Original Articles
Expression of Proteins Associated With Multidrug Resistance to Chemotherapy in Lung Cancer
Alfredo Paredes Larioa, Carlos Blanco Garcíab, Miguel Echenique Elizondoc,
, Carmen Lobod
Corresponding author
gepecelm@sc.ehu.es
Correspondence: Dr. M. Echenique Elizondo. Facultad de Medicina. UD San Sebastián. Universidad del País Vasco. P.° Dr. Begiristain, 105. 20014 San Sebastián. Guipúzcoa. España
Correspondence: Dr. M. Echenique Elizondo. Facultad de Medicina. UD San Sebastián. Universidad del País Vasco. P.° Dr. Begiristain, 105. 20014 San Sebastián. Guipúzcoa. España
a Servicio de Oncología, Hospital Donostia, San Sebastián, Guipúzcoa, Spain
b Servicio de Radioterapia, Hospital Donostia, San Sebastián, Guipúzcoa, Spain
c Departamento de Cirugía, Facultad de Medicina, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain
d Servicio de Patología, Hospital Donostia, San Sebastián, Guipúzcoa, Spain
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Multidrug Resistance to Chemotherapy in Lung Cancer" "tieneTextoCompleto" => 0 "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "479" "paginaFinal" => "484" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Alfredo Paredes Lario, Carlos Blanco García, Miguel Echenique Elizondo, Carmen Lobo" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Alfredo Paredes" "apellidos" => "Lario" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] ] ] 1 => array:3 [ "nombre" => "Carlos Blanco" "apellidos" => "García" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] ] ] 2 => array:4 [ "nombre" => "Miguel Echenique" "apellidos" => "Elizondo" "email" => array:1 [ 0 => "gepecelm@sc.ehu.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff3" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] 3 => array:3 [ "nombre" => "Carmen" "apellidos" => "Lobo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff4" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Oncología, Hospital Donostia, San Sebastián, Guipúzcoa, Spain" "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff1" ] 1 => array:3 [ "entidad" => "Servicio de Radioterapia, Hospital Donostia, San Sebastián, Guipúzcoa, Spain" "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff2" ] 2 => array:3 [ "entidad" => "Departamento de Cirugía, Facultad de Medicina, Universidad del País Vasco, San Sebastián, Guipúzcoa, Spain" "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff3" ] 3 => array:3 [ "entidad" => "Servicio de Patología, Hospital Donostia, San Sebastián, Guipúzcoa, Spain" "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff4" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence: Dr. M. Echenique Elizondo. Facultad de Medicina. UD San Sebastián. Universidad del País Vasco. P.° Dr. Begiristain, 105. 20014 San Sebastián. Guipúzcoa. España" ] ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2006-06-17" "fechaAceptado" => "2007-03-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Key words" "identificador" => "xpalclavsec154984" "palabras" => array:3 [ 0 => "Multidrug-resistance proteins" 1 => "Lung cancer" 2 => "Chemotherapy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec154983" "palabras" => array:3 [ 0 => "MDR-proteínas" 1 => "Cáncer de pulmón" 2 => "Quimioterapia" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objective</span><p class="elsevierStyleSimplePara elsevierViewall">Membrane transporters are proteins that play a crucial role in resistance to chemotherapy. The aim of this study was to assess the influence of membrane transporter protein expression on chemotherapeutic response.</p> <span class="elsevierStyleSectionTitle">Material and methods</span><p class="elsevierStyleSimplePara elsevierViewall">One hundred and forty seven samples of tumor tissue were collected from 143 patients; 35 samples were obtained by bronchoscopy and 112 were surgical specimens. A total of 101 samples from 99 patients were adequate for study. Cryopreserved samples were subjected to immunohistochemical analysis to detect 3 proteins associated with multidrug resistance: P-glycoprotein (Pgp), multidrugresistance–associated protein 1 (MRP1), and lung resistance protein (LRP).</p> <span class="elsevierStyleSectionTitle">Results</span><p class="elsevierStyleSimplePara elsevierViewall">In 16 cases none of the proteins were expressed. A single protein was expressed in 32 (3 Pgp, 11 MRP1, and 18 LRP); 2 in 34 cases (24 Pgp and LRP; 5 MRP1 and Pgp; 5 MRP1 and LRP); and all 3 in 17 cases. No significant relationship was found between age and the expression of Pgp (<span class="elsevierStyleItalic">P</span> =.74), MRP1 (<span class="elsevierStyleItalic">P</span> =.95), or LRP (<span class="elsevierStyleItalic">P</span> =.26). Nor were there significant differences in number (<span class="elsevierStyleItalic">P</span> =.72) or type of coexpressed proteins (<span class="elsevierStyleItalic">P</span> =.39) by sex, by tumor stage (number, <span class="elsevierStyleItalic">P</span> =.55; type, <span class="elsevierStyleItalic">P</span> =.21), or by tumor grade (number, <span class="elsevierStyleItalic">P</span> =.59; type, <span class="elsevierStyleItalic">P</span> =.51). There was a highly significant trend toward coexpression of Pgp and LRP (<span class="elsevierStyleItalic">P</span> <.01) but not of Pgp and MRP1 (<span class="elsevierStyleItalic">P</span> =.18) or MRP1 and LRP (<span class="elsevierStyleItalic">P</span> =.26). MRP1 was expressed less often in adenocarcinoma. LRP was expressed less often in squamous cell carcinoma than in adenocarcinoma and undifferentiated large cell carcinoma. Coexpression of Pgp, MRP1, and LRP was observed most often in squamous cell carcinoma.</p> <span class="elsevierStyleSectionTitle">Conclusions</span><p class="elsevierStyleSimplePara elsevierViewall">Proteins associated with multidrug resistance are commonly expressed in lung cancer. Of the 3 proteins studied, LRP was the one most often found. Coexpression of more than 1 of the proteins was found in a considerable percentage of patients. Pgp was mainly found to be coexpressed with LRP. Pgp expression and the number of coexpressed proteins seemed to have a negative impact on response to chemotherapy.</p>" ] "es" => array:1 [ "resumen" => "<span class="elsevierStyleSectionTitle">Objetivo</span><p class="elsevierStyleSimplePara elsevierViewall">Las proteínas transportadoras de membrana desempeñan un papel esencial en la resistencia a la quimioterapia. El objetivo del estudio ha sido intentar valorar la influencia de su expresión en la respuesta a la quimioterapia.</p> <span class="elsevierStyleSectionTitle">Material y métodos</span><p class="elsevierStyleSimplePara elsevierViewall">Se recogieron 147 muestras tumorales procedentes de 143 pacientes. De ellas, 35 eran broncoscó-picas y 112 quirúrgicas. Resultaron válidas para el estudio 101, correspondientes a 99 pacientes. Las muestras tumorales criocongeladas se sometieron a análisis inmunohistoquímico para la detección de las 3 proteínas relacionadas con resistencia a múltiples fármacos (MDR-proteínas): Pgp, Mrp1 y Lrp.</p> <span class="elsevierStyleSectionTitle">Resultados</span><p class="elsevierStyleSimplePara elsevierViewall">No expresaban ninguna proteína 16 casos. Se encontró expresión de una sola proteína en 32 casos (3 Pgp, 11 Mrp1 y 18 Lrp); de 2 proteínas en 34 casos (24 Pgp + Lrp; 5 Mrp1 + Pgp; 5 Mrp1 + Lrp), y de las 3 proteínas en 17. No encontramos relación significativa entre la edad y la expresión de Pgp (p = 0,74), Mrp1 (p = 0,95) o Lrp (p = 0,26). No observamos diferencias significativas entre sexos por el número (p = 0,72) ni por el tipo (p = 0,39) de proteínas expresadas de forma simultánea. Tampoco detectamos diferencias significativas entre estadios tumorales por el número (p = 0,55) ni por el tipo (p = 0,21) de MDR-proteínas. No encontramos diferencias significativas entre los diferentes grados histológicos ni por el número (p = 0,59) ni por el tipo (p = 0,51) de MDR-proteínas expresadas simultáneamente. La tendencia de Pgp y Lrp a expresarse asociadas resultó muy significativa (p < 0,01), pero no fue así en el caso de la asociación de Pgp y Mrp1 (p = 0,18) o Mrp1 y Lrp (p = 0,26). Los adenocarcinomas expresaron menos la Mrp1. Los carcinomas escamosos expresaron menos Lrp que los adenocarcinomas y carcinomas indiferenciados de células grandes. Los carcinomas escamosos fueron los que con más frecuencia expresaron Pgp, Mrp1 y Lrp de forma simultánea.</p> <span class="elsevierStyleSectionTitle">Conclusiones</span><p class="elsevierStyleSimplePara elsevierViewall">El cáncer de pulmón expresa con frecuencia MDR-proteínas. De las 3 estudiadas (Pgp, Mrp1 y Lrp), la más frecuentemente observada fue Lrp. En una proporción importante de pacientes se halló expresión simultánea de más de una MDR-proteína. Pgp se expresó fundamentalmente asociada a Lrp. La expresión de Pgp y el número de proteínas expresadas simultáneamente parecieron afectar de forma negativa a la respuesta a la quimioterapia.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "REFERENCES" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:35 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanisms of drug resistance" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "WT Beck" 1 => "WS Dalton" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "LibroEditado" => array:5 [ "titulo" => "Cancer, principles and practice of oncology" "paginaInicial" => "498" "paginaFinal" => "512" "edicion" => "6th ed." 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 6 | 5 | 11 |
| 2024 October | 27 | 15 | 42 |
| 2024 September | 23 | 16 | 39 |
| 2024 August | 40 | 38 | 78 |
| 2024 July | 24 | 20 | 44 |
| 2024 June | 31 | 22 | 53 |
| 2024 May | 27 | 28 | 55 |
| 2024 April | 17 | 25 | 42 |
| 2024 March | 22 | 19 | 41 |
| 2024 February | 20 | 17 | 37 |
| 2023 March | 5 | 7 | 12 |
| 2023 February | 14 | 18 | 32 |
| 2023 January | 16 | 24 | 40 |
| 2022 December | 18 | 34 | 52 |
| 2022 November | 19 | 23 | 42 |
| 2022 October | 21 | 35 | 56 |
| 2022 September | 17 | 33 | 50 |
| 2022 August | 17 | 41 | 58 |
| 2022 July | 19 | 33 | 52 |
| 2022 June | 12 | 26 | 38 |
| 2022 May | 15 | 27 | 42 |
| 2022 April | 14 | 28 | 42 |
| 2022 March | 18 | 32 | 50 |
| 2022 February | 19 | 24 | 43 |
| 2022 January | 21 | 29 | 50 |
| 2021 December | 14 | 47 | 61 |
| 2021 November | 16 | 63 | 79 |
| 2021 October | 13 | 47 | 60 |
| 2021 September | 15 | 61 | 76 |
| 2021 August | 15 | 31 | 46 |
| 2021 July | 12 | 24 | 36 |
| 2021 June | 12 | 36 | 48 |
| 2021 May | 20 | 35 | 55 |
| 2021 April | 22 | 38 | 60 |
| 2021 March | 16 | 17 | 33 |
| 2021 February | 11 | 12 | 23 |
| 2021 January | 11 | 16 | 27 |
| 2020 December | 7 | 14 | 21 |
| 2020 November | 10 | 12 | 22 |
| 2020 October | 9 | 4 | 13 |
| 2020 September | 5 | 1 | 6 |
| 2020 August | 6 | 13 | 19 |
| 2020 July | 9 | 10 | 19 |
| 2020 June | 6 | 11 | 17 |
| 2020 May | 5 | 13 | 18 |
| 2020 April | 9 | 15 | 24 |
| 2020 March | 3 | 15 | 18 |
| 2020 February | 7 | 15 | 22 |
| 2020 January | 11 | 14 | 25 |
| 2019 December | 8 | 6 | 14 |
| 2019 November | 6 | 15 | 21 |
| 2019 October | 5 | 12 | 17 |
| 2019 September | 5 | 10 | 15 |
| 2019 August | 6 | 2 | 8 |
| 2019 July | 10 | 21 | 31 |
| 2019 June | 7 | 13 | 20 |
| 2019 May | 5 | 16 | 21 |
| 2019 April | 22 | 46 | 68 |
| 2019 March | 15 | 26 | 41 |
| 2019 February | 6 | 13 | 19 |
| 2019 January | 3 | 15 | 18 |
| 2018 December | 10 | 13 | 23 |
| 2018 November | 10 | 10 | 20 |
| 2018 October | 17 | 20 | 37 |
| 2018 September | 12 | 9 | 21 |
| 2018 May | 5 | 0 | 5 |
| 2018 April | 6 | 7 | 13 |
| 2018 March | 9 | 3 | 12 |
| 2018 February | 6 | 7 | 13 |
| 2018 January | 7 | 6 | 13 |
| 2017 December | 4 | 7 | 11 |
| 2017 November | 4 | 7 | 11 |
| 2017 October | 3 | 5 | 8 |
| 2017 September | 6 | 6 | 12 |
| 2017 August | 8 | 11 | 19 |
| 2017 July | 5 | 6 | 11 |
| 2017 June | 9 | 7 | 16 |
| 2017 May | 7 | 8 | 15 |
| 2017 April | 2 | 2 | 4 |
| 2017 March | 3 | 1 | 4 |
| 2017 February | 1 | 5 | 6 |
| 2017 January | 3 | 6 | 9 |
| 2016 December | 3 | 5 | 8 |
| 2016 November | 4 | 4 | 8 |
| 2016 October | 8 | 6 | 14 |
| 2016 September | 6 | 3 | 9 |
| 2016 August | 8 | 5 | 13 |
| 2016 July | 2 | 0 | 2 |
| 2016 March | 2 | 0 | 2 |
| 2015 December | 2 | 0 | 2 |
| 2015 October | 345 | 13 | 358 |
| 2015 September | 463 | 12 | 475 |
| 2015 August | 487 | 12 | 499 |
| 2015 July | 231 | 9 | 240 |
| 2015 June | 144 | 8 | 152 |
| 2015 May | 53 | 15 | 68 |
| 2015 April | 43 | 10 | 53 |
| 2015 March | 32 | 5 | 37 |
| 2015 February | 27 | 5 | 32 |
| 2015 January | 40 | 5 | 45 |
| 2014 December | 32 | 6 | 38 |
| 2014 November | 30 | 4 | 34 |
| 2014 October | 40 | 7 | 47 |
| 2014 September | 28 | 6 | 34 |
| 2014 August | 35 | 10 | 45 |
| 2014 July | 18 | 7 | 25 |
| 2014 June | 39 | 4 | 43 |
| 2014 May | 28 | 7 | 35 |
| 2014 April | 54 | 8 | 62 |
| 2014 March | 52 | 11 | 63 |
| 2014 February | 40 | 8 | 48 |
| 2014 January | 27 | 7 | 34 |
| 2013 December | 39 | 13 | 52 |
| 2013 November | 32 | 6 | 38 |
| 2013 October | 37 | 9 | 46 |
| 2013 September | 41 | 7 | 48 |
| 2013 August | 38 | 4 | 42 |
| 2013 July | 46 | 12 | 58 |
| 2013 June | 37 | 8 | 45 |
| 2013 May | 42 | 6 | 48 |
| 2013 April | 33 | 7 | 40 |
| 2013 March | 7 | 3 | 10 |
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