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The identity of cells that establish the hematopoietic microenvironment (HME) in human bone marrow (BM), and of clonogenic skeletal progenitors found in BM stroma, has long remained elusive. We show that MCAM/CD146-expressing, subendothelial cells in human BM stroma are capable of transferring, upon transplantation, the HME to heterotopic sites, coincident(More)
PTK787/ZK 222584 (1-[4-chloroanilino]-4-[4-pyridylmethyl] phthalazine succinate) is a potent inhibitor of vascular endothelial growth factor (VEGF) receptor tyrosine kinases, active in the submicromolar range. It also inhibits other class III kinases, such as the platelet-derived growth factor (PDGF) receptor beta tyrosine kinase, c-Kit, and c-Fms, but at(More)
Skeletal muscle development occurs asynchronously and it has been proposed to be dependent upon the generation of temporally distinct populations of myogenic cells. This long-held hypothesis has not been tested directly due to the inability to isolate and analyze purified populations of myoblasts derived from specific stages of prenatal development. Using a(More)
Cells derived from blood vessels of human skeletal muscle can regenerate skeletal muscle, similarly to embryonic mesoangioblasts. However, adult cells do not express endothelial markers, but instead express markers of pericytes, such as NG2 proteoglycan and alkaline phosphatase (ALP), and can be prospectively isolated from freshly dissociated ALP(+) cells.(More)
BACKGROUND To identify predictive factors of disease-free survival (DFS) in patients with non-metastatic osteosarcoma of the extremity, treated with primary chemotherapy and delayed surgery. PATIENTS AND METHODS The relationship between patient-related and treatment-related factors and prognosis was evaluated in 300 patients treated from 1986 to 1992(More)
BACKGROUND Giant cell tumour of bone (GCTB) is a very rare, aggressive, and progressive osteolytic tumour for which no standard medicinal treatment or chemotherapy exists. We report interim safety and efficacy results from a phase 2 study of denosumab in patients with GCTB. METHODS We did an international, open-label, parallel-group, phase 2 trial of(More)
BACKGROUND To evaluate neoadjuvant trabectedin (1.5 mg/m(2) 24-h i.v. infusion every 3 weeks; three to six cycles) in patients with locally advanced myoxid liposarcoma (ML) previously untreated with chemotherapy or radiation. PATIENTS AND METHODS Primary efficacy end point was pathological complete response (pCR) or tumoral regression rate. Objective(More)
introduction Primary bone tumours are rare, accounting for <0.2% of malignant tumours registered at the EUROCARE database. They have a relatively high incidence in children and adolescents, but are still numerically outnumbered by benign bone tumours, which clinically may have a similar presentation. They are also frequently difficult to recognize as(More)
The chromatin accessibility complex (CHRAC) was originally defined biochemically as an ATP-dependent 'nucleosome remodelling' activity. Central to its activity is the ATPase ISWI, which catalyses the transfer of histone octamers between DNA segments in cis. In addition to ISWI, four other potential subunits were observed consistently in active CHRAC(More)
Mitotic kinases are the ultimate target of pathways sensing genotoxic damage and impinging on the cell cycle machinery. Here, we provide evidence that Aurora A (AurA) was inhibited upon generation of double-strand breaks in DNA. We demonstrate that AurA was not downstream of CDK1 and that inhibition of AurA and CDK1 by DNA damage occurred independently.(More)