Cancer kills about one American per minute, amounting to over 500,000 deaths in the United States and millions, worldwide, each year. There is a critical need for safe, effective, and affordable alternative treatment modalities, especially for inoperable, recurring, and chemo-resistant cancers, that do not respond well to current treatment regimen. An electrical-pulse-mediated, enhanced drug delivery technique known as electroporation is one way to effectively treat these patients. Electroporation-based Therapies for Cancer reviews electroporation-based.clinical studies in hospitals of various cancer treatments, including melanomas, head and neck cancers, and chest wall breast carcinomas. This technique is especially suitable for low- and middle-income countries, where lack of infrastructure and resources leads to cancer diagnoses at late stages. This quick, safe, economical, out-patient-based technique is a boon to these patients for palliative and other care with enhanced quality of life. This book features discussions by interdisciplinary authors including practicing oncological surgeons, medical professionals, and academic and other researchers of the basics and clinical medical applications of electroporation.
Key features include: • novel and recent clinical applications of electrochemotherapy for various cancers • an extensive study of a number of cell lines, including human breast cancer, lung cancer and leukemia using both reversible and irreversible electroporation techniques • In vitro study of delivery of various commonly prescribed breast cancer chemo and hormone drugs, such as Doxorubicin, Paclitaxel and Tamoxifen.
Dr Raji Sundararajan, PhD, is a Professor at the Electrical and Computer Engineering Technology Department, Purdue University. She obtained her initial training on electroporation at Johns Hopkins Medical School and has been doing research on electroporation for the past several years. She has authored and co-authored over 150 publications and was the recipient of the 2010 Indiana 'Women & Hi-Tech' award for 'Distinguished use of technology in healthcare Life Science', winning a prestigious one year fellowship to study regenerative medicine therapy using optoinjection and electroporation techniques at Purdue. A winner of several awards, Dr. Sundararajan is also a reviewer of NIH, NSF (including CAREER awards), US International Science & Technology Center, and US National Research Council proposals and various scholarly journals including International Journal of Cancer, Molecular Biotechnology, Journal of Biomedical Microdevices, Journal of Anticancer drugs, Sensors, Computers in Biology and several IEEE Transactions.

List of figures and tables xv

Acknowledgements xxv

About the editor xxvii

About the contributors xxix

Introduction xxxix

1 Electrochemotherapy - A novel cancer treatment 1

1.1 Why electrochemotherapy? 1

1.2 References 2

2 Clinical electrochemotherapy for chest wall recurrence from breast cancer 3

2.1 Introduction 4

2.2 Scope of the problem 5

2.3 Treatment options for chest wall recurrence 9

2.4 Clinical experience with electrochemotherapy 17

2.5 Electrochemotherapy: the engineer's point of view 22

2.6 Conclusions and perspectives 27

2.7 Acknowledgments 28

2.8 References 29

3 Clinical electrochemotherapy for advanced superficial melanoma 35

3.1 Introduction 36

3.2 Therapeutic options in advanced melanoma 38

3.3 Clinical experience with electrochemotherapy 40

3.4 Conclusions and perspectives 49

3.5 References 50

4 Low and high voltage electrochemotherapy for breast cancer: an in vitro model study 55

4.1 Introduction 56

4.2 Anatomy of the breast and its cancer 59

4.3 Drug delivery issues 59

4.4 Chemotherapy issues 61

4.5 Common adverse effects of anticancer drugs 62

4.6 Anticancer drug resistance 63

4.7 Electroporation and electrochemotherapy 65

4.8 Materials and methods 67

4.9 Results and discussion 80

4.10 Conclusions 97

4.11 Acknowledgments 99

4.12 References 99

5 Why electroporation is a useful technique for cancer treatments? 103

5.1 Introduction 103

5.2 What is electroporation (EP)? 106

5.3 Irreversible electroporation (IRE) 107

5.4 Electrochemotherapy (ECT) 107

5.5 Example of a hydrophilic agent used with electrochemotherapy 108

5.6 Local delivery by intratumoral injection versus systemic administration in EP 108

5.7 Prerequisites for effective ECT 109

5.8 ECT can overcome multidrug resistance 109

5.9 Intense nanosecond pulsed electric fields (nsPEFs) 110

5.10 Electroporation therapies can produce a reduction in blood flow to tumors 111

5.11 Properties of solid tumors 112

5.12 Why do tumors have increased susceptibility to (EP) permeabilizing pulses, compared to that of normal tissue? 113

5.13 Membrane composition and mineral concentrations of cancer cells affect the electrical properties 114

5.14 Oxygen levels vary in solid tumors 115

5.15 Glycolysis and pH 116

5.16 Conclusions 118

5.17 References 118

6 Electrically-enhanced proliferation control of cancer-stem-cells-like adult human mesenchymal stem cells - a novel modality of treatment 127

6.1 Introduction - stem cells 128

6.2 Mesenchymal stem cells 129

6.3 Cancer and cancer stem cells 129

6.4 Electrochemotherapy 133

6.5 In-vitro study of ECT on MSC 135

6.6 Materials and methods 135

6.7 Results and analyses 140

6.8 Discussion and conclusions 153

6.9 Future directions 154

6.10 Acknowledgments 155

6.11 References 155

7 An in vitro study of electroporation of leukemia and cervical cancer cells 161

7.1 Introduction 162

7.2 Materials and methods 167

7.3 Results and analysis 173

7.4 Conclusions 178

7.5 Acknowledgments 180

7.6 References 180

8 Low voltage nanosecond electroporation for breast cancer treatment: an in vitro study 185

8.1 Introduction 186

8.2 Materials and methods 187

8.3 Results and analysis 191

8.4 Discussion and conclusions 192

8.5 Acknowledgment 196

8.6 References 196

9 Low and high voltage electroporation of in vitro ovarian adenocarcinoma cells 199

9.1 Introduction 200

9.2 Materials and methods 203

9.3 Results and analysis 206

9.4 Discussion and summary 212

9.5 Acknowledgments 216

9.6 References 216

10 Irreversible electroporation: a drug-free cancer treatment 219

10.1 Introduction 220

10.2 Materials and methods 222

10.3 Results and analyses 228

10.4 Discussion and conclusions 238

10.5 Acknowledgments 241

10.6 References 241

11 Targeted delivery of siRNA and other difficult to transfect molecules using electroporation: current status and future scope 245

11.1 Introduction 245

11.2 siRNA - a potential therapeutic tool for cancer treatment 246

11.3 siRNA - gene targets in cancer 247

11.4 Delivery of siRNA 248

11.5 Electroporation-based siRNA delivery 250

11.6 Summary and future scope 255

11.7 References 255

12 Electric field distribution study of breast tumors 259

12.1 Introduction 260

12.2 Electric field concepts 261

12.3 Electrical properties of cells 261

12.4 Finite element modeling 263

12.5 Electric field intensity used in clinical electrochemotherapy 266

12.6 Electrodes used 267

12.7 Thermal effects of electroporation 267

12.8 Simulation 268

12.9 Breast modeling 268

12.10 Results and discussion 277

12.11 Conclusions 287

12.12 References 288

Index 293

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