NoveltIes in dermatology
New Therapies Targeting the Genetic Mutations Responsible for Different Types of Melanoma
Diferentes alteraciones genéticas causan diferentes melanomas y nuevas posibilidades terapéuticas
R. Botella-Estrada
, O. Sanmartín Jiménez
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Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain
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"apellidos" => "Botella-Estrada" "email" => array:1 [ 0 => "rbotellaes@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">¿</span>" "identificador" => "cor1" ] ] ] 1 => array:2 [ "nombre" => "O." "apellidos" => "Sanmartín Jiménez" ] ] "afiliaciones" => array:1 [ 0 => array:1 [ "entidad" => "Servicio de Dermatología, Instituto Valenciano de Oncología, Valencia, Spain" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Diferentes alteraciones genéticas causan diferentes melanomas y nuevas posibilidades terapéuticas" ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2009-12-29" "fechaAceptado" => "2010-01-21" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec84762" "palabras" => array:6 [ 0 => "Melanoma" 1 => "MAPK" 2 => "BRAF" 3 => "KIT" 4 => "Sorafenib" 5 => "Imatinib" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec84763" "palabras" => array:6 [ 0 => "Melanoma" 1 => "MAPK" 2 => "BRAF" 3 => "KIT" 4 => "Sorafenib" 5 => "Imatinib" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">A number of molecular alterations have been described for melanoma. Melanomas with BRAF mutations tend to be located in areas of intermittent sun exposure, whereas melanomas with KIT mutations mostly appear in acral areas, the mucosa, and areas of chronic sun exposure. Sorafenib, a BRAF inhibitor, has a cytostatic effect on most melanomas with mutations affecting the mitogen-activated protein kinase (MAPK) pathway, and is also capable of triggering apoptosis in a small subgroup of these melanomas. By inhibiting KIT, imatinib has a cytostatic and cytotoxic effect on melanomas with KIT mutations, and probably has the same effect on another subgroup of melanomas with other as yet imperfectly understood KIT mutations. For therapy to be effective, agents should be selected according to the pathways associated with the genetic mutations present in the melanoma.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p class="elsevierStyleSimplePara elsevierViewall">Se han descrito diversas alteraciones moleculares en el melanoma. Los melanomas con mutaciones de BRAF suelen localizarse en zonas con exposición solar intermitente mientras que las alteraciones genéticas de KIT ocurren con mayor frecuencia en los melanomas acrales, mucosos y en los que se localizan en áreas con exposición solar crónica. Sorafenib, un inhibidor de BRAF, tiene un efecto citostático en la mayoría de los melanomas con mutaciones en la vía MAP cinasa, aunque en un pequeño subgrupo de estos melanomas es también capaz de promover la apoptosis. Imatinib, a través de la inhibición de KIT, posee un efecto citostático y citotóxico en aquellos melanomas con mutaciones de KIT, y probablemente en otro subgrupo de melanomas con otras alteraciones genéticas de KIT aún no perfectamente definidas. Para que estos tratamientos sean efectivos es imprescindible que se hayan seleccionado adecuadamente los pacientes, estableciéndose la existencia de alteraciones genéticas en la vía sobre la que se va a actuar.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:1 [ "bibliografiaReferencia" => array:44 [ 0 => array:3 [ "identificador" => "bib1" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A single-institution validation of the AJCC staging system for stage IV melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "H.B. Neuman" 1 => "A. Patel" 2 => "N. Ishill" 3 => "C. Hanlon" 4 => "M.S. Brady" 5 => "A.C. Halpern" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1245/s10434-008-9915-0" "Revista" => array:6 [ "tituloSerie" => "Ann Surg Oncol" "fecha" => "2008" "volumen" => "15" "paginaInicial" => "2034" "paginaFinal" => "2041" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18465172" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib2" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Prognostic factors analysis of 17,600 melanoma patients: validation of the American Joint Committee on Cancer melanoma staging system" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C.M. Balch" 1 => "S.J. Soong" 2 => "J.E. Gershenwald" 3 => "J.F. Thompson" 4 => "D.S. Reintgen" 5 => "N. Cascinelli" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/jco.2001.19.16.3622" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2001" "volumen" => "19" "paginaInicial" => "3622" "paginaFinal" => "3634" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11504744" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib3" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Ries LAG, Eisner MP, Kosary CL, Hankey BF, Miller BA, Clegg L, et al. SEER Cancer Statistics Review, 1975-2002. Bethesda MD: National Cancer Institute. Available from: <a class="elsevierStyleInterRef" href="http://www.seer.cancer.gov/csr/1975_2002">http://www.seer.cancer.gov/csr/1975_2002</a>" ] ] ] 3 => array:3 [ "identificador" => "bib4" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Fast-growing and slow-growing melanomas" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Argenziano" 1 => "I. Zalaudek" 2 => "G. Ferrara" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1001/archderm.143.6.802" "Revista" => array:6 [ "tituloSerie" => "Arch Dermatol" "fecha" => "2007" "volumen" => "143" "paginaInicial" => "802" "paginaFinal" => "803" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17576955" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib5" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Malignant melanoma: genetics and therapeutics in the genomic era" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "L. Chin" 1 => "L.A. Garraway" 2 => "D.E. Fisher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1101/gad.1437206" "Revista" => array:6 [ "tituloSerie" => "Genes Dev" "fecha" => "2006" "volumen" => "20" "paginaInicial" => "2149" "paginaFinal" => "2182" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16912270" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib6" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A.J. Miller" 1 => "M.C. Mihm" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMra052166" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2006" "volumen" => "355" "paginaInicial" => "51" "paginaFinal" => "55" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16822996" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib7" "etiqueta" => "7." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "NRAS and BRAF mutations arise early during melanoma pathogenesis and are preserved throughout tumor progression" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "K. Omholt" 1 => "A. Platz" 2 => "L. Kanter" 3 => "U. Ringborg" 4 => "J. Hansson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2003" "volumen" => "9" "paginaInicial" => "6483" "paginaFinal" => "6488" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14695152" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib8" "etiqueta" => "8." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High frequency of BRAF mutations in nevi" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.M. Pollock" 1 => "U.L. Harper" 2 => "K.S. Hansen" 3 => "L.M. Yudt" 4 => "M. Stark" 5 => "C.M. Robbins" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1054" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2003" "volumen" => "33" "paginaInicial" => "19" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12447372" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib9" "etiqueta" => "9." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeting the mitogen activated protein kinase cascade to treat cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "J.S. Sebolt-Leopold" 1 => "R. Herrera" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Nature Rev Cancer" "fecha" => "2004" "volumen" => "4" "paginaInicial" => "937" "paginaFinal" => "947" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib10" "etiqueta" => "10." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "BRAFE600-associated senescencelike cell cycle arrest of human naevi" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Michaloglou" 1 => "L.C. Vredeveld" 2 => "M.S. Soengas" 3 => "C. Denoyelle" 4 => "T. Kuilman" 5 => "C.M. van der Horst" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/nature03890" "Revista" => array:6 [ "tituloSerie" => "Nature" "fecha" => "2005" "volumen" => "436" "paginaInicial" => "720" "paginaFinal" => "724" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16079850" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib11" "etiqueta" => "11." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CDKN2A variants in a population-based sample of Queensland families with melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Aitken" 1 => "J. Welch" 2 => "D. Duffy" 3 => "A. Milligan" 4 => "A. Green" 5 => "N. Martin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Natl Cancer Inst" "fecha" => "1999" "volumen" => "91" "paginaInicial" => "446" "paginaFinal" => "452" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10070944" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib12" "etiqueta" => "12." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "PTEN, a putative protein tyrosine phosphatase gene mutated in human brain, breast, and prostate cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Li" 1 => "C. Yen" 2 => "D. Liaw" 3 => "K. Podsypanina" 4 => "S. Bose" 5 => "S.I. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "1997" "volumen" => "275" "paginaInicial" => "1943" "paginaFinal" => "1947" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9072974" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib13" "etiqueta" => "13." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Examination of mutations in BRAF, NRAS, and PTEN in primary cutaneous melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "V.K. Goel" 1 => "A.J. Lazar" 2 => "C.L. Warneke" 3 => "M.S. Redston" 4 => "F.G. Haluska" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.jid.5700026" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2006" "volumen" => "126" "paginaInicial" => "154" "paginaFinal" => "160" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16417231" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib14" "etiqueta" => "14." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Germline mutations in genes within the MAPK pathway cause cardio-facio-cutaneous syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Rodríguez-Viciana" 1 => "O. Tetsu" 2 => "W.E. Tidyman" 3 => "A.L. Estep" 4 => "B.A. Conger" 5 => "M.S. Cruz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1126/science.1124642" "Revista" => array:6 [ "tituloSerie" => "Science" "fecha" => "2006" "volumen" => "311" "paginaInicial" => "1287" "paginaFinal" => "1290" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16439621" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib15" "etiqueta" => "15." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Distinct sets of genetic alterations in melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.A. Curtin" 1 => "J. Fridlyand" 2 => "T. Kageshita" 3 => "H.N. Patel" 4 => "K.J. Busam" 5 => "H. Kutzner" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa050092" "Revista" => array:6 [ "tituloSerie" => "N Engl J Med" "fecha" => "2005" "volumen" => "353" "paginaInicial" => "2135" "paginaFinal" => "2147" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16291983" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib16" "etiqueta" => "16." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Improving melanoma classification by integrating genetic and morphologic features" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Viros" 1 => "J. Fridlyand" 2 => "J. Bauer" 3 => "K. Lasithiotakis" 4 => "C. Garbe" 5 => "D. Pinkel" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "PLoS Medicine" "fecha" => "2008" "volumen" => "5" "paginaInicial" => "941" "paginaFinal" => "952" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib17" "etiqueta" => "17." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Suppression of BRAF (V599E) in human melanoma abrogates transformation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "S.R. Hingorani" 1 => "M.A. Jacobetz" 2 => "G.P. Robertson" 3 => "M. Herlyn" 4 => "D.A. Tuveson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2003" "volumen" => "63" "paginaInicial" => "5198" "paginaFinal" => "5202" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14500344" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib18" "etiqueta" => "18." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Oncogenic BRAF is required for tumor growth and maintenance in melanoma models" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.P. Hoeflich" 1 => "D.C. Gray" 2 => "M.T. Eby" 3 => "J.Y. Tien" 4 => "L. Wong" 5 => "J. Bower" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/0008-5472.CAN-05-2720" "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2006" "volumen" => "66" "paginaInicial" => "999" "paginaFinal" => "1006" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16424035" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib19" "etiqueta" => "19." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autocrine and paracrine regulation by cytokines and growth factors in melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "E. Lazar-Molnar" 1 => "H. Hegyesi" 2 => "S. Toth" 3 => "A. Falus" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/cyto.1999.0614" "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2000" "volumen" => "12" "paginaInicial" => "547" "paginaFinal" => "554" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10843728" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib20" "etiqueta" => "20." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Use of human tissue to assess the oncogenic activity of melanomaassociated mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "Y. Chudnovsky" 1 => "A.E. Adams" 2 => "P.B. Robbins" 3 => "Q. Lin" 4 => "P.A. Khavari" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/ng1586" "Revista" => array:6 [ "tituloSerie" => "Nat Genet" "fecha" => "2005" "volumen" => "37" "paginaInicial" => "745" "paginaFinal" => "749" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15951821" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib21" "etiqueta" => "21." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Safety, pharmacokinetics, and preliminary antitumor activity of sorafenib: a review of four phase I trials in patients with advanced refractory solid tumors" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D. Strumberg" 1 => "J.W. Clark" 2 => "A. Awada" 3 => "M.J. Moore" 4 => "H. Richly" 5 => "A. Hendlisz" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1634/theoncologist.12-4-426" "Revista" => array:6 [ "tituloSerie" => "Oncologist" "fecha" => "2007" "volumen" => "12" "paginaInicial" => "426" "paginaFinal" => "437" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17470685" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib22" "etiqueta" => "22." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phase I/II, pharmacokinetic and pharmacodynamic trial of BAY 43-9006 alone in patients with metastatic melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K.T. Flaherty" 1 => "M. Redlinger" 2 => "L.M. Shchucter" 3 => "C.D. Lathia" 4 => "B.L. Weber" 5 => "P.J. O’Dwyer" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2005" "volumen" => "23" "paginaInicial" => "3037" ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib23" "etiqueta" => "23." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sorafenib in advanced melanoma: a Phase II randomised discontinuation trial analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "T. Eisen" 1 => "T. Ahmad" 2 => "K.T. Flaherty" 3 => "M. Gore" 4 => "S. Kaye" 5 => "R. Marais" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bjc.6603291" "Revista" => array:6 [ "tituloSerie" => "Br J Cancer" "fecha" => "2006" "volumen" => "95" "paginaInicial" => "581" "paginaFinal" => "586" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16880785" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib24" "etiqueta" => "24." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Double-blind randomized phase II study of the combination of sorafenib and dacarbazine in patients with advanced melanoma: A report from the 11715 Study Group" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.F. McDermott" 1 => "J.A. Sosman" 2 => "R. Gonzalez" 3 => "F.S. Hodi" 4 => "G.P. Linette" 5 => "J. Richards" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.14.8288" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "2178" "paginaFinal" => "2185" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18445842" "web" => "Medline" ] ] ] ] ] ] ] ] 24 => array:3 [ "identificador" => "bib25" "etiqueta" => "25." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "CRAF inhibition induces apoptosis in melanoma cells with non-V600E BRAF mutations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.S. Smalley" 1 => "M. Xiao" 2 => "J. Villanueva" 3 => "T.K. Nguyen" 4 => "K.T. Flaherty" 5 => "R. Letrero" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/onc.2008.362" "Revista" => array:6 [ "tituloSerie" => "Oncogene" "fecha" => "2009" "volumen" => "28" "paginaInicial" => "85" "paginaFinal" => "94" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18794803" "web" => "Medline" ] ] ] ] ] ] ] ] 25 => array:3 [ "identificador" => "bib26" "etiqueta" => "26." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.T. Wan" 1 => "M.J. Garnett" 2 => "S.M. Roe" 3 => "S. Lee" 4 => "D. Niculescu-Duvaz" 5 => "V.M. Good" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Cell" "fecha" => "2004" "volumen" => "116" "paginaInicial" => "855" "paginaFinal" => "867" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15035987" "web" => "Medline" ] ] ] ] ] ] ] ] 26 => array:3 [ "identificador" => "bib27" "etiqueta" => "27." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "In melanoma, RAS mutations are accompanied by switching signalling from BRAF to CRAF and disrupted cyclic AMP signaling" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Dumaz" 1 => "R. Hayward" 2 => "J. Martin" 3 => "L. Ogilvie" 4 => "D. Hedley" 5 => "J.A. Curtin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/0008-5472.CAN-05-4227" "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2006" "volumen" => "66" "paginaInicial" => "9483" "paginaFinal" => "9491" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17018604" "web" => "Medline" ] ] ] ] ] ] ] ] 27 => array:3 [ "identificador" => "bib28" "etiqueta" => "28." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Genetic subgrouping of melanoma reveals new opportunities for targeted therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "K.S.M. Smalley" 1 => "K.L. Nathanson" 2 => "K.T. Flaherty" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/0008-5472.CAN-08-4305" "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2009" "volumen" => "69" "paginaInicial" => "3241" "paginaFinal" => "3244" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19351826" "web" => "Medline" ] ] ] ] ] ] ] ] 28 => array:3 [ "identificador" => "bib29" "etiqueta" => "29." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K.S. Smalley" 1 => "N.K. Haass" 2 => "P.A. Brafford" 3 => "M. Lioni" 4 => "K.T. Flaherty" 5 => "M. Herlyn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1535-7163.MCT-06-0084" "Revista" => array:6 [ "tituloSerie" => "Mol Cancer Ther" "fecha" => "2006" "volumen" => "5" "paginaInicial" => "1136" "paginaFinal" => "1144" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16731745" "web" => "Medline" ] ] ] ] ] ] ] ] 29 => array:3 [ "identificador" => "bib30" "etiqueta" => "30." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Targeting V600EB-Raf and Akt3 using nanoliposomal-small interfering RNA inhibits cutaneous melanocytic lesion development" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.A. Tran" 1 => "R. Gowda" 2 => "A. Sharma" 3 => "E.J. Park" 4 => "J. Adair" 5 => "M. Kester" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/0008-5472.CAN-07-6614" "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2008" "volumen" => "68" "paginaInicial" => "7638" "paginaFinal" => "7649" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18794153" "web" => "Medline" ] ] ] ] ] ] ] ] 30 => array:3 [ "identificador" => "bib31" "etiqueta" => "31." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Combined inhibition of MAPK and mTOR signalling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.G. Lasithiotakis" 1 => "T.W. Sinnberg" 2 => "B. Schittek" 3 => "K.T. Flaherty" 4 => "D. Kulms" 5 => "E. Maczey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/jid.2008.44" "Revista" => array:6 [ "tituloSerie" => "J Invest Dermatol" "fecha" => "2008" "volumen" => "128" "paginaInicial" => "2013" "paginaFinal" => "2023" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18323781" "web" => "Medline" ] ] ] ] ] ] ] ] 31 => array:3 [ "identificador" => "bib32" "etiqueta" => "32." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Lack of clinical efficacy of imatinib in metastatic melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Ugurel" 1 => "R. Hildenbrand" 2 => "A. Zimpfer" 3 => "P. La Rosée" 4 => "P. Paschka" 5 => "A. Sucker" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bjc.6602529" "Revista" => array:6 [ "tituloSerie" => "Br J Cancer" "fecha" => "2005" "volumen" => "92" "paginaInicial" => "1398" "paginaFinal" => "1405" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15846297" "web" => "Medline" ] ] ] ] ] ] ] ] 32 => array:3 [ "identificador" => "bib33" "etiqueta" => "33." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Multicenter phase II trial of high-dose imatinib mesylate in metastatic melanoma: Significant toxicity with no clinical efficacy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Wyman" 1 => "M.B. Atkins" 2 => "V. Prieto" 3 => "O. Eton" 4 => "D.F. McDermott" 5 => "F. Hubbard" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/cncr.21834" "Revista" => array:6 [ "tituloSerie" => "Cancer" "fecha" => "2006" "volumen" => "106" "paginaInicial" => "2005" "paginaFinal" => "2011" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16565971" "web" => "Medline" ] ] ] ] ] ] ] ] 33 => array:3 [ "identificador" => "bib34" "etiqueta" => "34." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Somatic activation of KIT in distinct subtypes of melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.A. Curtin" 1 => "K. Busam" 2 => "D. Pinkel" 3 => "B.C. Bastian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2006.06.2984" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2006" "volumen" => "24" "paginaInicial" => "4340" "paginaFinal" => "4346" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16908931" "web" => "Medline" ] ] ] ] ] ] ] ] 34 => array:3 [ "identificador" => "bib35" "etiqueta" => "35." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Dose-dependent, complete response to imatinib of a metastatic mucosal melanoma with a K642E KIT mutation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "J. Lutzky" 1 => "J. Bauer" 2 => "B.C. Bastian" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1755-148X.2008.00475.x" "Revista" => array:6 [ "tituloSerie" => "Pigment Cell Melanoma Res" "fecha" => "2008" "volumen" => "21" "paginaInicial" => "492" "paginaFinal" => "493" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18510589" "web" => "Medline" ] ] ] ] ] ] ] ] 35 => array:3 [ "identificador" => "bib36" "etiqueta" => "36." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Major response to imatinib mesylate in KIT-mutated melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "F.S. Hodi" 1 => "P. Friedlander" 2 => "C. Corless" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2007.14.0707" "Revista" => array:6 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2008" "volumen" => "26" "paginaInicial" => "2046" "paginaFinal" => "2051" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18421059" "web" => "Medline" ] ] ] ] ] ] ] ] 36 => array:3 [ "identificador" => "bib37" "etiqueta" => "37." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imatinib targeting of KIT-mutant oncoprotein in melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Jiang" 1 => "J. Zhou" 2 => "N.K. Yuen" 3 => "C.L. Corless" 4 => "M.C. Heinrich" 5 => "J.A. Fletcher" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/1078-0432.CCR-08-1144" "Revista" => array:6 [ "tituloSerie" => "Clin Cancer Res" "fecha" => "2008" "volumen" => "14" "paginaInicial" => "7726" "paginaFinal" => "7732" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19047099" "web" => "Medline" ] ] ] ] ] ] ] ] 37 => array:3 [ "identificador" => "bib38" "etiqueta" => "38." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Identification of a novel subgroup of melanomas with KIT/cyclin-dependent kinase-4 overexpression" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.S.M. Smalley" 1 => "R. Contractor" 2 => "T.K. Nguyen" 3 => "M. Xiao" 4 => "R. Edwards" 5 => "V. Muthusamy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1158/0008-5472.CAN-08-0235" "Revista" => array:6 [ "tituloSerie" => "Cancer Res" "fecha" => "2008" "volumen" => "68" "paginaInicial" => "5743" "paginaFinal" => "5752" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18632627" "web" => "Medline" ] ] ] ] ] ] ] ] 38 => array:3 [ "identificador" => "bib39" "etiqueta" => "39." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Correlation between KIT expression and KIT mutation in melanoma: a study of 173 cases with emphasis on the acrallentiginous/mucosal type" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => ".C.A. Torres-Cabala" 1 => "W.L. Wang" 2 => "J. Trent" 3 => "D. Yang" 4 => "S. Chen" 5 => "J. Galbincea" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/modpathol.2009.116" "Revista" => array:6 [ "tituloSerie" => "Mod Pathol" "fecha" => "2009" "volumen" => "22" "paginaInicial" => "1446" "paginaFinal" => "1456" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19718013" "web" => "Medline" ] ] ] ] ] ] ] ] 39 => array:3 [ "identificador" => "bib40" "etiqueta" => "40." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Melanoma hyperpigmentation is strongly associated with KIT alterations" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.M. Wu" 1 => "H. Álvarez" 2 => "P. García" 3 => "P.L. Rojas" 4 => "G. Wong" 5 => "A. Maitra" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/DAD.0b013e3181a23f3b" "Revista" => array:6 [ "tituloSerie" => "Am J Dermatopathol" "fecha" => "2009" "volumen" => "31" "paginaInicial" => "619" "paginaFinal" => "625" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19652585" "web" => "Medline" ] ] ] ] ] ] ] ] 40 => array:3 [ "identificador" => "bib41" "etiqueta" => "41." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gain-offunction mutation of KIT ligand on melanin synthesis causes familial progressive hyperpigmentation" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "Z.Q. Wang" 1 => "L. Si" 2 => "Q. Tang" 3 => "D. Lin" 4 => "Z. Fu" 5 => "J. Zhang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ajhg.2009.03.019" "Revista" => array:6 [ "tituloSerie" => "Am J Hum Genet" "fecha" => "2009" "volumen" => "84" "paginaInicial" => "672" "paginaFinal" => "677" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19375057" "web" => "Medline" ] ] ] ] ] ] ] ] 41 => array:3 [ "identificador" => "bib42" "etiqueta" => "42." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phase II trial of imatinib mesylate in patients with metastatic melanoma" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K.B. Kim" 1 => "O. Eton" 2 => "D.W. Davis" 3 => "M.L. Frazier" 4 => "D.J. McConkey" 5 => "A.H. Diwan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1038/sj.bjc.6604482" "Revista" => array:6 [ "tituloSerie" => "Br J Cancer" "fecha" => "2008" "volumen" => "99" "paginaInicial" => "734" "paginaFinal" => "740" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18728664" "web" => "Medline" ] ] ] ] ] ] ] ] 42 => array:3 [ "identificador" => "bib43" "etiqueta" => "43." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "c-Kit–dependent growth of uveal melanoma cells: A potential therapeutic target?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. All-Ericsson" 1 => "L. Girnita" 2 => "A. Müller-Brunotte" 3 => "B. Brodin" 4 => "S. Seregard" 5 => "A. Ostman" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Invest Ophthalmol Vis Sci" "fecha" => "2004" "volumen" => "45" "paginaInicial" => "2075" "paginaFinal" => "2082" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15223779" "web" => "Medline" ] ] ] ] ] ] ] ] 43 => array:3 [ "identificador" => "bib44" "etiqueta" => "44." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Imatinib in melanoma: a selective treatment option based on KIT mutation status?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "J.C. Becker" 1 => "E.B. Bröcker" 2 => "D. Schadendorf" 3 => "S. Ugurel" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1200/JCO.2006.08.9664" "Revista" => array:5 [ "tituloSerie" => "J Clin Oncol" "fecha" => "2007" "volumen" => "25" "paginaInicial" => "e9" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17327598" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/15782190/0000010100000005/v1_201304241523/S1578219010706612/v1_201304241523/en/main.assets" "Apartado" => array:4 [ "identificador" => "6170" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Novelties in Dermatology" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15782190/0000010100000005/v1_201304241523/S1578219010706612/v1_201304241523/en/main.pdf?idApp=UINPBA000044&text.app=https://actasdermo.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1578219010706612?idApp=UINPBA000044" ]
| año/Mes | Html | Total | |
|---|---|---|---|
| 2024 Noviembre | 8 | 19 | 27 |
| 2024 Octubre | 75 | 51 | 126 |
| 2024 Septiembre | 73 | 31 | 104 |
| 2024 Agosto | 94 | 57 | 151 |
| 2024 Julio | 58 | 44 | 102 |
| 2024 Junio | 65 | 32 | 97 |
| 2024 Mayo | 57 | 29 | 86 |
| 2024 Abril | 55 | 25 | 80 |
| 2024 Marzo | 61 | 32 | 93 |
| 2024 Febrero | 44 | 24 | 68 |
| 2024 Enero | 53 | 32 | 85 |
| 2023 Diciembre | 59 | 24 | 83 |
| 2023 Noviembre | 57 | 33 | 90 |
| 2023 Octubre | 73 | 27 | 100 |
| 2023 Septiembre | 48 | 29 | 77 |
| 2023 Agosto | 36 | 17 | 53 |
| 2023 Julio | 59 | 69 | 128 |
| 2023 Junio | 39 | 25 | 64 |
| 2023 Mayo | 45 | 27 | 72 |
| 2023 Abril | 40 | 16 | 56 |
| 2023 Marzo | 18 | 18 | 36 |
| 2023 Febrero | 26 | 29 | 55 |
| 2023 Enero | 44 | 28 | 72 |
| 2022 Diciembre | 47 | 38 | 85 |
| 2022 Noviembre | 20 | 27 | 47 |
| 2022 Octubre | 29 | 19 | 48 |
| 2022 Septiembre | 25 | 32 | 57 |
| 2022 Agosto | 22 | 33 | 55 |
| 2022 Julio | 14 | 26 | 40 |
| 2022 Junio | 14 | 32 | 46 |
| 2022 Mayo | 24 | 32 | 56 |
| 2022 Abril | 57 | 39 | 96 |
| 2022 Marzo | 70 | 38 | 108 |
| 2022 Febrero | 48 | 30 | 78 |
| 2022 Enero | 69 | 32 | 101 |
| 2021 Diciembre | 24 | 44 | 68 |
| 2021 Noviembre | 23 | 44 | 67 |
| 2021 Octubre | 42 | 53 | 95 |
| 2021 Septiembre | 62 | 40 | 102 |
| 2021 Agosto | 52 | 36 | 88 |
| 2021 Julio | 22 | 35 | 57 |
| 2021 Junio | 22 | 22 | 44 |
| 2021 Mayo | 33 | 32 | 65 |
| 2021 Abril | 68 | 37 | 105 |
| 2021 Marzo | 63 | 36 | 99 |
| 2021 Febrero | 63 | 27 | 90 |
| 2021 Enero | 39 | 14 | 53 |
| 2020 Diciembre | 33 | 16 | 49 |
| 2020 Noviembre | 31 | 20 | 51 |
| 2020 Octubre | 38 | 30 | 68 |
| 2020 Septiembre | 42 | 15 | 57 |
| 2020 Agosto | 37 | 19 | 56 |
| 2020 Julio | 16 | 14 | 30 |
| 2020 Junio | 21 | 22 | 43 |
| 2020 Mayo | 8 | 11 | 19 |
| 2020 Abril | 23 | 24 | 47 |
| 2020 Marzo | 11 | 20 | 31 |
| 2020 Febrero | 2 | 5 | 7 |
| 2020 Enero | 0 | 11 | 11 |
| 2019 Diciembre | 0 | 5 | 5 |
| 2019 Noviembre | 0 | 2 | 2 |
| 2019 Octubre | 0 | 1 | 1 |
| 2019 Septiembre | 0 | 4 | 4 |
| 2019 Agosto | 0 | 2 | 2 |
| 2019 Julio | 0 | 2 | 2 |
| 2019 Junio | 0 | 3 | 3 |
| 2019 Mayo | 1 | 39 | 40 |
| 2019 Abril | 0 | 1 | 1 |
| 2019 Marzo | 0 | 4 | 4 |
| 2019 Febrero | 0 | 4 | 4 |
| 2018 Marzo | 0 | 3 | 3 |
| 2018 Febrero | 13 | 1 | 14 |
| 2018 Enero | 16 | 5 | 21 |
| 2017 Diciembre | 11 | 8 | 19 |
| 2017 Noviembre | 16 | 1 | 17 |
| 2017 Octubre | 18 | 4 | 22 |
| 2017 Septiembre | 13 | 8 | 21 |
| 2017 Agosto | 21 | 6 | 27 |
| 2017 Julio | 23 | 3 | 26 |
| 2017 Junio | 22 | 6 | 28 |
| 2017 Mayo | 23 | 12 | 35 |
| 2017 Abril | 28 | 7 | 35 |
| 2017 Marzo | 26 | 3 | 29 |
| 2017 Febrero | 21 | 6 | 27 |
| 2017 Enero | 16 | 5 | 21 |
| 2016 Diciembre | 30 | 5 | 35 |
| 2016 Noviembre | 18 | 6 | 24 |
| 2016 Octubre | 25 | 10 | 35 |
| 2016 Septiembre | 25 | 4 | 29 |
| 2016 Agosto | 21 | 9 | 30 |
| 2016 Julio | 18 | 5 | 23 |
| 2016 Junio | 11 | 8 | 19 |
| 2016 Mayo | 10 | 9 | 19 |
| 2016 Abril | 6 | 3 | 9 |
| 2016 Marzo | 1 | 8 | 9 |
| 2016 Febrero | 5 | 1 | 6 |
| 2016 Enero | 10 | 7 | 17 |
| 2015 Diciembre | 7 | 1 | 8 |
| 2015 Noviembre | 7 | 10 | 17 |
| 2015 Octubre | 8 | 6 | 14 |
| 2015 Septiembre | 10 | 4 | 14 |
| 2015 Agosto | 15 | 3 | 18 |
| 2015 Julio | 31 | 6 | 37 |
| 2015 Junio | 37 | 4 | 41 |
| 2015 Mayo | 52 | 7 | 59 |
| 2015 Abril | 29 | 6 | 35 |
| 2015 Marzo | 29 | 8 | 37 |
| 2015 Febrero | 26 | 14 | 40 |
| 2015 Enero | 27 | 10 | 37 |
| 2014 Diciembre | 22 | 4 | 26 |
| 2014 Noviembre | 19 | 5 | 24 |
| 2014 Octubre | 29 | 12 | 41 |
| 2014 Septiembre | 29 | 10 | 39 |
| 2014 Agosto | 42 | 16 | 58 |
| 2014 Julio | 40 | 24 | 64 |
| 2014 Junio | 39 | 6 | 45 |
| 2014 Mayo | 39 | 14 | 53 |
| 2014 Abril | 31 | 8 | 39 |
| 2014 Marzo | 34 | 12 | 46 |
| 2014 Febrero | 51 | 13 | 64 |
| 2014 Enero | 40 | 7 | 47 |
| 2013 Diciembre | 31 | 12 | 43 |
| 2013 Noviembre | 29 | 17 | 46 |
| 2013 Octubre | 29 | 15 | 44 |
| 2013 Septiembre | 40 | 19 | 59 |
| 2013 Agosto | 29 | 19 | 48 |
| 2013 Julio | 36 | 27 | 63 |
| 2013 Junio | 26 | 15 | 41 |
| 2013 Mayo | 18 | 16 | 34 |
| 2013 Abril | 30 | 16 | 46 |
| 2013 Marzo | 26 | 14 | 40 |
| 2013 Febrero | 17 | 13 | 30 |
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