Patient derived tumor xenograft models : promise, potential and practice / edited by Rajesh Uthamanthil, Peggy Tinkey ; associate editor, Elisa de Stanchina.

Format:

Book

Contributor:

Uthamanthil, Rajesh, editor.

Tinkey, Peggy, editor.

De Stanchina, Elisa, editor.

Language:

English

Subjects (All):

Tumors--Animal models.

Tumors.

Physical Description:

1 online resource (488 p.)

Edition:

1st ed.

Place of Publication:

Amsterdam, [Netherlands] : Academic Press, 2017.

Summary:

Patient Derived Tumor Xenograft Models: Promise, Potential and Practice offers guidance on how to conduct PDX modeling and trials, including how to know when these models are appropriate for use, and how the data should be interpreted through the selection of immunodeficient strains.In addition, proper methodologies suitable for growing different.

Contents:

Front Cover

Patient Derived Tumor Xenograft Models

Patient Derived Tumor Xenograft Models: Promise, Potential and Practice

Copyright

Contents

List of Contributors

Biographies

EDITORS

ASSOCIATE EDITOR

Foreword

Preface

I - Mouse Xenograft Modelsof Cancer

1 - PDX Models: History and Development

INTRODUCTION

HISTORY OF PDX MOUSE MODELS

RESURGENCE OF PDX MODELS

APPLICATIONS OF PDX MODELS

Tumor Biology

Preclinical Research

Cancer Drug Screening

Personalized Cancer Therapy-Mouse Avatars

Biomarkers and Mechanisms of Drug Resistance

REFERENCES

2 - History of Mouse Cancer Models

IMMUNODEFICIENT MOUSE MODELS

HISTORY OF MOUSE MODELS IN CANCER RESEARCH

XENOGRAFTS

FUTURE DIRECTIONS OF MURINE MODELS IN BASIC RESEARCH

3 - Challenges and Limitations of Mouse Xenograft Models of Cancer

CONSIDER THE SOURCE: CELL LINES AS XENOGRAFTS

CONSIDER THE HOST: MOUSE XENOGRAFT MODELS

CONSIDER THE METHOD: TECHNIQUE AND ANALYSIS OF XENOGRAFT MODELS

CONCLUSION

4 - Tumor Heterogeneity

HERITABLE SOURCES OF HETEROGENEITY

Genomic Influences on Tumor Heterogeneity

Epigenomic Influences on Tumor Heterogeneity

CONTEXT-DEPENDENT SOURCES OF HETEROGENEITY

Tumor Microenvironment

Phenotypic Plasticity

EVOLUTION OF THE CANCER STEM CELL MODEL

CLINICAL IMPLICATIONS OF TUMOR HETEROGENEITY

Stratified Medicine

Resistance and Progression

PDX MODELS TO PRESERVE TUMOR HETEROGENEITY

ACKNOWLEDGMENTS

5 - Immunodeficient Mice: The Backbone of Patient-Derived Tumor Xenograft Models

INTRODUCTION TO THE IMMUNE SYSTEM AND ANTITUMOR IMMUNITY

Immunodeficient Mouse Models

Nude Mice

Severe Combined Immunodeficiency Mice

Nonobese Diabetic (NOD)-SCID Mice.

SCID-INTERLEUKIN-2 RECEPTOR COMMON GAMMA CHAIN (IL2RG) NULL MICE

Choosing Immunodeficient Mouse Models

Research Goals and Tumor Type

Background Strain

Leakiness

Life Span

Sensitivity to Radiation and Genotoxic Agents

Availability and Vendor

Immunodeficient Mice: Limitations and Future Development

LIMITATIONS OF USING IMMUNODEFICIENT MICE AS PATIENT-DERIVED XENOGRAFT HOSTS

Approaches to Improving Modeling in Patient-Derived Xenograft Mice

6 - Humanized Mice and PDX Models

HISTORY OF HUMANIZED MICE

RECONSTITUTION OF THE HUMAN IMMUNE SYSTEM IN IMMUNODEFICIENT MICE

Hu-PBL-SCID

Hu-SRC-SCID

SCID-Human

BLT Model

LIMITATIONS OF HUMANIZED MICE MODELS FOR CANCER BIOLOGY

UTILITY OF HUMANIZED MICE IN CANCER

Humanized Xenochimeric Mice (XactMice)

Humanized Tumor Mice

FUTURE DIRECTIONS

II - Components of a PDX Program

1 - Regulations of Patient-Derived Xenografts

REGULATIONS SURROUNDING THE PROCUREMENT OF HUMAN TISSUES FOR RESEARCH

Institutional Review Boards

Common Rule

Health Insurance Portability and Accountability Act

The Joint Commission, Clinical Laboratory Improvement Amendments of 1988, and the College of American Pathologists

OCCUPATIONAL AND ENVIRONMENTAL HEALTH REGULATIONS WHEN WORKING WITH PDX TUMORS

Oversight in the United States

Biosafety Committee

Chemical Hazards

REGULATORY ASPECTS OF ANIMAL USE FOR THE DEVELOPMENT AND EVALUATION OF PDX TUMORS

Institutional Animal Care and Use Committee

Oversight Bodies for Other Countries

Protocol Assessment

Other Regulations

Working Across Borders

ACKNOWLEDGMENT

2 - Acquisition and Storage of Clinical Samples to Establish PDX Models

COORDINATION

SCREENING

COLLECTION

DISTRIBUTION AND STORAGE

REFERENCES.

3 - Methodologies for Developing and Maintaining Patient-Derived Xenograft Mouse Models

SAMPLE PROCESSING TECHNIQUES

Fluids

Hematological Malignancies

Effusions and Ascites

Circulating Tumor Cells

Surgical Samples

Initial Sample Preparation

Fragments

Single-Cell Suspension

Mechanical Dissociation

Mechanical and Enzymatic Dissociation

Biopsies

IMPLANTATION TECHNIQUES

Subcutaneous Implantation

Orthotopic Implantation in the Gastric Wall13

Subrenal Capsule Implantation19

Orthotopic Lung Implantation22

Mammary Fat Pad Implantation1

Brain Orthotopic Implantation

TUMOR TAKE RATE AND GROWTH RATE

PROPAGATION AND PRESERVATION

4 - Pathology of Patient-Derived Xenograft Tumors

THE VARIOUS DOMAINS OF APPLICATION OF PATHOLOGY IN PATIENT-DERIVED XENOGRAFT STUDIES

Characterization of Xenograft Banks

Experimentation on Tumors

TECHNICAL CONSIDERATIONS

SUGGESTED SCHEDULES FOR HISTOLOGICAL ANALYSES

PITFALLS

5 - Genetic Profiling of Tumors in PDX Models

LABORATORY TECHNIQUES

Purification

Fluorescence-Activated Cell Sorting

Immunomagnetic

Quality Control

Species-Specific PCR Amplicon Length

BIOINFORMATIC TECHNIQUES

Computational Requirements

Alignment

Hybrid Genome Preparation

Eliminating Mouse Reads From Analysis

6 - Running a PDX Core Laboratory or a PDX Support Program

INFRASTRUCTURE

Regulatory and Administrative Infrastructure

Vivarium

Laboratory Space

Biobank and Data Center

Mouse Hospital

PERSONNEL

Education and Training

DATA STORAGE AND MANAGEMENT

Annotation of Patient Samples

Annotation of PDX Samples

Annotation of Histology and Genomic Data.

Annotation of In Vitro, Ex Vivo, and Preclinical Data

Query Capabilities and Data Access

COST ANALYSIS CONSIDERATIONS

Cost of Mice

Cost of Infrastructures

Cost of Labor

Cost of PDX Model Characterization

Cost of Data Management

7 - Veterinary Care

PATHOGENS AND OPPORTUNISTS

MOUSE STRAIN-SPECIFIC DISEASES

HUMANIZED MICE AND GRAFT-VERSUS-HOST DISEASE

RADIATION

CYTOTOXIC CHEMOTHERAPEUTIC DRUGS AND TREATMENTS

ENGRAFTED TUMORS

8 - Occupational Health and Safety

INTRODUCTION1-4

PDX MOUSE MODELS: UNIQUE OCCUPATIONAL HEALTH CONCERNS5-10

INFECTIOUS AGENTS OF CONCERN5,11-13

Ensuring Human Safety

Considerations with Sample Handling and Collection1

Considerations with Animal Handling and Husbandry Procedures

Conclusion

POTENTIAL INFECTIONS AGENTS

Tumor-Associated Viruses14

Hepatocellular Carcinoma15-19

Urogenital, Anogenital, and Oropharyngeal Cancers20,21

Lymphoma14,16,18,21-24

Nasopharyngeal Carcinoma14,18

Kaposi Sarcoma23,25

Glioblastoma, Medulloblastoma, and Neuroblastoma26-28

HIV/AIDS Related and Nonrelated Malignancies29,30

Other Infectious Agents of Concern

Arboviral Infections31-34

Babesiosis (Babesia microti)35-38

Brucellosis (Brucella spp.)39

Chagas Disease (Trypanosoma cruzi)40,41

Creutzfeldt-Jakob Disease42-45

Leptospirosis (Leptospira)2,10,46,47

Malaria (Plasmodium spp.)37,48-54

Tick-Borne Relapsing Fever (Borrelia)55-58

Syphilis (Treponema pallidum)59-63

Viral Hemorrhagic Fevers2,33,64,65

III - PDX Models for Tumors of Various Organ Systems

1 - Pediatric and Adult Brain Tumor PDX Models

BACKGROUND

METHODOLOGIES AND MODELS

Technical Considerations

TUMOR BIOLOGY

Adult Brain Tumors: Pathology and Molecular Drivers.

Pediatric Brain Tumors: Pathology and Molecular Drivers

GENOMIC CHARACTERIZATION

Preclinical Applications

Vision for the Future

SUPPORT

2 - Patient-Derived Xenograft Models of Prostate Tumors

BACKGROUND/OVERVIEW

METHODOLOGY AND MODELS

Tissue Preparation

Choice of Mouse Strain

Site of Implantation

PRECLINICAL/CLINICAL APPLICATIONS

FUTURE/CHALLENGES

3 - Patient-Derived Xenograft Model of Pancreatic Cancer

BACKGROUND AND SIGNIFICANCE

Tissue Collection and Processing

Mouse Strain

Implantation Site

Engraft Time and Success Rate

Engraft Technique

FUTURE AND CHALLENGES

4 - Modeling Breast Cancer Heterogeneity With Patient-Derived Xenografts

Tumor Source

Implantation Techniques

Sample Processing

Model Fidelity

Genomic Alterations

Gene Expression

Potential Clonal Evolution

Metastatic Capability of PDXs

Engraftment Success Linked to Poor Patient Outcome

PRECLINICAL UTILITY

CHALLENGES AND FUTURE DIRECTIONS

Accessible Sample Sources

Molecular Alterations for Target Validation

Increased Efficiency of Hormone Receptor-Positive PDXs

Personalized Therapy

5 - Patient-Derived Xenograft Models of Ovarian/Gynecologic Tumors

Animals

Orthotopic Versus Heterotopic Models

PDX Models of Endometrial and Cervical Cancer

6 - Patient-Derived Xenografts From Lung Cancer and Their Potential Applications.

Notes:

Description based upon print version of record.

Includes bibliographical references at the end of each chapters and index.

Description based on online resource; title from PDF title page (ebrary, viewed October 26, 2016).

Description based on publisher supplied metadata and other sources.

ISBN:

9780128040102

0128040106

OCLC:

961450463