title: Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients.
abstract: BACKGROUND
  To evaluate the modifications of circulating angiogenic factors, metalloproteinases and acute-phase cytokines after the first single zoledronic acid (ZA) intravenous infusion.
  
  
  METHODS
  Eighteen consecutive breast cancer patients with bone metastases were evaluated for circulating levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinase 1 (MMP-1), metalloproteinase 2 (MMP-2), interleukins 1beta, 6 and 8 (IL-1beta, IL-6, IL-8), interferon gamma, tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta1 just before and 2 and 7 days after ZA infusion.
  
  
  RESULTS
  The MMP-2 basal value showed a statistically significant decrease 48 h after ZA (p = 0.01), being at 7 days higher than the day 2 value (p = 0.03). The VEGF basal value showed a statistically significant decrease 48 h after ZA infusion (p = 0.03), increasing above the basal level at 7 days (p = 0.07). The bFGF basal level almost significantly decreased 2 days after infusion (p = 0.06), being at 7 days higher than the basal value (p = 0.09). Comparing the day 2 values with basal ones, the linear regression model showed a significant positive correlation between IL-8 and bFGF (p = 0.02), IL-8 and TNF-alpha (p < 0.0001), bFGF and TNF-alpha (p = 0.01), MMP-1 and TNF-alpha (p = 0.02).
  
  
  CONCLUSIONS
  ZA could exert an antiangiogenic activity and inhibition of tumor cell bone invasiveness by a transient reduction of VEGF, bFGF and MMP-2 circulating levels after infusion.
authors.affiliation: Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy. gia.fer@flashnet.it
authors.forename: Gianluigi
authors.initials: G
authors.lastname: Ferretti
authors.forename: Alessandra
authors.initials: A
authors.lastname: Fabi
authors.forename: Paolo
authors.initials: P
authors.lastname: Carlini
authors.forename: Paola
authors.initials: P
authors.lastname: Papaldo
authors.forename: Paola
authors.initials: P
authors.lastname: Cordiali Fei
authors.forename: Serena
authors.initials: S
authors.lastname: Di Cosimo
authors.forename: Nello
authors.initials: N
authors.lastname: Salesi
authors.forename: Diana
authors.initials: D
authors.lastname: Giannarelli
authors.forename: Andrea
authors.initials: A
authors.lastname: Alimonti
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Cocco
authors.forename: Giovanna
authors.initials: G
authors.lastname: D'Agosto
authors.forename: Valentina
authors.initials: V
authors.lastname: Bordignon
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Trento
authors.forename: Francesco
authors.initials: F
authors.lastname: Cognetti
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D001859:Bone Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000556:secondary; D001862:Bone Resorption / Q000517:prevention & control; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D016207:Cytokines / Q000097:blood*; D004164:Diphosphonates / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D045726:Metalloproteases / Q000097:blood*; D008875:Middle Aged; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D000077211:Zoledronic Acid
chemical_list: D043925:Angiogenesis Inducing Agents; D016207:Cytokines; D004164:Diphosphonates; D007093:Imidazoles; D007378:Interleukins; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D000077211:Zoledronic Acid; D007371:Interferon-gamma; D045726:Metalloproteases; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1