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Patient Derived Tumor Xenograft Models
Promise, Potential and Practice
1st Edition - October 13, 2016
Editors: Rajesh Uthamanthil, Peggy Tinkey, Elisa de Stanchina
Language: English
Paperback ISBN:9780128040102
9 7 8 - 0 - 1 2 - 8 0 4 0 1 0 - 2
eBook ISBN:9780128040614
9 7 8 - 0 - 1 2 - 8 0 4 0 6 1 - 4
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 appro…Read more
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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 type of tumors, acquisition of pathology, genomic and other data about the tumor, potential pitfalls, and confounding background pathologies that occur in these models are also included, as is a discussion of the facilities and infrastructure required to operate a PDX laboratory.
Offers guidance on data interpretation and regulatory aspects
Provides useful techniques and strategies for working with PDX models
Includes practical tools and potential pitfalls for best practices
Compiles all knowledge of PDX models research in one resource
Presents the results of first ever global survey on standards of PDX development and usage in academia and industry
Laboratory animal scientists, veterinarians, laboratory animal technicians and scientists working with the model, including cancer research scientists and pharmaceutical scientists
List of Contributors
Biographies
Foreword
Preface
Section I. Mouse Xenograft Models of Cancer
Chapter 1. PDX Models: History and Development
Introduction
History of PDX Mouse Models
Resurgence of PDX Models
Applications of PDX Models
Chapter 2. History of Mouse Cancer Models
Introduction
Immunodeficient Mouse Models
History of Mouse Models in Cancer Research
Xenografts
Future Directions of Murine Models in Basic Research
Chapter 3. Challenges and Limitations of Mouse Xenograft Models of Cancer
Introduction
Consider the Source: Cell Lines as Xenografts
Consider the Host: Mouse Xenograft Models
Consider the Method: Technique and Analysis of Xenograft Models
Conclusion
Chapter 4. Tumor Heterogeneity
Introduction
Heritable Sources of Heterogeneity
Context-Dependent Sources of Heterogeneity
Evolution of the Cancer Stem Cell Model
Clinical Implications of Tumor Heterogeneity
PDX Models to Preserve Tumor Heterogeneity
Chapter 5. Immunodeficient Mice: The Backbone of Patient-Derived Tumor Xenograft Models
Introduction
Introduction to the Immune System and Antitumor Immunity
SCID-Interleukin-2 Receptor Common Gamma Chain (IL2rg) Null Mice
Limitations of Using Immunodeficient Mice as Patient-Derived Xenograft Hosts
Chapter 6. Humanized Mice and PDX Models
Introduction
History of Humanized Mice
Reconstitution of the Human Immune System in Immunodeficient Mice
Limitations of Humanized Mice Models for Cancer Biology
Utility of Humanized Mice in Cancer
Future Directions
Section II. Components of a PDX Program
Chapter 1. Regulations of Patient-Derived Xenografts
Regulations Surrounding the Procurement of Human Tissues for Research
Occupational and Environmental Health Regulations When Working With PDX Tumors
Regulatory Aspects of Animal Use for the Development and Evaluation of PDX Tumors
Chapter 2. Acquisition and Storage of Clinical Samples to Establish PDX Models
Coordination
Screening
Collection
Distribution and Storage
Chapter 3. Methodologies for Developing and Maintaining Patient-Derived Xenograft Mouse Models
Sample Processing Techniques
Implantation Techniques
Tumor Take Rate and Growth Rate
Propagation and Preservation
Chapter 4. Pathology of Patient-Derived Xenograft Tumors
Introduction
The Various Domains of Application of Pathology in Patient-Derived Xenograft Studies
Technical Considerations
Suggested Schedules for Histological Analyses
Pitfalls
Conclusion
Chapter 5. Genetic Profiling of Tumors in PDX Models
Introduction
Laboratory Techniques
Bioinformatic Techniques
Chapter 6. Running a PDX Core Laboratory or a PDX Support Program
Infrastructure
Personnel
Data Storage and Management
Cost Analysis Considerations
Chapter 7. Veterinary Care
Introduction
Pathogens and Opportunists
Mouse Strain–Specific Diseases
Humanized Mice and Graft-Versus-Host Disease
Radiation
Cytotoxic Chemotherapeutic Drugs and Treatments
Engrafted Tumors
Conclusion
Chapter 8. Occupational Health and Safety
Introduction
PDX Mouse Models: Unique Occupational Health Concerns
Infectious Agents of Concern
Potential Infections Agents
Section III. PDX Models for Tumors of Various Organ Systems
Chapter 1. Pediatric and Adult Brain Tumor PDX Models
Background
Methodologies and Models
Tumor Biology
Genomic Characterization
Chapter 2. Patient-Derived Xenograft Models of Prostate Tumors
Background/Overview
Methodology and Models
Tumor Biology
Preclinical/Clinical Applications
Future/Challenges
Conclusion
Chapter 3. Patient-Derived Xenograft Model of Pancreatic Cancer
Background and Significance
Methodology and Models
Future and Challenges
Chapter 4. Modeling Breast Cancer Heterogeneity With Patient-Derived Xenografts
Background
Methodology and Models
Tumor Biology
Preclinical Utility
Challenges and Future Directions
Conclusion
Chapter 5. Patient-Derived Xenograft Models of Ovarian/Gynecologic Tumors
Background
Methodology and Models
Tumor Biology
Preclinical/Clinical Applications
Future/Challenges
Conclusion
Chapter 6. Patient-Derived Xenografts From Lung Cancer and Their Potential Applications
Background
Methodologies and Models
Tumor Biology
Applications of PDXs for Preclinical and Clinical Studies
Challenges and Perspectives
Conclusion
Chapter 7. PDX Models of Colorectal Tumors
Background and Overview
Methodology and Models
Tumor Biology
Preclinical and Clinical Applications
Future and Challenges
Conclusions
Chapter 8. Patient-Derived Tumor Xenografts in Hematologic Disorders
Overview and Classification of Hematopoietic and Lymphoid Tissue Tumors
In Vivo Models of Hematologic Disorders
The Role of Patient-Derived Tumor Xenografts in the Study of Lymphoproliferative Disorders
Conclusions
Chapter 9. Patient-Derived Xenografting of Human Melanoma
Background and Overview
Methodology and Models
Tumor Biology
Preclinical Applications: Use of PDX Melanomas to Model Patient Outcomes
Future/Challenges
Chapter 10. Advances in Organoid Culturing of Patient-Derived Tumors
Background
The History of Organoid Cancer Models
Conditional Reprogrammed Cells
Benign Organoid Cultures
Cancer Organoid Cultures
Prostate Cancer Organoids
Pancreas Cancer Organoids
Colorectal Cancer Organoids
Lung Cancer Conditional Reprogrammed Cells
Future Directions
Section IV. PDX Models in Cancer Research and Therapy Around the World
Chapter 1. Global Practices in PDX Programs
The Survey
PDX Programs: A Global Snapshot
Current Practices in Academic PDX Programs
From Academia to Commercialization
A Successful PDX Program
Recommendations for Improving Current PDX Practices
Summary and Concluding Comments
Chapter 2. Role of Companies and Corporations in the Development and Utilization of PDX Models
Introduction
PDX Inventory and Tumor Samples
Practice and Protocols
Model Development, Challenges, and Future Directions
Interview With Company Representatives Regarding Challenges and Future Directions in PDX Development
Summary and Concluding Comments
Appendix 1. Additional Information on Some Companies Providing and Supporting PDX Model Development
Section V. Challenges & Future of PDX Models
Chapter 1. Patient-Derived Tumor Xenograft: Present and Future Challenges and Applications
Introduction
Technical Improvements
PDX Molecular Characterization
Innovative PDX Derivative Models
The Host (Mouse) Aspect of PDX Models
Clinical Trials and Data Reporting
Current and Future Accessibility of PDX Models
Index
No. of pages: 486
Language: English
Edition: 1
Published: October 13, 2016
Imprint: Academic Press
Paperback ISBN: 9780128040102
eBook ISBN: 9780128040614
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Rajesh Uthamanthil
Dr. Rajesh Uthamanthil is the director of Comparative Medicine program at Fred Hutchinson Cancer Research Center, Seattle, WA. He received Doctorate in Veterinary Medicine and Veterinary Sciences from Kerala Agricultural University, PhD in Comparative Biosciences from the University of Wisconsin Madison and completed a post doctoral fellowship at Rice University. Dr. Uthamanthil has more than 16 years of experience in animal models of human disease, most of it focused on cancer.
Dr. Uthamanthil also directs the PDX core that support studies using PDX models at Fred Hutchinson Cancer Research Center. Dr. Uthamanthil has more than 20 peer reviewed publications in the area of translational research, has authored/co-authored two book chapters and has made more than 30 presentations in national and international conferences meetings.
Affiliations and expertise
Director, Comparative Medicine, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
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Peggy Tinkey
Dr. Peggy Tinkey received degrees in Veterinary Science and Veterinary Medicine from Texas A&M University, completed a postdoctoral fellowship in Pathology at Baylor College of Medicine and is a Diplomate of the American College of Laboratory Animal Medicine. She is a Professor of Comparative Medicine and Chairman of the Department of Veterinary Medicine and Surgery at the University of Texas M.D. Anderson Cancer Center, where she directs the animal research program
Dr. Tinkey has extensive experience in animal models of cancer, with an emphasis of mouse cancer models that includes genetically engineered and mutant mouse models, cell line xenograft models, and patient-derived xenograft models. She has published over 25 peer-reviewed manuscripts and book chapters on animal cancers and cancer models. She combines her expertise in animal models with extensive experience in regulatory medicine and has served on the UTMDACC institutional animal care and use and biosafety committees for more than 20 years.
Affiliations and expertise
Professor, Department of Veterinary Medicine and Surgery,The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Ed
Elisa de Stanchina
Dr. Elisa de Stanchina is the Director of the MSKCC Antitumor Assessment Core Facility, and over the past 8 years has overseen its evolution into a state-of-the-art “Mouse Hospital” that fosters preclinical drug development and coordinates efforts from basic scientists and clinicians to ensure that mouse trials effectively mimic treatment plans of human patients. She is an Associate Lab Member in the Molecular Pharmacology and Chemistry Program at Memorial Sloan Kettering Cancer Center (MSKCC). Her lab works closely with investigators to establish mouse models of cancer and has developed one of the largest Academic PDX core support programs in the U.S., with an extensive bank of clinically annotated models available to MSKCC Investigators and their collaborators. Her work has resulted in over 65 publications in prestigious peer-reviewed journals and she has recently authored one of the chapters in the new edition of the “Mouse Models of Cancer” book by CSHL Press.
Affiliations and expertise
Director, Antitumor Assessment Core Facility, Memorial Sloan Kettering Cancer Center, NY, USA
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