As studies using microarray technology have evolved, so have the data analysis methods used to analyze these experiments. The CAMDA conference plays a role in this evolving field by providing a forum in which investors can analyze the same data sets using different methods. Methods of Microarray Data Analysis IV is the fourth book in this series, and focuses on the important issue of associating array data with a survival endpoint. Previous books in this series focused on classification (Volume I), pattern recognition (Volume II), and quality control issues (Volume III). In this volume, four lung cancer data sets are the focus of analysis. We highlight three tutorial papers, including one to assist with a basic understanding of lung cancer, a review of survival analysis in the gene expression literature, and a paper on replication. In addition, 14 papers presented at the conference are included. This book is an excellent reference for academic and industrial researchers who want to keep abreast of the state of the art of microarray data analysis. Jennifer Shoemaker is a faculty member in the Department of Biostatistics and Bioinformatics and the Director of the Bioinformatics Unit for the Cancer and Leukemia Group B Statistical Center, Duke University Medical Center. Simon Lin is a faculty member in the Department of Biostatistics and Bioinformatics and the Manager of the Duke Bioinformatics Shared Resource, Duke University Medical Center.

DNA and RNA fractions have been isolated from the whole blood, serum, plasma, the surface of blood cells, urine, saliva and spinal fluid from both healthy individuals and clinical patients. Recent developments are presented concerning the isolation, quantification and analysis of these molecules and their use in the identification of specific nucleic acid fragments related to a variety of clinical disorders thereby permitting their early diagnosis and prognosis.

The purpose of this book is to provide an up to date review of the nature and consequences of epigenetic changes in cancer. Epigenetics literally means "above" genetics, and consists of heritable gene expression or other phenotypic states not accounted for by DNA base sequence. Epigenetic changes are now known to make a large contribution to various aspects of tumorigenesis. These changes include alterations in global and promoter specific DNA methylation, activating and repressive histone modifications, and changes in higher order chromatin structures. Each of these topics will be covered in this book.

The goal of this work is summarize the contribution that insertional mutagenesis has made to our understanding of cancer. A variety of insertional mutagens are presented that have been used to study a variety of tumor types in several model organisms. In addition, the impact of insertional mutagenesis in several gene therapy trials is discussed along with strategies to avoid such complications in future clinical trials.

The ?eld of cellular responses to DNA damage has attained widespread recognition and interest in recent years commensurate with its fundamental role in the ma- tenance of genomic stability. These responses, which are essential to preventing cellular death or malignant transformation, are organized into a sophisticated s- tem designated the "DNA damage response". This system operates in all living organisms to maintain genomic stability in the face of constant attacks on the DNA from a variety of endogenous by-products of normal metabolism, as well as exogenous agents such as radiation and toxic chemicals in the environment. The response repairs DNA damage via an intricate cellular signal transduction network that coordinates with various processes such as regulation of DNA replication, tr- scriptional responses, and temporary cell cycle arrest to allow the repair to take place. Defects in this system result in severe genetic disorders involving tissue degeneration, sensitivity to speci?c damaging agents, immunode?ciency, genomic instability, cancer predisposition and premature aging. The ?nding that many of the crucial players involved in DNA damage response are structurally and functionally conserved in different species spurred discoveries of new players through similar analyses in yeast and mammals. We now understand the chain of events that leads to instantaneous activation of the massive cellular responses to DNA lesions. This book summarizes several new concepts in this rapidly evolving ?eld, and the advances in our understanding of the complex network of processes that respond to DNA damage.

The mouse is a perfect model organism to study mammalian, and thus indirectly also human, embryology. Most scientific achievements that have had an important impact on the understanding of basic mechanisms governing embryo development in humans, originated from mouse embryology. Stem cell research, which now offers the promise of regenerative medicine, began with the isolation and culture of mouse embryonic stem cells by Martin Evans (who received the Nobel Prize in medicine in 2007 for this achievement) and Matthew Kaufman. This book provides an overview of mouse development, spanning from oocytes before fertilization to the state-of-the-art description of embryonic and adult stem cells. The chapters, written by the leading specialists in the field, deal with the most recent discoveries in this extremely fast-developing area of research.

Initially genetic disorders were all considered as rare diseases. At present, in the mid of 2009, the OMIM catalogue contains information on more than 12 000 entries of which about 2500 are available for clinical testing based on the identification of the responsible gene defect. However, altogether it has been estimated that about 8 percent of a population in the economically developed countries will during their lifetime suffer from a disease mainly as the result of their genetic constitution. Adding to that, it is estimated that all diseases have a genetic component, which will determine who will be at a higher than average risk for a certain disorder. Further it is postulated that in the near future, this genetic profiling could become useful in selecting an appropriate therapy adapted to the genetic constitution of the person. Thus, genetic disorders are not rare. Measuring quality of health care related processes became an issue in the 1990s, mainly in laboratory medicine, but also for hospitals and other health care systems. In many countries national authorities started to implement recommendations, guidelines or legal procedures regulating quality of health care delivery. In laboratory medicine, in parallel, the use of accreditation as a method assuring high quality standards in testing came in use. With the increasing possibilities of performing molecular genetic testing, genetic laboratories needed to become involved in this process. As many genetic disorders are rare, most laboratories worldwide offered analysis for a specific set of disorders, and, therefore, very early on a transborder flow of samples occurred. While international quality criteria (ISO) have been in existence for a number of years, the regulation of quality issues still may differ between countries. Based on their personal experience in the varying fields of quality research and clinical implementation of quality criteria in genetic services the authors of this book share their experience and give examples of the implementation of quality issues in national quality systems worldwide. This book, which is the result of the effort of many persons, is destined to aid laboratory managers and counsellors, health care managers and other stakeholders in national or international health care service to improve the services to the benefit of patients with suspected genetic disorders.

The term humanized mouse in this text refers to a mouse in which human tissues and cells have been transplanted and show the same biological function as they do in the human body. That is, the physiological properties and functions of tra- planted human tissues and cells can be analyzed in the mouse instead of using a living human body. It should therefore be possible to study the pathophysiology and treatment of human diseases in mice with good reproducibility. Thus, the hum- ized mouse can be used as a potent tool in both basic and clinical research in the future. The development of appropriate immunodeficient mice has been indispensable in the creation of the humanized mouse, which has been achieved through many years of efforts by several laboratories. The first stage on the road to the humanized mouse was the report on nude mice by Isaacson and Cattanach in 1962. Thereafter, nude mice were studied in detail by Falanagan and, in 1968, Pantelouris found that these mice have no thymus gland, which suggested that the mice lack transplan- tion immunity against xenografts such as human hematopoietic stem cells. At the Nude Mouse Workshops (organized by Regard, Povlsen, Nomura and colleagues) that were held nine times between 1972 and 1997, the possibility of creating a humanized mouse using nude mice was extensively examined. The results, however, showed that certain human cancers can be engrafted in nude mice, but unfortunately engraftment of normal human tissue was almost impossible.

"Tissue Morphogenesis: Methods and Protocols "highlights major techniques, both experimental and computational, for the study of tissue morphogenesis, divided into several sections, with specific focus on techniques to image, manipulate, model and analyze tissue morphogenesis. Chapters focus on imagining analysis of tissue morphogenesis, culture models of tissue morphogenesis, manipulating cells and tissues in vivo, novel model systems to investigate issue morphogenesis and computational models. 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 practical," ""Tissue Morphogenesis: Methods and Protocols" serves as a primary resource for both fundamental and practical understanding of the techniques used to uncover the basis of tissue morphogenesis.

The biomolecular basis underlying essential hypertension and end organ damage associated with hypertension is characterized as polygenic diseases with complexities such as "environment gene" and "gene-gene" interactions. Despite intensive research in this field, this molecular book is aimed at providing the state-of-the-art reviews which define how the biologic systems sense changes in environment, alter their activities or function, and cross talk with other neurohormonal systems to modulate cardiovascular/renal function and blood pressure. This title will attract scientists and investigators in both academic and industrial fields, and clinicians.

Regeneration, the homeostatic ability to maintain tissue structure in the face of normal cell turnover or loss of tissue damaged by trauma or disease, is an essential developmental process that continues throughout life. As recently as a decade ago, any serious discussion of the possibility of regeneration becoming a practical medical tool in the near future had the air of science fiction or over-optimistic speculation. The term "regenerative medicine" was certainly on many lips but few actually expected to soon see it applied in a clinical setting. A tidal wave of discovery has changed that and investigating the cellular mechanisms of natural regeneration has become one of the hottest topics in developmental biology and biomedicine in general. Many researchers entering the field find that the regeneration literature is still quite diffuse perhaps owing to the disparate biological systems that have been the object of study including hydra, planaria, newts, axolotls and more recently several mouse strains. The volume editors believe that an attempt to organize or systematize the literature is long overdue. In this volume, respected experts highlight the latest findings in vertebrate (including mammals) wound healing and regeneration. They present eleven reviews that cover a wide range of topics, from wound repair and its relationship to regeneration, through systems including lenticular, neural, and musculoskeletal tissues and limbs, to epigenetics and the role of the cell cycle. Nuclear reprogramming and cellular plasticity, which open the door for potential regenerative medical therapies for injury and degenerative disease, are recurring themes throughout the book. We are all now part of the regeneration revolution.

Developmental genetic studies of the spine and linkage and family-based association studies have led to recent advances in understanding the genetic etiology of idiopathic, neuromuscular, and congenital forms of scoliosis. The book is written by leaders in genetic and developmental research on scoliosis and developmental studies of the spine.

Angiogenesis is the growth of new blood vessels and is a key process which occurs during pathological disease progression. Excessive and damaging angiogenesis occurs in diseases such as cancer, diabetic retinopathies, age-related macular degeneration and atherosclerosis. In other diseases such as stroke and myocardial infarction, insufficient or improper angiogenesis results in tissue loss and ultimately higher morbidity and mortality. In this book we will begin by providing the reader with an overview of the process of angiogenesis including normal embryological development of blood vessels. The following chapters will each focus on a key angiogenic disease incorporating current scientific knowledge concerning the causes of activation of the "angiogenic switch", pathological consequences, current treatment options and future perspectives. Where appropriate, results from pre-clinical trials, novel imaging modalities and nanotechnological approaches will be incorporated into these sections. Finally, since it is now believed that the process of angiogenesis operated via different signalling mechanisms in different vascular beds, we will discuss our current understanding of this phenomenon. The target audience for this book would include researchers in all the basic sciences; post-graduate students at Universities and Institutes; pharmaceutical industries; clinicians working in vascular biology or tissue imaging; pathologists; neurologists; tumour biologists; ophthalmologists and cardiologists.

There are now compelling human epidemiological and animal experimental data that indicate the risk of developing adult-onset complex diseases and neurological disorders are influenced by persistent epigenetic adaptations in response to prenatal and early postnatal exposures to environmental factors. Epigenetics refers to heritable changes in gene function that occur without a change in the sequence of the DNA. The main components of the epigenetic code are DNA methylation, histone modifications, and non-coding RNAs. The epigenetic programs are established as stem cell differentiate during embryogenesis, and they are normally faithfully reproduced during mitosis. Moreover, they can also be maintained during meiosis, resulting in epigenetic transgenerational disease inheritance, and also potentially introducing phenotypic variation that is selected for in the evolution of new species. The objective of this two volume book is to provide evidence that environmental exposures during early development can alter the risk of developing medical conditions, such as asthma, autism, cancer, cardiovascular disease, diabetes, obesity, and schizophrenia later in life by modifying the epigenome. Consequently, epigenetic research promises to markedly improve our ability to diagnosis, prevent, and treat the pathological conditions of humans; however, it also introduces unique legal and ethical issues. This volume highlights the correlation between environmental factors and complex diseases, such as autism, addiction, neurological diseases, diabetes, obesity and cancer. It concludes with a chapter on legal and ethical implications of epigenetics.

MicroRNA (miRNA) is a cutting-edge topic in the scientific and medical fields. This is a timely and specialized book focusing on the current understanding of miRNAs and the potential for their application in cancer diagnosis, prognosis, and therapeutic targets. It also provides discussion of the lessons learned from translational miRNA studies and exploration of the next steps required to advance this field. The unique book comprises 22 in-depth chapters by gathering unparalleled topics of interest in miRNAs by international team of world-renowned experts in the field. The first fifteen chapters provide comprehensive and expert perspectives on the most common cancers from bench to bedside applications, there is no current book structured in this cancer-oriented way. The next seven chapters providing thorough overviews of miRNAs and cancer stem cells; miRNAs in cancer invasion and metastasis; miRNAs in predicting radiotherapy and chemotherapy response; as well as expounding the role of miRNA in anti-cancer drug resistance and as blood-based cancer biomarkers. Furthermore, this book explicates the interplay of miRNAs in cancer metabolism and an update on the pioneering RNAi-based treatment approaches is also presented. This specialized book will contribute great to the scientific and medical community by providing the up-to-date discoveries of miRNAs and their important roles in cancer translational research.

This book provides a state-of-the-art approach to the molecular basis of hematologic diseases and its translation into improved diagnostics and novel therapeutic strategies. Several representative hemato-oncologic malignancies are analyzed in detail: acute lymphoblastic leukemia, acute myeloid leukemia, B-cell Non-Hodgkin lymphomas, multiple myeloma, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. Experts in the field describe the molecular methods applied for modern diagnostics and therapies, such as hematopoietic stem cell transplantation, donor recipient matching, banking of biological material, analyses of post-transplant chimerism, and minimal residual disease monitoring. The volume concludes with an extensive section comprising thorough step-by-step protocols of molecular techniques in hematology, all of them validated in the authors' own laboratories.

The field of microRNA biology is really emerging in the last couple of years. Several investigators highlighted the importance of miRNAs in cancer. Although there is so much literature on microRNAs exist, a comprehensive book is still not available. Thus this book will be a great use to the scientists in the field of cancer biology. In addition, this book will be a good source of information for undergraduate, graduate students who want to develop their research careers in cancer biology.

Timing, racing, combating, struggling and targeting are some actions through which cellular fate could be reflected and evaluated. Interaction between cell territory and environment occur during pre-embryonic, fetal development, and post-natal periods. What the researchers observe as the outcome of telomeres behavior is only the peak of an ice mountain within a stormy ocean. Cellular life depends on programmed behavior of telomeres, capable to surprise the cells. Telomeres provide an introduction to the history of our cells which govern the quality of life and status of health. Telomeres as the cooperative territory are capable of stabilizing the chromosomal territory. The status of telomeres reflects the key information, announcing the real age of individuals, and may be a valuable marker for prognosis and predicting cancer. Telomere territory is characterized with a multi-disciplinary manner. Therefore, this book is aimed to offer a wide range of chapters, hoping to be useful for diverse audiences, including hematologists-oncologists, radiotherapists, surgeons, cancer researchers, and all the sectors who affect the macro- and micro- environmental domains. Finally, telomeres are sensitive, cooperative, and trustable targets. It is worth to state that 'telomeres are messengers of NATURE', let's to know them as they are.

Muscle disease represents an important health threat to the general population. There is essentially no cure. Gene therapy holds great promise to correct the genetic defects and eventually achieve full recovery in these diseases. Significant progresses have been made in the field of muscle gene therapy over the last few years. The development of novel gene delivery vectors has substantially enhanced specificity and efficiency of muscle gene delivery. The new knowledge on the immune response to viral vectors has added new insight in overcoming the immune obstacles. Most importantly, the field has finally moved from small experimental animal models to human patients. This book will bring together the leaders in the field of muscle gene transfer to provide an updated overview on the progress of muscle gene therapy. It will also highlight important clinical applications of muscle gene therapy.

Despite a half century of structural, biophysical and biochemical investigations of ribonucleic acids, they are still mysterious. RNAs stand at fertile crossroads of disciplines, integrating concepts from genomics, proteomics, dynamics as well as biochemistry and molecular biology. From 20 years it is clear, that genetic regulation of eukaryotic organisms has been misunderstood for the last years that the expression of genetic information is effected only by proteins. Basic understanding of nucleic acids has enhanced our foundation to probe novel biological functions. This is especially evident for RNA molecules whose functionality, maturation, and regulation require formation of correct secondary structure through encoded base-pairing interactions.

The rapidly developing field of systems biology is influencing many aspects of biological research and is expected to transform biomedicine. Some emerging offshoots and specialized branches in systems biology are receiving particular attention and are becoming highly active areas of research. This collection of invited reviews describes some of the latest cutting-edge experimental and computational advances in these emerging sub-fields of systems biology. In particular, this collection focuses on the study of mammalian embryonic stem cells; new technologies involving mass-spectrometry proteomics; single cell measurements; methods for modeling complex stochastic systems; network-based classification algorithms; and the revolutionary emerging field of systems pharmacology.

Trypanosomes are unicellular protozoa of ancient evolutionary origin that are responsible for several tropical diseases, such as African sleeping sickness. Over the last few decades, research in trypanosome biology has revealed many unique and fascinating features, many of which have helped to establish new paradigms in other biological systems. This applies in particular to studies in gene expression and regulation, which benefit enormously from the trypanosome genome projects and from the new genome-wide approaches recently introduced in trypanosome research. This volume covers the most important aspects of biosynthesis, processing, and functions of RNA in trypanosomes, ranging from transcription to RNA editing, mRNA splicing/translation/turnover, processing of transfer and ribosomal RNA, RNA interference, and current transcriptome-wide analyses. Recent progress in RNA-focused research in trypanosomatids promises to yield novel insights into trypanosome-specific features, as well as to reveal in the process new potential therapeutic strategies for combating these parasitic diseases.

JAK tyrosine kinases and STAT transcription factors constitute a signaling pathway, which is activated by cytokines. By activating gene transcription it regulates essential biological responses to environmental cues. The Jak-Stat pathway is involved in the regulation of cell development, differentiation, proliferation and apoptosis. Improper function may contribute to hematopoietic malignancies and cancer. This book provides comprehensive insights into the latest basic and clinical developments in the field. The first part reviews recent findings and new technologies pertaining to basics of Jak-Stat function. The second part describes the evolution of Jak-Stat signaling and the role of the pathway in invertebrate organisms. The third part focuses on Jak-Stat signaling in hematopoietic cells under both physiological and pathophysiological conditions. Finally, chapters in the fourth section describe the relationship of Jak-Stat signaling to various states of disease, particularly infection, leukemias and solid cancers. The book is intended for all scientists in molecular biology, biochemistry and cell biology dealing with biomedical issues.

Antibodies have long been used in the biomedical sciences as in vitro tools for the identification, purification and functional manipulation of target antigens. They are also being exploited in vivo for diagnostic and therapeutic applications and play an important role in cancer and AIDS research. This book summarizes preclinical studies from laboratories worldwide that have used intrabodies - intracellular antibodies - for gene therapy and research applications.

Steroids regulate differentiation, growth and functioning of many tissues via a nuclear receptor gene activation mechanism. Molecular biology has opened the way for more detailed investigation of the complex set of intracellular interactions contributing to organ-selective actions of steroids and steroid-like compounds such as vitamin D. In this volume leading experts address basic molecular mechanisms of tissue specificity and related issue, with the goal of attaining a better understanding of the underlying mechanisms of organ selective actions of steroids. Discussed is the extent to which tissue specificity might selectively be modified by chemical modification of the hormones and how this may be applied towards improved therapies by taking advantage of tissue selectivity.