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[Clinical studies on a rapid screening assay for anticancer agents with nude mice and isotopic evaluation]
Abstract:
A rapid method using nude mice has been established as an in vivo model for assessing the chemosensitivity of individual human tumors, in which the final evaluation is made with 3H-thymidine (3H-TdR) incorporation into the treated tumor. In 234 of 289 cancers, the chemosensitivity of anticancer agents was evaluated by this method. This assay proved to be feasible in a sufficiently high percentage of human primary tumors (81.0%). The rate of positive sensitivity against all tumors was 23.8% for MMC, 12.3% for 5-FU, 29.1% for CPM and 23.5% for ADM, respectively. The sensitivity of anticancer agents varied according to the type of cancer. Correlation between the sensitivity test and the end results after chemotherapy in cases of inoperable gastrointestinal cancers was investigated, prospectively. Out of 19 cases, the 50% survival time of 11 patients treated with sensitive agents was longer than that of 8 patients treated with insensitive agents. From a prospective-correlative study carried out on 25 patients, this assay appeared to be correlated with clinical response (overall agreement, 76.0%) with specific agreements of sensitivity and resistance of 37.5% and 94.1%, respectively. From these results, it seems reasonable to conclude that this sensitivity test using a human/nude mouse system is a useful screening assay for revealing appropriate agents for the treatment of patients with cancer.
Insights
A novel nude mouse model rapidly assesses individual human tumor chemosensitivity using 3H-thymidine incorporation. This in vivo assay shows promise for predicting patient response to chemotherapy and guiding treatment selection.
Area of Science:
- Oncology
- Pharmacology
- Animal Models
Context:
- Assessing anticancer agent efficacy is crucial for personalized cancer treatment.
- Existing chemosensitivity assays have limitations in speed and applicability to individual human tumors.
- The development of reliable in vivo models is essential for preclinical drug evaluation.
Purpose:
- To establish and validate a rapid in vivo chemosensitivity assay using nude mice for individual human tumors.
- To evaluate the feasibility and predictive accuracy of this assay in a clinical setting.
- To correlate the in vitro sensitivity test results with patient outcomes and clinical response.
Summary:
- A rapid in vivo method using nude mice was developed to assess human tumor chemosensitivity via 3H-thymidine incorporation.
- The assay demonstrated high feasibility (81.0%) across various human primary tumors.
- Chemosensitivity varied by cancer type, with specific drug sensitivities noted (e.g., MMC 23.8%, 5-FU 12.3%, CPM 29.1%, ADM 23.5%).
Impact:
- The assay showed a correlation with clinical outcomes in inoperable gastrointestinal cancers, with longer survival times for patients treated with sensitive agents.
- Prospective-correlative studies indicated a 76.0% overall agreement with clinical response, including high specificity for resistance (94.1%).
- This human/nude mouse chemosensitivity test serves as a valuable screening tool for selecting appropriate anticancer agents for individual patients.