Describe the objectives of the project (for example, addressing certain scientific unknowns, or scientific or clinical needs).
Cancer cachexia is a complex wasting syndrome characterized by involuntary skeletal muscle mass loss. This muscle wasting is dramatic and is directly responsible for about 20% of cancer deaths. The mechanisms involved in skeletal muscle wasting induced by cancer cells are poorly known and there currently exists no therapeutic treatment for cancer cachexia. Thus, there is urgent need to understand the cachexia process and find effective therapy, especially since cancer cachexia is estimated to affect up to 80% of advanced cancer patients. Physical exercise is well documented to affect skeletal muscle physiology. In this project, we will have 3 objectives. Objective 1 aims to Determine how breast and pancreatic cancer tumours cause cancer cachexia. Objective 2 aims to Determine whether exercise can counteract cancer cachexia. Objective 3 aims to Determine the role of transcription factors in cancer cachexia.
What are the potential benefits likely to derive from this project? Explain how science could be advanced, or humans, animals or environment may ultimately benefit from the project. Where applicable, differentiate between short-term benefits (within the duration of the project) and long-term benefits (which may accrue after the project is finished).
Our results will potentially lead to develop therapeutic strategies to fight cancer cachexia and improve survival and quality of live for many patients. We will test both male and female mice to address potential sex-dependent effects.
Predicted harms
In what procedures will the animals typically be used (for example, injections, surgical procedures)? Indicate the number and duration of these procedures.
See attachment "Hvilke prosedyrer skal hvert enkelt dyr igjennom i løpet av forsøket?"
What are the expected impacts/adverse effects on the animals, for example pain, weight loss, inactivity/reduced mobility, stress, abnormal behaviour, and the duration of those effects?
The tumor injection will cause cancer development in mice. As the project aims to study cancer cachexia, we will need the tumor injected mice to develop cachectic muscle, a situation expected to occur few weeks before death. These mice are thus expected to lose body weight and develop a wasting syndrome. Our evaluation of pain and human endpoint has been done based on a collaborator experience in the cancer field (Nina Richartz (FOTS 29016).
What species and numbers of animals are expected to be used? What are the expected severities and the numbers of animals in each severity category (per species)?
Species
Total number
Estimated numbers per severity
Non recovery
Mild
Moderate
Severe
Mice (Mus musculus)
300
0
40
200
60
Mice (Mus musculus)
520
0
40
480
0
What will happen to the animals kept alive at the end of the procedure?
Species
Estimated numbers of animals to be reused, to be returned to habitat/husbandry system or to be rehomed
Reused
Returned
Rehomed
Please provide reasons for the planned fate of the animals after the procedure.
At the end of the experiments, mice will be sacrificed in order to collect tissues. These tissues will be used for research purpose; better understanding of muscle cachexia.
Application of the Three Rs
1. Replacement
State which non-animal alternatives are available in this field and why they cannot be used for the purposes of the project.
We aim to investigate the development of cancer cachexia, the impact of exercise and transcription factor drug treatment on cancer cachexia. Performing our studies in intact mouse models is necessary as it closely recapitulates the cancer cachexia syndrome observed in humans.
No cellular models can mimic cancer cachexia or the effects of exercise training on skeletal muscle tissue.
2. Reduction
Explain how the numbers of animals for this project were determined. Describe steps that have been taken to reduce the number of animals to be used, and principles used to design studies. Where applicable, describe practices that will be used throughout the project to minimise the number of animals used consistent with scientific objectives. Those practices may include e.g. pilot studies, computer modelling, sharing of tissue and reuse.
We have the strict minimum number of animals to generate scientific results.
When possible we will use C57Bl6 mice from other FOTS applications to improve our 3Rs (reduction). For example, if a researcher/project is only using male mice (C57Bl6), we will use the female mice for our experiments (rather than killing the animals for no purpose).
3. Refinement
Give examples of the specific measures (e.g., increased monitoring, post-operative care, pain management, training of animals) to be taken, in relation to the procedures, to minimise welfare costs (harms) to the animals. Describe the mechanisms to take up emerging refinement techniques during the lifetime of the project.
Housing in IVC cage. Each cage will have environmental enrichment (nesting material, paper- and wood-derived material, plastic house) and animals will be manipulated weekly by experimenters (checking fur, eyes, locomotion, etc).
Anesthesia will be given during surgical procedures. An analgesic will be injected to minimize pain after surgical procedures after tumor cell injection and mice will be monitored regularly for any sign of distress.
Explain the choice of species and the related life stages.
C57/Bl6 mice are routinely used as cancer models. A genetically modified mouse line will also be used.
We want to study both females and males to determine whether the development of cancer cachexia is similar in males and females.
When addressing our 3 objectives, the age of mice used in the experimental groups will be similar so that comparison between groups is possible.
Project selected for Retrospective Assessment
Project selected for RA?
Yes
Deadline for RA
09-06-2027
Reasons for retrospective assessment
Contains severe procedures
Yes
Uses non-human primates
Other reason
Yes
Explanation of the other reason for retrospective assessment
The Norwegian Food Safety Authority must retrospectively assess all severe experiments. You are therefore required to submit necessary information making it possible for us to evaluate 1) whether the objectives of the project were achieved, 2) the harm inflicted on the animals, and 3) any elements that may contribute to further implementation of 3 R in future studies. This information must be submitted via FOTS.
Additional fields
National field 1
Field will not be published.
National field 2
Field will not be published.
National field 3
Field will not be published.
National field 4
Field will not be published.
National field 5
Field will not be published.
Project start date
Field will not be published.
Project end date
Field will not be published.
Project approval date
Field will not be published.
ICD code 1
Field will not be published.
ICD code 2
Field will not be published.
ICD code 3
Field will not be published.
Link to the previous NTS version outside the EC system