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CDK4/6 억제제와 DNA 손상 물질에 의해 유도된 노화 유방암세포에서 종양 미세환경 조절 인자 전사체 비교 분석
No full textDoctorI. INTRODUCTUON 1
1. Cellular senescence 1
2. Cancer senescence 4
3. Therapy-induced senescence 6
4. Remodeling of the TME by TIS 10
5. Proposal 13
II. MATERIALS AND METHOD 14
1. Cell culture 14
2. Reagents for senescence in the breast cancer cell lines 14
3. Induction of senescence in the breast cancer cell lines 14
4. Assessment of SA-β-galactosidase activity 15
5. Fluorescence Activated Cell Sorting (FACS) 15
6. Cell viability assay 15
7. RNA Extraction and quantitative real-time PCR 15
8. Western blotting 16
9. Enzyme-Linked Immunosorbent Assay (ELISA) 16
10. Tube formation assay 17
11. RNA sequencing and normalization of differentially expressed genes (DEGs) 17
12. Analysis of transcriptome and data visualization 17
13. Data availability statement 18
14. Statistical analysis 18
15. List of primer sequences 19
III. RESULTS 21
1. DNA-damaging agents and CDK4/6i induce a comparable level of senescence in breast cancer cells 21
2. Aromatase inhibitors (AI) exhibit no impact on CDK4/6i-induced senescence 26
3. TIS by DNA-damaging agents and CDK4/6i is distinctively regulated by genes associated with inflammation, tumor immunity, and angiogenesis 29
4. DNA-damaging agents-induced senescence demonstrate elevated expression levels of pro-tumorigenic cytokines and ligands compared to CDK4/6i 38
5. Angiogenesis is more abundantly enhanced by DNA-damaging agents- than by CDK4/6i-induced senescent tumor cells 46
6. The activities of antigen presentation and interferon signaling in CDK4/6i-induced senescence tumor cells are comparably enhanced with those of DNA-damaging agents 55
7. DNA-damaging agents and CDK4/6i induce senescence in HCC1428 breast cancer cells similar to MCF-7 64
8. TIS by DNA-damaging agents (Etoposide and Carboplatin) or CDK4/6i (Abemaciclib) differently regulate inflammatory cytokines and angiogenesis regulators, immune-related factors in breast cancer cell line 71
9. The activation of p53 and NF-κB signaling is notably more pronounced in senescence induced by DNA-damaging agents compared to CDK4/6i 76
IV. DISCUSSION 83
1. Senescence induced by various therapeutic agents 83
2. Pro-tumorigenic effects of TIS 84
3. Angiogenesis regulation of TIS 85
4. Anti-tumor immune activation of TIS 87
5. Signaling pathway of TIS 88
6. Implications and limitations 89
7. Further study 90
Ⅴ. CONCLUSION 92
Ⅵ. REFERENCE 94
국문요약 12
Roles of TRIM22 in autophagy and its association with Alzheimer's disease
No full textDoctorI. INTRODUCTION 1
1. Autophagy 1
2. Formation of autophagosome 2
3. Autophagosome-lysosome fusion 3
4. Autophagy and neurodegenerative disease 5
5. TRIM proteins 7
6. The aims of this study 9
II. MATERIALS AND METHODS 10
1. DNA constructs 10
2. Antibodies 11
3. Chemicals and reagents 11
4. Immunoblotting 12
5. Immunoprecipitation 12
6. Cell culture 13
7. Plasmid transfection and RNA interference 13
8. Generation of stable cell lines 14
9. Immunofluorescence staining and confocal microscopy 14
10. Generation of knockout cell lines 15
11. Flow cytometry 16
12. Protein purification and in vitro pull-down assays 16
13. Quantification of colocalization and statistical analysis 17
14. Proximity ligation assay (PLA) 18
III. RESULTS 19
Chapter 1. TRIM22 facilitates autophagosome-lysosome fusion by mediating the association of GABARAPs and PLEKHM 1 19
1. TRIM22 deficiency interferes with intracellular clearance 19
2. TRIM22 positively regulates autophagosome-lysosome fusion 25
3. TRIM22 interacts with GABARAPs and mediates their lysosomal localization 35
4. TRIM22 positively regulates autophagosome-lysosome fusion by mediating the association of GABARAPs with PLEKHM1 45
5. TRIM22 facilitates autophagosome-lysosome fusion by interacting with PLEKHM 53
6. The function of TRIM22 as an E3 ubiquitin ligase is distinct from its role in the regulation of autophagy 59
7. AD-related TRIM22 variant interferes with intracellular clearance by inhibiting autophagosome-lysosome fusion 73
Chapter 2. TRIM22 promotes autophagosome formation by recruiting autophagy pre-initiation and initiation complexes 90
1. TRIM22 promotes autophagosome formation by recruiting ULK1 complex 90
2. TRIM22 promotes autophagosome formation by recruiting class III PI3K complex 102
IV. DISCUSSION 110
V. REFERENCES 119
국문요약 13
허혈성 뇌졸중 환자의 약물복용 이행 영향요인
No full textMasterⅠ. 서론 1
A. 연구의 필요성 1
B. 연구목적 5
C. 용어의 정의 6
Ⅱ. 문헌고찰 9
A. 허혈성 뇌졸중 환자의 약물복용 이행 9
B. 허혈성 뇌졸중 환자의 약물복용 이행 영향요인 12
1. 약물지식 14
2. 건강정보이해능력 15
3. 사회적 지지 16
4. 우울 17
5. 약물복용 자기효능감 14
Ⅲ. 연구방법 20
A. 연구설계 20
B. 연구대상자 및 표집방법 20
C. 연구 도구 23
D. 자료수집방법 및 절차 29
E. 자료분석방법 29
F. 윤리적 고려 30
Ⅳ. 연구결과 31
A. 대상자의 일반 특성 31
B. 대상자의 질병관련 및 약물관련 특성 33
C. 대상자의 약물지식, 건강정보이해능력, 사회적 지지, 우울, 약물복용 자기효능감 및 약물복용 이행 정도 35
D. 대상자의 특성에 따른 약물복용 이행의 차이 38
E. 대상자의 약물지식, 건강정보이해능력, 사회적 지지, 우울, 약물복용 자기효능감 및 약물복용 이행간의 상관관계 42
F. 대상자의 약물복용 이행 영향요인 44
Ⅴ. 논의 47
A. 허혈성 뇌졸중 환자의 약물복용 이행정도 47
B. 허혈성 뇌졸중 환자의 약물복용 이행 영향요인 49
C. 기타 및 연구의 제한점 53
Ⅵ. 결론 및 제언 56
참고문헌 58
부 록 75
ABSTRACT 9
가변 및 불변 부위가 쥐-닭 키메라 면역글로불린 Y, 인간 면역글로불린 G1, 면역글로불린 E 항체의 물리화학적 특성 및 분비에 미치는 영향
No full textDoctorI. INTRODUCTION 1
II. MATERIALS AND METHODS 20
A. Construction of expression vectors 20
B. Purification of antibody proteins 22
C. Deglycosylation and periodic acid-Schiff (PAS) staining 22
D. Determination of thermostability of purified Abs 23
E. Nano-differential scanning fluorimetry (nanoDSF) 24
F. Measurement of functional stability of Abs under thermal stress 24
G. Determination of aggregation/degradation behavior of Abs under thermal stress 25
H. Size-exclusion chromatography (SEC) 25
I. Transient transfections 25
J. SDS-PAGE and immunoblotting 26
K. Cell culture and immunoprecipitation 26
L. Establishment of BiP-expressing HEK293 cell line 27
M. Sandwich enzyme-linked immunosorbent assay (ELISA) 28
N. In silico modeling of Fab proteins 28
O. Protease susceptibility assay 29
III. RESULT 30
A. The C domain of chicken Abs is compatible with the V domains of mouse Abs. 30
B. V-C combination affects to the antigen binding affinity of chimeric MC IgY. 35
C. V-C combination affects to the structural stability of chimeric MC IgY. 38
D. V-C combination affects to the functional stability of chimeric MC IgY under thermal stress condition. 41
E. V-C combination affects to aggregation/degradation behaviors of Abs 47
F. The presence of Cκ domain allows the secretion of fully assembled Ig fragments regardless of the presence of the VH or VL domains. 50
G. The presence of ψVκ domain does not only inhibit the secretion of HCs but can also lead to the loss of the LC's own secretory ability. 53
H. The presence of ψVκ domain interferes with HC-LC association. 56
I. The conformational change of the LC due to the presence of ψVκ domain may have caused the loss of association with HC and the ability of LC to secrete itself. 59
J. BiP binding to LC/ψVκ impairs its secretion capability. 61
K. The presence of ψVκ domain decreases the structured stability of LC. 64
L. The presence of LC leads the secretion of HC regardless of the formation of H-L interchain disulfides. 67
M. The presence of Cκ domain allows the individual secretion of IgG HC. 71
N. The presence of Cκ domain can facilitate the individual secretion of IgG4 HC. 74
O. The presence of V domains of IgE is prerequisite for the secretion of fully assembled IgE. 79
IV. DISCUSSION 82
V. CONCLUSION 89
REFERENCES 90
국문요약 9
응급실 간호사의 죽음인식, 삶의 의미와 임종간호태도의 관계
No full textMasterⅠ. 서론 1
A. 연구의 필요성 1
B. 연구의 목적 5
C. 용어의 정의 6
1. 죽음인식 6
2. 삶의 의미 6
3. 임종간호태도 7
Ⅱ. 문헌고찰 8
A. 간호사의 임종간호태도 8
B. 간호사의 죽음 인식, 삶의 의미와 임종간호태도 10
Ⅲ. 연구방법 14
A. 연구설계 14
B. 연구대상자 14
C. 연구도구 15
1. 죽음인식 15
2. 삶의 의미 16
3. 임종간호태도 16
D. 자료수집방법 17
E. 자료분석방법 18
F. 윤리적 고려 19
Ⅳ. 연구결과 20
1. 대상자의 일반적 특성 20
2. 대상자의 죽음인식, 삶의 의미와 임종간호태도의 정도 22
3. 대상자의 일반적 특성에 따른 죽음인식, 삶의 의미와 임종간호태도의 차이 24
4. 대상자의 죽음인식, 삶의 의미와 임종간호태도의 관계 28
Ⅴ. 논의 30
Ⅵ. 결론 및 제언 35
A. 결론 35
B. 제언 36
참고문헌 37
부록 45
ABSTRACT 5
Isoalantolactone Suppresses Tumor Progression by regulating Hippo-YAP Signaling in Cholangiocarcinoma cell
No full textMasterI. Introduction 1
II. Material and Methods 5
1. Antibodies 5
2. Chemicals 5
3. Cell culture and transfection 5
4. CRISPR/Cas9 system 6
5. Retroviral infection and generation of stable cell lines 6
6. Cell lysis and Western blotting 7
7. MTT assay 7
8. Cell apoptosis assay 8
9. Immunoprecipitation (IP) 8
10. Immunocytochemistry 9
11. RNA isolation and qRT-PCR (quantitative real-time polymerase chain reaction) 9
12. Wound healing assay 10
13. Clonal growth assay 11
14. TA cloning 11
15. Tumor isolation from mouse 12
III. Results 13
1. Cytotoxic effect of IALT induces apoptosis in SNU478 cells 13
2. IALT regulates YAP activity via Hippo pathway 16
3. Absence of LATS1/2 counteracts the effect of IALT in regulating YAP 21
4. IALT inhibits Cell growth, Cell Migration and Tumorigenesis by controlling YAP activity 30
IV. Discussion 37
V. References 40
국문 초록 4
A Modified Anterior Column Realignment With Partial Anterior Longitudinal Ligament Release in Oblique Lateral Interbody Fusion
No full textMasterI . Introduction 1
II . Methods 3
A. Study Participants 3
B. Surgical techinque 4
a. OLIF procedure 4
b. Modified Anterior Column Realignment 5
c. Posterior Procedure 6
C. Radiological Evaluation 6
D. Statistical Analysis 8
III . Results 10
A. Patients' Demographics 10
B. Radiological Outcomes 12
a . Disk Lordotic Angle 12
b. Anterior and Posterior Disk Heights 13
c . Sagittal Parameters 14
d. Fusion Rate and Cage Subsidence 15
C. Perioperative Complications 15
IV. Discussion 16
V. Conclusion 22
References 2
Deficiency of SPP1 induces Senescence of Melanocytes
No full textMasterⅠ. Introduction 1
Ⅱ. Material and methods 5
1. Cell culture 5
2. In vitro model of UVB-induced senescent melanocyte 5
3. Senescence Associated β-galactosidase (SA-β-Gal) Staining 6
4. Enzyme-linked immunosorbent assay (ELISA) 6
5. Melanin content and tyrosinase activity assay 6
6. shSPP1 lentivirus production 7
7. hSPP1 over expression lentivirus transfection 7
8. Real-time PCR 8
9. Western blot 8
10. MTT assay 9
11. DCF-DA ROS assay 9
12. Statistical analysis 9
Ⅲ. Results 10
1. Establishment of UVB-induced senescent melanocytes 10
2. Deficiency of SPP1 induces senescence of melanocytes. 17
3. Possibility of delayed senescence in up-regulation of SPP1 24
Ⅳ. Discussion 33
Ⅴ. References 36
Ⅵ. Supplementary Materials 39
Ⅶ. 국문요약 4
생성적 적대 신경망 기반 측두엽 서파 탐지 모델을 활용한 인지 장애 예측 모델 개발
No full textMasterⅠ. 서론 1
A. 기존 연구 3
Ⅱ. 이론적 배경 5
A. 신경퇴행성 질환 5
1. 측두엽 서파 6
2. 경도 인지 장애 7
B. 이상치 탐지 8
C. 생성적 적대적 신경망 ·10
Ⅲ. 제안된 모델: Skip-GANomaly++ 11
A. 생성 네트워크 13
1. 인코더 ·13
2. 디코더 15
B. 판별 네트워크 16
C. 학습 목표 17
D. 추론 19
Ⅳ. 실험 및 결과 20
A. 실험 준비 ·20
1. 데이터셋 21
2. 평가 방법 ·26
3. 구현 방법 ·27
B. 실험 결과-1: 벤치마크 데이터셋 28
C. 실험 결과-2: EEG 데이터셋 ·40
Ⅴ. 논의 및 결론 46
A. 제안된 모델의 하이퍼-파라미터 최적화 ·47
B. 기계 생성 노이즈 레이블 49
C. 인지 장애 탐지의 임상적 의의 50
D. 결론 51
참고문헌 52
ABSTRACT 5
국내 성인 B형간염표면항원 양성인 자에서 B형간염 의사진단 경험과 암검진 미수검의 연관성 : 국민건강영양조사 제4~8기 자료를 활용하여
No full textMasterⅠ. 서론 1
1. 연구의 배경 및 필요성 1
2. 연구의 목적 7
Ⅱ. 연구 방법 8
1. 연구설계 8
2. 연구대상 9
3. 연구변수 10
4. 자료분석 방법 12
Ⅲ. 연구결과 13
1. B형간염표면항원 양성인 자의 의사진단 경험률과 그 추이 13
2. B형간염표면항원 양성인 자의 암검진 수검률과 그 추이 15
3. 연구대상자의 일반적 특성 17
4. 연구대상자의 일반적 특성에 따른 B형간염 의사진단경험 19
5. 연구대상자의 일반적 특성에 따른 암검진 수검 22
6. B형간염 의사진단 경험과 암검진 수검의 연관성 25
Ⅳ. 고찰 29
Ⅴ. 결론 33
참고문헌 34
부록 40
ABSTRACT 5