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0 (hodnocen0 x )

EB

ONLINE

Tokyo : Springer Japan, 2015

1 online resource (330 pages)

ISBN 9784431556510 (electronic bk.)

ISBN 9784431556503

Print version: Nakao, Kazuwa Innovative Medicine Tokyo : Springer Japan,c2015 ISBN 9784431556503

Targeting Cancer Cell Metabolism -- Targeting Carnitine Palmitoyltransferase-1C -- Targeting Mutated Isocitrate Dehydrogenases -- Targeting Reactive Oxygen Species -- Exploiting Cancer Cell Aneuploidy -- Conclusion -- References -- Linear Polyubiquitination: A Crucial Regulator of NF-mB Activation -- The Ubiquitin Conjugation System -- The Canonical NF-mB Activation Pathways -- The Linear Ubiquitin Chains and Their Roles in NF-mB Activation -- Mechanism Underlying Linear Ubiquitin Chain-Mediated NF-mB Activation -- Perspectives -- References -- VCP, a Major ATPase in the Cells, as a Novel Drug Target for Currently Incurable Disorders -- Background -- VCP in Neurodegenerative Disorders -- Development of Novel Inhibitors (KUSs) of VCP ATPase Activity That Do Not Block VCP Cellular Functions -- KUSs Protected Cells Under ER Stress-Inducing Conditions ---

KUSs or Exogenous ATP Prevented ER Stress in Cultured Cells.

Targeting Cancer Cell Metabolism -- Targeting Carnitine Palmitoyltransferase-1C -- Targeting Mutated Isocitrate Dehydrogenases -- Targeting Reactive Oxygen Species -- Exploiting Cancer Cell Aneuploidy -- Conclusion -- References -- Linear Polyubiquitination: A Crucial Regulator of NF-mB Activation -- The Ubiquitin Conjugation System -- The Canonical NF-mB Activation Pathways -- The Linear Ubiquitin Chains and Their Roles in NF-mB Activation -- Mechanism Underlying Linear Ubiquitin Chain-Mediated NF-mB Activation -- Perspectives -- References -- VCP, a Major ATPase in the Cells, as a Novel Drug Target for Currently Incurable Disorders -- Background -- VCP in Neurodegenerative Disorders -- Development of Novel Inhibitors (KUSs) of VCP ATPase Activity That Do Not Block VCP Cellular Functions -- KUSs Protected Cells Under ER Stress-Inducing Conditions ---

Intro -- Preface -- Contents -- Part I: Basic Research for Innovative Medicine -- Diverting Glycolysis to Combat Oxidative Stress -- Chemical Definition and Sources of ROS -- Physiology of ROS -- Biochemical Mechanisms that Preserve Redox Homeostasis -- Metabolic Adaptations to ROS -- The Pentose Phosphate Pathway and NADPH Production -- Phosphofructokinase-1 Inhibition -- Glyceraldehyde 3-Phosphate Dehydrogenase Inhibition -- Pyruvate Kinase M2 Inhibition -- De Novo Serine Synthesis -- Conclusion -- References -- Metabolic Regulation by Nuclear Receptors -- Introduction -- NR Endogenous Ligands Are Dietary Sensors -- Gut and Gut Microbiota -- De Novo Lipogenesis -- Integrative Physiology-Nuclear Receptor-Mediated Crosstalk -- Fibroblast Growth Factors -- Lipids -- Concluding Remarks -- References -- Fighting Fire with Fire in Cancer -- Introduction -- Boosting the Immune System -- Targeting CTLA-4 -- IL-7 Treatment ---

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis -- Introduction -- Basic Characteristics of AM -- Pathophysiological Roles of AM in Inflammation -- Preclinical Pharmacological Effect of AM in Experimental Model of Colitis -- Exploratory Clinical Study of AM as a Therapeutic Agent for Refractory Ulcerative Colitis -- Conclusion -- References -- RNA Activation -- Introduction -- Molecular Mechanism -- saRNA-Associated Proteins -- Argonaute Proteins -- Heterogeneous Nuclear RNA-Binding Proteins -- Histone Modification Enzymes -- Target Site Selection of saRNA -- Application of saRNA -- Stem Cell Differentiation -- Clinical Therapy (Regenerative Medicine) -- Concluding Remarks -- References -- Part III: New Technology for Innovative Medicine ---

Genetic Models of Liver Fibrosis -- Reversibility of Hepatic Fibrosis -- Genomics of Fibrosis -- Framework for Antifibrotic Therapies -- Summary -- References.

Loss of Hippo Signaling in T Lymphocytes -- Loss of Hippo Signaling in Salivary Glands -- Loss of Hippo Signaling in Neurons -- Loss of Hippo Signaling in Bone -- Concluding Remarks -- References -- Inhibitory Immunoreceptors on Mast Cells in Allergy and Inflammation -- Introduction -- Allergin-1 -- Identification of Allergin-1 -- Expression of Allergin-1 -- Function of Allergin-1 -- In Vitro Analyses of Allergin-1 -- In Vivo Analyses of Allergin-1 -- CD300a -- Identification and Expression of CD300a -- Identification of a Ligand for CD300a -- Function of CD300a -- In Vitro Analyses of CD300a -- In Vivo Analyses of CD300a -- Blockade of CD300a-PS Interaction Prolonged Survival of Mice After CLP -- Conclusion -- References -- Doxycycline-Inducible Autoimmune Blistering Skin Disease Model ---

Pleiotropic Function of IL-6 -- Effect of IL-6 in Immune Response -- Effect of IL-6 in Acute-Phase Response -- Other Effects of IL-6 -- IL-6 Signaling Systems -- Regulatory Mechanisms of IL-6 Synthesis -- Transcriptional and Post-transcriptional Regulation of IL-6 -- Pathological Role of IL-6 in Autoimmune Inflammatory Diseases -- IL-6-Targeting Strategies: A New Era for the Treatment of Autoimmune Inflammatory Diseases -- Efficacy of Tocilizumab in Rheumatoid Arthritis -- Efficacy of Tocilizumab in Systemic Juvenile Idiopathic Arthritis -- Efficacy of Tocilizumab in Castleman’s Disease -- Efficacy of Tocilizumab in Other Autoimmune Inflammatory Diseases -- Mechanisms Through Which Tocilizumab Is Efficacious in Various Autoimmune Inflammatory Diseases -- Concluding Remarks -- References ---

Development of a Novel Rodent Model of NASH -- Identification of Hepatic Crown-Like Structure (hCLS) -- Macrophage-Induced C-Type Lectin (Mincle) -- Role of Mincle in Adipose Tissue Remodeling and Ectopic Fat Accumulation -- Summary -- References -- Multifaceted Translational Approach to Major Mental Illness -- Introduction -- Major Mental Illness Caused by a Combination of Multiple Genetic Risk Factors and Environmental Stressors in the Pathological Trajectory -- Research Infrastructure That Allows a Multifaceted Translational Approach to Major Mental Illness -- Two Representative Studies that Use the Research Infrastructure -- References -- Translational Research of Leptin in Lipodystrophy and Its Related Diseases -- Introduction -- Transgenic Mice Overexpressing Leptin -- Crossbreeding Experiment of LepTg Mice with A-ZIPTg Mice ---

KUSs Mitigated Pathologies of rd10, a Mouse Model of Retinitis Pigmentosa -- Discussion -- References -- Roles of E-cadherin in Hepatocarcinogenesis -- Introduction -- Results -- Physiological Function of E-cadherin in the Liver -- Progenitor Cell Proliferation in CDH1EL Mice -- Loss of E-cadherin Accelerates Oncogene-Addicted Liver Carcinogenesis -- Loss of E-cadherin Promotes Chemical-Induced HCC -- Relationship Between E-cadherin Loss and Mesenchymal and Stem Cell Markers in Human HCC -- Discussion -- References -- The Hippo Signaling Pathway: A Candidate New Drug Target for Malignant Tumors -- Introduction -- Loss of Hippo Signaling in the Liver -- Loss of Hippo Signaling in the Pancreas -- Loss of Hippo Signaling in the Intestine -- Loss of Hippo Signaling in the Lung -- Loss of Hippo Signaling in the Skin ---

TRP Channels: Their Function and Potentiality as Drug Targets -- Introduction -- Modulation of Trpa1 Channel Activity -- Oxidation Sensitivity of the Trpa1 Channel -- Modulation of Trpa1 by Other Activators and Inhibitors -- Subtype-Selective S-Nitrosylation by a Novel Nitrosamine -- TRPC Channels as Therapeutic Targets for Heart Failure -- Structure and Function of TRPC Channels -- Role of TRPC Channels in Pathological Cardiac Remodeling -- Negative Feedback Mechanism in TRPC Channels -- Suppression of Pathological Cardiac Hypertrophy by TRPC3/6 Inhibition -- Conclusion -- References -- Autophagic Cell Death and Cancer Chemotherapeutics -- Apoptosis and Other Types of Cell Death -- Autophagy -- Alternative Macroautophagy -- Autophagic Cell Death -- Cancer and Autophagic Cell Death -- Autophagic Cell Death and Cancer Chemotherapeutics -- References ---

Adrenomedullin as a Potential Therapeutic Agent for Refractory Ulcerative Colitis -- Introduction -- Basic Characteristics of AM -- Pathophysiological Roles of AM in Inflammation -- Preclinical Pharmacological Effect of AM in Experimental Model of Colitis -- Exploratory Clinical Study of AM as a Therapeutic Agent for Refractory Ulcerative Colitis -- Conclusion -- References -- RNA Activation -- Introduction -- Molecular Mechanism -- saRNA-Associated Proteins -- Argonaute Proteins -- Heterogeneous Nuclear RNA-Binding Proteins -- Histone Modification Enzymes -- Target Site Selection of saRNA -- Application of saRNA -- Stem Cell Differentiation -- Clinical Therapy (Regenerative Medicine) -- Concluding Remarks -- References -- Part III: New Technology for Innovative Medicine ---

Bullous Pemphigoid (BP), The Most Common Autoimmune Blistering Disease -- Clinical Features of BP -- Pathogenesis of BP -- COL17 as a Main AutoAg for BP -- BP Models Produced by "Humanization of Autoantigen" -- Generation of COL17-Humanized Mice.

Genetic Models of Liver Fibrosis -- Reversibility of Hepatic Fibrosis -- Genomics of Fibrosis -- Framework for Antifibrotic Therapies -- Summary -- References.

Leptin Replacement Therapy in Japanese Patients with Lipodystrophy -- Significance of Hepatic AMPK in the Metabolic Action of Leptin -- fMRI Analysis of Food-Related Brain Activity in Patients with Lipodystrophy -- Conclusions -- References -- Translational Research of the Activation of the C-Type Natriuretic Peptide (CNP)-Guanylyl Cyclase-B Pathway for Skeletal Dysplasia -- Introduction -- Skeletal Phenotypes of the CNP/GC-B System in Genetically Engineered Mice -- Importance of CNP/GC-B Signaling in Endochondral Bone Growth in Humans: Lessons from Rare Congenital Skeletal Disorders -- Translational Research into Activation of CNP/GC-B Signaling for Skeletal Dysplasias -- Conclusions and Future Prospects -- References -- Clarity and Challenges in Tissue Fibrosis -- Introduction -- Liver Fibrosis -- Mechanisms -- Role of Autophagy ---

Loss of Hippo Signaling in T Lymphocytes -- Loss of Hippo Signaling in Salivary Glands -- Loss of Hippo Signaling in Neurons -- Loss of Hippo Signaling in Bone -- Concluding Remarks -- References -- Inhibitory Immunoreceptors on Mast Cells in Allergy and Inflammation -- Introduction -- Allergin-1 -- Identification of Allergin-1 -- Expression of Allergin-1 -- Function of Allergin-1 -- In Vitro Analyses of Allergin-1 -- In Vivo Analyses of Allergin-1 -- CD300a -- Identification and Expression of CD300a -- Identification of a Ligand for CD300a -- Function of CD300a -- In Vitro Analyses of CD300a -- In Vivo Analyses of CD300a -- Blockade of CD300a-PS Interaction Prolonged Survival of Mice After CLP -- Conclusion -- References -- Doxycycline-Inducible Autoimmune Blistering Skin Disease Model ---

Pathogenesis of Non-alcoholic Steatohepatitis and Its Potential Therapeutic Strategies -- Introduction -- Interaction Between Adipocytes and Macrophages in Obese Adipose Tissue.

Pleiotropic Function of IL-6 -- Effect of IL-6 in Immune Response -- Effect of IL-6 in Acute-Phase Response -- Other Effects of IL-6 -- IL-6 Signaling Systems -- Regulatory Mechanisms of IL-6 Synthesis -- Transcriptional and Post-transcriptional Regulation of IL-6 -- Pathological Role of IL-6 in Autoimmune Inflammatory Diseases -- IL-6-Targeting Strategies: A New Era for the Treatment of Autoimmune Inflammatory Diseases -- Efficacy of Tocilizumab in Rheumatoid Arthritis -- Efficacy of Tocilizumab in Systemic Juvenile Idiopathic Arthritis -- Efficacy of Tocilizumab in Castleman’s Disease -- Efficacy of Tocilizumab in Other Autoimmune Inflammatory Diseases -- Mechanisms Through Which Tocilizumab Is Efficacious in Various Autoimmune Inflammatory Diseases -- Concluding Remarks -- References ---

Proceedings of the Uehara Memorial Foundation. Innovative Medicine: Basic Research and Development. Cardiac Reprogramming for Heart Repair -- Introduction -- Cell Fate Conversion by Transcription Factors.

Development of a Novel Rodent Model of NASH -- Identification of Hepatic Crown-Like Structure (hCLS) -- Macrophage-Induced C-Type Lectin (Mincle) -- Role of Mincle in Adipose Tissue Remodeling and Ectopic Fat Accumulation -- Summary -- References -- Multifaceted Translational Approach to Major Mental Illness -- Introduction -- Major Mental Illness Caused by a Combination of Multiple Genetic Risk Factors and Environmental Stressors in the Pathological Trajectory -- Research Infrastructure That Allows a Multifaceted Translational Approach to Major Mental Illness -- Two Representative Studies that Use the Research Infrastructure -- References -- Translational Research of Leptin in Lipodystrophy and Its Related Diseases -- Introduction -- Transgenic Mice Overexpressing Leptin -- Crossbreeding Experiment of LepTg Mice with A-ZIPTg Mice ---

Direct Reprogramming of Mouse Fibroblasts into Cardiomyocytes in Vitro.

KUSs Mitigated Pathologies of rd10, a Mouse Model of Retinitis Pigmentosa -- Discussion -- References -- Roles of E-cadherin in Hepatocarcinogenesis -- Introduction -- Results -- Physiological Function of E-cadherin in the Liver -- Progenitor Cell Proliferation in CDH1EL Mice -- Loss of E-cadherin Accelerates Oncogene-Addicted Liver Carcinogenesis -- Loss of E-cadherin Promotes Chemical-Induced HCC -- Relationship Between E-cadherin Loss and Mesenchymal and Stem Cell Markers in Human HCC -- Discussion -- References -- The Hippo Signaling Pathway: A Candidate New Drug Target for Malignant Tumors -- Introduction -- Loss of Hippo Signaling in the Liver -- Loss of Hippo Signaling in the Pancreas -- Loss of Hippo Signaling in the Intestine -- Loss of Hippo Signaling in the Lung -- Loss of Hippo Signaling in the Skin ---

Neonatal BP Model Induced by Maternally Transferred Abs to Human COL17 -- Active BP Model -- Doxycycline-Inducible BP Model -- Perspectives -- References -- T Cell Senescence and Autoimmunity -- Introduction: Immune Aging and Senescence- Associated T Cells -- SA-T Cells Represent an Endogenously Arising Follicular T Cell Population with Age -- SA-T Cells Increase Robustly in Bone Fide Lupus-Prone Mice -- SA-T Cells Show Typical Signs and Features of Cellular Senescence -- SA-T Cells Are Activated in Response to Autologous GC B Cells to Produce OPN that Protects Against B Cell Apoptosis in GCs -- Involvement of SA-T Cells in the Expansion of GCs and Autoimmunity in Lupus -- Conclusion and Perspectives -- References -- Part II: Translational Research for Innovative Medicine -- IL-6: A New Era for the Treatment of Autoimmune Inflammatory Diseases -- Introduction ---

TRP Channels: Their Function and Potentiality as Drug Targets -- Introduction -- Modulation of Trpa1 Channel Activity -- Oxidation Sensitivity of the Trpa1 Channel -- Modulation of Trpa1 by Other Activators and Inhibitors -- Subtype-Selective S-Nitrosylation by a Novel Nitrosamine -- TRPC Channels as Therapeutic Targets for Heart Failure -- Structure and Function of TRPC Channels -- Role of TRPC Channels in Pathological Cardiac Remodeling -- Negative Feedback Mechanism in TRPC Channels -- Suppression of Pathological Cardiac Hypertrophy by TRPC3/6 Inhibition -- Conclusion -- References -- Autophagic Cell Death and Cancer Chemotherapeutics -- Apoptosis and Other Types of Cell Death -- Autophagy -- Alternative Macroautophagy -- Autophagic Cell Death -- Cancer and Autophagic Cell Death -- Autophagic Cell Death and Cancer Chemotherapeutics -- References ---

001895034

express

(Au-PeEL)EBL6422590

(MiAaPQ)EBC6422590

(OCoLC)1156906627