Hepatic arterial infusion of recombinant platelet factor-4 suppresses metastases to the lungs from tumors implanted into the livers of rabbits.
BACKGROUND
This study evaluated the toxicity (Part I) and antitumor effects (Part II) associated with hepatic arterial infusion of recombinant platelet factor-4 (rPF4), an antiangiogenic protein.


METHODS
Healthy rabbits (Part I) and rabbits with tumors implanted in their livers (Part II) received saline or rPF4 via hepatic arterial infusion. Three saline-receiving and four rPF4-receiving animals died 2-3 days postinfusion from gastroduodenal thromboembolism. The remaining animals were necropsied 3, 7, 10, or 14 days postinfusion. Blood analyses and hepatic angiography were performed before infusion and at the time of sacrifice.


RESULTS
In Part I, focal coagulation necrosis of the hepatic parenchyma was observed in 1 of 11 rabbits that received saline and in 6 of 10 that received rPF4. In Part II, hepatic arterial infusion of rPF4 had no effect on growth of the implanted liver tumors. However, the protein significantly reduced the incidence of lung metastasis.


CONCLUSIONS
Intraarterial infusion of rPF4 significantly reduced the incidence of lung metastasis. Nonheparin systemic anticoagulation may be needed during catheterization and infusion procedures to prevent thromboemboli.
Yoshimitsu
K
K
Department of Diagnostic Radiology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Wright
K C
KC
Wallace
S
S
Charnsangavej
C
C
Mavligit
G M
GM
D000818:Animals; D001158:Arteries; D004386:Duodenum / Q000098:blood supply; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000473:pathology*; D008175:Lung Neoplasms / Q000517:prevention & control* / Q000556:secondary*; D009336:Necrosis; D009368:Neoplasm Transplantation; D010978:Platelet Factor 4 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011817:Rabbits; D011994:Recombinant Proteins; D013270:Stomach / Q000098:blood supply; D013923:Thromboembolism / Q000139:chemically induced
D011994:Recombinant Proteins; D010978:Platelet Factor 4