Organellar crosstalk and apoptosis in pancreatic cancer cells:
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| Main Author: | |
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| Format: | Thesis Book |
| Language: | English German |
| Published: |
2013
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| Subjects: | |
| Online Access: | Inhaltsverzeichnis |
| Item Description: | Zsfassung in engl. und dt. Sprache |
| Physical Description: | XIV, 153 S. Ill., graph. Darst. |
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| 245 | 1 | 0 | |a Organellar crosstalk and apoptosis in pancreatic cancer cells |c presented by Daniela Richter |
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| 300 | |a XIV, 153 S. |b Ill., graph. Darst. | ||
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| adam_text | IMAGE 1
TABLE O F CONTENTS I
TABLE OF CONTENTS
LIST OF FIGURES VII
LIST OF TABLES IX
LIST OF ABBREVIATIONS XI
1. ABSTRACT / ZUSAMMENFASSUNG 1
2. INTRODUCTION 5
2.1. GENERAL FEATURES OF PCD 6
2.2. ORGANELLAR COMPARTMENTS IN PCD 7
2.2.1. PLASMA MEMBRANE, ENDOSOMAL COMPARTMENTS AND GOLGI 7
2.2.2. THE LYSOSOME 11
2.2.3. THE MITOCHONDRION 13
2.2.4. THE NUCLEUS 16
2.2.5. THE ENDOPLASMIC RETICULUM (ER) 19
2.2.6. ORGANELLAR CROSSTALK IN APOPTOSIS 22
2.3. CELL DEATH DEREGULATION IN PANCREATIC CANCER 23
2.3.1. THE EXTRINSIC PATHWAY OF APOPTOSIS 25
2.3.2. THE INTRINSIC PATHWAY OF APOPTOSIS 26
2.3.3. THE CELL CYCLE 27
2.3.4. AUTOPHAGY 28
2.4. SUMMARY 28
3. AIMS 3 1
4. MATERIALS AND METHODS 33
4.1. MATERIALS 33
4.1.1. LABORATORY EQUIPMENT AND PLASTICWARE 33
4.1.2. CHEMICALS AND REAGENTS 34
4.1.3. ANTIBODIES 37
HTTP://D-NB.INFO/1036665135
IMAGE 2
II TABLE O F CONTENTS
4.1.4. OLIGONUCLEOTIDES 38
4.1.5. CONSTRUCTS 39
4.2. METHODS 39
4.2.1. CELL CULTURE 39
4.2.2. CELL DEATH AND ROS GENERATION ASSAY 40
4.2.3. QUANTITATIVE REALTIME-PCR 4 1
4.2.4. IMMUNOSTAINING 4 1
4.2.5. VISUALIZATION OF LYSOSOMES 42
4.2.6. WOUND HEALING ASSAY 42
4.2.7. WESTERN BLOT 42
4.2.8. COLLAGEN GEL INVASION ASSAY 4 3
4.2.9. IMMUNOPRECIPITATION WITH CATHEPSIN D 4 3
4.2.10. BAX CLUSTERING 44
4.2.11. MITOCHONDRIA FRAGMENTATION 44
4.2.12. FEATURE EXTRACTION 44
4.2.13. STATISTICS 45
5. RESULTS 1: AUTOMATED ANALYSIS OF ORGANELLAR FEATURES 4 9
5.1. MITOCHONDRIA 49
5.1.1. IMAGE ACQUISITION 50
5.1.2. AUTOMATED IMAGE PROCESSING 5 1
5.1.3. IMAGE PRE-PROCESSING 53
5.1.4. NUCLEI DETECTION 54
5.1.5. CELL SEGMENTATION STRATEGY 56
5.1.6. MITOCHONDRIA IDENTIFICATION 58
5.1.7. FEATURE EXTRACTION 60
5.1.8. PROCESSING OF FULL SIZE IMAGES 60
5.1.9. RANDOM FOREST CLASSIFICATION 63
IMAGE 3
TABLE O F CONTENTS III
5.1.10. FUZZY LOGIC MODELING 65
5.2. LYSOSOMES 68
5.2.1. AUTOMATED IMAGE ANALYSIS 68
5.2.2. IMAGE PRE-PROCESSING 68
5.2.3. SEGMENTATION 68
5.2.4. FEATURE EXTRACTION 69
5.3. ENDOSOMES 70
5.3.1. IMAGE PRE-PROCESSING 72
5.3.2. CLASSIFICATION 73
5.4. SUMMARY 74
6. RESULTS 2: MITOCHONDRIA AND CELL DEATH IN PANCREATIC CANCER CELLS 77
6.1. CELL DEATH INDUCTION IN PANC-1 CELLS 77
6.2. ART-INDUCED CELL DEATH IS DEPENDANT ON REACTIVE OXYGEN SPECIES
(ROS). ..79
6.3. ART CAUSES MITOCHONDRIA FRAGMENTATION AND BAX CLUSTERING 83
6.4. ART INDUCES TRANSCRIPTIONAL UPREGULATION OF PRO-APOPTOTIC BH3-ONLY
PROTEINS 84
6.5. TRANSCRIPTIONAL UPREGULATION TRANSLATES INTO INCREASED PROTEIN
LEVELS 88
6.6. TRANSCRIPTIONAL UPREGULATION AND CELL DEATH DEPEND ON JNK-SIGNALING
90
6.7. SUMMARY 9 1
7. RESULTS 3: LYSOSOMES IN ART-INDUCED CELL DEATH 93
7.1. ROS GENERATION AND CELL DEATH DEPEND ON LYSOSOMAL IRON AND A
FUNCTIONAL LYSOSOMAL COMPARTMENT 93
7.2. ART INDUCES ENDO-LYSOSOMAL CLUSTERING AT THE MICROTUBULE
ORGANIZATION CENTER 95
7.3. PERINUCLEAR CLUSTERS CONTAIN RECYCLING, EARLY AND LATE ENDOSOMES
AND LYSOSOMES 98
7.4. LC8 KNOCKDOWN INHIBITS CLUSTERING OF ENDO-LYSOSOMES, OVEREXPRESSION
OF RILP INDUCES IT 99
7.5. THE EFFECT OF ART ON CATHEPSIN SECRETION 101
IMAGE 4
IV TABLE O F CONTENTS
7.6. ART REDUCES INVASION OF PANC-1 CELLS 102
7.7. SUMMARY 103
8. RESULTS 4: NUCLEAR EVENTS IN ART-INDUCED CELL DEATH 105
8.1. ART INDUCED CELLS FAIL TO PROGRESS FROM METAPHASE TO ANAPHASE AND
SHOW MISALIGNED CHROMOSOMES 105
8.2. ART REDUCES PROLIFERATION OF PANC-1 CELLS IN A WOUND-HEALING ASSAY
106
8.3. IRON CHELATION, BUT NOT ROS SCAVENGING RESCUES FROM ART-INDUCED
CHROMOSOMAL MISALIGNMENT AND DYNEIN MISLOCALIZATION 108
8.4. ARTESUNATE CAUSES MISLOCALIZATION OF DYNEIN MOTOR PROTEIN 110
8.5. ARTESUNATE INTERFERES WITH BIPOLAR ATTACHMENT OF SPINDLE FIBRES TO
KINETOCHORES I L L
8.6. SUMMARY 112
9. DISCUSSION AND OUTLOOK 113
9.1. VERSATILE PIPELINES FOR THE ANALYSIS OF ORGANELLAR FEATURES 113
9.1.1. MITOCHONDRIAL MORPHOLOGY QUANTIFICATION 114
9.1.2. LYSOSOMAL MORPHOLOGY AND DISTRIBUTION ANALYSIS 114
9.1.3. ENDOSOMAL PATTERN RECOGNITION 115
9.1.4. MORPHOLOGICAL ANALYSIS PLATFORM 116
9.2. LYSOSOME, MITOCHONDRIA, E R - A TEAM IN ART-INDUCED CELL DEATH 116
9.2.1. ACTIVATION OF ART 116
9.2.2. EFFECTS ON MITOCHONDRIA - BIM AS A CENTRAL PLAYER? 117
9.2.3. EFFECTS ON ENDOSOMES AND LYSOSOMES - CELL DEATH AND INVASION 118
9.2.4. EFFECTS ON THE ER? 119
9.3. DYNEIN - A NEW PLAYER REGULATING INVASION AND PROLIFERATION? 120
9.4. GENERAL SUMMARY AND OUTLOOK 122
9.4.1. MULTI-ORGANELLAR ANALYSIS 122
9.4.2. GENERATION OF NEW LEAD STRUCTURES 122
9.4.3. THE ROLE OF AUTOPHAGY AND THE LYSOSOME 123
IMAGE 5
TABLE O F CONTENTS V
9.4.4. TARGETING DYNEIN IN CANCER 123
9.4.5. SUMMARY 123
10. APPENDIX 12 5
10.1. CELL PROFILER PIPELINES 125
10.1.1. MITOCHONDRIA 125
10.1.2. LYSOSOMES 131
10.1.3. ENDOSOMES 134
11. LITERATURE 139
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| language | English German |
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| spelling | Richter, Daniela Verfasser (DE-588)1034764632 aut Organellar crosstalk and apoptosis in pancreatic cancer cells presented by Daniela Richter 2013 XIV, 153 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zsfassung in engl. und dt. Sprache Heidelberg, Univ., Diss, 2013 (DE-588)4113937-9 Hochschulschrift gnd-content DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=026072897&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Richter, Daniela Organellar crosstalk and apoptosis in pancreatic cancer cells |
| subject_GND | (DE-588)4113937-9 |
| title | Organellar crosstalk and apoptosis in pancreatic cancer cells |
| title_auth | Organellar crosstalk and apoptosis in pancreatic cancer cells |
| title_exact_search | Organellar crosstalk and apoptosis in pancreatic cancer cells |
| title_full | Organellar crosstalk and apoptosis in pancreatic cancer cells presented by Daniela Richter |
| title_fullStr | Organellar crosstalk and apoptosis in pancreatic cancer cells presented by Daniela Richter |
| title_full_unstemmed | Organellar crosstalk and apoptosis in pancreatic cancer cells presented by Daniela Richter |
| title_short | Organellar crosstalk and apoptosis in pancreatic cancer cells |
| title_sort | organellar crosstalk and apoptosis in pancreatic cancer cells |
| topic_facet | Hochschulschrift |
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