title: Perioperative GMCSF limits the proangiogenic plasma protein changes associated with colorectal cancer resection.
abstract: OBJECTIVE
  Colorectal resection (CR) increases plasma VEGF levels which may promote residual tumor growth. This study assessed the effect of perioperative GMCSF on plasma levels of sVEGFR1, Ang-1 and Ang-2 and also the impact of post-GMCSF plasma on in vitro endothelial cell (EC) growth and invasion. Ang-2 increases while sVEGFR1 and Ang-1 impede angiogenesis.
  
  
  METHODS
  Fifty-nine CR cancer patients were randomized to 7 perioperative doses of GMCSF or saline for 3days prior and 4days after CR. Blood samples were taken pre-drug (PreRx) and on several postoperative days (POD). Protein levels were assessed and PreRx and POD 5 plasma added to EC cultures after which branch point formation (ECBPF) and invasion (ECI) were measured.
  
  
  RESULTS
  sVEGFR1 levels were significantly higher on POD 1 and POD 5 in both groups but the GMCSF POD 5 level was twice the control value (p=0.002). Ang-2 levels were higher on PODs 1 and 5 in both groups (p<0.05) but the control POD 5 value (vs. GMCSF) was greater (p=0.03). Ang-1 decreases were noted in all (p=not significant, ns). The control group POD 5 ECBPF was 35.8% greater than Pre Rx (p=0.001) while the GMCSF result was 18.0% lower (p=ns); the control POD 5 median percent change from baseline was greater than the GMCSF result(p=0.008). The POD 5 ECI was +12.2% for the control group vs. baseline (p=ns) and -17.2% for the GMCSF group (p=ns): the control median percent change was greater than in the GMCSF group(p=0.045).
  
  
  CONCLUSIONS
  CR-related plasma changes are proangiogenic (>Ang-2) and anti-angiogenic (>sVEGFR1); the net effect is promotion of in vitro ECBPF. GMCSF limits the proangiogenic changes (higher POD 5 sVEGFR1 levels and lower Ang-2 elevations, lower POD 5 ECBPF and ECI). The clinical import of these effects is unclear; perioperative GMCSF has anti-angiogenic plasma effects that may limit tumor growth. Further investigation is warranted.
authors.affiliation: Department of Surgery, Columbia University, New York Presbyterian Hospital, New York, USA.
authors.forename: H M C
authors.initials: HM
authors.lastname: Shantha Kumara
authors.forename: I
authors.initials: I
authors.lastname: Kirman
authors.forename: D
authors.initials: D
authors.lastname: Feingold
authors.forename: V
authors.initials: V
authors.lastname: Cekic
authors.forename: A
authors.initials: A
authors.lastname: Nasar
authors.forename: T
authors.initials: T
authors.lastname: Arnell
authors.forename: E
authors.initials: E
authors.lastname: Balik
authors.forename: A
authors.initials: A
authors.lastname: Hoffman
authors.forename: R
authors.initials: R
authors.lastname: Baxter
authors.forename: S
authors.initials: S
authors.lastname: Conte
authors.forename: R L
authors.initials: RL
authors.lastname: Whelan
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000601:surgery; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000097:blood* / Q000601:surgery; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000097:blood* / Q000188:drug therapy*; D016037:Single-Blind Method; D018709:Statistics, Nonparametric; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D016178:Granulocyte-Macrophage Colony-Stimulating Factor