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Candidate gene based studies have identified a handful of aberrant CpG DNA methylation events in prostate cancer (Brooks et al. 1998; Yegnasubramanian et al. 2004). However, large scale DNA methylation profiles have not been examined for normal prostates or prostate tumors. Additionally, the mechanisms behind these DNA methylation alterations are unknown. In this thesis, I describe the results of my efforts to better understand these previously unexplored areas of biology. For the study presented in this thesis, I quantitatively profiled 95 primary prostate tumors and 86 healthy prostate tissue samples for their DNA methylation levels at 26,333 CpGs representing 14,104 gene promoters by using the Illumina HumanMethylation27 platform. When the profiles of the prostate tissue samples were compared, I observed a substantial number of tumor-specific DNA methylation alterations. A 2-class Significance Analysis of this dataset revealed 5,912 CpG sites with increased DNA methylation and 2,151 CpG sites with decreased DNA methylation in tumors (FDR
This volume is based on the proceedings of a NATO-Gulbenkian Foundation sponsored Summer School held in May-June 1982 in Sintra Estoril, Portugal. Given the accelerated growth of knowledge in the field of eukaryotic gene expression, it seemed timely to hold a NATO Advanced Study Institute to discuss current developments in this area of biology and to evaluate the potential of emerging technologies such as gene transfer, recombinant DNA cloning and quantitative high resolution two-dimensional gel electrophoresis. The initial articles in t~is volume describe various differentiation models and address questions such as the relationships between differentiation and cell proliferation, biochemical changes accompanying differen tiation, expression of differentiated gene products and their regulation as well as gene organization of cytoskeletal proteins. The second section describes properties of neoplastic cells, surveys current assays for transformation and offers some new insights into the mechanisms involved in carcinogenesis. The third part is dedicated to viral oncogenesis and to the role of onco genes in cell transformation. Particular emphasis is given to the role of tyrosine kinases in cell transformation. The concluding section deals with various aspects of gene expression in normal and transformed cells with special emphasis given to studies using two dimensional gel electrophoresis, cell hybridization, gene transfer and immunological techniques.
An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.
“Infogest” (Improving Health Properties of Food by Sharing our Knowledge on the Digestive Process) is an EU COST action/network in the domain of Food and Agriculture that will last for 4 years from April 4, 2011. Infogest aims at building an open international network of institutes undertaking multidisciplinary basic research on food digestion gathering scientists from different origins (food scientists, gut physiologists, nutritionists...). The network gathers 70 partners from academia, corresponding to a total of 29 countries. The three main scientific goals are: Identify the beneficial food components released in the gut during digestion; Support the effect of beneficial food components on human health; Promote harmonization of currently used digestion models Infogest meetings highlighted the need for a publication that would provide researchers with an insight into the advantages and disadvantages associated with the use of respective in vitro and ex vivo assays to evaluate the effects of foods and food bioactives on health. Such assays are particularly important in situations where a large number of foods/bioactives need to be screened rapidly and in a cost effective manner in order to ultimately identify lead foods/bioactives that can be the subject of in vivo assays. The book is an asset to researchers wishing to study the health benefits of their foods and food bioactives of interest and highlights which in vitro/ex vivo assays are of greatest relevance to their goals, what sort of outputs/data can be generated and, as noted above, highlight the strengths and weaknesses of the various assays. It is also an important resource for undergraduate students in the ‘food and health’ arena.
The Transformed Cell deals with many of the differences that may exist between transformed cells and their normal counterparts. Topics covered range from malignancy and the cell surface to cell cycle regulation in normal and transformed cells; phenotypic expression of malignant transformation and its relationship to energy metabolism; and virus-induced transformation. The involvement of cyclic nucleotides in transformation is also discussed, together with intracellular pH and growth control in eukaryotic cells. This book is comprised of 12 chapters and begins with a brief description of terminology and basic concepts relating to cancer cells, as well as some comments on tumorigenicity and cell transformation. The next two chapters explore the evidence for and against the possible correlation of in vivo tumorigenicity to in vitro changes in the cytoskeletal system; anchorage-dependent growth; plasminogen activator production; agglutinability by lectins; and cell surface and plasma membrane properties. The regulation of cell proliferation and the relationships between ion movement and energy metabolism in normal and transformed cells are then examined, along with the transformation of normal cells by infection with new genetic material from tumor viruses. The remaining chapters focus on selected cellular properties that have been purported to differ between the normal and transformed cell, with particular reference to cyclic nucleotides; polyamine metabolism; cell viscosity; mobility of cellular water; intracellular pH; and element concentration. This monograph will be of interest to biologists and medical practitioners devoted to understanding cancer cell biology and cancer therapy.
It has been recognized for almost 200 years that certain families seem to inherit cancer. It is only in the past decade, however, that molecular genetics and epidemiology have combined to define the role of inheritance in cancer more clearly, and to identify some of the genes involved. The causative genes can be tracked through cancer-prone families via genetic linkage and positional cloning. Several of the genes discovered have subsequently been proved to play critical roles in normal growth and development. There are also implications for the families themselves in terms of genetic testing with its attendant dilemmas, if it is not clear that useful action will result. The chapters in The Genetics of Cancer illustrate what has already been achieved and take a critical look at the future directions of this research and its potential clinical applications.
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.
This book is immensely useful for graduate students as well as researchers to understand the basics of molecular biology and Recombinant DNA Technology. It provides a comprehensive overview of different approaches for the synthesis of recombinant proteins from E. coli including their cloning, expression and purification. Recent advances in genomics, proteomics, and bioinformatics have facilitated the use of Recombinant DNA Technology for evaluating the biophysical and biochemical properties of various proteins. The book starts with an introductory chapter on gene cloning, protein expression and purification and its implication in current research and commercial applications. Each chapter provides a lucid set of principles, tools and techniques for both students and instructors. The protocols described have been aptly exemplified, and troubleshooting techniques have been included to aid better understanding. Moreover, the set of questions at the end of each chapter have been particularly formulated to help effective learning.