Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients.
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.
Ferretti
Gianluigi
G
Division of Medical Oncology A, Regina Elena Cancer Institute, Rome, Italy. gia.fer@flashnet.it
Fabi
Alessandra
A
Carlini
Paolo
P
Papaldo
Paola
P
Cordiali Fei
Paola
P
Di Cosimo
Serena
S
Salesi
Nello
N
Giannarelli
Diana
D
Alimonti
Andrea
A
Di Cocco
Barbara
B
D'Agosto
Giovanna
G
Bordignon
Valentina
V
Trento
Elisabetta
E
Cognetti
Francesco
F
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
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