Characteristics of patients with fragility hip fractures in the northern Kyushu district in Japan: a multicenter prospective registry based on an electronic data capture system.

Osteoporosis has become a worldwide public health problem, in part due to the fact that it increases the risk of fragility hip fractures (FHFs). The epidemiological assessment of FHFs is critical for their prevention; however, datasets for FHFs in Japan remain scarce. This was a multicenter, prospective, observational study in the northern district of Kyushu Island.

Suberoylanilide hydroxamic acid (SAHA) induces apoptosis or autophagy-associated cell death in chondrosarcoma cell lines.

Background: Since chondrosarcoma has a high resistance to conventional chemotherapy and radiotherapy, surgical resection is currently the only effective treatment. Histone deacetylase (HDAC) inhibitor exert anticancer effects, but have not been tested in chondrosarcoma.

Materials And Methods: We investigated the phenotypic change in chondrosarcoma cells treated with SAHA by cell viability assay, Western blot, flow cytometric analysis and electron microscopy.

The mechanism of cross-resistance to proteasome inhibitor bortezomib and overcoming resistance in Ewing's family tumor cells.

EWS-Fli1 plays important roles in oncogenesis of Ewing's family tumors (EFTs). We have reported that EWS-Fli1 inhibits p21(waf1/cip1) and p27(kip1) expressions, which are degraded by the ubiquitin-proteasome pathway. Bortezomib efficiently up-regulated p21(waf1/cip1) and p27(kip1) expression, and induced apoptosis accompanied by the expression of cleaved-PARP, DR4 and activated caspase-8 in EFT cells.

The effects of histone deacetylase inhibitors on the induction of differentiation in chondrosarcoma cells.

Purpose: Histologically, chondrosarcomas represent the degree of chondrogenic differentiation, which is associated with the prognosis of the disease. Histone acetylation and deacetylation play key roles in the regulation of chondrocytic differentiation. Here, we describe the antitumor effects of histone deacetylase (HDAC) inhibitors as differentiating reagents on chondrosarcomas.

The possible role of EWS-Fli1 in evasion of senescence in Ewing family tumors.

The chromosomal translocation t(11;22) yields the EWS-Fli1 fusion gene and is associated with oncogenesis of Ewing family tumors (EFT). In this study, using the RNA interference method, we show that EWS-Fli1-targeting small interfering RNAs (siRNA) depleted EWS-Fli1 protein and caused growth inhibition in EFT cells with the accumulation of p27 protein and the down-regulation of Skp2 protein in dose-dependent, time-dependent, and sequence-specific manners. Depletion of EWS-Fli1 subacutely elicited a senescence-like phenotype, but not apoptosis, in EFT cells.

Focal adhesion kinase is activated in invading fibrosarcoma cells and regulates metastasis.

Focal adhesion kinase (FAK) is a nonreceptor tyrosine kinase that is overexpressed in several human cancers, and induces survival, proliferation and motility of cells in culture. Phosphorylation of FAK has been studied extensively in vitro, but little is known about its regulation during tumor invasion in vivo. In the current study, green fluorescent protein (GFP) was expressed stably in an invasive murine fibrosarcoma cell line for the purpose of discrimination between tumor and normal cells.

Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing's sarcoma cells.

Despite recent improvements in multimodal therapies for osteosarcoma (OS) and Ewing's family of tumors (EFTs), the prognosis of relapsed cases remains very poor because of the resistance to chemotherapy. Histone deacetylase inhibitors (HDACIs), including members of the cyclic tetrapeptide family such as FK228 and apicidin, are novel antitumor agents that can induce cell cycle arrest and apoptosis in various cancer cells. HDACIs also exhibit potent antitumor effects on OS and EFTs.

Antitumor effects of histone deacetylase inhibitor on Ewing's family tumors.

A chimeric protein, EWS-Fli1, identified in most Ewing's family tumors (EFTs) has been shown to be associated with the tumorigenicity of EFTs. We have previously reported that p21(Waf1/Cip1) expression was inhibited by EWS-Fli1 in EFTs. Histone deacetylase inhibitors (HDACIs) are known to up-regulate p21(Waf1/Cip1) expression in various cells and show promise as a cancer therapy.

Transactivation of cyclin E gene by EWS-Fli1 and antitumor effects of cyclin dependent kinase inhibitor on Ewing's family tumor cells.

Chromosomal translocation t(11; 22)(q24; q12) is detected in approximately 90% of Ewing's family tumors (EFTs) including Ewing's sarcoma and primitive neuroectodermal tumor. This results in the formation of the EWS-Fli1 fusion gene, which produces EWS-Fli1 fusion protein. This chimerical gene product acts as an aberrant transcriptional activator, which may be responsible for the tumorigenesis of EFTs.

The prognostic and therapeutic relevance of p27kip1 in Ewing's family tumors.

Purpose: Ewing's family tumors (EFTs) display the characteristic fusion gene EWS-Fli1. We have reported EWS-Fli1 may promote the cell cycle progression accompanied by the suppression of the expression of cyclin-dependent kinase inhibitor p27(kip1) in EFT cells. Here, we describe the prognostic and therapeutic relevance of p27 in EFTs.

Identification of p21WAF1/CIP1 as a direct target of EWS-Fli1 oncogenic fusion protein.

Translocation t(11;22) is a karyotypic abnormality detected in over 90% of Ewing's family tumors. This translocation results in the EWS-Fli1 fusion gene, which has been shown to be a potent, single-step transforming gene. We reported previously that suppression of the EWS-Fli1 fusion protein altered the expression of G(1) regulatory cyclins and cyclin-dependent kinase inhibitors both at mRNA and protein levels, resulting in G(1) growth arrest in Ewing's family tumor cell lines.