The impact of myostatin and activin A on breast cancer bone metastases:
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| Format: | Abschlussarbeit Buch |
| Sprache: | English |
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2023
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| Beschreibung: | XIII, 111 Blätter Illustrationen, Diagramme 30 cm |
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| 100 | 1 | |a Reinhardt, Julia |d 1991- |e Verfasser |0 (DE-588)1256607525 |4 aut | |
| 245 | 1 | 0 | |a The impact of myostatin and activin A on breast cancer bone metastases |c vorgelegt von Julia Reinhardt |
| 264 | 1 | |a Münster |c 2023 | |
| 300 | |a XIII, 111 Blätter |b Illustrationen, Diagramme |c 30 cm | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 502 | |b Dissertation |c Westfälische Wilhelms-Universität Münster |d 2023 | ||
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II.
TABLE
OF
CONTENTS
I.
ABSTRACT
.
II
II.
TABLE
OF
CONTENTS
.
IV
III.
LIST
OF
ABBREVIATIONS
.
VII
IV.
LIST
OF
FIGURES
.
XI
V.
LIST
OF
TABLES
.XIII
1.
INTRODUCTION
.
1
1.1
BONE
STRUCTURE
.
1
1.2
BONE
REMODELING
.
3
1.3
CLASSIFICATION
OF
BREAST
CANCER
.
6
1.4
BREAST
CANCER
MOUSE
MODELS
.
7
1.5
PATHOLOGY
AND
PROGRESSION
OF
BONE
METASTASES
IN
BREAST
CANCER
.
9
1.6
INTERACTIONS
BETWEEN
TUMOR
CELLS,
OSTEOCLASTS
AND
OSTEOBLASTS
-
A
VICIOUS
CYCLE
.
12
1.7
THE
TGF-P
SUPERFAMILY
.
14
1.8
EXPRESSION
AND
SIGNALING
OF
ACTIVIN
A
AND
MYOSTATIN
.
15
1.9
INFLUENCE
OF
ACTIVIN
A
AND
MYOSTATIN
ON
BONE
HOMEOSTASIS
.
17
1.10
ROLE
OF
ACTIVIN
A
AND
MYOSTATIN
IN
THE
PROGRESSION
OF
BREAST
CANCER
BONE
METASTASES
.
19
1.11
INHIBITION
OF
TGF-P
FAMILY
MEMBERS
BY
FOLLISTATIN
.
20
1.12
AIMS
OF
THIS
STUDY
.
22
2.
MATERIALS
AND
METHODS
.
24
2.1
MATERIALS
.
24
2.1.1
CONSUMABLES
.
24
2.1.2
DEVICES
AND
SOFTWARE
.
25
2.1.3
CHEMICALS,
SUBSTANCES
AND
KITS
.26
2.1.4
BUFFERS
AND
SOLUTIONS
.
27
2.1.5
CELL
CULTURE
MEDIA
.
28
2.1.6
RECOMBINANT
PROTEINS
AND
INHIBITORS
.
29
2.1.7
ANTIBODIES
.
29
2.2 HUMAN
SAMPLES
.
30
2.3
ANIMAL
EXPERIMENTAL
METHODS
.
30
2.3.1
SYNGENEIC
4T1
BREAST
CANCER
MOUSE
MODEL
.
30
2.3.2
XENOGRAFT
MDA
BREAST
CANCER
MOUSE
MODEL
.
31
2.4
CELL
CULTURE
METHODS
.
32
2.4.1
ISOLATION
AND
CULTIVATION
OF
PRIMARY
MURINE
BONE
MARROW
MONOCYTIC
CELLS
.
32
2.4.2
DIFFERENTIATION
OF
BONE
MARROW
MONOCYTIC
CELLS
TO
OSTEOCLASTS
.
32
2.4.3.
CULTIVATION
OF
4T
1
AND
MDA
BREAST
CANCER
CELLS
.
32
2.4.4.
CELL
STIMULATION
AND
INHIBITOR
EXPERIMENTS
.
33
2.4.5.
RESORPTION
ASSAYS
.
33
2.5
.
PCT
ANALYSES
OF
MOUSE
TIBIA
.
34
2.5.1
TRABECULAR
BONE
PARAMETERS
.
35
2.5.2
CORTICAL
BONE
PARAMETERS
.
36
2.6
HISTOLOGICAL
METHODS
.
38
2.6.1
IMMUNOHISTOCHEMICAL
STAINING
FOR
ACTIVIN
A
AND
MYOSTATIN
.
38
2.6.2
HEMATOXYLIN-EOSIN
STAINING
OF
PARAFFIN
SECTIONS
.
38
2.6.3
TRAP-STAINING
OF
PARAFFIN
SECTIONS
.
39
2.6.4
HISTOMORPHOMETRIC
ANALYSIS
.
39
2.6.5
TRAP-STAINING
OF
IN
VITRO
GENERATED
OSTEOCLASTS
.
40
2.7
PROTEIN
BIOCHEMICAL
METHODS
.40
2.7.1
ENZYME-LINKED
IMMUNOSORBENT
ASSAY
(ELISA)
.40
2.8
STATISTICAL
EVALUATION
.
41
3.
RESULTS
.42
3.1
MYOSTATIN
AND
ACTIVIN
A
POSITIVE
BREAST
CANCER
CELLS
LOCATED
IN
THE
OSTEOCLAST
BONE-MATRIX
NICHE
42
3.2
SECRETION
OF
MYOSTATIN
BY
OSTEOCLASTS
AND
MURINE
4T1
BREAST
CANCER
CELLS
.44
3.3
ENHANCED
OSTEOCLAST
DIFFERENTIATION
BY
CANCER
CELL-OSTEOCLAST
INTERACTION
IS
MEDIATED
BY
MYOSTATIN
.44
3.4
ENHANCED
OSTEOCLAST
RESORPTION
THROUGH
CANCER
CELL-OSTEOCLAST
INTERACTION
IS
MEDIATED
BY
MYOSTATIN
.47
3.5
ANTI-MYOSTATIN
TREATMENT
LEADS
TO
INCREASED
BODY
AND
MUSCLE
WEIGHT
IN
THE
4T1
BREAST
CANCER
MOUSE
MODEL
.
50
3.6
ANTI-MYOSTATIN
TREATMENT
OF
A
4T1
BREAST
CANCER
MOUSE
MODEL
HAS
NO
EFFECT
ON
BREAST
CANCER
CELL
GROWTH
.
51
3.7
ANTI-MYOSTATIN
TREATMENT
EFFECTIVELY
REDUCES
BONE
LESIONS
AND
OSTEOCLAST
FORMATION
IN
A
4T1
BREAST
CANCER
MOUSE
MODEL
.
54
3.8
THE
EFFECT
OF
SIMULTANEOUS
INHIBITION
OF
ACTIVIN
A
AND
MYOSTATIN
ON
OSTEOCLASTOGENESIS
.
56
3.9
ENHANCED
OSTEOCLAST
DIFFERENTIATION
AND
RESORPTION
IS
MEDIATED
BY
ACTIVIN
A
AND
MYOSTATIN
AND
SIGNIFICANTLY
REDUCED
BY
FSTAHBS-MFC
.
56
3.10
TUMOR
CELL
INDUCED
OSTEOCLAST
DIFFERENTIATION
AND
RESORPTION
IS
SIGNIFICANTLY
REDUCED
BY
FST
AHBS
-
ITI
F
C
.
59
3.11
FSTAHBS-MFC
REDUCES
THE
INCREASED
RESORPTION
OF
OSTEOCLASTS
MEDIATED
BY
ACTIVIN
A
AND
MYOSTATIN
BY
TUMOR
CELL-OSTEOCLAST
INTERACTION
.
62
3.12
SIMULTANEOUS
INHIBITION
OF
ACTIVIN
A
AND
MYOSTATIN
BY
FSTAHBS-MFC
HAS
NO
EFFECT
ON
BREAST
CANCER
CELL
GROWTH
IN
A
4T1
MOUSE
MODEL
.
65
3.13
FSTAHBS-MFC
TREATMENT
EFFECTIVELY
REDUCES
BONE
LESIONS
AND
OSTEOCLAST
FORMATION
IN
A
4T1
BREAST
CANCER
MOUSE
MODEL
.
68
3.14
FSTAHBS-MFC
TREATMENT
HAS
NO
EFFECT
ON
BREAST
CANCER
CELL
GROWTH
IN
A
MDA
MOUSE
MODEL.
.70
3.15
FSTAHBS-MFC
TREATMENT
EFFECTIVELY
REDUCES
BONE
LESIONS
AND
OSTEOCLAST
FORMATION
IN
AN
MDA
BREAST
CANCER
MOUSE
MODEL
.
74
4.
DISCUSSION
.
76
1.
EXPRESSION
OF
MYOSTATIN
AND
ACTIVIN
A
IN
HUMAN
BIOPSIES
FROM
PATIENTS
WITH
BREAST
CANCER
BONE
METASTASES
.
76
2.
MYOSTATIN
AND
ACTIVIN
A
ARE
MAJOR
PLAYERS
IN
THE
INTERACTION
OF
BREAST
CANCER
CELLS
AND
OSTEOCLASTS
77
3.
INHIBITION
OF
MYOSTATIN
AND
ACTIVIN
A
HAS
NO
EFFECT
ON
BREAST
CANCER
CELL
GROWTH
IN
BREAST
CANCER
MOUSE
MODELS
.
79
4.
ENHANCED
OSTEOCLASTOGENESIS
THROUGH
INTERACTION
BETWEEN
BREAST
CANCER
CELLS
AND
OSTEOCLASTS
IS
MEDIATED
BY
MYOSTATIN
AND
ACTIVIN
A
.
80
5.
PHARMACOLOGICAL
INHIBITION
OF
MYOSTATIN
AND
ACTIVIN
A
EFFECTIVELY
AMELIORATES
BONE
LESIONS
AND
OSTEOCLAST
FORMATION
IN
BREAST
CANCER
BONE
METASTASIS
MODEL
.
82
5.
OUTLOOK
.
86
VI.
BIBLIOGRAPHY
.
87
VII.
LEBENSLAUF
.
107
VIII.
PUBLIKATIONEN,
ABSTRACTS
UND
VORTRAGE
.
109
IX.
DANKSAGUNG
.
110
X.
EIDESSTATTLICHE
ERKLARUNG
.
111 |
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| indexdate | 2024-12-06T15:10:56Z |
| institution | BVB |
| language | English |
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| physical | XIII, 111 Blätter Illustrationen, Diagramme 30 cm |
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| spelling | Reinhardt, Julia 1991- Verfasser (DE-588)1256607525 aut The impact of myostatin and activin A on breast cancer bone metastases vorgelegt von Julia Reinhardt Münster 2023 XIII, 111 Blätter Illustrationen, Diagramme 30 cm txt rdacontent n rdamedia nc rdacarrier Dissertation Westfälische Wilhelms-Universität Münster 2023 (DE-588)4113937-9 Hochschulschrift gnd-content B:DE-101 application/pdf https://d-nb.info/1309937117/04 Inhaltsverzeichnis DNB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=035261903&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p dnb 20240314 DE-101 https://d-nb.info/provenance/plan#dnb |
| spellingShingle | Reinhardt, Julia 1991- The impact of myostatin and activin A on breast cancer bone metastases |
| subject_GND | (DE-588)4113937-9 |
| title | The impact of myostatin and activin A on breast cancer bone metastases |
| title_auth | The impact of myostatin and activin A on breast cancer bone metastases |
| title_exact_search | The impact of myostatin and activin A on breast cancer bone metastases |
| title_full | The impact of myostatin and activin A on breast cancer bone metastases vorgelegt von Julia Reinhardt |
| title_fullStr | The impact of myostatin and activin A on breast cancer bone metastases vorgelegt von Julia Reinhardt |
| title_full_unstemmed | The impact of myostatin and activin A on breast cancer bone metastases vorgelegt von Julia Reinhardt |
| title_short | The impact of myostatin and activin A on breast cancer bone metastases |
| title_sort | the impact of myostatin and activin a on breast cancer bone metastases |
| topic_facet | Hochschulschrift |
| url | https://d-nb.info/1309937117/04 http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=035261903&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT reinhardtjulia theimpactofmyostatinandactivinaonbreastcancerbonemetastases |
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