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Conventionally Fractionated Adaptive Radiation Therapy of Bladder Cancer an Individualized Approach

ABSTRACT: This is a single-arm, prospective, Phase II, multi-center clinical trial designed to demonstrate that adaptive radiotherapy for muscle invasive bladder cancer will translate into a decreased rate of acute gastrointestinal toxicity compared with the historically reported rate for non-adaptive intensity modulated radiation therapy (IMRT).

DISEASE(S): Urinary Bladder Neoplasms,Muscle-invasive Bladder Carcinoma

PROVIDER: 2710638 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:- Background and Aims: Oxygen can fall to low concentrations within plant tissues, either because of environmental factors that decrease the external oxygen concentration or because the movement of oxygen through the plant tissues cannot keep pace with the rate of oxygen consumption. Recent studies document that plants can decrease their oxygen consumption in response to relative small changes in oxygen concentrations to avoid internal anoxia. The molecular mechanisms underlying this response have not been identified yet. The aim of this study was to use transcript and metabolite profiling to investigate the genomic response of Arabidopsis roots to a mild decrease in oxygen concentrations. - Methods: Arabidopsis seedlings were grown on vertical agar plates at 21, 8, 4 and 1% (v/v) external oxygen for 0.5, 2 and 48h. Roots were analyzed for changes in transcript levels using Affymetrix whole genome DNA microarrays, and for changes in metabolite levels using routine GC-MS based metabolite profiling. Root extension rates were monitored in parallel to investigate adaptive changes in growth. - Key results: Results show that root growth was inhibited and transcript and metabolite profiles were significantly altered in response to a moderate decrease in oxygen concentrations. Low oxygen leads to a preferential up-regulation of genes that might be important to trigger adaptive responses in the plant. A small but highly specific set of genes is induced very early in response to a moderate decrease in oxygen concentrations. Genes that were down-regulated mainly encoded proteins involved in energy-consuming processes. In line with this, root extension growth was significantly decreased which will ultimately save ATP and decrease oxygen consumption. This was accompanied by a differential regulation of metabolite levels at short and long term incubation at low oxygen. - Conclusions: Results show that there are adaptive changes in root extension involving large-scale reprogramming of gene expression and metabolism when oxygen concentration is decreased in a very narrow range. Experiment Overall Design: Arabidopsis seedlings were grown on vertical agar plates and treated with various oxygen concentrations (1%, 4%, 8%, and 21% as a control), 350ppm CO2 and N2 (rest) for different time periods (0.5 hours, 2 hours and 2 days. At the end of the experiment, the roots of the seedlings were immediately frozen in liquid nitrogen and used for gene expression analysis.

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Conventionally Fractionated Adaptive Radiation Therapy of Bladder Cancer an Individualized Approach

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