Análisis de la interacción de fengicina en modelos de membranas bacterianas

Las fengicinas son lipopéptidos cíclicos producidos por algunas cepas de Bacillus como es el caso de Bacillus velezensis. Las fengicinas han demostrado tener actividad antimicrobiana contra bacterias fitopatógenas de relevancia en cultivos agrícolas, así como contra patógenos humanos multirresistent...

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Autores:
Ortega Patiño, Juan David
Tipo de recurso:
Trabajo de grado de pregrado
Fecha de publicación:
2025
Institución:
Universidad de Antioquia
Repositorio:
Repositorio UdeA
Idioma:
spa
OAI Identifier:
oai:bibliotecadigital.udea.edu.co:10495/45819
Acceso en línea:
https://hdl.handle.net/10495/45819
Palabra clave:
Paredes celulares de las bacterias
Bacterial cell walls
Membranas lipídicas
Lipid membranes
Resistencia a los medicamentos en microorganismos
Drug resistance in microorganisms
Espectroscopia infrarroja
Infrared spectroscopy
Lipopéptidos
Lipopeptides
Pseudomonas aeruginosa
Bacillus
Fengicinas
Modelos de membrana
Estudios biofísicos
http://aims.fao.org/aos/agrovoc/c_760
http://id.loc.gov/authorities/subjects/sh85010842
http://id.loc.gov/authorities/subjects/sh85077293
http://id.loc.gov/authorities/subjects/sh85039709
http://id.loc.gov/authorities/subjects/sh85066329
https://id.nlm.nih.gov/mesh/D055666
https://id.nlm.nih.gov/mesh/D011550
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
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openAccess
License
http://creativecommons.org/licenses/by-nc-sa/4.0/
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network_acronym_str UDEA2
network_name_str Repositorio UdeA
repository_id_str
dc.title.spa.fl_str_mv Análisis de la interacción de fengicina en modelos de membranas bacterianas
title Análisis de la interacción de fengicina en modelos de membranas bacterianas
spellingShingle Análisis de la interacción de fengicina en modelos de membranas bacterianas
Paredes celulares de las bacterias
Bacterial cell walls
Membranas lipídicas
Lipid membranes
Resistencia a los medicamentos en microorganismos
Drug resistance in microorganisms
Espectroscopia infrarroja
Infrared spectroscopy
Lipopéptidos
Lipopeptides
Pseudomonas aeruginosa
Bacillus
Fengicinas
Modelos de membrana
Estudios biofísicos
http://aims.fao.org/aos/agrovoc/c_760
http://id.loc.gov/authorities/subjects/sh85010842
http://id.loc.gov/authorities/subjects/sh85077293
http://id.loc.gov/authorities/subjects/sh85039709
http://id.loc.gov/authorities/subjects/sh85066329
https://id.nlm.nih.gov/mesh/D055666
https://id.nlm.nih.gov/mesh/D011550
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
title_short Análisis de la interacción de fengicina en modelos de membranas bacterianas
title_full Análisis de la interacción de fengicina en modelos de membranas bacterianas
title_fullStr Análisis de la interacción de fengicina en modelos de membranas bacterianas
title_full_unstemmed Análisis de la interacción de fengicina en modelos de membranas bacterianas
title_sort Análisis de la interacción de fengicina en modelos de membranas bacterianas
dc.creator.fl_str_mv Ortega Patiño, Juan David
dc.contributor.advisor.none.fl_str_mv Manrique Moreno, Marcela
dc.contributor.author.none.fl_str_mv Ortega Patiño, Juan David
dc.contributor.researchgroup.none.fl_str_mv Grupo de Bioquímica Estructural de Macromoléculas
dc.subject.lcsh.none.fl_str_mv Paredes celulares de las bacterias
Bacterial cell walls
Membranas lipídicas
Lipid membranes
Resistencia a los medicamentos en microorganismos
Drug resistance in microorganisms
Espectroscopia infrarroja
Infrared spectroscopy
topic Paredes celulares de las bacterias
Bacterial cell walls
Membranas lipídicas
Lipid membranes
Resistencia a los medicamentos en microorganismos
Drug resistance in microorganisms
Espectroscopia infrarroja
Infrared spectroscopy
Lipopéptidos
Lipopeptides
Pseudomonas aeruginosa
Bacillus
Fengicinas
Modelos de membrana
Estudios biofísicos
http://aims.fao.org/aos/agrovoc/c_760
http://id.loc.gov/authorities/subjects/sh85010842
http://id.loc.gov/authorities/subjects/sh85077293
http://id.loc.gov/authorities/subjects/sh85039709
http://id.loc.gov/authorities/subjects/sh85066329
https://id.nlm.nih.gov/mesh/D055666
https://id.nlm.nih.gov/mesh/D011550
ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
dc.subject.decs.none.fl_str_mv Lipopéptidos
Lipopeptides
Pseudomonas aeruginosa
dc.subject.agrovoc.none.fl_str_mv Bacillus
dc.subject.proposal.spa.fl_str_mv Fengicinas
Modelos de membrana
Estudios biofísicos
dc.subject.agrovocuri.none.fl_str_mv http://aims.fao.org/aos/agrovoc/c_760
dc.subject.lcshuri.none.fl_str_mv http://id.loc.gov/authorities/subjects/sh85010842
http://id.loc.gov/authorities/subjects/sh85077293
http://id.loc.gov/authorities/subjects/sh85039709
http://id.loc.gov/authorities/subjects/sh85066329
dc.subject.meshuri.none.fl_str_mv https://id.nlm.nih.gov/mesh/D055666
https://id.nlm.nih.gov/mesh/D011550
dc.subject.ods.none.fl_str_mv ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edades
description Las fengicinas son lipopéptidos cíclicos producidos por algunas cepas de Bacillus como es el caso de Bacillus velezensis. Las fengicinas han demostrado tener actividad antimicrobiana contra bacterias fitopatógenas de relevancia en cultivos agrícolas, así como contra patógenos humanos multirresistentes a antibióticos. Sin embargo, el mecanismo por el cual las fengicinas ejercen su actividad antimicrobiana no ha sido totalmente dilucidado. En el siguiente trabajo, se evaluó la interacción de un extracto de fengicinas producidas por Bacillus velezensis con modelos representativos de membranas de Pseudomonas aeruginosa (P. aeruginosa), estos modelos permiten evaluar la afinidad del lipopéptido cíclico por los lípidos de la membrana y así identificar interacciones responsables de su actividad biológica. Las Fengicinas fueron obtenidas mediante la técnica de precipitación ácida de bacterias de la cepa Bacillus velezensis MEP218. Para evaluar la actividad de las fengicinas se prepararon bicapas lipídicas soportadas a partir de los lípidos sintéticos de P. aeruginosa y también de extractos de lípidos totales de P. aeruginosa PA01 obtenidos por la metodología de Bligh y Dyer y se evaluaron por espectroscopia infrarroja. Los resultados obtenidos demuestran que el extracto de Fengicinas tiene la capacidad de inducir cambios en el comportamiento termotrópico de los modelos lipídicos. El análisis de los resultados indicó que el mecanismo de acción del péptido podría estar relacionado con una interacción no selectiva con los lípidos de membrana de P. aeruginosa. En particular, su interacción con la cardiolipina fue predominante, como lo evidenciaron los análisis espectroscópicos, los cuales mostraron una transición de fase más pronunciada e intensa.
publishDate 2025
dc.date.accessioned.none.fl_str_mv 2025-05-07T15:15:11Z
dc.date.issued.none.fl_str_mv 2025
dc.type.none.fl_str_mv Trabajo de grado - Pregrado
dc.type.coar.none.fl_str_mv http://purl.org/coar/resource_type/c_7a1f
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dc.type.content.none.fl_str_mv Text
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dc.identifier.uri.none.fl_str_mv https://hdl.handle.net/10495/45819
url https://hdl.handle.net/10495/45819
dc.language.iso.none.fl_str_mv spa
language spa
dc.relation.references.none.fl_str_mv Gauba A, Rahman KM. Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria. Antibiotics. 2023;12(11):1590. doi: 10.3390/antibiotics12111590
Nicolson GL. The Fluid - Mosaic Model of Membrane Structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. Biochim Biophys Acta - Biomembr [Internet]. 2014;1838(6):1451–66. Available from: http://dx.doi.org/10.1016/j.bbamem.2013.10.019
Lombard J. Once upon a time the cell membranes: 175 years of cell boundary research. Biol Direct. 2014;9(1):1–35.
Ramos-Martín F, D’Amelio N. Biomembrane lipids: When physics and chemistry join to shape biological activity. Biochimie [Internet]. 2022;203:118–38.
Kilelee E, Pokorny A, Yeaman MR, Bayer AS. Lysyl-phosphatidylglycerol attenuates membrane perturbation rather than surface association of the cationic antimicrobial peptide 6W-RP-1 in a model membrane system: Implications for daptomycin Resistance. Antimicrob Agents Chemother. 2010;54(10):4476–9.
Deleu M, Paquot M, Nylander T. Effect of fengycin, a lipopeptide produced by Bacillus subtilis, on model biomembranes. Biophys J [Internet]. 2008;94(7):2667–79.
Moraes-Filho JP, Quigley EMM. Microbiota intestinal e função dos probióticos na síndrome do intestino irritável: Uma revisão. Arq Gastroenterol. 2015;52(4):331–8.
Madigan MT, Martinko JM, Bender KS, Buckley DH, Stahl DA. Brock. Biología de los microorganismos. 14a ed. Madrid: Pearson Educación; 2015. Capítulo 4, Estructura y función celular en bacterias y arqueas; p. 105-146.
biotechmind. Pared Celular [Imagen]. Disponible en: https://biotechmind.wordpress.com/wp-content/uploads/2015/04/parede- celular.jpg
Chen N, Jiang C. Antimicrobial peptides: Structure, mechanism, and modification. Eur J Med Chem. 2023;115377. doi:10.1016/j.ejmech.2023.115377.
Kumar A, Manna A, Ghosh S, Sikdar S, Sahu R, Kumar P, et al. Advances in Cancer Biology - Metastasis Molecular mechanisms of the lipopeptides from Bacillus subtilis in the apoptosis of cancer cells - A review on its Current Status in different cancer cell lines. Adv Cancer Biol - Metastasis [Internet]. 2021;3(November):100019. Available from: https://doi.org/10.1016/j.adcanc.2021.100019
Bhattacharjya S, Zhang Z, Ramamoorthy A. LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases. Biomolecules [Internet]. 2024;14(3).
Huang HW. DAPTOMYCIN, its membrane-active mechanism vs. that of other antimicrobial peptides. Biochim Biophys Acta - Biomembr [Internet]. 2020;1862(10):183395.
Wu CY, Chen CL, Lee YH, Cheng YC, Wu YC, Shu HY, et al. Nonribosomal synthesis of fengycin on an enzyme complex formed by fengycin synthetases. J Biol Chem [Internet]. 2007;282(8):5608–16.
Kenfaoui, J., Dutilloy, E., Benchlih, S., Lahlali, R., Ait-Barka, E., & Esmaeel, Q. (2024). Bacillus velezensis: A versatile ally in the battle against phytopathogens—insights and prospects. Applied Microbiology and Biotechnology, Volume(Issue), páginas. https://doi.org/10.1007/s00253-024- 13255-7
Lin TP, Chen CL, Chang LK, Tschen JSM, Liu ST. Functional and transcriptional analyses of a fengycin synthetase gene, fenC, from Bacillus subtilis. J Bacteriol [Internet]. 1999;181(16):5060–7.
Gutiérrez P, Orduz S. PÉPTIDOS ANTIMICROBIANOS : ESTRUCTURA , FUNCIÓN Y APLICACIONES. 2003;25(78):5–15.
Manrique-Moreno M, Santa-González GA, Gallego V. Bioactive cationic peptides as potential agents for breast cancer treatment. Biosci Rep. 2021;41(12):BSR20211218C. doi:10.1042/BSR20211218C.
Cubillos, J. E., & Caycedo Lozano, L. (s.f.). Los péptidos antimicrobianos y sus propiedades como macromoléculas: una revisión sistemática. Hemeroteca UNAD.
Stuart B. Infrared Spectroscopy: Fundamentals and Applications. Chichester (UK): John Wiley & Sons; 2004.
Griffiths PR, de Haseth JA. Fourier Transform Infrared Spectrometry. 2nd ed. Moscow (ID): University of Idaho; Athens (GA): University of Georgia; 2007.
Bruker. What is FT-IR spectroscopy? Bruker. Available from: https://www.bruker.com/es/products-and-solutions/infrared-and-raman/ft-ir- routine-spectrometer/what-is-ft-ir-spectroscopy.html
Zecchi KA. Electro-mechanical properties of lipid membranes at their phase transition. 2013
Breil, C., Abert Vian, M., Zemb, T., Kunz, W., & Chemat, F. (2017). Bligh and Dyer and Folch Methods for Solid–Liquid–Liquid Extraction of Lipids from Microorganisms. Comprehension of Solvatation Mechanisms and towards Substitution with Alternative Solvents. International Journal of Molecular Sciences, 18(4), Article 708. DOI: 10.3390/ijms18040708
Medeot DB, Bertorello Cuenca M, Liaudat JP, Alvarez F, Flores Cáceres ML, Jofré E. Improvement of biomass and cyclic lipopeptides production in Bacillus amyloliquefaciens MEP218 by modifying carbon and nitrogen. sources and ratios of the culture media. Biol Control. 2017 Dec;115:119- antim128. doi:10.1016/j.biocontrol.2017.10.002.
Lyon R, Jones RA, Shropshire H, Aberdeen I, Scanlan DJ, Millard A, Chen Y. Membrane lipid renovation in Pseudomonas aeruginosa - implications for phage therapy? Environ Microbiol. 2022 Oct;24(10):4533-4546. doi: 10.1111/1462-2920.16136. Epub 2022 Aug 14. PMID: 35837865; PMCID: PMC9804370.
Epand, R.M.; Epand, R.F. Lipid Domains in Bacterial Membranes and the Action of Antimicrobial Agents. Biochim. Biophys. Acta (BBA)-Biomembr. 2009, 1788, 289–294.
Nair SS, Göbl C, Kleffmann T, Pletzer D, Smith B, Fellner M. Comparative lipidomics profiles of planktonic and biofilms of methicillin-resistant and - susceptible Staphylococcus aureus.
Lewis RNAH, McElhaney RN. Membrane lipid phase transitions and phase organization studied by Fourier transform infrared spectroscopy. Biochim Biophys Acta - Biomembr [Internet]. 2013;1828(10):2347–58. Available from: http://dx.doi.org/10.1016/j.bbamem.2012.10.018.
Steenbergen JN, Alder J, Thorne GM, Tally FP. Daptomycin: a lipopeptide antibiotic for the treatment of serious Gram-positive infections. J Antimicrob Chemother. 2005;55(3):283-8. doi:10.1093/jac/dkh546.
L.M. González-Jaramillo, F.J. Aranda, J.A. Teruel, V. Villegas-Escobar, A. Ortiz, Antimycotic activity of fengycin C biosurfactant and its interaction with phosphatidylcholine model membranes, Colloids Surf. B Biointerfaces 156 (2017) 114–122.
Kleetz J, Welter L, Mizza AS, Aktas M, Narberhaus F. Phospholipid N- methyltransferases produce various methylated phosphatidylethanolamine derivatives in thermophilic bacteria. Genet Mol Biol. 2021;44(3):e20210050.
Wilderman PJ, Vasil AI, Martin WE, Murphy RC, Vasil ML. Pseudomonas aeruginosa synthesizes phosphatidylcholine by use of the phosphatidylcholine synthase pathway. J Bacteriol. 2002;184(17):4792- 4799.
Venkatraman K, Lee CT, Budin I. Setting the curve: the biophysical properties of lipids in mitochondrial form and function. Department of Chemistry and Biochemistry, and the Department of Molecular Biology, University of California San Diego, La Jolla, CA, USA
Nair SS, Göbl C, Kleffmann T, Pletzer D, Smith B, Fellner M. Comparative lipidomics profiles of planktonic and biofilms of methicillin-resistant and - susceptible Staphylococcus aureus.
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spelling Manrique Moreno, MarcelaOrtega Patiño, Juan DavidGrupo de Bioquímica Estructural de Macromoléculas2025-05-07T15:15:11Z2025https://hdl.handle.net/10495/45819Las fengicinas son lipopéptidos cíclicos producidos por algunas cepas de Bacillus como es el caso de Bacillus velezensis. Las fengicinas han demostrado tener actividad antimicrobiana contra bacterias fitopatógenas de relevancia en cultivos agrícolas, así como contra patógenos humanos multirresistentes a antibióticos. Sin embargo, el mecanismo por el cual las fengicinas ejercen su actividad antimicrobiana no ha sido totalmente dilucidado. En el siguiente trabajo, se evaluó la interacción de un extracto de fengicinas producidas por Bacillus velezensis con modelos representativos de membranas de Pseudomonas aeruginosa (P. aeruginosa), estos modelos permiten evaluar la afinidad del lipopéptido cíclico por los lípidos de la membrana y así identificar interacciones responsables de su actividad biológica. Las Fengicinas fueron obtenidas mediante la técnica de precipitación ácida de bacterias de la cepa Bacillus velezensis MEP218. Para evaluar la actividad de las fengicinas se prepararon bicapas lipídicas soportadas a partir de los lípidos sintéticos de P. aeruginosa y también de extractos de lípidos totales de P. aeruginosa PA01 obtenidos por la metodología de Bligh y Dyer y se evaluaron por espectroscopia infrarroja. Los resultados obtenidos demuestran que el extracto de Fengicinas tiene la capacidad de inducir cambios en el comportamiento termotrópico de los modelos lipídicos. El análisis de los resultados indicó que el mecanismo de acción del péptido podría estar relacionado con una interacción no selectiva con los lípidos de membrana de P. aeruginosa. En particular, su interacción con la cardiolipina fue predominante, como lo evidenciaron los análisis espectroscópicos, los cuales mostraron una transición de fase más pronunciada e intensa.Resistencia bacterianaCOL0156275PregradoQuímico51 páginasapplication/pdfspaUniversidad de AntioquiaQuímicaInstituto de QuímicaMedellín, ColombiaFacultad de Ciencias Exactas y NaturalesCampus Medellín - Ciudad Universitariahttp://creativecommons.org/licenses/by-nc-sa/4.0/info:eu-repo/semantics/openAccessAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://purl.org/coar/access_right/c_abf2Paredes celulares de las bacteriasBacterial cell wallsMembranas lipídicasLipid membranesResistencia a los medicamentos en microorganismosDrug resistance in microorganismsEspectroscopia infrarrojaInfrared spectroscopyLipopéptidosLipopeptidesPseudomonas aeruginosaBacillusFengicinasModelos de membranaEstudios biofísicoshttp://aims.fao.org/aos/agrovoc/c_760http://id.loc.gov/authorities/subjects/sh85010842http://id.loc.gov/authorities/subjects/sh85077293http://id.loc.gov/authorities/subjects/sh85039709http://id.loc.gov/authorities/subjects/sh85066329https://id.nlm.nih.gov/mesh/D055666https://id.nlm.nih.gov/mesh/D011550ODS 3: Salud y bienestar. Garantizar una vida sana y promover el bienestar de todos a todas las edadesAnálisis de la interacción de fengicina en modelos de membranas bacterianasTrabajo de grado - Pregradohttp://purl.org/coar/resource_type/c_7a1fhttp://purl.org/redcol/resource_type/TPTexthttp://purl.org/coar/version/c_b1a7d7d4d402bcceinfo:eu-repo/semantics/bachelorThesisinfo:eu-repo/semantics/draftGauba A, Rahman KM. Evaluation of Antibiotic Resistance Mechanisms in Gram-Negative Bacteria. Antibiotics. 2023;12(11):1590. doi: 10.3390/antibiotics12111590Nicolson GL. The Fluid - Mosaic Model of Membrane Structure: Still relevant to understanding the structure, function and dynamics of biological membranes after more than 40 years. Biochim Biophys Acta - Biomembr [Internet]. 2014;1838(6):1451–66. Available from: http://dx.doi.org/10.1016/j.bbamem.2013.10.019Lombard J. Once upon a time the cell membranes: 175 years of cell boundary research. Biol Direct. 2014;9(1):1–35.Ramos-Martín F, D’Amelio N. Biomembrane lipids: When physics and chemistry join to shape biological activity. Biochimie [Internet]. 2022;203:118–38.Kilelee E, Pokorny A, Yeaman MR, Bayer AS. Lysyl-phosphatidylglycerol attenuates membrane perturbation rather than surface association of the cationic antimicrobial peptide 6W-RP-1 in a model membrane system: Implications for daptomycin Resistance. Antimicrob Agents Chemother. 2010;54(10):4476–9.Deleu M, Paquot M, Nylander T. Effect of fengycin, a lipopeptide produced by Bacillus subtilis, on model biomembranes. Biophys J [Internet]. 2008;94(7):2667–79.Moraes-Filho JP, Quigley EMM. Microbiota intestinal e função dos probióticos na síndrome do intestino irritável: Uma revisão. Arq Gastroenterol. 2015;52(4):331–8.Madigan MT, Martinko JM, Bender KS, Buckley DH, Stahl DA. Brock. Biología de los microorganismos. 14a ed. Madrid: Pearson Educación; 2015. Capítulo 4, Estructura y función celular en bacterias y arqueas; p. 105-146.biotechmind. Pared Celular [Imagen]. Disponible en: https://biotechmind.wordpress.com/wp-content/uploads/2015/04/parede- celular.jpgChen N, Jiang C. Antimicrobial peptides: Structure, mechanism, and modification. Eur J Med Chem. 2023;115377. doi:10.1016/j.ejmech.2023.115377.Kumar A, Manna A, Ghosh S, Sikdar S, Sahu R, Kumar P, et al. Advances in Cancer Biology - Metastasis Molecular mechanisms of the lipopeptides from Bacillus subtilis in the apoptosis of cancer cells - A review on its Current Status in different cancer cell lines. Adv Cancer Biol - Metastasis [Internet]. 2021;3(November):100019. Available from: https://doi.org/10.1016/j.adcanc.2021.100019Bhattacharjya S, Zhang Z, Ramamoorthy A. LL-37: Structures, Antimicrobial Activity, and Influence on Amyloid-Related Diseases. Biomolecules [Internet]. 2024;14(3).Huang HW. DAPTOMYCIN, its membrane-active mechanism vs. that of other antimicrobial peptides. Biochim Biophys Acta - Biomembr [Internet]. 2020;1862(10):183395.Wu CY, Chen CL, Lee YH, Cheng YC, Wu YC, Shu HY, et al. Nonribosomal synthesis of fengycin on an enzyme complex formed by fengycin synthetases. J Biol Chem [Internet]. 2007;282(8):5608–16.Kenfaoui, J., Dutilloy, E., Benchlih, S., Lahlali, R., Ait-Barka, E., & Esmaeel, Q. (2024). Bacillus velezensis: A versatile ally in the battle against phytopathogens—insights and prospects. Applied Microbiology and Biotechnology, Volume(Issue), páginas. https://doi.org/10.1007/s00253-024- 13255-7Lin TP, Chen CL, Chang LK, Tschen JSM, Liu ST. Functional and transcriptional analyses of a fengycin synthetase gene, fenC, from Bacillus subtilis. J Bacteriol [Internet]. 1999;181(16):5060–7.Gutiérrez P, Orduz S. PÉPTIDOS ANTIMICROBIANOS : ESTRUCTURA , FUNCIÓN Y APLICACIONES. 2003;25(78):5–15.Manrique-Moreno M, Santa-González GA, Gallego V. Bioactive cationic peptides as potential agents for breast cancer treatment. 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