Neuroblastoma is a tumour derived from cells of the nervous system and is the most common solid tumour in childhood. MYCN amplified and 11q-deleted neuroblastoma, two high-risk neuroblastoma were investigated in this study. RAD51 gene family includes six central genes for the dsDNA breaks repair by homologous recombination, which has been reported as important in varying types of cancer. The study aims to investigate if the dysregulation of this gene family could be involved in the unstable genome of 11q-deleted neuroblastoma, and to better understand the link between both high-risk tumours. The RAD51 family genes’ expression level was measured by RT-qPCR in samples of 11q-deleted and MYCN-amplified neuroblastoma that were treated with a UVC treatment and were recovered during varying hours. R2 database and DAVID were used to study the RAD51 family’s expression levels, associated event-free survivability, and altered pathways. RAD51 family is highly dysregulated in these tumours, four genes of six were found to be altered in high-risk neuroblastoma. Four of six genes presented altered expression levels in 11q-loss, and three of six in the MYCN-amplified case after the UVC treatment. The event-free survival probability analysis shown that the levels of expressions associated with high-risk neuroblastoma coincide with those that represent a poor life expectancy. Altered pathways were different in each type of tumour. 11q-deletion neuroblastoma’s pathways were associated with the nervous system development, and MYCN-amplified was related to the immune system. This study suggests that 11q-loss neuroblastoma presents a greater RAD51 family dysregulation compared with MYCN-amplified one, which could explain why its genome is unstable.

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Reduced levels of white adipocyte hormone adiponectin have been observed in obese individuals with type 2 diabetes (T2D). Higher adiponectin levels are monotonically associated with a lower risk of T2D and hence increasing circulating adiponectin levels is of great interest in diabetic research. A novel compound, called fibroblast growth factor 21 (FGF21), is showing great potential in treatment of obesity and T2D. In animal models with obesity and T2D FGF21 increases glucose uptake, improves lipid homeostasis, decreases fat mass and increases circulating adiponectin levels. In this study, theaim is to explore the acute effect of FGF21 on white adipocyte adiponectin secretion. Adiponectinsecretion experiments were performed on primary murine adipocytes incubated with FGF21 for 30minutes and adiponectin levels were measured with ELISA and normalised to total protein content.To study the signalling pathway of FGF21, a separate batch of murine adipocytes were pretreated with an Epac and PI3K inhibitor prior to addition of FGF21. Results from this thesis show that FGF21potently stimulates short-term adiponectin release via PI3K-dependent pathways with no effect on adiponectin synthesis.

Endometrial adenocarcinoma is a cancer that develops from the endometrium, from cells thatform the glands in the endometrium. Animal models such as the BDII rat have thecharacteristic property that they are prone to cancers, characterized by rapid tumor growth,that resemble human cancers. Such rat models are therefore used to study gene expression andsignal pathways in cancer. Cancer cells have the ability to invade surrounding tissues throughlymphatic and/or vascular circulation to produce secondary tumors at new sites. TheRho/ROCK pathway orchestrates cell motility thereby contributing in significantly tometastasis. ROCK, through phosphorylation of myosin phosphatase target subunit 1(MYPT1), inhibits MYPT1 and induces actomyosin contraction which contributes to manycellular processes. In this study, we were interested in investigating the expression of MYPT1and ROCK1 genes in malignant and non-malignant endometrial cell lines in BDII rat model,in human endometrial cancer cells represented by the Ishikawa cells line, and in humanembryonic kidney 293 (HEK293) human non-malignant control cells. Although statisticalsignificance was not reached due to the small sample size, a difference in the gene expressionlevels in malignant and non-malignant cells was observed. The results from the present studyshowed a higher expression of MYPT1 and ROCK1 genes in cancer cells (rat and human)compared to non-cancer cells, and we can conclude that this implicates the significance of theMYPT1/ROCK pathway in endometrial cancer and its deregulation.