Ординатура / Офтальмология / Английские материалы / Ocular Oncology_Albert, Polans_2003

Activated inflammatory cells, immunology, uveal melanoma, apoptotic deletion of, 257

AlphaAcry-E6 + E7 mice, pRb in pathogenesis of murine RB, 156–157

AlphaA-crystalline-E6/E7 transgenic mice, retinoblastoma, 478–479

Analysis of tumor cells death, vitamin D analogues, 301–302

Angiogenesis, uveal melanoma, 89–90 Ankara, Turkey, treatment of

retinoblastoma, 354

Antitumor immunity, uveal melanoma, 231–254

CD4+ helper T cells, 234–236 CD8z+ cytotoxic T cells, 234

class I antigen-processing pathway, 241 class II antigen-processing pathway, 242–

243

class II pathway, for tumor antigens, 247–249

costimulatory molecules, 237–238 cross-priming versus direct recognition,

243–244

current immunotherapies, 244–246 effector T cells, 232–233

geographic specificity, CD4+ T-helper cells, 236

human model, 249

major histocompatibility complex, 240 successful activation of CTL requires

T-helper cells, 246 tumor antigens, 239–240

Apoptosis

suppression of, retinoblastoma protein, 137–139

[Apoptosis]

uveal melanoma, 88–89

Apoptosis in retinoblastoma tumors-role of p53, molecular biology, 217–221

Arrest of tumor growth, mechanism of, vitamin D analogues, 312–314

Athymic xenograft model

1alpha-OH-D2 in, effectiveness, vitamin D analogues, toxicity of, 307

16,23-D3 in, effectiveness, vitamin D analogues, toxicity of, 307 effectiveness of toxicity, calcitriol treatment in, vitamin D

analogues, 304

effectiveness, toxicity of ergocalciferol in, vitamin D analogues, 303– 304

B16 melanoma cells, uveal melanoma, 278, 279–283, 289–290

Bangalore, India, treatment of retinoblastoma, 354

Biochemical pathways, uveal melanocytes, 189–210

cell culture, uveal melanocytes, 190 cyclic adenosine monophosphate system,

197–198

growth requirement, uveal melanocytes, 196

growth requirements, uveal melanocytes, 195–197

isolation, cultivation of uveal melanocytes, 191–195

normal uveal melanocytes, 189–190 signal transduction pathways, normal uveal melanocytes, 197–199

500

Brachytherapy retinoblastoma, 359–360

complications, 360 history, 359 indications, 359 results, 360 technique, 359–360

uveal melanoma, 322, 327–330

Calcitriol, LHbeta-tag, effectiveness, vitamin D analogues, toxicity of, 304– 307

Calcium-binding proteins, uveal melanocytes interaction, 205–206

Calcium channel syste, uveal melanocytes interaction, 199

Candidate M3-to-Mn events, 112–114 chromosome 16q loss, narrowed to

member of cadherin family, 113– 114

gains at 1q, 2p, and loss at 16q as M3-to- Mn events, 112–113

genomic gains, losses, 112–113 isochromosome 6p, oncogene, RBKIN,

113

loss at 16q, M3-to-Mn events, 112–113 maintenance of genetic stabilities by

PRB, 113

CD4+ helper T cells, antitumor immunity, uveal melanoma, 234–236

CD8z+ cytotoxic T cells, antitumor immunity, uveal melanoma, 234

Cell cycle progression, inhibition of, by pRb, 133–135

Cell cycle re-entry, inhibition of, retinoblastoma protein, 140

Cell death, in retinoblastoma, 216

Cell fate, retinoblastoma tumors, 213–217 Cell invasion ability, uveal melanocytes

interaction, 206

Cellulitis, orbital, with retinoblastoma, 25 Charged-particle radiation, uveal

melanoma, 322 Charged-particle radiotherapy, uveal

melanoma, 330–332 Chemoreduction, retinoblastoma, 365–

369 complications, 368 history, 365 indications, 365 results, 366–368 technique, 365

Index

Chemotherapeutic agents, mouse models, genetically engineered, retinoblastoma, transgenic mouse models of retinoblastoma, 483

Chemotherapy, retinoblastoma, 119 Chimeric RB1 / mice, pocket family gene

deficient knockout, chimeric mice, 158–159

Choroidal body melanomas, 412–421 Chromosome 1

tumorigenesis, 74

uveal malanoma, 68, 74 uveal melanoma, 68

Chromosome 3 tumorigenesis and, 71–72 uveal melanoma, 71–72

Chromosome 6, 73–74 tumorigenesis, 73–74 uveal melanoma, 66–68

Chromosome 6 abnormalities, uveal melanoma, 85–86

Chromosome 8 tumorigenesis, 72–73 uveal melanoma, 72–73

Ciliary body melanomas, 412–421 Class I antigen-processing pathway,

antitumor immunity, uveal melanoma, 241

Class II antigen-processing pathway, antitumor immunity, uveal melanoma, 242–243

Clinical trials retinoblastoma, 403–408 uveal melanoma, 379–402

Complement activation, immunology, uveal melanoma, inhibition of, 257

Computed tomography, in diagnosis of retinoblastoma, 29–30

Conditional (cell type-specific) knockout mice, retinoblastoma, 471

Costimulatory molecules, antitumor immunity, uveal melanoma, 237–238

Cryotherapy, retinoblastoma, 364–365 complications, 365

history, 364 indications, 364

mechanism of action, 364 results, 365

technique, 364

Cytokines, uveal melanocytes interaction, 201

Index

Delayed-type hypersensitivity, immunology, uveal melanoma, inhibition of, 257

Detection of uveal melanoma, 40–41 Diagnosis, uveal melanoma, 2–5

clinical features, 2–4 diagnostic modalities, 4–5

Diffuse infiltrating growth pattern, as sign of retinoblastoma, 22–23

Ectopic intracranial retinoblastoma, 55–56 Endophytic growth pattern, as sign of

retinoblastoma, 21 Enucleation

retinoblastoma, 355–356 complications, 356 results, 356

uveal melanoma, 6, 322, 337–340 Environmental exposure, uveal melanoma,

40

Epidemiological studies, retinoblastoma, 404–407

design issues, 404–406 eligibility criteria, 405–406

interdisciplinary approach, 404–405 outcome measurements, 406 standardized common protocol, 405

Epidemiology retinoblastoma, 47–61

demographics, 50–53 age at diagnosis, 50–51 gender, 51

number of discrete tumors, 53 number of eyes affected, 52 race, 51

socioeconomic group, 51–52 extraophthalmic lesions, disorders associated with, 55–59

ectopic intracranial retinoblastoma, 55–56

malignant neoplasms, 56–59 frequency, 47–50

incidence, 47–49 prevalence, 49–50 risk factors, 53–55

family history, 53 parental age, 54–55 primitive neuroectodermal

intracranial tumors, earlyonset, 55

retinoblastoma gene, loss, inactivation of, 53–54

501

[Epidemiology]

uveal melanoma, 35–45

detection of uveal melanoma, 40–41 distribution of cases, 37–38

future research, 41 patient characteristics, 38 risk factors, 38–40

environmental exposure, 40 genetic susceptibility, 39–40 hormones, 39

personal characteristics, 38–39 Epipodophyllotoxin-induced secondary

leukemia, retinoblastoma, 119 Exophytic growth pattern, as sign of

retinoblastoma, 21–22 Extension, extraocular, with

retinoblastoma, 25

External-beam radiation, retinoblastoma, 356–359

complications, 358–359 history, 356–357 indications, 357 results, 358

technique, 357

External beam radiation therapy, mouse models, genetically engineered, retinoblastoma, transgenic mouse models of retinoblastoma, 483 External-beam radiation therapy, uveal

melanoma, 322 External-beam radiotherapy, uveal

melanoma, 334–335

Extraocular extension, with retinoblastoma, 25

Extraocular involvement, uveal melanoma, 340–342

Extraocular retinoblastoma, 491–500 incidence of, 492

intensive chemotherapy and autologous rescue, treatment with, 495–496

mechanism of disease, 492 risk factors, 492–493

standard chemotherapy, treatment of with, 493–495

central nervous system disease, 495 extraocular disease-optic nerve, 494 extraretinal intraocular disease, 494 hematogenous disease, 495

orbital disease, 495

trilateral retinoblastoma, 496–497 Extraophthalmic lesions, disorders

associated with, 55–59

502

[Extraophthalmic lesions]

ectopic intracranial retinoblastoma, 55– 56

malignant neoplasms, 56–59

Familial uveal melanoma, 83 Family history, retinoblastoma, 53

Feline uveal melanoma induced by Gardner strain of feline sarcoma virus, 275– 276

Fluorescein angiography, 28

in diagnosis of retinoblastoma, 28

Gamma knife, uveal melanoma, 322, 332– 334

Genetically engineered mouse models, retinoblastoma, 467–489

conditional (cell type-specific) knockout mice, 471

knockout mice, 469–470 methods for creation, 468–472 Rb gene inactivation, genetically

engineered mice, 479–483 conditional Rb knockout mice, 481–

482

p107 inactivation, murine retinoblastoma, 480–481

Rb heterozygous, homozygous knockout mice, 479–480

Rb knockout mice, 482–483 Rb-deficient chimeric mice, 480

transgenic mice, 468–469 transgenic mouse, 472–479

alphaA-crystalline-E6/E7 transgenic mice, 478–479

IRBP-E7 and IRBP-E7/p53 / mice, 475–478

IRBP-tag transgenic mice, 476 LHbeta-tag transgenic mice, 472–474 opsin-tag transgenic mice, 474–475 PNMT-tag transgenic mice, 478

transgenic mouse models of retinoblastoma, 483–484

chemotherapeutic agents, 483 external beam radiation therapy, 483 vitamin D analogues, 483–484

Genetic susceptibility, uveal melanoma, 39– 40

Genetics, uveal melanoma, 2, 63–79 cytogenetic studies, 64–71

chromosome 1, 68 chromosome 6, 66–68

Index

[Genetics]

monosomy 3, isochromosome 8q, 64– 66

other chromosome changes, 68–69 familial uveal melanoma, 83

future of, 70–71

gene expression, uveal melanoma, 81–102 predisposing congenital conditions, uveal

melanoma, 83

somatic mutations, uveal melanoma, 83– 92

chromosome 6 abnormalities, 85–86 loss of 1p, 86

other chromosomal abnormalities, 86

cytogenetics, 83–87 gain of 8q, 85

monosomy of 3, 84–85

gene expression alterations, 87–92 angiogenesis, 89–90

apoptosis, 88–89

cell cycle regulation, 87–88 invasion, 90–92

tumorigenesis, genes involved in, 71–75 chromosome 1, 74

chromosome 3, 71–72 chromosome 6, 73–74 chromosome 8, 72–73

Genomic changes, retinoblastoma, 103– 128

candidate M3-to-MN events, 112–114 chromosome 16q loss, narrowed to

member of cadherin family, 113– 114

gains at 1q, 2p, and loss at 16q as M3- to-Mn events, 112–113

genomic gains, losses, 112–113 isochromosome 6p, oncogene,

RBKIN, 113

maintenance of genetic stabilities by PRB, 113

chemotherapy, 119 epipodophyllotoxin-induced secondary

leukemia, 119 impact of loss of RB1 mouse embryo, 105

in mouse embryo, in humans, 105–106 leukemic risk, with retinoblastoma, 119 loss of PRB, default pathway of retinal

differentiation, 107 M1, M2 events, 108–112

mosaicism, RB1 mutations, 111

Index

[Genomic changes]

murine model, comparable to human retinoblastoma, 107

phenotype-genotype correlations, 111– 112

examples of low-penetrance families, 112

exogenous inactivation of PRB, 112 primary tumors for PRB inactivation,

112

RB1 ‘‘null’’ mutations and penetrance, 111

pRB family members, 106–107 programmed cell death in retinal

development, 114 role of p75NTR, 114

telomerase activity in cancers, 114– 115

telomerase and immortality, 114–115 radiation therapy, 118

retinal cell, 104–108 developmental window, 104–105

mice, humans, differences, similarities in, 105–107

retina, 104–105

retinoblastoma resistance to therapy, 115–118

multidrug P-glycoprotein in cancer, 116–117

multidrug-resistance genes, 115–118 overview, 115–116

retinoma way station, 107–108 attributes, benign human retinoma,

107–108

malignant transformation, 108 predisposed by RB1 mutations, 108

therapy-induced mutations, second primary tumors in retinoblastoma patients, 118–119

Germline RB1+/ mice, pocket family gene deficient knockout, chimeric mice, 158

Glaucoma, neovascular, with retinoblastoma, 24–25

Greene melanoma, uveal melanoma, 277– 278

Greene melanoma cells, uveal melanoma, 279, 289

Growth factors, uveal melanocytes interaction, 200–201

Growth patterns, as signs of retinoblastoma, 21–23

503

Homozygous knockout mice, Rb heterozygous, 479–480

Hormones

uveal melanocytes interaction, 201–202 uveal melanoma, 39

Ibadan, Nigeria, treatment of retinoblastoma, 354

Immune privilege, immunology, uveal melanoma, 257

Immunity, antitumor, uveal melanoma, 231–254

Immunohistochemistry, vitamin D analogues, 302

Immunology, uveal melanoma

activated inflammatory cells, apoptotic deletion of, 257

complement activation, inhibition of, 257

delayed-type hypersensitivity, inhibition of, 257

immune privilege, 257 circumvention of, 258–259

immunosuppressive factors, 255–268 inflammatory cells, exclusion of, 257 innate immune system, 260–262 NK-cell activity, inhibition of, 257 ocular immune privilege, 255–258 proinflammatory cytokine secretion,

inhibition of, 257

T-cell proliferation, inhibition of, 257 Immunosuppressive factors, immunology,

uveal melanoma, 255–268 Impact of loss of RB1

mouse embryo, 105

in mouse embryo, in humans, 105–106 Infiltrating growth pattern, as sign of

retinoblastoma, 22–23 Inflammatory cells, immunology, uveal

melanoma, exclusion of, 257 Integrins, uveal melanocytes interaction,

206–207

Intraretinal lesions, as signs of retinoblastoma, 21

In vitro effects of calcitriol, vitamin D analogues, 303

IRBP-E2F1, IRBP-E2F1; p53 / mice, pRb in pathogenesis of murine RB, 158

IRBP-E7, IRBP-E7; p53 / mice, pRb

in pathogenesis of murine RB, 157–158 IRBP-E7 and IRBP-E7/p53 / mice,

retinoblastoma, 475–478

504

IRBP-tag mice, pRb in pathogenesis of murine RB, 156

IRBP-tag transgenic mice, retinoblastoma, 476

Knockout mice, retinoblastoma, 469–470 Knudson’s two hit hypothesis, molecular genetics, retinoblastoma, 451–452

Laser therapies, uveal melanoma, 322, 323– 327

Leukemia, epipodophyllotoxin-induced secondary, retinoblastoma, 119 Leukemic risk, with retinoblastoma, 119 Leukocoria, as sign of retinoblastoma, 20 LHbeta-tag mice, pRb in pathogenesis of

murine RB, 154 LHbeta-tag transgenic mice,

retinoblastoma, 472–474 LHbeta-tag transgenic model

1alpha-OH-D2, effectiveness, vitamin D analogues, toxicity of, 307–312 16,23-D3DD, effectiveness, vitamin D

analogues, toxicity of, 307 LINAC stereotactic radiotherapy, uveal

melanoma, 332–334

Local resection, uveal melanoma, 8–9 Local tumor resection, uveal melanoma,

335–337

Loss of PRB, default pathway of retinal differentiation, 107

Low-penetrance retinoblastoma, retinoblastoma tumor, 460–461

M1, M2 events, 108–112

Magnetic resonance imaging, in diagnosis of retinoblastoma, 30

Major histocompatibility complex, antitumor immunity, uveal melanoma, 240

Malignant neoplasms, retinoblastoma and, 56–59

Matrix metalloproteinases, uveal melanocytes interaction, 206

Melanocytes, uveal, biochemical pathways, 189–210

calcium channel system, 199

cell culture, uveal melanocytes, 190 cyclic adenosine monophosphate system,

197–198 cytokines, 201

effects of substances on, 200

Index

[Melanocytes]

expression of substances, 204–207 calcium-binding proteins, 205–206 cell invasion ability, 206 integrins, 206–207

matrix metalloproteinases, 206 tissue plasminogen activator, 205

vascular endothelial growth factor, 204 growth factors, 200–201

growth requirement, uveal melanocytes, 196

growth requirements, uveal melanocytes, 195–197

hormones, 201–202 isolation, cultivation of uveal

melanocytes, 191–195 neurotransmitters, 202–203

normal uveal melanocytes, 189–190 prostaglandins, 203–204

protein kinase C (PKC) system, 198–199 serine/threonine kinase system, 199 signal transduction pathways, normal

uveal melanocytes, 197–199 tyrosine kinase system, 198

Models, uveal melanoma, 269–298 chemical and radiation induced uveal

proliferations, 274–275 intraocular inoculation of tissue culture

melanoma cells in animal eyes, 276– 290

cell lines, 277–279 B16 melanoma, 278

Greene melanoma, 277–278 human uveal melanoma, 278–279

chick embryo model, 290 hamster model, 279–284 murine model, 279–284

B16 melanoma cells, 279–283 Greene melanoma cells, 279 human uveal melanoma cells, 283–

284

ocular immune privilege, 276–277 rabbit model, 284–290

B16 melanoma cells, 289–290 Greene melanoma cells, 289 spontaneously occurring uveal tumors in

animals, 271–274

ocular melanoma in cats, 273 ocular melanoma in dogs, 271–273 pigmented ocular tumors in other

animals, 273–274 transgenic mice, 270–271

Index

[Models]

viral-induced uveal proliferations, 275– 276

feline uveal melanoma induced by Gardner strain of feline sarcoma virus, 275–276

uveal melanoma induced by SV40, 276 Molecular genetics, retinoblastoma, 451–

465

Knudson’s two hit hypothesis, 451–452 Monosomy 3, isochromosome 8q

uveal malanoma, 64–66 uveal melanoma, 64–66

Monosomy of 3, uveal melanoma, 84–85 Mosaicism, RB1 mutations, 111 Mosaiscism, retinoblastoma tumor, 458 Mouse models, genetically engineered,

retinoblastoma, 467–489

conditional (cell type-specific) knockout mice, 471

knockout mice, 469–470 methods for creation, 468–472 Rb gene inactivation, genetically

engineered mice, 479–483 conditional Rb knockout mice, 481–

482

p107 inactivation, murine retinoblastoma, 480–481

Rb heterozygous, homozygous knockout mice, 479–480

Rb knockout mice, 482–483 Rb-deficient chimeric mice, 480

transgenic mice, 468–469 transgenic mouse, 472–479

alphaA-crystalline-E6/E7 transgenic mice, 478–479

IRBP-E7 and IRBP-E7/p53 / mice, 475–478

IRBP-tag transgenic mice, 476 LHbeta-tag transgenic mice, 472–474 opsin-tag transgenic mice, 474–475 PNMT-tag transgenic mice, 478

transgenic mouse models of retinoblastoma, 483–484

chemotherapeutic agents, 483 external beam radiation therapy, 483 vitamin D analogues, 483–484

Murine model, comparable to human retinoblastoma, 107

Murine retinoblastoma, p107 inactivation, retinoblastoma, 480–481

505

Mutation detection, retinoblastoma tumor, 456–458

Neovascular glaucoma, with retinoblastoma, 24–25

Neurotransmitters, uveal melanocytes interaction, 202–203

NK-cell activity, immunology, uveal melanoma, inhibition of, 257

Observation, for uveal melanoma, 322 Occupational exposure, uveal melanoma,

40

Ocular immune privilege, immunology, uveal melanoma, 255–258

Opsin-tag mice, pRb in pathogenesis of murine RB, 154–156

Opsin-tag transgenic mice, retinoblastoma, 474–475

Orbital cellulitis, with retinoblastoma, 25

P53, molecular regulation, cell fate, retinoblastoma, 211–230

apoptosis in retinoblastoma tumors-role of p53, molecular biology, 217–221

cell death, in retinoblastoma, 216 cell fate

in human retinoblastoma, 214 retinoblastoma tumors, 213–217

molecular etiology, 211–212 p53 in development of invasive

retinoblastoma, 221–222 transgenic mouse models of

retinoblastoma, 223–224 tumors-cell of origin, 212–213

P107 inactivation, retinoblastoma, murine retinoblastoma, 480–481

Parental age, retinoblastoma and, 54–55 PCR amplification

VDR cDNA from human RB samples, vitamin D analogues, 302–303

VDR cDNA from mouse model of retinoblastoma, vitamin D analogues, 303

Periocular chemotherapy, 368–369 Phenotype-genotype correlations, retinoblastoma, 111–112

examples of low-penetrance families, 112 exogenous inactivation of PRB, 112 primary tumors for PRB inactivation,

112

506

[Phenotype-genotype correlations]

RB1 ‘‘null’’ mutations and penetrance, 111

Phosphorylation, pRb, retinoblastoma protein, 132–133

Photocoagulation retinoblastoma, 361

complications, 362 history, 361 indications, 361

mechanism of action, 361 results, 362

technique, 362 Photocoagulation

uveal melanoma, 323–327 Photocoagulation therapy, uveal

melanoma, 322

Photodynamic therapy, uveal melanoma, 322–327

PNMT-tag transgenic mice, retinoblastoma, 478

Pocket family gene deficient knockout, chimeric mice, 158–160

PRB family members, 106–107

PRb in pathogenesis of human RB, 160– 167

+2p, 165

consistent chromosomal gains, 161–163 +1q, 161–162

+1q and/or +6p, 163 +6p/i(6p), 163

consistent chromosomal losses, 163–165 -16/del(16q), 164

-17/del(17p), 164 LOS for 1p, 165

modules of RB pathogenesis, 165–167 p107, 165

telomerase activity, 165

Predisposing congenital conditions, uveal melanoma, 83

Primitive neuroectodermal intracranial tumors, early-onset, 55

Programmed cell death in retinal

development, 114 role of p75NTR, 114

telomerase activity in cancers, 114–115 telomerase and immortality, 114–115

Proinflammatory cytokine secretion, immunology, uveal melanoma, inhibition of, 257

Prostaglandins, uveal melanocytes interaction, 203–204

Index

Protein, retinoblastoma, 129–188

pocket family gene deficient knockout, chimeric mice, 158–160

chimericRB1 / mice, 158–159 germline RB1+/ mice, 158 introduction of additional mutations

in RB1+/ mice, 159 RB1 / ;p107 / chimeras, 159–160

pRb

cancer, 148–150 cell cycle, 145–148

pRb and cancer, 148–150 pRb and cell cycle, 145–148

Protein

pRb in pathogenesis of human RB, 160– 167

+2p, 165

consistent chromosomal gains, 161– 163

+1q, 161–162

+1q and/or +6p, 163 +6p/i(6p), 163

consistent chromosomal losses, 163– 165

-16/del(16q), 164 -17/del(17p), 164

LOS for 1p, 165

modules of RB pathogenesis, 165–167 p107, 165

telomerase activity, 165

pRb in pathogenesis of murine RB, 153– 160

alphaAcry-E6 + E7 mice, 156–157 insights from transgenic mice, 154 IRBP-E2F1, IRBP-E2F1; p53 /

mice, 158

IRBP-E7, IRBP-E7; p53 / mice, 157–158

IRBP-tag mice, 156 LHbeta-tag mice, 154 opsin-tag mice, 154–156 RNMT-tag mice, 156

pRb in retinogenesis, 150–153 developing retina, RB1 expression in,

150–151

RB-1 deficient knockout, chimeric mice, 151–153

pRb regulation, function, 131–135 apoptosis, suppression of, 137–139 cell cycle progression, inhibition of, by

pRb, 133–135

cell cycle re-entry, inhibition of, 140

Index

[Protein]

pRb, phosphorylation, 132–133 terminal cell cycle arrest, induction of,

136

terminal differentiation by pRb, promotion of, 135–140

tissue-specific genes, transcriptional activation of, 139–140

pRb structure, 140–145 A/B pocket, 141–142 C terminus, 142

low-penetrance pRb mutants, 143– 145

N terminus, 142–143

Protein kinase C (PKC) system, uveal melanocytes, 198–199

Radiation therapy, retinoblastoma, 118 Radiotherapy, uveal melanoma, 6–8, 322,

327–335

Rb gene inactivation, genetically engineered mice, retinoblastoma, 479–483

conditional Rb knockout mice, 481– 482

p107 inactivation, murine retinoblastoma, 480–481

Rb knockout mice, 482–483 Rb-deficient chimeric mice, 480

RB1 gene structure, 452–455 RB1 gene, 452–453

retinoblastoma protein, pRb, 453 RB1+/ mice, mutations, pocket family

gene deficient knockout, chimeric mice, 159

RB1 / ;p107 / chimeras, pocket family gene deficient knockout, chimeric mice, 159–160

Rb-deficient chimeric mice, retinoblastoma, 480

Reproductive factors, uveal melanoma, 39 Resection, local, uveal melanoma, 8–9 Resistance to therapy, retinoblastoma, 115–

118

multidrug P-glycoprotein in cancer, 116– 117

multidrug-resistance genes, 115–118 overview, 115–116

Retinal cell, 104–108 developmental window, 104–105

mice, humans, differences, similarities in, 105–107

retina, 104–105

507

Retinoblastoma, 19–34, 429–450 advanced presentations, 24–25

extraocular extension, 25 neovascular glaucoma, 24–25 orbital cellulitis, 25

clinical features, 20–26 clinical trials in, 403–408 diagnostic approaches, 27–30

computed tomography, 29–30 fluorescein angiography, 28 magnetic resonance imaging, 30 ultrasonography, 28–29

differential diagnosis, 26–27 early signs, 20

leukocoria, 20 strabismus, 20 epidemiology, 47–61

demographics, 50–53 age at diagnosis, 50–51 gender, 51

number of discrete tumors, 53 number of eyes affected, 52 race, 51

socioeconomic group, 51–52 extraocular, treatment of, 491–500 extraophthalmic lesions, disorders

associated with, 55–59

ectopic intracranial retinoblastoma, 55–56

malignant neoplasms, 56–59 frequency, 47–50

incidence, 47–49 prevalence, 49–50 risk factors, 53–55

family history, 53 parental age, 54–55 primitive neuroectodermal

intracranial tumors, earlyonset, 55

retinoblastoma gene, loss, inactivation of, 53–54

genetically engineered mouse models, 467–489

genetics of, 451–465

genomic changes with, 103–128 growth patterns, 21–23

diffuse infiltrating growth pattern, 22– 23

endophytic growth pattern, 21 exophytic growth pattern, 21–22 intraretinal lesions, 21

management, 31

508

[Retinoblastoma] p53, 211–230 pathology, 31

prognosis of, 429–450 protein, 129–188 retinocytoma, 25

spontaneously regressed retinoblastoma, 26

treatment of, 353–378 trilateral retinoblastoma, 25

vitamin D analogues for, 299–320 Retinoblastoma protein, 129–188 Retinoblastoma tumor

genetic anomalies associated to pRB inactivation, 461

mutations of RB1, 456 nature of first hit, 458–459 second hit, 459–460

Retinocytoma, 25

Retinoma way station, 107–108

attributes, benign human retinoma, 107– 108

malignant transformation, 108 predisposed by RB1 mutations, 108

Risk factors, uveal melanoma, 38–40 environmental exposure, 40 genetic susceptibility, 39–40 hormones, 39

personal characteristics, 38–39 RNMT-tag mice, pRb in pathogenesis of

murine RB, 156

Sa˜o Paulo, Brazil, treatment of retinoblastoma, 354

Serine/threonine kinase system, uveal melanocytes interaction, 199

Singapore, treatment of retinoblastoma, 354

Somatic mutations, uveal melanoma, 83–92 cytogenetics, 83–87

gain of 8q, 85 monosomy of 3, 84–85

gene expression alterations, 87–92 angiogenesis, 89–90

apoptosis, 88–89

cell cycle regulation, 87–88 invasion, 90–92 metastasis, 90–92 proliferation, 87–88

loss of 1p, 86

other chromosomal abnormalities, 86 Spontaneously regressed retinoblastoma, 26

Index

Strabismus, as sign of retinoblastoma, 20 Structural alterations, uveal melanoma, 81–

102

T-cell proliferation, immunology, uveal melanoma, inhibition of, 257 Terminal cell cycle arrest, induction of, retinoblastoma protein, 136

Terminal differentiation by pRb, promotion of, retinoblastoma protein, 135–140

Therapy, uveal melanoma, 321–352 brachytherapy, uveal melanoma, 327–330 charged-particle radiotherapy, uveal

melanoma, 330–332

enucleation, uveal melanoma, 337–340 external-beam radiotherapy, uveal

melanoma, 334–335 extraocular involvement, uveal melanoma, 340–342

gamma knife, uveal melanoma, 332–334 laser therapies, uveal melanoma, 323–327 local tumor resection, uveal melanoma,

335–337

observation, for uveal melanoma, 322 radiotherapy, uveal melanoma, 327–335 thermoradiotherapy, uveal melanoma,

335

Therapy-induced mutations, second primary tumors in retinoblastoma patients, 118–119

Thermoradiotherapy, uveal melanoma, 335 Thermotherapy, uveal melanoma, 9–10,

323–327

Tissue plasminogen activator, uveal melanocytes interaction, 205 Tissue-specific genes, transcriptional

activation of, retinoblastoma protein, 139–140

Transgenic mice, retinoblastoma, 468–469 Transgenic mouse models of

retinoblastoma, attenuated herpes simplex virus, 484

Transgenic mouse, retinoblastoma, 472–479 Transpupillary thermotherapy

retinoblastoma, 362–364 complications, 363–364 history, 362 indications, 363

mechanism of action, 362 results, 363–364 technique, 363