Treatment of malignant brain tumors using Buparlisib and Trametinib
Background
Malignant brain tumors are associated with poor patient prognosis, and current treatments are not effective. To study brain metastases, appropriate preclinical models are needed. We have established unique animal models for studying metastatic progression, by injecting human metastatic tumor cells into the left cardiac ventricle of immunodeficient mice. We will study treatment effects by using Buparlisib and Trametinib. We have preliminary data, showing that brain metastasis cells are effectively inhibited in vitro.
Aim of the research
The aim of this project is to show that Buparlisib and Trametinib either alone or combined can be used effectively to treat patients with malignant brain
Expected harm to the animals
The compounds that we want to test on the mice, do not cause any harm to the animals, as they are already approved for use on patients. Injections and imaging is causing mild harm to the animals, while tumor growth in the brain will cause moderate harm to the animals.
Expected benefit for science and society
We hope to achieve an improved treatment of patients with malignant brain tumors.
How many and kind of animals to be used
96 nod/scid mice.
How the demand on RRR is to be achieved
We need to use animal models in our research, as in vitro models do not reflect the 3d structural behavior and physiological conditions in animals, and these conditions are crucial for intracranial tumor growth. Therefore, in vitro experiments are not sufficient to obtain our aim, which is to bring new treatment into the clinic.
Refinement: The injection techniques used, is causing mild harm to the animals. We use 2 trained people during the injections, one responsible for the injections, and the other responsible for animal care. The animals are placed onto a heating pad, and we use ultrasound guidance during intracardiac injections, which ensure fast and accurate injections. We use analgetics, to make the injection procedure as indulgent as possible. During imaging, two trained persons are present, one to prepare and monitor the animals, and the other to operate the imaging instrumentation. Heating is used. The imaging procedures do not cause any harm to the animals.
Regarding tumor development; the animals are monitored daily by trained people, and weighed twice/week. Regular imaging as described is important, as this will reveal tumor burden before detecting any symptoms in animal behavior. The last two weeks before sacrifice, the animals show progressive signs of discomfort, and analgetics will be considered.
Reduction: We are using ultrasound-guided injections of tumor cells into the left cardiac ventricle of the mice, which increases our success rate from previous 80% (when we did free-hand injections) to 100%. Thus, we can cut down the number of animals in each experimental group with 2 animals (from 14 to 12 animals).
Malignant brain tumors are associated with poor patient prognosis, and current treatments are not effective. To study brain metastases, appropriate preclinical models are needed. We have established unique animal models for studying metastatic progression, by injecting human metastatic tumor cells into the left cardiac ventricle of immunodeficient mice. We will study treatment effects by using Buparlisib and Trametinib. We have preliminary data, showing that brain metastasis cells are effectively inhibited in vitro.
Aim of the research
The aim of this project is to show that Buparlisib and Trametinib either alone or combined can be used effectively to treat patients with malignant brain
Expected harm to the animals
The compounds that we want to test on the mice, do not cause any harm to the animals, as they are already approved for use on patients. Injections and imaging is causing mild harm to the animals, while tumor growth in the brain will cause moderate harm to the animals.
Expected benefit for science and society
We hope to achieve an improved treatment of patients with malignant brain tumors.
How many and kind of animals to be used
96 nod/scid mice.
How the demand on RRR is to be achieved
We need to use animal models in our research, as in vitro models do not reflect the 3d structural behavior and physiological conditions in animals, and these conditions are crucial for intracranial tumor growth. Therefore, in vitro experiments are not sufficient to obtain our aim, which is to bring new treatment into the clinic.
Refinement: The injection techniques used, is causing mild harm to the animals. We use 2 trained people during the injections, one responsible for the injections, and the other responsible for animal care. The animals are placed onto a heating pad, and we use ultrasound guidance during intracardiac injections, which ensure fast and accurate injections. We use analgetics, to make the injection procedure as indulgent as possible. During imaging, two trained persons are present, one to prepare and monitor the animals, and the other to operate the imaging instrumentation. Heating is used. The imaging procedures do not cause any harm to the animals.
Regarding tumor development; the animals are monitored daily by trained people, and weighed twice/week. Regular imaging as described is important, as this will reveal tumor burden before detecting any symptoms in animal behavior. The last two weeks before sacrifice, the animals show progressive signs of discomfort, and analgetics will be considered.
Reduction: We are using ultrasound-guided injections of tumor cells into the left cardiac ventricle of the mice, which increases our success rate from previous 80% (when we did free-hand injections) to 100%. Thus, we can cut down the number of animals in each experimental group with 2 animals (from 14 to 12 animals).