CONTENTS

PREFACE

List of Contributors

Biomarkers with Prognostic Potential in Prostate Cancer

Christos K. Kontos*, Margaritis Avgeris and Andreas Scorilas

INTRODUCTION

PROTEIN-CODING GENES AS MOLECULAR BIOMARKERS IN CAP

Kallikrein-related Peptidases (KLKs)

Androgen Receptor (AR)

Secreted Frizzled-Related Proteins 1 (SFRP1) and 2 (SFRP2)

Phosphatase and Tensin Homolog (PTEN)

Insulin-like Growth Factor (IGF) System

Transforming Growth Factor Beta (TGF-β) Isoforms

Interleukin-6 (IL-6)

Chromogranin A (CHGA)

Erythroblast Transformation-specific (ETS) Transcription Factors

α-methylacyl-CoA Racemase (AMACR)

Endoglin (ENG)

NON-CODING GENES AS MOLECULAR BIOMARKERS IN CAP

Long Non-coding RNAs (lncRNAs)

MicroRNAs (miRNAs)

MOLECULAR BIOMARKERS DERIVED FROM EXOSOMES AND OTHER EXTRACELLULAR VESICLES

CONCLUSION

KEY ISSUES

CONSENT FOR PUBLICATION

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

REFERENCE

Overview of Chemoresistance in Cancerous Cells

Mahima Kaushik1,2,*, Swati Mahendru2, Mohan Kumar2, Swati Chaudhary2, Saami Ahmed2, Sonia 2 and Shrikant Kukreti2,*

INTRODUCTION TO CANCER AND CHEMOTHERAPY

COMMON CAUSES OF CANCER

CANCER THERAPIES

(i). Surgery

(ii). Radiation Therapy

(iii). Targeted Therapy

a. Immunotherapy

b. Hormone Therapy

(iv). Chemotherapy

Cytotoxic Chemotherapy

OVERVIEW OF CHEMORESISTANCE

FACTORS RESPONSIBLE FOR CHEMORESISTANCE

a. Genetic Factors

(i). Alteration in Drug Transport Across the Cell Membrane

(ii). Enhanced DNA Repair Mechanism

(iii). Modification of Drug Target

(iv). Inhibition of Apoptosis

(v). Alteration in Drug Metabolism

b. Epigenetic Factors

(i). DNA Methylation

(ii). Histone Modification

(iii). MicroRNA Regulation

c. Tumor Microenvironment (TME)

Cancer Cell Heterogeneity

(i). Soluble Factor Mediated Drug Resistance (SFM-DR)

(ii). Cell Adhesion Mediated Drug Resistance (CAM-DR)

MOLECULAR MECHANISMS OF DRUG RESISTANCE

a. Platinum Based Drugs

b. Antimetabolites

c. Alkylating Agents

d. Enzyme Inhibitors

e. Anti Microtubule Agents

OVERCOMING CHEMORESISTANCE

a. Combination Therapy

b. Nanoparticulate Drug Delivery System

c. Gene Delivery Through RNA Interference (RNAi)

d. Novel Approaches to Overcome Chemoresistance

(i). Micro RNA Based Strategies

(ii). Targeting Specific Transcription Factors

(iii). Phytochemical Modulation of Apoptosis and Autophagy

(iv). Elimination of Drug-resistant Cell Types

RECENT INTERVENTIONS FOR APPROACHING CANCER BETTER

(a). Molecular Signatures of Cancer Using Bioinformatics and Systems Biology Approach

(b). Chemoresistance Biomarkers and Drug Companion Diagnostics

OUTLOOK AND FUTURE DIRECTIONS

CONSENT FOR PUBLICATION

CONFLICT OF INTEREST

ACKNOWLEDGEMENT

REFERENCES

Perspective on Trends in Drug Discovery: Deciphering GPCRs through Integration of Systems and Synthetic Biology

Aman Chandra Kaushik1,2 and Shakti Sahi1,*

INTRODUCTION

Current Pharmacological and Non-Pharmacological Therapies for Diseases

Pharmacophore Hypothesis

3D Quantitative Structure Activity Relationships (3D QSAR)

Molecular Dynamics (MD) Simulation Studies

G protein-coupled Receptors

Structure and function of the G protein-coupled Receptors

Mechanism of GPCRs

Models of Activation by Diffusible Agonists

Classification of GPCR

The Adhesion Receptor Family

The Secretin Receptor Family

The Glutamate Receptor Family

The Frizzled/Taste2 Receptor Family

Rhodopsin family

Methodology

New trends of Drug Discovery of Orphan GPCRs through integration of Systems and Switching Biology

Systems Biology as a new trends for Drug Discovery of G protein-coupled Receptor

The Role of Molecular and Cellular Biology in Regulatory Pathway Systems of G protein-coupled receptor using Systems Biology approach

Synthetic/switching biology as a new trends for Drug Discovery

First wave of synthetic biology

Second wave of synthetic biology

CONCLUDING REMARKS

CONSENT FOR PUBLICATION

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

REFERENCE

Ribavirin Against Viral, Neoplastic and Inflammatory Diseases: Focus on Mechanisms of Action

Danijela Savic*, Ivana Bjelobaba, Sanja Pekovic and Irena Lavrnja

INTRODUCTION

RIBAVIRIN AGAINST VIRUSES

Ribavirin Chemistry

Virus Sensitivity to Ribavirin

Hepatitis C Virus

Respiratory Syncytial Virus

Lassa Virus

Pharmacokinetics of Ribavirin

Ribavirin Uptake

Ribavirin Metabolism

Mechanisms of Antiviral Action of Ribavirin

RMP as an Inhibitor of IMPDH

Actions of RTP

Additional Indirect Mechanisms of Ribavirin

The Future of Ribavirin as an Antivirus drug

RIBAVIRIN AGAINST CANCER CELLS

IMPDH as a Cancer Target

eIF4E as the Cancer Target

The Prospect of Ribavirin in Cancer

RIBAVIRIN IN NEUROINFLAMMATION

MS and EAE

Targets of Ribavirin in EAE

CONCLUDING REMARKS

CONSENT FOR PUBLICATION

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

REFERENCES

Carbon Nanotubes and Drug Targets

Malay K. Das* and Anupam Sarma

INTRODUCTION

Types of Carbon Nanotubes

Production of Carbon Nanotubes

PHARMACOLOGY OF CARBON NANOTUBES

Mechanism of Cellular Uptake of Carbon Nanotubes

Toxicity of Carbon Nanotubes

In vitro Toxicological Studies of Carbon Nanotubes

In vivo Toxicological Studies of Carbon Nanotubes

Human Toxicity of Carbon Nanotubes

PHARMACOKINETICS OF CARBON NANOTUBES

Factors Affecting CNT Biodistribution

CNT Surface Modification

Non-covalently Functionalized (or Coated) CNT

Covalently-functionalized CNT

Surface Density of Functionalization

PEGylation of CNTs

Other Factors Affecting the Biodistribution of CNTs

TARGETED AND CONTROLLED DRUG DELIVERY VIA CNTS

CNTs Drug Delivery to Lymphatic System

CNTs Drug Delivery to Tumor

CNTs Drug Delivery to Central Nervous System (CNS)

CNTs Drug Delivery for Gene Therapy

CNTs for Vaccine Delivery

CNTs for Macrophages Targeting

REGULATORY CONSIDERATIONS OF CNTS

CONCLUSION AND FUTURE PERSPECTIVES

CONSENT FOR PUBLICATION

CONFLICT OF INTEREST

ACKNOWLEDGEMENT

REFERENCES

Tautomycetin, Protein Phosphatase 1 Specific Inhibitor, opened the Door for understanding the Role of PP1 in Minkowski Space

Makoto Ubukata*

INTRODUCTION

Discoveries of Tautomycin (TM) and Tautomycetin (TC) as Protein Phosphatase Inhibitors

Usage of tautomycetin (TC) as specific PP1 inhibitor

Relationship Between ATM Kinase and Protein Phosphatase 1 (PP1) via Ribosomal Protein S6 (RPS6) Revealed by Tautomycetin (TC)

Tautomycetin (TC) as a Novel Immunosuppressant

Low Concentration TC Selectively Inhibits Growth of Colorectal Cancer Cells via p21cip1 Induction

Tautomycetin (TC) Modulates LPS-induced Toll-like Receptor (TLR) Response via Inhibition of PP1/GADDA34 Holoenzyme

Selective Inhibitor of PP1/GADD34 Holoenzyme can Ameliorate Protein-misfolding Diseases, Amyotrophic Lateral Sclerosis (ALS) and Multiple Sclerosis (MS)

Is Protein Phosphatase 1 (PP1) a Regulator of Mammalian Circadian Clock?

CONCLUSION

APPENDIX

CONSENT FOR PUBLICATION

CONFLICT OF INTEREST

ACKNOWLEDGEMENT

REFERENCES

Phosphodiesterases as Drug Targets in Selected Respiratory Diseases

Juraj Mokry1,2,* and Daniela Mokra2,3

INTRODUCTION

PHOSPHODIESTERASES

PDE INHIBITORS

Non-selective PDE Inhibitors

Mechanism of Action

Mechanism of Action at Higher Doses

Mechanism of Action at Lower Doses

Adverse Effects

Selective PDE Inhibitors

PDE3 Inhibitors

PDE4 Inhibitors

PDE5 Inhibitors

PDE7 Inhibitors

Dual/multi-isoform Selective PDE Inhibitors

ROLE OF PDE AND POTENTIAL USE OF PDE INHIBITORS IN CHRONIC OBSTRUCTIVE PULMONARY DISEASE

ROLE OF PDE AND POTENTIAL USE OF PDE INHIBITORS IN BRONCHIAL ASTHMA

ROLE OF PDE AND POTENTIAL USE OF PDE INHIBITORS IN ACUTE LUNG INJURY

Definitions of Acute Lung Injury

Acute Lung Injury in Adults and Older Children

Pathophysiological Features

Treatment Approaches in ALI/ARDS

Use of PDE Inhibitors in ALI/ARDS

ARDS of Pulmonary Origin

ARDS of Extrapulmonary Origin (Sepsis, Shock and Multiple Organ Failure)

Pulmonary Hypertension Related to ALI/ARDS

Acute Lung Injury in the Neonates

Respiratory Distress Syndrome (RDS)

Bronchopulmonary Dysplasia (BPD) or Chronic Lung Disease (CLD)

Meconium Aspiration Syndrome (MAS)

Persistent Pulmonary Hypertension of the Newborn (PPHN)

Congenital Pneumonia and Neonatal Sepsis

CONCLUSIONS

CONSENT FOR PUBLICATION

CONFLICT OF INTEREST

ACKNOWLEDGEMENTS

LIST OF SELECTIVE PDE INHIBITORS

REFERENCES

SUBJECT INDEX