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The link between genetic induced obesity and cancer

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1 Formål
Obesity is linked to 15-20% of deaths related to cancer. As the global obesity epidemic intensifies, understanding the connection between obesity and cancer is a critical health issue. In particular, research that specifically aims at determining how cancer cells exploit the obese environment in the cancer patient is essential. In this study, we aim to map the role of obesity-induced tumor growth in genetic models of obesity (ob/ob mice). This will allow us to draw conclusions independent of dietary factors.

2 Skadevirkninger
The mice will be exposed to tumors. Our main endpoint is tumor formation. The tumors will thus be removed well before they reach a lethal size (typically around 100-200 mmm3). At this point the mice do typically not experience any systemic effects of the formed tumor

3 Forventet nytteverdi
Metabolic reprogramming is a tumor hallmark. Tumor reliance of glucuse and glutamine has both been established and are both being used for diagnostics (PET scanning) and as therapeutic targets. However, our understanding of how the metabolism of the host affects tumor and in particular tumor formation is not well known. We hope that this pilot study will lead to further insights into tumor metabolism.

4 Antall dyr og art
These studies will be performed in C57BL6 Ob/Ob and wild-type littermate mice. We ask to perform these studies using two breast cancer models and two pancreas cancer models. Total number of mice: 294

5 Hvordan etterleve 3R
Replace: Tumor growth and progression is a complex process, encompassing events such as invasive growth, angiogenesis, interaction with immune cells, and other members of the microenvironment. The use of traditional 2D and 3D in vitro assays does unfortunately not recapitulate all of these processes.
Reduce: We continuously aim at using the fewest possible mice for each experiment. The combined experience from our and other groups over the past 8 years has established that the minimum number of animals required to detect significant biological meaningful differences in tumor initiation studies is 6 mice per cohort.
Refine: The group has extensive experience in performing tumor implantation procedures, which ensure fast and reliable injections that inflict as little pain as possible for the mice. Here, both pre- and post-surgical analgesia will be used for pain relief.