ISSN:
1573-904X
Keywords:
chemosensitivity
;
histoculture
;
head and neck tumors
;
pharmacodynamics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract This investigation was to establish a clinically relevant experimental model to evaluate the pharmacodynamics of drugs used for head and neck cancers. A total of 83 surgical samples of primary and lymph nodal metastatic tumors was obtained from 66 patients. Fragments of these tumors were cultured on a collagen gel matrix. The tumor cell labeling index (LI) was determined by [3H]thymidine incorporation and autoradiography. Seventeen tumors (20%) were contaminated. About 80% of the remaining 65 tumors were successfully cultured for at least 2 weeks. The cultured tumor fragments retained the morphology and architecture of the freshly removed specimens; both tumor and stromal cells were present. The tumor cell LI after 2–3 weeks in culture, determined from the most proliferative area of the tissue, averaged 77 ± 12% for primary tumors and 78 ± 12% for nodal metastases. The activity of three clinically active agents, 5-fluorouracil (FU), cisplatin (DDP), and mitomycin C (MMC), was evaluated in 47 tumors. All three drugs inhibited the tumor LI. The concentrations needed to produce a 50% inhibition of the tumor LI (IC50) were within the clinically achievable concentration range. The intertumor variation in the IC50 for FU (60-fold) was considerably greater than that for DDP and MMC (7- to 8-fold). The nodal metastatic tumors appeared to be less sensitive to FU than the primary tumors, while there were no apparent differences for DDP or MMC. Tumors from patients previously treated with chemotherapy and/or radiotherapy appeared less sensitive to FU and DDP than tumors from untreated patients, but the differences were not statistically significant. Interestingly, tumors from previously treated patients were significantly more sensitive to MMC than tumors from untreated patients. The maintenance of the morphology of the fresh tumor and the observed intertumor variability in IC50 values indicate the preservation of intra- and intertumor heterogeneity in the histocultures. In summary the viability and high success rate of growth of human head and neck tumors in organ-like culture and the chemosensitivity of the cultured tumors to clinically active agents at clinically achievable concentrations support the use of this experimental model for pharmacodynamic evaluation.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1018935628085
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