Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos
ilustraciones, gráficas, tablas
- Autores:
-
Fonseca Sepúlveda, Eileen Viviana
- Tipo de recurso:
- Fecha de publicación:
- 2021
- Institución:
- Universidad Nacional de Colombia
- Repositorio:
- Universidad Nacional de Colombia
- Idioma:
- spa
- OAI Identifier:
- oai:repositorio.unal.edu.co:unal/80932
- Palabra clave:
- 610 - Medicina y salud
Inmunohistoquímica
Osteosarcoma
Transición Epitelial-Mesenquimal
Immunohistochemistry
Osteosarcoma
Epithelial-Mesenchymal Transition
Snail
Twist-1
Osteosarcoma
Transición mesénquima-epitelio
Sarcomas
- Rights
- openAccess
- License
- Reconocimiento 4.0 Internacional
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Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos |
| dc.title.translated.eng.fl_str_mv |
Presence of epithelial-mesenchymal transition markers by immunohistochemistry in pediatric osteosarcoma and association with clinical outcomes |
| title |
Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos |
| spellingShingle |
Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos 610 - Medicina y salud Inmunohistoquímica Osteosarcoma Transición Epitelial-Mesenquimal Immunohistochemistry Osteosarcoma Epithelial-Mesenchymal Transition Snail Twist-1 Osteosarcoma Transición mesénquima-epitelio Sarcomas |
| title_short |
Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos |
| title_full |
Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos |
| title_fullStr |
Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos |
| title_full_unstemmed |
Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos |
| title_sort |
Presencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicos |
| dc.creator.fl_str_mv |
Fonseca Sepúlveda, Eileen Viviana |
| dc.contributor.advisor.spa.fl_str_mv |
Olaya Morales, Natalia Linares Ballesteros, Adriana |
| dc.contributor.author.spa.fl_str_mv |
Fonseca Sepúlveda, Eileen Viviana |
| dc.contributor.researchgroup.spa.fl_str_mv |
Grupo de investigación en Oncohematología Pediátrica |
| dc.contributor.subjectmatterexpert.spa.fl_str_mv |
Patiño Calderón, Esteban Felipe Aponte Barrios, Nelson |
| dc.subject.ddc.spa.fl_str_mv |
610 - Medicina y salud |
| topic |
610 - Medicina y salud Inmunohistoquímica Osteosarcoma Transición Epitelial-Mesenquimal Immunohistochemistry Osteosarcoma Epithelial-Mesenchymal Transition Snail Twist-1 Osteosarcoma Transición mesénquima-epitelio Sarcomas |
| dc.subject.decs.spa.fl_str_mv |
Inmunohistoquímica Osteosarcoma Transición Epitelial-Mesenquimal |
| dc.subject.decs.eng.fl_str_mv |
Immunohistochemistry Osteosarcoma Epithelial-Mesenchymal Transition |
| dc.subject.proposal.eng.fl_str_mv |
Snail Twist-1 |
| dc.subject.proposal.spa.fl_str_mv |
Osteosarcoma Transición mesénquima-epitelio Sarcomas |
| description |
ilustraciones, gráficas, tablas |
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2021 |
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2021-12 |
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2022-02-10T16:36:00Z |
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2022-02-10T16:36:00Z |
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Trabajo de grado - Especialidad Médica |
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info:eu-repo/semantics/masterThesis |
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http://purl.org/redcol/resource_type/TM |
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https://repositorio.unal.edu.co/handle/unal/80932 |
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Universidad Nacional de Colombia |
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Repositorio Institucional Universidad Nacional de Colombia |
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https://repositorio.unal.edu.co/ |
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spa |
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spa |
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Bireme |
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Sannino G, Marchetto A, Kirchner T, Grünewald TGP. Epithelial-to-mesenchymal and mesenchymal-to-epithelial transition in mesenchymal tumors: A paradox in sarcomas? Cancer Res. 2017;77(17):4556–61. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging Biological Principles of Metastasis. Cell. 2017;168(4):670–91. Stamatopoulos A, Stamatopoulos T, Gamie Z, Kenanidis E, Ribeiro RDC, Rankin KS, et al. Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice. J Bone Oncol. 2019;16(March):100231. Ware KE, Gilja S, Xu S, Shetler S, Jolly MK, Wang X, et al. Induction of mesenchymal-epithelial transitions in sarcoma cells. J Vis Exp. 2017;2017(122):1–11. Sadykova LR, Ntekim AI, Muyangwa-Semenova M, Rutland CS, Jeyapalan JN, Blatt N, et al. Epidemiology and Risk Factors of Osteosarcoma. Cancer Invest. 2020;38(5):259–69. Somarelli JA, Shetler S, Jolly MK, Wang X, Bartholf Dewitt S, Hish AJ, et al. Mesenchymal-Epithelial Transition in Sarcomas Is Controlled by the Combinatorial Expression of MicroRNA 200s and GRHL2. Mol Cell Biol. 2016;36(19):2503–13. Domann FE, Fitzgerald MP, Gourronc F, Teoh MLT, Provenzano MJ, Case AJ, et al. Human chondrosarcoma cells acquire an epithelial-like gene expression pattern via an epigenetic switch: Evidence for mesenchymal-epithelial transition during sarcomagenesis. Sarcoma. 2011 Alba-Castellón L, Batlle R, Francí C, Fernández-Aceñero MJ, Mazzolini R, Peña R, et al. Snail1 Expression Is Required for Sarcomagenesis. Neoplasia (United States). 2014;16(5):413–21. Alba-Castellón L, Batlle R, Francí C, Fernández-Aceñero MJ, Mazzolini R, Peña R, et al. Snail1 Expression Is Required for Sarcomagenesis. Neoplasia (United States). 2014;16(5):413–21. Zhu QQ, Ma C, Wang Q, Song Y, Lv T. The role of TWIST1 in epithelial-mesenchymal transition and cancers. Tumor Biol. 2016;37(1):185–97. Dongre A, Weinberg RA. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69–84. Kaufhold S, Bonavida B. Central role of Snail1 in the regulation of EMT and resistance in cancer: A target for therapeutic intervention. J Exp Clin Cancer Res. 2014;33(1):1–19. Seo J, Ha J, Kang E, Cho S. The role of epithelial–mesenchymal transition-regulating transcription factors in anti-cancer drug resistance. Arch Pharm Res. 2021;44(3):281–92. Kang E, Seo J, Yoon H, Cho S. The post‐translational regulation of epithelial–mesenchymal transition‐inducing transcription factors in cancer metastasis. Int J Mol Sci. 2021;22(7). Yang J, Du X, Wang G, Sun Y, Chen K, Zhu X, et al. Mesenchymal to epithelial transition in sarcomas. Eur J Cancer. 2014;50(3):593–601. Gill J, Gorlick R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol. 2021;18(10):609–24. Yu X, Yustein JT, Xu J. Research models and mesenchymal/epithelial plasticity of osteosarcoma. Cell Biosci. 2021;11(1):1–12. Adisa A, Udeabor S, Orlowska A, Sader R, Ghanaati S. Immunohistochemical expression of Twist, E-cadherin and N- cadherin in ameloblastoma. Afr J Biomed Res. 2018;21:327–31. Yang H, Zhang Y, Zhou Z, Jiang X, Shen A. Transcription factor Snai1-1 induces osteosarcoma invasion and metastasis by inhibiting E-cadherin expression. Oncol Lett. 2014;8(1):193–7. Yin K, Liao Q, He H, Zhong D. Prognostic value of Twist and E-cadherin in patients with osteosarcoma. Med Oncol. 2012;29(5):3449–55. Tang Y, Weiss SJ. Snail/Slug-YAP/TAZ complexes cooperatively regulate mesenchymal stem cell function and bone formation. Cell Cycle. 2017;16(5):399–405. Wang Z, Chen X, Zhao Y, Jin Y, Zheng J. G-protein-coupled estrogen receptor suppresses the migration of osteosarcoma cells via post-translational regulation of Snail. J Cancer Res Clin Oncol. 2019;145(1):87–96. Wang Y, Shi J, Chai K, Ying X, Zhou B. The Role of Snail in EMT and Tumorigenesis. Curr Cancer Drug Targets. 2014;13(9):963–72. Ding L, Wang C, Cui Y, Han X, Zhou Y, Bai J, et al. S-phase kinase-Associated protein 2 is involved in epithelial-mesenchymal transition in methotrexate-resistant osteosarcoma cells. Int J Oncol. 2018;52(6):1841–52. Entz-Werlé N, Stoetzel C, Berard-Marec P, Kalifa C, Brugiere L, Pacquement H, et al. Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas. Int J Cancer. 2005;117(3):349–55. Entz-Werlé N, Choquet P, Neuville A, Kuchler-Bopp S, Clauss F, Danse JM, et al. Targeted Apc;twist double-mutant mice: A new model of spontaneous osteosarcoma that mimics the human disease. Transl Oncol. 2010;3(6):344–53. Entz-Werle N, Lavaux T, Metzger N, Stoetzel C, Lasthaus C, Marec P, et al. Involvement of MET/TWIST/APC combination or the potential role of ossification factors in pediatric high-grade osteosarcoma oncogenesis. Neoplasia. 2007;9(8):678–88. |
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31 páginas |
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Universidad Nacional de Colombia |
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Bogotá - Medicina - Especialidad en Oncohematología Pediátrica |
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Departamento de Pediatría |
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Facultad de Medicina |
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Bogotá, Colombia |
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Reconocimiento 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Olaya Morales, Natalia91d2cfb9042693363d21ae623c6ee672600Linares Ballesteros, Adrianaae0dbedd389c3f8ce13af7bc87702da9Fonseca Sepúlveda, Eileen Vivianaee9c3f33fea7b9658ac1f86ec370c648Grupo de investigación en Oncohematología PediátricaPatiño Calderón, Esteban FelipeAponte Barrios, Nelson2022-02-10T16:36:00Z2022-02-10T16:36:00Z2021-12https://repositorio.unal.edu.co/handle/unal/80932Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/ilustraciones, gráficas, tablasIntroducción: La transición epitelio-mesénquima (TEM) es la capacidad celular de cambiar su fenotipo original de forma transitoria y ha sido identificado como un mecanismo tumoral asociado con características clínicas agresivas como presencia de enfermedad distante y diseminada. En sarcomas, estos mecanismos no están bien dilucidados. Este trabajo evalúa la expresión de dos factores de transcripción involucrados en la regulación de la TEM mediante inmunohistoquímica: Snail y Twist-1 en osteosarcoma en pacientes pediátricos y su asociación con variables y desenlaces clínicos. Materiales y métodos: estudio de corte retrospectivo en pacientes entre 0-18 años con osteosarcoma. Se realizó estudio de inmunohistoquímica para Twist-1 y Snail y se recolectaron variables clínicas relacionadas con la enfermedad. Fue realizado el análisis de correlación mediante la prueba de chi cuadrado entre las variables clínicas y la positividad de los marcadores y se evaluó la correlación entre la supervivencia global y cada inmunomarcador mediante log rank test. Resultados: 53 pacientes fueron incluidos. En Snail, el patrón de inmunomarcación más frecuente fue a nivel citoplasmático con 26 casos (49,1%) y esto se correlacionó de forma estadísticamente significativa con la presencia de metástasis múltiples (p=0,02) y metástasis de localización ósea distante del primario (p=0,01). Solo 2 casos fueron positivos para Snail a nivel nuclear. Twist fue positivo a nivel nuclear en 45 casos (84,9%) y 13 casos (28,8%) con marcación intensa; 10 casos tenían marcación nuclear y citoplasmática al mismo tiempo. No se encontraron asociaciones con ningún tipo de marcación de Twist y las variables clínicas analizadas. Conclusiones: Snail y Twist-1, se expresan en diferentes localizaciones, de forma frecuente en osteosarcomas pediátricos. Snail citoplasmático se correlacionó de forma estadística enfermedad metastastica y diseminada. La positividad de ambos marcadores sugiere la activación de estas proteínas como reguladores de eventos de TEM/TME en osteosarcomas pediátricos y se plantea un rol esencial en los fenómenos que se relacionan con la agresividad clínica de la enfermedad. Se requieren estudios adicionales que confirmen o descarten nuestros hallazgos. (Texto tomado de la fuente).Introduction: The epithelial-mesenchymal transition (EMT) is the cellular capacity to change its original phenotype in a transitory way, it has been identified as a tumor mechanism associated with aggressive clinical characteristics such as the presence of distant and disseminated disease. In sarcomas, these mechanisms are not well elucidated. This work evaluates the expression of two transcription factors involved in the regulation of EMT by immunohistochemistry: Snail and Twist-1 in osteosarcoma in pediatric patients and their association with clinical variables and outcomes. Materials and methods: a retrospective study in patients between 0-18 years old with osteosarcoma. An immunohistochemical study was performed for Twist-1 and Snail and clinical variables related to the disease were collected. Correlation analysis was performed using the chi-square test between the clinical variables and the positivity of the markers, and the correlation between overall survival and each immunomarker was evaluated using the log rank test. Results: 53 patients were included. In Snail, the most frequent immunostaining pattern was at the cytoplasmic level with 26 cases (49.1%) and this correlated in a statistically significant way with the presence of multiple metastases (p=0.02) and distant bone metastases from the primary (p=0.01). Only 2 cases were positive for Snail at the nuclear level. Twist-1 was positive at the nuclear level in 45 cases (84.9%) and 13 cases (28.8%) with intense marking; 10 cases had nuclear and cytoplasmic labeling at the same time. No associations were found with any type of Twist marking and the clinical variables analyzed. Conclusions: Snail and Twist-1 are expressed in different locations and are frequently found in pediatric osteosarcomas. Cytoplasmic Snail was statistically correlated with metastatic and disseminated disease. The positivity of both markers suggests the activation of these proteins as regulators of EMT events in pediatric osteosarcomas and an essential role in the phenomena related to the clinical aggressiveness of the disease is considered. Additional studies are required to confirm or rule out our findings.Grupo de investigación en Oncohematología PediátricaEspecialidades MédicasEspecialista en Oncohematología Pediátrica31 páginasapplication/pdfspaUniversidad Nacional de ColombiaBogotá - Medicina - Especialidad en Oncohematología PediátricaDepartamento de PediatríaFacultad de MedicinaBogotá, ColombiaUniversidad Nacional de Colombia - Sede Bogotá610 - Medicina y saludInmunohistoquímicaOsteosarcomaTransición Epitelial-MesenquimalImmunohistochemistryOsteosarcomaEpithelial-Mesenchymal TransitionSnailTwist-1OsteosarcomaTransición mesénquima-epitelioSarcomasPresencia de marcadores de transición epitelio-mesénquima por inmunohistoquímica en osteosarcoma pediátrico y asociación con desenlaces clínicosPresence of epithelial-mesenchymal transition markers by immunohistochemistry in pediatric osteosarcoma and association with clinical outcomesTrabajo de grado - Especialidad Médicainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMBiremeSannino G, Marchetto A, Kirchner T, Grünewald TGP. Epithelial-to-mesenchymal and mesenchymal-to-epithelial transition in mesenchymal tumors: A paradox in sarcomas? Cancer Res. 2017;77(17):4556–61.Lambert AW, Pattabiraman DR, Weinberg RA. Emerging Biological Principles of Metastasis. Cell. 2017;168(4):670–91.Stamatopoulos A, Stamatopoulos T, Gamie Z, Kenanidis E, Ribeiro RDC, Rankin KS, et al. Mesenchymal stromal cells for bone sarcoma treatment: Roadmap to clinical practice. J Bone Oncol. 2019;16(March):100231.Ware KE, Gilja S, Xu S, Shetler S, Jolly MK, Wang X, et al. Induction of mesenchymal-epithelial transitions in sarcoma cells. J Vis Exp. 2017;2017(122):1–11.Sadykova LR, Ntekim AI, Muyangwa-Semenova M, Rutland CS, Jeyapalan JN, Blatt N, et al. Epidemiology and Risk Factors of Osteosarcoma. Cancer Invest. 2020;38(5):259–69.Somarelli JA, Shetler S, Jolly MK, Wang X, Bartholf Dewitt S, Hish AJ, et al. Mesenchymal-Epithelial Transition in Sarcomas Is Controlled by the Combinatorial Expression of MicroRNA 200s and GRHL2. Mol Cell Biol. 2016;36(19):2503–13.Domann FE, Fitzgerald MP, Gourronc F, Teoh MLT, Provenzano MJ, Case AJ, et al. Human chondrosarcoma cells acquire an epithelial-like gene expression pattern via an epigenetic switch: Evidence for mesenchymal-epithelial transition during sarcomagenesis. Sarcoma. 2011Alba-Castellón L, Batlle R, Francí C, Fernández-Aceñero MJ, Mazzolini R, Peña R, et al. Snail1 Expression Is Required for Sarcomagenesis. Neoplasia (United States). 2014;16(5):413–21.Alba-Castellón L, Batlle R, Francí C, Fernández-Aceñero MJ, Mazzolini R, Peña R, et al. Snail1 Expression Is Required for Sarcomagenesis. Neoplasia (United States). 2014;16(5):413–21.Zhu QQ, Ma C, Wang Q, Song Y, Lv T. The role of TWIST1 in epithelial-mesenchymal transition and cancers. Tumor Biol. 2016;37(1):185–97.Dongre A, Weinberg RA. New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer. Nat Rev Mol Cell Biol. 2019;20(2):69–84.Kaufhold S, Bonavida B. Central role of Snail1 in the regulation of EMT and resistance in cancer: A target for therapeutic intervention. J Exp Clin Cancer Res. 2014;33(1):1–19.Seo J, Ha J, Kang E, Cho S. The role of epithelial–mesenchymal transition-regulating transcription factors in anti-cancer drug resistance. Arch Pharm Res. 2021;44(3):281–92.Kang E, Seo J, Yoon H, Cho S. The post‐translational regulation of epithelial–mesenchymal transition‐inducing transcription factors in cancer metastasis. Int J Mol Sci. 2021;22(7).Yang J, Du X, Wang G, Sun Y, Chen K, Zhu X, et al. Mesenchymal to epithelial transition in sarcomas. Eur J Cancer. 2014;50(3):593–601.Gill J, Gorlick R. Advancing therapy for osteosarcoma. Nat Rev Clin Oncol. 2021;18(10):609–24.Yu X, Yustein JT, Xu J. Research models and mesenchymal/epithelial plasticity of osteosarcoma. Cell Biosci. 2021;11(1):1–12.Adisa A, Udeabor S, Orlowska A, Sader R, Ghanaati S. Immunohistochemical expression of Twist, E-cadherin and N- cadherin in ameloblastoma. Afr J Biomed Res. 2018;21:327–31.Yang H, Zhang Y, Zhou Z, Jiang X, Shen A. Transcription factor Snai1-1 induces osteosarcoma invasion and metastasis by inhibiting E-cadherin expression. Oncol Lett. 2014;8(1):193–7.Yin K, Liao Q, He H, Zhong D. Prognostic value of Twist and E-cadherin in patients with osteosarcoma. Med Oncol. 2012;29(5):3449–55.Tang Y, Weiss SJ. Snail/Slug-YAP/TAZ complexes cooperatively regulate mesenchymal stem cell function and bone formation. Cell Cycle. 2017;16(5):399–405.Wang Z, Chen X, Zhao Y, Jin Y, Zheng J. G-protein-coupled estrogen receptor suppresses the migration of osteosarcoma cells via post-translational regulation of Snail. J Cancer Res Clin Oncol. 2019;145(1):87–96.Wang Y, Shi J, Chai K, Ying X, Zhou B. The Role of Snail in EMT and Tumorigenesis. Curr Cancer Drug Targets. 2014;13(9):963–72.Ding L, Wang C, Cui Y, Han X, Zhou Y, Bai J, et al. S-phase kinase-Associated protein 2 is involved in epithelial-mesenchymal transition in methotrexate-resistant osteosarcoma cells. Int J Oncol. 2018;52(6):1841–52.Entz-Werlé N, Stoetzel C, Berard-Marec P, Kalifa C, Brugiere L, Pacquement H, et al. Frequent genomic abnormalities at TWIST in human pediatric osteosarcomas. Int J Cancer. 2005;117(3):349–55.Entz-Werlé N, Choquet P, Neuville A, Kuchler-Bopp S, Clauss F, Danse JM, et al. Targeted Apc;twist double-mutant mice: A new model of spontaneous osteosarcoma that mimics the human disease. Transl Oncol. 2010;3(6):344–53.Entz-Werle N, Lavaux T, Metzger N, Stoetzel C, Lasthaus C, Marec P, et al. Involvement of MET/TWIST/APC combination or the potential role of ossification factors in pediatric high-grade osteosarcoma oncogenesis. Neoplasia. 2007;9(8):678–88.Este trabajo fue financiado por el grupo de investigación en Oncohematología Pediátrica a través del centro de costos Preceptorship 400032.EstudiantesInvestigadoresMaestrosORIGINAL1032437828.2021.pdf1032437828.2021.pdfTesis de Especialidad en Oncohematología Pediátricaapplication/pdf912526https://repositorio.unal.edu.co/bitstream/unal/80932/1/1032437828.2021.pdf4202243d387e8c36824687d6cff1dc6dMD51LICENSElicense.txtlicense.txttext/plain; charset=utf-84074https://repositorio.unal.edu.co/bitstream/unal/80932/2/license.txt8153f7789df02f0a4c9e079953658ab2MD52THUMBNAIL1032437828.2021.pdf.jpg1032437828.2021.pdf.jpgGenerated Thumbnailimage/jpeg4574https://repositorio.unal.edu.co/bitstream/unal/80932/3/1032437828.2021.pdf.jpg3b4ae2b66599581ef35fe69ecbbb0f5dMD53unal/80932oai:repositorio.unal.edu.co:unal/809322024-08-02 23:11:20.395Repositorio Institucional Universidad Nacional de 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