The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines:
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| Main Author: | |
|---|---|
| Format: | Book |
| Language: | English |
| Published: |
Berlin
Mensch & Buch
2006
|
| Edition: | 1. Aufl. |
| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Zugl.: Berlin, Humboldt.-Univ., Diss., 2006 |
| Physical Description: | 288 S. graph. Darst. 210 mm x 148 mm |
| ISBN: | 9783866640986 3866640986 |
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| 245 | 1 | 0 | |a The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines |c Hongyu Liu |
| 250 | |a 1. Aufl. | ||
| 264 | 1 | |a Berlin |b Mensch & Buch |c 2006 | |
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Record in the Search Index
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| adam_text | Contents 1
Contents
Contents I
Abbreviations Ill
1 Introduction 1
1.1 Treatment of acute lymphocytic leukemia (ALL) 1
1.1.1 Treatment of human ALL I
1.1 2 Philadelphia chromosome positive ALL (Ph+ALL) and its treatment 3
1.2 Peroxisome proliferator activated receptor (PPAR) 8
1.2.1 The mechanism of action of PPARs 8
12.2 Function of PPARy, PPARa and their ligands 11
1.2.3 PPAR in cancer 14
1.3 Aim of the study 19
2 Material and Methods 21
2.1 Devices 21
2.2 Agonists and antagonists for PPARa and PPARy used in this study.. 22
2.3 Cell culture and bacteria culture 22
2.3.1 Cell lines characterization 22
2.3.2 Maintenance of cell lines 23
2.3.3 Cell viability test trypan blue exclusion test 23
2.3.4 Culture of Escherichia coli (E.coli) 24
2.4 Quantification of cell proliferation and apoptosis 24
2.4.1 MTT assay 24
2.4.2 Cell cycle analysis 25
2 4 3 Measure of apoptosis by Terminal deoxynucleotidyl transferase mediated UTP nick
end labelling (TUNEL) 26
2 4 4 Measurement of apoptosis by cell death ELISAPLUS kit 27
2.4.5 Measurement of caspase 8 and caspase 9 activity 28
2.5 Western blotting analysis 29
2.5.1 Cell lysate preparation and concentration measurement 29
2.5.2 Materials and solutions for Western blot 30
2.5.3 Procedure 32
2.6 Electrophoretic mobility shift assay (EMSA) 33
2.6 1 Materials and solutions 33
2.6.2 Procedure 34
2.7 RT PCR and quantitative PCR (real time PCR) 36
2.7.1 Materials 36
2.7.2 Procedure 37
2.8 Transient transfection of PPARy responsive element into ALL cells... 41
2.8.1 Material 41
2.8.2 Procedure 42
2.9 Statistical analysis 43
2.9.1 Student s t test 43
2.9.2 Combination index (Cl) 43
II Contents
3 Results 45
3.1 Expression of PPARy and PPARa in ALL cell lines 45
3.1.1 Expression of PPARy 45
3.1.2 Expression of PPARa 46
3.2 Effects of ligands of PPARy and PPARa/y in ALL cell lines 47
3.2.1 Effects in cell proliferation inhibition 47
3.2.2 Effects in cell cycle progression 50
3.2.3 Effects in cell apoptosis induction 51
3.2.4 Alteration of cell cycle and apoptosis related proteins by PPARy ligand PGZ
and 15d PGJ2 or the PPARa/y ligand TZD18 58
3.3 Involvement of PPARy and PPARa in the effects of ligands for
PPARy and PPARa/y 61
3.3.1 Function of PPARy gene 61
3.3.2 The influence of PPARy antagonists on cell growth 62
3.3.3 The effect of a new PPARy ligand GW7845 on cell growth 63
3.3.4 The effect of PPARa ligand WY14.643 on cell growth 64
3.3.5 The role of PPARy and PPARa in TZD18 induced cell growth inhibition 65
3.4 The effects of PPARy or PPARa/y ligands on NF kB activity 66
3.4.1 Regulation of NF kB binding activity by 15d PGJ2 and TZD18 67
3.4.2 Downregulation of cytoplasmic kBa expression by the PGZ and 15d PGJ2 68
3.5 The combination effect of TZD18 with imatinib in Ph+ALL 69
4 Discussion 72
4.1 PPAR ligands inhibit the cell growth on human ALL cells 72
4.2 PPARy and PPARa are not involved in the effects of PPAR ligands.... 72
4.3 Mechanisms of cell growth inhibition 74
4.3.1 PPAR ligands inhibit proliferation through G1 phase arrest 75
4.3 2 PPAR ligands have no effect on cell differentiation 79
4.3.3 PPAR ligands induce apoptosis of ALL cells 80
4.4 The cell cycle and apoptosis related genes are possibly
regulated through Rel/NF KB signaling 83
4.5 The addictive effect of TZD18 with imatinib in Ph+ALL 86
4.6 Conclusion 86
5 References 87
6 Abstract 111
7 Zusammenfassung 114
8 Acknowledgement 117
9 Curriculum Vitae 118
10 Eidesstattliche Erklarung 121
|
| adam_txt |
Contents 1
Contents
Contents I
Abbreviations Ill
1 Introduction 1
1.1 Treatment of acute lymphocytic leukemia (ALL) 1
1.1.1 Treatment of human ALL I
1.1 2 Philadelphia chromosome positive ALL (Ph+ALL) and its treatment 3
1.2 Peroxisome proliferator activated receptor (PPAR) 8
1.2.1 The mechanism of action of PPARs 8
12.2 Function of PPARy, PPARa and their ligands 11
1.2.3 PPAR in cancer 14
1.3 Aim of the study 19
2 Material and Methods 21
2.1 Devices 21
2.2 Agonists and antagonists for PPARa and PPARy used in this study. 22
2.3 Cell culture and bacteria culture 22
2.3.1 Cell lines characterization 22
2.3.2 Maintenance of cell lines 23
2.3.3 Cell viability test trypan blue exclusion test 23
2.3.4 Culture of Escherichia coli (E.coli) 24
2.4 Quantification of cell proliferation and apoptosis 24
2.4.1 MTT assay 24
2.4.2 Cell cycle analysis 25
2 4 3 Measure of apoptosis by Terminal deoxynucleotidyl transferase mediated UTP nick
end labelling (TUNEL) 26
2 4 4 Measurement of apoptosis by cell death ELISAPLUS kit 27
2.4.5 Measurement of caspase 8 and caspase 9 activity 28
2.5 Western blotting analysis 29
2.5.1 Cell lysate preparation and concentration measurement 29
2.5.2 Materials and solutions for Western blot 30
2.5.3 Procedure 32
2.6 Electrophoretic mobility shift assay (EMSA) 33
2.6 1 Materials and solutions 33
2.6.2 Procedure 34
2.7 RT PCR and quantitative PCR (real time PCR) 36
2.7.1 Materials 36
2.7.2 Procedure 37
2.8 Transient transfection of PPARy responsive element into ALL cells. 41
2.8.1 Material 41
2.8.2 Procedure 42
2.9 Statistical analysis 43
2.9.1 Student's t test 43
2.9.2 Combination index (Cl) 43
II Contents
3 Results 45
3.1 Expression of PPARy and PPARa in ALL cell lines 45
3.1.1 Expression of PPARy 45
3.1.2 Expression of PPARa 46
3.2 Effects of ligands of PPARy and PPARa/y in ALL cell lines 47
3.2.1 Effects in cell proliferation inhibition 47
3.2.2 Effects in cell cycle progression 50
3.2.3 Effects in cell apoptosis induction 51
3.2.4 Alteration of cell cycle and apoptosis related proteins by PPARy ligand PGZ
and 15d PGJ2 or the PPARa/y ligand TZD18 58
3.3 Involvement of PPARy and PPARa in the effects of ligands for
PPARy and PPARa/y 61
3.3.1 Function of PPARy gene 61
3.3.2 The influence of PPARy antagonists on cell growth 62
3.3.3 The effect of a new PPARy ligand GW7845 on cell growth 63
3.3.4 The effect of PPARa ligand WY14.643 on cell growth 64
3.3.5 The role of PPARy and PPARa in TZD18 induced cell growth inhibition 65
3.4 The effects of PPARy or PPARa/y ligands on NF kB activity 66
3.4.1 Regulation of NF kB binding activity by 15d PGJ2 and TZD18 67
3.4.2 Downregulation of cytoplasmic kBa expression by the PGZ and 15d PGJ2 68
3.5 The combination effect of TZD18 with imatinib in Ph+ALL 69
4 Discussion 72
4.1 PPAR ligands inhibit the cell growth on human ALL cells 72
4.2 PPARy and PPARa are not involved in the effects of PPAR ligands. 72
4.3 Mechanisms of cell growth inhibition 74
4.3.1 PPAR ligands inhibit proliferation through G1 phase arrest 75
4.3 2 PPAR ligands have no effect on cell differentiation 79
4.3.3 PPAR ligands induce apoptosis of ALL cells 80
4.4 The cell cycle and apoptosis related genes are possibly
regulated through Rel/NF KB signaling 83
4.5 The addictive effect of TZD18 with imatinib in Ph+ALL 86
4.6 Conclusion 86
5 References 87
6 Abstract 111
7 Zusammenfassung 114
8 Acknowledgement 117
9 Curriculum Vitae 118
10 Eidesstattliche Erklarung 121 |
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| dewey-tens | 610 - Medicine and health |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| edition | 1. Aufl. |
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| illustrated | Illustrated |
| index_date | 2024-07-02T15:33:23Z |
| indexdate | 2024-07-09T20:43:19Z |
| institution | BVB |
| isbn | 9783866640986 3866640986 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-014968811 |
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| physical | 288 S. graph. Darst. 210 mm x 148 mm |
| publishDate | 2006 |
| publishDateSearch | 2006 |
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| publisher | Mensch & Buch |
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| spelling | Liu, Hongyu Verfasser (DE-588)132114151 aut The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines Hongyu Liu 1. Aufl. Berlin Mensch & Buch 2006 288 S. graph. Darst. 210 mm x 148 mm txt rdacontent n rdamedia nc rdacarrier Zugl.: Berlin, Humboldt.-Univ., Diss., 2006 Akute lymphatische Leukämie swd Ligand <Biochemie> swd Peroxisom swd Proliferation swd Rezeptor swd (DE-588)4113937-9 Hochschulschrift gnd-content HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014968811&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Liu, Hongyu The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines Akute lymphatische Leukämie swd Ligand <Biochemie> swd Peroxisom swd Proliferation swd Rezeptor swd |
| subject_GND | (DE-588)4113937-9 |
| title | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines |
| title_auth | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines |
| title_exact_search | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines |
| title_exact_search_txtP | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines |
| title_full | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines Hongyu Liu |
| title_fullStr | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines Hongyu Liu |
| title_full_unstemmed | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines Hongyu Liu |
| title_short | The Effects of PPAR Ligands in Human Acute Lymphocytic Leukemia Cell Lines |
| title_sort | the effects of ppar ligands in human acute lymphocytic leukemia cell lines |
| topic | Akute lymphatische Leukämie swd Ligand <Biochemie> swd Peroxisom swd Proliferation swd Rezeptor swd |
| topic_facet | Akute lymphatische Leukämie Ligand <Biochemie> Peroxisom Proliferation Rezeptor Hochschulschrift |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014968811&sequence=000002&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT liuhongyu theeffectsofpparligandsinhumanacutelymphocyticleukemiacelllines |