Aim 2. Toxicity testing. In these experiments we aim to establish the maximum tolerated dose (MTD) of each drug, using the recommended dosing schedule. We will measure weight gain/loss and will assess toxicity through additional parameters (e.g. haematology analysis).
Aim 3. Efficacy testing. In these experiments we will measure the effects of drugs on the progression of the leukaemia, measured as the proportion of human leukaemic cells in the peripheral blood. We will do this either as a typical efficacy study, or as a single mouse trial. We may also measure the progression of the leukaemia using bioluminescence in concert with the proportion of human leukaemic cells in the blood. At the experimental endpoints mice will be euthanased and engraftment …show more content…
Weight monitoring occurs weekly or more frequently if there are signs of toxicity due to drug treatment. Tail vein bleeding for haematology or biochemical markers assessment also occurs throughout the study period at a maximum frequency of once per week. In order to obtain a blood sample from the tail vein, the mice are first heated, with careful monitoring, in front of an infra-red heat lamp. They are then placed in a restraint that leaves them with free body movement; however their tail is partially immobilised by the researcher holding it. Then either of the lateral tail veins is punctured with a needle and blood is collected drop-wise. No more than 0.14 mL of blood is taken. This volume is the minimum required to complete the haematology and biochemistry analyses. Animals will be euthanased at set endpoints. Typically the main endpoint is the end of a three week monitoring period which begins after the last drug dose; however there can be earlier timepoints to look for signs of toxicity only noticeable upon necropsy (e.g. organ toxicity due to the drug
Aim 3. Efficacy testing. In these experiments we will measure the effects of drugs on the progression of the leukaemia, measured as the proportion of human leukaemic cells in the peripheral blood. We will do this either as a typical efficacy study, or as a single mouse trial. We may also measure the progression of the leukaemia using bioluminescence in concert with the proportion of human leukaemic cells in the blood. At the experimental endpoints mice will be euthanased and engraftment …show more content…
Weight monitoring occurs weekly or more frequently if there are signs of toxicity due to drug treatment. Tail vein bleeding for haematology or biochemical markers assessment also occurs throughout the study period at a maximum frequency of once per week. In order to obtain a blood sample from the tail vein, the mice are first heated, with careful monitoring, in front of an infra-red heat lamp. They are then placed in a restraint that leaves them with free body movement; however their tail is partially immobilised by the researcher holding it. Then either of the lateral tail veins is punctured with a needle and blood is collected drop-wise. No more than 0.14 mL of blood is taken. This volume is the minimum required to complete the haematology and biochemistry analyses. Animals will be euthanased at set endpoints. Typically the main endpoint is the end of a three week monitoring period which begins after the last drug dose; however there can be earlier timepoints to look for signs of toxicity only noticeable upon necropsy (e.g. organ toxicity due to the drug