towards improved death receptor targeted therapy for ... - TI Pharma

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Contents Chapter 1 General Introduction and Outline of the thesis 9 Chapter 2 Non-canonical kinase signaling by the death ligand TRAIL in cancer cells: discord in the death receptor family 15 Chapter 3 MAPK p38 and JNK have opposing activities on TRAIL-induced apoptosis activation in NSCLC cells that involves RIP1 and caspase-8 and is mediated by Mcl-1 39 Chapter 4 Kinome profiling of non-canonical TRAIL signaling reveals RIP1-Src-STAT3 dependent invasion in resistant non-small cell lung cancer cells 59 Chapter 5 Inhibition of Hsp90 by 17-AAG enhances TRAILinduced apoptosis in non-small cell lung cancer cells 83 Chapter 6 The novel thymidylate synthase inhibitor Trifluorothymidine (TFT) and TRAIL synergistically eradicate non-small cell lung cancer cells 99 Chapter 7 Accumulation of thymidine-derived sugars in thymidine phosphorylase overexpressing cells 117 Chapter 8 Summarizing discussion and future perspectives 135 Chapter 9 Summary in Dutch – Nederlandse Samenvatting 145 Acknowledgements – Dankwoord 151 Curriculum vitae 155 ‐ 7 ‐
‐ 8 ‐
Page 2 and 3: TRAIL-induced kinases activation an
Page 4 and 5: TRAIL‐induced kinases activation
Page 6: “In order to be irreplaceable one
Page 11 and 12: Chapter 1 GENERAL INTRODUCTION Canc
Page 13 and 14: Chapter 1 OUTLINE OF THE THESIS As
Page 15 and 16: Chapter 1 Reference List 1. Jemal A
Page 17 and 18: Chapter 2 ABSTRACT Tumor necrosis f
Page 19 and 20: Chapter 2 INTRODUCTION The death li
Page 21 and 22: Chapter 2 In preclinical studies, a
Page 23 and 24: Chapter 2 Table 1| Summary of the k
Page 25 and 26: Chapter 2 proliferation could be pr
Page 27 and 28: Chapter 2 Figure 2. Canonical and n
Page 29 and 30: Chapter 2 associated with TRAIL res
Page 31 and 32: Chapter 2 adhesion molecules [109].
Page 33 and 34: Chapter 2 Reference List 1. Ashkena
Page 35 and 36: Chapter 2 37. Tolcher AW, Mita M, M
Page 37 and 38: Chapter 2 melanoma cells from TRAIL
Page 39 and 40: Chapter 2 and ERK pathways. Circula
Page 41 and 42: Chapter 3 ABSTRACT Tumor necrosis f
Page 43 and 44: Chapter 3 inhibitors and TRAIL rece
Page 45 and 46: Chapter 3 of amplification of the t
Page 47 and 48: Chapter 3 P38 and JNK have opposing
Page 49 and 50: Chapter 3 Figure 2 (continued). (e)
Page 51 and 52: Chapter 3 previously established H4
Page 53 and 54: Chapter 3 effect on TRAIL‐induced
Page 55 and 56: Chapter 3 induced apoptosis in H460
Page 57 and 58:
Chapter 3 Reference List 1. Jemal A
Page 59 and 60:
Chapter 3 40. Domina AM, Vrana JA,
Page 61 and 62:
Chapter 4 ABSTRACT Tumor necrosis f
Page 63 and 64:
Chapter 4 role in the activation of
Page 65 and 66:
Chapter 4 the tip with a diameter o
Page 67 and 68:
Chapter 4 RESULTS TRAIL induces a s
Page 69 and 70:
Chapter 4 vehicle control or with 5
Page 71 and 72:
Chapter 4 Non‐canonical TRAIL res
Page 73 and 74:
Chapter 4 A549‐shRIP1 cells clear
Page 75 and 76:
Chapter 4 Figure 7. Inhibition of S
Page 77 and 78:
Chapter 4 DISCUSSION The TRAIL rece
Page 79 and 80:
Chapter 4 Src‐independent mechani
Page 81 and 82:
Chapter 4 variants. Cell Death Dis
Page 83 and 84:
Chapter 4 ‐ 82 ‐
Page 85 and 86:
Chapter 5 ABSTRACT TRAIL is an inte
Page 87 and 88:
Chapter 5 targets and subsequent pr
Page 89 and 90:
Chapter 5 RESULTS Synergistic activ
Page 91 and 92:
Chapter 5 ng/ml TRAIL (Fig. 3B). Ap
Page 93 and 94:
Chapter 5 by sub‐G1 levels in the
Page 95 and 96:
Chapter 5 DISCUSSION In the present
Page 97 and 98:
Chapter 5 Reference List 1. Jemal A
Page 99 and 100:
Page 101 and 102:
Chapter 6 ABSTRACT TRAIL is a tumor
Page 103 and 104:
Chapter 6 various stress stimuli [1
Page 105 and 106:
Chapter 6 Subsequently, the membran
Page 107 and 108:
Chapter 6 B H460 A549 Figure 1. Rep
Page 109 and 110:
Chapter 6 TRAIL‐dependent cell de
Page 111 and 112:
Chapter 6 B H460 A549 C Figure 4 (c
Page 113 and 114:
Chapter 6 Figure 5 (continued). Mec
Page 115 and 116:
Chapter 6 regulation and checkpoint
Page 117 and 118:
Chapter 6 mechanism of immune evasi
Page 119 and 120:
Chapter 7 ABSTRACT Thymidine phosph
Page 121 and 122:
Chapter 7 Figure 1. Schematic overv
Page 123 and 124:
Chapter 7 that was measured before
Page 125 and 126:
Chapter 7 RESULTS TdR conversion to
Page 127 and 128:
Chapter 7 dR is secreted from the c
Page 129 and 130:
Chapter 7 Figure 4. Accumulation of
Page 131 and 132:
Chapter 7 angiogenic properties. Ho
Page 133 and 134:
Chapter 7 activity of enzymes. Natu
Page 135 and 136:
Page 137 and 138:
Chapter 8 SUMMARIZING DISCUSSION AN
Page 139 and 140:
Chapter 8 Recently, various differe
Page 141 and 142:
Chapter 8 in phase II clinical tria
Page 143 and 144:
Chapter 8 Reference List 1. Herbst
Page 145 and 146:
Page 147 and 148:
Chapter 9 NEDERLANDSE SAMENVATTING
Page 149 and 150:
Chapter 9 waargenomen. Het gebruik
Page 151 and 152:
Chapter 9 CONCLUSIE Het activeren v
Page 153 and 154:
zelfs na werktijden (lees 23:45) ko
Page 155 and 156:
Verder wil ik ook dr. Eric Ronken b
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