Handbook of Animal Models and its Uses in Cancer Research

Preface
Contents
About the Editors
Contributors
Part I: Animal Models for Cancer Research
1 Importance of Animal Models in the Field of Cancer Research
Introduction
Animals in Research: Past and Present
Biological and Medical Research Involving Animals During the Early Twentieth Century
Animal Models Concept
Tumor Xenograft Animal Model
What Does Research Involving Animals Consist Of?
Do Researchers Use Any Species of Animal in Their Research?
The Mouse
The Rat
The Rabbit
Zebra Fish
Birds
Armadillo
Guinea Pigs
Amphibians and Reptiles
Hamsters
Gerbils
Chinchillas
Research on Animals: What Are They Used For?
Why Is There a Need to Use Animals?
What Are the Advantages of Employing Animals in the Study, and How Does Animal Research Assist Animals?
What Are the ``Animal Rights´´ Issues?
Animal Use in Research: Ethical Concerns
Alternatives to Animal Research
Conclusion and Perspective
References
2 Cancer Study: Cell to the Animal Models
Introduction
Proteomics of Cancer Stem Cells, Molecular Pathways, and Epithelial-Mesenchymal Transition (EMT)
Proteomics of Cancer Cells and Microsatellite Instability
Genomics and Cell Lines for Animal Models and Genetic Modification Technologies in Cancer Models
Cell Line-Derived Mouse Cancer Models
Patient-Derived Tumor Xenografts (PDTXs) in Cancer Models
Experimental Models and Nanotechnologies
Conclusions and Perspectives
References
3 Animal Models for Cancer Research: The Choice of the Right Model System
Introduction
Alternative Model Systems
In Silico Model Systems
In Vitro Model Systems
In Vivo Model Systems
Types of Animal Models
Ethics in Animal Experimentation
The Best Model Decision Algorithms of a Cancer Researcher
Conclusion
References
4 Cellular Interactions Networking in Interactive Models of Diseases
Chapter Learning
Introduction
Disease Biology: Noncommunicable/Communicable/Metabolic Syndromes
Causative Analysis; Etiology of Disease Immunopathogenesis, Molecular Events, Cellular Events
Profiling and Diagnostic Approaches in Disease Biology: Experimental/Computational/Mathematical
Experimental Profiling
Computational Profiling
Multifactorial/Combinatorial Designs in Disease Diagnostics/Prognosis and Interventions
Interactome: Molecular Niche
Physical and Functional Interactions
Network of Networks
Drafting Interactome Networks
Network Biomarkers
Interaction Networks and Dynamic Network Biomarkers
Interactome Network Types
Gene Regulatory Networks
Metabolic or Protein: Protein Interactome Networks
Metabolic Networks
Designing Interactome Networks with Cellular Networks
Transcriptome: Interactome Profiling Networks
Phenomics: Phenotype Profiling Networks
Gene Interaction Networks
Conclusion and Perspectives
References
5 Mice as Experimental Models for Cancer Research
Introduction
Strategies Adopted for Developing Different Types of Cancer in Mouse Model
The Transplanted Cancer Models
The Genetically Engineered Models (GEM)
Induced Cancer Model
Gene-Targeting Technology
RNA Silencing Techniques with RNA Interference (RNAi) or Artificial MicroRNAs (amiRNA)
Different Carcinogens Used for Inducing Different Types of Cancer
Primary Cancer Models for Studying Cancer of Different Organs
Brain Cancer
Retinoblastoma Cancer
Blood Cancer or Leukemia
Lung Cancer
Breast Cancer
Esophageal Cancer
Pancreatic Cancer
Liver Cancer
Colon Cancer
Prostate Cancer
Cervical Cancer
Skin Cancer
Conclusion
References
6 Use of Stem Cells on Animal Model of Cancer Research
Introduction
Types of Stem Cells in Current Research
Embryonic Stem Cells [ESCs] with Induced Pluripotent Stem Cells (iPSCs)
Neural Stem Cells (NSCs)
Mesenchymal Stem Cells (MSCs)
Hematopoietic Stem Cells (HSCs)
Cancer Stem Cells (CSCs) and Animal Models in Cancer Research
Cancer Stem Cell Models
Drosophila Models
Stem Cells from Large Animals
Mouse Models
Zebrafish Models
Dog Models
Pig Models
Factors Influencing Novel Stem Cell Therapeutic Approach in Targeting Tumor Cells
Possible Stem Cell Therapies in Cancer Disease Models
Challenges in Usage/Implantation of Animal Models in Cancer Research
Conclusion and Future Directions
References
7 Role of Animal Models in the Development of Bacteria-Based Live Therapeutics to Fight Cancer
Introduction
Bacteria in Cancer
Bacteria in Cancer Diagnostics
Bacteria as a Prognostic Marker in Detecting Cancer
Bacteria as Biosensor
Engineered Bacteria to Detect Inflammation
Bacteria in Imaging of Cancer
Diagnosis of Cancer Using Microbial DNA and RNA Signatures
Bacteria for Cancer Therapy
Tumor Elimination by Live Bacteria
Recombinant Bacteria as Cancer Theranostics
Tumor Colonizing Bacteria
Probiotics-Based Cancer Therapy
Designer Probiotics
Probiotics-Conjugated Nanoparticles
Conclusions
References
8 Repurposing of Drug: Utility of Animal Models
Introduction
Purpose of Drug Repositioning
Methods of Drug Repositioning
Drug Repositioning in Animal Models
Recent Developments in Drug Repurposing
Repurposing Strategies
Genome
Phenome
Chemical Structures of Drugs
Drug Combinations
Repurposing Approaches
Machine Learning
Network Models
Validation Approaches
Possible Repositioning Alternatives
Cell Culture: An Alternative to an Animal Model
Challenges with Repositioning
Drugs Repositioned During the COVID Era
Conclusion
References
9 Zebrafish as an Animal Model for Cancer Research
Introduction
Zebrafish: A Metabolic Diseases Model
Cancer Model Establishment in Zebrafish
Mechanisms for Developing Cancer Models in Zebrafish
Transplantation of Tumor Cells in Zebrafish
Tumor Angiogenesis in Zebrafish
Tumor Metastasis in Zebrafish
Zebrafish Cancer Model in Drug Discovery
Compound Administration and Pharmacokinetics
Conclusion
References
10 Contribution of Zebrafish in Cancer Research: Tiny but Not Trivial
Introduction
Screening of Cancer Using Zebrafish Model
Transplantation of Cancer Cell Lines Via Allograft and Xenograft
Transgenic and Mutant Zebrafish as Cancer Research Model
Identification and Screening of Novel Cancer Molecular Markers and Therapeutic Approaches Using Zebrafish Model
Demerits of Zebrafish as a Cancer Research Model
Conclusion
References
11 Bioreactor-Based Tissue Models as an Alternative Approach in Cancer Research
Introduction
Main Text
Spinner Flask Bioreactor Systems
Perfusion Bioreactor Systems
Rotary Cell Culture Systems (RCCS)
Spheroids
Organoids
Microfluidic Chips
Cell Cultures and Genome Editing in Cancer
Conclusion
References
12 Animal Model of Human Cancer: Malignant Lymphoma/Colon Cancer/Lung Cancer/Liver Cancer/Brain Tumors/Skin Cancer
Introduction
Fundamental Animal Models in Cancer Research
Malignant Lymphoma
Colon Cancer
Lung Cancer
Liver Cancer
Brain Cancer
Melanoma of Skin Cancer
Conclusion
References
13 Animal Models in Cancer Research: Breast Cancer
Introduction
Murine Models
Chemically Induced Models
Transplanted Tumors Models: Cell Line-Derived Xenografts/Patient-Derived Xenografts
Radiation-Induced and Genetically Engineered Models
Genetically Engineered Mice Models (GEMM)
In Silico Models
In Vivo/in Vitro Models of Metastasis 2D/3D and Chemoresistance
Canine and Feline Models
Comparative Canine Mammary Tumor (CMT)
Comparative Feline Mammary Tumor
Conclusions
References
14 Animal Models for Bone Metastasis Study
Introduction
Remodeling of Bone Is a Tightly Regulated Process
Formation of Bone Metastases in Different Types of Cancer
Bone Metastases in Breast Cancer
Bone Metastases in Lung Cancer
Bone Metastases in Prostate Cancer
Bone Disease Observed in Multiple Myeloma
Techniques to Induce Bone Metastasis in Model Organism
Systemic Dissipation of Tumor Cells
Orthotopic Injection into Primary Tumor Site
Direct Injection into Bone
Transgenic and Chemical Induction
Animal Models of Bone Metastasis
Rodent Models of Bone Metastases
Rabbit Model of Bone Metastases
Cat and Dog as a Model of Bone Metastases
Conclusion
Imaging Techniques to Investigate Bone Metastasis
Bioluminescent Imaging of Bone Metastases
Fluorescent Imaging of Bone Metastases
High-Resolution Radiography of Bone Metastases
Micro-Computed Tomography of Bone Metastases
Micro-Positron Emission Tomography and Micro-Single-Photon Emission Tomography
Therapeutic Interventions to Prevent Bone Metastasis
Radiotherapy in Treatment of Bone Metastases
Radiopharmaceuticals in Treatment of Bone Metastases
Bisphosphonates in Treatment of Bone Metastases
Pamidronate
Zoledronic Acid
Ibandronate
Denosumab
Candidate Molecules with Potential to Act Anti-osteolytic
Conclusion
Limitations and Future Prospective
References
15 Available Preclinical Tools for Neuroblastoma
Introduction
Mouse Models of NB
Zebrafish Models for NB
Chick Chorioallantoic Membrane (CAM) Model of NB
Concluding Remarks
References
16 Animal Models in Cancer Research
Introduction
Murine Models in Cancer Research
Transplantation Murine Models
Autochthonous Murine Models
Genetically Engineered Murine Models
Humanized Murine Models
Zebra Fish as a Model for Cancer Investigations
Zebra Fish in Cancer Research
Transplantation Models
Genetic Model of Cancer in Zebra Fish
Gene Disruption Using Chemical Mutagens
Transgenic Zebrafish
Ectopic Expression of Targeted Gene in the Embryo
Genome Editing in Zebra Fish
Zebrafish Models in Drug Discovery
Limitations to the Use of Zebrafish
Fruit Fly as an Animal Model for Cancer Research
Cancer in Drosophila
Cancer Research with Higher Animals
Conclusion
References
17 Animal Models of Gynecological Cancers
Introduction
Ovarian Cancer
Animal Models to Study Different Types of Ovarian Cancer
Syngeneic Mouse Models of Ovarian Cancer
Applications of Syngeneic Mouse Models
Challenges and Limitations of Syngeneic Mouse Models
Patient-Derived Xenograft Models of Ovarian Cancer
Applications of Patient-Derived Xenograft Models
Challenges and Limitations of Patient-Derived Xenograft Models
Specialized Mouse Models of Ovarian Cancer
Applications of Genetically Engineered Mouse Models
Challenges and Limitations of Genetically Engineered Mouse Models
Humanized Mouse Models of Ovarian Cancer
Endometrial Cancer
Animal Models to Study Different Types of Endometrial Cancer
Rodent Models of Endometrial Cancer
Transgenic Mouse Models of Endometrial Cancer
Patient-Derived Xenografts (PDXs) of Endometrial Cancer
Conclusion
References
18 In Vivo, Ex Vivo, and In Vitro Model Systems for Liver Cancer Research
Introduction
Diagnosis and Staging of HCC
Imaging Techniques
Detection of HCC
Biopsy and Histopathology
Staging of HCC
Serum Tumor Markers for Detection of HCC
In Vitro Model Systems of HCC
Primary Human Hepatocytes
Liver-Derived Cells
Stem Cell-Derived Liver-Like Cells
In Vivo Experimental Models of HCC
Rat Experimental Models
Mouse Experimental Models
Syngeneic and Xenograft Experimental Models
Genetically Modified Experimental Models
Zebrafish Liver Cancer Experimental Model
Woodchuck Experimental Model
Chick Embryo Model
Ex Vivo Models in Liver Cancer Research
Conclusion
References
19 Animal Models for Prostate Cancer Research: A Mechanistic Outlook on the Challenges and Recent Progress
Introduction
Animal Models of Prostate Cancer; the Challenges
Purposefulness of Animals Models in Prostate Cancer Research
Animal Models to Understand the Stages of PCa Development
Benign Prostatic Hyperplasia
Prostatic Intraepithelial Neoplasia
High-Grade Prostatic Intraepithelial Neoplasia
Prostate Adenocarcinoma
Animal Models for Studying Aggressive Phenotypes of Prostate Cancer
Development of Castration-Resistance of Prostate Cancer
Metastasis
Transgenic Models (Mice)
Xenograft Models of Rat Origin
Xenograft Models Canine Origin
Multipurpose Animal Models to Study Prostate Cancer
Key Signaling Pathways Associated with Molecular Pathogenesis of Prostate Cancer
PI3K/Akt/mTOR Pathway
RTK/ERK Pathway
TGFβ Pathway
Wnt Pathway
AR Signaling Pathway
Conclusion and Future Perspectives
References
20 Animal Models for Angiogenesis on Cancer Research
Introduction
Tumor Angiogenesis/Angiogenic Switch
Animal Models Used in Angiogenesis Study
Rodent and Mice as a Model
Corneal Micro-pocket Assay
Rodent Mesentery Angiogenesis Assay
Dorsal Air Sac Model
Disk Angiogenesis System
Sponge Implant Assay
Chamber Assay
Chick
Chick Chorioallantoic Membrane (CAM) Assay
The Chick Embryo Aortic Arch Assay
Zebrafish
Xenopus Tadpole
Drugs for Angiogenesis
Limitations
Conclusion and Future Direction
References
21 Genetically Engineered and Spontaneous Animal Model: Utilization in Preclinical Cancer Therapy Development
Introduction
Genetically Induced Cancer Models
CRISPR-/Cas-Mediated Zebrafish Cancer Models
Transgenic Zebrafish as Cancer Model
Advantages of Genetically Engineered Models over Xenografts
Spontaneous Models
Large Animal Models in Spontaneous Cancer Research
Conclusion and Future Perspectives
References
22 DEN-Induced Hepatocellular Carcinoma in Animal Model
Introduction
Effects of Herbal Medicine Against DEN-Induced HCC
Curcumin
Terminalia arjuna
Annona squamosa
Tinospora cordifolia
Bacoside A
Saffron
Luteolin
Leucas aspera
Graptopetalum paraguayense
Oldenlandia diffusa
Celastrol
Tetilla dactyloidea
Ajwa Dates, Phoenix dactylifera
Garcinia mangostana
Wedelia calendulacea
Cynanchum auriculatum (Baishouwu)
Echinacoside
Ginger
Cow Ark with Allium sativum
Conclusion
References
23 Chorioallantoic Membrane (CAM) and In Ovo Models as Potential Platforms for Testing Cancer Agents
Introduction
Practical Benefits of Patient-Derived Xenografts in Oncology
Focus of Studies Grafting Fresh Human Tumor Tissue on the CAM Angiogenesis
Concordance with the Parent Tumor
Micrometastasis
Assessment of Cancer Therapies
Embryo Survival and Take Rate
Tumor Heterogeneity in the CAM Model
Improving the Take Rate of Xenograft in the CAM Model for Different Tumor Types
The CAM Model of Metastasis
Angiogenesis of CAM Models
Using the CAM Model to Establish Ovarian Cancer PDX (Ovarian Cancer Patient-Derived Xenografts): A Case Study
CAM Procedure for Patient Samples: A High-Level Overview
The OC CAM Xenograft General Protocol
Incubation of Eggs
CAM Preparation
Fragments of OC Tumor Grafted on CAM
Ultrasound Scan Imaging of the CAM Xenograft
Ultrasound Using Three-Dimensional Power Doppler
The 3D Ultrasound Images Have Been Analyzed
PDX Tumor Harvesting and Storage
CAM-PDX and Histopathology
Conclusion
References
24 Engineering and Studying Syngeneic Animal Tumors and Large Animal Endogenous Tumor Models
Introduction
Canine Model
Lymphoma
Urothelial Carcinoma
Carcinoma of the Breast
Melanoma
Osteosarcoma
Immune Cells and Immunology of Canines
Cancer Vaccine
Immunotherapies
Mice Model Categories
Genetically Engineered Mouse Models (GEMMs)
Genetically Engineered Mouse Models of OSCC
Cell Line Derived Models
Xenografts
Patient-Derived Xenograft Model in Ovarian Cancer
Patient-Derived Xenograft Model in Prostate Model
Syngenic Models
Chemically Induced Mouse Model
OSCC Mouse Model Induced by 4NQO
Other Carcinogen-Induced Mouse Model
Humanized Mouse Models
Conclusion
References
25 Orthotopic PDX and CDX Mice Model for Cancer Stem Cell Research
Introduction
Primary Tumor Tissues or Cells
The Heterotopic and Orthotopic Implantation
Development of Next-Generation PDX and CDX Models in Humanized Mice
Hu-PBL Mouse Model
Hu-SRC Mouse Model
Hu-BLT Mouse Model
Usefulness of PDX and CDX Model in Cancer Research
Usefulness in Tumorigenesis Research
Usefulness in Preclinical Cancer Research
Evaluation of Novel Anticancer Drugs
Finding of Cancer Stem Cells and Cancer Biomarkers
Next Generation Humanized Mice
Generation of TME in Hu-PDX Mice for Cancer Immunotherapies
The Genetic-Modified T Cells Used in Humanized Mice
The Immune Checkpoint Blockade Therapy Using Humanized Mice
Use of Humanized Mice for NK Cells Therapies
Conclusions
References
26 Animal Models for Small Cell Lung Cancer Research: Current Status and Future Perspectives
Introduction
Small Cell Lung Carcinoma
Etiological Factors Leading to SCLC
Diagnosis of SCLC
Clinical Features
Different Stages of SCLC
Animal Model System for SCLC
Mouse Model System
Genetically Engineered Mouse Model System
Patient-Derived Xenografts
Cell of Origin of SCLC
Zebra Fish as Model System
Conclusion
Future Perspective
References
27 Melatonin Induced in Cancer as a Frame of Zebrafish Model
Introduction
Genetics
Zebrafish Tumors from Chemical Mutation
Mutant Lines of Zebrafish
Xenotransplantation
Angiogenesis
Transgenic Lines of Zebrafish
Role of Melatonin in Cancer
Conclusion
References
Part II: Application of Animal Models in Cancer Therapeutics
28 Role of Telomere and Telomerase Activator in Ageing and Cancer
Introduction
Telomere
Telomere Structure and Telomere Homeostasis
Factors Effecting Telomere Length Determination
Oxidative Stress
Reactive Oxygen Species
Oxidative Stress in Cancer and Aging
Telomere Length and Age
Aging-Related Genes and Their Roles
Aging-Related Diseases (ARD´s)
Modern Therapies and Animal Models Involved in Aging Research
Telomerase
Role of Telomerase Activator
Activation of Telomerase Activator
Telomerase activator and Telomere Length
Role of Telomere in Tumor Progression
In vivo Study on the Role of Telomere and Telomerase in Tumor Progression
Cancer Model in Animals
Animal Model for Colon Cancer
Animal Model for Pancreatic Cancer
Animal Model for Lung Cancer
Discussion
Consent for Publication
References
29 Genetics of Pancreatic Carcinogenesis: Current Molecular Insights from Animal Models
Introduction
Impulsive Cancer Animal Models
Chemically Instigated Animal Models
Transgenic Mouse Model of Pancreatic Cancer
KIC Model of PDAC
KPC Model of PDAC
KD Model of PDAC
PDAC Model with Kras (TGFBR2 Knockout)
TetO-Cre Induced by Tetracycline
Formation of Animal Models Based on Cell Lines
Cell Line Selection
Cell Metastasis and Colonization
Production of Tumor Cells
Subcutaneous/Orthotopic Xenografts
Subcutaneous Model
Orthotopic Model
Imaging of Xenograft Models
Diagnostic and Therapeutic Use of Animal Models of Improved PDAC
Conclusion
References
30 Optical Techniques for Treatment and Tissue Evaluation Using Skin Models for Preclinical Studies
Introduction
Animal Models
Healthy Skin
Skin Tumors
Chorioallantoic Membrane
Optical Treatments
Photodynamic Therapy
Photothermal Therapy
Damage Evaluation Techniques
Histology
Fluorescence
Ultrasound Image
Optical Coherence Tomography
Conclusion
References
31 Tumor Models of Retinoblastoma: In Vivo, Ex Vivo, and In Vitro Models
Introduction
Ex Vivo Models of Retinoblastoma
Patient-Derived Xenograft Models
3D Organoid Models
Tumorspheres
In Vivo Models in Rb
Estimation of Biomarkers of Rb in Various Models
Analysis of Biomarkers
Phosphoproteomics
Micro RNAs
Cell-Free DNA Analysis in Aqueous Humor
Genomic cfDNA Analysis of Aqueous Humor
Blood and Plasma Biomarkers
Proto-Oncoproteins: MDMX and MDM2
Tissue-Specific Biomarkers: Vascular Endothelial Growth Factor
Limitations and Future Perspectives
Current Therapeutic Modalities: Comparative Analysis of Models
Primary Treatments and Its Limitations
Noninvasive Therapy: Management for Early Intraocular Tumors
Chemotherapy
External Beam Radiotherapy (EBR)
Enucleation
Extraocular Management
Prerequisite for Animal Model Study
Conventional Therapies: Comparative Analysis of Models
Advanced Therapeutics
Gene Therapy
CAR-T Cell
Small Molecules
mAbs
Conclusion
References
32 A Study on the Role of Phytochemicals in the Preclinical Neuronal Cancer Model
Introduction
Phytochemicals Being Used in Current Cancer Therapy
Phytochemicals with Anticancer Properties in Preclinical and Clinical Stages
Capsaicin
Berries
Spinach
Aloe Vera
Phytochemicals Being Studied for Neuronal Cancer
Camellia nitidissima Chi (CNC)
Garcinia morella
Olive Leaf Extract (OLE)
Withaferin A (WA)
Luteolin
Zeaxanthin
Curcumin
Ginsenosides
Resveratrol
Quercetin
Vomifoliol
Andrographolide
Polymethoxy Flavones from Citrus
Tinospora cordifolia
Conclusion and Future Perspectives
References
33 Perspectives of Stem Cell Therapy: A Promising Therapeutic for Cancer Model and Alzheimer´s Disease
Introduction
Stem Cell Therapy for Cancer Model
Pluripotent Stem Cells (PSCs)
Adult Stem Cells (ASCs)
Cancer Stem Cells (CSCs)
Cancer Therapy Model Using Stem Cell Modifications
Stem Cell Tumor Therapies Applications
Medicine of Regenerative
Immunotherapy for Cancer
Cancer Target with CSCs
Screening and Selection of Anticancer Drugs
Alzheimer´s Disease (AD)
Pathogenesis of AD
Amyloid and Tau Hypotheses
Cholinergic Hypothesis
General Treatment for AD
AD and Stem Cell Therapies
Endogenous Repair
Exogenous Cell Therapy
ESCs
NSCs
MSCs
iPSCs
Stem Cell-Based Rehabilitation Challenges for AD Treatment
Guidelines for Stem Cell-Based Treatment
Immunotherapy for AD
Nanotechnology for AD
Gene Therapy for AD
Identifying Anti-Alzheimer Drug Contenders Via Computational Analysis
Conclusion
References
34 Animal Model of Inflammatory Bowel Disease Leading to Cancer and Role of Genetic Variation in Colitis-Associated Cancer
Introduction
Colorectal Cancer in Mouse Model
Mouse Models of Chemically Induced Colorectal Cancer
Transplant Model of CRC in Mice
Mouse Model of Inflammatory Bowel Disease
Chemically Induced Model of Inflammatory Bowel Disease
2,4,6 Trinitro-Benzene Sulfonic Acid (TNBS) Colitis
Dextran Sodium Sulphate-Induced IBD and IBD-Associated CRC
Oxazolone Colitis
Role of Genetic Variation in Mouse Model of Colitis-Associated Cancer
Introduction to the Genetics and Cancer Association
Hereditary Nonpolyposis Colorectal Cancer
MUTYH-Associated Polyposis
Hamartomatous Polyposis Syndrome
Genetic Variation in IBD-Associated Colorectal Cancer
Concluding Remark
References
35 Selected Methods for Toxicity Testing of Chemical and Biological Compounds Using Animals
Introduction
Toxicometry
Purpose, Scope, and Criteria for Toxicometric Studies
Purpose of Toxicometric Studies
Scope of Toxicometric Studies
Criteria for Toxicometric Studies
Stages of Testing
Acute Toxicity
Classical Procedure
Fixed-Dose Procedure
Acute Toxic Class Method
The Up-and-Down Procedure
Evaluation of Local Skin Irritation/Corrosion
Skin Sensitization Assessment
Short-Term (Subacute) Toxicity
Subchronic Toxicity
Chronic Toxicity
Classification of Chemicals
Conclusion
References
36 Terpenoids as Chemopreventive Agents and Their Interpretation in Animal Models and Human Clinical Trials
Introduction
Monoterpenes
Diterpenes
Triterpenes
Tetraterpenes
Sesquiterpenoids
Conclusions
References
37 Role of Animal Research to Understand the Prospects for Chemoprevention of Cancer
Introduction
Importance of Animal Models
Mouse Models in Cancer Research
Small Animal Models
Large Animal Models
Organ Site in Specific Animal Models
Conclusion
References
38 Stem Cell-Derived Exosomes: A Promising Therapeutic Role in Animal Models with Colorectal Cancer
Introduction
Biogenesis of Exosomes
Exosome Classification
Exosome Composition
Exosome Components
Exosomal Proteins
Noncoding Exosomal RNAs
MicroRNA
lncRNA
Circular RNA (circRNA)
Exosomal Source, Uptake, and Function
Exosome Isolation
Exosome Preservation and Storage
Exosome Characterization
Stem Cells
Colorectal Cancer Stem Cells
Stem Cell-Derived Exosomes
Exosomes from MSCs Generated from Adult Bone Marrow
MSC Exosomes Generated from the Umbilical Cord
Exosomes Produced by MSCs Generated from Adipose Tissue
Tumor and Stem Cell-Derived Exosomes
Angiogenesis
Growth of Tumors
Invasion and Metastasis
Role of Stem Cell-Derived Exosomes and CRC
Stem Cell-Derived Exosome Role in Animal Models with Colorectal Cancer
Conclusion
References
39 Experimental Model for Pancreatic Cancer and Its Therapeutic Implications in Clinical Research
Introduction
Opportunistic Risk Factors
Amendable Risk Factors
Unamendable Risk Factors
Pathology of Pancreatic Cancer
Molecular Pathways in Pancreatic Cancer
K-Ras Oncogene
P16/CDKN2A Gene
Tumor Protein P53 (p53)
SMAD4
Epidermal Growth Factor (EGF)
Insulin-Like Growth Factors (IGF)
Fibroblast Growth Factor (FGF)
Vascular Endothelial Growth Factor (VEGF)
Animals Models in Pancreatic Cancer
Rats
Hamster
Immune-Deficient Mice
Establishment of Tumorogenesis in Animal Model
Subcutaneous Xenograft Models
Orthotopic Xenograft Models
Genetically Engineered Models of Pancreatic Cancer
Ideal Animal Model for Clinical Aspects
Conclusion
References
40 Human Embryonic Stem Cells as a Therapy for Alzheimer´s Disease
Introduction
Pathogenesis and Proteinopathy of Alzheimer´s Disease
Stem Cell and Its Potency
Stem Cells in Alzheimer´s Disease
Human Embryonic Stem Cells
Human Embryonic Stem Cells: A Prospect in Targeting AD
Induction of Hippocampal Neurogenesis
Secreting Paracrine Factors: Role of Brain-Derived Neurotrophic Factor (BDNF)
Restoring Cholinergic Functions
Anti-hyperphosphorylation of Tau
Antiamyloidogenic Potential
Mitochondrial Biogenesis
Signaling Pathways Mediating hESCs Function
Wnt Signaling
References
41 Triple-Negative Breast Cancer (TNBC): Clinical Features and Therapeutic Targets
Introduction
Biological Warnings of TNBC
Epidemiology
Diagnosis and Treatment
Lumpectomy
Mastectomy
Radiation
Chemotherapy
Cytotoxic Treatment
Therapeutic Targets: At the Level of Gene
Immunotherapy
Treatment with Neoadjuvant
Breastfeeding and Triple-Negative Breast Cancer
Advanced Medications
Molecular Pathways of TNBC
Ras/MAPK Pathway
PI3K/AKT/mTOR Pathway
Models of TNBC
Transgenic Mouse Models (MMTV-PyMT)
Patient-Derived Xenografts (PDXs)
Genetically Engineered Mouse Models (GEMMs)
Conclusion
Reference
42 Therapeutic Molecular Targets of Cancer and Animal Models: Adequacy and Drawbacks
Introduction
Rodent Models in Oncology
Xenograft Mouse Model
Chemically Induced Rodent Model
Genetically Engineered Mouse Model
Therapeutic Molecular Targets of Cancer
Therapeutic Molecular Target for EGFR-Mutated Non-Small Cell Lung Cancer
Therapeutic Molecular Target for FLT3-ITD Mutation in Acute Myeloid Leukemia
Therapeutic Molecular Target for VEGF and mTOR Pathway in Renal Cell Carcinoma
Conclusions
References
43 Therapeutic Approaches and Models in Retinoblastoma
Introduction
Conclusion
References
44 Transmissible Animal Tumors as Models for Cancer Research
Introduction
Transmissible Cancers
Canine Transmissible Venereal Tumor (CTVT)
Devil Facial Tumor Disease (DFTD)
Clam Leukemia (CL)
Transplantable and Transmissible Tumors in Animal Models
Conclusion and Future Perspectives
References
Part III: Animal Models for Cancer Drug Discovery: Recent Advances
45 RNA Interference in Experimental Animal Models: Its Application in Cancer Research and Therapy
Introduction
RNA Interference
Cancer and RNAi
Gene Silencing Through siRNA and shRNA
Gene Silencing Through MicroRNAs
Animal Models
Various Models Used
Genes to Target
Delivery of RNAi In Vivo
RNAi and Cytotoxicity
Conclusions and Future Scope
References
46 Association of Animal Models in the Field of Translational Medicine: Prediction and Validation
Introduction
Validity of Preclinical Animal Research
Internal Validity
External Validity
Association of Internal and External Validity
How to Refine the Preclinical Animal Models
Conclusion
References
47 Detection of Tumors Through Fluorescence Conjugated Dye in Animal Model
Introduction
Cancer Research on Animal Model
Cancer Imaging and Targeting with Near-Infrared Dyes
Newly Developed NIR Dyes for Cancer Imaging
Recent Approaches to Create Multifunctional NIR Dyes with Cancer-Targeting Properties
Cancer Imaging and Targeting with NIR Dyes Coupled with Target Molecules
Nanoparticles with NIR Dye Embedded in Them for Cancer Targeting and Imaging
NIR Dyes Are Multifunctional and Native for Cancer Detection and Imaging
Bioluminescence Imaging (BLI) Technique
Conclusion
References
48 Recent Advances of Metal-Based Anticancer Agents and Their In Vivo Potential Against Various Types of Malignancies
Introduction
In Vivo Anticancer Activities of Platinum Complexes
Mechanism of Action of Platinum Complexes
In Vivo Anticancer Activities of Gold Complexes
In Vivo Anticancer Activities of Copper Complexes
Antitumor Activities of Ru, Pd, and Ir Derivatives
Conclusion
References
49 Mouse as a Preclinical Model for Studying Small Noncoding RNAs Involved in Colorectal Cancer
Introduction
Small RNA and Their Types
microRNA (miRNA)
Piwi-Interacting RNA (piRNA)
Small Interfering RNA (siRNA)
Transfer RNA-Derived Fragments (tRFs)
Small Nucleolar RNA (snoRNA)
Small RNA Associated with CRC
Mouse Model in CRC Research
Chemical Induced Mice Models
Peritoneal Model
Xenograft Mice Model
Transgenic Mice Model
A Mouse Model for Small RNA Research
Advantage of a Mouse Model in CRC Research
Issues of Using Mouse Models in CRC Research
Conclusion
Future Perspective
References
50 Radiopharmaceuticals: A New Era in Cancer Therapy - Light on Initial Findings on Animal Model
Introduction
Radiopharmaceuticals: An Overview
RP Nomenclature
Diagnostic RPs
Transition of Diagnostic to Therapeutic RPs
Mechanism
Preclinical Research on RPT: Initial Findings in an Animal Model
Biodistribution and Dosimetry in Animal Research
Common RPT Agents Under Research
Targeted Cancer Therapy in Experimental Animal Research
Therapeutic Radiopharmaceuticals from Animals to Humans
Challenges
Conclusion
References
51 Cancer Modeling: Modern Imaging Applications in the Development of a Unique Animal Model System to Analyze Cancer Advanceme...
Introduction
Toward Ideal Diagnostic and Therapeutic Agents Based on Cancer Biology
Reporter Systems
Imaging Cancer Cells and Their Environment in Living Organisms
Biosensors of Key Genetic Processes in Cancer Cells
Magnetic Nanoparticles Are Promising Cancer Theranostics
Application of Nanotechnology in Cancer Imaging
Magnetic Particle Imaging
Benefits of Magnetic Particle Imaging Include
Examples of Nanoparticles Success in Different Organs Tumors
Pancreas Cancer
Breast Cancer
Prostate Cancer
Lung Cancer
Photothermal Therapy
Magnetic Nanoparticle-Guided Drug Delivery
Nanoparticles for siRNA Delivery for Cancer Treatment
Magnetic Nanoparticles for Dual Imaging and Drug Delivery
Multifunctional/Multimodal Nanoparticles
Personalized Therapeutic Response
Best Animal Model for Tumor Imaging and Therapy
Future Perspectives
Conclusion
References
52 The Molecular and Biochemical Variations During Cancer Prognosis in Mouse Models
Introduction
Transgenic Mice
Patient-Derived Xenografts
Applications/Advantages of PDX Models
Limitations of PDX Models
Conclusion
References
53 Animal Model-Based Studies to Evaluate the Lipid-Based Drug Delivery Nanocarriers for Cancer Treatment
Introduction
Historical Perspective of Animal Models
Experimental Animal Model in Cancer Research
Nude Mice
Hamsters
Rabbits
Zebrafish and Amphibians
Current Trends in Cancer Management
Microarray
Nanotechnology
Lipid-Based Nanoparticle for Cancer Therapy
Lipid Nanoparticles
Solid Lipid Nanoparticles
Liposomes
Lipid-Based Nanocomposite Carriers
Animal Models Used in Lipid Nanoparticle-Based Cancer Therapy
Lipid Nanoparticle-Based Chemotherapy in Xenograft Animal Model
Lipid Nanoparticle-Based Chemotherapy in Chemically Induced Animal Model
Lipid Nanoparticle-Based Chemotherapy in Genetically Modified Animal Model
Conclusion
References
54 Zebrafish: A Versatile Animal Model to Study Tumorigenesis Process and Effective Preclinical Drug Screening for Human Cance...
Introduction
Zebrafish as animal model
Zebrafish Life Cycle, Maintenance, and Breeding
Zebrafish Cancer Models
Tumor Induction Through Mutagenesis
Transgenic Lines for Tumor Studies
Tumour Cell Transplantation in Zebrafish
Approaches for Preclinical Drug Screening Using Zebrafish as an Animal Model
Phytotherapeutic Testing Using Zebrafish Embryos
Conclusions
References
55 Preclinical Animal Models of Cancer: Applications and Limitations
Introduction
Mouse Model
Humanized Mouse Model
Immunodeficient Mouse Model
Patient-Derived Tumor Xenograft Models
Murine Tumor Mouse Models
Genetically Engineered Mouse Models
Challenges Faced by GEMMs
Tumor Cell Lines with Identical Genes
Challenges Faced by Tumor Models with Identical Genes
Zebrafish (Danio rerio)
Pig (Sus scrofa)
Genetically Modified Pigs
Porcine Cancer Models
Porcine Tumor Xenograft Model
Applications of Animal Models
Xenografts
Genetically Engineered Animal Models
Zebrafish: Make a Good Animal Model
Major Limitations of Animal Models
Conclusions
References
56 Alternative Animal Models in Cancer Research
Introduction
Primary Cell Line
Cancer Cell Lines
Cancer Stem Cells
Spheroids
Embedded Ex Vivo Tumor Sections
3D Invasion Models
Avascular Microfluidic Models
Tumor-Microvessel Models
Predefined ECM Scaffold
Human Organ on a Chip
Integrated Discrete Multiple Organ Co-culture
Assays Commonly Used in in Vitro Models
Mouse Models
Genetically Induced Cancer Models
RNA Interference Mouse Model of Cancer
Patient-Derived Xenograft
Limitations
Zebrafish Models
Zebrafish as Genetic Models of Cancer
Zebrafish as Transplantation Model
Zebrafish for Neoplasia Studies
Limitations of Using Zebrafish Cancer Model
Future Perspective
Drosophila Melanogaster
Caenorhabditis Elegans
Limitations
Pig Cancer Model
Chick Embryo
Computational Cancer Models
Limitation of Animal Models in Cancer Research
Conclusion
References
57 Preclinical Models in Colorectal Cancer Drug Discovery
Introduction
Carcinogen-Induced Models
Transplant Models
Ectopic Xenografts
Orthotopic Xenografts and Patient-Derived CRC Xenografts
Transgenic Animal Models
Conclusion
References
58 Clinical Utility of Noncoding RNAs as Systemic Biomarkers in Animal Models
Introduction
Noncoding RNAs: Potential Biomarker in Cancer
Role of ncRNAs in Various Cancer Types
Lung Cancer (LC)
Breast Cancer (BC)
Pancreatic Cancer (PC)
Colorectal Cancer (CRC)
Leukemia
Thyroid Cancer (TC)
Role of ncRNA in Chemotherapy and Radiotherapy Sensitivity
Challenges of ncRNA Study in Animal Model
Conclusion and Future Perspective
References
59 Applications of Nanomedicine in Animal Models of Cancer
Introduction
Nanoparticles as Drug Delivery Systems and Its Categories
Multifunctional Nanoparticles for Tumor Imaging
Zebrafish Cancer Models
Xenograft Models
Genetic Models
Chemical Models
Breast Cancer In Vitro Models for the Development of Nanomedicine
Tumor Growth and Metastasis Assessment
Prospective Nanotechnologies to Advance Cancer Therapy
Cancer Diagnostics on the Nanoscale
Role of Nanomedicine in Cancer Therapy
Conclusion
References
Index