RESUMO
The poor prognosis of patients with advanced bone and soft-tissue sarcoma has not changed in the past several decades, highlighting the necessity for new therapeutic approaches. Immunotherapies, including oncolytic viral (OV) therapy, have shown great promise in a number of clinical trials for a variety of tumor types. However, the effective application of OV in treating sarcoma still remains to be demonstrated. Although few pre-clinical studies using distinct OVs have been performed and demonstrated therapeutic benefit in sarcoma models, a side-by-side comparison of clinically relevant OV platforms has not been performed. Four clinically relevant OV platforms (Reovirus, Vaccinia virus, Herpes-simplex virus and Rhabdovirus) were screened for their ability to infect and kill human and canine sarcoma cell lines in vitro, and human sarcoma specimens ex vivo. In vivo treatment efficacy was tested in a murine model. The rhabdovirus MG1 demonstrated the highest potency in vitro. Ex vivo, MG1 productively infected more than 80% of human sarcoma tissues tested, and treatment in vivo led to a significant increase in long-lasting cures in sarcoma-bearing mice. Importantly, MG1 treatment induced the generation of memory immune response that provided protection against a subsequent tumor challenge. This study opens the door for the use of MG1-based oncolytic immunotherapy strategies as treatment for sarcoma or as a component of a combined therapy.
Assuntos
Terapia Viral Oncolítica/métodos , Rhabdoviridae/fisiologia , Sarcoma/terapia , Sarcoma/virologia , Animais , Neoplasias Ósseas/terapia , Neoplasias Ósseas/virologia , Linhagem Celular Tumoral , Cães , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Osteossarcoma/terapia , Osteossarcoma/virologia , Sarcoma de Ewing/terapia , Sarcoma de Ewing/virologia , Sarcoma Sinovial/terapia , Sarcoma Sinovial/virologiaRESUMO
Acetabular fracture patterns in the elderly, with increased involvement of the anterior column, quadrilateral plate comminution, medialization of the femoral head, and marginal impaction, differ from those noted among a younger cohort. Poor prognostic factors for open reduction and internal fixation (ORIF) are posterior wall comminution, marginal impaction of the acetabulum, a femoral head impaction fracture, a so-called gull sign, and hip dislocation. The rate of conversion to total hip arthroplasty following formal ORIF has been reported to be 22% at a mean of twenty-nine months. Total hip replacement after an acetabular fracture generally yields good clinical results; however, in the acute setting, it must be combined with proper stable fracture fixation.