An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NFκB in human osteosarcoma

Andela, Valentine B; Siddiqui, Farzan; Groman, A; Rosier, Randy N.

doi:10.1136/jcp.2004.017640

Cited by 21 publications

(16 citation statements)

References 9 publications

(7 reference statements)

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“…11 Importantly, an increased activation of NF-kB has also recently been identified in a human osteosarcoma cell line and is thought to contribute to the maintenance of a highly proliferative malignant phenotype. [12][13][14][15][16][17] To inhibit NF-kB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-kB has been developed. 18 When the NF-kB decoy ODN is transfected into cells, it binds competitively to activated NF-kB and prevents transactivation of the target genes.…”

Section: Introductionmentioning

confidence: 99%

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

et al. 2010

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Nuclear factor-kappa B (NF-kB) has a pivotal role in the progression and distant metastasis of cancers, including malignant bone tumors. To inhibit NF-kB activation, a new molecular therapy using synthetic double-stranded oligodeoxynucleotide (ODN) as a 'decoy' cis element against NF-kB has been developed. To determine whether pulmonary metastasis of osteosarcoma is reduced by inhibiting the action of NF-kB, NF-kB decoy ODN was transfected into the nuclei of murine osteosarcoma cells with high pulmonary metastatic potential, the LM8 cell line, using a three-dimensional alginate spheroid culture model. An in vitro study demonstrated the successful transfection of LM8 cells cultured in alginate beads by 'naked' NF-kB decoy ODN and that the activation of NF-kB signaling was significantly suppressed. Tumor growth was not affected by transfection of NF-kB decoy ODN, however, the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule 1 (ICAM-1) mRNA was markedly decreased. Furthermore, the transfection of 'naked' NF-kB decoy ODN effectively suppressed pulmonary metastasis in an in vivo alginate bead transplantation model. Our results suggest that NF-kB has a central and specific role in the regulation of tumor metastasis and could be a molecular target for development of anti-metastatic treatments for osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

et al. 2010

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“…Over‐expression of Runx2 in transgenic mice within the osteoblast lineage inhibits osteoblast maturation, increases bone resorption, and causes osteopenia with multiple fractures (Liu et al, 2001; Geoffroy et al, 2002). Runx2 is also clearly detected in clinical osteosarcoma samples (Andela et al, 2005; Lu et al, 2008; Sadikovic et al, 2009; Won et al, 2009; Kurek et al, 2010). Analysis of genomic DNA from osteosarcoma patients with amplication of the 6p12–p21 chromosomal interval, which spans the Runx2 locus, increases the Runx2 gene copy number and aberrantly elevates Runx2 expression (Lau et al, 2004; Lu et al, 2008; Sadikovic et al, 2009).…”

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confidence: 99%

Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma

et al. 2011

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The American Association for the Study of Liver Diseases guidelines recommend the use of all available markers for improving the accuracy of the diagnosis of small hepatocellular carcinoma (HCC). To determine whether clathrin heavy chain (CHC), a novel HCC marker, is effective in combination with glypican 3 (GPC3), heat shock protein 70, and glutamine synthetase, we compared the performances of a three-marker panel (without CHC) and a four-marker panel (with CHC) in a series of small HCCs ( 2 cm) and nonsmall HCCs by core biopsy with a 20-to 21-gauge needle. The series included 39 nonsmall HCCs and 47 small HCCs (86 in all); the latter showed a well-differentiated histology [small grade 1 (G1)] in 30 cases (63.8%). The panel specificity was analyzed with the adjacent/extranodular cirrhotic liver (n 5 30) and low-grade (n 5 15) and high-grade dysplastic nodules (n 5 16) as a control group. Absolute specificity (100%) for HCC was obtained only when at least two of the markers were positive (which two markers were positive did not matter). The addition of CHC to the panel increased the diagnostic accuracy for small HCCs (from 76.9% to 84.3%), and there was an important gain in sensitivity (from 46.8% to 63.8%). The four-marker panel had lower rates of accuracy (67.4%) and sensitivity (50%) for small G1 HCCs versus nonsmall G1 HCCs (93.9% and 88.2%, respectively). In seven cases (including six small G1 HCCs), there was no staining with any of the markers. Cirrhotic control livers were stained for CHC in four cases (13.3%) and for GPC3 in one case (3.3%). Conclusion: The addition of CHC to the panel supports the diagnosis of small HCCs in challenging nodules on thin core biopsy samples. Small G1 HCCs include a group of earlier tumors characterized by a more silent phenotype and the progressive acquisition of the markers under study. The search for additional markers for early HCC diagnosis is warranted. (HEPATOLOGY 2011; 53:1549-1557 See Editorial on Page 1427 H epatocellular carcinoma (HCC) is one of the most common malignancies worldwide, and its incidence is growing in association with viral (hepatitis C virus) and nonviral (nonalcoholic steatohepatitis) chronic liver diseases. 1 HCC is a lethal cancer, and improved survival relies on the detection of small ( 2 cm) and early tumors, which are less likely to have disseminated. Radiology is the main technique used to detect HCC in the setting of cirrhosis; typical imaging shows HCCs > 2 cm in more than 90% of cases. However, when the radiological features of hepatic liver nodules in cirrhosis are not typical, the American Association for the Study of Liver Diseases (AASLD) guidelines recommend the use

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“…[22][23][24] Preliminary studies suggest that antibodies against these molecules have diagnostic or prognostic utility in benign and malignant bone tumors. [25][26][27][28] However, a comprehensive analysis using a large number of diverse bone tumors has yet to be studied for the utility of immunohistochemistry of these markers.…”

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confidence: 99%

Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers

et al. 2012

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The molecules Indian hedgehog (IHH), SP7 (also known as osterix), sex-determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and TWIST1 regulate the normal differentiation of osteo-and chondrogenic cells from precursors during skeletal development and remodeling. The aberrant function of the same molecules has been implicated in the pathogenesis of bone tumors. Preliminary studies suggest that antibodies against these molecules have practical, diagnostic or prognostic utility in tumors. However, a comprehensive analysis of the expression of these molecules in a large, diverse set of bone tumors has yet to be reported. The goals of this study were to compare the immunohistochemical profiles of IHH, SP7, SOX9, RUNX2 and TWIST1 among bone tumors and to determine the optimum panel for diagnostic utility. Tissue microarrays prepared from 206 undecalcified tumors (71 osteosarcomas, 26 osteoblastomas/osteoid osteomas, 50 giant cell tumors, 5 chondromyxoid fibromas and 54 chondroblastomas) were stained with antibodies to IHH, SP7, SOX9, RUNX2 and TWIST1. The stains were scored for intensity (0À3 þ ) and distribution. The results were analyzed by cluster analysis. Optimum antibody panels for diagnostic sensitivity and specificity were calculated. Analysis revealed six main clusters that corresponded well to tumor types and suggested a close relationship between the stromal cells of giant cell tumor and the osteoblasts of osteosarcoma. The expression profile of chondromyxoid fibroma and chondroblastoma also suggested related differentiation. The distribution of osteoblastomas and osteoid osteomas was more heterogeneous. RUNX2, SOX9 and TWIST1 represented the most sensitive and specific immunohistochemical panel to distinguish among these diagnoses with the limitation that no result could discriminate between chondroblastoma and chondromyxoid fibroma. IHH and SP7 did not yield additional utility.

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An immunohistochemical analysis to evaluate an inverse correlation between Runx2/Cbfa1 and NFκB in human osteosarcoma

Cited by 21 publications

References 9 publications

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Transfection of NF-κB decoy oligodeoxynucleotide suppresses pulmonary metastasis by murine osteosarcoma

Diagnostic accuracy of clathrin heavy chain staining in a marker panel for the diagnosis of small hepatocellular carcinoma

Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers

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