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Combination therapy of 5-FU and α-galactosylceramide enhances the anti-tumor effect in CT26 cancer model

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dc.contributor.advisor서, 해영-
dc.contributor.author김, 민경-
dc.date.accessioned2023-11-16T05:43:53Z-
dc.date.available2023-11-16T05:43:53Z-
dc.date.issued2023-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/26830-
dc.language.isoen-
dc.titleCombination therapy of 5-FU and α-galactosylceramide enhances the anti-tumor effect in CT26 cancer model-
dc.title.alternativeCT26 대장암 모델에서 5-FU와 알파-갈락토실세라마이드의 병용 요법으로 인한 항종양 효과 강화-
dc.typeThesis-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000032837-
dc.subject.keywordMesenchymal stem cell-
dc.subject.keywordcytosine deaminase-
dc.subject.keyword5-Fluorocytosine-
dc.subject.keywordα-galactosylceramide-
dc.subject.keywordimmunotherapy-
dc.subject.keyword중간엽 줄기세포-
dc.subject.keyword5-플루오르사이토신-
dc.subject.keyword알파-갈락토실세라마이드-
dc.subject.keyword면역항암요법-
dc.description.degreeDoctor-
dc.contributor.department대학원 의생명과학과-
dc.contributor.affiliatedAuthor김, 민경-
dc.date.awarded2023-
dc.type.localTheses-
dc.citation.date2023-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.description.tableOfContentsA. INTRODUCTION 1

B. MATERIALS AND METHODS 9

1. Cell culture and maintenance 9

2. Animals 9

3. Reagent preparation 10

4. 5-FU sensitivity test 10

5. CT26 cancer model 10

6. Evaluation of the tumor cell killing effect of 5-FU in vivo 10

7. Hematoxylin and eosin (H&E) staining 11

8. Bystander effect test 11

9. Evaluation of anti-cancer effect by combined administration of MSC/CD and various doses of 5-FC in CT26 cancer model 12

10. Evaluation of in vivo therapeutic efficacy of MSC/CD, 5-FC in CT26 cancer model 12

11. Evaluation of anticancer effects by combined administration of MSC/CD, 5-FC, and various PAMP molecules in the CT26 cancer model 12

12. Evaluation of appropriate dosing timing and frequency of α-GalCer for combination with MSC/CD and 5-FC in CT26 cancer Model 13

13. Evaluation of in vivo therapeutic efficacy of MSC/CD, 5-FC, and α-GalCer in CT26 cancer Model 13

14. Evaluation of white blood cell (WBC) changes 14

15. Measurement of in vivo cytokines 14

16. Measurement of in vivo immune cells 15

17. Assessment of hepatoxicity by α-GalCer 15

18. Evaluation of anticancer effect by administration of MSC/CD, 5-FC, and/or α-GalCer in BNL cancer model 16

19. Quantification and statistical analysis 16

C. RESULTS 18

1. Cell death effect of 5-FU in CT26 cells 18

2. MSC/CD with 5-FC showed highly effective cell death in CT26-GFP cells 21

3. MSC/CD with 5-FC demonstrates moderate in vivo anticancer effects in a colon cancer model 24

4. α-GalCer is an immunomodulator that has a synergic effect with MSC/CD with 5-FC 27

5. Combination of MSC/CD with 5-FC and α-GalCer exhibits enhanced anticancer effects in a colon cancer model 29

6. Administration of MSC/CD and α-GalCer affects NKT cells and intratumoral cytokines 35

7. Effects of MSC/CD and/or α-GalCer administration on intratumoral antigen-presenting cells (APCs) and cytokine levels 39

8. Effects of MSC/CD and α-GalCer administration on CD4+ T cell and CD8+ T cell counts and cytotoxicity of these cells 43

9. Effects of MSC/CD and α-GalCer Administration on Immunosuppressive Cells and Cytokine Levels 48

10. The Enhanced Anticancer Efficacy of α-GalCer Alone in the BNL hepatocarcinoma model 52

11. Toxicity evaluation of α-GalCer and combined administration of α-GalCer and MSC/CD 54

D. DISCUSSION 62

E. REFERENCES 67

국문요약 76
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