Mécanismes impliqués dans la régulation de la biogenèse mitochondriale de tumeurs rénales (carcinomes à cellules claires et oncocytomes)

Le but de ce travail était de comprendre les mécanismes liés aux déficiences mitochondriales dans les cancers.Dans des tumeurs rénales graves, les CRCC, l absence du gène vhl fonctionnel est corrélée à la diminution des complexes des OXPHOS. La stabilisation du facteur de transcription HIF ("Hypoxia-inducible factor") due à la déficience de vhl doit être associée à une augmentation de la production de ROS pour induire ce phénomène. Si HIF est stabilisé par du CoCl2, celui-ci peut exercer un effet toxique additionnel en inhibant le clivage du précurseur d'une sous unité de la cytochrome c oxydase, la COX4, et empêcher ainsi l'assemblage de ce complexe. Dans les oncocytomes rénaux, tumeurs bénignes caractérisées par une prolifération mitochondriale, l'identification de mutations de l'ADN mitochondrial du complexe I et/ou du complexe IV suggère que la prolifération soit due à une induction de la biogenèse similaire à celle observée dans des pathologies mitochondriales typiquesThis thesis aimed at better understanding the origins of mitochondrial disorders in renal tumors. The CRCC that are often associated with poor prognosis in patients, and characterized by vhl invalidation, exhibit a decrease in OXPHOS complexes. This phenomenon could be due both to HIF (Hypoxia-inducible factor) stabilization induced by the lack of pVHL in CRCC and to an increase in ROS production. HIF can also be stabilized by cobalt treatment but this compound brings additional toxic effects, since it inhibits the processing of a precursor of the cytochrome c oxidase 4 subunit and therefore prevents the cytochrome c oxidase assembly.On the opposite, renal oncocytoma, that are non-malignant tumors are characterized by mitochondrial proliferation. We identified mutations in mitochondrial DNA genes of complex I or IV, which might suggest that the mitochondrial proliferation in these tumors is similar to that observed in typical mitochondrial pathologiesLYON1-BU.Sciences (692662101) / SudocSudocFranceF

Psychological functioning associated with prostate cancer : cross-sectional comparison of patients treated with radiotherapy, brachytherapy, or surgery

This study compared the prevalence of psychological difficulties (i.e., anxiety and depression), psychophysiological problems (i.e., insomnia and fatigue), and sexual difficulties across three modalities of treatment for prostate cancer (radiotherapy, brachytherapy, and radical prostatectomy). A total of 861 men completed a battery of questionnaires assessing anxiety, depression, fatigue, insomnia, and quality of life. Patients who initially received radiotherapy had higher levels of depression, anxiety, and fatigue and a lower quality of life, and were more likely to report clinical levels of depression and fatigue. Patients who initially received surgery were more likely to report clinical levels of sexual difficulties but less likely to report clinical levels of depression and fatigue, while patients who received brachytherapy were less likely to report sexual difficulties. Although cross-sectional, these findings raise the possibility of a differential influence of treatments for prostate cancer on some aspects of psychological functioning