When studying animal cancer models, the animals may experience tumor growth and possibly metastasis. Human endpoints should be determined thoughtfully to minimize pain and stress prior to the start of the study. To maximize data collection and minimize suffering, the animal’s health and welfare must be monitored regularly as the tumour progresses.
Tumour size and humane endpoint
Tumour size should not be the sole humane thendpoint in experiment planning. The following criteria should also be considered:
- Ulceration or bleeding on tumour
- Position of tumour affecting normal behaviour, eating or drinking
- Body Condition Score
- Overall condition of animal
For subcutaneous implanted tumour, the tumour growth rate is dependent on the cell line, animal strain, and the availability of treatment. The xenograft growth rate should be referenced when determining animal monitor schedule.
Non-subcutaneous tumours & induced tumours
When the tumour cannot be measured by a caliper, in-vivo imaging techniques should be used to monitor tumour growth.
Why should I keep my animal’s tumour under 2cm3?
Currently, the guidelines for solid tumour size is 2cm3 or <15% bodyweight. Solid tumours can be measured by a Caliper. The tumour burden is estimated by mass of tumour (volume=g)/Body weight.
In human, up to 85% of cancer patients report pain and discomfort, it is reasonable to assume laboratory animals experience pain and stress as tumour progresses.
Chronic pain and stress in animals can be a potential source of experimental deviation, with alterations in physiological, immunological, endocrine and behaviour. In addition, stress is known to affect cancer progression. Therefore it is important to limit unnecessary suffering of the animal to gain better research outcomes.
Stress is known to be an immunomodulator. Studies have suggested β-adrenergic receptors, activated by adrenaline and noradrenaline via psychological stress, inflammation and physical activities, can alter magnitude and quality of immune response, which ultimately affects progression of malignancies.
Immobilized Restraint stress promotes tumour growth in CAL27 xenograft model, higher level of plasma catecholamines, more MMP-2 and VEGF2. Similarly, a model with C42 xenografts also found restraint stress promotes prostate carcrinogenesis in an adrenaline-dependent manner3.