Searchable abstracts of presentations at key conferences on calcified tissues

ba0003pp94 | Cancer and bone: basic, translational and clinical | ECTS2014

Preclinical efficacy of PF-04942847, a novel HSP90 inhibitor, in osteosarcoma

Lamoureux Francois , Baud'Huin Marc , Ory Benjamin , Heymann Dominique , Redini Francoise

Introduction and objective: Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants the development of new strategies to improve overall patient survival. Among new therapeutic approaches, heat shock protein (HSP) 90 is a molecular chaperone involved in the maturation and stability of various oncogenic proteins leading to tumor cells survival. In this study, we assessed the in vitro a...

ba0001pp137 | Cancer and bone: basic, translational and clinical | ECTS2013

Clusterin inhibition using OGX-011 synergistically enhances zoledronic acid activity in osteosarcoma

Lamoureux Francois , Baud'huin Marc , Ory Benjamin , Gleave Martin , Heymann Dominique , Redini Francoise

Despite recent improvements in therapeutic management of osteosarcoma, ongoing challenges in improving the response to chemotherapy warrants new strategies still needed to improve overall patient survival. Among new therapeutic approaches, zoledronic acid represents a promising adjuvant molecule to chemotherapy to limit the osteolytic component of bone tumors. However, zoledronic acid triggers the elevation of heat shock proteins (Hsp), including Hsp27 and clusterin (CLU), whi...

ba0001pp139 | Cancer and bone: basic, translational and clinical | ECTS2013

New PI3Kα-specific inhibitor, BYL719: therapeutic interest in osteosarcoma

Gobin Berengere , Baud'huin Marc , Charrier Celine , Hervouet Soizic , Lezot Frederic , Blanchard Frederic , Heymann Dominique

It has been established that disturbances of intracellular signaling pathways strongly contribute to the oncologic process. Indeed, phosphatidylinositol-3-kinase (PI3K) became a key target in cancer therapy, due to its high frequency of mutation and/or gain of function of its catalytic subunits in cancer cells. In this context, we investigated the in vitro and in vivo effects of a new PI3Kα inhibitor, BYL719 (Novartis Pharma), on bone cells and its thera...

ba0001pp144 | Cancer and bone: basic, translational and clinical | ECTS2013

Selective BET bromodomains epigenetic signaling inhibition as a therapeutic strategy in primary bone tumors

Lamoureux Francois , Baud'huin Marc , Rodriguez Lidia , Jacques Camille , Berreur Martine , Bradner James E , Redini Francoise , Heymann Dominique , Ory Benjamin

Osteosarcoma is the most frequent primary bone tumor that develops mainly in young adults. The survival rate at 5 years is below 30% for patients with poor response to treatment or with metastasis.The histones modifications are of critical importance in maintaining the transcription program of both normal and tumor cells. The bromodomain and extra-terminal domain (BET) protein family is an important class of ‘histone reading protein’ capable to...

ba0003pp103 | Cancer and bone: basic, translational and clinical | ECTS2014

Selective inhibition of BET bromodomains epigenetic signaling interferes with the bone-associated tumor vicious cycle

Lamoureux Francois , Baud'huin Marc , Calleja Lidia Rodriguez , Jacques Camille , Redini Francoise , Lecanda Fernando , Bradner James E. , Heymann Dominique , Ory Benjamin

The vicious cycle established between bone associated tumors and bone resorption is the central problem with therapeutic strategies against primary bone tumors and bone metastasis. The bromodomain and extra-terminal domain (BET) protein family is an important class of ‘histone reading protein’ capable to recognize the N-acetylation of lysine residues on histone tails. BET bromain proteins have recently been described as regulators of MYC expression in various tumors....

ba0001pp394 | Osteoporosis: treatment | ECTS2013

Effects of a new conjugate drug in a rat model of postmenopausal osteoporosis

Liu Careesa , Young Robert , Grynpas Marc

Introduction: Standard clinical treatments for postmenopausal osteoporosis utilize resorption-inhibiting drugs such as bisphosphonates, which selectively bind to bone mineral but also suppress bone formation over time. Prostaglandin E2 (PGE2) has bone-anabolic effects in vivo, but its clinical utility is hindered by side effects upon systemic administration. Since PGE2 acts on bone via the EP4 receptor, our approach utilizes a specific...

ba0002p42 | (1) | ICCBH2013

The effect of glucocorticoids on bone indices in children with rheumatic and oncological conditions

Harrington Jennifer , Sochett Etienne , Grynpas Marc

Children with chronic medical conditions are at increased risk for bone fragility from multiple mechanisms, related both to the underlying condition and its treatment, in particular glucocorticoids. The differential effects of the underlying medical disease on bone micro-architecture have not been well elucidated.Objectives: To describe the bone micro-architectural characteristics in children with rheumatic and oncological disorders treated with glucocor...