Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
2013
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| Schlagworte: | |
| Online-Zugang: | Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130320-1140390-0-4 Inhaltsverzeichnis |
| Beschreibung: | 129 Bl. Ill., graph. Darst. |
Internformat
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Datensatz im Suchindex
| _version_ | 1804152082714853376 |
|---|---|
| adam_text | TECHNISCHE UNIVERSITAT MUNCHEN
PANKREAS-FORSCHUNGSLABOR
CHIRURGISCHE KLINIK UND POLIKLINIK
KLINIKUM RECHTS DER ISAR
IDENTIFICATION AND CHARACTERIZATION
OF MOLECULAR SUBTYPES OF
HUMAN PANCREATIC DUCTAL ADENOCARCINOMA
BO KONG
VOLLSTANDIGER ABDRUCK DER VON DER FAKULTAT
FUR MEDIZIN DER
TECHNISCHEN UNIVERSITAT MUNCHEN ZUR
ERLANGUNG DES
AKADEMISCHEN GRADES EINES DOCTOR OF PHILOSOPHY GENEHMIGTEN
DISSERTATION
VORSITZENDER: UNIV.-PROF. DR. FLORIAN R. GRETEN
PRUFER DER DISSERTATION:
1. UNIV.-PROF. DR. BERNHARD
HOLZMANN
2. APL. PROF. DR.
ACHIM KRUGER
3. APL. PROF. DR. ANDREAS
JUNG,
LUDWIG-MAXIMILIANS-UNIVERSITAT
MUNCHEN
DIE DISSERTATION WURDEN AM 05.02.2013 BEI DER TECHNISCHEN
UNIVERSITAT MUNCHEN EINGEREICHT UND DURCH
DIE FAKULTAT FUR MEDIZIN
AM 20.03.2013 ANGENOMMEN.
HTTP://D-NB.INFO/1051412811
TABLE OF CONTENTS
1. INTRODUCTION 5
1.1. PANCREATIC CANCER BIOLOGY 5
1.2.
MOLECULAR SUBTYPES AND TREATMENT RESPONSES
IN HUMAN
PDAC ... 7
1.3. HNF1A/MIA2 AXIS AND
ER STRESS/UPR SYSTEM IN PANCREATIC
PHYSIOLOGY AND CANCER BIOLOGY 9
1.4. TSC1-TSC2 COMPLEX AND MTORC1 ARE
COMMON GATEKEEPERS OF
PANCREATIC MALIGNANCY 11
2. AIMS OF THIS STUDY 17
3. MATERIALS
AND METHODS 19
3.1. MATERIALS 19
3.2. METHODS 30
4. RESULTS 37
4.1. HNF1A CONTROLS MIA2 EXPRESSION
IN PDAC 37
4.2. THE
MIA2
I141M
VARIANT IS LINKED WITH A SECRETORY DEFECT AND
IS
CORRELATED WITH PATIENT SURVIVAL 40
4.3. THE
MIA2
I141M
VARIANT INCREASES SENSITIVITY OF PANCREATIC CANCER
CELLS TO GEMCITABINE 44
4.4. THE
MIA2
I141M
VARIANT IS ASSOCIATED WITH INCREASED EXPRESSION
LEVELS OF ERN1/XBP1 IN PDAC
TISSUES 48
4.5. ERN1
IS RESPONSIBLE FOR
INCREASED CHEMOSENSITIVITY IN MIA2
I141M
CARRIERS 53
4.6. TSC1
DEFICIENCY INDUCES DEGENERATION OF THE
PANCREAS 55
4.7. TSC1
HAPLOINSUFFICIENCY PROMOTES TUMOR FORMATION DRIVEN
BY
PTEN DEFICIENCY AND EXPRESSION OF KRAS
G12D
60
4.8. KRAS
G12D
/ERK OR PI3K/AKT
TOGETHER WITH TSC1 HAPLOINSUFFICIENCY
DRIVE HYPERACTIVATION OF MTORC1
IN PANCREATIC CELL 63
4.9. KRASG12D/ERK OR PI3K/AKT TOGETHER WITH TSC1
HAPLOINSUFFICIENCY
DRIVE HYPERACTIVATION OF MTORC1 IN PANCREATIC CELL 66
4.10. KRAS
G12D
;
TSC1
FLY+
CANCER CELLS ARE DEFECTIVE IN
RELEASING VEGFA
BECAUSE OF HYPOXIA-INDUCED ER STRESS 68
4.11. T CELL IMMUNITY PREVENTS
CYSTIC LESIONS FROM
MALIGNANT
TRANSFORMATION IN PTEN
FUFL
;
TSC1
FL/+
MICE 76
4.12. TSC1
HAPLOINSUFFICIENCY AND P53 DEFICIENCY PROMOTES
THE
PANCREATIC MALIGNANCY 78
4.13. IDENTIFICATION
OF ALDH1A3-POSITIVE SUBTYPE OF HUMAN PDAC 83
5. DISCUSSION 89
5.1. HNF1A/MIA2
SECRETORY NETWORK INTERACTS WITH ER STRESS/UPR
SYSTEM 89
5.2. A CENTRAL
ROLE OF THE
TSC1-TSC2 COMPLEX AND OF MTORC1
IN
PANCREATIC EXOCRINE MALIGNANCY IN MICE 92
2
5.3. MOLECULAR SUBTYPES
OF HUMAN PDAC 97
6. SUMMARY 100
7. ABBREVIATIONS 103
8. REFERENCES 106
9. SUPPLEMENTARY DATA 123
10. CURRICULUM VITAE 126
11. ACKNOWLEDGEMENTS 128
3
|
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| spelling | Kong, Bo Verfasser aut Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma Bo Kong 2013 129 Bl. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier München, Techn. Univ., Diss., 2013 (DE-588)4113937-9 Hochschulschrift gnd-content Erscheint auch als Online-Ausgabe urn:nbn:de:bvb:91-diss-20130320-1140390-0-4 http://mediatum.ub.tum.de/node?id=1140390 Verlag kostenfrei Volltext https://nbn-resolving.org/urn:nbn:de:bvb:91-diss-20130320-1140390-0-4 Resolving-System DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=027218962&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
| spellingShingle | Kong, Bo Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma |
| subject_GND | (DE-588)4113937-9 |
| title | Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma |
| title_auth | Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma |
| title_exact_search | Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma |
| title_full | Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma Bo Kong |
| title_fullStr | Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma Bo Kong |
| title_full_unstemmed | Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma Bo Kong |
| title_short | Identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma |
| title_sort | identification and characterization of molecular subtypes of human pancreatic ductal adenocarcinoma |
| topic_facet | Hochschulschrift |
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