https://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&feed=atom&action=historyBufe 2017 TRACT PhD project abstract - Revision history2024-03-28T21:28:41ZRevision history for this page on the wikiMediaWiki 1.36.1https://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&diff=171373&oldid=prevBeno Marija at 14:25, 23 January 20192019-01-23T14:25:37Z<p></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>As it was found out during the last years that cells undergo a distinct metabolic remodeling when turning into tumour cells, the investigation of this process might be highly relevant for future cancer research <sup>4</sup>. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have already identified the glycolytic pathway as a potential targetable pathway. With this, particularly mitochondria, which are the main energy producers of the cell and are involved in multiple regulatory pathways, may play key factors in the carcinogenesis and therefore should be focused over the course of this work.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>As it was found out during the last years that cells undergo a distinct metabolic remodeling when turning into tumour cells, the investigation of this process might be highly relevant for future cancer research <sup>4</sup>. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have already identified the glycolytic pathway as a potential targetable pathway. With this, particularly mitochondria, which are the main energy producers of the cell and are involved in multiple regulatory pathways, may play key factors in the carcinogenesis and therefore should be focused over the course of this work.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The stated PhD project will be conducted in the frame of the European Union's program “TRACT”, funded by a Marie Skłodowska-Curie fellowship. With the company <del style="font-weight: bold; text-decoration: none;">OROBOROS INSTRUMENTS </del>as a partner, it will aim at the examination of metabolic transformation mechanisms in OC with the attempt of identifying new drug targets for future therapeutic development and new diagnostic strategies.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The stated PhD project will be conducted in the frame of the European Union's program “TRACT”, funded by a Marie Skłodowska-Curie fellowship. With the company <ins style="font-weight: bold; text-decoration: none;">Oroboros Instruments </ins>as a partner, it will aim at the examination of metabolic transformation mechanisms in OC with the attempt of identifying new drug targets for future therapeutic development and new diagnostic strategies.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The work will further characterize the bioenergetic and metabolic properties of normal, metaplastic, dysplastic and cancerous oesophageal cells and identify differences between these stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using an <del style="font-weight: bold; text-decoration: none;">OROBOROS </del>Oxygraph 2k (O2k)-Fluorometer enabling the screening of real-time bioenergetics and metabolism of cells by the combination of high resolution respirometry (HRR) with fluorometry. By this, not only the cellular respiration (O<sub>2</sub> consumption) of cells or mitochondria can be analyzed, but also multiple other metabolic parameters including the mitochondrial membrane potential, ATP production (indirectly via the concentration of free Mg<sup>2+</sup>), Ca<sup>2+</sup> production and reactive oxygen (ROS) production (via H<sub>2</sub>O<sub>2</sub> concentration) <sup>5</sup>. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. To name an example, the production of ROS in mitochondria is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, probably leading to degenerative diseases or cancer <sup>6</sup>. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing or increasing it by adding specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OC.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The work will further characterize the bioenergetic and metabolic properties of normal, metaplastic, dysplastic and cancerous oesophageal cells and identify differences between these stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using an <ins style="font-weight: bold; text-decoration: none;">Oroboros </ins>Oxygraph 2k (O2k)-Fluorometer enabling the screening of real-time bioenergetics and metabolism of cells by the combination of high resolution respirometry (HRR) with fluorometry. By this, not only the cellular respiration (O<sub>2</sub> consumption) of cells or mitochondria can be analyzed, but also multiple other metabolic parameters including the mitochondrial membrane potential, ATP production (indirectly via the concentration of free Mg<sup>2+</sup>), Ca<sup>2+</sup> production and reactive oxygen (ROS) production (via H<sub>2</sub>O<sub>2</sub> concentration) <sup>5</sup>. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. To name an example, the production of ROS in mitochondria is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, probably leading to degenerative diseases or cancer <sup>6</sup>. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing or increasing it by adding specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OC.</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using <sup>2</sup>H/<sup>13</sup>C NMR to complement the respiratory and fluorometric measurements conducted with the O2k at <del style="font-weight: bold; text-decoration: none;">OROBOROS INSTRUMENTS</del>. The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma as well as human tissue biopsies of different stages of cancer -namely intestinal metaplasia, dysplasia, adenocarcinoma and non-cancerous tissue as control. For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using <sup>2</sup>H/<sup>13</sup>C NMR to complement the respiratory and fluorometric measurements conducted with the O2k at <ins style="font-weight: bold; text-decoration: none;">Oroboros Instruments</ins>. The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma as well as human tissue biopsies of different stages of cancer -namely intestinal metaplasia, dysplasia, adenocarcinoma and non-cancerous tissue as control. For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>By comparing the different types of cancerous tissue with the cell culture models of adenocarcinoma, the representativeness and reliability of the utilized cell models regarding their metabolic properties will be tested. With the inclusion of human tissues, the relevance and applicability of this study for the clinic is particularly ensured.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>By comparing the different types of cancerous tissue with the cell culture models of adenocarcinoma, the representativeness and reliability of the utilized cell models regarding their metabolic properties will be tested. With the inclusion of human tissues, the relevance and applicability of this study for the clinic is particularly ensured.</div></td></tr>
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</table>Beno Marijahttps://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&diff=134524&oldid=prevKandolf Georg at 11:42, 19 April 20172017-04-19T11:42:28Z<p></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div># Camara AKS, Lesnefsky EJ, Stowe DF. Potential Therapeutic Benefits of Strategies Directed to Mitochondria, Antioxidants & Redox Signaling, 13(3):279-347 (2010), doi:10.1089/ars.2009.2788.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div># Camara AKS, Lesnefsky EJ, Stowe DF. Potential Therapeutic Benefits of Strategies Directed to Mitochondria, Antioxidants & Redox Signaling, 13(3):279-347 (2010), doi:10.1089/ars.2009.2788.</div></td></tr>
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</table>Kandolf Georghttps://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&diff=133303&oldid=prevBufe Anja at 00:48, 29 March 20172017-03-29T00:48:24Z<p></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>On the whole, the main aim of this thesis is the identification of differences in the metabolic profiles of the examined states of cancer and, in hand with this, the metabolic transformation mechanisms taking place in OC. In so doing a basis of differential novel drug targets will be established and the progression of means to enhance the chemotherapeutic sensitivity of cancer cells identified.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>On the whole, the main aim of this thesis is the identification of differences in the metabolic profiles of the examined states of cancer and, in hand with this, the metabolic transformation mechanisms taking place in OC. In so doing a basis of differential novel drug targets will be established and the progression of means to enhance the chemotherapeutic sensitivity of cancer cells identified.</div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">== References ==</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"># Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide, IARC CancerBase, No. 11 (2013).</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"># Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA. SEER Cancer Statistics Review, 1975-2013, National Cancer Institute (2016).</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"># McCormick Matthews LH, Noble F, Tod J, et al. Systematic review and meta-analysis of immunohistochemical prognostic biomarkers in resected oesophageal adenocarcinoma, British Journal of Cancer, 113(1):107-118 (2015), doi:10.1038/bjc.2015.179.</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"># Smolková K, Plecitá-Hlavatá L, Bellance N, Benard G, Rossignol R, Ježek P. Waves of gene regulation suppress and then restore oxidative phosphorylation in cancer cells, The International Journal of Biochemistry & Cell Biology, 43(7):950-968 (2011), ISSN 1357-2725, doi: 10.1016/j.biocel.2010.05.003.</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"># Fasching M, Gradl P and Gnaiger E. The O2k-Fluo LED2-Module, Mitochondrial Physiology Network, 17.05(08):1-6 (2015).</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"># Camara AKS, Lesnefsky EJ, Stowe DF. Potential Therapeutic Benefits of Strategies Directed to Mitochondria, Antioxidants & Redox Signaling, 13(3):279-347 (2010), doi:10.1089/ars.2009.2788.</ins></div></td></tr>
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</table>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&diff=133302&oldid=prevBufe Anja at 00:33, 29 March 20172017-03-29T00:33:45Z<p></p>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2017</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|year=2017</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|event=TRACT</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|event=TRACT</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>|abstract=The <del style="font-weight: bold; text-decoration: none;">stated project will be conducted </del>in the <del style="font-weight: bold; text-decoration: none;">frame of the European Union's TRACT program</del>, <del style="font-weight: bold; text-decoration: none;">funded </del>by a <del style="font-weight: bold; text-decoration: none;">Marie Skłodowska</del>-<del style="font-weight: bold; text-decoration: none;">Curie fellowship</del>. <del style="font-weight: bold; text-decoration: none;">With </del>the <del style="font-weight: bold; text-decoration: none;">company OROBOROS INSTRUMENTS as </del>a <del style="font-weight: bold; text-decoration: none;">partner</del>, <del style="font-weight: bold; text-decoration: none;">it will aim at </del>the <del style="font-weight: bold; text-decoration: none;">examination </del>of <del style="font-weight: bold; text-decoration: none;">metabolic transformation mechanisms </del>in oesophageal cancer (OOC) <del style="font-weight: bold; text-decoration: none;">with </del>the <del style="font-weight: bold; text-decoration: none;">attempt </del>of <del style="font-weight: bold; text-decoration: none;">identifying new drug targets for future therapeutic development</del>.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>|abstract=<ins style="font-weight: bold; text-decoration: none;">To this day, cancer is still among the leading causes of death worldwide and predicted to catch up with heart diseases, which holds the first position for now, very soon <sup>1</sup>. </ins>The <ins style="font-weight: bold; text-decoration: none;">treatment is complex and </ins>in <ins style="font-weight: bold; text-decoration: none;">many cases ineffective. Especially for patients diagnosed with oesophageal cancer (OC) </ins>the <ins style="font-weight: bold; text-decoration: none;">odds are bad</ins>, <ins style="font-weight: bold; text-decoration: none;">which could be told </ins>by a <ins style="font-weight: bold; text-decoration: none;">5</ins>-<ins style="font-weight: bold; text-decoration: none;">year survival rate of only about 18%. Furthermore, the number of new cases and deaths did not markedly decrease over the last years for this type of cancer <sup>2</sup>. One reason for this is that up to this point no clinically useful molecular prognostic biomarkers exist and treatment options are very poor <sup>3</sup>. Therefore, it is strongly required to explore new ways and tools to carry on the fight against OC and cancerous diseases in general</ins>.</div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">As it was found out during </ins>the <ins style="font-weight: bold; text-decoration: none;">last years that cells undergo </ins>a <ins style="font-weight: bold; text-decoration: none;">distinct metabolic remodeling when turning into tumour cells</ins>, the <ins style="font-weight: bold; text-decoration: none;">investigation of this process might be highly relevant for future cancer research <sup>4</sup>. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants </ins>of <ins style="font-weight: bold; text-decoration: none;">drug resistance </ins>in <ins style="font-weight: bold; text-decoration: none;">oral and </ins>oesophageal cancer (OOC) <ins style="font-weight: bold; text-decoration: none;">have already identified the glycolytic pathway as a potential targetable pathway. With this, particularly mitochondria, which are the main energy producers of the cell and are involved in multiple regulatory pathways, may play key factors in the carcinogenesis and therefore should be focused over </ins>the <ins style="font-weight: bold; text-decoration: none;">course </ins>of <ins style="font-weight: bold; text-decoration: none;">this work</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">Metabolic transformation is a universal property of tumor formation and is a rich source of targets for development of therapeutic interventions 1. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have identified the glycolytic pathway as a potential targetable pathway. Hence, this work will further characterize the bioenergetic and metabolic properties of normal, dysplastic and cancerous oral cancer cells and identify differences between the different stages of carcinogenesis. </del>The <del style="font-weight: bold; text-decoration: none;">study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements </del>will be conducted <del style="font-weight: bold; text-decoration: none;">using the Oroboros Respirometer Multisensor system Oxygraph2k (O2k) enabling the screening of real-time bioenergetics and metabolism </del>in the <del style="font-weight: bold; text-decoration: none;">different stages </del>of <del style="font-weight: bold; text-decoration: none;">OCC. Due to </del>the <del style="font-weight: bold; text-decoration: none;">combination of high resolution respirometry (HRR) with optical methods</del>, <del style="font-weight: bold; text-decoration: none;">namely fluorometry and spectrophotometry, in the oxygraph, besides cellular respiration, cellular functions and metabolic parameters including mitochondrial membrane potential, ATP production (indirectly via the concentration of free Mg<sup>2+</sup>), Ca<sup>2+</sup> production and reactive oxygen (ROS) production (via H<sub>2</sub>O<sub>2</sub> concentration) will be analyzed</del>. <del style="font-weight: bold; text-decoration: none;">These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. By inhibiting or upregulating </del>the <del style="font-weight: bold; text-decoration: none;">activity of specific enzymes or complexes of the respiratory chain, their functions in the progression of cancer might be proved and compared to other cell types. To name an example, the production of ROS is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, leading to degenerative diseases or cancer. By measuring the oxidative stress </del>as a <del style="font-weight: bold; text-decoration: none;">signal of hydrogen peroxide production and decreasing/increasing it by the addition of specific chemicals</del>, it <del style="font-weight: bold; text-decoration: none;">could be further evaluated how significant </del>the <del style="font-weight: bold; text-decoration: none;">effects </del>of <del style="font-weight: bold; text-decoration: none;">ROS production might be </del>in the development <del style="font-weight: bold; text-decoration: none;">of OOC.</del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>The <ins style="font-weight: bold; text-decoration: none;">stated PhD project </ins>will be conducted in the <ins style="font-weight: bold; text-decoration: none;">frame </ins>of the <ins style="font-weight: bold; text-decoration: none;">European Union's program “TRACT”</ins>, <ins style="font-weight: bold; text-decoration: none;">funded by a Marie Skłodowska-Curie fellowship</ins>. <ins style="font-weight: bold; text-decoration: none;">With </ins>the <ins style="font-weight: bold; text-decoration: none;">company OROBOROS INSTRUMENTS </ins>as a <ins style="font-weight: bold; text-decoration: none;">partner</ins>, it <ins style="font-weight: bold; text-decoration: none;">will aim at </ins>the <ins style="font-weight: bold; text-decoration: none;">examination </ins>of <ins style="font-weight: bold; text-decoration: none;">metabolic transformation mechanisms </ins>in <ins style="font-weight: bold; text-decoration: none;">OC with </ins>the <ins style="font-weight: bold; text-decoration: none;">attempt of identifying new drug targets for future therapeutic </ins>development and <ins style="font-weight: bold; text-decoration: none;">new diagnostic strategies</ins>.</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway </del>and <del style="font-weight: bold; text-decoration: none;">glutaminolysis using <sup>2</sup>H/<sup>13</sup>C NMR to complement the respiration/fluorometric measurements conducted with the O2k at OROBOROS INSTRUMENTS in Innsbruck</del>.</div></td><td colspan="2"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma<del style="font-weight: bold; text-decoration: none;">, provided by TCD, </del>as well as human tissue biopsies of different stages of cancer <del style="font-weight: bold; text-decoration: none;">(</del>intestinal metaplasia, dysplasia <del style="font-weight: bold; text-decoration: none;">and </del>adenocarcinoma<del style="font-weight: bold; text-decoration: none;">) </del>and non-cancerous tissue<del style="font-weight: bold; text-decoration: none;">, which will be provided by the surgery of Innsbruck (Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie der Medizinische Universität Innsbruck)</del>. For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">The work will further characterize the bioenergetic and metabolic properties of normal, metaplastic, dysplastic and cancerous oesophageal cells and identify differences between these stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using an OROBOROS Oxygraph 2k (O2k)-Fluorometer enabling the screening of real-time bioenergetics and metabolism of cells by the combination of high resolution respirometry (HRR) with fluorometry. By this, not only the cellular respiration (O<sub>2</sub> consumption) of cells or mitochondria can be analyzed, but also multiple other metabolic parameters including the mitochondrial membrane potential, ATP production (indirectly via the concentration of free Mg<sup>2+</sup>), Ca<sup>2+</sup> production and reactive oxygen (ROS) production (via H<sub>2</sub>O<sub>2</sub> concentration) <sup>5</sup>. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. To name an example, the production of ROS in mitochondria is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, probably leading to degenerative diseases or cancer <sup>6</sup>. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing or increasing it by adding specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OC.</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using <sup>2</sup>H/<sup>13</sup>C NMR to complement the respiratory and fluorometric measurements conducted with the O2k at OROBOROS INSTRUMENTS. </ins>The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma as well as human tissue biopsies of different stages of cancer <ins style="font-weight: bold; text-decoration: none;">-namely </ins>intestinal metaplasia, dysplasia<ins style="font-weight: bold; text-decoration: none;">, </ins>adenocarcinoma and non-cancerous tissue <ins style="font-weight: bold; text-decoration: none;">as control</ins>. For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k<ins style="font-weight: bold; text-decoration: none;">.</ins></div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">By comparing the different types of cancerous tissue with the cell culture models of adenocarcinoma, the representativeness and reliability of the utilized cell models regarding their metabolic properties will be tested. With the inclusion of human tissues, the relevance and applicability of this study for the clinic is particularly ensured</ins>.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">By comparing </del>the <del style="font-weight: bold; text-decoration: none;">different types of cancerous tissue with the cell culture model of adenocarcinoma</del>, the <del style="font-weight: bold; text-decoration: none;">representativeness </del>of <del style="font-weight: bold; text-decoration: none;">the utilized cell model can be confirmed and adopted or modified if necessary. By including human tissue in </del>this <del style="font-weight: bold; text-decoration: none;">study, the relevance and applicability for the clinic </del>is <del style="font-weight: bold; text-decoration: none;">ensured.</del></div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;">On </ins>the <ins style="font-weight: bold; text-decoration: none;">whole</ins>, the <ins style="font-weight: bold; text-decoration: none;">main aim </ins>of this <ins style="font-weight: bold; text-decoration: none;">thesis </ins>is the <ins style="font-weight: bold; text-decoration: none;">identification of </ins>differences in the metabolic profiles of the <ins style="font-weight: bold; text-decoration: none;">examined states of cancer </ins>and<ins style="font-weight: bold; text-decoration: none;">, in hand with this, the </ins>metabolic transformation mechanisms <ins style="font-weight: bold; text-decoration: none;">taking place </ins>in <ins style="font-weight: bold; text-decoration: none;">OC. In so doing a basis of </ins>differential novel drug targets <ins style="font-weight: bold; text-decoration: none;">will be established </ins>and <ins style="font-weight: bold; text-decoration: none;">the progression of </ins>means to enhance the chemotherapeutic sensitivity of cancer cells identified.</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> </div></td><td colspan="2"></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;">By identifying </del>the differences in the metabolic profiles of the <del style="font-weight: bold; text-decoration: none;">stated cells </del>and metabolic transformation mechanisms in <del style="font-weight: bold; text-decoration: none;">OOC, </del>differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells <del style="font-weight: bold; text-decoration: none;">are intended to be </del>identified.</div></td><td colspan="2"></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|mipnetlab=AT Innsbruck OROBOROS</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|mipnetlab=AT Innsbruck OROBOROS</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>}}</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>}}</div></td></tr>
</table>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&diff=133272&oldid=prevBufe Anja at 08:26, 28 March 20172017-03-28T08:26:32Z<p></p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 08:26, 28 March 2017</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Metabolic transformation is a universal property of tumor formation and is a rich source of targets for development of therapeutic interventions 1. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have identified the glycolytic pathway as a potential targetable pathway. Hence, this work will further characterize the bioenergetic and metabolic properties of normal, dysplastic and cancerous oral cancer cells and identify differences between the different stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using the Oroboros Respirometer Multisensor system Oxygraph2k (O2k) enabling the screening of real-time bioenergetics and metabolism in the different stages of OCC. Due to the combination of high resolution respirometry (HRR) with optical methods, namely fluorometry and spectrophotometry, in the oxygraph, besides cellular respiration, cellular functions and metabolic parameters including mitochondrial membrane potential, ATP production (indirectly via the concentration of free Mg<sup>2+</sup>), Ca<sup>2+</sup> production and reactive oxygen (ROS) production (via H<sub>2</sub>O<sub>2</sub> concentration) will be analyzed. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. By inhibiting or upregulating the activity of specific enzymes or complexes of the respiratory chain, their functions in the progression of cancer might be proved and compared to other cell types. To name an example, the production of ROS is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, leading to degenerative diseases or cancer. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing/increasing it by the addition of specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OOC.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Metabolic transformation is a universal property of tumor formation and is a rich source of targets for development of therapeutic interventions 1. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have identified the glycolytic pathway as a potential targetable pathway. Hence, this work will further characterize the bioenergetic and metabolic properties of normal, dysplastic and cancerous oral cancer cells and identify differences between the different stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using the Oroboros Respirometer Multisensor system Oxygraph2k (O2k) enabling the screening of real-time bioenergetics and metabolism in the different stages of OCC. Due to the combination of high resolution respirometry (HRR) with optical methods, namely fluorometry and spectrophotometry, in the oxygraph, besides cellular respiration, cellular functions and metabolic parameters including mitochondrial membrane potential, ATP production (indirectly via the concentration of free Mg<sup>2+</sup>), Ca<sup>2+</sup> production and reactive oxygen (ROS) production (via H<sub>2</sub>O<sub>2</sub> concentration) will be analyzed. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. By inhibiting or upregulating the activity of specific enzymes or complexes of the respiratory chain, their functions in the progression of cancer might be proved and compared to other cell types. To name an example, the production of ROS is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, leading to degenerative diseases or cancer. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing/increasing it by the addition of specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OOC.</div></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using <del style="font-weight: bold; text-decoration: none;">2H</del>/<del style="font-weight: bold; text-decoration: none;">13C </del>NMR to complement the respiration/fluorometric measurements conducted with the O2k at OROBOROS INSTRUMENTS in Innsbruck.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using <ins style="font-weight: bold; text-decoration: none;"><sup>2<</ins>/<ins style="font-weight: bold; text-decoration: none;">sup>H/<sup>13</sup>C </ins>NMR to complement the respiration/fluorometric measurements conducted with the O2k at OROBOROS INSTRUMENTS in Innsbruck.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma, provided by TCD, as well as human tissue biopsies of different stages of cancer (intestinal metaplasia, dysplasia and adenocarcinoma) and non-cancerous tissue, which will be provided by the surgery of Innsbruck (Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie der Medizinische Universität Innsbruck). For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma, provided by TCD, as well as human tissue biopsies of different stages of cancer (intestinal metaplasia, dysplasia and adenocarcinoma) and non-cancerous tissue, which will be provided by the surgery of Innsbruck (Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie der Medizinische Universität Innsbruck). For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.</div></td></tr>
</table>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&diff=133271&oldid=prevBufe Anja at 08:25, 28 March 20172017-03-28T08:25:36Z<p></p>
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">Revision as of 08:25, 28 March 2017</td>
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<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=The stated project will be conducted in the frame of the European Union's TRACT program, funded by a Marie Skłodowska-Curie fellowship. With the company OROBOROS INSTRUMENTS as a partner, it will aim at the examination of metabolic transformation mechanisms in oesophageal cancer (OOC) with the attempt of identifying new drug targets for future therapeutic development.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>|abstract=The stated project will be conducted in the frame of the European Union's TRACT program, funded by a Marie Skłodowska-Curie fellowship. With the company OROBOROS INSTRUMENTS as a partner, it will aim at the examination of metabolic transformation mechanisms in oesophageal cancer (OOC) with the attempt of identifying new drug targets for future therapeutic development.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
<tr><td class="diff-marker" data-marker="−"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div>Metabolic transformation is a universal property of tumor formation and is a rich source of targets for development of therapeutic interventions 1. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have identified the glycolytic pathway as a potential targetable pathway. Hence, this work will further characterize the bioenergetic and metabolic properties of normal, dysplastic and cancerous oral cancer cells and identify differences between the different stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using the Oroboros Respirometer Multisensor system Oxygraph2k (O2k) enabling the screening of real-time bioenergetics and metabolism in the different stages of OCC. Due to the combination of high resolution respirometry (HRR) with optical methods, namely fluorometry and spectrophotometry, in the oxygraph, besides cellular respiration, cellular functions and metabolic parameters including mitochondrial membrane potential, ATP production (indirectly via the concentration of free <del style="font-weight: bold; text-decoration: none;">Mg2</del>+), <del style="font-weight: bold; text-decoration: none;">Ca2</del>+ production and reactive oxygen (ROS) production (via <del style="font-weight: bold; text-decoration: none;">H2O2 </del>concentration) will be analyzed. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. By inhibiting or upregulating the activity of specific enzymes or complexes of the respiratory chain, their functions in the progression of cancer might be proved and compared to other cell types. To name an example, the production of ROS is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, leading to degenerative diseases or cancer. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing/increasing it by the addition of specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OOC.</div></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div>Metabolic transformation is a universal property of tumor formation and is a rich source of targets for development of therapeutic interventions 1. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have identified the glycolytic pathway as a potential targetable pathway. Hence, this work will further characterize the bioenergetic and metabolic properties of normal, dysplastic and cancerous oral cancer cells and identify differences between the different stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using the Oroboros Respirometer Multisensor system Oxygraph2k (O2k) enabling the screening of real-time bioenergetics and metabolism in the different stages of OCC. Due to the combination of high resolution respirometry (HRR) with optical methods, namely fluorometry and spectrophotometry, in the oxygraph, besides cellular respiration, cellular functions and metabolic parameters including mitochondrial membrane potential, ATP production (indirectly via the concentration of free <ins style="font-weight: bold; text-decoration: none;">Mg<sup>2</ins>+<ins style="font-weight: bold; text-decoration: none;"></sup></ins>), <ins style="font-weight: bold; text-decoration: none;">Ca<sup>2</ins>+<ins style="font-weight: bold; text-decoration: none;"></sup> </ins>production and reactive oxygen (ROS) production (via <ins style="font-weight: bold; text-decoration: none;">H<sub>2</sub>O<sub>2</sub> </ins>concentration) will be analyzed. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. By inhibiting or upregulating the activity of specific enzymes or complexes of the respiratory chain, their functions in the progression of cancer might be proved and compared to other cell types. To name an example, the production of ROS is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, leading to degenerative diseases or cancer. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing/increasing it by the addition of specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OOC.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using 2H/13C NMR to complement the respiration/fluorometric measurements conducted with the O2k at OROBOROS INSTRUMENTS in Innsbruck.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using 2H/13C NMR to complement the respiration/fluorometric measurements conducted with the O2k at OROBOROS INSTRUMENTS in Innsbruck.</div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma, provided by TCD, as well as human tissue biopsies of different stages of cancer (intestinal metaplasia, dysplasia and adenocarcinoma) and non-cancerous tissue, which will be provided by the surgery of Innsbruck (Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie der Medizinische Universität Innsbruck). For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma, provided by TCD, as well as human tissue biopsies of different stages of cancer (intestinal metaplasia, dysplasia and adenocarcinoma) and non-cancerous tissue, which will be provided by the surgery of Innsbruck (Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie der Medizinische Universität Innsbruck). For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.</div></td></tr>
<tr><td colspan="2"></td><td class="diff-marker" data-marker="+"></td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins style="font-weight: bold; text-decoration: none;"></ins></div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>By comparing the different types of cancerous tissue with the cell culture model of adenocarcinoma, the representativeness of the utilized cell model can be confirmed and adopted or modified if necessary. By including human tissue in this study, the relevance and applicability for the clinic is ensured.</div></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div>By comparing the different types of cancerous tissue with the cell culture model of adenocarcinoma, the representativeness of the utilized cell model can be confirmed and adopted or modified if necessary. By including human tissue in this study, the relevance and applicability for the clinic is ensured.</div></td></tr>
<tr><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td><td class="diff-marker"></td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><br/></td></tr>
</table>Bufe Anjahttps://wiki.oroboros.at/index.php?title=Bufe_2017_TRACT_PhD_project_abstract&diff=133270&oldid=prevBufe Anja: Created page with "{{Abstract |title=Metabolic profiles in normal, dysplastic and cancerous oral cells. |authors=Bufe A |year=2017 |event=TRACT |abstract=The stated project will be conducted in..."2017-03-28T08:20:29Z<p>Created page with "{{Abstract |title=Metabolic profiles in normal, dysplastic and cancerous oral cells. |authors=Bufe A |year=2017 |event=TRACT |abstract=The stated project will be conducted in..."</p>
<p><b>New page</b></p><div>{{Abstract<br />
|title=Metabolic profiles in normal, dysplastic and cancerous oral cells.<br />
|authors=Bufe A<br />
|year=2017<br />
|event=TRACT<br />
|abstract=The stated project will be conducted in the frame of the European Union's TRACT program, funded by a Marie Skłodowska-Curie fellowship. With the company OROBOROS INSTRUMENTS as a partner, it will aim at the examination of metabolic transformation mechanisms in oesophageal cancer (OOC) with the attempt of identifying new drug targets for future therapeutic development.<br />
<br />
Metabolic transformation is a universal property of tumor formation and is a rich source of targets for development of therapeutic interventions 1. Pilot studies performed in the Queen’s University of Belfast (QUB) using a pathway based approach to identify determinants of drug resistance in oral and oesophageal cancer (OOC) have identified the glycolytic pathway as a potential targetable pathway. Hence, this work will further characterize the bioenergetic and metabolic properties of normal, dysplastic and cancerous oral cancer cells and identify differences between the different stages of carcinogenesis. The study will include comparison of oxygen consumption, extracellular acidity and metabolic flux under normoxic and hypoxic conditions. The measurements will be conducted using the Oroboros Respirometer Multisensor system Oxygraph2k (O2k) enabling the screening of real-time bioenergetics and metabolism in the different stages of OCC. Due to the combination of high resolution respirometry (HRR) with optical methods, namely fluorometry and spectrophotometry, in the oxygraph, besides cellular respiration, cellular functions and metabolic parameters including mitochondrial membrane potential, ATP production (indirectly via the concentration of free Mg2+), Ca2+ production and reactive oxygen (ROS) production (via H2O2 concentration) will be analyzed. These parameters are often altered in cancerous cells and might therefore be interesting for diagnostic and therapeutic interventions. By inhibiting or upregulating the activity of specific enzymes or complexes of the respiratory chain, their functions in the progression of cancer might be proved and compared to other cell types. To name an example, the production of ROS is known to be an essential component of multiple cellular pathways; however, an overload of oxidative stress can also cause genetic and functional damage, leading to degenerative diseases or cancer. By measuring the oxidative stress as a signal of hydrogen peroxide production and decreasing/increasing it by the addition of specific chemicals, it could be further evaluated how significant the effects of ROS production might be in the development of OOC.<br />
Over the course of a 9-month secondment at the Trinity College of Dublin (TCD) under the supervision of Prof. Richard Porter, metabolic flux will be measured additionally through glycolysis, pentose phosphate pathway and glutaminolysis using 2H/13C NMR to complement the respiration/fluorometric measurements conducted with the O2k at OROBOROS INSTRUMENTS in Innsbruck.<br />
The stated experiments and investigations will be performed with cell culture models of oesophageal adenocarcinoma, provided by TCD, as well as human tissue biopsies of different stages of cancer (intestinal metaplasia, dysplasia and adenocarcinoma) and non-cancerous tissue, which will be provided by the surgery of Innsbruck (Universitätsklinik für Visceral-, Transplantations- und Thoraxchirurgie der Medizinische Universität Innsbruck). For the conduction of the experiments, an ethics committee vote is obtained. To enable the repeated measurement of the samples, parts of all received samples are intended to be cryopreserved. Anyway, the feasibility of the cryopreservation of these tissues remains to be tested and will be proven by simultaneous comparative measurements of the cellular functions and metabolism of cryopreserved as well as fresh tissues with the O2k.<br />
By comparing the different types of cancerous tissue with the cell culture model of adenocarcinoma, the representativeness of the utilized cell model can be confirmed and adopted or modified if necessary. By including human tissue in this study, the relevance and applicability for the clinic is ensured.<br />
<br />
By identifying the differences in the metabolic profiles of the stated cells and metabolic transformation mechanisms in OOC, differential novel drug targets and means to enhance the chemotherapeutic sensitivity of cancer cells are intended to be identified.<br />
|mipnetlab=AT Innsbruck OROBOROS<br />
}}<br />
{{Labeling<br />
|area=Respiration<br />
|diseases=Cancer<br />
|organism=Human<br />
|tissues=Other cell lines<br />
|preparations=Intact cells, Permeabilized cells, Permeabilized tissue<br />
|instruments=Oxygraph-2k, O2k-Fluorometer<br />
}}</div>Bufe Anja