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array:24 [ "pii" => "S2173578617300914" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2017.06.003" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "951" "copyright" => "AEU" "copyrightAnyo" => "2016" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Actas Urol Esp. 2017;41:445-50" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "HTML" => 1 ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0210480616302030" "issn" => "02104806" "doi" => "10.1016/j.acuro.2016.11.005" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "951" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Actas Urol Esp. 2017;41:445-50" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 23 "formatos" => array:2 [ "HTML" => 19 "PDF" => 4 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Artículo original</span>" "titulo" => "Modelo murino experimental de cáncer renal" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "445" "paginaFinal" => "450" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Experimental murine model of renal cancer" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 919 "Ancho" => 2337 "Tamanyo" => 87046 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Realización del primer implante.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "B. Padilla-Fernández, M.B. García-Cenador, P. Rodríguez-Marcos, J.F. López-Marcos, P. Antúnez-Plaza, J.M. Silva-Abuín, D. López-Montañés, F.J. García-Criado, M.F. Lorenzo-Gómez" "autores" => array:9 [ 0 => array:2 [ "nombre" => "B." "apellidos" => "Padilla-Fernández" ] 1 => array:2 [ "nombre" => "M.B." "apellidos" => "García-Cenador" ] 2 => array:2 [ "nombre" => "P." "apellidos" => "Rodríguez-Marcos" ] 3 => array:2 [ "nombre" => "J.F." "apellidos" => "López-Marcos" ] 4 => array:2 [ "nombre" => "P." "apellidos" => "Antúnez-Plaza" ] 5 => array:2 [ "nombre" => "J.M." "apellidos" => "Silva-Abuín" ] 6 => array:2 [ "nombre" => "D." "apellidos" => "López-Montañés" ] 7 => array:2 [ "nombre" => "F.J." "apellidos" => "García-Criado" ] 8 => array:2 [ "nombre" => "M.F." "apellidos" => "Lorenzo-Gómez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173578617300914" "doi" => "10.1016/j.acuroe.2017.06.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578617300914?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480616302030?idApp=UINPBA00004N" "url" => "/02104806/0000004100000007/v1_201708260049/S0210480616302030/v1_201708260049/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2173578617300926" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2016.12.012" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "972" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Actas Urol Esp. 2017;41:451-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 2 "formatos" => array:2 [ "HTML" => 1 "PDF" => 1 ] ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Predicting the effectiveness of extracorporeal shock wave lithotripsy on urinary tract stones. Risk groups for accurate retreatment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "451" "paginaFinal" => "457" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Predicción de efectividad de litotricia extracorpórea por ondas de choque en cálculos del tracto urinario. Grupos de riesgo para precisar retratamiento" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1067 "Ancho" => 1648 "Tamanyo" => 208645 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Measurement area (cm<span class="elsevierStyleSup">2</span>) and maximum density (HU).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Hevia, Á. García, F.J. Ancizu, I. Merino, J.M. Velis, A. Tienza, R. Algarra, P. Doménech, F. Diez-Caballero, D. Rosell, J.I. Pascual, J.E. Robles" "autores" => array:12 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Hevia" ] 1 => array:2 [ "nombre" => "Á." "apellidos" => "García" ] 2 => array:2 [ "nombre" => "F.J." "apellidos" => "Ancizu" ] 3 => array:2 [ "nombre" => "I." "apellidos" => "Merino" ] 4 => array:2 [ "nombre" => "J.M." "apellidos" => "Velis" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Tienza" ] 6 => array:2 [ "nombre" => "R." "apellidos" => "Algarra" ] 7 => array:2 [ "nombre" => "P." "apellidos" => "Doménech" ] 8 => array:2 [ "nombre" => "F." "apellidos" => "Diez-Caballero" ] 9 => array:2 [ "nombre" => "D." "apellidos" => "Rosell" ] 10 => array:2 [ "nombre" => "J.I." "apellidos" => "Pascual" ] 11 => array:2 [ "nombre" => "J.E." "apellidos" => "Robles" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480617300165" "doi" => "10.1016/j.acuro.2016.12.008" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480617300165?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578617300926?idApp=UINPBA00004N" "url" => "/21735786/0000004100000007/v1_201708260050/S2173578617300926/v1_201708260050/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2173578617300902" "issn" => "21735786" "doi" => "10.1016/j.acuroe.2017.06.002" "estado" => "S300" "fechaPublicacion" => "2017-09-01" "aid" => "979" "copyright" => "AEU" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Actas Urol Esp. 2017;41:437-44" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 1 "HTML" => 1 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Role of PET-CT with <span class="elsevierStyleSup">18</span>F-fluorocholine in biochemical recurrence after treatment of prostate cancer with curative intent" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "437" "paginaFinal" => "444" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Papel de la tomografía por emisión de positrones-tomografía computerizada con <span class="elsevierStyleSup">18</span>F-fluorocolina en la recidiva bioquímica tras tratamiento con intención curativa del cáncer de próstata" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1641 "Ancho" => 3102 "Tamanyo" => 149841 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">(A) ROC curve showing discriminant capacity of the trigger PSA number between negative and positive <span class="elsevierStyleSup">18</span>F-FCH PET-CT. The best cut-off point for the trigger PSA was 3.5<span class="elsevierStyleHsp" style=""></span>ng/ml, which correctly discriminated 73% of patients with a sensitivity of 70% and a specificity of 78%. (B) ROC curve showing discriminant capacity of PSArr between negative and positive <span class="elsevierStyleSup">18</span>F-FCH PET-CT. The best cut-off point for PSArr was 0.25<span class="elsevierStyleHsp" style=""></span>ng/ml/month, which correctly discriminated 72% of patients with a sensitivity and specificity of 72% and 63%, respectively.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "I. Puche-Sanz, E. Triviño-Ibáñez, F. Vázquez-Alonso, J.M. Llamas-Elvira, J.M. Cózar-Olmo, A. Rodríguez-Fernández" "autores" => array:6 [ 0 => array:2 [ "nombre" => "I." "apellidos" => "Puche-Sanz" ] 1 => array:2 [ "nombre" => "E." "apellidos" => "Triviño-Ibáñez" ] 2 => array:2 [ "nombre" => "F." "apellidos" => "Vázquez-Alonso" ] 3 => array:2 [ "nombre" => "J.M." "apellidos" => "Llamas-Elvira" ] 4 => array:2 [ "nombre" => "J.M." "apellidos" => "Cózar-Olmo" ] 5 => array:2 [ "nombre" => "A." "apellidos" => "Rodríguez-Fernández" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0210480617300426" "doi" => "10.1016/j.acuro.2017.02.002" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0210480617300426?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173578617300902?idApp=UINPBA00004N" "url" => "/21735786/0000004100000007/v1_201708260050/S2173578617300902/v1_201708260050/en/main.assets" ] "en" => array:21 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Experimental murine model of renal cancer" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "445" "paginaFinal" => "450" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "B. Padilla-Fernández, M.B. García-Cenador, P. Rodríguez-Marcos, J.F. López-Marcos, P. Antúnez-Plaza, J.M. Silva-Abuín, D. López-Montañés, F.J. García-Criado, M.F. Lorenzo-Gómez" "autores" => array:9 [ 0 => array:3 [ "nombre" => "B." "apellidos" => "Padilla-Fernández" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "M.B." "apellidos" => "García-Cenador" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "P." "apellidos" => "Rodríguez-Marcos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "J.F." "apellidos" => "López-Marcos" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 4 => array:3 [ "nombre" => "P." "apellidos" => "Antúnez-Plaza" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 5 => array:3 [ "nombre" => "J.M." "apellidos" => "Silva-Abuín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 6 => array:3 [ "nombre" => "D." "apellidos" => "López-Montañés" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 7 => array:3 [ "nombre" => "F.J." "apellidos" => "García-Criado" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 8 => array:4 [ "nombre" => "M.F." "apellidos" => "Lorenzo-Gómez" "email" => array:1 [ 0 => "mflorenzogo@yahoo.es" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Servicio de Urología, Hospital Universitario de Canarias, Tenerife, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Cirugía, Universidad de Salamanca, Salamanca, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Anatomía Patológica, Hospital Universitario de Salamanca, Salamanca, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Servicio de Urología, Hospital San Pedro, Logroño, Spain" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Modelo murino experimental de cáncer renal" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1078 "Ancho" => 1504 "Tamanyo" => 71938 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Realization of the second implant.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Renal cell carcinoma (RCC) accounts for 2–3% of tumors that affect humans, being more frequent in developed countries,<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">1</span></a> with an annual increase in incidence of 2%. They correspond to 90–95% of the malignant neoplasms that affect the kidney. In the European Union, 30,000 new cases/year are diagnosed, and approximately 15,000 patients die from this cause.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">RCCs encompasses a broad spectrum of histopathologic features described in 2004 by the WHO<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a> and modified in 2013 by the <span class="elsevierStyleItalic">International Society of Urological Pathology Vancouver Classification</span><a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">4</span></a> according to their cellular microscopic characteristics, prognosis, and genetic and molecular characteristics (See Supplementary Material).<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">5</span></a> Clear cell renal carcinoma is the most common histological variety. RCC staging is performed following the TNM classification of the American Joint Committee on Cancer<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">6</span></a> and Fuhrman grade, which is exclusively nuclear and correlates with prognosis.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Currently, the only curative treatment of renal cancer is surgical excision.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">7</span></a> In our study, 33% had metastases in the diagnosis and 25% of patients with localized disease who had been treated with curative intent developed progression (local recurrence or distant metastasis).<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a> In the treatment of advanced disease, surgery is proposed with curative intent only if it is possible to eliminate all tumor foci; if this is not possible, it can be performed as a palliative treatment if the patient has pain and/or bleeding. There is evidence to support the use of cytoreductive nephrectomy prior to systemic treatment, which is useful to correctly identify the histological strains and to decide the most appropriate targeted treatment. The application of this approach has demonstrated to be superior to systemic treatment alone and is currently undergoing Phase 3 clinical trials to finish clarifying its role.<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">9–11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The treatment of RCC has evolved following discoveries in molecular biology, such as the inactivation of the VHL gene that leads to the accumulation of hypoxia-inducible factor and the overexpression of vascular endothelial growth factor and platelet-derived growth factor,<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> with drugs against specific targets being developed that are used in renal cancer after having been used in other tumors. In the literature, there are few articles on murine models to investigate renal cell cancer.<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">13–15</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The objective of this study is to determine the reproducibility in a murine model of renal tumors of various histological strains that could be useful for investigating the response to target drugs.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><p id="par0035" class="elsevierStylePara elsevierViewall">Development and analysis of the “in vivo” model: tumor xenograft model of a subcutaneous RCC.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Tumor tissue</span><p id="par0040" class="elsevierStylePara elsevierViewall">In this experimental model, samples of human tumor tissue were obtained immediately and freshly from the surgical piece in the operating room (during nephrectomy) or pathological anatomy department, by inserting them into a 50<span class="elsevierStyleHsp" style=""></span>cc of sterile bottle containing PBS and penicillin/streptomycin (Sigma) and amphotericin B (Sigma) solutions.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The specimen is kept cold and transferred to the laboratories where, under sterile conditions and in the laminar flow hood (TELSTAR CV-30/70), it is placed in a Petri dish with the same solution and is fragmented into sections of approximately 3<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm for implantation.</p><p id="par0050" class="elsevierStylePara elsevierViewall">One sample is introduced into a tube for freeze-drying (Nalgene<span class="elsevierStyleSup">®</span> – Cryoware™) and is stored at −80<span class="elsevierStyleHsp" style=""></span>° C (Forma Scientific Model 917) for further studies.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Preliminary elaboration</span><p id="par0055" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0060" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Surface preparation:</span> all surfaces coming into contact with animals will be disinfected and covered with sterile drapes.</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0065" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Instrument preparation:</span> any instrument used for handling experimental animals is washed in an ultrasonic bath (Branson 2510), and depending on its characteristics, the instrument will be previously introduced into bags with indicators, sealed and sterilized in autoclave (Steam Sterilizer Trade RAYPA<span class="elsevierStyleSup">®</span>) or in bags with indicators, sealed and sterilized with ethylene oxide (Amprolene<span class="elsevierStyleSup">®</span> – Amprolene AN74i gas sterilizer).</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0070" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Preparation of water and food:</span> water is purified in autoclave and food is sterilely acquired by irradiation (global rodent diet 2918-Harlan).</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">•</span><p id="par0075" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Staff preparation:</span> staff must wash hands and forearms with antiseptic soap (Desinfloor<span class="elsevierStyleSup">®</span> – Fagesa) putting on then a sterile gown/and sterile dressing (Foliodress<span class="elsevierStyleSup">®</span> – Hartmann) and sterile surgical gloves (Peha-taft-Hartmann).</p></li></ul></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Reception and maintenance of animals</span><p id="par0080" class="elsevierStylePara elsevierViewall">The animal used was the immunodeficient male mice CB-17/scid-IrcHanHsd-PRKDC provided by Harlan™.</p><p id="par0085" class="elsevierStylePara elsevierViewall">This animal is chosen because in order to inoculate tumor cells, the mice are required to be genetically modified to avoid tumor rejection. All manipulation of experimental animals is performed under strict sterile conditions within a laminar flow hood and/or isolated stabling cabinet (KiMo<span class="elsevierStyleSup">®</span> – TDI Isolator).</p><p id="par0090" class="elsevierStylePara elsevierViewall">Animals are received when they are 7 weeks old. The mice are distributed in cages with a filter closure system and sterile bottles (5 animals per cage) and are housed in the insulating enclosure where they will stay for one week in a period of accommodation with <span class="elsevierStyleItalic">ad libitum</span> access to water and food. They are checked daily and once a week are weighed (model TE2101, Sartorius) and the cage is changed.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">First phase: preparation of the animals for the first implant</span><p id="par0095" class="elsevierStylePara elsevierViewall">In strictly sterile conditions and in laminar flow hood, the mice are anesthetized with a system for small animals (Datex-Ohmeda) using isoflurane (Forane<span class="elsevierStyleSup">®</span> – Abbott) as an anesthetic. With the animal in prone position, providone-iodine (Betadine<span class="elsevierStyleSup">®</span> Medical – Asta) is applied and with the aid of surgical instruments (forceps, kocker, dissecting scissors, cocher, needle holders – P&B – Germany), cold scalpel and electric scalpel (Integra™ Elektron<span class="elsevierStyleSup">®</span> 630), an infrascapular incision of approximately 1<span class="elsevierStyleHsp" style=""></span>cm is performed, exposing the dorsal musculature and sectioning 2<span class="elsevierStyleHsp" style=""></span>mm muscle aponeurosis, fixing a tumor sample 3<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>3<span class="elsevierStyleHsp" style=""></span>mm with suture of 6/0 (Vicryl+, Ethicon, suture is coated with antiseptic triclosan). The implant was hydrated with physiological saline solution (B/BRAUN) using 10<span class="elsevierStyleHsp" style=""></span>ml syringes and IM needles (BD Plastipak™). Suture of the incision with 5/0 suture (Vicryl+, Ethicon, suture is coated with antiseptic triclosan) and administration by povidone iodine gauze. Finally, the animal is housed under the described conditions.</p><p id="par0100" class="elsevierStylePara elsevierViewall">In this phase, after the first implant, three study groups are described (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0025"><p id="par0105" class="elsevierStylePara elsevierViewall">Group I (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5): kidney xenograft implantation with a fresh fragment of non-tumor human renal tissue. This tissue is obtained from the partial nephrectomy sample of a renal nodule by imaging tests corresponding to healthy tissue after anatomopathological study.</p></li><li class="elsevierStyleListItem" id="lsti0030"><p id="par0110" class="elsevierStylePara elsevierViewall">Group IIA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5): tumor xenograft implantation with a fresh fragment of a chromophobe renal tumor.</p></li><li class="elsevierStyleListItem" id="lsti0035"><p id="par0115" class="elsevierStylePara elsevierViewall">Group IIIA (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5): tumor xenograft implantation with a fresh fragment of a clear cell carcinoma, Fuhrman grade 2.</p></li></ul></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">The tissue is removed from a renal tumor after removal of the tumor, the histological type and grade being known after the anatomopathological analysis of the surgical specimen. The decision to use this tumor as a sample for xenograft depends on the diagnosis according to the complementary radiological tests.</p><p id="par0125" class="elsevierStylePara elsevierViewall">When the implant acquires a sufficient size, the animals are euthanized with a lethal dose of thiopental (sodium pentothal), proceeding to obtain tissue for anatomopathological and immunohistochemical study and for the implant in the working groups of the second phase.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Second phase: removal of the first implant and realization of the second</span><p id="par0130" class="elsevierStylePara elsevierViewall">In order to standardize the tumor growth conditions, the initial implant is removed when it has grown sufficiently, and it is divided into fragments of approximately 2<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>2<span class="elsevierStyleHsp" style=""></span>mm, storing a cryocolonelate and implanting the rest in 20 animals according to the technique described. The animal is housed under the described conditions.</p><p id="par0135" class="elsevierStylePara elsevierViewall">After the extraction of the first implant and the second implant, two study groups are described (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>):<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0040"><p id="par0140" class="elsevierStylePara elsevierViewall">Group IIB (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10): implant of tumor graft from group IIA into the kidney.</p></li><li class="elsevierStyleListItem" id="lsti0045"><p id="par0145" class="elsevierStylePara elsevierViewall">Group IIIB (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>10): implant of tumor graft from group IIIA into the kidney.</p></li></ul></p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Follow-up and monitoring</span><p id="par0150" class="elsevierStylePara elsevierViewall">Tumor size is monitored using a calibrator and ultrasound, and the presence of metastases is determined by CAT used for animals. The growth and number of lesions are also monitored with ultrasound.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Necropsy and histological study</span><p id="par0155" class="elsevierStylePara elsevierViewall">In the same way as in the first phase, when a size equal to or greater than locally advanced or metastatic carcinoma is reached again, animals are euthanized with sodium pentothal and tissue is obtained for anatomopathological and immunohistochemical study.</p><p id="par0160" class="elsevierStylePara elsevierViewall">Descriptive statistics are used to show results.</p><p id="par0165" class="elsevierStylePara elsevierViewall">This study was approved by the Clinical Research Ethics Committee of the University Hospital of Salamanca (reference: CEIC: EO 11/225) and by the Bioethics Committee of the University of Salamanca.</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results</span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results of the first phase</span><p id="par0170" class="elsevierStylePara elsevierViewall">The results of the first phase, following completion of the first implant and growth of the graft to a sufficient size (mass growth with infiltration of adjacent tissues is evaluated by ultrasonography and/or CT for small animals), were as follows (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>):<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0050"><p id="par0175" class="elsevierStylePara elsevierViewall">Group I: the subcutaneous xenograft did not grow. The animals were euthanized at 6 months and no renal tissue was found.</p></li><li class="elsevierStyleListItem" id="lsti0055"><p id="par0180" class="elsevierStylePara elsevierViewall">Group IIA: the xenograft grew at 150 days in all animals. Pathological anatomy: chromophobe RCC.</p></li><li class="elsevierStyleListItem" id="lsti0060"><p id="par0185" class="elsevierStylePara elsevierViewall">Group IIIA: the xenograft grew at 240 days in all mice. Pathological anatomy: clear cell RCC, Fuhrman grade 2.</p></li></ul></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results of the second phase</span><p id="par0190" class="elsevierStylePara elsevierViewall">After the first implant was removed, the second phase was conducted where the second implant was performed. When a tumor size equal to or greater than locally advanced or metastatic carcinoma was reached, the mice were euthanized and the samples were studied. The results after this second phase were as follows (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>):<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0065"><p id="par0195" class="elsevierStylePara elsevierViewall">Group IIB: increase in the implant size in all mice. Animals are euthanized at 150 days. Pathological anatomy: chronic inflammatory reaction of lympho-monocyte predominance (occasional histiocytes) with abscessed foci and dystrophic calcification, peripheral lipoblasts and chronic foreign granulomatous reaction.</p></li><li class="elsevierStyleListItem" id="lsti0070"><p id="par0200" class="elsevierStylePara elsevierViewall">Group IIIB: the tumor grows in all mice. Euthanized at 17–238 days. Pathological anatomy: clear cell RCC, Fuhrman grade 2.</p></li></ul></p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0205" class="elsevierStylePara elsevierViewall">In this study we describe a murine animal model capable of reproducing the biological behavior of clear cell RCC.</p><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Why a murine model?</span><p id="par0210" class="elsevierStylePara elsevierViewall">The subcutaneous implantation of tumor cells has been used to study the <span class="elsevierStyleItalic">in vivo</span> behavior of many tumors.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a> The murine model offers many advantages over other animal models<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a>:<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0075"><span class="elsevierStyleLabel">•</span><p id="par0215" class="elsevierStylePara elsevierViewall">It shares numerous biochemical processes with human beings.</p></li><li class="elsevierStyleListItem" id="lsti0080"><span class="elsevierStyleLabel">•</span><p id="par0220" class="elsevierStylePara elsevierViewall">They have a very short generation time, are very prolific, and easily adapt to life in vivarium, making it possible to control environmental variables in experiments.</p></li><li class="elsevierStyleListItem" id="lsti0085"><span class="elsevierStyleLabel">•</span><p id="par0225" class="elsevierStylePara elsevierViewall">The genome is described almost completely.</p></li><li class="elsevierStyleListItem" id="lsti0090"><span class="elsevierStyleLabel">•</span><p id="par0230" class="elsevierStylePara elsevierViewall">At least 80% of the mouse DNA is identical to that of the human.</p></li></ul></p><p id="par0235" class="elsevierStylePara elsevierViewall">The advantages of these models, compared to human tumor cell lines, are the possibility of studying the effect of mutations predisposing to cancer in a uniform genetic background and of performing basic studies and <span class="elsevierStyleItalic">in vivo</span> therapeutic trials.<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">17–19</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Why a renal cell cancer model?</span><p id="par0240" class="elsevierStylePara elsevierViewall">The treatment of renal cancer has undergone a paradigm shift after the development of molecular biology. The knowledge of new therapeutic targets led to the approval of new drugs for the systemic treatment of renal cancer: sorafenib, sutinib, bevacizumab, pazopanib, temsirolimus and everolimus.</p><p id="par0245" class="elsevierStylePara elsevierViewall">RCC is currently one of the tumors on which more drugs are being tested, with multiple clinical trials evaluating the efficacy of new treatments.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">12</span></a> Although the response rate has increased in patients, they are still not totally curative, so it is necessary to continue doing research in this field, which requires the validation of an experimental model that allows for comparison between treatments.</p><p id="par0250" class="elsevierStylePara elsevierViewall">The study we present has been developed with maximum methodological rigor. The number of animals complies with the legislation in force: the minimum number of animals needed to check the (reproducibility) hypothesis.</p><p id="par0255" class="elsevierStylePara elsevierViewall">The results indicate that fresh tumor tissue obtained during the nephrectomy of patients with clear cell RCC has sufficient carcinogenic capacity to develop the tumor in the mice, reliably reproducing the biological characteristics of the tumor in humans. However, the tissue obtained from the patients with chromophobe RCC did not present such capacity. Therefore, this model is not valid for this histological variety.</p><p id="par0260" class="elsevierStylePara elsevierViewall">After the literature search, we did not find an identical model to compare the results, although there are multiple studies that expose chemically induced murine RCC models (by intraperitoneal injection of dimethylnitrosamines<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">20</span></a>), tumors induced by intravenous injection of streptomycin<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">21</span></a> or estrogen-induced tumors, among others.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a> This is an original study in this field, and no other renal cancer tumor model created by the subcutaneous implantation of a fresh human tumor graft has been described before.</p><p id="par0265" class="elsevierStylePara elsevierViewall">Gonzaga et al. described in 2002 an experimental model of RCC using Wistar rats and using an inoculum of Walker 256 carcinosarcoma type tumor cells that was implanted directly in the right kidney of the animal, generating an orthotopic animal model. This model shows rapid growth and invasiveness and metastasis, being the only murine model found in the literature that reproduces the behavior of RCC.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">In 2007, Hakimé et al<span class="elsevierStyleItalic">.</span> created another murine model to measure the efficacy of antiangiogenic therapy combined with radiofrequency in the treatment of RCC, subcutaneously implanting a sample of RCC obtained from a tumor bank (human 786–0) in nude mice. When the tumor size reached 12<span class="elsevierStyleHsp" style=""></span>mm, they started the treatment, therefore, it is not valid to assess the reproducibility of the biological behavior of the RCC, nor the capacity of local recurrence or distant metastasis.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">In the same line, Jun et al. in 2015 devised a murine model with nude mice to test the efficacy of dual antiangiogenic therapy in combination with radiofrequency in the treatment of RCC,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> also using cells from the human tumor bank 786–0, which were injected subcutaneously into the inguinal region of the animal allowing growth for 14 days until the tumor size acquired approximately 1<span class="elsevierStyleHsp" style=""></span>cm<span class="elsevierStyleSup">3</span>. As in the previous article, although they are valid models to test the effectiveness of the treatments on the reduction of tumor size, it does not allow to verify if the biological behavior of the tumors generated in these models is equal to the behavior of RCC in humans.</p><p id="par0280" class="elsevierStylePara elsevierViewall">Therefore, we emphasize the importance of the search for animal tumor models that allow the study of the biological and molecular characteristics of the different tumors in order to be able to test the efficacy of the various treatments that are in the research phase in the current time.</p><p id="par0285" class="elsevierStylePara elsevierViewall">It would be convenient to develop a second phase of research to test, on the model we have described, the current drugs used in the treatment of clear cell renal cell carcinoma.</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Conclusions</span><p id="par0290" class="elsevierStylePara elsevierViewall">The experimental murine model with athymic Balb/c nude mice is useful for reproducing clear cell renal cell tumors. It exhibits the same histological characteristics and aggressiveness as native human tumors, which encourages the development of the second experimental phase for this study.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interest</span><p id="par0295" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres886503" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec872655" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres886504" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec872656" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:7 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Tumor tissue" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Preliminary elaboration" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Reception and maintenance of animals" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "First phase: preparation of the animals for the first implant" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Second phase: removal of the first implant and realization of the second" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Follow-up and monitoring" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Necropsy and histological study" ] ] ] 6 => array:3 [ "identificador" => "sec0050" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0055" "titulo" => "Results of the first phase" ] 1 => array:2 [ "identificador" => "sec0060" "titulo" => "Results of the second phase" ] ] ] 7 => array:3 [ "identificador" => "sec0065" "titulo" => "Discussion" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0070" "titulo" => "Why a murine model?" ] 1 => array:2 [ "identificador" => "sec0075" "titulo" => "Why a renal cell cancer model?" ] ] ] 8 => array:2 [ "identificador" => "sec0080" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0085" "titulo" => "Conflict of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-09-25" "fechaAceptado" => "2016-11-17" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec872655" "palabras" => array:3 [ 0 => "Renal carcinoma" 1 => "Experimental model" 2 => "Validation" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec872656" "palabras" => array:3 [ 0 => "Carcinoma renal" 1 => "Modelo experimental" 2 => "Validación" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The objective of this study was to determine the reproducibility in a murine model of renal tumors of various histological strains that could be useful for investigating the response to target drugs.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Development and analysis of the “in vivo” model: tumor xenograft of renal cell carcinomas with Balb/c nude athymic mice. Nontumourous human renal tissue was implanted in the interscapular region of 5 mice, chromophobe renal cell carcinoma was implanted in 5 mice (which, after checking its growth, was prepared for implantation in another 10 mice) and Fuhrman grade 2 clear cell renal cell carcinoma (CCRCC) was implanted in 5 mice (which was also subsequently implanted in 10 mice).</p><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We monitored the tumor size, onset of metastases and increase in size and number of tumors. When the size had reached a point greater than or equal to locally advanced or metastatic carcinoma, the animals were euthanised for a pathological and immunohistochemical study and a second phase of implantation.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The subcutaneous xenograft of the healthy tissue did not grow. The animals were euthanised at 6 months and no renal tissue was found. The chromophobe renal cell carcinoma cells grew in the initial phase (100%); however, in the second phase, we observed a chronic lymphomonocyte inflammatory reaction and a foreign body reaction. The CCRCC grew at 5–8 months both in the first and second phase (100%), maintaining the tumor type and grade.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The model with athymic Balb/c nude mice is useful for reproducing CCRCC, with the same histological characteristics and aggressiveness as native human tumors, promoting the development of the second experimental phase.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El objetivo fue conocer la reproductibilidad en modelo murino de tumores renales de diferentes estirpes histológicas que podría ser útil para investigar la respuesta a fármacos diana.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Desarrollo y análisis del modelo <span class="elsevierStyleItalic">in vivo</span>: xenoinjerto tumoral de carcinoma de células renales con ratones atímicos nude Balb/c. Se implanta tejido renal humano no tumoral en la región interescapular de 5 ratones, tumor renal tipo cromófobo en 5 ratones que tras comprobarse su crecimiento se preparó para implante en otros 10 ratones y tumor renal tipo carcinoma renal de células claras (CRCC) Fuhrman 2 en 5 ratones que también se implantó posteriormente en 10 ratones.</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se monitoriza el tamaño tumoral, la aparición de metástasis y el aumento de tamaño y número de las mismas. Cuando alcanza tamaño igual o superior a carcinoma localmente avanzado o metastásico los animales son sacrificados para estudio anatomopatológico, inmunohistoquímico y segunda fase de implante.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">El xenoinjerto subcutáneo del tejido sano no creció, se sacrificaron a los 6 meses sin hallar tejido renal. El carcinoma renal de células cromófobas creció en la primera fase (100%), pero en la segunda fase se observó reacción inflamatoria crónica linfomonocitaria y a cuerpo extraño. El CRCC creció a los 5-8 meses, tanto en la primera como en la segunda fase (100%), manteniendo el tipo y el grado tumoral.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">El modelo con ratones atímicos nude Balb/c es útil para reproducir CRCC, con las mismas características y agresividad histológica al tumor humano nativo, alentando al desarrollo de la segunda fase experimental.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Padilla-Fernández B, García-Cenador MB, Rodríguez-Marcos P, López-Marcos JF, Antúnez-Plaza P, Silva-Abuín JM, et al. Experimental murine model of renal cancer. Actas Urol Esp. 2017;41:445–450.</p>" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0305" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0095" ] ] ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 919 "Ancho" => 2337 "Tamanyo" => 82823 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Realization of the first implant.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1078 "Ancho" => 1504 "Tamanyo" => 71938 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Realization of the second implant.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Growth of the graft \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pathological anatomy \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">I \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No remains of renal tissue \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IIA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chromophobe RCC \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IIIA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">240 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clear RCC. Fuhrman 2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1497955.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Results of the first phase.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Growth of the graft \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Pathological anatomy \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">150 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Foreign body reaction \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IIIB \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17–238 days \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Clear RCC. Fuhrman 2 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1497956.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Results of the second phase.</p>" ] ] 4 => array:5 [ "identificador" => "upi0005" "tipo" => "MULTIMEDIAECOMPONENTE" "mostrarFloat" => false "mostrarDisplay" => true "Ecomponente" => array:2 [ "fichero" => "mmc1.pdf" "ficheroTamanyo" => 71903 ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bib0115" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Globocan 2000: cancer incidence, mortality and prevalence worldwide" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J. Ferlay" 1 => "F. Bray" 2 => "P. Pisan" 3 => "D. 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