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The effect of cytosine deaminase-expressing mesenchymal stem cells in orthotopic glioma model of immune competent mice
| DC Field | Value | Language |
|---|---|---|
| dc.contributor.advisor | Haeyoung Suh-Kim | - |
| dc.contributor.author | VUHAIHA | - |
| dc.date.accessioned | 2022-11-29T02:32:26Z | - |
| dc.date.available | 2022-11-29T02:32:26Z | - |
| dc.date.issued | 2017-08 | - |
| dc.identifier.other | 25875 | - |
| dc.identifier.uri | https://dspace.ajou.ac.kr/handle/2018.oak/19965 | - |
| dc.description | 학위논문(석사)--아주대학교 일반대학원 :의생명과학과,2017. 8 | - |
| dc.description.tableofcontents | INTRODUCTION 1 Glioblastoma multiforme (GBM) 1 Anti-cancer therapies for GBM patients 1 Immunotherapy 1 Suicide gene therapies 2 Stem cells as cellular vehicle of therapeutic genes . 3 Temozolomide 4 MATERIALS AND METHODS 7 Cultivation of syngeneic murine glioma cell lines 7 Characterization of GL261 cell line 7 In vitro suicide effect of MSC/CD 8 In vitro bystander effects 8 Isobologram analysis 8 In vivo therapeutic effects 9 Histological analysis 9 MRI analysis of tumor growth 10 Statistics analysis 10 RESULTS 11 5-FU Sensitivity of glioma cells was preserved after reporter gene labeling 11 In vitro Suicide effects of MSC/CD 12 In vitro Bystander effects of MSC/CD against GL261/GFP cells 13 Combination effect of TMZ and 5FU in GL261/GFP cells in vitro 16 Combination effect of MSC/CD+5-FC and TMZ in GL261/GFP cells 17 Tumor growth kinetics 18 In vivo therapeutic effect 20 Contribution of immune-component factors in preclinical model 23 Critical function of immune system influent to tumor rejection in preclinical model 25 DISCUSSION 27 CONCLUSIONS 29 Supplementary data 30 REFERENCES 31 | - |
| dc.language.iso | eng | - |
| dc.publisher | The Graduate School, Ajou University | - |
| dc.rights | 아주대학교 논문은 저작권에 의해 보호받습니다. | - |
| dc.title | The effect of cytosine deaminase-expressing mesenchymal stem cells in orthotopic glioma model of immune competent mice | - |
| dc.title.alternative | The effect of cytosine deaminase-expressing mesenchymal stem cells in orthotopic glioma model of immune competent mice | - |
| dc.type | Thesis | - |
| dc.contributor.affiliation | 아주대학교 일반대학원 | - |
| dc.contributor.alternativeName | VU HAI HA | - |
| dc.contributor.department | 일반대학원 의생명과학과 | - |
| dc.date.awarded | 2017. 8 | - |
| dc.description.degree | Master | - |
| dc.identifier.localId | 1199333 | - |
| dc.identifier.url | http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000025875 | - |
| dc.subject.keyword | 5-Fluorocytosine | - |
| dc.subject.keyword | 5-Fluorouracil | - |
| dc.subject.keyword | Cytosine deaminase | - |
| dc.subject.keyword | Mesenchymal stem cells | - |
| dc.subject.keyword | Temozolomide | - |
| dc.description.alternativeAbstract | Glioblastoma multiforme (GBM) is the tumor common deriving from glia and aggressive primary brain tumor. Current standard therapy provides only modest improvements in progression-free and overall survival of patients. Most of the preclinical studies for glioma utilize immune deficient animals, which limits the assessment of role of immune system in glioma progression and therapy. However, the contribution of innate immune system in glioma progression cannot be excluded in clinical settings. In this study, an orthotopic glioma mouse model were established using a syngeneic mouse glioma cell line, GL261 in immune competent wild type C57BL/6 mice. GL261 cells (3x104 cells) were transplanted to the striatum and tumor growth kinetics was assessed by MRI imaging and histological analyses. The therapeutic effects of mesenchymal stem cells (MSC) that was previously engineered to express a suicide gene, cytosine deaminase (MSC/CD) was evaluated in this model. MSC/CD with administration of a prodrug 5-florocytosine (5-FC) was effective to suppress tumor growth. Therapeutic effect of MSC/CD with 5-FC was further enhanced when followed by treatment of temozolomide. Compared to nude mice, the overall survival of the animals treated with MSC/CD and 5-FC was higher in C57BL/6 mice, suggesting contribution of systemic immune system. Histological analysis revealed that more immune cells including macrophage/microglia, T lymphocytes were infiltrated to the tumor sites. The result indicate that combination therapy of MSC/CD with 5-FC and TMZ possess potent anticancer effects by direct chemoablation and subsequent activation of innate immune system. | - |
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- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
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