index 567 [rd.springer.com]978-1-59259-323-1/1.pdf · amplification, 89 cyclin d1 expression, 16...

Index 567

Acetyl aminofluorene (AAF)

Aberrant methylation, 14–15, 20–22

Acetyl aminofluorene (AAF), 482

Activated carcinogensgenes, 48

Active ECM remodeling, 360Adenocarcinoma, 3

AIDS, 80histopathological and molecular

abnormalities, 21tmetastasis

CAM study, 243–249p53 immunostaining, 5f

AG3340, 353Ah-receptor-PAH complex, 47AIDS. see Acquired immune

deficiency syndrome (AIDS)Allele-specific mutations (ASM), 20Allelotyping lung cancer cell lines, 15Altered surface markers, 259–266Alternative G-protein coupling, 62Amine precursor uptake and

decarboxylase (APUD) cells, 66Angiogenesis, 269–270, 329–343, 391

568 Index

Anilinoquinazoline inhibitor, 540f

MAPK and JNK activity, 306fAnti-angiogenic factors, 269–270

AOEs, 211APC, 20Ape, 416fAPO-1, 259Apoptosis, 10, 48, 127–141, 259, 530

anti-Fas antibody-mediated,260–262

assays, 284–286chemotherapeutic drugs, 128D-Arg6, D-Trp7,9, NmePhe8-

substance P (6-11), 299–306factors, 270

prognostic relevance, 269–282growth summary, 311thistograms, 263fmeasurement

material, 300method, 302

morphological assessment,283–296

vs necrosis, 283–284rates, 529regulators

angiogenesis, 359–360

Index 569

gene alterations analysis, 413–434Basement membranes (BMs), 349

(bFGF), 269, 330–332, 335–336,

telomerase activity detection, 407BCE cell proliferation assay, 384

BJAB cellsanalysis, 262fhistograms, 263f

BleomycinKS, 79

Blockingnonspecific binding sites, 139

Blood supplytumor growth, 329

Blotting, 131Blue-light fluorescence

microscopy, 284BMs, 349Bombesin (BN) autocrine loop

GRP, 9BP. see Benzo[a]pyrene (BP)BPDE, 46–47

DNA-adducts, 49–50Bradford method, 139Bronchial epithelium

tissue microdissection technique, 8Bronchial tree

squamous cell carcinoma, 36–37Bronchioloalveolar carcinoma

CAM study, 243–249

570 Index

immunohistochemical staining, 472

Cell linegrowth profiles, 547

Cell lysates preparationraf-1 activity


Cell proliferation assayillustrated, 394fVEGF activity

material, 392–393method, 393–395

Cell-surface Fas proteinexpression, 259

analysis, 262fCellular density

change, 310Cellular prognostic factor analysis

case study, 271–276Central nervous system lymphoma, 76C-erbB-1, 114CGH studies, 9, 10Chemoresistance

EGFR, 128

Index 571

motility, migration, metastases, 116

Clara cell 10 kD promoters, 469–471.

motility, migration, metastases,

Comparative genomic hybridization

Cultured cellsmethod, 535fstainability


surgical material, 527–540CWR22R xenograft, 510–514CXC chemokines, 361Cyclin D1-CDK4-retinoblastoma

pathway, 11Cyclin-dependent kinase inhibitors

(CDKN), 89downregulation, 90

Cyclin-dependent kinases (CDK),89, 270

amplification, 89Cyclin D1 expression, 16Cyclins, 270Cyclooxygenase-2 (COX-2)

localization, 223tumor expressed factor, 340

Cyclooxygenase-2 (COX-2) proteinexpression

immunohistochemical analysis

572 Index

Cytosolic C-terminal domain, 113Differential splicing

RNA, 358Differentiation assays

growth summary, 311tDiscontinuous percoll gradient

programmed cell death pathways,309–324

DMBT1, 12DNA damage repair enzymes, 47–48DNA extraction

non RI protocolsmaterial, 232method, 234–235

DNA flippingphosphatidylserine, 284

DNA fragmentationagarose gel electrophoresis, 130f,

131–132chemosensitivity and apoptosis

of tyrphostin AC1478material, 134–135method, 137–138

DNA isolationras family mutation detection

Index 573

EGFR. see Epidermal growth factorreceptor (EGFR)

Elastase, 350tElectron microscopy

apoptosis determinationmaterial, 287–288method, 290–293

morphologymaterial, 287method, 290

Electrophoresisk-ras mutation detection

3, 194material, 192

ELISA, 66EMMPRIN (extracellular matrix

metalloproteinase inducer), 351Endogenous anti-angiogenic

molecules, 331tEndogenous pro-angiogenic

molecules, 331tEndostatin, 332Endothelial cell proliferation assay

angiostatin mobilization

574 Index

Epidermal growth factor receptor(EGFR), 113, 114–115, 127, 331

motility, migration, metastasis,

relationship to chemosensitivity

signal-transduction modulation,

structure, role in transformation,

tyrosine kinase inhibition, 115,

Epstein-Barr virus (EBV) infection, 76

Exon analysisBER

material, 428method, 431–432

Extracellular matrix (ECM), 349remodeling, 360VEGF, 358

Extracellular matrixmetalloproteinase inducer, 351

Extracellular SOD, 211

F

FACScan analysisFas assessment


Fas receptor, 259FFPE, 90FGF

vessel formation, 337–338FHIT, 12–13, 15, 23, 45, 231Fiber loading

hollow fiber assaymaterial, 548method, 550–554

Index 575

pyridyl)-1-butanone (NNK),

L-myc amplification detection,

Gastrin releasing peptide receptor

Genesactivated carcinogens, 48

Gene silencingpromoter methylation, 101–102

Genetic abnormalitiessequential development, 16–22

Genetically encoded programmedcell death, 259

Genetic alterations, 3–23Genetic changes, 44–46

accumulation, 18–19tumor-type specific, 15

Genetic damage repair, 43Genetic defects

multiplicity, 44Genetic factors, 466Genetic instability, 13–14Genetic-marker experiments,

520–521Genetic mutation

angiogenic switch, 334Genomic amplification, 107Genomic DNA preparation

NER-deficient mice, 487GFP

576 Index

of primary cultures, 529–530

HGF. see Hepatocyte growth factor(HGF)

H460-GRP SOI model, 463HHV-8, 77HIC (hypermethylated in cancer),

102High VEGF expression, 367Histochemical marker genes,

509–510, 521rationale for using, 508–509

Histological examinationCAM identification and

detection, 246, 247Histone deacetylases, 101HIV infection, 75Hollow fiber assay

cell count estimations, 561cell growth profiles, 560–561study design, 546


total protein/Western-blotanalysis, 561–562

Horseradish peroxidase (HRP)

Index 577

Human AP endonuclease (Ape), 416f

molecular epidemiology, 43–53Human herpes virus-8 (HHV-8), 77

Human plasminogen isolation and

Human umbilical vein endothelial

sensitive detection, 101–108

IL-8, 332IL-1β, 77IMB

flow chart, 173IGF axis

3, 179–180material, 175–176

Immune responsesangiogenic switch, 334

Immunoblottingraf-1 activity


Immunocompromised hostsneoplasm development, 75–76

Immunocytochemistryapoptosis determination


Immunohistochemical analysislocalization, 223–229

Immunohistochemical assays, 90γGCS

material, 214

578 Index

Immunohistochemical dual analysisDNA fragmentation, kTG, tTG

chemosensitivity and apoptosis oftyrphostin AG 1478, 128–132

Inhibitorsc-Met, 119–120γGCS


In situ hybridizationparaffin-embedded tissue

sections, 145–164TGF-β, 162fTGF-β preparation


TGF-β transcripts detectionmaterial, 150–151method, 155–157

Insulin-like growth factor (IGF), 167axis

changes, 170–172detection method, 170–172

BP-3 IMBCM, 175f

BP-rPs, 170BPs

characteristics, 169t

Index 579

JNK/MAPK activity measurement

K-ras mutation, 6, 16, 37, 466detection

enriched-PCR analysis, 105fKS, 75–80KSHV, 77kTG, 309

L

LacZ-tagged 3T3 cells, 509–510Ladder-like pattern, 13–14Large cell carcinoma, 3Large cell neuroendocrine cancer

histology, 33fLarge cell neuroendocrine cancer

(LCNEC), 34–35Laser capture microdissection

(LCM), 8–9LCM, 8–9LCNEC, 34–35LCR. see Ligase chain reaction

(LCR)Left lung, 462–463Leidenfrost effect, 249Lewis lung carcinoma (LLC-LM),

375–377

580 Index

Lewis lung carcinoma

Lung neoplasiaclassification, 31–36neuroendocrine differentiation,

31–36Lung section characterization

mutant p53material, 474method, 475

Lung tumorscancer cell lines

comparison, 6characterization, 472

Lung tumors chemical inductionXpc Trp53, 488

Lymphoblastoid cell lines, 5–7Lymphocyte function-associated

antigen (LFA-1), 243–249Lyophilization of conditioned

mediumIGF axis


LZ-CWR22R cells, 512fLZ-CWR22R clone H cells, 510–511

Index 581

Matrigel-suspended clone H cells, 512fMatrix metalloproteinase (MMP),

Matrix metalloproteinase-2 (MMP-2)

Methylationaberrant, 14–15, 20–22aberrant promoter, 44–45CDH13 gene, 15CpG islands, 15, 23

promoter, 15de novo, 101DNA, 14ECAD, 15markers, 101–102p16, 20p16 and MGMT, 107promoter

role, 44–45TIMP-3, 15

Methylation-specific PCR (MSP)p16 identification


web site, 107Methyl-guanine-DNA-

methyltransferase, 102Methylnitrosamino-1-(3-pyridyl)-1-

butanone (NNK), 468CC10/dnp53

582 Index

Microsomal epoxide hydrolase, 46–47

Mismatch-repair (MMR) pathway, 413

Matrix metalloproteinase

MSP. see Methylation-specific PCR(MSP)

MTT dye conversion assaymaterial, 549method, 559–560

MUC1expressionphotomicrograph, 257f

MUCI expression, 251–257Mucin-type glycoprotein expression

abnormalities, 251Multidrug resistance proteins

(MRP), 212Multiple molecular biological

technique, 146Multistage pathogenesis

sequential histologic andmolecular changes, 19f

Mutant-enriched PCR protocols, 107Mutant K-RAS genes, 22–23Mutant p53 mouse model

lung-specific expression, 465–477Mutant TP53 genes, 22–23Mutated in Multiple Advanced

Index 583

Neuroendocrine phenotype, 66–67Neuron-restrictive silencer factor

Non-Hodgkin’s lymphoma, 76HIV-AIDS, 82–83intermediate and high grade,

82–83Non-small cell lung cancer

(NSCLC)neuroendocrine features, 34–35pathogenesis, 17tvs SCLC, 31–36, 45

Northern analysisLLC-LM cells, 376

Northern-blot analysis, 146Northern blotting, 131NOS

tumor expressed factor, 340NSCLC. see Non-small cell lung

cancer (NSCLC)N-terminal extracellular ligand-

binding domain, 113Nucleotide-excision repair (NER)

deficient micechemically induced lung

cancer, 481–490pathway, 413

584 Index

EGFR signal transduction, 115

tumor-suppressor gene, 89–97, 102

histology and molecular studiesmutant mice


immunohistochemical proteinexpression, 6

immunostaining, 16lung tumor chemical induction

mutant micematerial, 486method, 488

lung tumor incidencemutant mice, 485t

missense mutation, 465–477molecular marker, 48mutations, 48–51

passive smoking, 51significance, 49–50smokers vs nonsmokers, 51smoking, 50–51

pathway, 466protein, 44transgene expression, 467ttumor suppressor gene, 44,

465–477

Index 585

animal model system, 441–451

primer sequence, 192t, 195f

PCR-RFLPnon RI protocols


PD-ECGF. see Platelet-derivedendothelial cell growth factor(PD-ECGF)

PDGF, 332. see Platelet-derivedgrowth factor (PDGF)

vessel formation, 337–338PDGFR, 117PDTC

MO73 cells, 116PEP

hypermethylated p16 allelesmaterial, 103method, 106

Phosphatidylinositol 3-kinase, 115,119, 127

PhosphorylationEGFR, 128

Plasminogen activator, 335Plasminogen activator inhibitor-1

(PAI-1), 358

586 Index

Polyacrylamide gel electrophoresis

Polycyclic aromatic hydrocarbons

Polymerase chain reaction (PCR).

IHC staining patterns, 91t, 92f

Probing blotsIGF axis


Probing Western blotkTG, tTG, anti-PARP antibody


Prognostic factorspurposes, 276–277

Programmed cell death, 10, 127–141.see also Apoptosis

chemotherapeutic drugs, 128genetically encoded, 259growth summary, 311ttyrphostin AG 1478, 128

Proliferation cell nuclear antigen(PCNA), 270, 472

Proliferation ratesin vivo and primary cultures, 529f

Proliferative and vascularpermeabilization activities

VEGF, 391–397Proliferative factors, 270–271

Index 587

Pulmonary carcinoid tumors, 33–34

Pyrrolidine dithiocarbonate (PDTC)

Radioactively labeled ligand probes

RB, 44overexpression, 97and p16

IHC staining patterns, 91t, 92fphosphorylation

catalysis, 89protein

G1-S progression, 11p16 tumor-suppressor pathway

abrogation, 89–97Reactive oxygen species (ROS),

113, 211c-Kit, 116c-Met, 119EGFR, 114–115JNK activation, 299

Receptor tyrosine kinase (RTK)role, 113–120

Recessive oncogenes, 10–11Reed-Sternberg cells, 83Regional hypermethylation, 14–15Retinoblastoma gene, 89Retinoic acid receptor-β (RAR-β),

20, 102Reverse transcription polymerase

588 Index

Reactive oxygen species

Reverse transcription

Small cell lung cancer

electrophoresis (SDS-PAGE)Selective Tumor gene Expression of

Peptides essential for Survival

SHCEGFR signal transduction, 115

Shortest regions of overlap(SROs), 231

Short-tandem DNA repeats, 13–14Signal transduction

c-Kit, 117c-Met, 119EGFR, 115

Signal transduction-promotingapoptosis, 62

Single transmembrane α helix, 11316-cyclin D1-CDK4-retinoblastoma

pathway, 11Small cell lung cancer (SCLC), 3, 35

cellular morphology, 32histology, 33fhistopathological and molecular

abnormalities, 21tneuroendocrine phenotype, 61–68vs NSCLC, 31–36, 45pathogenesis, 17tproliferation assay


Index 589

Solid tumor cell culture, 533–534

histopathological and molecular

Subcutaneous implant models, 457Substrate gel electrophoresis

angiostatin mobilizationregulation

material, 378–379method, 381

Superoxide dismutase (SOD),119, 211

Surfactant protein C (SP-C), 469Surgical material cultures

culturematerial, 531method, 533–534

drug treatmentsmaterial, 532method, 534–535

endpointsmaterial, 532method, 535

plate setupmaterial, 532method, 534

preparation

590 Index

intravenous implantation, 501–502

(telomeric repeat amplification

TGF, 331TGF-α, 114TGF-β. see Transforming growth

factor-β (TGF-β);Transforming growth factor-β(TGF-β)

ThalidomideKS, 79

3H-thymidine, 529–5303H-thymidine incorporation assay

chemosensitivity and apoptosisof tyrphostin AG1478


Thrombospondin, 332Thymidine, 529–530Thymidine incorporation assay

chemosensitivity and apoptosisof tyrphostin AG1478


Thymocytesglucocorticoid-induced death, 132

Index 591

inhalation systems smoke, 450

animal model system, 441–451

Tobacco smoke carcinogen-induced

TP53 gene, 11, 16, 49–50, 231abnormalities, 16heterozygous condition, 483mutations, 6TSG product, 10

TransfectionFas assessment

efficiency, 265material, 260–261method, 262–264

Transformationstructure and expression

c-Kit, 115–116c-Met, 117–120EGFR, 114

Transforming growth factor(TGF), 331

Transforming growth factor-α(TGF-α), 114

Transforming growth factor-β(TGF-β)

hybridization probesmaterial, 148–150

592 Index

Transmission electron microscopy

amplification protocol) assay

TRAPeze telomerase detection kit

Trp53 heterozygous condition, 483

Tumor growthassessment

animal models, 462–463Tumor heterogeneity

microenvironment, 337Tumor incidence

control data summary, 446tTumor multiplicities

control data summary, 445tTumor necrosis factor-α (TNF-α), 77Tumor-progression model, 519–520Tumor-specific metastasis

reporter gene-tagged tumor cells,507–521

Tumor-suppressive genes (TSGs),11–12

HIV-AIDS, 81Tumor vessels

formationmechanisms, 335

macrostructure andmicrostructure, 336–337

TUNNEL (terminaldeoxynucleotidyltransferase-mediated nick-end labeling)

Index 593

Upstream stimulatory factor (USF), 67

Vascular endothelial growth factor(VEGF), 269, 330, 335–336

Vascular permeability assayillustrated, 396fVEGF activity


Vascular permeability factor (VPF).see also Vascular endothelialgrowth factor (VEGF)

VEGF activity, 392–397Vasopressin, 63VCAM-1, 243–249VEGF. see Vascular endothelial

growth factor (VEGF)VEGFR-1

vessel formation, 337–338VEGFR-2

vessel formation, 337–338VG1 immunoreactivity, 362VHL, 13Vinblastine

KS, 79VLA-4, 116VLA-5, 116Von Hippel-Lindau (VHL), 13

594 Index

kTG, tTG, anti-PARP antibodyXpc mutant mice, 482

breeding and genotypingmaterial, 483–485method, 486–488

lung tumor chemical inductionmaterial, 486method, 488

Xpc Trp53 double mutant mice, 483Xpc Trp53 mutant mice

breeding and genotypingmaterial, 483–485method, 486–488

histology and molecular studiesmaterial, 486method, 488–489

lung tumor chemical inductionmaterial, 486method, 488

lung tumor incidence, 485tXPD genes, 48X-ray crystallography

recombinant MMP, 353XRCC1 genes, 48

Z

index 567 [rd.springer.com]978-1-59259-323-1/1.pdf · amplification, 89 cyclin d1 expression, 16...

Documents