Visit our Expo - Redox and Inflammation signaling 2012

Session X : Cell death in cancer Poster X, 35
A Bench-to-Bed-Side Approach for the Identification and Validation of Novel
Compounds to Induce Apoptosis of Cancer Cells
Maria Hägg1, Takayuki Ueno1, Maria Berndtsson1, Aleksandra M. Havelka1, Frank
Neumann2, Heiko van der Kuip3, Thomas E. Murdter3, Maria C. Shoshan1, Masakazu
Toi4 and Stig Linder1
1Cancer Center Karolinska, Department of Oncology and Pathology, R8:03, Karolinska
Institute and Hospital, S-171 76 Stockholm, Sweden. 2BIOAXXESS Technology, Moor
Court Farm, Upper Pendock WR13 6JW, UK, fneumann@bioaxxess.com, 3Dr
Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, D-
70376 Stuttgart, Germany, 4Department of Surgery and Breast Oncology, Tokyo
Metropolitan Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, 113-8677,
Tokyo, Japan
Cell based screening offers the advantage that active, cell permeable, agents such as those that
induce tumor apoptosis can directly be identified. Two-dimensional tissue culture conditions
are, however, very different from those of the human tumor environment and it is difficult to
decide which compounds should be developed for further pre-clinical and clinical studies.
We here describe an approach based on the assessment of a caspase-cleaved protein fragment
of cytokeratin-18 released from apoptotic cells that can be used to identify apoptosis-inducing
drugs, assess their potency to induce apoptosis in organ cultures of human tumors, and finally
monitor carcinoma cell apoptosis in vivo by using plasma samples from drug-treated mice
bearing human tumor xenografts. Finally, this assay can be used to address nearly in real time
the drug-induced tumor cell apoptosis by using patient blood samples.
This method should be useful to facilitate the drug development process by bridging the gap
between screening of drugs to clinical phase I studies.
[1] Linder S, Havelka AM, Ueno T, Shoshan MC. Determining tumor apoptosis and necrosis
in patient serum using cytokeratin 18 as a biomarker.
Cancer Lett. (2004) 214: 1-9
- 368 -