INDEX

Note: Page numbers followed by “f ” indicate figures, and “t” indicate tables.

AAcute coronary syndromes (ACS), 47–49

Acute myocardial infarction (AMI), 45–47

Adipokines

adiponectin, 83

HOMA, 80

leptin, 83–84

markers and inflammatory molecules/

mediators, 80, 81t

peroxisome proliferator-activated

receptors, 85

resistin, 84

visfatin, 84–85

AdnaTest BreastCancer, 194–195

AmpliGrid, 202

Anticancer therapy, 55–57

Arrhythmias, 54–55

BBreast cancer

CTC (see Circulating tumor cells (CTC))

early, 207–208

metastatic, 208–209

B-type natriuretic peptide (BNP)

bioactivity, 4, 6f

BNP1–32

antiremodeling effect, 8–9

chronic subcutaneous

administration, 8–9

degradation, 4, 6f

GC-A agonist, 8

nesiritide, 8

BNP3–32 and BNP5–32, 9–10

clinical implications, 25–26

corin (see Corin)

functional deficiency, 3

NT-proBNP1–76, 7–9

paradox, 11

precursors, 3

preproBNP1–134 amino acid

sequence, 4, 5f

ProBNP1–108

clearance rate, 20–21

glycosylated/nonglycosylated

processing, 20–21

His-tag processing, 19–20, 21f

O-linked glycosylation, 21–25, 23f

sensitive biomarker, 10

propeptide convertases, 11–12

signal peptide, 4–7

utility, 3

CCardiac troponins

assays

enzyme immunoassay, 38–39

preanalytical factors, 41

principle of test, 39

standardization, 42–43, 42f, 43f

ultra-/high-sensitivity assays, 39

biologic variability, 57–59, 58f, 58t

cardiac myofibrillar apparatus, 35

complex function, 36, 37f

isoforms, 36–37

posttranslational changes, 38

proteins, 35

proteolysis, 38

TnT (see Troponin T (TnT))

Cardiovascular diseases

BNP (see B-type natriuretic peptide

(BNP))

myocardial damage diagnosis (see Cardiac

troponins)

CellSearch, 192

Chemokine (C–C motif ) ligand 2

(CCL2), 89

Circulating tumor cells (CTC)

enrichment/isolation methods

AdnaTest BreastCancer, 194–195

affinity-based chip (CTC-chip), 193

CAM, 195

CellSearch, 192

DEP chip, 193–194

deterministic hydrodynamic flow, 193

225

226 Index

Circulating tumor cells (CTC) (Continued )

Dynabeads, 191

EasySep, 191

electrical biosensor, 196

epithelial tumor cell isolation, 188

Ficoll-Hypaque, 189, 189f

flow-based immunomagnetic

detection, 192

fluid biopsy, 196

iCeap, 196–197

magnetic activated cell sorting,

190–191

microvortex-generating

herringbone-chip, 193

NV1066, 195–196

OncoQuick, 189–190

RosetteSep, 191–192

screencell isolation, 188–189

size-based microfluidic separation, 194

identification of

cytometry (see Cytometry)

qRT-PCR, 199–200

RT-PCR, 199

markers, 205–206, 206t

metastasis

arrest in distant organs, 185

circulation, 184–185

clones formation, 176

colonization, 186

epithelial-mesenchymal transition,

181–182

extracellular matrix, local invasion,

178–180

hematogenous pathway, 178, 179f

intravasation, 183–184

invadopodia, 182–183

linear progression model, 176, 177f

metastatic dormancy, 186

parallel progression model, 176, 177f

tumor cell dissemination, 177–178,

178f

tumor cell migration, 180–181

tumor self-seeding, 177

molecular and genetic characterization

AmpliGrid, 202

array CGH, 202

CGH, 201–202

FISH, 200–201

IHC, 200

ISH (see In situ hybridization)

microarray, 204–205

multimarker quantitative real-time

RT-PCR, 202

Collagen matrix adhesion assay (CAM), 195

Colorectal cancer/carcinoma (CRC), Reg

proteins

abnormal expression of, 160

anti-apoptosis factor, 161

cell growth, 160

metastasis and invasion, 160–161

in precancerous lesions, 160

Comparative genomic hybridization

(CGH), 201–202

Corin

animal models, 15–16

human corin

expression and circulating levels, 15

gene structure, 12, 13f

human disease states and gender

differences, 17–19, 20t

protein localization, 13

SNP, 16–17

mRNA expression, 12

proBNP processing, 13–14

protease inhibitors, 14

role, 13

soluble corin, 14

CTC. See Circulating tumor cells (CTC)

Cytokeratin-18 (CK-18), 102–103

Cytometry

automated microscopic system, 198

EPISPOT, 198

FAST, 197

LSC, 198

DDEP chip, 193–194

Deterministic hydrodynamic flow, 193

Dilated cardiomyopathy, 53

Dynabeads, 191

EEasySep, 191

Electrical biosensor, 196

Epithelial immunospot technique

(EPISPOT), 198

227Index

Epithelial tumor cell isolation, 188

Esophageal cancer, Reg proteins

diagnosis of, 158

treatment and prognosis, 158

FFiber-optic array scanning technology

(FAST), 197

Fibrosis, hepatic

cytokines

cytokeratin-18, 102–103

transforming growth factor beta, 102

diagnostic panels, 103–104

indirect markers of

ActiTest, 97

AST/ALT ratio, 95–96

AST to platelet ratio index, 96

FIB-4 index, 96

FibroIndex, 96

FibroMeter, 96–97

FibroTest/Fibrosure, 97

Hepascore, 97

PGA index, 96

Steatotest, 97–98

matrix degradation

matrix metalloproteinase-2 and

MMP-9, 101

TIMP-1 and TIMP-2, 101

matrix deposition

chondrex, 100

hyaluronic acid, 99–100

laminin, 99

procollagen type I carboxy-terminal

peptide, 98

procollagen type III amino-terminal

peptide, 98–99

type I and IV collagens, 99

Ficoll-Hypaque, 189, 189f

Fluid biopsy, 196

Fluorescence in situ hybridization (FISH),

200–201

GGastric adenocarcinoma, Reg proteins

cancer cell growth and metastasis, 159

gastritis, 158–159

serum test and drug resistance, 159

HHeart failure (HF), 53

Hepatocellular carcinomas, Reg

proteins, 163

Homeostatis model assessment (HOMA), 80

Hypertrophic cardiomyopathy (HCM), 54

IImmunohistochemistry (IHC), 200

In situ hybridization

CTCscope, 203

Quantigene ViewRNA system, 204

RNAscope, 203–204

Intact CTC enumeration and analysis

procedure (iCeap), 196–197

Invadopodia, 182–183

LLaser scanning cytometer (LSC), 198

Liver disease. See Nonalcoholic

steatohepatitis

Liver function tests

alanine aminotransferase and aspartate

aminotransferase, 78–79

alkaline phosphatase, 79

bilirubin, 79–80

ferritin, 79

gamma-glutamyl-transpeptidase, 79

MMagnetic activated cell sorting, 190–191

Metastatic dormancy, 186

Microarray

multiplexed PCR-coupled liquid bead

array, 205

Pico profiling, 204–205

Microvortex-generating

herringbone-chip, 193

NNesiritide, 8

Nonalcoholic steatohepatitis (NASH)

adipokines

adiponectin, 83

HOMA, 80

leptin, 83–84

228 Index

Nonalcoholic steatohepatitis (NASH)

(Continued )

markers and inflammatory molecules/

mediators, 80, 81t

peroxisome proliferator-activated

receptors, 85

resistin, 84

visfatin, 84–85

clinical and diagnostic approach, 76–77

cytokines and inflammation biomarkers

CCL2, 89

C-reactive protein, 89–90

fibroblast growth factor, 88

IL-6, 87

IL-8, 87–88

NF-kB and JNK, 89

TNF-a, 86–87toll-like receptor 4 complex, 89

fibrosis

CK-18, 102–103

diagnostic panels, 103–104

direct markers of, 98–101

indirect markers of, 95–98

TGF-b, 102genetic modifiers and novel markers,

104–106

hispanics vs. whites, 70–71

hyperlipidemia, 70–71

liver function tests

ALP, 79

ALT and AST, 78–79

bilirubin, 79–80

ferritin, 79

GGT, 79

oxidative stress markers

antioxidant markers, 91–92

iron metabolism, 93–94

lipid peroxidation markers, 90–91

nitrosative stress markers, 93

8-OHdG, 92–93

plasma protein carbonyl, 92–93

pathogenesis and histological features

elevated circulating insulin levels, 72–75

fat accumulation, 72–75

hepatocyte inflammation, 72–75

intralobular inflammation, 72–75

lipid peroxidation, 72–75

lipotoxicity, 72–75

microvesicular steatosis, 72–75

necrotic inflammation, 72–75, 75f

oxidative stress, 72–75

reactive oxygen species, 72–75

prevalence of, 70–71, 71f

secondary causes of, 70–71, 72t

OOncoQuick, 189–190

Oxidative stress markers

antioxidant markers, 91–92

iron metabolism, 93–94

lipid peroxidation markers, 90–91

nitrosative stress markers, 93

8-OHdG, 92–93

plasma protein carbonyl, 92–93

PPancreatic cancer, Reg protein

diagnostic applications of, 162–163

dysregulation, 162

Pancreatitis, Reg protein, 161–162

Physical separation methods, free thyroid

hormone

advantages, 143

derivatization vs. nonderivatization, 143

disadvantages, 143

equilibrium dialysis, 139–140, 142t

ion suppression, 142–143

ultrafiltration methods, 140–141, 142t

Prothrombin, GGT, and Apolipoprotein-A1

(PGA) index, 96

Pulmonary artery

embolism, 51–52

hypertension, 52–53

RRegenerating gene (Reg) protein

in digestive system

CRC, 160–161

distribution of, 156, 156f

esophageal cancer, 158

gastric adenocarcinoma, 158–159

hepatocellular carcinomas, 163

in pancreatic cancer, 162

in pancreatitis, 161–162

Reg4 distribution patterns, 156

signaling pathways, 163–165

229Index

expression of, 157, 157f

structure of, 155–156

types, 155, 155t

Resistin, 84

RosetteSep, 191–192

SScreencell isolation, 188–189

Single-nucleotide polymorphism

(SNP), 16–17

Size-based microfluidic separation, 194

TThyroid disease

free thyroxine (FT4) measurement

binding protein, 133–134

clinical usage, 144

drugs, 137–138

genetic abnormalities, 138

heterophile and autoantibodies, 138

inaccurate measurement, 144–145

inverse log-linear relationship, TSH,

129–131, 130t, 131f

nonthyroidal illness, 136–137

one-step assays, 132–133

physical separation methods

(see Physical separation methods, free

thyroid hormone)

pregnancy, 134–136

renal failure, 136

standardization, 143–144

two-step assays, 133

free triiodothyronine (FT3) measurement

binding protein, 133–134

drugs, 137–138

inaccurate measurement, 144–145

nonthyroidal illness, 136–137

one-step assays, 132–133

physical separation methods

(see Physical separation methods, free

thyroid hormone)

pregnancy, 134–136

renal failure, 136

two-step assays, 133

total thyroxine (TT4) measurement, 132

total triiodothyronine (TT3), 131–132,

144–145

TSH (see Thyroid stimulating hormone

(TSH))

Thyroid stimulating hormone (TSH)

inverse log–linear relationship, FT4,

129–131, 130t, 131f

and T3, 131–132

Transforming growth factor beta (TGF-b),102

Troponins. See Cardiac troponins

Troponin T (TnT)

anticancer therapy, 55–57

arrhythmias, 54–55

cardiomyopathies, 53–54

heart failure, 53

myocardial necrosis

ACS, 47–49

AMI, 45–47

causes, 45, 46t

coronary artery bypass grafting, 45

diagnosis, 44

differential diagnosis, 49–50

high-sensitive assays usage, 51

percutaneous coronary intervention,

44–45

stent thrombosis, 45

pulmonary artery embolism, 51–52

pulmonary artery hypertension, 52–53

Tumor cell

dissemination, 177–178, 178f

migration, 180–181

Tumor necrosis factor-alpha (TNF-a),86–87

Tumor self-seeding, 177

UUltrafiltration methods, 140–141, 142t

VVisfatin, 84–85