Relationship between human tumour angiogenic profile and combretastatin-induced vascular shutdown: an exploratory study.
Combretastatin-A4-phosphate (CA4P) acts most effectively against immature tumour vasculature. We investigated whether histological angiogenic profile can explain the differential sensitivity of human tumours to CA4P, by correlating the kinetic changes demonstrated by dynamic MRI (DCE-MRI) in response to CA4P, with tumour immunohistochemical angiogenic markers. Tissue was received from 24 patients (mean age 59, range 32-73, 18 women, 6 men). An angiogenic profile was performed using standard immunohistochemical techniques. Dynamic MRI data were obtained for the same patients before and 4 h after CA4P. Three patients showed a statistically significant fall in K(trans) following CA4P, and one a statistically significant fall in IAUGC(60). No statistically significant correlations were seen between the continuous or categorical variables and the DCE-MRI kinetic parameters other than between ang-2 and K(trans) (P=0.044). In conclusion, we found no strong relationships between changes in DCE-MRI kinetic variables following CA4P and the immunohistochemical angiogenic profile.
Gaya
A
A
Department of Clinical Oncology, Guy's & St Thomas' Hospitals, London SE1 7EH, UK. andrew.gaya@gstt.nhs.uk
Daley
F
F
Taylor
N J
NJ
Tozer
G
G
Qureshi
U
U
Padhani
A
A
Pedley
R B
RB
Begent
R
R
Wellsted
D
D
Stirling
J J
JJ
Rustin
G
G
D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D042501:Angiogenic Proteins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000071063:Endoglin; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D005260:Female; D019786:Gadolinium DTPA; D006801:Humans; D007150:Immunohistochemistry; D039661:Integrin beta3 / Q000378:metabolism; D018810:Magnetic Resonance Angiography / Q000379:methods; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000098:blood supply* / Q000188:drug therapy*; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D011956:Receptors, Cell Surface / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*
D000199:Actins; D042501:Angiogenic Proteins; D015703:Antigens, CD; D000972:Antineoplastic Agents, Phytogenic; C064206:ENG protein, human; D000071063:Endoglin; C061248:ITGB3 protein, human; D039661:Integrin beta3; D011956:Receptors, Cell Surface; D013267:Stilbenes; C058728:fosbretabulin; D019786:Gadolinium DTPA