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

Appendicular osteosarcoma (OS) is a primary mesenchymal tumor arising from malignantly transformed osteoblasts. In people, OS is the most common nonhematopoietic, primary skeletal neoplasm diagnosed in adolescents and is the second leading cause of cancer-related fatalities within this age group. Despite aggressive therapeutic management, including limb-sparing surgeries and dose-intense systemic chemotherapies, 30-40% of patients will experience progressive metastatic disease within 5 years of diagnosis. In order to reduce the fatality rate associated with recurrent or metastatic OS, a more thorough understanding of OS pathogenesis and biology is required. Towards this pursuit, comparative animal models of OS have been developed and are actively being studied to expand our fundamental understanding of OS. It is anticipated that specific animal models of OS, which most accurately recapitulate the natural disease process in people, will be most useful for advancing our understanding of OS biology, and will facilitate the discovery of disease pathogenesis and the identification of novel therapeutic strategies for managing this lethal metastatic bone sarcoma.
 ...
PMID:Animal models of osteosarcoma. 2073 17

Giant cell tumor of bone (GCTB) is a skeletal neoplasm, a locally aggressive tumor that occasionally metastasizes to the lungs. To identify novel biomarkers associated with GCTB progression and metastasis, we performed a miRNA microarray on ten primary tumors of GCTB, of which five developed lung metastases and the rest remained metastasis-free. Between metastatic and non-metastatic GCTB, 12 miRNAs were differentially expressed (such as miR-136, miR-513a-5p, miR-494, miR-224, and miR-542-5p). A decreased level of miR-136 in metastatic versus non-metastatic GCTB was significantly confirmed by the quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) (p=0.04). To identify potential target genes for the differentially expressed miRNAs, we used three target prediction databases. Then, to functionally validate the potential target genes of the differentially expressed miRNAs, we re-analyzed our previous gene expression data from the same ten patients. Eight genes such as NFIB, TNC, and FLRT2 were inversely expressed relative to their predicted miRNA regulators. NFIB expression correlated in metastatic GCTB with no or low expression of miR-136, and this gene was selected for further verification with qRT-PCR and immunohistochemistry. Verification of NFIB mRNA and protein by qRT-PCR showed elevated expression levels in metastatic GCTBs. Further, the protein expression level of NFIB was tested in an independent validation cohort of 74 primary archival GCTB specimens. In the primary tumors that developed metastases compared to the disease-free group, NFIB protein was moderately to strongly expressed at a higher frequency. Thus, in GCTB, miR-136 and NFIB may serve as prognostic makers.
 ...
PMID:MicroRNA expression profiles in metastatic and non-metastatic giant cell tumor of bone. 2317 52