Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas

Ilustraciones, gráficos

Autores:: Duque Arbelaez, Jorge Eduardo

Tipo de recurso:

Fecha de publicación:: 2024

Institución:: Universidad Nacional de Colombia

Repositorio:: Universidad Nacional de Colombia

Idioma:

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repository_id_str
dc.title.spa.fl_str_mv	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas
dc.title.translated.eng.fl_str_mv	Determination of exosomal PD-L1 in patients with advanced neoplasms
title	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas
spellingShingle	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas 610 - Medicina y salud 660 - Ingeniería química Biomarcadores de Tumor Neoplasias Biopsia Líquida Proteína PD-L1 Neoplasias Pulmonares Exosomas Neoplasmas Cáncer Marcadores tumorales Marcadores serológicos Neoplasmas - Investigaciones Tecnología médica Biotecnología Exosomas Biopsia liquida Cultivo in vitro Exosomes In vitro culture Liquid biopsy Elisa PD1 PD-L1
title_short	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas
title_full	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas
title_fullStr	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas
title_full_unstemmed	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas
title_sort	Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas
dc.creator.fl_str_mv	Duque Arbelaez, Jorge Eduardo
dc.contributor.advisor.none.fl_str_mv	Vasquez Araque, Neil Aldrin
dc.contributor.author.none.fl_str_mv	Duque Arbelaez, Jorge Eduardo
dc.contributor.researcher.none.fl_str_mv	Diego Pulgarin Laura Mira
dc.contributor.researchgroup.spa.fl_str_mv	Biotecnología Animal
dc.subject.ddc.spa.fl_str_mv	610 - Medicina y salud 660 - Ingeniería química
topic	610 - Medicina y salud 660 - Ingeniería química Biomarcadores de Tumor Neoplasias Biopsia Líquida Proteína PD-L1 Neoplasias Pulmonares Exosomas Neoplasmas Cáncer Marcadores tumorales Marcadores serológicos Neoplasmas - Investigaciones Tecnología médica Biotecnología Exosomas Biopsia liquida Cultivo in vitro Exosomes In vitro culture Liquid biopsy Elisa PD1 PD-L1
dc.subject.decs.none.fl_str_mv	Biomarcadores de Tumor Neoplasias Biopsia Líquida Proteína PD-L1 Neoplasias Pulmonares Exosomas
dc.subject.lemb.none.fl_str_mv	Neoplasmas Cáncer Marcadores tumorales Marcadores serológicos Neoplasmas - Investigaciones Tecnología médica Biotecnología
dc.subject.proposal.spa.fl_str_mv	Exosomas Biopsia liquida Cultivo in vitro
dc.subject.proposal.eng.fl_str_mv	Exosomes In vitro culture Liquid biopsy
dc.subject.proposal.none.fl_str_mv	Elisa PD1 PD-L1
description	Ilustraciones, gráficos
publishDate	2024
dc.date.accessioned.none.fl_str_mv	2024-04-04T14:21:21Z
dc.date.available.none.fl_str_mv	2024-04-04T14:21:21Z
dc.date.issued.none.fl_str_mv	2024-04-03
dc.type.spa.fl_str_mv	Trabajo de grado - Maestría
dc.type.driver.spa.fl_str_mv	info:eu-repo/semantics/masterThesis
dc.type.version.spa.fl_str_mv	info:eu-repo/semantics/acceptedVersion
dc.type.content.spa.fl_str_mv	Text
dc.type.redcol.spa.fl_str_mv	http://purl.org/redcol/resource_type/TM
status_str	acceptedVersion
dc.identifier.uri.none.fl_str_mv	https://repositorio.unal.edu.co/handle/unal/85865
dc.identifier.instname.spa.fl_str_mv	Universidad Nacional de Colombia
dc.identifier.reponame.spa.fl_str_mv	Repositorio Institucional Universidad Nacional de Colombia
dc.identifier.repourl.spa.fl_str_mv	https://repositorio.unal.edu.co/
url	https://repositorio.unal.edu.co/handle/unal/85865 https://repositorio.unal.edu.co/
identifier_str_mv	Universidad Nacional de Colombia Repositorio Institucional Universidad Nacional de Colombia
dc.relation.indexed.spa.fl_str_mv	LaReferencia
dc.relation.references.spa.fl_str_mv	Abusamra, A. J., Zhong, Z., Zheng, X., Li, M., Ichim, T. E., Chin, J. L., & Min, W. P. 2005. Tumor exosomes expressing Fas ligand mediate CD8+ T-cell apoptosis. Blood Cells, Molecules, and Diseases, 35(2), 169-173. Antoni Ribas and Siwen Hu-Lieskovan What does PD-1 positive or negative mean. J Exp Med. 2016 Dec 12; 213(13): 2835–2840. Aguiar P, Del Giglio A, Alastair P et al Cost–effectiveness and budget impact of lung cancer immunotherapy in South America: strategies to improve Access, Oncology central 8 AUG 2018. Alborelli, I., Leonards, K., Rothschild, S. I., Leuenberger, L. P., Savic Prince, S., Mertz, K. D., Jermann, P. 2020. Tumor mutational burden assessed by targeted NGS predicts clinical benefit from immune checkpoint inhibitors in non‐small cell lung cancer. The Journal of pathology, 250(1), 19-29. Addeo, A., Friedlaender, A., Banna, G. L., & Weiss, G. J. 2021. TMB or not TMB as a biomarker: That is the question. Critical Reviews in Oncology/Hematology, 163, 103374. Bartel, D. P. 2004. MicroRNAs: genomics, biogenesis, mechanism, and function. cell, 116(2), 281-297. Chang, G. C., Yang, T. Y., Chen, K. C,. Hsu, K., Huang, Y., Su, K., Yu, S., & Tseng, J. 2020. ALK variants, PD-L1 expression and their association with outcomes in ALK- positive NSCLC patients. Scientific Reports. 10, 21063. Chatterjee, S. K., & Zetter, B. R. 2005. Cancer biomarkers: knowing the present and predicting the future. Future Oncology. Feb;1(1):37-50. Chen, G., Huang, A. C., Zhang, W., Zhang, G., Wu, M., Xu, W., ... & Guo, W. (2018). Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response. Nature, 560(7718), 382-386. Duréndez-Sáez, E.; Calabuig-Fariñas, S.; Torres-Martínez, S.; Moreno-Manuel, A.; Herreros-Pomares, A.; Escorihuela, E.; Mosqueda, M.; Gallach, S.; Guijarro, R.;Serna, E.; et al. Analysis of Exosomal Cargo Provides Accurate Clinical, Histologic and Mutational Information in Non-Small Cell Lung Cancer. Cancers 2022, 14, 3216. Fernández‐Messina, L., Gutiérrez‐Vázquez, C., Rivas‐García, E., Sánchez‐Madrid, F., & de la Fuente, H. 2015. Immunomodulatory role of microRNAs transferred by extracellular vesicles. Biology of the Cell, 107(3), 61-77. Filipazzi, P., Bürdek, M., Villa, A., Rivoltini, L., & Huber, V. (2012). Recent advances on the role of tumor exosomes in immunosuppression and disease progression. In Seminars in cancer biology. 22(4): 342-349. Academic Press. Frelaut, M., Le Tourneau, C., & Borcoman, E. (2019). Hyperprogression under immunotherapy. International journal of molecular sciences, 20(11), 2674. Ferlay, J., Colombet, M., Soerjomataram, I., Siegel, R., Torre, L. y Jemal, A. (2018). Estimaciones globales y regionales de la incidencia y mortalidad de 38 tipos de cáncer: GLOBOCAN 2018. Organización Mundial de la Salud, Agencia Internacional para la Investigación del Cáncer: Lyon, Francia, 14. Girolami I, Pantanowitz L, Barberis M, Paolino G, Brunelli M, Vigliar e, Munari E, Satturwar S, troncone G, Eccher A. Challenges facing pathologists evaluating PD-L1 in Head and Neck squamous cell carcinoma. J Oral Pathol Med. 2021 Oct;50(9):864-873. doi:10.1111/jop.13220. Epub 2021 Jul 8. PMID 34157159. Han, Y., Liu, D., & Li, L. 2020. PD-1/PD-L1 pathway: current research in cancer. American Journal Cancer Research 10(3):727-742 Hita-Millan, J., Carracedo, A., & Fernandez-Rozadilla, C. (2021, September 28). Liquid biopsy biomarkers for immunotherapy in non-small cell lung carcinoma: Lessons learned and the road ahead. Journal of personalized medicine. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8540302. Herbst, R. S., Soria, J. C., Kowanetz, M., Fine, G. D., Hamid, O., Gordon, M. S., & Sandler, A. (2014). Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature, 515(7528), 563-567. Ji, M., Liu, Y., Li, Q., Li, X. D., Zhao, W. Q., Zhang, H., ... & Wu, C. P. 2015. PD-1/PD-L1 pathway in non-small-cell lung cancer and its relation with EGFR mutation. Journal of translational medicine, 13(1), 1-6. Kim, D. H., Kim, H., Choi, Y. J., Kim, S. Y., Lee, J. E., Sung, K. J., Sung, Y. H., Pack, C., Jung, M., Hahn, B., Kim, K., Kim, W. S., Nam, S. J., Choi, S., Yun, M., Lee, J. C., & Rho, J. K. (2019). Exosomal PD-L1 promotes tumor growth through immune escape in non-small cell lung cancer. Experimental & molecular medicine, 51(8), 1-13. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, Schadendorf D, Dummer R, Smylie M, Rutkowski P, et al. Combined nivolumab and ipilimumab or monotherapy in untreated Melanoma. N Engl J Med. 2015;373(1):23–34. PMID: 26027431. doi:10.1056/NEJMoa1504030. Li, Z., Song, W., Rubinstein, M. et al. Recent updates in cancer immunotherapy: a comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing. J Hematol Oncol 11, 142 (2018). https://doi.org/10.1186/s13045- 018-0684-3. Li, C., Li, C., Zhi, C. et al. Clinical significance of PD-L1 expression in serum-derived exosomes in NSCLC patients. J Transl Med 17, 355 (2019). https://doi.org/10.1186/s12967-019-2101-2. Litvin, I. E., Paganella, M. P., Wendland, E. M., & Roehe, A. V. (2020). Prognosis of PD-L1 in human breast cancer: Protocol for a systematic review and meta-Analysis. Systematic Reviews, 9(1). https://doi.org/10.1186/S13643-020-01306-9/TABLES/1. Markus Eckstein, Alessia Cimadamore, Arndt Hartmann, Antonio Lopez-Beltran, Liang Cheng, Marina Scarpelli, Rodolfo Montironi, and Thomas Gevaert. PD-L1 assessment in urothelial carcinoma: a practical approach Ann Transl Med. 2019 Nov; 7(22): 690. doi: 10.21037/atm.2019.10.24. Marrugo-Ramirez, J., Mir, M., & Samitier,J. 2018. Blood Based Cancer Biomarkers in Liquid biopsy: A Promising Non-invasive Alternative to Tissue Biopsy. International Journal of Molecular Sciences. 19,2877. Melo, S. A., Sugimoto, H., O’Connell, J. T., Kato, N., Villanueva, A., Vidal, A., Que, L., Vitkin, E., Perelman, L. T., Melo, C., Lucci, A., ... & Kalluri, R. (2014). Cancer exosomes perform cell-independent microRNA biogenesis and promote tumorigenesis. Cancer cell, 26(5), 707-721. Michael M. Boyiadzis, John M. Kirkwood, John L. Marshall, Colin C. Pritchard, Nilofer S. Azad, and James L. Gulley. Significance and implications of FDA approval of pembrolizumab for biomarker-defined disease. J Immunother Cancer. 2018; 6: 35. Published online 2018 May 14. doi: 10.1186/s40425-018-0342-x. Ministerio de Salud y Protección Social. (2022). Infografías cáncer en cifras INC - Instituto Nacional de Cancerología. https://www.cancer.gov.co/portafolio-1/salud-publica/grupos/grupo-vigilancia-epidemiologica-del-cancer/infografias-cancer-cifras-inc. Nunes-Xavier, C. E., Angulo, J. C., Pulido, R., López, J. I. (2019). A critical insight into the clinical translation of PD-1/PD-L1 blockade therapy in clear cell renal cell carcinoma. Current urology reports, 20(1), 1. O’Keeffe, L. M., Taylor, G., Huxley, R. R., Mitchell, P., Woodward, M., & Peters, S. A. (2018). Smoking as a risk factor for lung cancer in women and men: a systematic review and meta-analysis. BMJ open, 8(10), e021611. Passiglia, F., Rizzo, S., Di Maio, M., Galvano, A., Badalamenti, G., Listì, A., Russo, A. 2018. The diagnostic accuracy of circulating tumor DNA for the detection of EGFR-T790M mutation in NSCLC: a systematic review and meta-analysis. Scientific reports, 8(1), 1- 10. Rabinowits, G., Gercel-Taylor, C., Day, J. M., Taylor, D. D., & Kloecker, G. H. 2009. Exosomal microRNA: a diagnostic marker for lung cancer. Clin.Lung Cancer.10:42-46. Salmaninejad, A., Valilou, S. F., Shabgah, A. G., Aslani, S., Alimardani, M., Pasdar, A., & Sahebkar, A. (2019). PD‐1/PD‐L1 pathway: Basic biology and role in cancer immunotherapy. Journal of cellular physiology, 234(10), 16824-16837. Sanmamed, M. F., & Chen, L. (2014). Inducible expression of B7-H1 (PD-L1) and its selective role in tumor site immune modulation. Cancer journal, 20(4), 256. Sharpe, A., Pauken, K. The diverse functions of the PD1 inhibitory pathway. Nat Rev Immunol 18, 153–167 (2018). https://doi.org/10.1038/nri.2017.108. Shephard, Alex P. et al. “Prostate cancer exosomes as modulators of the tumor microenvironment.” Journal of Cancer Metastasis and Treatment 3 (2017): 288. Sispro. (2020). Boletín No. 01 Día mundial del cáncer de pulmón. https://www.sispro.gov.co/observatorios/oncancer/Paginas/onc_boletin_01_cancer_pulmon.aspx. Szu- Chun Yang, Huang-Tz Ou.( 2023) .Cost effectiveness of first line immunotherapies for advanced non-small cell lung cancer. Cancer medicine, 18 January 2023. https://doi.org/10.1002/cam4.5632. Tan, S., Zhang, CH. & Gao, G. Seeing is believing anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy. Sig Transduct Target Ther 1, 16029 (2016). https://doi.org/10.1038/sigtrans.2016.29. The Global Cancer Observatory. (2020). Cancer Today. Globocan. https://gco.iarc.fr/today/ Wang M., Zhao J., Zhang L., Wei F., Lian Y., Wu Y., Guo C. Role of tumor microenvironment in tumorigenesis. J. Cancer. 2017; 8:761–773. doi: 10.7150/jca.17648. Webber, J., Yeung, V., & Clayton, A. (2015, April). Extracellular vesicles as modulators of the cancer microenvironment. In Seminars in cell & developmental biology (Vol. 40, pp. 27-34). Academic Press. Whiteside, T. L. (2018). The emerging role of plasma exosomes in diagnosis, prognosis, and therapies of patients with cancer. Contemporary Oncology, 22(1A), 38. Whiteside, T. L. (2016). Exosomes and tumor-mediated immune suppression. The Journal of clinical investigation, 126(4), 1216-1223. Wu, M., Huang, Q., Xie, Y. et al. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation. J Hematol Oncol 15, 24 (2022). https://doi.org/10.1186/s13045-022-01242-2. Xu, F., Fei, Z., Dai, H., Xu, J., Fan, Q., Shen, S., Zhang, Y., Ma, Q., Chu, J., Peng, F., Zhou, F., Liu, Z., & Wang, C. (2022). Mesenchymal Stem Cell-Derived Extracellular Vesicles with High PD-L1 Expression for Autoimmune Diseases Treatment. Advanced Materials (Deerfield Beach, Fla.), 34(1). https://doi.org/10.1002/ADMA.202106265. Yarchoan, M., Lee, A., Hopkins, A., Montesion, M., Murugesan, K., Vithayathil, T., Zaidi, N., Azad, N., Laheru, D., Frampton, G., Jaffee, E. (2019). PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. JCI insight. 4. 10.1172/jci.insight.126908. Zhang, Y., Liu, Y., Liu, H. et al. Exosomes: biogenesis, biologic function and clinical potential. Cell Biosci 9, 19 (2019). https://doi.org/10.1186/s13578-019-0282-2. Zhang, X., Yuan, X., Shi, H., Wu, L., Qian, H., & Xu, W. (2015). Exosomes in cancer: small particle, big player. Journal of hematology & oncology, 8(1), 1-131. Zhang, J., Yan, Y., Li, J., Adhikari, R., & Fu, L. (2020, April 30). PD-1/PD-L1 based combinational cancer therapy: Icing on the cake. Frontiers. https://www.frontiersin.org/articles/10.3389/fphar.2020.00722/full.
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dc.format.extent.spa.fl_str_mv	58 páginas
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dc.publisher.spa.fl_str_mv	Universidad Nacional de Colombia
dc.publisher.program.spa.fl_str_mv	Medellín - Ciencias - Maestría en Ciencias - Biotecnología
dc.publisher.faculty.spa.fl_str_mv	Facultad de Ciencias
dc.publisher.place.spa.fl_str_mv	Medellín, Colombia
dc.publisher.branch.spa.fl_str_mv	Universidad Nacional de Colombia - Sede Medellín
institution	Universidad Nacional de Colombia
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spelling	Atribución-NoComercial-SinDerivadas 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Vasquez Araque, Neil Aldrin6d5964bd6a6f80645304976920c2ff07Duque Arbelaez, Jorge Eduardodddc2c814b18f2bdf39a348669f1bddeDiego PulgarinLaura MiraBiotecnología Animal2024-04-04T14:21:21Z2024-04-04T14:21:21Z2024-04-03https://repositorio.unal.edu.co/handle/unal/85865Universidad Nacional de ColombiaRepositorio Institucional Universidad Nacional de Colombiahttps://repositorio.unal.edu.co/Ilustraciones, gráficosEl campo de los biomarcadores en cáncer constituye una extensa área de investigación aún en fase de exploración. Muchas de las complicaciones asociadas con el cáncer derivan de la carencia de un diagnóstico expedito y las limitaciones para monitorear la enfermedad una vez iniciada la terapia. Las técnicas actualmente empleadas suelen requerir intervenciones invasivas o el uso de costosos equipos de imagenología, inaccesibles para gran parte de la población. Los biomarcadores presentes en biopsias líquidas, como la sangre u orina, poseen el potencial de proporcionar información sobre el estado tumoral. En este contexto, los exosomas generados por los tumores y presentes en los biofluidos ofrecen la posibilidad de medir marcadores de su membrana, garantizando un diagnóstico preciso. El presente estudio establece parámetros definidos para la recolección, procesamiento y análisis de muestras sanguíneas de pacientes con neoplasias avanzadas que expresan el marcador PD-L1 exosomal. Los exosomas derivados de la línea tumoral de cáncer de pulmón A549 y de pacientes se separan y purifican mediante columnas de afinidad y/o ultrafiltración. Posteriormente, se caracterizan mediante técnicas como la cuantificación de proteína total con Bradford, NTA, DLS, TEM y evaluación de su capacidad de inmunomodulación, alcanzando hasta un 67,16% de inhibición de la proliferación de células mononucleares de sangre periférica. Finalmente, se cuantifica la proteína PD-L1 mediante ensayos de ELISA. Se constata que los niveles de expresión de PD-L1 exosomal en los pacientes con cáncer son significativamente superiores, 10 veces más a los observados en los pacientes sanos voluntarios. Además, la cantidad de proteína PD-L1 es considerablemente más elevada (2 veces más) en las muestras de exosomas que en la fracción soluble de la sangre u orina. La medición de PD-L1 exosomal emerge como una herramienta prometedora para futuros análisis en poblaciones más extensas de pacientes con neoplasias que expresan este marcador mediante inmunohistoquímica. Esta técnica podría facilitar un seguimiento más preciso, auxiliando al oncólogo en la toma de decisiones clínicas. (Tomado de la fuente)The field of biomarkers in cancer is a vast area of research that is still being explored. Many of the complications associated with cancer stem from the lack of an expeditious diagnosis and the limitations of monitoring the disease once therapy has been initiated. The techniques currently employed often require invasive interventions or the use of expensive imaging equipment, inaccessible to a large part of the population. Biomarkers present in liquid biopsies, such as blood or urine, have the potential to provide information on tumor status. In this context, exosomes generated by tumors and present in biofluids offer the possibility to measure markers of their membrane, guaranteeing an accurate diagnosis. The present study establishes defined parameters for the collection, processing and analysis of blood samples from patients with advanced neoplasms expressing the exosomal PD-L1 marker. Exosomes derived from the A549 lung cancer tumor line and from patients are separated and purified by affinity columns and/or ultrafiltration. Subsequently, they are characterized by techniques such as total protein quantification with Bradford, NTA, DLS, TEM and evaluation of their immunomodulation capacity, reaching up to 67.16% inhibition of peripheral blood mononuclear cell proliferation. Finally, PD-L1 protein is quantified by ELISA assays. It is found that the levels of exosomal PD-L1 expression in cancer patients are significantly higher, 10-fold higher than those observed in healthy volunteer patients. In addition, the amount of PD-L1 protein is significantly higher (2-fold) in exosome samples than in the soluble fraction of blood or urine. Measurement of exosomal PD-L1 emerges as a promising tool for future analysis in larger populations of patients with malignancies expressing this marker by immunohistochemistry. This technique could facilitate a more accurate follow-up, assisting the oncologist in clinical decision making.MaestríaMaestría en Ciencias - Biotecnología6.1. Diseño experimental En este proyecto se evaluó la proteína PD-L1 como un biomarcador específico tumoral. Inicialmente in vitro en una línea celular de cáncer de pulmón, luego se determinó en biopsias líquidas de pacientes con cáncer en estadios avanzados. Las biopsias líquidas (sangre y orina) y tumorales fueron obtenidas de pacientes pertenecientes a la institución IPS Centro Oncológico de Antioquia Ubicado en Envigado Antioquia. A los pacientes se les informó el objetivo del estudio de forma verbal y escrita, así como los riesgos inherentes a la toma de muestra, se diligenció y firmaron el consentimiento informado donde expresaron su participación voluntaria y espontánea en el estudio. Este procedimiento fue realizado bajo la supervisión de un profesional del área de la salud. Estas células no tuvieron como destino ningún tipo de banco de células, y al finalizar los experimentos, las células fueron descartadas como desecho biológico en las instituciones clínicas y en la Universidad Nacional de Colombia. Dado que tales muestras fueron de utilidad para el desarrollo del proyecto, la Universidad Nacional siguió el protocolo de bioseguridad para los desechos generados en el procesamiento de las muestras, las cuales nunca representaron riesgo biológico ni causaron accidentes biológicos a los investigadores ni al medio ambiente; implementado los protocolos de la Dirección Nacional de Laboratorios siguiendo lo establecido por el estatuto metropolitano del medio ambiente del Valle de Aburrá (Acuerdo 007 de mayo 17 de 1993 del Concejo de Medellín), el código sanitario nacional (Ley 9 de 1979), el estatuto de seguridad industrial (Resolución 2.400 de 1979) y demás normas y recomendaciones internacionales que regulan la materia. Además, en el laboratorio se implementó las regulaciones para la recolección, almacenamiento y transporte biológico tanto del material obtenido como del procesado por medio de la Resolución Número 01164 de 2002.BiotecnologiaBiotecnología.Sede Medellín58 páginasapplication/pdfUniversidad Nacional de ColombiaMedellín - Ciencias - Maestría en Ciencias - BiotecnologíaFacultad de CienciasMedellín, ColombiaUniversidad Nacional de Colombia - Sede Medellín610 - Medicina y salud660 - Ingeniería químicaBiomarcadores de TumorNeoplasiasBiopsia LíquidaProteína PD-L1Neoplasias PulmonaresExosomasNeoplasmasCáncerMarcadores tumoralesMarcadores serológicosNeoplasmas - InvestigacionesTecnología médicaBiotecnologíaExosomasBiopsia liquidaCultivo in vitroExosomesIn vitro cultureLiquid biopsyElisaPD1PD-L1Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadasDetermination of exosomal PD-L1 in patients with advanced neoplasmsTrabajo de grado - Maestríainfo:eu-repo/semantics/masterThesisinfo:eu-repo/semantics/acceptedVersionTexthttp://purl.org/redcol/resource_type/TMLaReferenciaAbusamra, A. 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Frontiers. https://www.frontiersin.org/articles/10.3389/fphar.2020.00722/full.Exosomas SAS ColombiaInvestigadoresLICENSElicense.txtlicense.txttext/plain; charset=utf-85879https://repositorio.unal.edu.co/bitstream/unal/85865/1/license.txteb34b1cf90b7e1103fc9dfd26be24b4aMD51ORIGINALTesis de Maestría en Ciencias - Biotecnología.pdfTesis de Maestría en Ciencias - Biotecnología.pdfTesis de Maestría en Ciencias - Biotecnologíaapplication/pdf1825783https://repositorio.unal.edu.co/bitstream/unal/85865/2/Tesis%20de%20Maestr%c3%ada%20en%20Ciencias%20-%20Biotecnolog%c3%ada.pdf3516c170c397c04ec3362557e9e6a3aeMD52THUMBNAILTesis de Maestría en Ciencias - Biotecnología.pdf.jpgTesis de Maestría en Ciencias - Biotecnología.pdf.jpgGenerated Thumbnailimage/jpeg4047https://repositorio.unal.edu.co/bitstream/unal/85865/3/Tesis%20de%20Maestr%c3%ada%20en%20Ciencias%20-%20Biotecnolog%c3%ada.pdf.jpg50943ffa8b99c4f9336339d594eb62d6MD53unal/85865oai:repositorio.unal.edu.co:unal/858652024-08-23 23:11:49.457Repositorio Institucional Universidad Nacional de Colombiarepositorio_nal@unal.edu.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

Determinacion de PD-L1 exosomal en pacientes con neoplasias avanzadas

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