BEVACIZUMAB EFFECT ON TOPOTECAN PHARMACOKINETICS ...
BEVACIZUMAB EFFECT ON TOPOTECAN PHARMACOKINETICS ... BEVACIZUMAB EFFECT ON TOPOTECAN PHARMACOKINETICS ...
LIST OF ABBREVIATIONS ABC ATP-binding cassette ADA Anti-drug antibodies ARMS Alveolar rhabdomyosarcoma AUC Area under concentration-time AUCt Area under concentration-time in tumor AUCp Area under concentration-time in plasma BCRP Breast cancer resistance protein BEV Bevacizumab bFGF Basic fibroblast growth factor COG Children’s oncology group CGH Comparative genomic hybridization CPT-11 Irinotecan CSF Cerebrospinal fluid CYP Cytochrome p450 ECF Extracellular fluid ECM Extracellular matrix ERMS Embryonal rhabdomyosarcoma HPLC High-performance liquid chromatography IFP Interstitial fluid pressure IIV Inter-individual variability IRS Intergroup rhabdomyosarcoma study group IC Intracerebral IP Intraperitoneally IV Intravenously MDBT Multiple doses of bevacizumab treatment MLEM Maximal likelihood expectation maximization MMPs Matrix metalloproteinases MMP-2 Matrix metalloproteinase-2 MT1-MMP Membrane type 1 metalloproteinase MVD Microvessel density NMR Nuclear magnetic resonance PBS Phosphate buffered saline PD Pharmacodynamic PDGF Platelet-derived growth factor PET Positron emission tomography PK Pharmacokinetics PTX Paclitaxel P-gp P-glycoprotein 1 QAR Quantitative autoradiography RD Embryonal rhabdomyosarcoma cell line RH30 Alveolar rhabdomyosarcoma cell line RMS Rhabdomyosarcoma SD Standard deviation x
SDBT Single dose of bevacizumab treatment SC Subcutaneous TIMP-2 TIMP metallopeptidase inhibitor 2 TMZ Temozolomide TNP-470 O-(N-chloroacetyl-carbamoyl)-fumagillol TPT Topotecan VEGF Vascular endothelial growth factor VEGFR Vascular endothelial growth factor receptor xi
- Page 1 and 2: BEVACIZUMAB EFFECT ON TOPOTECAN PHA
- Page 3 and 4: ACKNOWLEDGEMENTS I would like to th
- Page 5 and 6: overall effect of BEV on TPT pharma
- Page 7 and 8: 2.3.1 The effect of BEV on the phar
- Page 9: LIST OF FIGURES Figure 1. TPT effic
- Page 13 and 14: hypertension and the pathologic ext
- Page 15 and 16: 1.1.3 Strategies to improve drug pe
- Page 17 and 18: 1.2.2 Role of vascular endothelial
- Page 19 and 20: enhanced the tumor response to conv
- Page 21 and 22: non-favorable sites [109]. So devel
- Page 23 and 24: low sensitivity. Additionally, it r
- Page 25 and 26: tumor distribution of TMZ in V+ SC
- Page 27 and 28: over-pruned microvessel [146, 147].
- Page 29 and 30: 1.7 Summary Although the overall su
- Page 31 and 32: CHAPTER 2. THE EFFECT OF BEVACIZUMA
- Page 33 and 34: 2.2.4 Tumor model and treatment Ort
- Page 35 and 36: Table 1. (SDBT) TPT penetration stu
- Page 37 and 38: Figure 2. TPT penetration plus effi
- Page 39 and 40: Figure 3. A pharmacokinetic model f
- Page 41 and 42: 2.2.10 Statistical analyses For eac
- Page 43 and 44: Figure 6. Representative plasma and
- Page 45 and 46: Figure 7. The effect of BEV on the
- Page 47 and 48: Figure 8. The effect of BEV on the
- Page 49 and 50: Table 6. Population PK parameters o
- Page 51 and 52: variability for Kte decreased from
- Page 53 and 54: Figure 11. The effect of different
- Page 55 and 56: efflux transporters. TPT is a campt
- Page 57 and 58: Furthermore, although the volume of
- Page 59 and 60: 19. Sleeman, J., A. Schmid, and W.
SDBT<br />
Single dose of bevacizumab treatment<br />
SC<br />
Subcutaneous<br />
TIMP-2 TIMP metallopeptidase inhibitor 2<br />
TMZ<br />
Temozolomide<br />
TNP-470<br />
O-(N-chloroacetyl-carbamoyl)-fumagillol<br />
TPT<br />
Topotecan<br />
VEGF<br />
Vascular endothelial growth factor<br />
VEGFR<br />
Vascular endothelial growth factor receptor<br />
xi
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