No description available.

Currently, many patients with early-stage localized prostate cancer (PrCa) (D’Amico: low risk or low-intermediate risk) do not receive immediate therapy but are monitored within systematic AS programs. Prospective trials showed rates of stage reclassification and progression to the treatment of 20–40% over 2–5 years. However, in certain patients, PrCa progresses rapidly to an advanced stage that requires combined modality therapies, which carry increased risk for toxicity and poor outcomes. There is a need to identify biomarkers that can predict the risk for disease progression in this population. Research showed that dysregulation of metabolism is an important hallmark of cancer progression. Here, we pursued a pilot investigation of enzymes of de novo lipogenesis [ATP-citrate lyase (ACLY), Acetyl-CoA Carboxylase (ACC)], lipid oxidation [a-Methylacyl-CoA Racemase (AMACR)], glucose uptake [facilitative glucose transporter 1 (GLUT1)], and folate – glutamate metabolism (PSMA: prostate-specific membrane antigen) as potential biomarkers of PrCa progression in AS patients. With ethics approval from the Hamilton Integrated Research Ethics Board (HiREB), 40 AS patients were accrued prospectively from the Niagara Health System PrCa diagnostic program clinics and were asked to donate their biopsy tissue. 28 patients progressed on repeat biopsies at 12 or 24 months after initial diagnosis and were included in the “Progressed” group, and 12 did not who were included in the “Non-Progressed” group. Baseline diagnostic prostate core biopsy tissues of both groups were evaluated with H&E and immunohistochemistry (IHC) staining for ACLY, ACC, GLUT1, AMACR and PSMA expression (quantified by H-score). H-scores were evaluated in benign and malignant components (epithelial cells) and were compared between the two groups of patients. We observed statistically significant increased GLUT1 expression in malignant epithelial cells of the progressed group compared to the non-progressed group. Also, we found statistically significant increased PSMA expression in the benign epithelial cells of the progressed group compared to the non-progressed group. Further, our results demonstrated a statistically significant increase in ACLY and ACC expression in malignant epithelial cells compared to benign epithelial cells in the progressed group, while AMACR was detected solely in the malignant component. Overall, the results of this pilot study are consistent with the notion of induction of glycolytic metabolism, de novo lipogenesis and increased PSMA expression associated with the risk for PrCa progression. The levels of expression of PSMA within benign epithelial cells and GLUT1 within malignant epithelial cells may have value as predictive markers of risk for PrCa progression in AS patients. Future studies should investigate this concept systematically in larger AS cohorts. / Thesis / Master of Science (MSc) / Currently, many patients with localized prostate cancer do not receive immediate therapy and are monitored within systematic active surveillance (AS) programs. The main aim of AS management is to prevent overtreatment and treatment-related complications in patients who would otherwise have a good quality of life despite dealing with prostate cancer. However, many of these patients, especially those with low intermediate-risk prostate cancer have a significant risk for disease progression and metastasis. Additionally, there is a lack of promising tissue biomarkers to predict the risk for progression in AS patients at the time of initial diagnosis. Research showed that metabolism dysregulation is an essential hallmark of cancer progression, including prostate cancer. In this pilot study, we examined whether the expression of enzymes involved in lipid, glucose and protein metabolism could have value as biomarkers of risk for prostate cancer progression in patients managed with AS. The expression of five metabolic enzymes (ACLY, ACC, GLUT1, AMACR and PSMA) was examined in tumor and benign regions of diagnostic biopsies of the prostate obtained from men managed with AS. Our early results suggest that the expression of enzymes of protein (PSMA) and glucose (GLUT1) metabolism may have value as biomarkers of risk for prostate cancer progression and should be investigated further in systematic studies.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

Morphologic and metabolic change is a known property of the adult brain. A number of behavioural tasks alter local cerebral blood flow and glucose utilisation. The expression of the glucose transporter 1 (GLUT1), which allows the entry of glucose to the brain, also has been shown to change in response to long-lasting neuronal activation. However, little is known about the effect of acute neuronal activation on GLUT1 expression. Using immunohistochemistry and Western blot, we investigated cerebral GLUT1 expression and vasculature density in mice undergoing a 48-hour voluntary wheel running period. The results showed that the striatum was the main region where GLUT1 protein was up-regulated: There was a trend for GLUT1 expression and blood vessels density to be associated with the distance run during the experiment. These results indicate that short-term increased neuronal activation is associated with rapid changes in glucose transport and possibly vascular remodelling.

No description available.

The intestinal epithelium is able to adapt to varying blood flow and, thus, oxygen availability. Still, the adaptation fails under pathologic situations. A better understanding of the mechanisms underlying the epithelial adaptation to hypoxia could help to improve the therapeutic approach. We hypothesized that the short-term adaptation to hypoxia is mediated via AMP-activated protein kinase (AMPK) and that it is coupled to the long-term adaptation by a common regulation mechanism, the HIF-hydroxylase enzymes. Further, we hypothesized the transepithelial transport of glucose to be part of this short-term adaptation. We conducted Ussing chamber studies using isolated lagomorph jejunum epithelium and cell culture experiments with CaCo-2 cells. The epithelia and cells were incubated under 100% and 21% O2, respectively, with the panhydroxylase inhibitor dimethyloxalylglycine (DMOG) or under 1% O2. We showed an activation of AMPK under hypoxia and after incubation with DMOG by Western blot. This could be related to functional effects like an impairment of Na+-coupled glucose transport. Inhibitor studies revealed a recruitment of glucose transporter 1 under hypoxia, but not after incubation with DMOG. Summing up, we showed an influence of hydroxylase enzymes on AMPK activity and similarities between hypoxia and the effects of hydroxylase inhibition on functional changes.

No description available.

Les glandes sous-maxillaires sécrètent au repos la majorité de la salive totale. Parmi ses principales substances la constituant, la salive contient également du glucose. Le but de ce travail de recherche est de tenter de comprendre le mécanisme de transport du glucose dans la salive. Des études immunohistochimiques ont été menées sur tissus sous-maxillaires humains. GLUT1, GLUT4 et SGLT1 ont été détectés au niveau des cellules ductales des glandes sous-maxillaires alors que les cellules acinaires semblent équipées principalement de GLUT1 et SGLT1. GLUT2, dans les cellules ductales humaines, semble présent de manière peu importante.Sur glandes sous-maxillaires de rats, les études d’immunohistochimie, de Western blot et de qRT-PCR ont révélé la présence de GLUT1, de GLUT4 et de SGLT1 au niveau des cellules ductales. Les cellules acinaires, quant à elles, révèlent la présence de GLUT1 et de SGLT1. Les études concernant la capture de glucose et le métabolisme de glucose sur glandes sous-maxillaires de rats ont indiqué que le glucose était transporté par les cellules ductales et les cellules acinaires. Cependant, les cellules ductales transportent plus rapidement le glucose et le métabolisent 2 à 3 fois plus que les cellules acinaires. Les cellules ductales, en présence d’agents inhibiteurs tels que la cytochalasine B ou la phloridzine, capturent moins de glucose par le biais de GLUT1 et SGLT1, respectivement. Dans les cellules acinaires, seule la cytochalasine B inhibe le transport du glucose. SGLT1 semble très peu fonctionnel au niveau des cellules acinaires. L’une des originalités de ce travail repose également sur la mise en évidence de la présence du transporteur GLUT4, insulino-dépendant, dans les cellules ductales de glandes sous-maxillaires. Sur anneaux ductaux, l’insuline a démontré sa capacité à stimuler la capture de glucose. Eu égard à leur localisation préférentiellement basolatérale, la présence de 3 transporteurs (GLUT1, GLUT4 et SGLT1) dans les cellules ductales et de 2 transporteurs (SGLT1 et GLUT1) dans les cellules acinaires devrait permettre à ces cellules de subvenir à leurs besoins métaboliques. Ceci est particulièrement important au niveau des cellules ductales où un remaniement majeur des flux ioniques nécessite un soutien métabolique conséquent, surtout en période prandiale. / Doctorat en Sciences dentaires / info:eu-repo/semantics/nonPublished