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Everolimus in combination with crizotinib synergistically inhibits the growth of ALK-positive anaplastic large cell lymphoma cells

DC Field Value Language
dc.contributor.advisor윤성수-
dc.contributor.author허문단-
dc.date.accessioned2017-07-19T10:26:27Z-
dc.date.available2017-07-19T10:26:27Z-
dc.date.issued2014-08-
dc.identifier.other000000021957-
dc.identifier.urihttps://hdl.handle.net/10371/132709-
dc.description학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2014. 8. 윤성수.-
dc.description.abstractAnaplastic large cell lymphoma (ALCL) is a rare, aggresive type of non-Hodgkin lymphoma, more than half of which harbors an aberrant NPM-ALK fusion protein. Both mTOR inhibitor everolimus and ALK inhibitor crizotinib have shown promising antitumor activity in ALK-positive cancer cell lines. However, their combined effect has not yet been investigated. This study aimed to evaluate the combined effect of everolimus and crizotinib in ALK-positive ALCL cell lines, Karpas 299 and SU-DHL-1. Western blot and flow cytometry were performed to elucidate the mechanism of combined effect as well. The results show that the combination of everolimus and crizotinib synergistically inhibit the growth of ALK-positive ALCL cells. Crizotinib attenuated ERK and AKT phosphorylation caused by everolimus. The combination treatment induced G1 cell-cycle arrest and increased apoptosis in ALK-positive ALCL cells. The synergistic effect of everolimus and crizotinib was also found in the non-small cell lung cancer cell line, NCI-H2228, that harbors a EML4-ALK fusion gene. In summary, everolimus combined with crizotinib synergistically inhibited the growth of ALK-positive ALCL cells by inhibiting ALK and mTOR phosphorylation and thus indirectly preventing aberrant ERK and AKT phosphorylation. Our results suggest that this combination could be used to improve the therapeutic outcome in patients with ALK-positive ALCL.-
dc.description.tableofcontentsAbstract i
Contents iii
List of Figures iv

Introduction 1
Materials and Methods 4
Results 8
Discussion 23
References 31
국문 초록 38
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dc.formatapplication/pdf-
dc.format.extent1324770 bytes-
dc.format.mediumapplication/pdf-
dc.language.isoen-
dc.publisher서울대학교 대학원-
dc.subjectmTOR-
dc.subjectEverolimus-
dc.subjectCrizotinib-
dc.subjectAnaplastic large cell lymphoma-
dc.subjectAnaplastic lymphoma kinase-
dc.subject.ddc610-
dc.titleEverolimus in combination with crizotinib synergistically inhibits the growth of ALK-positive anaplastic large cell lymphoma cells-
dc.typeThesis-
dc.description.degreeMaster-
dc.citation.pagesv, 39-
dc.contributor.affiliation의과대학 의학과-
dc.date.awarded2014-08-
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College of Medicine/School of Medicine (의과대학/대학원)Dept. of Medicine (의학과)Theses (Master's Degree_의학과)
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