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Hepatic arterial infusion of recombinant platelet factor-4 suppresses metastases to the lungs from tumors implanted into the livers of rabbits.
Cancer
May 1995
Department of Diagnostic Radiology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
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.
Background: When administered locally, recombinant platelet factor 4 (rPF4), a known angiogenesis inhibitor, has been shown to effectively suppress murine melanoma and human colon carcinoma primary tumor growth in mice. It was tentatively concluded that this effect was due to the inhibition of tumor neovascularization.
Purpose: This study has evaluated the effects of systemically administered rPF4 on the growth and establishment of experimental B16F10 melanoma lung metastases in syngeneic mice.
Platelet factor 4 injection produces acute pulmonary hypertension in the awake lamb.
Anesthesiology
January 1995
Department of Anesthesia, Harvard Medical School, Beth Israel Hospital, Boston, Massachusetts.
Background: Reversal of heparin anticoagulation by intravenous protamine sulfate consistently produces acute pulmonary vasoconstriction mediated by the release of thromboxane in the awake lamb. Recently, recombinant platelet factor 4 (rPF4) has been cloned, expressed in Escherichia coli, and infused to reverse heparin anticoagulation in the rat, without producing adverse hemodynamic or pulmonary morphologic effects. The authors sought to learn whether intravenous administration of PF4 is devoid of side effects in the pulmonary circulation of lambs.
View Article and Find Full Text PDFPlatelet factor 4 efficiently reverses heparin anticoagulation in the rat without adverse effects of heparin-protamine complexes.
Circulation
March 1992
Department of Physiology, Temple University School of Medicine, Philadelphia, PA 19140.
Background: It has been observed that the reversal of heparin anticoagulation in humans by protamine sulfate (PS) results in various adverse reactions including leukopenia, thrombocytopenia, activation of complement, increased vascular permeability, systemic hypotension, pulmonary vasoconstriction, and pulmonary edema. The purpose of this study was to compare the efficacy and effects of native platelet factor 4 (PF4) and recombinant platelet factor 4 (rPF4) with those of PS in heparin neutralization in vivo, using a rat model.
Methods And Results: Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the right femoral vein and carotid artery were cannulated.
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