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[Growth chamber assay, a novel chemosensitivity test which eliminates normal stromal cells]
Abstract:
The chemosensitivity test with growth chamber (GC), a semi permeable polymer matrix, was conducted using human tumor xenografts, comparing the results with those of in vivo nude mouse system. Xenografts used were MX-1, St-4, Co-3, and Co-4. Normal stromal cells, SM-74, a cell line derived from human adult skin fibroblast, and Clone-A-31, a cell line from BALB/c nu/nu nude mice were used as the control. Dissociated tumor cell suspension in 200 microliters of Medium 199 was plated into GC (80,000 cells, chamber) and incubated with a various concentration of mitomycin C(MMC), cisplatin (DDP), 5-fluorouracil (5-FU), and adriamycin (ADM) at the various concentrations. After incubation of 1 wk, the activity of hexosaminidase was measured with ELISA assay using p-nitrophenyl-N-acetyl-glucosaminide. The antitumor activity of the agents against human tumor xenografts was dose dependent, and the antitumor spectra obtained by GC assay was essentially identical to in vivo nude mouse system. On the other hand, no evaluable optical density could be obtained with normal stromal cells, SM-74 and Clone-A-31. The optimal cutoff concentration of each drugs to predict the in vivo results was estimated to be 10 micrograms/ml for MMC, 15 micrograms/ml for DDP and 5-FU, and 0.7 microgram/ml for ADM. The predictability of GC assay was 77%, including 89% sensitivity and 70% specificity. Since GC assay could eliminate the normal stromal cells because of the characteristic of chamber surface, this assay was thought to be useful for the clinical chemosensitivity test of human cancers containing a large number of normal stromal cells.
Insights
A novel growth chamber (GC) assay accurately predicts patient tumor chemosensitivity, showing results identical to traditional nude mouse models. This method effectively excludes normal cells, offering a promising tool for clinical cancer treatment selection.
Area of Science:
- Oncology
- Biotechnology
- Pharmacology
Context:
- Evaluating the efficacy of chemotherapy requires reliable predictive models.
- Traditional in vivo nude mouse models are effective but resource-intensive.
- Developing cost-effective and accurate in vitro chemosensitivity assays is crucial for personalized cancer therapy.
Purpose:
- To assess the efficacy of a novel growth chamber (GC) assay for predicting human tumor chemosensitivity.
- To compare the predictive accuracy of the GC assay with established in vivo nude mouse models.
- To determine the optimal drug concentrations for predicting in vivo responses using the GC assay.
Summary:
- Human tumor xenografts (MX-1, St-4, Co-3, Co-4) were tested in a growth chamber (GC) assay using mitomycin C, cisplatin, 5-fluorouracil, and adriamycin.
- The GC assay demonstrated dose-dependent antitumor activity and produced results essentially identical to in vivo nude mouse systems.
- Normal stromal cells (SM-74, Clone-A-31) did not yield evaluable results, indicating the assay's specificity for tumor cells.
Impact:
- The GC assay achieved 77% predictability, with 89% sensitivity and 70% specificity, closely mirroring in vivo outcomes.
- This assay's ability to exclude normal stromal cells makes it a valuable tool for clinical chemosensitivity testing in human cancers.
- The GC assay offers a potentially more efficient and clinically relevant method for guiding chemotherapy selection.