I-1 overexpression in tumor tissues was significantly associated with the presence of bone metastasis (p=0.02, p=0.02, p<0.0001, p=0.04, and p=0.03, respectively). No differences were found in the expression of these transcripts in the corresponding normal tissues. This preliminary study provides a promising tool that may help in the management of RCC patients with bone metastasis. Indeed, these predictive markers could be useful to identify subclinical disease, improve staging, and guide treatment decisions.
 ...
PMID:Identification of a novel biomarker signature associated with risk for bone metastasis in patients with renal cell carcinoma. 2054 84