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...

ba0001pp141 | Cancer and bone: basic, translational and clinical | ECTS2013

Therapeutic interest of Imatinib Mesylate in osteosarcoma

Gobin Berengere , Moriceau Gatien , Ory Benjamin , Brion Regis , Redini Francoise , Heymann Dominique

Osteosarcoma is the most common primary malignant bone tumor, characterized by osteoid production and/or osteolytic lesions of bone. A lack of response to chemotherapeutic treatments points out the importance of exploring new therapeutic ways. Imatinib Mesylate (Glivec, Novartis Pharma), a tyrosine kinase inhibitor, has been originally developed for the treatment of chronic myeloid leukemia. Several studies revealed that Imatinib Mesylate inhibits osteoclast differentiation th...

ba0002p31 | (1) | ICCBH2013

Craniofacial consequences of high dose zoledronic acid injections in onco-pediatric patients

Lezot Frederic , Chesneau Julie , Battaglia Severine , Brion Regis , Farges Jean-Christophe , Heymann Dominique , Redini Francoise

Background: High doses of zoledronic acid (ZOL), one of the most potent inhibitors of bone resorption; is currently evaluated in a phase III clinical trial in Europe for the treatment of malignant pediatric primary bone tumors. The impact of such an intensive treatment on the craniofacial skeleton is a critical question in the context of patients with actively growing skeleton; in particular in the light of our previous studies evidencing that endochondral bone formation was t...

ba0003pp93 | Cancer and bone: basic, translational and clinical | ECTS2014

Inhibition of TGF-β signaling pathway blocks the development of osteosarcoma lung metastases

Lamora Audrey , Talbot Julie , Bougras Gwenola , Deley Marie Cecile Le , Heymann Dominique , Redini Francoise , Verrecchia Franck

Osteosarcoma is the main malignant primary bone tumor in children and adolescents for whom the prognosis remains poor, especially when metastases are present at diagnosis (survival rate drops to 20% when lung metastases were detected). Because TGF-β has been shown to promote metastases in many solid tumors, we investigated the effects of inhibition of the TGF-β/Smad cascade on osteosarcoma behavior. To this end, two independent procedures, a pharmacological approach ...

ba0006oc19 | (1) | ICCBH2017

Mesenchymal stromal stem cells in pediatric orthopedic oncology, focus on osteosarcoma

Trichet Valerie , Nail Louis-Romee Le , Guiho Romain , Layrolle Pierre , Redini Francoise

Introduction: Conventional therapy of osteosarcoma, a primary malignant bone tumor, includes surgical excision with wide resection, which leads to physical and aesthetic defects. Allografts for reconstruction of bone and joints and adipose tissue autologous grafts for soft tissue defects can be supplemented with mesenchymal stromal/stem cells (MSCs). Additionally MSCs may be used in tumor-targeted cell therapy. However MSCs may have adverse effects on osteosarcoma development,...

ba0001pp142 | Cancer and bone: basic, translational and clinical | ECTS2013

Over-expression of Smad7 in osteosarcoma cells inhibits primary tumor growth, the associated bone osteolysis and the development of lung metastasis in murine xenograft model

Lamora Audrey , Talbot Julie , Gobin Berengere , Leduc Marion , Taurelle Julien , Brion Regis , Heymann Dominique , Redini Francoise , Verrecchia Franck

Osteosarcoma, the main malignant primary bone tumor, affects a ‘young’ population composed of children and young adults. Current treatment consists of tumor resection associated with chemotherapy. Unfortunately in many cases, a lack of response to anti-tumor drugs is observed, leading to development of metastases and to the patient’s death. Because TGF-β promotes metastases from many solid epithelial tumors, we investigated the effect of inhibitory Smad7 ov...

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...