Elucidation of Sorafenib resistance mechanisms in hepatocellular carcinoma

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buir.advisorGöktuna, Serkan İsmail
dc.contributor.authorBoyacıoğlu, Zeynep
dc.date.accessioned2018-07-27T07:46:11Z
dc.date.available2018-07-27T07:46:11Z
dc.date.copyright2018-07
dc.date.issued2018-07
dc.date.submitted2018-07-25
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.descriptionCataloged from PDF version of article.en_US
dc.descriptionThesis (M.S.): Bilkent University, Department of Molecular Biology and Genetics, İhsan Doğramacı Bilkent University, 2018.en_US
dc.descriptionIncludes bibliographical references (leaves 58-65).en_US
dc.description.abstractHepatocellular Carcinoma (HCC) is the sixth most common type of cancer and the second leading cause of cancer-related deaths worldwide. Currently, Sorafenib is the only approved first-line treatment option for unresectable advanced HCC patients. Although Sorafenib can be beneficial for some patients, overall survival can only be extended for 4 months. One of the main reasons is the development of Sorafenib resistance. Many studies have been conducted to decipher the mechanisms underlying this drug resistance, yet much more still awaits for elucidation. This study suggests a novel involvement of a player, an antiviral kinase, which was previously described as an oncogenic protein. Strikingly in our investigation, Sorafenib resistance seems to be caused by the loss of this interferon related kinase. This protein expression is ablated in Sorafenib resistant Hep3B cell line. Loss of this protein by shRNA confers Sorafenib resistance to naïve Hep3B cells. Reversely, protein rescue can re-sensitize these resistant cells to Sorafenib. We also report in this work for the first time that this Sorafenib resistant Hep3B cell line exhibits partial EMT signature. Over all, this study paves way for further studies investigating the implication of this antiviral protein in Sorafenib resistance mechanism in HCC.en_US
dc.description.degreeM.S.en_US
dc.description.provenanceSubmitted by Betül Özen (ozen@bilkent.edu.tr) on 2018-07-27T07:46:11Z No. of bitstreams: 1 Zeynep Boyacıoğlu Thesis.pdf: 1371849 bytes, checksum: 37884ac79a1ad4193b956fe78c3f88f3 (MD5)en
dc.description.provenanceMade available in DSpace on 2018-07-27T07:46:11Z (GMT). No. of bitstreams: 1 Zeynep Boyacıoğlu Thesis.pdf: 1371849 bytes, checksum: 37884ac79a1ad4193b956fe78c3f88f3 (MD5) Previous issue date: 2018-07en
dc.description.statementofresponsibilityby Zeynep Boyacıoğlu.en_US
dc.embargo.release2019-01-25
dc.format.extentx, 65 leaves : charts (some color) ; 30 cm.en_US
dc.identifier.itemidB158735
dc.identifier.urihttp://hdl.handle.net/11693/47682
dc.language.isoEnglishen_US
dc.publisherBilkent Universityen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectHCCen_US
dc.subjectSorafenib Resistanceen_US
dc.subjectHep3Ben_US
dc.subjectOncogenic Antiviral Proteinsen_US
dc.titleElucidation of Sorafenib resistance mechanisms in hepatocellular carcinomaen_US
dc.title.alternativeHepatoselüler karsinomda Sorafenib direnç mekanizmalarının belirlenmesien_US
dc.typeThesisen_US

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Dept. of Molecular Biology and Genetics - Master's degree