Original Articles
Use of Gene Therapy in a Subcutaneous Murine Model of Lung Cancer
Manuel Rodrigo Garzóna,
, Íñigo Tirapu Fernández de la Cuestab, Ainhoa Arina Iraetab, Miguel Noel Centelles Llorenteb, Javier Zulueta Francésa
Corresponding author
manrrogar@yahoo.es
Correspondence: Dr. M. Rodrigo Garzón. P.° de la Estación, 42, 9.° B. 23008 Jaén. España
Correspondence: Dr. M. Rodrigo Garzón. P.° de la Estación, 42, 9.° B. 23008 Jaén. España
a Servicio de Neumología, Clínica Universitaria de Navarra, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Navarra, Spain
b Departamento de Medicina Interna, Clínica Universitaria de Navarra, Centro de Investigación Médica Aplicada (CIMA), Universidad de Navarra, Pamplona, Navarra, Spain
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Rodrigo Garzón. P.° de la Estación, 42, 9.° B. 23008 Jaén. España" ] ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2005-09-13" "fechaAceptado" => "2006-02-28" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec154196" "palabras" => array:6 [ 0 => "Gene therapy" 1 => "Lung cancer" 2 => "Adenovirus" 3 => "Thymidine kinase" 4 => "Interleukin 12" 5 => "Dendritic cells" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec154195" "palabras" => array:6 [ 0 => "Tratamiento génico" 1 => "Cáncer de pulmón" 2 => "Adenovirus" 3 => "Timidincinasa" 4 => "Interleucina 12" 5 => "Células dendríticas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">To assess the effectiveness of in vivo gene therapy to treat subcutaneous tumors generated from murine lung cancer cells.</p> <span class="elsevierStyleSectionTitle">Material and Methods</span><p class="elsevierStyleSimplePara elsevierViewall">C57BL/6 mice received subcutaneus injections of 5×10<span class="elsevierStyleSup">5</span> cells from the murine Lewis lung cancer cell line. By 10 days, subcutaneous tumors of approximately 5 mm diameter were formed. At that point, treatment was provided by intratumor injection of a replication-defective recombinant adenovirus carrying the gene for thymidine kinase (AdCMV-Tk) or interleukin (IL) 12 (AdCMV-IL12), or by injection of syngeneic dendritic cells previously transduced with adenovirus containing the IL-12 gene (DC-IL12). Control groups were treated with saline or adenovirus containing the gene for β-galactosidase (AdCMV-LacZ), which functions as a reporter gene and does not have a therapeutic effect. The number of animals in each group ranged from 14 to 25 in experiments using adenovirus and from 10 to 12 in experiments using dendritic cells. Tumor size was followed for 3 weeks in the case of treatment with adenovirus and 4 weeks for treatment with dendritic cells.</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">A significant reduction in subcutaneous tumor growth was observed in the groups treated with AdCMV-Tk, AdCMV-IL12, and DC-IL12 compared with control groups treated with saline or AdCMV-LacZ. The difference was statistically significant from day 7 of treatment in the AdCMV-Tk group, from day 9 in the AdCMV-IL12 group, and from day 10 in the DC-IL12 group, and in all cases it was maintained until the end of the follow-up period.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">Gene therapy with AdCMV-Tk, AdCMV-IL12, or DC-IL12 is effective in our model of subcutaneous tumors arising from cells of the Lewis lung cancer cell line. The treatment leads to a significant reduction in tumor growth compared with control groups.</p>" ] "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">Demostrar la utilidad del tratamiento génico (TG) <span class="elsevierStyleItalic">in vivo</span> en los tumores subcutáneos de cáncer de pulmon murino.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Se inyectaron a ratones C57BL/6 por vía subcutánea 5 × 10<span class="elsevierStyleSup">5</span> células de la línea de cáncer de pulmón murino de Lewis. A los 10 días se formaron tumores subcutáneos de unos 5 mm de diámetro. En ese momento se trataron mediante inyección intratumoral con un adenovirus recombinante defectivo portador del gen de la timidincinasa (AdCMV-Tk), o del gen de la interleucina 12 (AdCMV-IL12), o con células dendríticas (CD) singénicas transducidas con el gen de la interleucina 12 (CD-IL12). Como grupos control se incluyeron tumores tratados con suero salino o con un adenovirus con el gen de la β-galactosidasa (AdCMV-LacZ), que es un gen indicador sin efecto terapéutico. El número de animales por grupo osciló entre 14 y 25 con adenovirus y entre 10 y 12 con CD. A continuación se realizó un seguimiento del tamaño tumoral desde el primer día de tratamiento hasta la tercera (adenovirus) o cuarta (CD) semanas para comparar su evolución.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">Se objetivó una disminución significativa del crecimiento de los tumores subcutáneos en los grupos tratados con AdCMV-Tk, AdCMV-IL12 y CD-IL12 comparados con los grupos control tratados con suelo salino y AdCMV-LacZ. En el grupo AdCMV-Tk esta diferencia fue estadísticamente significativa desde el día 7, en AdCMV-IL12 desde el día 9 y en CD-IL12 desde el día 10 y se mantuvo hasta el final del seguimiento.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">El TG con AdCMV-Tk, AdCMV-IL12 o CD-IL12 es efectivo en nuestro modelo de tumores subcutáneos de células de carcinoma pulmonar de Lewis, ya que es capaz de disminuir su tasa de crecimiento de forma significativa respecto a los grupos de control.</p>" ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "<p class="elsevierStyleNotepara">This study was supported by grants from the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), 1999, and Fundación Echebano, 2000.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:30 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The future of human gene therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "GM Rubanyi" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Mol Aspects Med" "fecha" => "2001" "volumen" => "22" "paginaInicial" => "113" "paginaFinal" => "142" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11470139" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene therapy as drug development" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "BJ Carter" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/mthe.2000.0040" "Revista" => array:6 [ "tituloSerie" => "Mol Ther" "fecha" => "2000" "volumen" => "1" "paginaInicial" => "211" "paginaFinal" => "212" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10933936" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gene therapy for lung disease: hype or hope?" 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 6 | 11 |
| 2024 October | 26 | 23 | 49 |
| 2024 September | 36 | 17 | 53 |
| 2024 August | 45 | 39 | 84 |
| 2024 July | 27 | 23 | 50 |
| 2024 June | 29 | 27 | 56 |
| 2024 May | 30 | 29 | 59 |
| 2024 April | 13 | 29 | 42 |
| 2024 March | 23 | 21 | 44 |
| 2024 February | 22 | 21 | 43 |
| 2023 June | 0 | 2 | 2 |
| 2023 March | 1 | 2 | 3 |
| 2023 February | 14 | 17 | 31 |
| 2023 January | 24 | 31 | 55 |
| 2022 December | 21 | 25 | 46 |
| 2022 November | 22 | 25 | 47 |
| 2022 October | 24 | 28 | 52 |
| 2022 September | 20 | 20 | 40 |
| 2022 August | 12 | 36 | 48 |
| 2022 July | 23 | 41 | 64 |
| 2022 June | 17 | 25 | 42 |
| 2022 May | 16 | 41 | 57 |
| 2022 April | 29 | 30 | 59 |
| 2022 March | 38 | 39 | 77 |
| 2022 February | 24 | 22 | 46 |
| 2022 January | 17 | 41 | 58 |
| 2021 December | 16 | 45 | 61 |
| 2021 November | 22 | 58 | 80 |
| 2021 October | 26 | 55 | 81 |
| 2021 September | 18 | 57 | 75 |
| 2021 August | 18 | 29 | 47 |
| 2021 July | 15 | 23 | 38 |
| 2021 June | 23 | 35 | 58 |
| 2021 May | 11 | 27 | 38 |
| 2021 April | 27 | 57 | 84 |
| 2021 March | 19 | 18 | 37 |
| 2021 February | 18 | 17 | 35 |
| 2021 January | 12 | 19 | 31 |
| 2020 December | 16 | 19 | 35 |
| 2020 November | 20 | 15 | 35 |
| 2020 October | 9 | 7 | 16 |
| 2020 September | 6 | 4 | 10 |
| 2020 August | 8 | 11 | 19 |
| 2020 July | 14 | 13 | 27 |
| 2020 June | 3 | 2 | 5 |
| 2020 May | 29 | 15 | 44 |
| 2020 April | 26 | 17 | 43 |
| 2020 March | 38 | 16 | 54 |
| 2020 February | 65 | 15 | 80 |
| 2020 January | 34 | 19 | 53 |
| 2019 December | 12 | 13 | 25 |
| 2019 November | 15 | 15 | 30 |
| 2019 October | 6 | 5 | 11 |
| 2019 September | 4 | 14 | 18 |
| 2019 August | 10 | 11 | 21 |
| 2019 July | 24 | 19 | 43 |
| 2019 June | 46 | 6 | 52 |
| 2019 May | 49 | 9 | 58 |
| 2019 April | 7 | 26 | 33 |
| 2019 March | 10 | 16 | 26 |
| 2019 February | 12 | 10 | 22 |
| 2019 January | 6 | 8 | 14 |
| 2018 December | 9 | 11 | 20 |
| 2018 November | 9 | 4 | 13 |
| 2018 October | 15 | 10 | 25 |
| 2018 September | 8 | 6 | 14 |
| 2018 May | 4 | 0 | 4 |
| 2018 April | 11 | 5 | 16 |
| 2018 March | 3 | 2 | 5 |
| 2018 February | 5 | 7 | 12 |
| 2018 January | 4 | 3 | 7 |
| 2017 December | 4 | 8 | 12 |
| 2017 November | 2 | 2 | 4 |
| 2017 October | 2 | 5 | 7 |
| 2017 September | 6 | 10 | 16 |
| 2017 August | 6 | 7 | 13 |
| 2017 July | 2 | 0 | 2 |
| 2017 June | 6 | 11 | 17 |
| 2017 May | 4 | 8 | 12 |
| 2017 April | 2 | 3 | 5 |
| 2017 March | 2 | 2 | 4 |
| 2017 February | 0 | 2 | 2 |
| 2017 January | 1 | 1 | 2 |
| 2016 December | 6 | 6 | 12 |
| 2016 November | 17 | 8 | 25 |
| 2016 October | 18 | 7 | 25 |
| 2016 September | 14 | 8 | 22 |
| 2016 August | 10 | 3 | 13 |
| 2016 July | 13 | 3 | 16 |
| 2016 March | 5 | 0 | 5 |
| 2015 December | 2 | 0 | 2 |
| 2015 October | 49 | 14 | 63 |
| 2015 September | 68 | 11 | 79 |
| 2015 August | 44 | 18 | 62 |
| 2015 July | 58 | 7 | 65 |
| 2015 June | 56 | 8 | 64 |
| 2015 May | 49 | 15 | 64 |
| 2015 April | 54 | 14 | 68 |
| 2015 March | 35 | 2 | 37 |
| 2015 February | 34 | 5 | 39 |
| 2015 January | 43 | 7 | 50 |
| 2014 December | 104 | 5 | 109 |
| 2014 November | 49 | 9 | 58 |
| 2014 October | 74 | 7 | 81 |
| 2014 September | 53 | 9 | 62 |
| 2014 August | 49 | 13 | 62 |
| 2014 July | 51 | 5 | 56 |
| 2014 June | 68 | 9 | 77 |
| 2014 May | 59 | 11 | 70 |
| 2014 April | 68 | 11 | 79 |
| 2014 March | 57 | 8 | 65 |
| 2014 February | 52 | 11 | 63 |
| 2014 January | 42 | 6 | 48 |
| 2013 December | 45 | 7 | 52 |
| 2013 November | 51 | 6 | 57 |
| 2013 October | 47 | 6 | 53 |
| 2013 September | 52 | 6 | 58 |
| 2013 August | 74 | 21 | 95 |
| 2013 July | 62 | 14 | 76 |
| 2013 June | 36 | 15 | 51 |
| 2013 May | 51 | 6 | 57 |
| 2013 April | 30 | 4 | 34 |
| 2013 March | 13 | 4 | 17 |
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