Title
The potential of platinum-DNA adduct determination in ex vivo treated tumor fragments for the prediction of sensitivity to cisplatin chemotherapy
Author
Welters, M.J.P.
Braakhuis, B.J.M.
Jacobs-Bergmans, A.J.
Kegel, A.
Baan, R.A.
van der Vijgh, W.J.F.
Fichtinger-Schepman, A.M.J.
Centraal Instituut voor Voedingsonderzoek TNO TNO Voeding
Publication year
1999
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.
Subject
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
To reference this document use:
http://resolver.tudelft.nl/uuid:4b335aea-2325-4e05-8dc9-6d8ffcfcddd6
DOI
https://doi.org/10.1023/a:1008324803494
TNO identifier
234881
ISSN
0923-7534
Source
Annals of Oncology, 10 (1), 97-103
Document type
article