Development of a modified hollow fibre assay for studying agents targeting the tumour neovasculature.
BACKGROUND
Previous studies have shown extensive vascularisation surrounding subcutaneously implanted fibres when the duration of the US National Cancer Institute (NCI) hollow fibre assay was prolonged.


METHODS
The feasibility of adapting the NCI assay for evaluating agents targeting the tumour vasculature was investigated in vitro and in vivo. Finally, in the optimised assay, changes in neovasculature formation around the fibres following treatment with the anti-vascular agent paclitaxel were quantified by immunohistochemistry.


RESULTS
Correlations between cell number seeded, time in culture and vascular endothelial growth factor (VEGF) secretion were seen. In vivo studies showed that transplanting single rather than 3 fibres at a site reduced inflammation, reducing the length of the fibre transplanted, as did without any significant loss in cell growth over 21 days. A statistically significant reduction in neovascularisation surrounding the fibres was seen accompanying paclitaxel treatment.


CONCLUSIONS
Modifications made here to the NCI hollow fibre assay demonstrate its potential for analysing anti-tumour vasculature agents.
Shnyder
S D
SD
Cancer Research Unit, Tom Connors Cancer Research Centre, University of Bradford, Richmond Road, Bradford, UK. S.D.Shnyder@Bradford.ac.uk
Hasan
J
J
Cooper
P A
PA
Pilarinou
E
E
Jubb
E
E
Jayson
G C
GC
Bibby
M C
MC
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D006801:Humans; D008175:Lung Neoplasms / Q000098:blood supply* / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000473:pathology; D017239:Paclitaxel / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D020533:Angiogenesis Inhibitors; D000972:Antineoplastic Agents, Phytogenic; D042461:Vascular Endothelial Growth Factor A; D017239:Paclitaxel