dcd794034b194cbf9e86028af96a4238  intjoumolsci_a2013v14p8306.pdf
1b1fa618bc1cbc954b08451018ed5113c2f04ccb  intjoumolsci_a2013v14p8306.pdf
cdafffade7aeaa96c1a01be6e285a61737eb867d40ac4e7f649ef8122defa3c8  intjoumolsci_a2013v14p8306.pdf

Title:          Development of a Preclinical Therapeutic Model of Human Brain Metastasis with Chemoradiotherapy 
Subject:        Currently, survival of breast cancer patients with brain metastasis ranges from 2 to 16 months. In experimental brain metastasis studies, only 10% of lesions with the highest permeability exhibited cytotoxic responses to paclitaxel or doxorubicin. Therefore, radiation is the most frequently used treatment, and sensitizing agents, which synergize with radiation, can improve the efficacy of the therapy. In this study we used 435-Br1 cells containing the fluorescent protein (eGFP) gene and the photinus luciferase (PLuc) gene to develop a new brain metastatic cell model in mice through five in vivo/in vitro rounds. 
BR-eGFP-CMV/Luc-V5 brain metastatic cells induce parenchymal brain metastasis within 60.8 ± 13.8 days of intracarotid injection in all mice. We used this model to standardize a preclinical chemoradiotherapy protocol comprising three 5.5 Gy fractions delivered on consecutive days (overall dose of 16.5 Gy) which improved survival with regard to controls (60.29 ± 8.65 vs. 47.20 ± 11.14). Moreover, the combination of radiotherapy with temozolomide, 60 mg/Kg/day orally for five consecutive days doubled survival time of the mice 121.56 ± 52.53 days (Kaplan-Meier Curve, p < 0.001). This new preclinical chemoradiotherapy protocol proved useful for the study of radiation response/resistance in brain metastasis, either alone or in combination with new sensitizing agents. 
Keywords:       brain metastasis; breast cancer; experimental models; radiation; 
temozolomide; therapy
Author:         Antonio Martínez-Aranda, Vanessa Hernández, Cristina Picón, Ignasi Modolell and Angels Sierra
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Jhove (Rel. 1.6, 2011-01-04)
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    Title: Development of a Preclinical Therapeutic Model of Human Brain Metastasis with Chemoradiotherapy 
    Author: Antonio Martínez-Aranda, Vanessa Hernández, Cristina Picón, Ignasi Modolell and Angels Sierra
    Subject: Currently, survival of breast cancer patients with brain metastasis ranges from 2 to 16 months. In experimental brain metastasis studies, only 10% of lesions with the highest permeability exhibited cytotoxic responses to paclitaxel or doxorubicin. Therefore, radiation is the most frequently used treatment, and sensitizing agents, which synergize with radiation, can improve the efficacy of the therapy. In this study we used 435-Br1 cells containing the fluorescent protein (eGFP) gene and the photinus luciferase (PLuc) gene to develop a new brain metastatic cell model in mice through five in vivo/in vitro rounds. 
BR-eGFP-CMV/Luc-V5 brain metastatic cells induce parenchymal brain metastasis within 60.8 ± 13.8 days of intracarotid injection in all mice. We used this model to standardize a preclinical chemoradiotherapy protocol comprising three 5.5 Gy fractions delivered on consecutive days (overall dose of 16.5 Gy) which improved survival with regard to controls (60.29 ± 8.65 vs. 47.20 ± 11.14). Moreover, the combination of radiotherapy with temozolomide, 60 mg/Kg/day orally for five consecutive days doubled survival time of the mice 121.56 ± 52.53 days (Kaplan-Meier Curve, p < 0.001). This new preclinical chemoradiotherapy protocol proved useful for the study of radiation response/resistance in brain metastasis, either alone or in combination with new sensitizing agents. 
    Keywords: brain metastasis; breast cancer; experimental models; radiation; 
temozolomide; therapy
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               <rdf:li xml:lang="x-default">Currently, survival of breast cancer patients with brain metastasis ranges from 2 to 16 months. In experimental brain metastasis studies, only 10% of lesions with the highest permeability exhibited cytotoxic responses to paclitaxel or doxorubicin. Therefore, radiation is the most frequently used treatment, and sensitizing agents, which synergize with radiation, can improve the efficacy of the therapy. In this study we used 435-Br1 cells containing the fluorescent protein (eGFP) gene and the photinus luciferase (PLuc) gene to develop a new brain metastatic cell model in mice through five in vivo/in vitro rounds. &#xD;&#xA;BR-eGFP-CMV/Luc-V5 brain metastatic cells induce parenchymal brain metastasis within 60.8 ± 13.8 days of intracarotid injection in all mice. We used this model to standardize a preclinical chemoradiotherapy protocol comprising three 5.5 Gy fractions delivered on consecutive days (overall dose of 16.5 Gy) which improved survival with regard to controls (60.29 ± 8.65 vs. 47.20 ± 11.14). Moreover, the combination of radiotherapy with temozolomide, 60 mg/Kg/day orally for five consecutive days doubled survival time of the mice 121.56 ± 52.53 days (Kaplan-Meier Curve, p &lt; 0.001). This new preclinical chemoradiotherapy protocol proved useful for the study of radiation response/resistance in brain metastasis, either alone or in combination with new sensitizing agents. </rdf:li>
            </rdf:Alt>
         </dc:description>
         <dc:subject>
            <rdf:Bag>
               <rdf:li>brain metastasis</rdf:li>
               <rdf:li>breast cancer</rdf:li>
               <rdf:li>experimental models</rdf:li>
               <rdf:li>radiation</rdf:li>
               <rdf:li>temozolomide</rdf:li>
               <rdf:li>therapy</rdf:li>
            </rdf:Bag>
         </dc:subject>
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      </rdf:Description>
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