Use of the hollow fiber assay for the discovery of novel anticancer agents from fungi.
The hollow fiber assay (HFA) is a drug discovery tool to aid investigators in the prioritization of lead compounds identified by in vitro testing for further development in animal models of disease. In the HFA, cells are cultured in hollow fibers containing pores of a diameter (500 kDa) large enough for proteins and other macromolecules to enter, but too small for the cells to escape. The fibers are filled with cells, sealed and placed in the peritoneal cavity of immunodeficient mice. The mice undergo a predetermined treatment regimen after which the fibers are retrieved and the cells evaluated for activity of a target relevant to the disease modeled. The HFA combines advantages of both in vitro and in vivo assay systems. It uses the same cell lines used in culture systems, is a rapid assay, and requires fewer animals and less test substance than conventional xenograft systems. Like traditional in vivo assays, the test substance is evaluated in a live animal, which affords an initial assessment of associated toxicity and pharmacokinetic properties of the test substance.
College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Cedric J
CJ
Pearce
Daniel D
DD
Lantvit
Qi
Q
Shen
David
D
Jarjoura
Xiaoli
X
Zhang
Nicholas H
NH
Oberlies
David J
DJ
Kroll
Mansukh C
MC
Wani
Jimmy
J
Orjala
Djaja D
DD
Soejarto
Norman R
NR
Farnsworth
Esperanza J Carcache
EJ
de Blanco
James R
JR
Fuchs
A Douglas
AD
Kinghorn
Steven M
SM
Swanson
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001688:Biological Products / Q000494:pharmacology*; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D055808:Drug Discovery / Q000295:instrumentation*; D005260:Female; D051379:Mice
D000970:Antineoplastic Agents; D001688:Biological Products