دانلود کتاب CURRENT ADVANCES IN THE SCIENCE OF OSTEOSARCOMA : research.

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Preface
Osteosarcoma: The State of Affairs Dictates a Change in Clinical Practice and Clinical Trial Design
Contents
Contributors
1: Genomic Complexity of Osteosarcoma and Its Implication for Preclinical and Clinical Targeted Therapies
General Introduction
Genomics of Human Osteosarcoma
Cell Line Genomics
Cell Line Models of Metastatic Disease
PDX Models
Preclinical Models for Drug Testing
Other PDX Studies
References Cited
2: Genomics and the Immune Landscape of Osteosarcoma
Introduction
Genomic Landscape of Osteosarcoma
Key Altered Genes and Pathways Associated with OS Genome Instability and Oncogenesis
TP53
RB1 and Other DNA Damage Repair Pathways
Telomere Lengthening Pathways
IGF Signaling/PI3K-mTOR
Other Genomic Events Associated with OS Genome Instability
Genome Doubling
Chromothripsis
Kataegis
The Osteosarcoma Immune Landscape and Immunogenomic Interplay
OS Immune Landscape
OS Genomic Features Associated with the Immune Response
Neoantigens
Aneuploidy
Genetic Alterations and Pathways
Translational Applications
Conclusion
References
3: RECQ DNA Helicases and Osteosarcoma
Introduction
RECQ Family of DNA Helicases and Cancer Predisposition
Structure and Functions of the RECQL4 DNA Helicase
Rothmund-Thomson Syndrome (RTS): Nature’s Model of Osteosarcoma
Understanding the Role of RECQL4 in Osteosarcoma Development Using Mouse Models
Recql4 Global Knockout Mouse Models
Recql4 Conditional (Bone-Specific) Mouse Models
Clinical Implications for Understanding RECQ Gene Defects and Potentially Targeting RECQ-Related Pathways for Cancer Therapy
References
4: Targeting the Cancer Epigenome with Histone Deacetylase Inhibitors in Osteosarcoma
Introduction
Targeting the Cancer Epigenome
Broad Reprogrammers
Targeted Reprogrammers
Histone Acetylation in Cancer
Histone Acetyltransferases
Histone Deacetylases
Nonhistone Protein Acetylation in Cancer
Histone Deacetylase Inhibitors in Cancer
Safety and Tolerance of Histone Deacetylase Inhibitors
Preclinical Evidence for Histone Deacetylase Inhibitors in Osteosarcoma
Emergence of HDACi in Drug Screening Studies for Osteosarcoma
Mechanisms of HDACi Efficacy in Osteosarcoma
Clinical Evidence for Histone Deacetylase Inhibitors in Osteosarcoma
HDACs as Biomarkers in Osteosarcoma
HDACi in Clinical Trials for Osteosarcoma
Combination Therapy with Histone Deacetylase Inhibitors in Osteosarcoma
Challenges in the Development of Histone Deacetylase Inhibitor Therapy for Osteosarcoma
Conclusions
References
5: Oncolytic Viruses and Their Potential as a Therapeutic Opportunity in Osteosarcoma
Introduction
Tumor Microenvironment
Immunologic Landscape and Immunoediting
Osteosarcoma TME
Tumor Mutational Burden
Immunoevasion
Oncolytic Virotherapy in Osteosarcoma
Oncolytic DNA Viruses
Adenovirus
Herpes Simplex Virus
Vaccinia Virus
Protoparvovirus
Oncolytic RNA Viruses
Reovirus
Semliki Forest Virus
Vesicular Stomatitis Virus
Measles Virus
Poliovirus
Newcastle Disease Virus
Maraba Virus
Combination Therapy
Challenges to Oncolytic Virotherapy
Future Directions
References
6: Applying Osteosarcoma Immunology to Understand Disease Progression and Assess Immunotherapeutic Response
Introduction
Assessing Osteosarcoma Disease Progression
Osteosarcoma Immunology: Innate Immune System
Myeloid Lineage
Granulocytes
Mononuclear Phagocytic System: Monocytes, Macrophages, and Dendritic Cells
Monocytes
Macrophages
Dendritic Cells
Myeloid-Derived Suppressor Cells
Osteosarcoma Immunology: Adaptive Immune System
Lymphoid Lineage
T Lymphocytes
Helper T Cells
Cytotoxic T Cells
Regulatory T Cells
Lymphocytes
Natural Killer Cells
Assessing Immunotherapeutic Response in Osteosarcoma
Checkpoint Blockade
Other Immunotherapeutics
Cytokine Stimulation
Dendritic Cell Vaccines
Genetically Modified T Cells
Macrophage Activation
Peptide Vaccines
Future Perspectives
References
7: Targetable Intercellular Signaling Pathways Facilitate Lung Colonization in Osteosarcoma
Introduction
The Metastatic Bottleneck
Cell-Autonomous Mechanisms that Facilitate Metastatic Lung Colonization in Osteosarcoma
Mechanisms that Resist Late Apoptosis Drive the Persistence of Disseminated Osteosarcoma Cells
Increased Expression of HSAP5 Facilitates Management of ER Stress During Metastatic Progression
Efficient Translation of Complex Transcripts Is Required for Osteosarcoma Metastatic Progression
Epigenetic Changes Influence Gene Expression Programs to Promote Metastasis
Tumor-Host Interactions that Mediate Osteosarcoma Lung Metastasis
Elements of Both Host- and Tumor-Derived Extracellular Matrix Promote Osteosarcoma Survival and Stemness During Metastasis
Interactions with Resident Immune Surveillance Mechanisms and Infiltrating Cells Facilitate Immune Evasion
Tumor-Educated Mesenchymal Stem Cells Facilitate Growth of Disseminated Osteosarcoma Cells Through IL6 Production
Bidirectional Cytokine Signaling Between Osteosarcoma Cells and Lung Parenchyma Regulates Metastatic Progression
Conclusions
References
8: Wnt Signaling in Osteosarcoma
Introduction
Overview of Wnt/β-Catenin Signaling Pathway
The Canonical Wnt Pathway
The Noncanonical Wnt Pathways
Wnt Signaling in Osteosarcoma
Wnt Antagonists in Osteosarcoma
WIF1
sFRP
DKK-1: Tumor Suppressor or Pro-tumorigenic Factor?
DKK-3
SOST
Naturally Occurring Small Molecules
Other Small Molecules
Other Drugs Recently Shown to Inhibit OS
Therapy Against Wnt Target Genes in Osteosarcoma
Wnt/B-catenin Signaling and Stem Cells
Summary
References
9: Receptor Tyrosine Kinases in Osteosarcoma: 2019 Update
AXL
EPHB2
FGFR2
IGF1R
RET
Multi-TKIs
References
10: The Role of ALDH in the Metastatic Potential of Osteosarcoma Cells and Potential ALDH Targets
Introduction
ALDH in Other Molecular Pathways
Notch
mTOR
ALDH Inhibition with Disulfiram
In Vivo Studies
Copper
Retinal
Conclusions
References
11: Autophagy in Osteosarcoma
Introduction
Regulation of Autophagy in Osteosarcoma
Autophagy and Tumorigenesis
Cell Survival Versus Cell Death
Dual Role of Autophagy in Osteosarcoma
Heat Shock Proteins and Autophagy
Autophagy Inhibition: From Drug Development to Challenges into Clinical Translation
Summary
References
12: The Fas/FasL Signaling Pathway: Its Role in the Metastatic Process and as a Target for Treating Osteosarcoma Lung Metastases
Introduction
Fas Pathway Is Involved in Development of OS Metastases in the Lungs
Expression of Fas Receptor Correlates with OS Metastatic Potential in Animal Models and in Patient Specimens
Functional Fas, FasL, and Downstream Fas Signaling Are Important for OS Lung Metastasis Progression
Fas Signaling Plays an Important Role in Response of OS to Therapy
Regulation of the Fas Signaling Pathway
Epigenetic Regulation of Fas Expression
Regulation of Fas Expression in OS Cells by miRNA
Summary
References
13: Exosomes: Dynamic Mediators of Extracellular Communication in the Tumor Microenvironment
Introduction
The Role of Exosomes in Cancer
The Role of Exosomes in Drug Resistance
The Role of Exosomes in Angiogenesis and Lymphogenesis
The Role of Exosomes in Cancer Cell Proliferation and Survival
The Role of Exosomes in Cancer Migration, Invasion, and Metastasis
The Role of Exosomes in Cancer and Immune Cell Interactions
The Emerging Role of Exosomes in Osteosarcoma
Conclusions
References
14: Comparative Immunology and Immunotherapy of Canine Osteosarcoma
Introduction
The Immunology of Canine OSA
Mutational Burden
Immune Landscape
Monocytes/Macrophages
Myeloid-Derived Suppressor Cells
Regulatory T Cells
T Cells
Checkpoint Molecule Expression
Metastatic Lesions
Immunotherapy of Canine OSA
Immune Modulatory Agents
Coley’s Toxins
BCG
Muramyl Tripeptides
Cytokines
Losartan
Bisphosphonates
Active Vaccination
Bacterial Vaccines
Listeria monocytogenes
Salmonella Typhimurium
DNA Vaccines
Oncolytic Viruses
FasL-Mediated Inflammation
Cell-Based Therapies
Tall 104 Cells
Polyclonal Activated T Cells
NK Cell Therapies
CAR T Cell Technology
Additional Strategies for Induction of ICD
References
Index