title: The effects of surgery, with or without rhGM-CSF, on the angiogenic profile of patients treated for colorectal carcinoma.
abstract: 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.
authors.affiliation: Department of Surgery, VU Medical Center, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
authors.forename: Francis P K
authors.initials: FP
authors.lastname: Wu
authors.forename: Johan R
authors.initials: JR
authors.lastname: Westphal
authors.forename: Klaas
authors.initials: K
authors.lastname: Hoekman
authors.forename: Anneke K
authors.initials: AK
authors.lastname: Mels
authors.forename: Markwin G
authors.initials: MG
authors.lastname: Statius Muller
authors.forename: Robert W
authors.initials: RW
authors.lastname: de Waal
authors.forename: Rob H J
authors.initials: RH
authors.lastname: Beelen
authors.forename: Paul A M
authors.initials: PA
authors.lastname: van Leeuwen
authors.forename: Sybren
authors.initials: S
authors.lastname: Meijer
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cuesta
mesh_terms: 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
chemical_list: 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