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Title
Copyright
End User License Agreement
Contents
Preface
List of Contributors
Hepatocellular Carcinoma: Diagnosis, Molecular Pathogenesis, Biomarkers, and Conventional Therapy
Biswajit Mukherjee*, 1, Manasadeepa Rajagopalan2, Samrat Chakraborty1, Prasanta Ghosh1, Manisheeta Ray1, Ramkrishna Sen1 and Iman Ehsan1
INTRODUCTION
CANCER AND ITS TYPES
Primary Liver Cancer
Hepatocellular Carcinoma (HCC)
Intrahepatic Cholangiocarcinoma (Bile Duct Cancer)
Angiosarcoma and Hemangiosarcoma
Hepatoblastoma
Secondary Liver Cancer
DETAIL DESCRIPTION OF HCC
Staging System in HCC
Risk Factors for HCC
Pathophysiology of HCC
Molecular and Cellular Features of the Tumor Microenvironment
Importance of Cancer Stem Cells in HCC
Inflammation and HCC
Oxidative Stress in HCC
Epithelial-Mesenchymal Transition (EMT)
Hypoxia and HCC
Impairment of Cell Cycle in HCC
Loss of Senescence Control
Apoptosis and HCC
Cellular Signalling Pathways in HCC
EGF/TGF-α pathway
Insulin Growth Factor (IGF) Pathway
HGF/c-Met Pathway
Signaling Pathways Involved in Neovascularization in HCC
MAPK Pathways
PI3K/Akt/mTOR Pathway
Signaling Pathways Related to Cell Differentiation and Development
Wnt-β Catenin Pathway
Hedgehog (Hh) Signaling
Notch Pathway
Hippo Pathway
Target Receptor(s) and Biomarker Proteins in HCC
Asialoglycoprotein Receptor
Glypican-3 (GPC3)
Transferrin Receptor (TfR)
Heat Shock Protein 70 (HSP70)
Tumor-Associated Glycoprotein-72 (TAG-72)
Golgi Protein73 (GP73)
Ki-67 Antigen
Somatostatin Receptor (SSTR)
Homodimeric Glycoprotein (AF-20)
Osteopontin (OPN)
Des-γ-Carboxyprothrombin
α-Fetoprotein (AFP)
Squamous Cell Carcinoma Antigen (SCCA)
Hepatocyte Paraffin 1 (HepPar1)
APO-J
DKK-1 (Dickkopf-p1).
Human Carbonyl Reductase 2 (HCR2)
Midkine
Nerve Growth Factor (NGF)
Vascular Endothelial Growth Factor (VEGF)
Transforming Growth Factor-β (TGF-β)
Epidermal Growth Factor (EGFR)
Hepatocyte Growth Factor (HGF)
α-1-Fucosidase
Annexin A2
Micro RNA
Circular RNAs
Cancer Stem Markers
CD44
CD133
CD90
Epithelial Cell Adhesion Molecule (EpCAM)
SURVEILLANCE AND HCC
TREATMENT STRATEGIES
Curative Treatments
Surgical Resection
Surgical Resection in Advanced HCC
Anatomical Resection
Laparoscopic Resection of The Liver
Surgical Resection of Re-Occurring HCC
Liver Transplantation
Ablation
Palliative Treatment
Embolizing Therapies for HCC
Transarterial Chemoembolization (TACE)
Radiotherapy
Systemic Therapies of HCC
First-line Therapy
Second-line Therapy
Multi-Target Tyrosine Kinase Inhibitors
Immune Checkpoint Inhibitor
FUTURE PERSPECTIVES
CONCLUSIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Hepatocellular Carcinoma and Therapeutic Challenges
Somenath Datta1,*
INTRODUCTION
HCC SURVEILLANCE AND DIAGNOSIS
CURRENT HCC THERAPEUTICS AND THEIR CHALLENGES
Importance of Staging Systems and Their Challenges in Prognostic Assessments
Surgical Resection and Liver Transplantation: Challenges in HCC Therapeutics
Non-surgical Therapies: Locoregional Therapies and Their Challenges
Percutaneous Ablation
Trans-Arterial Therapies
Systemic Therapies and Their Challenges
Multi-kinase Inhibitors (MKIs) and Challenges with Drug Resistance
Current Challenges with Drug-resistance
Current Immunotherapies and Their Challenges
Nanotechnology-Based HCC Therapeutics: Current Opportunities and Challenges
HCC THERAPEUTICS: FUTURE PERSPECTIVES AND CONCLUSIONS
CONSENT FOR PUBLICATION.
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Nanoformulations and Their Therapeutic Advantages
D. Nedra Karunaratne1,*, Thusini D. Wijerathne1, Nuwanthi P. Katuwavila2 and Geethi K. Pamunuwa3
INTRODUCTION
Brief Introduction to Nanomedicine
Designing Nanoformulations for Therapeutics
Types of Therapeutic Nanoformulations
Targeted Delivery Applications
Advantages of Nanoformulations
Methods of Administration
Increased Solubility and Absorption
Delivery to Target Tissues
Maintaining a Steady Drug Concentration in the System
Penetrating Impermeable Barriers
APPLICATIONS OF NANOFORMULATIONS IN CANCER THERAPY
Nanoformulations as Therapeutics in Cancer Treatment
Liposomes
Conventional Liposomes
Stealth Liposomes
Immunoliposomes
Thermosensitive Liposomes
pH-Sensitive Liposomes
Photosensitive Liposomes
Cationic Liposomes
Commercial Liposomal Anticancer Products
Polymeric Nanoparticles
Solid Lipid Nanoparticles
Metal Nanoparticles
Dendrimers
Emulsions
Nanoformulation Targeting Strategies
Passive Targeting
Active Targeting
Other Nanoparticle-Based Strategies for Cancer Therapy
Dual Delivery
Triggered Cancer Therapy
THERAPEUTIC ADVANTAGES OF NANOFORMULATIONS IN HEPATOCELLULAR CARCINOMA
Nanoformulations for Hepatocellular Carcinoma
Types of Nanoformulations
Mechanism of Action of Nanoformulations in Hepatocellular Carcinoma
Vitamin Based Active Targeting
Antibody-Based Active Targeting
Peptide-Based Active Targeting
Aptamer Mediated Active Targeting
Key Milestones
Limitations
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Nanoformulations to Limit Challenges of Conventional Therapy Against Hepatocellular Carcinoma - An Overview.
Suresh Ajmeera1 and V. Badireenath Konkimalla1,*
INTRODUCTION
Anticancer Drugs in HCC and its Limitations
HCC Chemotherapy and Molecular Targets
Small Molecule and Antibody-Based Inhibitors in HCC
miRNAs Based Therapeutics in HCC
Multidrug Therapy in HCC
Need for Nanoformulations in HCC
Site-specific Drug Transporter Systems in HCC
Nanoformulations in HCC - a Detailed Summary
Current Status Clinical Trials for different Nanoformulation used in HCC
FUTURE SCOPE
CONCLUDING REMARKS
LIST OF ABBREVIATIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Nanotherapeutics for the Treatment of Hepatocellular Carcinoma
Kishor Mazumder1,2,3,4,*, Md. Emran Hossain2 and Asma Aktar2
INTRODUCTION
HEPATOCELLULAR CARCINOMA: AN OVERVIEW
Pathogenesis of HCC and Molecular Targets
Current Treatment Approaches for HCC
Barriers for Management of HCC
NANOTHERAPEUTICS: A NOVEL APPROACH
Method of Preparing Nanoparticles
NANOTHERAPEUTIC APPROACHES FOR MANAGEMENT OF HCC
HCC TARGETING MECHANISMS BY NANOPARTICLES
Active Targeting
Active Targeting of Ligands by Specific Macromolecules
Active Targeting of Small Molecular Ligands
Passive Targeting
Stimuli-Responsive Nanocarriers Targeting
Magnetic Field Responsive Nanoparticles
pH-Responsive Nanoparticles
Hypoxia-Responsive Nanoparticles
NANOTHERANOSTIC APPROACH FOR MANAGEMENT OF HCC
IMPACT OF PHYSICOCHEMICAL FACTORS OF NANOPARTICLES ON HCC MANAGEMENT
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
A Summarized View of Lipid, Polyplex, Inorganic, and Carbon-Based Nanotherapeutics for Hepatocellular Carcinoma Treatment
Riddhi Trivedi1, Sanjay Arora1, Richard N. L. Lamptey1, Bivek Chaulagain1, Jagdish Singh1,* and Buddhadev Layek1,*.
INTRODUCTION
Nanotherapeutics for Hepatocellular Carcinoma (HCC)
Lipid-based Nanotherapeutics
Polymer-Based Nanotherapeutics
Inorganic Nanoparticles
Carbon-Based Nanotherapeutics
Nanotherapeutics Under Clinical Trials
CONCLUSIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGMENT
REFERENCES
Aptamers and Their Potential in Site-Specific Nanotherapy Against Hepatocellular Carcinoma
Debasmita Dutta1,2, Samrat Chakraborty2,3, Biswajit Mukherjee2, Moumita Dhara2 and Laboni Das4
INTRODUCTION
Therapeutic Approach for HCC: Active vs. Passive Targeting and Aptamer.
Aptamer as a Targeting Molecule and its Modifications for In Vivo Stability
Aptamer and HCC
Aptamers and In Vivo Imaging in HCC
Aptamers and Targeted Delivery in HCC
Aptamer-Functionalized Theranostic in HCC
Mechanisms of Aptamer Internalization
Factors Affecting In Vivo Therapeutic Potency of Aptamer
Resistant to Nuclease Enzyme
Renal Filtration
Safety of Aptamers
SELEX Technology for the Identification and Selection of Aptamers
Purified Membrane Protein-Based SELEX
Live Cell-Based SELEX
Some Prospective Use of Aptamers in HCC Therapy
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Preclinical Studies on Nanocarrier-Mediated Delivery of Radiosensitizing Agents to Brain and Pancreatic Cancer with a Future Projection to Liver Cancer
Peter Sminia1,*, Pei Pei Che1,2, Ben J. Slotman1 and Elisa Giovannetti2,3
INTRODUCTION
Nanocarrier-Mediated Drug Delivery to Brain Tumours
Nanocarrier Delivery of the Targeted MAPK Inhibitor Binimetinib
Nanocarrier Delivery of the Natural Compound Curcumin
Section III
Nanotechnological Strategies in Pancreatic Cancer
Applications of Gold Nanoparticles in Pancreatic Cancer
Section IV.
Perspective for Liver Cancer Therapy.
Title
Copyright
End User License Agreement
Contents
Preface
List of Contributors
Hepatocellular Carcinoma: Diagnosis, Molecular Pathogenesis, Biomarkers, and Conventional Therapy
Biswajit Mukherjee*, 1, Manasadeepa Rajagopalan2, Samrat Chakraborty1, Prasanta Ghosh1, Manisheeta Ray1, Ramkrishna Sen1 and Iman Ehsan1
INTRODUCTION
CANCER AND ITS TYPES
Primary Liver Cancer
Hepatocellular Carcinoma (HCC)
Intrahepatic Cholangiocarcinoma (Bile Duct Cancer)
Angiosarcoma and Hemangiosarcoma
Hepatoblastoma
Secondary Liver Cancer
DETAIL DESCRIPTION OF HCC
Staging System in HCC
Risk Factors for HCC
Pathophysiology of HCC
Molecular and Cellular Features of the Tumor Microenvironment
Importance of Cancer Stem Cells in HCC
Inflammation and HCC
Oxidative Stress in HCC
Epithelial-Mesenchymal Transition (EMT)
Hypoxia and HCC
Impairment of Cell Cycle in HCC
Loss of Senescence Control
Apoptosis and HCC
Cellular Signalling Pathways in HCC
EGF/TGF-α pathway
Insulin Growth Factor (IGF) Pathway
HGF/c-Met Pathway
Signaling Pathways Involved in Neovascularization in HCC
MAPK Pathways
PI3K/Akt/mTOR Pathway
Signaling Pathways Related to Cell Differentiation and Development
Wnt-β Catenin Pathway
Hedgehog (Hh) Signaling
Notch Pathway
Hippo Pathway
Target Receptor(s) and Biomarker Proteins in HCC
Asialoglycoprotein Receptor
Glypican-3 (GPC3)
Transferrin Receptor (TfR)
Heat Shock Protein 70 (HSP70)
Tumor-Associated Glycoprotein-72 (TAG-72)
Golgi Protein73 (GP73)
Ki-67 Antigen
Somatostatin Receptor (SSTR)
Homodimeric Glycoprotein (AF-20)
Osteopontin (OPN)
Des-γ-Carboxyprothrombin
α-Fetoprotein (AFP)
Squamous Cell Carcinoma Antigen (SCCA)
Hepatocyte Paraffin 1 (HepPar1)
APO-J
DKK-1 (Dickkopf-p1).
Human Carbonyl Reductase 2 (HCR2)
Midkine
Nerve Growth Factor (NGF)
Vascular Endothelial Growth Factor (VEGF)
Transforming Growth Factor-β (TGF-β)
Epidermal Growth Factor (EGFR)
Hepatocyte Growth Factor (HGF)
α-1-Fucosidase
Annexin A2
Micro RNA
Circular RNAs
Cancer Stem Markers
CD44
CD133
CD90
Epithelial Cell Adhesion Molecule (EpCAM)
SURVEILLANCE AND HCC
TREATMENT STRATEGIES
Curative Treatments
Surgical Resection
Surgical Resection in Advanced HCC
Anatomical Resection
Laparoscopic Resection of The Liver
Surgical Resection of Re-Occurring HCC
Liver Transplantation
Ablation
Palliative Treatment
Embolizing Therapies for HCC
Transarterial Chemoembolization (TACE)
Radiotherapy
Systemic Therapies of HCC
First-line Therapy
Second-line Therapy
Multi-Target Tyrosine Kinase Inhibitors
Immune Checkpoint Inhibitor
FUTURE PERSPECTIVES
CONCLUSIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Hepatocellular Carcinoma and Therapeutic Challenges
Somenath Datta1,*
INTRODUCTION
HCC SURVEILLANCE AND DIAGNOSIS
CURRENT HCC THERAPEUTICS AND THEIR CHALLENGES
Importance of Staging Systems and Their Challenges in Prognostic Assessments
Surgical Resection and Liver Transplantation: Challenges in HCC Therapeutics
Non-surgical Therapies: Locoregional Therapies and Their Challenges
Percutaneous Ablation
Trans-Arterial Therapies
Systemic Therapies and Their Challenges
Multi-kinase Inhibitors (MKIs) and Challenges with Drug Resistance
Current Challenges with Drug-resistance
Current Immunotherapies and Their Challenges
Nanotechnology-Based HCC Therapeutics: Current Opportunities and Challenges
HCC THERAPEUTICS: FUTURE PERSPECTIVES AND CONCLUSIONS
CONSENT FOR PUBLICATION.
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Nanoformulations and Their Therapeutic Advantages
D. Nedra Karunaratne1,*, Thusini D. Wijerathne1, Nuwanthi P. Katuwavila2 and Geethi K. Pamunuwa3
INTRODUCTION
Brief Introduction to Nanomedicine
Designing Nanoformulations for Therapeutics
Types of Therapeutic Nanoformulations
Targeted Delivery Applications
Advantages of Nanoformulations
Methods of Administration
Increased Solubility and Absorption
Delivery to Target Tissues
Maintaining a Steady Drug Concentration in the System
Penetrating Impermeable Barriers
APPLICATIONS OF NANOFORMULATIONS IN CANCER THERAPY
Nanoformulations as Therapeutics in Cancer Treatment
Liposomes
Conventional Liposomes
Stealth Liposomes
Immunoliposomes
Thermosensitive Liposomes
pH-Sensitive Liposomes
Photosensitive Liposomes
Cationic Liposomes
Commercial Liposomal Anticancer Products
Polymeric Nanoparticles
Solid Lipid Nanoparticles
Metal Nanoparticles
Dendrimers
Emulsions
Nanoformulation Targeting Strategies
Passive Targeting
Active Targeting
Other Nanoparticle-Based Strategies for Cancer Therapy
Dual Delivery
Triggered Cancer Therapy
THERAPEUTIC ADVANTAGES OF NANOFORMULATIONS IN HEPATOCELLULAR CARCINOMA
Nanoformulations for Hepatocellular Carcinoma
Types of Nanoformulations
Mechanism of Action of Nanoformulations in Hepatocellular Carcinoma
Vitamin Based Active Targeting
Antibody-Based Active Targeting
Peptide-Based Active Targeting
Aptamer Mediated Active Targeting
Key Milestones
Limitations
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Nanoformulations to Limit Challenges of Conventional Therapy Against Hepatocellular Carcinoma - An Overview.
Suresh Ajmeera1 and V. Badireenath Konkimalla1,*
INTRODUCTION
Anticancer Drugs in HCC and its Limitations
HCC Chemotherapy and Molecular Targets
Small Molecule and Antibody-Based Inhibitors in HCC
miRNAs Based Therapeutics in HCC
Multidrug Therapy in HCC
Need for Nanoformulations in HCC
Site-specific Drug Transporter Systems in HCC
Nanoformulations in HCC - a Detailed Summary
Current Status Clinical Trials for different Nanoformulation used in HCC
FUTURE SCOPE
CONCLUDING REMARKS
LIST OF ABBREVIATIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Nanotherapeutics for the Treatment of Hepatocellular Carcinoma
Kishor Mazumder1,2,3,4,*, Md. Emran Hossain2 and Asma Aktar2
INTRODUCTION
HEPATOCELLULAR CARCINOMA: AN OVERVIEW
Pathogenesis of HCC and Molecular Targets
Current Treatment Approaches for HCC
Barriers for Management of HCC
NANOTHERAPEUTICS: A NOVEL APPROACH
Method of Preparing Nanoparticles
NANOTHERAPEUTIC APPROACHES FOR MANAGEMENT OF HCC
HCC TARGETING MECHANISMS BY NANOPARTICLES
Active Targeting
Active Targeting of Ligands by Specific Macromolecules
Active Targeting of Small Molecular Ligands
Passive Targeting
Stimuli-Responsive Nanocarriers Targeting
Magnetic Field Responsive Nanoparticles
pH-Responsive Nanoparticles
Hypoxia-Responsive Nanoparticles
NANOTHERANOSTIC APPROACH FOR MANAGEMENT OF HCC
IMPACT OF PHYSICOCHEMICAL FACTORS OF NANOPARTICLES ON HCC MANAGEMENT
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
A Summarized View of Lipid, Polyplex, Inorganic, and Carbon-Based Nanotherapeutics for Hepatocellular Carcinoma Treatment
Riddhi Trivedi1, Sanjay Arora1, Richard N. L. Lamptey1, Bivek Chaulagain1, Jagdish Singh1,* and Buddhadev Layek1,*.
INTRODUCTION
Nanotherapeutics for Hepatocellular Carcinoma (HCC)
Lipid-based Nanotherapeutics
Polymer-Based Nanotherapeutics
Inorganic Nanoparticles
Carbon-Based Nanotherapeutics
Nanotherapeutics Under Clinical Trials
CONCLUSIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGMENT
REFERENCES
Aptamers and Their Potential in Site-Specific Nanotherapy Against Hepatocellular Carcinoma
Debasmita Dutta1,2, Samrat Chakraborty2,3, Biswajit Mukherjee2, Moumita Dhara2 and Laboni Das4
INTRODUCTION
Therapeutic Approach for HCC: Active vs. Passive Targeting and Aptamer.
Aptamer as a Targeting Molecule and its Modifications for In Vivo Stability
Aptamer and HCC
Aptamers and In Vivo Imaging in HCC
Aptamers and Targeted Delivery in HCC
Aptamer-Functionalized Theranostic in HCC
Mechanisms of Aptamer Internalization
Factors Affecting In Vivo Therapeutic Potency of Aptamer
Resistant to Nuclease Enzyme
Renal Filtration
Safety of Aptamers
SELEX Technology for the Identification and Selection of Aptamers
Purified Membrane Protein-Based SELEX
Live Cell-Based SELEX
Some Prospective Use of Aptamers in HCC Therapy
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENT
REFERENCES
Preclinical Studies on Nanocarrier-Mediated Delivery of Radiosensitizing Agents to Brain and Pancreatic Cancer with a Future Projection to Liver Cancer
Peter Sminia1,*, Pei Pei Che1,2, Ben J. Slotman1 and Elisa Giovannetti2,3
INTRODUCTION
Nanocarrier-Mediated Drug Delivery to Brain Tumours
Nanocarrier Delivery of the Targeted MAPK Inhibitor Binimetinib
Nanocarrier Delivery of the Natural Compound Curcumin
Section III
Nanotechnological Strategies in Pancreatic Cancer
Applications of Gold Nanoparticles in Pancreatic Cancer
Section IV.
Perspective for Liver Cancer Therapy.