Explorations of combinational therapy in cancer : targeting the tumor and its microenvironment by combining chemotherapy with chemopreventive approaches
Wijngaarden, J.W. van
Citation
Wijngaarden, J. W. van. (2011, June 29). Explorations of combinational therapy in cancer : targeting the tumor and its
microenvironment by combining chemotherapy with chemopreventive approaches. Retrieved from https://hdl.handle.net/1887/17745
Version: Corrected Publisher’s Version
License: Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden Downloaded
from: https://hdl.handle.net/1887/17745
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Explorations of
combinational thErapy in cancEr
Targeting the tumor and its microenvironment
by combining chemotherapy with chemopreventive approaches
Explorations of
combinational thErapy in cancEr
Targeting the tumor and its microenvironment
by combining chemotherapy with chemopreventive approaches
Proefschrift ter verkrijging van
de graad van Doctor aan de Universiteit leiden, op gezag van rector magnicus prof.mr. p.f. van der heijden,
volgens besluit van het college voor promoties te verdedigen op woensdag 29 juni 2011
klokke 13.45 uur
door
Johannes Willem van Wijngaarden geboren te purmerend
in 1977
promotiecommissie
promotor prof. dr. c.W.G.m. lwik co-promotor Dr. E.r. van beek overige leden prof. dr. s.E. papapoulos
prof. dr. V.W.m. van hinsbergh (VU amsterdam) prof. dr. p.h. reitsma
the studies presented in this thesis were performed at the department of Endocrinology and metabolic Diseases at the leiden University medical center, leiden, the netherlands.
the research described in this thesis was supported by grants from the the netherlands organisation for scientic research (pGn 902-17-090) and the Dutch cancer society (rUl2000-2196).
lay-out and cover-design: Josine Krom, josineck@yahoo.com printed by: Whrmann print service.
the printing of this thesis was nancially supported by the 'Jurriaanse stichting' which is greatfully acknowledged.
Contents Chapter
1. General introduction 1. tumorigenesis 2. tumor progression
2.1 role of the tumor microenvironment 2.2 tumor angiogenesis
2.3 tumor metastasis
2.4 the principles of Darwinian evolution in cancer 3. tumor therapy
3.1 conventional tumor therapy: chemo monotherapy and drug resistance 3.2 conventional tumor therapy:
combination chemotherapy and multi-drug resistance 3.3 chemopreventive tumor therapy; anti-angiogenesis therapy 3.4 Vascular targeting
3.5 Exploring the tumor microenvironment as anti-cancer target 4. outline of this thesis
2. Identication of differentially expressed genes in a renal cell carinoma tumor model after endostatin-treatment
3. An in vitro model that can distinguish between effects on angiogenesis and on established vasculature: actions of TNP-470, marimastat and the tubulin-binding agent Ang-510
4. Celecoxib enhances doxorubicin-induced cytotoxicity in MDA-MB231 cells by NF-kappaB-mediated increase of intracellular doxorubicin accumulation
pages
9 11 13 13 15 17 19 20 20 21
22 25 25 28 39
65
81
5. Synergistic effect of bisphosphonate and docetaxel on the growth of bone metastasis in an animal model of established metastatic bone disease
6. General discussion
1. Differential gene expression in a renal cell carcinoma model after treatment with endostatin
2. a new model to identify and discriminate between new potential anti-angionic drugs and vascular disruptive agents
3. combination therapies in overcoming treatment resistance:
enhancing doxorubicin- cytotoxicity by nf-κb-mediated increase of doxorubicin accumulation
4. combination therapies in overcoming treatment resistance:
targeting tumor stroma of bone metastases with bone resorption inhibitors
5. conclusions and future perspectives
7. Summary
Samenvatting List of abbreviations Acknowledgements Curriculum vitae List of publications
103
119 121 124 126
128
130
145 149 152 157 159 161
