Please use this identifier to cite or link to this item: https://hdl.handle.net/10316/82805
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dc.contributor.advisorRibeiro, Ana Bela Sarmento Antunes Cruz-
dc.contributor.advisorCarda, José Pedro do Nascimento-
dc.contributor.authorFaria, Margarida Isabel dos Santos-
dc.date.accessioned2018-12-20T04:44:23Z-
dc.date.available2018-12-20T04:44:23Z-
dc.date.issued2018-03-08-
dc.date.submitted2019-01-21-
dc.identifier.urihttps://hdl.handle.net/10316/82805-
dc.descriptionTrabalho Final do Mestrado Integrado em Medicina apresentado à Faculdade de Medicina-
dc.description.abstractA leucemia linfocítica crónica de células B (LLC-B), uma neoplasia de linfócitos B monoclonais, corresponde à leucemia mais frequente nos adultos. Os esquemas de quimioimunoterapia tradicionais, que atuam nas células leucémicas, têm vindo a constituir a base do tratamento da LLC e com estes é possível atingir remissões completas em doentes não previamente tratados. No entanto, a elevada toxicidade destes fármacos limita o seu uso a doentes jovens e fit. Nos últimos anos, a compreensão da heterogeneidade dos mecanismos fisiopatológicos subjacentes à sobrevivência, proliferação e homing das células leucémicas, permitiu o desenvolvimento de terapêuticas alvo: inibidores do BCR, anticorpos monoclonais e inibidores da BCL-2. Estes novos agentes têm vindo a ser crescentemente usados em doentes com doença recidivante, em doentes com del(17p)/mutação TP53 e em doentes less fit. Novos inibidores do BCR, da BCL-2 e novos imunomodeladores com novos alvos estão a ser estudados na LLC, alguns dos quais serão explorados nesta dissertação. ABSTRACT Chronic lymphocytic leukemia of B cells (B-CLL), a clonal disease of B-lymphocytes, is the most common leukemia in adulthood. Traditional chemoimmunotherapy has been the basis of CLL treatment approaches, which have focused ontar1geting leukemic cells as an autonomous malignant cell population. They are able toachieve complete remissions in most untreated patients. However, their higher toxicitylimits its use to young and fit patients. In recent years, the understanding regarding theheterogeneity of CLL’s physiopathology on leukemic cell’s survival, proliferation,survival and homing of the leukemic cells allowed the development of kinetic inhibitorsthat target BCR signalling, monoclonal antibodies and BCL-2 inhibitors. These newagents have been increasingly used in patients with relapsed disease, in patients withdel(17p)/TP53 mutation and in less fit patients. New BCR and BCL-2 inhibitors and newimmunomodulatory drugs with new targets are on study in CLL, some of which will beexplored in this dissertation.por
dc.description.abstractChronic lymphocytic leukemia of B cells (B-CLL), a clonal disease of B-lymphocytes, is the most common leukemia in adulthood. Traditional chemoimmunotherapy has been the basis of CLL treatment approaches, which have focused on targeting leukemic cells as an autonomous malignant cell population. They are able to achieve complete remissions in most untreated patients. However, their higher toxicity limits its use to young and fit patients. In recent years, the understanding regarding the heterogeneity of CLL’s physiopathology on leukemic cell’s survival, proliferation, survival and homing of the leukemic cells allowed the development of kinetic inhibitors that target BCR signalling, monoclonal antibodies and BCL-2 inhibitors. These new agents have been increasingly used in patients with relapsed disease, in patients with del(17p)/TP53 mutation and in less fit patients. New BCR and BCL-2 inhibitors and new immunomodulatory drugs with new targets are on study in CLL, some of which will beexplored in this dissertation. RESUMO A leucemia linfocítica crónica de células B (LLC-B), uma neoplasia de linfócitosB monoclonais, corresponde à leucemia mais frequente nos adultos. Os esquemas de quimioimunoterapia tradicionais, que atuam nas células leucémicas, têm vindo aconstituir a base do tratamento da LLC e com estes é possível atingir remissões completasem doentes não previamente tratados. No entanto, a elevada toxicidade destes fármacoslimita o seu uso a doentes jovens e fit. Nos últimos anos, a compreensão daheterogeneidade dos mecanismos fisiopatológicos subjacentes à sobrevivência,proliferação e homing das células leucémicas, permitiu o desenvolvimento de terapêuticoalvo: inibidores do BCR, anticorpos monoclonais e inibidores da BCL-2. Estes novosagentes têm vindo a ser crescentemente usados em doentes com doença recidivante, emdoentes com del(17p)/mutação TP53 e em doentes less fit. Novos inibidores do BCR, daBCL-2 e novos imunomodeladores com novos alvos estão a ser estudados na LLC, algunsdos quais serão explorados nesta dissertação.eng
dc.language.isopor-
dc.rightsclosedAccess-
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.subjectLEUCEMIA LINFOCÍTICA CRÓNICApor
dc.subjectQUIMIOIMUNOTERAPIApor
dc.subjectINIBIDORES BCRpor
dc.subjectINIBIDORES BCL-2por
dc.subjectANTICORPOS MONOCLONAISpor
dc.subjectCHRONIC LYMPHOCYTIC LEUKEMIAeng
dc.subjectCHEMOIMMUNOTHERAPYeng
dc.subjectBTK/BCR INHIBITORSeng
dc.subjectBCL-2 INHIBITIONeng
dc.subjectMONOCLONAL ANTIBODY THERAPYeng
dc.titleAbordagem terapêutica à leucemia linfocítica crónicapor
dc.title.alternativeTHERAPEUTIC APPROACH TO CHRONIC LYMPHOCYTIC LEUKEMIAeng
dc.typemasterThesis-
degois.publication.locationFaculdade de Medicina da Universidade de Coimbra-
degois.publication.titleABORDAGEM TERAPÊUTICA À LEUCEMIA LINFOCÍTICA CRÓNICApor
dc.peerreviewedyes-
dc.identifier.tid202051315-
thesis.degree.disciplineMedicina-
thesis.degree.grantorUniversidade de Coimbra-
thesis.degree.level1-
thesis.degree.nameMestrado Integrado em Medicina-
uc.degree.grantorUnitFaculdade de Medicina-
uc.degree.grantorID0500-
uc.contributor.authorFaria, Margarida Isabel dos Santos::0000-0002-3676-2176-
uc.degree.classification18-
uc.degree.presidentejuriSantos, Catarina Isabel Batista Geraldes-
uc.degree.elementojuriCortesão, Emilia Nobre Barata Roxo-
uc.degree.elementojuriCarda, José Pedro do Nascimento-
uc.contributor.advisorRibeiro, Ana Bela Sarmento Antunes Cruz-
uc.contributor.advisorCarda, José Pedro do Nascimento-
item.openairetypemasterThesis-
item.languageiso639-1pt-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.grantfulltextreserved-
item.fulltextCom Texto completo-
crisitem.advisor.researchunitCNC - Center for Neuroscience and Cell Biology-
crisitem.advisor.orcid0000-0002-4142-4841-
Appears in Collections:UC - Dissertações de Mestrado
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