In the approach to the analysis of disease, including, of course, cancer, two major thrusts may be distinguished. These may be referred to, in shorthand, as agents and processes: the causative agents (chemical, microbial, physical, environmental, and psychosocial) and the organismic processes, initiated and furthered by the agents, culminating in observable pathology (at the macromolecular, cytological, histological, organ function, locomotor, and behavioral levels). The past 25 years, since the appearance of the first volume of the predecessor series (1) authored by the Editors of this present volume, have seen an impressive number of studies on chemicals (and other agents) as etiologic factors in the induction of cancer. The major emphasis has been on the discovery of many chemical carcinogens of widely different structures, their metabolism by various tissues and cells, and, in turn, their molecular-biochemical effects on the cells. This rapidly expanded body of information, as effectively covered in the predecessor volumes, is an excellent entree to the second half of the overall problem of chemical carcinogenesis, the processes. The active agents trigger a large array of molecular-biochemical alterations to which the target cells, target tissues, and target organisms respond in many select and common ways. This second major aspect of the induction of cancer by chemicals (and by other agents)- the sequence of cellular and tissue changes clearly relevant to cancer-remains the challenge for the future.

Affecting over a hundred million individuals worldwide, retinal diseases are among the leading causes of irreversible visual impairment and blindness, and appropriate study models, especially animal models, are essential to furthering our understanding of the etiology, pathology, and progression of these endemic diseases. In Animal Models for Retinal Diseases, recognized experts in the field highlight valuable techniques as well as animal models for the prominent retinal diseases in order to aid in the evaluation, development, and improvement of therapeutic strategies. Beginning with an overview of the morphology of the retina, visual behavior, and genetics and genomics approaches for retinal research, the book continues by covering animal models for the research of specific human retinal diseases, e.g., retinal degeneration, age-related macular degeneration, retinopathy of prematurity, diabetic retinopathy, glaucoma, retinal ischemia, and retinal inflammation. As a volume in the successful Neuromethods series, the chapters provide authoritative reviews of the most commonly used approaches in the field. Vital and easy to use, Animal Models for Retinal Diseases serves to support the important future research of ocular investigators, ophthalmologists, and neuroscientists currently delving into this fascinating field of study.

Aerosol therapy has significantly improved the treatment of a variety of respiratory diseases. Besides the treatment of respiratory diseases there is currently also a great interest to use the lungs as a portal to introduce drugs for systemic therapy.
The success of therapy with the application of aerosolized medicaments depends on the possibility to deliver the proper amount of drug to the appropriate sites in the respiratory system, thus limiting the side effects to a minimum. Aerosolized delivery of drugs to the lung is optimized if, for a given chemical composition of a medicine, the target of deposition and the required mass of drug to be deposited are precisely defined.
The next step is the specification of the number of respirable particles or droplets, to be generated by appropriate devices. Another very important factor for successful aerosol therapy is the condition of the patient coupled with his or her inhalation technique.

The title of this monograph, Brain Tumor Research and Therapy, is the name of the Conference itself, which had its inaugural meeting in the United States in 1975 andhas since progressed to the international scale. In Japan, the first conference ofits kind was organized by Dr. Takao Hoshino and me and was held at Nikko in 1980, hence its name, the Nikko Conference on Brain Tumor Research and Therapy. Though it started as a small, closed meeting, the conference has grown considerably, and in 1992 it was reorganized as the Japanese Conference on Brain Tumor Research and Therapy and was opened to all neurosurgeons and neuropathologists interested in the study of brain tumor problems and who are participating in this field. The main purpose of the Conference on Brain Tumor Research and Therapy is the candid and informed discussion of the most up-to-date developments in basic re search and clinical treatment of brain tumors. The 3rd Japanese Conference on Brain Tumor Research and Therapy was held at Nasu (Tochigi Prefecture), Japan, in No vember 1994. It was a great honor to welcome many distinguished guests from over seas who kindly attended each session and made valuable contributions.

This book provides a practical guide to analysis of simple and complex method comparison data, using Stata, SAS and R. It takes the classical Limits of Agreement as a starting point, and presents it in a proper statistical framework. The model serves as a reference for reporting sources of variation and for providing conversion equations and plots between methods for practical use, including prediction uncertainty.Presents a modeling framework for analysis of data and reporting of results from comparing measurements from different clinical centers and/or different methods.Provides the practical tools for analyzing method comparison studies along with guidance on what to report and how to plan comparison studies and advice on appropriate software.Illustrated throughout with computer examples in R.Supported by a supplementary website hosting an R-package that performs the major part of the analyses needed in the area.Examples in SAS and Stata for the most common situations are also provided.Written by an acknowledged expert on the subject, with a long standing experience as a biostatistician in a clinical environment and a track record of delivering training on the subject.

Biostatisticians, clinicians, medical researchers and practitioners involved in research and analysis of measurement methods and laboratory investigations will benefit from this book. Students of statistics, biostatistics, and the chemical sciences will also find this book useful.

"Mycobacterium tuberculosis" is one of the most notorious pathogens on earth, causing the death of approximately 1.5 million people annually. A major problem in the fight against tuberculosis is the emergence of strains that have acquired resistance to all available antibiotics. One key to the success of "M. tuberculosis" as a pathogen is its ability to circumvent host immune responses at different levels. This is not only a result of the special makeup of "M. tuberculosis" in terms of genetic diversity and DNA metabolism and its possession of specialized secretion systems, but also of its ability to hijack the host s innate immune defence mechanisms.

In this volume, researchers from different disciplines provide a topical overview of the diverse mechanisms that contribute to the virulence of "M. tuberculosis," ranging from their genetic, metabolic and molecular makeup, as well as the complex strategies these bacteria utilize to escape immune destruction within infected hosts."

A comprehensive state-of-the-art summary of breast cancer research and treatment by leading authorities. The book's many distinguished contributors illuminate the biology and genetics of breast cancer, including what is known about the hereditary breast cancer genes, BRCA1 and 2, the cutting-edge cytogenic approaches, and the biology of breast cancer metastasis. In addition, the authors describe current and future methods of breast cancer treatment in depth, and discuss environment and diet as risk factors for the disease. Breast Cancer: Molecular Genetics, Pathogenesis, and Therapeutics constitutes an excellent reference and resource for all those clinical and experimental oncologists, as well as genetic counselors nurses, who need to understand the latest developments in breast cancer biology, risk, and treatment.

This book covers the latest developments in rolling circle amplification (RCA) technology with applications in clinical diagnostic tests and molecular medicine. Topics covered include new enzymes useful in RCA, techniques involving RCA for enhanced signal amplification, novel RCA diagnostics, sensors for expediting RCA detection, and prospective RCA-based therapeutics. This is a valuable book for university professors and students in the field of biomedical engineering and biomolecular pharmacology as well as R&D managers of biotechnology and biopharmaceutical companies. Specifically, this book: Reviews prospective RCA-based therapeutics, including RCA-derived DNA nanoparticles that strongly bind to cancer cells Expands readers' understanding of sensor systems for expediting detection of RCA products by using probe-tagged magnetic nanobeads Maximizes reader insights into novel RCA diagnostics, such as PNA openers-assisted RCA for detection of single target cells and in situ RCA diagnosis of cancer cells and malignant tissues Presents innovative methods for quasi-exponential enhancement of RCA-generated signals, such as nicking enzyme-assisted cascade RCA and RCA coupled with loop-mediated amplification Advance Praise for Rolling Circle Amplification (RCA): "This book provides a badly needed compendium of innovative RCA methods and applications. It should help further increase the community of scientists that have employed RCA in research and diagnostic programs."- Charles Cantor, Professor Emeritus of Biomedical Engineering, Boston University Executive Director, Retrotope Inc. (USA) "In this new book Vadim Demidov has assembled an enticing menu of articles that illustrate the evolution of the RCA field, including improved protein parts for building superior DNA nanomachines, enhanced modalities of amplification and detection, diagnostic applications, and even a sampling of potential therapeutic applications. The reader will appreciate that while RCA has come of age, there is no lack of exciting surprises, turns, and twists in the continuing evolution of the technology."- Paul Lizardi, Professor of Pathology, Yale University School of Medicine (retired) Investigator, University of Granada, Spain, President, PetaOmics, Inc., San Marcos, Texas.

These proceedings report on the conference "Math Everywhere," celebrating the 60th birthday of the mathematician Vincenzo Capasso. The conference promoted ideas Capasso has pursued and shared the open atmosphere he is known for. Topic sections include: Deterministic and Stochastic Systems. Mathematical Problems in Biology, Medicine and Ecology. Mathematical Problems in Industry and Economics. The broad spectrum of contributions to this volume demonstrates the truth of its title: Math is Everywhere, indeed.

This book covers the latest results in the field of risk analysis. Presented topics include probabilistic models in cancer research, models and methods in longevity, epidemiology of cancer risk, engineering reliability and economical risk problems. The contributions of this volume originate from the 5th International Conference on Risk Analysis (ICRA 5). The conference brought together researchers and practitioners working in the field of risk analysis in order to present new theoretical and computational methods with applications in biology, environmental sciences, public health, economics and finance.

Continuous regeneration of the cornea is necessary to maintain this tissue in the transparent state that is essential for vision. Therapy for repair of the damaged anterior cornea is currently addressed through the transplantation of donor corneas or the delivery of limbal epithelial stem cells (LESC) to the ocular surface using amniotic membrane (AM) as a supporting scaffold. Research on the bioengineering of corneal equivalents as replacement tissue is underway to develop viable corneal prosthetics. Corneal Regenerative Medicine: Methods and Protocols provides a concise overview of essential techniques in the field of corneal regenerative medicine, highlighting novel strategies to guide the management of key therapies within this area of medicine. Divided into four convenient sections, topics include the identification, characterisation and cultivation of LESC, as well as the investigation of biopolymers used as the basis for corneal substitutes. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Corneal Regenerative Medicine: Methods and Protocols covers the fundamental techniques useful for both the laboratory and clinical settings.

Interest in the ability of myocardium to adapt to ischaemic stress has continued to grow since the discovery of ischaemic preconditioning in 1986. In 1993, two reports heralded the recognition of a delayed preconditioning response in the heart, now commonly known as the second window' of protection. Since then, a number of studies have described the ability of delayed preconditioning and related adaptive phenomena to protect against a variety of pathologies in the ischaemic and reperfused myocardium. Our understanding of the cellular mechanisms of sub-acute adaptive cardioprotection has advanced considerably during this period. This compilation of state-of-the-art reviews by those who have made significant contributions to this field provides detailed and critical analysis of this research, from molecular basis to potential clinical relevance. The book aims to provide an authoritative, comprehensive and thoroughly up-to-date overview for scientists and clinicians engaged in, or observing, this rapidly-developing area of heart research. It will also be of interest to those engaged in research on other tissues where ischaemia-reperfusion pathology is of major concern.

This volume provides readers with the basic principles and fundamentals of extrusion technology and a detailed description of the practical applications of a variety of extrusion processes, including various pharma grade extruders. In addition, the downstream production of films, pellets and tablets, for example, for oral and other delivery routes, are presented and discussed utilizing melt extrusion. This book is the first of its kind that discusses extensively the well-developed science of extrusion technology as applied to pharmaceutical drug product development and manufacturing. By covering a wide range of relevant topics, the text brings together all technical information necessary to develop and market pharmaceutical dosage forms that meet current quality and regulatory requirements. As extrusion technology continues to be refined further, usage of extruder systems and the array of applications will continue to expand, but the core technologies will remain the same.

Carl Edward Sagan's (1934-1996) one of the famous quotation was "Who are we? We find that we live on an insignificant planet of a humdrum star lost in a galaxy tucked away in some forgotten corner of a universe in which there are far more galaxies than people." From past to date, well-known molecules, enzymes, proteins, lipids and carbohydrates are studied in the pathogenesis of several diseases both as a diagnostic/prognostic biomarker and therapeutic agent. The underlying mechanism of unexplained diseases and failure of therapies are frequently studied with well-known biomarkers, but remain unclear in many cases. As Dr. Sagan said other keys are still waiting to be known in some forgotten corner of a body universe, we find strength to propose that one of them can be the growth factor with cytokine activity named "Midkine" This book summarizes the extensive up-to-date literature overeview with the lastest work of experts about midkine in a detailed format that conveys its role as both a pathologic factor and therapeutic agent.

Is talent the only key to scientific success? In fact, the answer is: No'. Management and organisation do make a real, significant difference between success and failure in science. This book presents a clear survey of the critical success factors in biomedical research laboratories. Based on an international, comparative study of 71 research laboratories in medical faculties, large health research institutes and innovative pharmaceutical companies, ready-to-use guidelines are offered to those who are responsible for the management of research groups. Dr. Omta is biochemist and has played a key role in the development of the EU Biotechnology Network. He has performed the comparative study for this book in the position of Managing Director of the Institute for Research in Extramural Medicine in Amsterdam. The author has recently been appointed as Associate Professor at the Faculty of Management and Organisation at the University of Groningen, the Netherlands. This work is a unique guide for heads, professors, or managers of (biomedical) research laboratories in universities, research institutes and innovative pharmaceutical companies, who are seeking rational tools for increasing the performance and effectiveness of their research groups.

Cancer drug discovery has been and continues to be a process of ingenuity, serendip ity, and dogged determination. In an effort to develop and discover better therapies against cancer, investigators all over the world have increased our knowledge of cell biology, biochemistry, and molecular biology. The goal has been to define therapeuti cally exploitable differences between normal and malignant cells. The result has been an increased understanding of cellular and whole-organism biology and an increased respect for the flexibility and resiliency ofbiologically systems. Thus, as some new therapeutic targets have been defined and new therapeutic strategies have been attempted, so have some new biological hurdles resulting from tumor evasion of the intended therapeutic attack been discovered. Historically, anticancer drugs have originated from all available chemical sources. Synthetic molecules from the chemical industry, especially dyestuffs and warfare agents, and natural products from plants, microbes, and fungi have all been potential sources of pharmaceuticals, including anticancer agents. There is no shortage of molecules; the challenge has been and continues to be methods of identifying molecules that have the potential to be therapeutically important in human malignant disease. "Screening" remains the most important and most controversial method in cancer drug discovery. In vitro screens have generally focused on cytotoxicity and have identified several highly cytotoxic molecules. Other endpoints available in vitro are inhibition of proliferation, 3 inhibition of [ H]thymidine incorporation into DNA and various viability assays, based most frequently on dye exclusion or metabolism.

Pancreatic islets make up the endocrine pancreas and they contain the only source of insulin in the body, beta cells. Hence, access to high quality preparations of pancreatic islets is fundamental for in vitro studies and to test pre-clinical applications in animal models in vivo. Access to healthy human islets is also crucial to improve transplantation procedures for diabetes. Given the susceptibility of pancreatic islets to the enzymatic digestion and mechanical stress required to obtain them, the isolation of islets is often considered as the delicate "work of a craftsman". This book, which is aimed at beginners and experts alike, is a survey of the current state-of-the-art in this field and it centres on the challenges, pitfalls and peculiarities of pancreatic islet isolation in the different species used in pre-clinical and clinical applications. It explores the similarities and differences between human islets and those from other relevant species (rodents, pigs and non-human primates), and how these influence islet isolation. The ultimate goal of this book is to improve the outcome of islet isolation and transplantation in pre-clinical and clinical applications.

The use of human beings as research subjects poses distinctive ethical issues. Subjects of medical research are exposed to risks of harm for the sake of generating scientific knowledge that can benefit future patients and society. Ethical analysis of the challenges posed by research involving human subjects requires careful attention to the contextual details of scientific experimentation. This book contains 22 essays by Franklin G. Miller on research ethics written over a 15-year period. With the exception of the first essay, all have been previously published in bioethics and medical journals. The book is arranged into four parts. Part One addresses a general ethical perspective on the protection of human subjects in clinical research, including paternalism in research regulation and acceptable limits to research risks. The essays in Part Two examine ethical issues in study design. It includes ethical analyses of controversial types of medical experimentation-studies that provoke psychiatric symptoms, induce infections, provide patients with placebos that withhold proven effective treatments or administer fake invasive procedures, test experimental treatments in cancer patients who have exhausted all standard treatment options, and employ the use of deception to generate scientifically valid data. Part Three offers a systematic critique of "the therapeutic orientation" to clinical trials and the principle of clinical equipoise, which is widely regarded as a fundamental norm for randomized treatment studies. Part Four takes up a range of ethical issues relating to informed consent for research participation, including examination of "the therapeutic misconception" and presentation of a novel approach to the validity of consent: "the fair transaction model." An abiding theme, developed in many of the essays is that the ethics of clinical research is importantly different from the ethics of medical care.

The aim of this volume is to provide a wide range of techniques and aspects of mouse retinal phenotyping and characterization. Chapters guide readers through morphological and functional properties of the mouse retina and techniques for the analysis of outer to mid-retina and mid- to inner retina. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Mouse Retinal Phenotyping: Methods and Protocols aims to ensure successful results in the further study of this vital field.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

This volume provides insight into recent developments on experimental and clinical strategies for cancer gene therapy. Gene Therapy of Solid Cancers: Methods and Protocols guides readers through protocols on gene therapeutic strategies in combination with helpful technical notes. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Concise and easy-to-use, Gene Therapy of Solid Cancers: Methods and Protocols aims to ensure successful results in the further study of this vital field.

This book introduces the reader to modern computational and statistical tools for translational epigenomics research. Over the last decade, epigenomics has emerged as a key area of molecular biology, epidemiology and genome medicine. Epigenomics not only offers us a deeper understanding of fundamental cellular biology, but also provides us with the basis for an improved understanding and management of complex diseases. From novel biomarkers for risk prediction, early detection, diagnosis and prognosis of common diseases, to novel therapeutic strategies, epigenomics is set to play a key role in the personalized medicine of the future. In this book we introduce the reader to some of the most important computational and statistical methods for analyzing epigenomic data, with a special focus on DNA methylation. Topics include normalization, correction for cellular heterogeneity, batch effects, clustering, supervised analysis and integrative methods for systems epigenomics. This book will be of interest to students and researchers in bioinformatics, biostatistics, biologists and clinicians alike. Dr. Andrew E. Teschendorff is Head of the Computational Systems Genomics Lab at the CAS-MPG Partner Institute for Computational Biology, Shanghai, China, as well as an Honorary Research Fellow at the UCL Cancer Institute, University College London, UK.

Cutting edge technologies can propel a simple finding in basic science to a concept that can be of immense value to the society. While applying novel techniques to unravel the mysteries of biological processes, an offshoot of applied branch emerged. This field, which is now widely referred to as Translational Research utilizes basic science findings and translates these findings into innovative concepts for the benefit of mankind. This branch of science has evolved into a multidisciplinary juggernaut encompassing all known fields of science as varied as biomedicine, environment, law, economics, sociology, etc. With the ever increasing interest in this branch and the dreams and aspirations that this field can bring, basic science researchers are now taking a bold step into this new realm, merging different fields of knowledge to come up with novel inventions. This book "Translational research in environmental and occupational stress" provides and insight into the research that led to discoveries, inventions and development of novel technologies which will have a tremendous impact on the future of mankind.