Related Experiment Videos
Tissue concentrations of doxorubicin in animal models with engrafted intraocular tumours
L White1, K K Chan, A Barrientos
1Children's Leukaemia and Cancer Research Unit, Prince of Wales Children's Hospital, University of New South Wales, Sydney, Australia.
Abstract:
The role of chemotherapy in the management of retinoblastoma remains unclear. In order to evaluate the responsiveness to conventional or experimental agents, a xenograft model had been developed, where human retinoblastoma is heterotransplanted to the anterior chambers of nude mouse eyes. Because doxorubicin had been found to be ineffective in therapeutic studies utilizing the model, experiments were conducted to evaluate the concentration of the drug in tissues, including intraocular engrafted tumour. The presence of doxorubicin was demonstrated in xenograft containing mouse eyes as well as in tumours of a comparable rabbit model. Distribution in extraocular tissues was consistent with previously published data. It is concluded that failure of response to doxorubicin in the xenograft model is not explained by lack of tumour penetration by the drug.
Insights
Chemotherapy
Area of Science:
- Ophthalmology
- Oncology
- Pharmacology
Background:
- The role of chemotherapy in retinoblastoma management is not well-defined.
- A human retinoblastoma xenograft model in nude mice was developed to assess treatment responsiveness.
- Doxorubicin showed ineffectiveness in prior therapeutic studies using this model.
Purpose of the Study:
- To investigate the distribution of doxorubicin in ocular and tumor tissues within a retinoblastoma xenograft model.
- To determine if poor drug penetration explains doxorubicin's ineffectiveness.
Main Methods:
- Human retinoblastoma cells were heterotransplanted into the anterior chambers of nude mouse eyes.
- Doxorubicin concentration was measured in various tissues, including intraocular xenografts.
- A comparable rabbit model was also used for doxorubicin distribution analysis.
Main Results:
- Doxorubicin was detected in the eyes and intraocular tumors of the xenograft model mice.
- Doxorubicin presence was also confirmed in tumors from a rabbit model.
- Drug distribution in extraocular tissues aligned with existing literature.
Conclusions:
- The ineffectiveness of doxorubicin in the retinoblastoma xenograft model is not due to a lack of tumor penetration.
- Further research is needed to understand the mechanisms behind doxorubicin resistance in retinoblastoma.