Odri, G.A., Dumoucel, S., Picarda, G. et al. (10 more authors) (2010) Zoledronic Acid as a New Adjuvant Therapeutic Strategy for Ewing's Sarcoma Patients. Cancer Research, 70 (19). pp. 7610-7619. ISSN 0008-5472
Abstract
Ewing's sarcoma (ES) is the second most frequent pediatric bone tumor also arising in soft tissues (15% of cases). The prognosis of patients with clinically detectable metastases at diagnosis, not responding to therapy or with disease relapse, is still very poor. Among new therapeutic approaches, bisphosphonates represent promising adjuvant molecules to chemotherapy to limit the osteolytic component of bone tumors and to protect from bone metastases. The combined effects of zoledronic acid and mafosfamide were investigated on cell proliferation, viability, apoptosis, and cell cycle distribution of human ES cell lines differing in their p53 and p16/ink4 status. ES models were developed to reproduce both soft tissue and intraosseous tumor development. Mice were treated with 100 μg/kg zoledronic acid (two or four times per week) and/or ifosfamide (30 mg/kg, one to three cycles of three injections). ES cell lines showed different sensitivities to zoledronic acid and mafosfamide at the cell proliferation level, with no correlation with their molecular status. Both drugs induced cell cycle arrest, but in the S or G2M phase, respectively. In vivo, zoledronic acid had no effect on soft tissue tumor progression, although it dramatically inhibited ES development in bone. When combined with ifosfamide, zoledronic acid exerted synergistic effects in the soft tissue model: Its combination with one cycle of ifosfamide resulted in an inhibitory effect similar to three cycles of ifosfamide alone. This very promising result could allow clinicians to diminish the doses of chemotherapy.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2010 AACR |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 19 May 2016 13:14 |
Last Modified: | 03 Nov 2016 10:56 |
Published Version: | http://dx.doi.org/10.1158/0008-5472.CAN-09-4272 |
Status: | Published |
Publisher: | American Association for Cancer Research |
Identification Number: | 10.1158/0008-5472.CAN-09-4272 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98197 |