The effects of surgery, with or without rhGM-CSF, on the angiogenic profile of patients treated for colorectal carcinoma.
Wound healing is a process with immunological and angiogenic aspects. rhGM-CSF is known to stimulate the immune system and angiogenesis via multiple pathways. In this study we investigated the combined effects of surgery, with or without rhGM-CSF, on angiogenic parameters in patients with a colorectal carcinoma. In this phase II randomized, placebo-controlled trial, 16 patients were assigned to perioperative rhGM-CSF (2.8 microg/kg body weight) treatment or saline. Patients received subcutaneous injections from three days before surgery until four days after. IL-6, VEGF, endostatin and angiostatin levels were measured perioperatively. rhGM-CSF enhanced the production of IL-6 and VEGF, but had no effect on the antiangiogenic agents endostatin and angiostatin. Surgery induced a transient decrease of endostatin. Two types of angiostatin (kringle 1-3 and kringle 1-4) became visible postoperatively. We conclude that this study demonstrated the immediate initiation of angiogenesis postoperatively, reflected by the increase of VEGF and a transient decrease of endostatin, followed by the appearance of two angiostatin bands, which confirms physiological wound healing in these cancer patients.
Wu
Francis P K
FP
Department of Surgery, VU Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Westphal
Johan R
JR
Hoekman
Klaas
K
Mels
Anneke K
AK
Statius Muller
Markwin G
MG
de Waal
Robert W
RW
Beelen
Rob H J
RH
van Leeuwen
Paul A M
PA
Meijer
Sybren
S
Cuesta
Miguel A
MA
D000293:Adolescent; D000328:Adult; D000368:Aged; D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D043168:Angiostatins / Q000032:analysis; D002277:Carcinoma / Q000737:chemistry / Q000188:drug therapy* / Q000601:surgery; D015179:Colorectal Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000601:surgery; D003131:Combined Modality Therapy; D043169:Endostatins / Q000032:analysis; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis
D043925:Angiogenesis Inducing Agents; D043169:Endostatins; D015850:Interleukin-6; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D043168:Angiostatins