array:24 [
  "pii" => "S087321591530163X"
  "issn" => "08732159"
  "doi" => "10.1016/S0873-2159(15)30163-X"
  "estado" => "S350"
  "fechaPublicacion" => "2009-07-01"
  "aid" => "7"
  "copyright" => "Sociedade Portuguesa de Pneumologia/SPP"
  "copyrightAnyo" => "2009"
  "documento" => "simple-article"
  "crossmark" => 0
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "rev"
  "cita" => "Rev Port Pneumol. 2009;15:669-82"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 2620
    "formatos" => array:3 [
      "EPUB" => 247
      "HTML" => 1532
      "PDF" => 841
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S0873215915301641"
    "issn" => "08732159"
    "doi" => "10.1016/S0873-2159(15)30164-1"
    "estado" => "S350"
    "fechaPublicacion" => "2009-07-01"
    "aid" => "8"
    "copyright" => "Sociedade Portuguesa de Pneumologia/SPP"
    "documento" => "simple-article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Rev Port Pneumol. 2009;15:683-96"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 2340
      "formatos" => array:3 [
        "EPUB" => 257
        "HTML" => 1403
        "PDF" => 680
      ]
    ]
    "pt" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Cadernos de Anatomia Patol&#243;gica&#47;Pathology Notebooks</span>"
      "titulo" => "Os genes ERCC1 e RRM1 no carcinoma broncopulmonar"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "pt"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "683"
          "paginaFinal" => "696"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "ERCC1 and RRM1 genes in lung cancer"
        ]
      ]
      "contieneResumen" => array:2 [
        "pt" => true
        "en" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Lina Carvalho, Ant&#243;nio Silva, Cl&#225;udia Andrade, Cl&#225;udia Barroso, Cl&#225;udia Farinha, Jos&#233; Carlos Fernandes, Raquel Landeiro"
          "autores" => array:7 [
            0 => array:2 [
              "nombre" => "Lina"
              "apellidos" => "Carvalho"
            ]
            1 => array:2 [
              "nombre" => "Ant&#243;nio"
              "apellidos" => "Silva"
            ]
            2 => array:2 [
              "nombre" => "Cl&#225;udia"
              "apellidos" => "Andrade"
            ]
            3 => array:2 [
              "nombre" => "Cl&#225;udia"
              "apellidos" => "Barroso"
            ]
            4 => array:2 [
              "nombre" => "Cl&#225;udia"
              "apellidos" => "Farinha"
            ]
            5 => array:2 [
              "nombre" => "Jos&#233; Carlos"
              "apellidos" => "Fernandes"
            ]
            6 => array:2 [
              "nombre" => "Raquel"
              "apellidos" => "Landeiro"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215915301641?idApp=UINPBA00004E"
    "url" => "/08732159/0000001500000004/v1_201509151451/S0873215915301641/v1_201509151451/pt/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S0873215915301628"
    "issn" => "08732159"
    "doi" => "10.1016/S0873-2159(15)30162-8"
    "estado" => "S350"
    "fechaPublicacion" => "2009-07-01"
    "aid" => "6"
    "copyright" => "Sociedade Portuguesa de Pneumologia&#47;SPP"
    "documento" => "simple-article"
    "crossmark" => 0
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "rev"
    "cita" => "Rev Port Pneumol. 2009;15:655-67"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 4076
      "formatos" => array:3 [
        "EPUB" => 251
        "HTML" => 1419
        "PDF" => 2406
      ]
    ]
    "pt" => array:11 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Artigo de Revis&#227;o&#47;Review Article</span>"
      "titulo" => "Ventila&#231;&#227;o n&#227;o invasiva"
      "tienePdf" => "pt"
      "tieneTextoCompleto" => 0
      "tieneResumen" => array:2 [
        0 => "pt"
        1 => "en"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "655"
          "paginaFinal" => "667"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "en" => array:1 [
          "titulo" => "Non-invasive ventilation"
        ]
      ]
      "contieneResumen" => array:2 [
        "pt" => true
        "en" => true
      ]
      "contienePdf" => array:1 [
        "pt" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Susana Ferreira, Carla Nogueira, Sara Conde, Nat&#225;lia Taveira"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Susana"
              "apellidos" => "Ferreira"
            ]
            1 => array:2 [
              "nombre" => "Carla"
              "apellidos" => "Nogueira"
            ]
            2 => array:2 [
              "nombre" => "Sara"
              "apellidos" => "Conde"
            ]
            3 => array:2 [
              "nombre" => "Nat&#225;lia"
              "apellidos" => "Taveira"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "pt"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0873215915301628?idApp=UINPBA00004E"
    "url" => "/08732159/0000001500000004/v1_201509151451/S0873215915301628/v1_201509151451/pt/main.assets"
  ]
  "pt" => array:15 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Artigo de Revis&#227;o&#47;Review Article</span>"
    "titulo" => "Modelos experimentais em oncologia&#58; O contributo da cultura de c&#233;lulas para o conhecimento da biologia do cancro"
    "tieneTextoCompleto" => 0
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "669"
        "paginaFinal" => "682"
      ]
    ]
    "autores" => array:1 [
      0 => array:3 [
        "autoresLista" => "Mariana Cruz, Margarida Enes, Marta Pereira, Mar&#237;lia Dourado, Ana Bela Sarmento Ribeiro"
        "autores" => array:5 [
          0 => array:3 [
            "nombre" => "Mariana"
            "apellidos" => "Cruz"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Margarida"
            "apellidos" => "Enes"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Marta"
            "apellidos" => "Pereira"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">1</span>"
                "identificador" => "af0005"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Mar&#237;lia"
            "apellidos" => "Dourado"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">2</span>"
                "identificador" => "af0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">3</span>"
                "identificador" => "af0015"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Ana Bela Sarmento"
            "apellidos" => "Ribeiro"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">2</span>"
                "identificador" => "af0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">4</span>"
                "identificador" => "af0020"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:4 [
          0 => array:3 [
            "entidad" => "Aluna do 6&#46;&#186; ano de Medicina da Faculdade de Medicina da Universidade de Coimbra 2007-2008"
            "etiqueta" => "1"
            "identificador" => "af0005"
          ]
          1 => array:3 [
            "entidad" => "Professora da Faculdade de Medicina da Universidade de Coimbra"
            "etiqueta" => "2"
            "identificador" => "af0010"
          ]
          2 => array:3 [
            "entidad" => "Disciplina de Fisiopatologia&#44; mestrado integrado em Medicina Dent&#225;ria&#46;"
            "etiqueta" => "3"
            "identificador" => "af0015"
          ]
          3 => array:3 [
            "entidad" => "Instituto de Bioqu&#237;mica e disciplina de Biologia Molecular Aplicada&#46; Mestrado integrado em Medicina"
            "etiqueta" => "4"
            "identificador" => "af0020"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "en" => array:1 [
        "titulo" => "Experimental models in oncology&#58; Contribution of cell culture on understanding the biology of cancer"
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2008-08-08"
    "fechaAceptado" => "2009-02-05"
    "PalabrasClave" => array:2 [
      "pt" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palavras-chave"
          "identificador" => "xpalclavsec570217"
          "palabras" => array:4 [
            0 => "Cultura de c&#233;lulas"
            1 => "oncologia"
            2 => "c&#233;lulas dendr&#237;ticas"
            3 => "terap&#234;utica"
          ]
        ]
      ]
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Key-words"
          "identificador" => "xpalclavsec570216"
          "palabras" => array:4 [
            0 => "Cell culture"
            1 => "oncology"
            2 => "dendritic cells"
            3 => "therapy"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "pt" => array:2 [
        "titulo" => "Resumo"
        "resumen" => "<span id="as0005" class="elsevierStyleSection elsevierViewall"><p id="sp0005" class="elsevierStyleSimplePara elsevierViewall">A cultura de tecidos surgiu no s&#233;culo xx &#40;Harrison&#44; 1907&#41; para estudar o comportamento das c&#233;lulas animais em ambiente homeost&#225;tico e em situa&#231;&#245;es de <span class="elsevierStyleItalic">stress</span>&#46;</p><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">A capacidade de estudar as c&#233;lulas a n&#237;vel molecular relaciona-se com a forma como as c&#233;lulas podem crescer e ser manipuladas em laborat&#243;rio&#46; A cultura de c&#233;lulas <span class="elsevierStyleItalic">in vitro</span> permitiu estudar crescimento&#44; diferencia&#231;&#227;o e morte celular e efectuar manipula&#231;&#245;es gen&#233;ticas necess&#225;rias ao perfeito conhecimento da estrutura e fun&#231;&#245;es dos genes&#46;</p><p id="sp0015" class="elsevierStyleSimplePara elsevierViewall">A cultura de c&#233;lulas estaminais humanas veio colmatar algumas limita&#231;&#245;es inerentes aos restantes modelos de cultura&#46; Ao que parece&#44; as c&#233;lulas estaminais cancer&#237;genas mant&#234;m-se quiescentes nos locais metast&#225;ticos at&#233; serem activadas por sinais apropriados do microambiente&#46;</p><p id="sp0020" class="elsevierStyleSimplePara elsevierViewall">V&#225;rios estudos revelaram que diferentes tipos de cancros podem surgir da transforma&#231;&#227;o maligna de c&#233;lulas estaminais&#46; A elimina&#231;&#227;o destas c&#233;lulas progenitoras tumorais &#233; essencial para o desenvolvimento de novas abordagens terap&#234;uticas mais eficazes em cancros agressivos&#46; Por outro lado&#44; a utiliza&#231;&#227;o de c&#233;lulas dendr&#237;ticas modificadas em cultura poder&#225; contribuir para a produ&#231;&#227;o de uma potencial vacina terap&#234;utica eficaz para obter a regress&#227;o tumoral&#46;</p><p id="sp0025" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Rev Port Pneumol 2009&#59; XV &#40;4&#41;&#58; 669-682</span></p></span>"
      ]
      "en" => array:2 [
        "titulo" => "Abstract"
        "resumen" => "<span id="as0010" class="elsevierStyleSection elsevierViewall"><p id="sp0030" class="elsevierStyleSimplePara elsevierViewall">In the beginning of the 20<span class="elsevierStyleSup">th</span> century&#44; tissue culture was started with the aim of studying the behaviour of animal cells in normal and stress conditions&#46;</p><p id="sp0035" class="elsevierStyleSimplePara elsevierViewall">The cell study at molecular level depends on their capacity of growing and how they can be manipulated in laboratory&#46; <span class="elsevierStyleItalic">In vitro</span> cell culture allows us the possibility of studying biological key processes&#44; such as growth&#44; differentiation and cell death&#44; and also to do genetic manipulations essential to the knowledge of structure and genes function&#46;</p><p id="sp0040" class="elsevierStyleSimplePara elsevierViewall">Human stem cells culture provides strategies to circumvent other models&#8217; deficiencies&#46;</p><p id="sp0045" class="elsevierStyleSimplePara elsevierViewall">It seems that cancer stem cells remain quiescent until activation by appropriated micro-environmental stimulation&#46;</p><p id="sp0050" class="elsevierStyleSimplePara elsevierViewall">Several studies reveal that different cancer types could be due to stem cell malignant transformations&#46; Removal of these cells is essential to the development of more effective cancer therapies for advanced disease&#46; On the other hand&#44; dendritic cells modified in culture may be used as a therapeutic vaccine in order to induce tumour withraw&#46;</p><p id="sp0055" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleBold">Rev Port Pneumol 2009&#59; XV &#40;4&#41;&#58; 669-682</span></p></span>"
      ]
    ]
    "lecturaRecomendada" => array:1 [
      0 => array:3 [
        "vista" => "all"
        "titulo" => "<span class="elsevierStyleSectionTitle" id="st0025">Bibliografia</span>"
        "seccion" => array:1 [
          0 => array:2 [
            "vista" => "all"
            "bibliografiaReferencia" => array:37 [
              0 => array:3 [
                "identificador" => "bb0005"
                "etiqueta" => "1&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:1 [
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "Bruce Alberts"
                              1 => "D&#46; Bray"
                              2 => "J&#46; Lewis"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Libro" => array:5 [
                          "edicion" => "3"
                          "titulo" => "Biologia molecular da c&#233;lula"
                          "fecha" => "1997"
                          "editorial" => "Editora Artes M&#233;dicas"
                          "editorialLocalizacion" => "Porto Alegre"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              1 => array:3 [
                "identificador" => "bb0010"
                "etiqueta" => "2&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "The culture of cell culture"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "M&#46; Susan Lindee"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:6 [
                          "tituloSerie" => "Science"
                          "fecha" => "2007"
                          "volumen" => "316"
                          "numero" => "5831"
                          "paginaInicial" => "1568"
                          "paginaFinal" => "1569"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              2 => array:3 [
                "identificador" => "bb0015"
                "etiqueta" => "3&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Culture of animal cells &#8211; A manual of basic technique"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "R&#46; Ian Freshney"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Libro" => array:4 [
                          "edicion" => "Second edition"
                          "fecha" => "1987"
                          "editorial" => "Alan R Liss&#44; Inc"
                          "editorialLocalizacion" => "New York"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              3 => array:3 [
                "identificador" => "bb0020"
                "etiqueta" => "4&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Cancer stem cells&#58; redefining the paradigm of cancer treatment strategies"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "Michael Dean"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1124/mi.6.3.5"
                        "Revista" => array:6 [
                          "tituloSerie" => "Molecular Interventions"
                          "fecha" => "2006"
                          "volumen" => "6"
                          "paginaInicial" => "140"
                          "paginaFinal" => "148"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16809475"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              4 => array:3 [
                "identificador" => "bb0025"
                "etiqueta" => "5&#46;"
                "referencia" => array:1 [
                  0 => array:1 [
                    "host" => array:2 [
                      0 => array:1 [
                        "Libro" => array:3 [
                          "titulo" => "Stem cells and the future of regenerative medicine &#8211; Free executive summary"
                          "fecha" => "2002"
                          "editorial" => "National Academy of Sciences"
                        ]
                      ]
                      1 => array:1 [
                        "WWW" => array:1 [
                          "link" => "http&#58;&#47;&#47;www&#46;nap&#46;edu&#47;catalog&#47;10195&#46;html"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              5 => array:3 [
                "identificador" => "bb0030"
                "etiqueta" => "6&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Concise Review&#46; Recent advances on the significance of stem cells in tissue regeneration and cancer therapies"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:2 [
                              0 => "Murielle Mimeault"
                              1 => "K&#46; Batra Surinder"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1634/stemcells.2006-0066"
                        "Revista" => array:7 [
                          "tituloSerie" => "Stem cells"
                          "fecha" => "2006"
                          "volumen" => "24"
                          "numero" => "11"
                          "paginaInicial" => "2319"
                          "paginaFinal" => "2345"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16794264"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              6 => array:3 [
                "identificador" => "bb0035"
                "etiqueta" => "7&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Stem cells&#44; cancer and cancer stem cells"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:4 [
                              0 => "Tannishtha Reya"
                              1 => "S&#46;J&#46; Morrison"
                              2 => "M&#46;F&#46; Clarke"
                              3 => "I&#46;L&#46; Weissman"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1038/35102167"
                        "Revista" => array:6 [
                          "tituloSerie" => "Nature"
                          "fecha" => "2001"
                          "volumen" => "414"
                          "paginaInicial" => "105"
                          "paginaFinal" => "111"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11689955"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              7 => array:3 [
                "identificador" => "bb0040"
                "etiqueta" => "8&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "The function of stem cells and their future roles in health care"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "S&#46;H&#46; Cedar"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.12968/bjon.2006.15.2.20372"
                        "Revista" => array:7 [
                          "tituloSerie" => "Br J Nurs"
                          "fecha" => "2006"
                          "volumen" => "15"
                          "numero" => "2"
                          "paginaInicial" => "104"
                          "paginaFinal" => "107"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16493287"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              8 => array:3 [
                "identificador" => "bb0045"
                "etiqueta" => "9&#46;"
                "referencia" => array:1 [
                  0 => array:1 [
                    "referenciaCompleta" => "Margarida Vieira&#44; Gomes A&#44; Castelo-Branco G&#44; Santos R&#46; C&#233;lulas estaminais em obstetr&#237;cia e ginecologia&#44; Parte I&#58; conceitos gerais e aplica&#231;&#245;es&#46; <a href="http://www.crioestaminal.pt/web/eng/pdfs">www&#46;crioestaminal&#46;pt&#47;web&#47;eng&#47;pdfs</a>&#46;"
                  ]
                ]
              ]
              9 => array:3 [
                "identificador" => "bb0050"
                "etiqueta" => "10&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Considerations for targeting malignant stem cells in leukemia"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:2 [
                              0 => "Monica L Guzman"
                              1 => "C&#46;T&#46; Jordan"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:6 [
                          "tituloSerie" => "Cancer Control"
                          "fecha" => "2004"
                          "volumen" => "11"
                          "paginaInicial" => "97"
                          "paginaFinal" => "104"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15024346"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              10 => array:3 [
                "identificador" => "bb0055"
                "etiqueta" => "11&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Treatment of non small cell lung cancer stage IV &#8211; ACCP Evidence Based Pratice Guidelines"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => true
                            "autores" => array:3 [
                              0 => "M&#46;A&#46; Socinski"
                              1 => "R&#46; Crowell"
                              2 => "T&#46;E&#46; Hensing"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:5 [
                          "tituloSerie" => "Chest"
                          "fecha" => "2007"
                          "volumen" => "132"
                          "paginaInicial" => "89"
                          "paginaFinal" => "277"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              11 => array:3 [
                "identificador" => "bb0060"
                "etiqueta" => "12&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Erlotinib e mat&#225;stases cerebrais"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "F&#46; Barata"
                              1 => "T&#46; Costa"
                              2 => "A&#46; Figueiredo"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:6 [
                          "tituloSerie" => "Rev Port Pneumol"
                          "fecha" => "2008"
                          "volumen" => "XIV"
                          "numero" => "supl 3"
                          "paginaInicial" => "S35"
                          "paginaFinal" => "S42"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              12 => array:3 [
                "identificador" => "bb0065"
                "etiqueta" => "13&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Lung cancer"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "Philip C&#46; Hoffman"
                              1 => "A&#46;M&#46; Mauer"
                              2 => "E&#46;E&#46; Vokes"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1016/S0140-6736(00)82038-3"
                        "Revista" => array:6 [
                          "tituloSerie" => "Lancet"
                          "fecha" => "2000"
                          "volumen" => "355"
                          "paginaInicial" => "479"
                          "paginaFinal" => "485"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10841143"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              13 => array:3 [
                "identificador" => "bb0070"
                "etiqueta" => "14&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Inibidores da tirosina-cinase no CPNPC avan&#231;ado&#58; A prop&#243;sito de um caso cl&#237;nico"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:2 [
                              0 => "Ana Ferreira Alves"
                              1 => "M&#46; Liebermann"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1016/S0873-2159(15)30318-4"
                        "Revista" => array:7 [
                          "tituloSerie" => "Rev Port Pneumol"
                          "fecha" => "2008"
                          "volumen" => "14"
                          "numero" => "supl 3"
                          "paginaInicial" => "S23"
                          "paginaFinal" => "S28"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25967683"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              14 => array:3 [
                "identificador" => "bb0075"
                "etiqueta" => "15&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:1 [
                        "titulo" => "NCCN Clinical Practice Guidelines in Oncology"
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:2 [
                          "tituloSerie" => "Non-Small Cell Lung Cancer"
                          "fecha" => "2008"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              15 => array:3 [
                "identificador" => "bb0080"
                "etiqueta" => "16&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Epidermal growth receptor biology &#40;IMC-C225&#41;"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => true
                            "autores" => array:1 [
                              0 => "E&#46;S&#46; Kim"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:6 [
                          "tituloSerie" => "Cur Op Onc"
                          "fecha" => "2001"
                          "volumen" => "13"
                          "numero" => "6"
                          "paginaInicial" => "506"
                          "paginaFinal" => "513"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              16 => array:3 [
                "identificador" => "bb0085"
                "etiqueta" => "17&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Erlotinib no controlo tumoral prolongado do carcinona do pulm&#227;o de n&#227;o pequenas c&#233;lulas avan&#231;ado &#40;CPNPC&#41;"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:5 [
                              0 => "Teresa Guimar&#227;es"
                              1 => "A&#46; Castro"
                              2 => "N&#46; Cortes&#227;o"
                              3 => "J&#46; Ferreira"
                              4 => "F&#46; Jo&#227;o"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1016/S0873-2159(15)30329-9"
                        "Revista" => array:7 [
                          "tituloSerie" => "Rev Port Pneumol"
                          "fecha" => "2008"
                          "volumen" => "14"
                          "numero" => "supl 3"
                          "paginaInicial" => "S9"
                          "paginaFinal" => "S15"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25967896"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              17 => array:3 [
                "identificador" => "bb0090"
                "etiqueta" => "18&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Reduced erlotinib sensitivity of epidermal growth factor receptor-mutant non-small cell lung cancer following cisplatin exposure&#58; A cell culture model of second-line erlotinib treatment"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:8 [
                              0 => "T&#46;M&#46; Chin"
                              1 => "M&#46;P&#46; Quinlan"
                              2 => "A&#46; Singh"
                              3 => "L&#46;V&#46; Sequist"
                              4 => "T&#46;J&#46; Lynch"
                              5 => "D&#46;A&#46; Haber"
                              6 => "S&#46;V&#46; Sharma"
                              7 => "J&#46; Settleman"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1158/1078-0432.CCR-08-0093"
                        "Revista" => array:7 [
                          "tituloSerie" => "Clin Cancer Res"
                          "fecha" => "2008"
                          "volumen" => "14"
                          "numero" => "21"
                          "paginaInicial" => "6867"
                          "paginaFinal" => "6876"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18980981"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              18 => array:3 [
                "identificador" => "bb0095"
                "etiqueta" => "19&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Erlotinib na segunda linha de tratamento do cancro do pulm&#227;o de n&#227;o pequenas c&#233;lulas &#8211; Caso cl&#237;nico"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:4 [
                              0 => "A&#46; Ara&#250;jo"
                              1 => "M&#46; Soares"
                              2 => "I&#46; Azevedo"
                              3 => "A&#46; Ara&#250;jo"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1016/S0873-2159(15)30317-2"
                        "Revista" => array:7 [
                          "tituloSerie" => "Rev Port Pneumol"
                          "fecha" => "2008"
                          "volumen" => "14"
                          "numero" => "supl 3"
                          "paginaInicial" => "S17"
                          "paginaFinal" => "S22"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25967682"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              19 => array:3 [
                "identificador" => "bb0100"
                "etiqueta" => "20&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Angiogenesis and Lung Cancer&#58; Prognostic and therapeutic implications"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "Roy S Herbst"
                              1 => "A&#46; Onn"
                              2 => "A&#46; Sandler"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1200/JCO.2005.18.853"
                        "Revista" => array:6 [
                          "tituloSerie" => "J Clin Oncol"
                          "fecha" => "2005"
                          "volumen" => "23"
                          "paginaInicial" => "3243"
                          "paginaFinal" => "3256"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15886312"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              20 => array:3 [
                "identificador" => "bb0105"
                "etiqueta" => "21&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Designing a Vaccine for cancer&#58; a look into dendritic cell cancer vaccine"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "Jonathan M Ng"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:5 [
                          "tituloSerie" => "McMaster Educater"
                          "fecha" => "2004"
                          "volumen" => "3"
                          "paginaInicial" => "13"
                          "paginaFinal" => "18"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              21 => array:3 [
                "identificador" => "bb0110"
                "etiqueta" => "22&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Dendritic cell-based vaccines for the treatment of cancer"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "J&#46;J&#46; Mul&#233;"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:3 [
                          "tituloSerie" => "Michigan Oncology Journal&#44; Summer"
                          "fecha" => "1998"
                          "itemHostRev" => array:3 [
                            "pii" => "S0210480610004420"
                            "estado" => "S300"
                            "issn" => "02104806"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              22 => array:3 [
                "identificador" => "bb0115"
                "etiqueta" => "23&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Immuno-gene therapy of cancer with tumor-mRNA transfected dendritic cells"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:2 [
                              0 => "J&#46;A&#46; Kyte"
                              1 => "G&#46; Gaudernack"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:2 [
                          "tituloSerie" => "Cancer Immunology Immunother"
                          "fecha" => "2006"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              23 => array:3 [
                "identificador" => "bb0120"
                "etiqueta" => "24&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Immunotherapy of cancer with dendritic cell-based vaccines"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "E&#46; Gilboa"
                              1 => "S&#46;K&#46; Nair"
                              2 => "H&#46;K&#46; Lyerly"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:7 [
                          "tituloSerie" => "Cancer Immunology Immunother"
                          "fecha" => "1998"
                          "volumen" => "46"
                          "numero" => "2"
                          "paginaInicial" => "82"
                          "paginaFinal" => "87"
                          "itemHostRev" => array:3 [
                            "pii" => "S0022534708006186"
                            "estado" => "S300"
                            "issn" => "00225347"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              24 => array:3 [
                "identificador" => "bb0125"
                "etiqueta" => "25&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:1 [
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "H&#46; Bohnenkamp"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:2 [
                      0 => array:1 [
                        "Libro" => array:2 [
                          "titulo" => "Process development for the generation of matured monocyte-derived dendritic cells suitable for clinical aplication"
                          "fecha" => "2006"
                        ]
                      ]
                      1 => array:1 [
                        "WWW" => array:1 [
                          "link" => "www&#46;Fz-juelich&#46;de&#47;ibt&#47;cell&#47;matured-dendritic-cells"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              25 => array:3 [
                "identificador" => "bb0130"
                "etiqueta" => "26&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Dendritic cell therapy for GU malignancies"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "J&#46; Vieweg"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:2 [
                      0 => array:1 [
                        "Revista" => array:3 [
                          "tituloSerie" => "State of the science &#8211; Genitourinary"
                          "fecha" => "2002"
                          "paginaInicial" => "14"
                        ]
                      ]
                      1 => array:1 [
                        "WWW" => array:1 [
                          "link" => "www&#46;webtie&#46;org&#47;SOTS&#47;Meetings&#47;Genitourinary&#47;SUO&#95;12&#95;13&#95;14&#95;2002&#47;lectures&#46;htm"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              26 => array:3 [
                "identificador" => "bb0135"
                "etiqueta" => "27&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "An effective cancer vaccine modality&#58; lentiviral modification of dendritic cells expressing multiple cancer-specific antigens"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:4 [
                              0 => "B&#46; Wang"
                              1 => "J&#46; He"
                              2 => "C&#46; Lui"
                              3 => "L&#46;J&#46; Chang"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1016/j.vaccine.2006.02.025"
                        "Revista" => array:6 [
                          "tituloSerie" => "Vaccine"
                          "fecha" => "2006"
                          "volumen" => "24"
                          "paginaInicial" => "3477"
                          "paginaFinal" => "3489"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16530303"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              27 => array:3 [
                "identificador" => "bb0140"
                "etiqueta" => "28&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Dendritic cell therapy with improved outcome in glioma multiformr &#8211; A case report"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:2 [
                              0 => "J&#46;A&#46; Khan"
                              1 => "S&#46; Yaqin"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:5 [
                          "tituloSerie" => "J Zhejiang University Sc B"
                          "fecha" => "2006"
                          "volumen" => "7"
                          "paginaInicial" => "114"
                          "paginaFinal" => "117"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              28 => array:3 [
                "identificador" => "bb0145"
                "etiqueta" => "29&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Genetically modified dendritic cells for cancer immunotherapy"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:1 [
                              0 => "A&#46; Ribas"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:6 [
                          "tituloSerie" => "Curr Gene Therapy"
                          "fecha" => "2005"
                          "volumen" => "5"
                          "numero" => "6"
                          "paginaInicial" => "619"
                          "paginaFinal" => "628"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              29 => array:3 [
                "identificador" => "bb0150"
                "etiqueta" => "30&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Dendritic cells in cancer immunotherapy"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:2 [
                              0 => "L&#46; Fong"
                              1 => "E&#46;G&#46; Engleman"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:5 [
                          "tituloSerie" => "Annual Rev Immunol"
                          "fecha" => "2000"
                          "volumen" => "18"
                          "paginaInicial" => "245"
                          "paginaFinal" => "273"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              30 => array:3 [
                "identificador" => "bb0155"
                "etiqueta" => "31&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:4 [
                              0 => "E&#46;J&#46; Small"
                              1 => "P&#46; Fratesi"
                              2 => "D&#46;M&#46; Reese"
                              3 => "G&#46; Strang"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:5 [
                          "tituloSerie" => "J Clinical Oncol"
                          "fecha" => "2000"
                          "volumen" => "18"
                          "paginaInicial" => "3894"
                          "paginaFinal" => "3903"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              31 => array:3 [
                "identificador" => "bb0160"
                "etiqueta" => "32&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Vaccinations of melanoma patients with peptide or tumor lysatepulsed dendritic cells"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:4 [
                              0 => "F&#46;O&#46; Nestle"
                              1 => "S&#46; Alijagic"
                              2 => "M&#46; Gilliet"
                              3 => "Y&#46; Sun"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:7 [
                          "tituloSerie" => "Nat Med"
                          "fecha" => "1998"
                          "volumen" => "4"
                          "numero" => "3"
                          "paginaInicial" => "328"
                          "paginaFinal" => "332"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9500607"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              32 => array:3 [
                "identificador" => "bb0165"
                "etiqueta" => "33&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Dendritic cell vaccines for cancer immunotherapy"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:2 [
                              0 => "J&#46;M&#46; Timmerman"
                              1 => "R&#46; Levy"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:5 [
                          "tituloSerie" => "Annual Rev Medicine"
                          "fecha" => "1999"
                          "volumen" => "50"
                          "paginaInicial" => "507"
                          "paginaFinal" => "529"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              33 => array:3 [
                "identificador" => "bb0170"
                "etiqueta" => "34&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Vaccination of colorectal cancer patients with CEA-loaded dendritic cells&#58; antigen specific T cell responses in DTH skin test"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "W&#46;J&#46; Lesterhuis"
                              1 => "L&#46;J&#46; Vries"
                              2 => "D&#46;H&#46; Schuurhuis"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:5 [
                          "tituloSerie" => "Annual Oncology"
                          "fecha" => "2006"
                          "volumen" => "17"
                          "paginaInicial" => "974"
                          "paginaFinal" => "980"
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              34 => array:3 [
                "identificador" => "bb0175"
                "etiqueta" => "35&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Dendritic cell-based immunotherapy for ovarian cancer"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => true
                            "autores" => array:3 [
                              0 => "A&#46;D&#46; Santin"
                              1 => "S&#46; Bellone"
                              2 => "L&#46;J&#46; Underwood"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:1 [
                        "Revista" => array:7 [
                          "tituloSerie" => "Minerva Ginecol"
                          "fecha" => "2002"
                          "volumen" => "54"
                          "numero" => "2"
                          "paginaInicial" => "133"
                          "paginaFinal" => "144"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12032451"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              35 => array:3 [
                "identificador" => "bb0180"
                "etiqueta" => "36&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Sensitization of malignant glioma to chemotherapy through dendritic cell vaccination"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "G&#46; Liu"
                              1 => "K&#46;L&#46; Black"
                              2 => "J&#46;S&#46; Yu"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1586/14760584.5.2.233"
                        "Revista" => array:7 [
                          "tituloSerie" => "Expert Rev Vaccines"
                          "fecha" => "2006"
                          "volumen" => "5"
                          "numero" => "2"
                          "paginaInicial" => "233"
                          "paginaFinal" => "247"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16608423"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
              36 => array:3 [
                "identificador" => "bb0185"
                "etiqueta" => "37&#46;"
                "referencia" => array:1 [
                  0 => array:2 [
                    "contribucion" => array:1 [
                      0 => array:2 [
                        "titulo" => "Current state and perspectives of dendritic cell vaccination in cancer immunotherapy"
                        "autores" => array:1 [
                          0 => array:2 [
                            "etal" => false
                            "autores" => array:3 [
                              0 => "A&#46; Farkas"
                              1 => "C&#46; Conrad"
                              2 => "G&#46; Tonel"
                            ]
                          ]
                        ]
                      ]
                    ]
                    "host" => array:1 [
                      0 => array:2 [
                        "doi" => "10.1159/000092592"
                        "Revista" => array:6 [
                          "tituloSerie" => "Skin Pharmacol Physiol"
                          "fecha" => "2006"
                          "volumen" => "19"
                          "paginaInicial" => "124"
                          "paginaFinal" => "131"
                          "link" => array:1 [
                            0 => array:2 [
                              "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16612139"
                              "web" => "Medline"
                            ]
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "pt"
  "url" => "/08732159/0000001500000004/v1_201509151451/S087321591530163X/v1_201509151451/pt/main.assets"
  "Apartado" => array:4 [
    "identificador" => "43356"
    "tipo" => "SECCION"
    "pt" => array:2 [
      "titulo" => "Artigos de revis&#227;o"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "pt"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/08732159/0000001500000004/v1_201509151451/S087321591530163X/v1_201509151451/pt/main.pdf?idApp=UINPBA00004E&text.app=https://journalpulmonology.org/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S087321591530163X?idApp=UINPBA00004E"
]
Share
Journal Information
Vol. 15. Issue 4.
Pages 669-682 (July - August 2009)
Share
Share
Download PDF
More article options
Vol. 15. Issue 4.
Pages 669-682 (July - August 2009)
Artigo de Revisão/Review Article
Open Access
Modelos experimentais em oncologia: O contributo da cultura de células para o conhecimento da biologia do cancro
Experimental models in oncology: Contribution of cell culture on understanding the biology of cancer
Visits
6033
Mariana Cruz1, Margarida Enes1, Marta Pereira1, Marília Dourado2,3, Ana Bela Sarmento Ribeiro2,4
1 Aluna do 6.º ano de Medicina da Faculdade de Medicina da Universidade de Coimbra 2007-2008
2 Professora da Faculdade de Medicina da Universidade de Coimbra
3 Disciplina de Fisiopatologia, mestrado integrado em Medicina Dentária.
4 Instituto de Bioquímica e disciplina de Biologia Molecular Aplicada. Mestrado integrado em Medicina
This item has received

Under a Creative Commons license
Article information
Resumo

A cultura de tecidos surgiu no século xx (Harrison, 1907) para estudar o comportamento das células animais em ambiente homeostático e em situações de stress.

A capacidade de estudar as células a nível molecular relaciona-se com a forma como as células podem crescer e ser manipuladas em laboratório. A cultura de células in vitro permitiu estudar crescimento, diferenciação e morte celular e efectuar manipulações genéticas necessárias ao perfeito conhecimento da estrutura e funções dos genes.

A cultura de células estaminais humanas veio colmatar algumas limitações inerentes aos restantes modelos de cultura. Ao que parece, as células estaminais cancerígenas mantêm-se quiescentes nos locais metastáticos até serem activadas por sinais apropriados do microambiente.

Vários estudos revelaram que diferentes tipos de cancros podem surgir da transformação maligna de células estaminais. A eliminação destas células progenitoras tumorais é essencial para o desenvolvimento de novas abordagens terapêuticas mais eficazes em cancros agressivos. Por outro lado, a utilização de células dendríticas modificadas em cultura poderá contribuir para a produção de uma potencial vacina terapêutica eficaz para obter a regressão tumoral.

Rev Port Pneumol 2009; XV (4): 669-682

Palavras-chave:
Cultura de células
oncologia
células dendríticas
terapêutica
Abstract

In the beginning of the 20th century, tissue culture was started with the aim of studying the behaviour of animal cells in normal and stress conditions.

The cell study at molecular level depends on their capacity of growing and how they can be manipulated in laboratory. In vitro cell culture allows us the possibility of studying biological key processes, such as growth, differentiation and cell death, and also to do genetic manipulations essential to the knowledge of structure and genes function.

Human stem cells culture provides strategies to circumvent other models’ deficiencies.

It seems that cancer stem cells remain quiescent until activation by appropriated micro-environmental stimulation.

Several studies reveal that different cancer types could be due to stem cell malignant transformations. Removal of these cells is essential to the development of more effective cancer therapies for advanced disease. On the other hand, dendritic cells modified in culture may be used as a therapeutic vaccine in order to induce tumour withraw.

Rev Port Pneumol 2009; XV (4): 669-682

Key-words:
Cell culture
oncology
dendritic cells
therapy
Full text is only aviable in PDF
Bibliografia
[1.]
Bruce Alberts, D. Bray, J. Lewis.
Biologia molecular da célula, 3, Editora Artes Médicas, (1997),
[2.]
M. Susan Lindee.
The culture of cell culture.
Science, 316 (2007), pp. 1568-1569
[3.]
R. Ian Freshney.
Culture of animal cells – A manual of basic technique.
Second edition, Alan R Liss, Inc, (1987),
[4.]
Michael Dean.
Cancer stem cells: redefining the paradigm of cancer treatment strategies.
Molecular Interventions, 6 (2006), pp. 140-148
[5.]
Stem cells and the future of regenerative medicine – Free executive summary, National Academy of Sciences, (2002),
[6.]
Murielle Mimeault, K. Batra Surinder.
Concise Review. Recent advances on the significance of stem cells in tissue regeneration and cancer therapies.
Stem cells, 24 (2006), pp. 2319-2345
[7.]
Tannishtha Reya, S.J. Morrison, M.F. Clarke, I.L. Weissman.
Stem cells, cancer and cancer stem cells.
Nature, 414 (2001), pp. 105-111
[8.]
S.H. Cedar.
The function of stem cells and their future roles in health care.
Br J Nurs, 15 (2006), pp. 104-107
[9.]
Margarida Vieira, Gomes A, Castelo-Branco G, Santos R. Células estaminais em obstetrícia e ginecologia, Parte I: conceitos gerais e aplicações. www.crioestaminal.pt/web/eng/pdfs.
[10.]
Monica L Guzman, C.T. Jordan.
Considerations for targeting malignant stem cells in leukemia.
Cancer Control, 11 (2004), pp. 97-104
[11.]
M.A. Socinski, R. Crowell, T.E. Hensing, et al.
Treatment of non small cell lung cancer stage IV – ACCP Evidence Based Pratice Guidelines.
Chest, 132 (2007), pp. 89-277
[12.]
F. Barata, T. Costa, A. Figueiredo.
Erlotinib e matástases cerebrais.
Rev Port Pneumol, XIV (2008), pp. S35-S42
[13.]
Philip C. Hoffman, A.M. Mauer, E.E. Vokes.
Lung cancer.
[14.]
Ana Ferreira Alves, M. Liebermann.
Inibidores da tirosina-cinase no CPNPC avançado: A propósito de um caso clínico.
Rev Port Pneumol, 14 (2008), pp. S23-S28
[15.]
NCCN Clinical Practice Guidelines in Oncology.
Non-Small Cell Lung Cancer, (2008),
[16.]
E.S. Kim, et al.
Epidermal growth receptor biology (IMC-C225).
Cur Op Onc, 13 (2001), pp. 506-513
[17.]
Teresa Guimarães, A. Castro, N. Cortesão, J. Ferreira, F. João.
Erlotinib no controlo tumoral prolongado do carcinona do pulmão de não pequenas células avançado (CPNPC).
Rev Port Pneumol, 14 (2008), pp. S9-S15
[18.]
T.M. Chin, M.P. Quinlan, A. Singh, L.V. Sequist, T.J. Lynch, D.A. Haber, S.V. Sharma, J. Settleman.
Reduced erlotinib sensitivity of epidermal growth factor receptor-mutant non-small cell lung cancer following cisplatin exposure: A cell culture model of second-line erlotinib treatment.
Clin Cancer Res, 14 (2008), pp. 6867-6876
[19.]
A. Araújo, M. Soares, I. Azevedo, A. Araújo.
Erlotinib na segunda linha de tratamento do cancro do pulmão de não pequenas células – Caso clínico.
Rev Port Pneumol, 14 (2008), pp. S17-S22
[20.]
Roy S Herbst, A. Onn, A. Sandler.
Angiogenesis and Lung Cancer: Prognostic and therapeutic implications.
J Clin Oncol, 23 (2005), pp. 3243-3256
[21.]
Jonathan M Ng.
Designing a Vaccine for cancer: a look into dendritic cell cancer vaccine.
McMaster Educater, 3 (2004), pp. 13-18
[22.]
J.J. Mulé.
Dendritic cell-based vaccines for the treatment of cancer.
Michigan Oncology Journal, Summer, (1998),
[23.]
J.A. Kyte, G. Gaudernack.
Immuno-gene therapy of cancer with tumor-mRNA transfected dendritic cells.
Cancer Immunology Immunother, (2006),
[24.]
E. Gilboa, S.K. Nair, H.K. Lyerly.
Immunotherapy of cancer with dendritic cell-based vaccines.
Cancer Immunology Immunother, 46 (1998), pp. 82-87
[25.]
H. Bohnenkamp.
Process development for the generation of matured monocyte-derived dendritic cells suitable for clinical aplication, (2006),
[26.]
J. Vieweg.
Dendritic cell therapy for GU malignancies.
State of the science – Genitourinary, (2002), pp. 14
[27.]
B. Wang, J. He, C. Lui, L.J. Chang.
An effective cancer vaccine modality: lentiviral modification of dendritic cells expressing multiple cancer-specific antigens.
Vaccine, 24 (2006), pp. 3477-3489
[28.]
J.A. Khan, S. Yaqin.
Dendritic cell therapy with improved outcome in glioma multiformr – A case report.
J Zhejiang University Sc B, 7 (2006), pp. 114-117
[29.]
A. Ribas.
Genetically modified dendritic cells for cancer immunotherapy.
Curr Gene Therapy, 5 (2005), pp. 619-628
[30.]
L. Fong, E.G. Engleman.
Dendritic cells in cancer immunotherapy.
Annual Rev Immunol, 18 (2000), pp. 245-273
[31.]
E.J. Small, P. Fratesi, D.M. Reese, G. Strang.
Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells.
J Clinical Oncol, 18 (2000), pp. 3894-3903
[32.]
F.O. Nestle, S. Alijagic, M. Gilliet, Y. Sun.
Vaccinations of melanoma patients with peptide or tumor lysatepulsed dendritic cells.
Nat Med, 4 (1998), pp. 328-332
[33.]
J.M. Timmerman, R. Levy.
Dendritic cell vaccines for cancer immunotherapy.
Annual Rev Medicine, 50 (1999), pp. 507-529
[34.]
W.J. Lesterhuis, L.J. Vries, D.H. Schuurhuis.
Vaccination of colorectal cancer patients with CEA-loaded dendritic cells: antigen specific T cell responses in DTH skin test.
Annual Oncology, 17 (2006), pp. 974-980
[35.]
A.D. Santin, S. Bellone, L.J. Underwood, et al.
Dendritic cell-based immunotherapy for ovarian cancer.
Minerva Ginecol, 54 (2002), pp. 133-144
[36.]
G. Liu, K.L. Black, J.S. Yu.
Sensitization of malignant glioma to chemotherapy through dendritic cell vaccination.
Expert Rev Vaccines, 5 (2006), pp. 233-247
[37.]
A. Farkas, C. Conrad, G. Tonel.
Current state and perspectives of dendritic cell vaccination in cancer immunotherapy.
Skin Pharmacol Physiol, 19 (2006), pp. 124-131
Copyright © 2009. Sociedade Portuguesa de Pneumologia/SPP
Download PDF
Pulmonology
Article options
Tools

Are you a health professional able to prescribe or dispense drugs?