Index
337 A
Adhesion molecules, see also E-cadherin;
Integrins; N-cadherin, classification, 134
metastasis role overview, 133, 134 parathyroid hormone-related peptide
interactions in prostate cancer, 158, 159
Angiogenesis,
anticoagulants in prevention, 183, 184 coagulation relationship in cancer,
182, 183
docetaxel inhibition, 259 fibronectin role, 211 integrin roles, 139
platelet growth factor release in tumor angiogenesis, 178
transforming growth factor-`
stimulation, 62 tumor cell access to bone, 4 Apoptosis,
docetaxel induction, 257, 258 integrin mediation, 208, 209
parathyroid hormone-related peptide inhibition, 157, 158
Appendicular metastasis, management, 231
Atrasentan, bone metastasis treatment prospects, 219
B Bcl-2,
antisense combination therapy with docetaxel for metastatic prostate cancer, 277
docetaxel effects on phosphorylation, 257, 258
Bisphosphonates,
delivery of other drugs to bone, 280, 281 hypercalcemia of malignancy
management, 309
mechanisms of action, 307, 308 metastatic bone disease treatment,
breast cancer, 311, 312 drug types, 218, 219
prevention studies, 314, 315 prospects, 316
prostate cancer, 312, 313 rationale, 6, 7, 191, 192 renal cell cancer, 313
multiple myeloma management, 310, 311
osteoporosis management in cancer, 315, 316
side effects, 313, 314
skeletal-related event management, 310 structure, 305, 307
BMPs, see Bone morphogenetic proteins Bone grafts, limitations in metastasis
management, 232, 233
Bone morphogenetic proteins (BMPs), bone tissue engineering, 237 osteoblast stimulation, 111 osteopontin upregulation, 117 Bone sialoprotein (BSP),
functions, 212 integrin receptor, 212
metastatic prostate cancer expression, 76, 77
prognostic value, 212 regulation of expression, 77 Bone tissue engineering,
animal models, 236, 238 cell-based therapy, 233, 234
characterization of engineered cells and tissues, 235, 236
factor-based therapies, 234 goals, 233
matrix-based therapies, 234, 235 osteogenic cells,
expansion, 237 harvesting, 236, 237
stimulatory factors, 237, 238 prospects, 238
sources of cells and tissues, 235 Breast cancer,
bisphosphonate management of metastasis, 311, 312 bone metastasis,
incidence, 3 sites, 229 chemotherapy, 257
docetaxel treatment of metastasis, 262–265
osteolytic metastasis, 4
osteopontin expression, 109, 110 BSP, see Bone sialoprotein
C
Cadherins, see E-cadherin; N-cadherin Calcium-sensing receptor (CaR),
parathyroid hormone-related peptide interactions in prostate cancer, 159
CaR, see Calcium-sensing receptor Catenins, defects in cancer, 140, 141 CD44, osteopontin interactions, 115 Chemokines,
cancer cell homing to organs, 4 matrix metalloproteinase interactions,
91, 92
therapeutic targeting, 220
Clusterin, antisense combination therapy with docetaxel for metastatic
prostate cancer, 278
CMF, see Cumulative mean function Coagulation, see also Deep vein thrombosis;
Pulmonary embolism,
angiogenesis relationship in cancer, 182, 183
anticoagulants in angiogenesis prevention, 183, 184 cancer activation, 182
hypercoagulability in cancer, 178 platelet derangements in cancer, 178, 179 tumor growth and metastasis, 179, 180 tumor types and anticoagulant
sensitivity, 181, 182
Collagen, integrin receptors, 211, 212 COX-2, see Cyclooxygenase-2
Cumulative mean function (CMF), recurrent skeletal-related event analysis, 196–198
Cyclooxygenase-2 (COX-2), tetracycline inhibition, 298
D
Deep vein thrombosis (DVT), treatment in cancer patients, 180, 181 Docetaxel,
bone targeting, 279–282 mechanisms of action,
angiogenesis inhibition, 259 apoptosis induction, 257, 258 immunostimulation, 260 microtubule stabilization, 257 metastatic cancer treatment,
breast cancer, 262–265 lung cancer,
non-small-cell lung cancer, 265–270
small cell lung cancer, 270 prostate cancer,
Bcl-2 antisense combination therapy, 277
clusterin antisense combination therapy, 278
hormone refractory cancer trials, 275, 276, 283
insulin-like growth factor binding protein antisense combination therapy, 279 preclinical model findings, 272,
274, 275 pharmacokinetics, 260 structure, 256
toxicity, 261, 262
Doxycycline, see Tetracyclines DVT, see Deep vein thrombosis E
E-cadherin,
functional overview, 139 gene silencing in cancer, 140
metastasis suppression evidence, 140 mutation in cancer, 140, 141
structure, 139, 140
ECM, see Extracellular matrix EGF, see Epidermal growth factor EMT, see Epithelial–mesenchymal
transition Endothelin-1 (ET-1),
antagonists in bone metastasis treatment, 219
bone metastasis role, 6 Epidermal growth factor (EGF),
osteoblast stimulation, 111 osteopontin upregulation, 117
Epithelial–mesenchymal transition (EMT), cell migration, 79, 80
developmental biology, 78 gene expression and cell
differentiation, 79 signals, 79
therapeutic targeting in cancer, 80 tumors, 79, 80
ET-1, see Endothelin-1 Extracellular matrix (ECM),
adhesion in metastasis, 133
remodeling in tumor invasion, 87, 88 therapeutic targeting, 81
F
FAK, see Focal adhesion kinase
Femoral metastasis, management, 231, 232 FGF, see Fibroblast growth factor
Fibroblast growth factor (FGF), therapeutic targeting, 81
tumor secretion and bone metastasis role, 6
Fibronectin (FN), angiogenesis role, 211 cell types in synthesis, 210 integrin receptor, 210, 211 structure, 210
FN, see Fibronectin
Focal adhesion kinase (FAK), integrin signaling, 207 metastasis role, 137
Forteo, bone metastasis treatment prospects, 219
Fractures,
cancer types in causation, 229, 230 radiotherapy considerations, 331, 332 risks in cancer, 331
surgical management,
appendicular metastasis, 231 complications, 232, 233 femoral metastasis, 231, 232 humeral metastasis, 232 spinal metastasis, 230, 231 tissue engineering, see Bone tissue
engineering
H
Heparin, see Low-molecular-weight heparin
Hepatocyte growth factor (HGF), osteopontin upregulation, 117 HGF, see Hepatocyte growth factor HM, see Hypercalcemia of malignancy Humeral metastasis, management, 232 Hypercalcemia of malignancy (HM),
bisphosphonate management, 309 causes, 20
clinical manifestations, 20, 21 diagnosis of parathyroid hormone-
related peptide-associated disease, 21, 22
treatment, 22, 23 I
IGFs, see Insulin-like growth factors IL-1, see Interleukin-1
IL-6, see Interleukin-6 IL-8, see Interleukin-8 IL-11, see Interleukin-11 Implants, failure in metastasis
management, 232
Insulin-like growth factors (IGFs), binding proteins,
antisense combination therapy with docetaxel for metastatic prostate cancer, 279
antitumor effects, 64
growth factor binding, 65, 66 IGFBP-3,
cell surface receptors, 66 nuclear localization, 67 transforming growth factor-`
effect mediation, 67, 68 prostate cancer levels and
progression, 279 resistance and tumorigenesis
promotion, 65 subcellular localization, 64 bone as reservoir, 59
bone metastasis role overview, 67–70 bone tissue engineering, 237
cancer overexpression, 64 osteoblast stimulation, 111 receptors and signaling, 63, 279
therapeutic targeting, 81 Integrins,
activation and redox status, 205, 206 activation of receptors, 136, 137 angiogenesis role, 139
apoptosis mediation, 208, 209
cell migration/invasion role, 137, 138 cell motility mediation, 209
cell survival mediation, 138, 139 growth factor crosstalk, 136–138,
207, 208
ligands in cancer, see specific ligands metastasis role overview, 111, 213,
214, 217, 218
osteopontin interactions, 113–115, 136 platelet–cell interaction mediation, 179 recognition sequences, 209, 210 signal transduction, 206, 207
subunits and structure, 135, 202–205 tetraspanin interactions, 135, 136 therapeutic targeting, 220, 221 tumor expression and prognostic
value, a5`1, 214, 215 _6`1, 214 _6`4, 215
_v`3, 114, 216, 217 _v`5, 216
tumor invasion role, 214 Interleukin-1 (IL-1),
bone metastasis role, 111
matrix metalloproteinase interactions, 91, 92
Interleukin-6 (IL-6),
osteoclast regulation, 306
parathyroid hormone-related peptide interactions, 155
tetracycline effects on osteoblast secretion, 297
Interleukin-8 (IL-8), parathyroid hor- mone-related peptide interactions, 155, 156
Interleukin-11 (IL-11),
osteoblast production after cancer cell stimulation, 127
osteoclast regulation, 306
osteolytic bone metastasis role, 127–129 physiological actions, 125
prognostic value in metastatic cancer, 129, 130
receptor signaling, 125 tumor secretion, 126, 127 L
Laminin, integrin receptors, 212 LMWH, see Low-molecular-weight
heparin
Low-molecular-weight heparin (LMWH),
angiogenesis prevention, 184 mechanism of action, 181
metastasis inhibition studies, 184 venous thromboembolism treatment
in cancer, 180, 181
Lung, parathyroid hormone-related peptide in function,
adult lung expression, 161 fetal lung expression, 160 injury mediation, 162 Lung cancer,
chemotherapy, 257
docetaxel treatment of metastasis, non-small-cell lung cancer, 265–270 small cell lung cancer, 270
parathyroid hormone-related peptide, expression, 162, 163
pathophysiology, 163
prognostic value, 164, 165, 167 M
MAPK, see Mitogen-activated protein kinase
Matrix metalloproteinases (MMPs), activation, 89
bone metastasis role, 6, 111 classification and substrate
specificity, 88 domains, 88
immune cell expression, cell specificity, 90
cell–cell and cell–matrix interactions, 92, 93
cytokine/chemokine interactions, 91, 92
mucosal defense, 90, 91 tumor invasion role, 94–96 osteopontin interactions, 115, 116
tetracycline inhibition, 296
therapeutic targeting with inhibitors, 8, 9, 81
tissue inhibitors, 89, 90, 96 transforming growth factor-`
induction, 62, 63
Mitogen-activated protein kinase (MAPK),
integrin signaling, 207
parathyroid hormone-related peptide interactions, 155
MMPs, see Matrix metalloproteinases Mucins, tumor expression, 177 Multiple myeloma, bisphosphonate
management of skeletal complications, 310, 311 N
N-cadherin, metastasis role, 141 Nitric oxide synthase (NOS),
osteopontin inhibition of induction, 113
NOS, see Nitric oxide synthase O
OPG, see Ostepontegrin OPN, see Osteopontin
Osteoblastic metastasis, overview, 4, 110 Osteocalcin,
metastatic prostate cancer expression, 76, 77
regulation of expression, 77
Osteolytic metastasis, overview, 4, 110 Osteomimicry, see Prostate cancer Osteopontin (OPN),
bone metastasis role overview, 111–112 growth factor receptor pathway
interactions, 116, 117 integrin interactions, 113–114, 212 metastatic cancer expression,
breast cancer, 109, 110 prostate cancer, 76, 77, 109 physiological functions, 108 protease interactions, 115–116 protein–protein interactions, 108 receptors, 76, 113–115, 212 regulation of expression, 77 structure, 108
therapeutic targeting, 118
tumor cell survival mechanisms, 113 Osteoporosis, bisphosphonate
management in cancer, 315, 316 Ostepontegrin (OPG),
osteoclast regulation, 306
parathyroid hormone-related peptide downregulation, 111
prostate cancer expression, 152, 153 RANK ligand binding, 5
therapeutic targeting, 8, 219 P
Palliative radiation therapy, see Radiation therapy
Parathyroid hormone-related peptide (PTHrP),
bone resorption role, 111 gene,
features, 14, 147
regulators of expression, 14 hypercalcemia of malignancy role,
see Hypercalcemia of malignancy immunoassays, 21, 22
lung function,
adult lung expression, 161 cancer,
expression, 162, 163 pathophysiology, 163
prognostic value, 164, 165, 167 fetal lung expression, 160
injury mediation, 162 osteoclast activation, 5 physiologic functions,
cellular function, 17, 18 growth regulation, 148–150 renal effects, 18
skeletal actions, 18, 29 processing, 148
prostate cancer,
adhesion molecule interactions, 158, 159
androgen regulation, 158 apoptosis inhibition, 157, 158 calcium regulation system
interactions, 159
cell line expression levels and effect studies, 150, 151, 154
cytokine/lymphokine interactions, 155, 156
growth regulation, 150
metastasis expression, 151, 152 receptor expression, 154, 155 regulation of osteokine expression,
152, 153
tumor transplant model studies in mice, 159, 160
receptors and signaling, 16, 17, 147–149 splice variants, 147
structure-function relationships, 14–16, 149, 156, 157
therapeutic targeting, 8, 219 transforming growth factor-`
stimulation, 63, 111 tumor secretion, 13, 14, 20
vitamin D-induced down regulation, 43, 45–47
Paxillin, integrin–growth factor receptor interaction mediation, 136–138 PDGF, see Platelet-derived growth factor PDT, see Photodynamic therapy
PE, see Pulmonary embolism Photodynamic therapy (PDT),
bone optical properties, 245
minimally invasive surgical access, 246 musculoskeletal applications, 244, 245 photosensitizers for bone metastasis,
247–249
preclinical models of bone metastasis, burden quantification, 247
overview, 246, 247 principles, 244
prospects for bone metastasis management, 249 safety, 244
Platelet-derived growth factor (PDGF), osteoblast stimulation, 111
osteopontin upregulation, 117 Platelets,
cancer derangements and tumor cell interactions, 178, 179
CD40 ligand expression, 178 growth factor release in tumor
angiogenesis, 178 Prostate cancer,
bisphosphonate management of metastasis, 312, 313 bone homing mechanisms, 75
bone metastasis incidence, 3 docetaxel treatment of metastasis,
Bcl-2 antisense combination therapy, 277
clusterin antisense combination therapy, 278
hormone refractory cancer trials, 275, 276, 283
insulin-like growth factor binding protein antisense combination therapy, 279
preclinical model findings, 272, 274, 275
epithelial–mesenchymal transition, 78–80
hormone refractory cancer management, 256 osteoblastic metastasis, 4, 307 osteomimicry,
definition, 76
gene expression and regulation, 76, 77
therapeutic targeting, 81 osteopontin expression, 76, 77, 109 parathyroid hormone-related peptide,
adhesion molecule interactions, 158, 159
androgen regulation, 158 apoptosis inhibition, 157, 158 calcium regulation system
interactions, 159
cell line expression levels and effect studies, 150, 151, 154
cytokine/lymphokine interactions, 155, 156
growth regulation, 150
metastasis expression, 151, 152 receptor expression, 154, 155 regulation of osteokine expression,
152, 153
tumor transplant model studies in mice, 159, 160
PTHrP, see Parathyroid hormone-related peptide
Pulmonary embolism (PE), treatment in cancer patients, 180, 181
R
Radiation therapy,
brachytherapy, 324 dosing, 323
failure and palliative radiation therapy retreatment, 327, 328 fracture management considerations,
331, 332
half-body external beam radiation therapy, 326
mechanism of action, 323, 330 palliative external beam radiation
therapy, 324–326 prospects, 333
radiation sources, 324 side effects, 330, 331
spinal metastasis, 244, 332, 333 systemic radionuclide delivery, 329, 330 RANK,
ligands, 5
osteoclast regulation, 306
osteolytic bone metastasis role, 111 prostate cancer expression with
ligand, 152, 153 therapeutic targeting, 8, 220 Ras,
epithelial–mesenchymal transition signaling, 80
integrin signaling, 207
Renal cell cancer, bisphosphonate management of metastasis, 313 S
Seed and soil theory, metastasis, 108 Skeletal-related event (SRE),
analysis techniques, 193–196, 198, 199 bisphosphonate management, 310 composite endpoint in clinical trials,
192, 193
recurrent event analysis, 196, 197 Spinal metastasis,
compression management overview, 332 radiation therapy, 244, 332, 333 surgical decompression, 230, 231 vertebroplasty,
complications, 243 indications, 231
SRE, see Skeletal-related event T
Taxotere, see Docetaxel
Tetracyclines,
antitumor activity of doxycycline, 294–296
bone cell effects, 296, 297 bone metastasis management
prospects, 298, 299
cyclooxygenase-2 inhibition, 298 discovery and history of use, 293, 294 matrix metalloproteinase
inhibition, 296 mechanism of action, 294 neural tissue effects, 298
structure–activity relationships, 294 therapeutic application
and mechanisms, 9 TF, see Tumor cell tissue factor
TGF-`, see Transforming growth factor-`
Thrombin, metastasis role, 178 Tissue engineering, see Bone tissue
engineering
Transforming growth factor-` (TGF-`), bone as reservoir, 59
bone metastasis role overview, 5, 6, 67–70
cancer cell signaling alterations, receptor mutations, 60 resistance to cytostasis and
apoptosis, 61 Smad function, 60, 61
epithelial–mesenchymal transition role, 79, 80
insulin-like growth factor binding protein-3 mediation of effects, 67, 68
integrin upregulation, 138 osteoblast stimulation, 111 osteopontin upregulation, 117 physiological actions, 60 receptors and signaling, 60 therapeutic targeting, 81, 220 tumor environment effects,
angiogenesis stimulation, 62 immunosurveillance escape, 62 matrix metalloproteinase
induction, 62, 63 parathyroid hormone-related
peptide stimulation, 63, 111 Tumor cell tissue factor (TF),
angiogenesis promotion, 178, 182
inhibitor in angiogenesis and metastasis inhibition, 183, 184
U
uPA, see Urokinase plasminogen activator
Urokinase plasminogen activator (uPA), osteopontin interactions, 115, 116 metastasis role, 111
receptor–integrin interactions, 213 V
Vascular endothelial growth factor (VEGF),
bone tissue engineering, 237 platelet release in tumor
angiogenesis, 178
VEGF, see Vascular endothelial growth factor
Vitamin D, analog design,
A-ring modification, 37 E-ring replacement, 38 mechanism of action, 38 side chain modification, 37 anticancer effects in animal models,
39, 40
deficiency and cancer risk, 38, 39 nongenomic effects, 32, 41
parathyroid hormone-related peptide downregulation and bone metastasis prevention, 43, 45–47 parathyroid hormone-related peptide interactions in prostate cancer, 159 physiological actions, 30–32
receptor,
activation, 32, 39 coactivators, 36 corepressors, 36 domains, 32–35 heterodimers, 35
nonsteroid nuclear receptor overview, 33, 34 resistance to therapy, 41, 43
response elements and transcription, 35, 41
synthesis and metabolism, 29, 30 Vitronectin (VN),
functions, 211 integrin receptor, 211 VN, see Vitronectin W
Wnt, multiple myeloma signaling, 306
