Le CaP est fréquent et demeure une cause principale de mortalité et de morbidité chez l'homme. Il persiste un dilemme clinique concernant la prise en charge optimale des patients atteints de CaP en maladie localisée en raison de l'estimation imparfaite du risque de progression. Ainsi, il importe de développer de nouveaux biomarqueurs pour améliorer la classification du risque de progression après un traitement à visée curative. Le CaP est une maladie hormono-sensible pour laquelle les voies des estrogènes demeurent encore peu étudiées. Certaines études récentes supportent une association entre les niveaux des dérivés de l'estradiol et le risque de CaP. Nous croyons que l'estradiol (E₂) et ses dérivés des voies de la 2-, 4- et 16- hydroxylation, pourraient représenter des marqueurs de progression en raison de leurs propriétés de nature proliférative, angiogénique et apoptotique. La quantification absolue et précise de ces dérivés est désormais possible en raison du développement d'une méthode robuste de spectrométrie de masse en tandem avec chromatographie liquide par notre équipe de recherche. Notre étude portait sur l'évaluation de l'association entre les niveaux urinaires des dérivés de l'estradiol et les issues oncologiques défavorables, soient la récidive biochimique, la survenue de métastases et le décès. Des hommes atteints d'un CaP en stade de maladie localisée ont été sélectionnés dans la cohorte prospective et multi-institutionnelle PROCURE pour les étapes de découverte (n=259) et de validation (n=253). Notre étude a montré que la voie de la 16-hydroxylation semble favorable (rapport de risque (HR) entre 0.74-0.75; p<0.006) mettant en évidence un risque plus faible de récidive biochimique. À l'inverse, la voie de la 2-hydroxylation semble défavorable avec un risque accru de développer une maladie métastatique et de décès de près de 1.6 fois (p=0.028). Le potentiel prédictif de ces dérivés de l'estradiol est supporté par la plausibilité biologique. Ces composés stéroïdiens semblent pertinents à étudier plus en détail comme marqueurs pronostiques potentiels en CaP. / Prostate cancer (PCa) is a main and persisting cause of mortality and morbidity in men. A clinical equipoise remains concerning the optimal management of localized PCa. Indeed, the estimation of the risk of progression still needs to be perfected. Hence, the development or improvement of biomarkers to improve the estimation of the risk of progression after curative-aimed treatment is needed. PCa is a hormone-sensible disease in which estrogenic hormones have not been studied extensively. There were recent studies that supported an association between E₂ derivates and PCa risk. We believe that the E₂ derivates of the 2-, 4- and 16-hydroxylation could represent markers of progression risk through their proliferative, angiogenic and apoptotic related properties. The absolute and comprehensive quantification of these derivates was recently made possible with the development, by our research team, of a robust tandem mass spectrometry with liquid chromatography method. Our study aimed to estimate the associations between urinary levels of E₂ derivates and unfavorable oncologic outcomes, namely biochemical recurrence, metastasis, and death. Men with localized PCa were selected in the prospective and multi-institutional PROCURE cohort for the discovery cohort (n=259) and validation cohort (n=253). Our study has demonstrated that the 16-hydroxylation pathway seemed favorable and associated with a decreased risk of biochemical recurrence (hazard ratio between 0.74-0.75; p<0.006). On the contrary, the 2-hydroxylation pathway seemed unfavorable and associated with an increased risk of metastasis or death by close to 1.6-fold (p=0.028). The potential of E₂ derivates as biomarkers of progression is supported by biological plausibility and clinical evidence. Hence, these steroid compounds are most relevant targets that must be further studied as potential prognostic biomarkers of PCa.

The detection of predators by prey species is crucial in order to escape the threat posed by a predator. In mammals, the olfactory sensory system is commonly used to detect odors emitted by predators, and to determine how threatening the situation actually is. However, knowledge about this ability is still sparse and in some cases conflicting. The aim of the present study was therefore to assess whether CD-1 mice (Mus musculus) show behaviors such as avoidance, anxiety and/or decreased activity when exposed to any of the three odorants: cat bladder urine, horse voided urine or a fruity odor (N-pentyl acetate), with a blank solvent as an alternative in a two-compartment test arena. I found no significant differences between avoidance (the time that the mice spent in the different compartments), anxiety (the numbers of fecal pellets dropped by the mice), or the overall activity (the number of switches between the two compartments), when the mice were exposed to the three different odors. The fact that the cat urine derived from the bladder of the cat may explain the lack of avoidance responses, since bladder urine might not contain the same chemical components as voided urine. Bladder urine might therefore also lack the chemical components that signal “predator” to the mice. In conclusion, mice do not respond differently to the odor of cat bladder urine than to horse voided urine or to the fruity odor of N-pentyl acetate.

Introduction: It has been reported that the principal source of exposure for humans to inorganic arsenic (As) comes from drinking water. It is known that selenium (Se) competes with the reductive metabolism and methylation of As and Se compete for the availability of glutathione. The overarching goal of this dissertation research is to assess relationships between arsenic intake from water and other fluids with urinary arsenic output and then to assess how urinary arsenic output is modified by selenium exposure. Methods: Households in the Binational Arsenic Exposure Survey (BAsES) were selected for their varying groundwater arsenic concentrations. A first morning urine void and water samples from all household drinking sources were collected for As quantification. Relationships were examined between various urinary arsenic biomarkers and estimated arsenic exposures. The association between urinary arsenic biomarkers and dietary intake and urinary output of selenium was also evaluated. Results: Arizonans reported consuming 18.5 mL/kg-day of water and 34.3 mL/kg-day from all fluids. In contrast, participants from Mexico reported 3.5 mL/kg-day of water and 12.3 mL/kg-day from all fluids. Median urinary inorganic As concentration among Arizona participants (ranging from 1.2 to 2.0 µg/L) was lower than among participants from Mexico (range 2.5 to 6.2 µg/L). Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p<0.001), urinary inorganic arsenic concentration (p<0.001), and urinary sum of species (p<0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. No statistically significant relationships were seen between urinary methylated arsenic biomarkers with either dietary intake of selenium or the urinary selenium concentration. Conclusion: Water was the primary contributor to total fluid intake among Arizonans while Mexico participants primarily consumed carbonated beverages. Arsenic intake from water was significantly associated with urinary arsenic output; however, the concentration of arsenic consumed explained a small fraction of urinary arsenic levels. While selenium can biologically interact with arsenic in the liver, no relationship between urinary arsenic biomarkers were identified with either dietary intake of selenium or urinary output of selenium.

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Typewritten copy Includes bibliographical references.