Preclinical testing of drugs against sarcoma
1.Purpose:
We have performed a high-throughput in vitro drug screen of drugs already in clinical use or under trial for other cancer types, and now wish to validate these in vitro findings in our patient-derived xenografts (PDXs) in mice.
2.Distress:
Tumours will be grown subcutaneous so the mice will not develop systemic disease or metastases. However, due to surgical implantation and long time treatment and monitoring, we classify the severity of the experiment as moderate.
3. Expected benefit:
For the experiments, we plan to evaluate efficacy of two drugs in up to five sarcoma models. The results should give us an indication where they could be translated to a clinical setting.
4. Number of animals and what kind
We plan to use 120 immunodeficient mice (NSG).
5. How to adhere to 3R
We are expecting minimum impact of the treatment on the animal welfare. The administration of the drugs will be executed by trained technicians.
These mice are the only animals which will successfully engraft a manner of human cell lines and patient material, essential to development of therapeutics.The only in vitro alternative is the use of cell lines and primary patient material in culture. However , these results do not always translate into efficacy in intact biological entities.In addition, we cannot use cell culture studies evaluate systemic toxic or efficacy effects, thus the use of animal models is unavoidable.
The number of animals described in this application is the minimum number of animals required to definitively answer the current research hypothesis.
Due to the fact that the vehicle used for both drugs is saline, we'll test both drugs in parallel with only one Control group.
Animals will be closely monitored by experienced technicians that can very early discover any sign of illness or severe distress, and can make the decision of euthanasia, if necessary. Details are given in the"score form". All cages will have environmental enrichment.
We have performed a high-throughput in vitro drug screen of drugs already in clinical use or under trial for other cancer types, and now wish to validate these in vitro findings in our patient-derived xenografts (PDXs) in mice.
2.Distress:
Tumours will be grown subcutaneous so the mice will not develop systemic disease or metastases. However, due to surgical implantation and long time treatment and monitoring, we classify the severity of the experiment as moderate.
3. Expected benefit:
For the experiments, we plan to evaluate efficacy of two drugs in up to five sarcoma models. The results should give us an indication where they could be translated to a clinical setting.
4. Number of animals and what kind
We plan to use 120 immunodeficient mice (NSG).
5. How to adhere to 3R
We are expecting minimum impact of the treatment on the animal welfare. The administration of the drugs will be executed by trained technicians.
These mice are the only animals which will successfully engraft a manner of human cell lines and patient material, essential to development of therapeutics.The only in vitro alternative is the use of cell lines and primary patient material in culture. However , these results do not always translate into efficacy in intact biological entities.In addition, we cannot use cell culture studies evaluate systemic toxic or efficacy effects, thus the use of animal models is unavoidable.
The number of animals described in this application is the minimum number of animals required to definitively answer the current research hypothesis.
Due to the fact that the vehicle used for both drugs is saline, we'll test both drugs in parallel with only one Control group.
Animals will be closely monitored by experienced technicians that can very early discover any sign of illness or severe distress, and can make the decision of euthanasia, if necessary. Details are given in the"score form". All cages will have environmental enrichment.