TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer:
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Abschlussarbeit Buch |
| Sprache: | English |
| Veröffentlicht: |
Ulm
2020
|
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis Inhaltsverzeichnis |
| Beschreibung: | xv, 120 Blätter Illustrationen 30 cm |
Internformat
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| 100 | 1 | |a Kretz, Anna-Laura |e Verfasser |0 (DE-588)1224430417 |4 aut | |
| 245 | 1 | 0 | |a TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer |c submitted by Anna-Laura Kretz |
| 264 | 1 | |a Ulm |c 2020 | |
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Datensatz im Suchindex
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|---|---|
| adam_text | TABLE
OF
CONTENT
LIST
OF
ABBREVIATIONS
AND
ACRONYMS
..................................................................................
VI
LIST
OF
UNITS
AND
SYMBOLS
.................................................................................................
XIV
1
I
NTRODUCTION
...............................................................................................................
1
1.1
PANCREATIC
CANCER
....................................................................................................
1
1.1.1
THE
PANCREAS
AND
EPIDEMIOLOGY
OF
PANCREATIC
CANCER
.....................................
1
1.1.2
PATHOGENESIS
AND
DEFINING
FEATURES
..................................................................
3
1.1.3
THERAPY
............................................................................................................
5
1.2
A
FAMILY
PORTRAIT
OF
CYCLIN-DEPENDENT
KINASES
........................................................
6
1.2.1
CDKS
-
DIRECTORS
OF
THE
CELL
CYCLE
.............................................................
11
1.2.2
CDKS
-
DRIVERS
OF
TRANSCRIPTIONAL
REGULATION
................................................
14
1.2.3
THE
CRITICAL
TRANSCRIPTIONAL
GUARDIAN
CDK9
(PITALRE)
IN
CANCER
...............
16
1.3
THE
TRAIL
SYSTEM
...............................................................................................
17
1.4
THE
APOPTOTIC
*
TRAIL
*
........................................................................................
19
1.4.1
TRAIL-INDUCED
EXTRINSIC
APOPTOSIS
..............................................................
21
1.4.2
TRAIL-INDUCED
INTRINSIC
APOPTOSIS
...............................................................
21
1.4.3
TRAIL
RECEPTOR
AGONISTS
IN
CLINICAL
TRIALS
.........................................................
22
1.4.4
TRAIL RESISTANCE
MECHANISMS
IN
CANCER
......................................................
23
1.5
AIMS
AND
OBJECTIVES
..............................................................................................
28
2
M
ATERIAL
&
M
ETHODS
...............................................................................................
31
2.1
MATERIAL
.................................................................................................................
31
2.1.1
ANTIBODIES
......................................................................................................
31
2.1.2
BACTERIAL
TRIBES
..............................................................................................
32
2.1.3
BIOLOGICALS
.....................................................................................................
32
2.1.4 BUFFERS
AND
SOLUTIONS
.....................................................................................
32
2.1.5
CELL
CULTURE
MEDIA
AND
SUPPLEMENTS
..............................................................
35
2.1.6
CHEMICALS
AND
BIOCHEMICALS
.........................................................................
35
2.1.7
CONSUMABLES
..................................................................................................
37
2.1.8
HUMAN
CELL
LINES
............................................................................................
38
2.1.9
IN
OVO
CAM
MODEL
........................................................................................
39
2.1.10
INSTRUMENTS
AND
EQUIPMENT
............................................................................
39
2.1.11
KITS
AND
READY-TO-USE
SOLUTIONS
.....................................................................
40
2.1.12
SOFTWARE
.........................................................................................................
41
2.1.13
SPECIFIC
INHIBITORS
AND
CYTOSTATIC
AGENTS
.......................................................
42
2.1.14
VECTORS
...........................................................................................................
42
2.2
METHODS
................................................................................................................
43
2.2.1
CELL
BIOLOGICAL
METHODS
.................................................................................
43
2.2.2
BIOCHEMICAL
METHODS
....................................................................................
51
2.2.3
MOLECULAR
BIOLOGICAL
METHODS
.......................................................................
53
2.2.4
BACTERIA
METHODS
...........................................................................................
54
2.2.5
IN
OVO
CHORIO-ALLANTOIC
MEMBRANE
(CAM)
MODEL
........................................
54
2.2.6
IMMUNOHISTOCHEMICAL
METHODS
.....................................................................
55
2.2.7
STATISTICAL
ANALYSIS
........................................................................................
56
3
R
ESULTS
.......................................................................................................................
57
3.1
CDK9
HAS
ONCOGENIC
FUNCTIONS
IN
PDAC
.............................................................
57
3.1.1
CDK9
AS
DRUGGABLE
TARGET
IN
PDAC
.............................................................
57
3.1.2
CDK9
INHIBITION REDUCES
PDAC
CELL
SURVIVAL
................................................
59
3.1.3
CDK9
INHIBITION
HINDERS
CLONOGENICITY
IN
PDAC
..........................................
61
3.1.4
CDK9
INHIBITION
PROMOTES
APOPTOSIS
IN
PDAC
CELLS
.....................................
62
3.1.5
CDK9
INHIBITION
HAS
ANTI-MIGRATORY
AND
ANTI-INVASIVE
EFFECTS
ON
PDAC
CELLS.
65
3.1.6
CDK9
INHIBITION
DIMINISHES
TUMOUR
GROWTH
IN
OVO
......................................
67
3.2
CDK9
INHIBITION BOOSTS
TRAIL-MEDIATED
KILLING
OF
PDAC
CELLS
.......................
69
3.2.1
CDK9
INHIBITION
AND
TRAIL
SYNERGISE
TO
WARD
OFF
CLONOGENICITY
OF
PDAC
CELLS
..................................................................................................
71
IV
3.2.2
CDK9
INHIBITION
COMBINED
WITH
TRAIL
IS
EFFECTIVE
IN
PRIMARY
PDAC
CELLS
..
72
3.2.3
CDK9
INHIBITION
SENSITISES
PDAC
CELLS
TO
TRAIL-INDUCED
APOPTOSIS
........
73
3.2.4
CDK9
INHIBITION PLUS
TRAIL
AT
HIGH-LEVEL
BCL-XL
.....................................
76
3.3
CDK9
INHIBITION
SENSITISES
PDAC
CELLS
TO
CHEMOTHERAPY
AND
BREAKS
COMBINED WITH
TRAIL
THROUGH
CHEMORESISTANCE
.............................................................................
77
4
D
ISCUSSION
..................................................................................................................
81
4.1
CDK9
HAS
ONCOGENIC
FUNCTIONS
IN
PDAC
CELLS
....................................................
82
4.2
CDK9
INHIBITION
SENSITISES
PDAC
CELLS
TO
TRAIL-INDUCED
APOPTOSIS
................
87
4.3
THE
COMBINATION
OF
CDK9
INHIBITION
AND
TRAIL
IS
EFFICIENT
IN
CHEMORESISTANT
PDAC
CELLS
..............................................................................................................
89
5
S
UMMARY
....................................................................................................................
91
R
EFERENCES
.........................................................................................................................
93
A
CKNOWLEDGEMENT
.........................................................................................................
117
V
|
| adam_txt |
TABLE
OF
CONTENT
LIST
OF
ABBREVIATIONS
AND
ACRONYMS
.
VI
LIST
OF
UNITS
AND
SYMBOLS
.
XIV
1
I
NTRODUCTION
.
1
1.1
PANCREATIC
CANCER
.
1
1.1.1
THE
PANCREAS
AND
EPIDEMIOLOGY
OF
PANCREATIC
CANCER
.
1
1.1.2
PATHOGENESIS
AND
DEFINING
FEATURES
.
3
1.1.3
THERAPY
.
5
1.2
A
FAMILY
PORTRAIT
OF
CYCLIN-DEPENDENT
KINASES
.
6
1.2.1
CDKS
-
DIRECTORS
OF
THE
CELL
CYCLE
.
11
1.2.2
CDKS
-
DRIVERS
OF
TRANSCRIPTIONAL
REGULATION
.
14
1.2.3
THE
CRITICAL
TRANSCRIPTIONAL
GUARDIAN
CDK9
(PITALRE)
IN
CANCER
.
16
1.3
THE
TRAIL
SYSTEM
.
17
1.4
THE
APOPTOTIC
*
TRAIL
*
.
19
1.4.1
TRAIL-INDUCED
EXTRINSIC
APOPTOSIS
.
21
1.4.2
TRAIL-INDUCED
INTRINSIC
APOPTOSIS
.
21
1.4.3
TRAIL
RECEPTOR
AGONISTS
IN
CLINICAL
TRIALS
.
22
1.4.4
TRAIL RESISTANCE
MECHANISMS
IN
CANCER
.
23
1.5
AIMS
AND
OBJECTIVES
.
28
2
M
ATERIAL
&
M
ETHODS
.
31
2.1
MATERIAL
.
31
2.1.1
ANTIBODIES
.
31
2.1.2
BACTERIAL
TRIBES
.
32
2.1.3
BIOLOGICALS
.
32
2.1.4 BUFFERS
AND
SOLUTIONS
.
32
2.1.5
CELL
CULTURE
MEDIA
AND
SUPPLEMENTS
.
35
2.1.6
CHEMICALS
AND
BIOCHEMICALS
.
35
2.1.7
CONSUMABLES
.
37
2.1.8
HUMAN
CELL
LINES
.
38
2.1.9
IN
OVO
CAM
MODEL
.
39
2.1.10
INSTRUMENTS
AND
EQUIPMENT
.
39
2.1.11
KITS
AND
READY-TO-USE
SOLUTIONS
.
40
2.1.12
SOFTWARE
.
41
2.1.13
SPECIFIC
INHIBITORS
AND
CYTOSTATIC
AGENTS
.
42
2.1.14
VECTORS
.
42
2.2
METHODS
.
43
2.2.1
CELL
BIOLOGICAL
METHODS
.
43
2.2.2
BIOCHEMICAL
METHODS
.
51
2.2.3
MOLECULAR
BIOLOGICAL
METHODS
.
53
2.2.4
BACTERIA
METHODS
.
54
2.2.5
IN
OVO
CHORIO-ALLANTOIC
MEMBRANE
(CAM)
MODEL
.
54
2.2.6
IMMUNOHISTOCHEMICAL
METHODS
.
55
2.2.7
STATISTICAL
ANALYSIS
.
56
3
R
ESULTS
.
57
3.1
CDK9
HAS
ONCOGENIC
FUNCTIONS
IN
PDAC
.
57
3.1.1
CDK9
AS
DRUGGABLE
TARGET
IN
PDAC
.
57
3.1.2
CDK9
INHIBITION REDUCES
PDAC
CELL
SURVIVAL
.
59
3.1.3
CDK9
INHIBITION
HINDERS
CLONOGENICITY
IN
PDAC
.
61
3.1.4
CDK9
INHIBITION
PROMOTES
APOPTOSIS
IN
PDAC
CELLS
.
62
3.1.5
CDK9
INHIBITION
HAS
ANTI-MIGRATORY
AND
ANTI-INVASIVE
EFFECTS
ON
PDAC
CELLS.
65
3.1.6
CDK9
INHIBITION
DIMINISHES
TUMOUR
GROWTH
IN
OVO
.
67
3.2
CDK9
INHIBITION BOOSTS
TRAIL-MEDIATED
KILLING
OF
PDAC
CELLS
.
69
3.2.1
CDK9
INHIBITION
AND
TRAIL
SYNERGISE
TO
WARD
OFF
CLONOGENICITY
OF
PDAC
CELLS
.
71
IV
3.2.2
CDK9
INHIBITION
COMBINED
WITH
TRAIL
IS
EFFECTIVE
IN
PRIMARY
PDAC
CELLS
.
72
3.2.3
CDK9
INHIBITION
SENSITISES
PDAC
CELLS
TO
TRAIL-INDUCED
APOPTOSIS
.
73
3.2.4
CDK9
INHIBITION PLUS
TRAIL
AT
HIGH-LEVEL
BCL-XL
.
76
3.3
CDK9
INHIBITION
SENSITISES
PDAC
CELLS
TO
CHEMOTHERAPY
AND
BREAKS
COMBINED WITH
TRAIL
THROUGH
CHEMORESISTANCE
.
77
4
D
ISCUSSION
.
81
4.1
CDK9
HAS
ONCOGENIC
FUNCTIONS
IN
PDAC
CELLS
.
82
4.2
CDK9
INHIBITION
SENSITISES
PDAC
CELLS
TO
TRAIL-INDUCED
APOPTOSIS
.
87
4.3
THE
COMBINATION
OF
CDK9
INHIBITION
AND
TRAIL
IS
EFFICIENT
IN
CHEMORESISTANT
PDAC
CELLS
.
89
5
S
UMMARY
.
91
R
EFERENCES
.
93
A
CKNOWLEDGEMENT
.
117
V |
| any_adam_object | 1 |
| any_adam_object_boolean | 1 |
| author | Kretz, Anna-Laura |
| author_GND | (DE-588)1224430417 |
| author_facet | Kretz, Anna-Laura |
| author_role | aut |
| author_sort | Kretz, Anna-Laura |
| author_variant | a l k alk |
| building | Verbundindex |
| bvnumber | BV047451157 |
| ctrlnum | (OCoLC)1228810277 (DE-599)DNB1229467998 |
| discipline | Medizin |
| discipline_str_mv | Medizin |
| format | Thesis Book |
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| id | DE-604.BV047451157 |
| illustrated | Illustrated |
| index_date | 2024-07-03T18:03:18Z |
| indexdate | 2024-07-10T09:12:31Z |
| institution | BVB |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-032853151 |
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| physical | xv, 120 Blätter Illustrationen 30 cm |
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| spelling | Kretz, Anna-Laura Verfasser (DE-588)1224430417 aut TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer submitted by Anna-Laura Kretz Ulm 2020 xv, 120 Blätter Illustrationen 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Universität Ulm 2020 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1229467998/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032853151&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p aepgnd 0,08110 20210421 DE-101 https://d-nb.info/provenance/plan#aepgnd 2\p aepgnd 0,02635 20210421 DE-101 https://d-nb.info/provenance/plan#aepgnd |
| spellingShingle | Kretz, Anna-Laura TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer |
| subject_GND | (DE-588)4113937-9 |
| title | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer |
| title_auth | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer |
| title_exact_search | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer |
| title_exact_search_txtP | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer |
| title_full | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer submitted by Anna-Laura Kretz |
| title_fullStr | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer submitted by Anna-Laura Kretz |
| title_full_unstemmed | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer submitted by Anna-Laura Kretz |
| title_short | TRAILblazing: cyclin-dependent kinase 9 (CDK9) as target in pancreatic cancer |
| title_sort | trailblazing cyclin dependent kinase 9 cdk9 as target in pancreatic cancer |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1229467998/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=032853151&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT kretzannalaura trailblazingcyclindependentkinase9cdk9astargetinpancreaticcancer |
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