Proteomic Analysis of Soft Tissue Tumor Implants Treated with a Novel Polybisphosphonate

Cancer Genomics - Proteomics

EMAN BARHOUSH⁴  MARCELA MÁRQUEZ²  STEN NILSSON²  ANDERS R. HOLMBERG²  STEVE BOBIS³  ZAKIA SHINWARI⁴  AYODELE ALAIYA⁴  GORAN MATIC³  JONATHAN FOX¹ 

[1] Waters U.K. Limited, Manchester, U.K. Waters U.K. Limited, Manchester, U.K. Waters U.K. Limited, Manchester, U.K.;Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden;Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia Department of Comparative Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia;Proteomics Unit, Stem Cell & Tissue Re-Engineering Program, Riyadh, Saudi Arabia Proteomics Unit, Stem Cell & Tissue Re-Engineering Program, Riyadh, Saudi Arabia Proteomics Unit, Stem Cell & Tissue Re-Engineering Program, Riyadh, Saudi Arabia

关键词: Soft tissue;    tumor implants;    osteodex;    proteomic analysis;    breast cancer;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

Background: Osteodex is a novel bi-functional macromolecular polybisphosphonate developed for treatment of bone metastases in prostate and breast cancer. High efficacy of osteodex has been demonstrated both in vitro and in vivo. The present study investigates whether osteodex is also efficacious on soft tissue tumor lesions. Materials and Methods: Twelve female nude mice were injected with MDA-MB-231 cells orthotopically. Osteodex was administered i.v. at 2.5 mg/kg, once per week for five weeks. Tumor volumes were measured during the treatment period, the animals were sacrificed, and samples collected for proteomic analysis. Results: The non-treated mice developed multiple tumors greater than 4 cm with pronounced ulceration, while the treated mice had tumors smaller than 1 cm, without ulceration. While general condition of treated mice was good, non-treated animals were in poor condition. Sixteen out of 300 identified proteins were differentially expressed, with statistically significant expression changes of more than two-fold differences between treated and non-treated groups. These proteins were identified using non-gel based nano-liquid chromatography coupled with a Synapt G2 instrument. Conclusion: We conclude that osteodex showed significant treatment efficacy on soft tissue tumor implants. The study provides a global view of changes in protein expression profiles following osteodex treatment. Some functions of the identified proteins might be used to explain the specific treatment efficacy of osteodex.

【 授权许可】

Unknown