Skeletal consequences of RANKL-blocking antibody (IK22-5) injections during growth: mouse strain disparities and synergic effect with zoledronic acid.

High doses of bone resorption inhibitors are currently under evaluation in pediatric oncology. Previous works have evidenced transient arrest in long bone and skull bone growth and tooth eruption blockage when mice were treated with zoledronic acid (ZOL). The question of potential similar effects with a RANKL-blocking antibody (IK22.

BYL719, a new α-specific PI3K inhibitor: single administration and in combination with conventional chemotherapy for the treatment of osteosarcoma.

It has been established that disturbances in intracellular signaling pathways play a considerable part in the oncologic process. Phosphatidylinositol-3-kinase (PI3K) has become of key interest in cancer therapy because of its high mutation frequency and/or gain in function of its catalytic subunits in cancer cells. We investigated the therapeutic value of BYL719, a new specific PI3Kα inhibitor that blocks the ATP site, on osteosarcoma and bone cells.

Orthopaedic implant failure: aseptic implant loosening--the contribution and future challenges of mouse models in translational research.

Aseptic loosening as a result of wear debris is considered to be the main cause of long-term implant failure in orthopaedic surgery and improved biomaterials for bearing surfaces decreases significantly the release of micrometric wear particles. Increasingly, in-depth knowledge of osteoimmunology highlights the role of nanoparticles and ions released from some of these new bearing couples, opening up a new era in the comprehension of aseptic loosening. Mouse models have been essential in the progress made in the early comprehension of pathophysiology and in testing new therapeutic agents for particle-induced osteolysis.

Imatinib mesylate exerts anti-proliferative effects on osteosarcoma cells and inhibits the tumour growth in immunocompetent murine models.

Osteosarcoma is the most common primary malignant bone tumour characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments shows the importance of exploring new therapeutic methods. Imatinib mesylate (Gleevec, Novartis Pharma), a tyrosine kinase inhibitor, was originally developed for the treatment of chronic myeloid leukemia.

NVP-BEZ235, a dual PI3K/mTOR inhibitor, inhibits osteosarcoma cell proliferation and tumor development in vivo with an improved survival rate.

Despite recent improvements in chemotherapy and surgery, the problem of non-response osteosarcoma to chemotherapy remains, and is a parameter that is critical for prognosis. The present work investigated the therapeutic value of NVP-BEZ235, a dual class I PI3K/mTOR inhibitor. NVP-BEZ235 inhibited osteosarcoma cell proliferation by inducing G0/G1 cell cycle arrest with no caspase activation.