title: Proteomic analysis of soft tissue tumor implants treated with a novel polybisphosphonate.
abstract: 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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Proteomics Unit, Stem Cell & Tissue Re-Engineering Program, King Faisal Specialist Hospital and Research Centre, (KFSH&RC) P.O. Box 3354, Riyadh, 11211 Saudi Arabia. AAlaiya@kfshrc.edu.sa.
authors.forename: Ayodele
authors.initials: A
authors.lastname: Alaiya
authors.forename: Jonathan
authors.initials: J
authors.lastname: Fox
authors.forename: Steve
authors.initials: S
authors.lastname: Bobis
authors.forename: Goran
authors.initials: G
authors.lastname: Matic
authors.forename: Zakia
authors.initials: Z
authors.lastname: Shinwari
authors.forename: Eman
authors.initials: E
authors.lastname: Barhoush
authors.forename: Marcela
authors.initials: M
authors.lastname: Márquez
authors.forename: Sten
authors.initials: S
authors.lastname: Nilsson
authors.forename: Anders R
authors.initials: AR
authors.lastname: Holmberg
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D004164:Diphosphonates / Q000494:pharmacology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D040901:Proteomics / Q000379:methods; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates
keywords: Soft tissue; breast cancer; osteodex; proteomic analysis; tumor implants