Repository hosted by TU Delft Library

Home · Contact · About · Disclaimer ·
 

The potential of platinum-DNA adduct determination in ex vivo treated tumor fragments for the prediction of sensitivity to cisplatin chemotherapy

Publication files not online:

Author: Welters, M.J.P. · Braakhuis, B.J.M. · Jacobs-Bergmans, A.J. · Kegel, A. · Baan, R.A. · Vijgh, W.J.F. van der · Fichtinger-Schepman, A.M.J.
Type:article
Date:1999
Institution: Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding
Source:Annals of Oncology, 1, 10, 97-103
Identifier: 234881
doi: doi:10.1023/A:1008324803494
Keywords: Nutrition · Ex vivo · Response · Antineoplastic agent · Animal experiment · Animal model · Cancer chemotherapy · Cancer graft · Clinical article · Head and neck carcinoma · Mouse · Nonhuman · Nude mouse · Prediction · Squamous cell carcinoma · Testis cancer · Tumor biopsy · Clinical trial · Comparative study · Culture technique · Drug resistance · Genetics · Head and neck tumor · Prediction and forecasting · Testis tumor · Adult · Aged · Antineoplastic Agents · Carcinoma, Squamous Cell · Cisplatin · Culture Techniques · DNA Adducts · Drug Resistance, Neoplasm · Female · Head and Neck Neoplasms · Humans · Male · Middle Aged · Predictive Value of Tests · Sensitivity and Specificity · Testicular Neoplasms

Abstract

Background: Response to cisplatin-therapy is assumed to be related to the formation of platinum (Pt)-DNA adducts. Measurement of these adducts prior to therapy could be of value to improve cisplatin based cancer therapy. Materials and methods: We determined Pt-GG and Pt-AG adduct levels by use of 32P-postlabeling after ex vivo cisplatin treatment of fragments of head and neck squamous cell carcinoma (HNSCC) xenografts (five lines), and of tumor biopsies from patients with HNSCC (n = 8) and testicular cancer (n = 8). Results: Adduct levels in fragments (3 x 3 x 3 mm) exposed to 10 to 80 μM cisplatin for one hour, showed positive correlations with the in vivo response to cisplatin treatment (P < 0.05), as well as with the xenograft adduct levels observed after in vivo cisplatin treatment (P < 0.02). After an additional five-hour drug-free incubation period the correlations were absent. When patient tumor fragments were exposed ex vivo to 80 μM cisplatin for one hour, adduct levels were similar in HNSCC and testicular cancer. Persistence of adducts was observed for testicular cancer in the additional drug-free period. The adduct levels in the samples of two HNSCC patients who received cisplatin chemotherapy were in line with the hypothesis that higher adduct levels are associated with a better response. Conclusion: Our preliminary results show that analysis of DNA adducts following ex vivo drug treatment is a feasible approach towards a predictive assay, which warrants further investigation.