Download or read book Identification of Novel Therapeutic Targets and Tumor Suppressor Genes in Colon Cancer Using Genome wide High throughput Approaches written by Sarah Bazzocco and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Cancer Genomics written by Daniel Gaston and published by Elsevier Inc. Chapters. This book was released on 2013-11-21 with total page 50 pages. Available in PDF, EPUB and Kindle. Book excerpt: Colorectal cancer (CRC) is the third most common form of cancer and a leading cause of cancer-related mortality in both men and women, particularly in Western and developed nations. The high mortality rate has been attributed to the fact that colon cancer is often diagnosed at a late stage. Three primary subtypes of CRC have been described based on their molecular pathology and their underlying genetics: chromosomal instability (CIN), microsatellite instability (MSI), and CpG island hypermethylation. Over the last 30 years, molecular and genetic studies have determined a number of key genetic pathways that are subverted in CRC, including those involving APC, KRAS, and the p53 tumor suppressor. More recently, high-throughput, genome-wide studies have begun to characterize the broader genomic features of CRC. These high-throughput studies provide an ever expanding, and increasingly complex view of the molecular underpinnings of CRC. The chief goal of these studies being the identification of new therapeutic targets, as well as the definition of prognostic and diagnostic biological markers of CRC. Here, we highlight the key genetic and molecular pathways underlying CRC, as well as more recent insights into this disease uncovered by genomic studies.
Download or read book Genes and Cancer written by Guy-Joseph Lemamy and published by BoD – Books on Demand. This book was released on 2019-09-11 with total page 127 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a malignant tumor caused by DNA damage, which leads to uncontrolled cell growth. Tumor progression is locally favored by the mitogenic effects of hormones or growth factors, which stimulate the tumor's growth, or the activation of vascular endothelial growth factor receptor, which induces angiogenesis and leads to metastasis. About 300 out of 25,000 genes that set up the human genome are involved in cancer pathology. These genes are divided into three groups: oncogenes, tumor suppressor genes, and DNA repair genes. Activated oncogenes promote the development of cancer, whereas the tumor suppressor and DNA repair genes have a protective role by respectively inhibiting cell cycle progression and inducing apoptosis, or by repairing DNA damage occurring during the cell cycle. This book discusses the issue of tumor suppressor genes through chapters written by experts using advanced biochemistry, cell, and molecular biology tools. The tumor suppressor genes can be used as markers of risk to identify populations with high risk or targets for cancer treatment and therapeutic resistance. We hope that the work provided in this book will be useful for researchers and students and will increase knowledge of the understanding of cancer and improve its treatment.
Download or read book Genome wide Approaches for Discovery of Novel Genetic and Epigenetic Events in Gastrointestinal Cancer written by Ryan E Fecteau and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a disease caused by the sequential acquisition of genetic and epigenetic changes that transform a normal cell into an ungovernable malignancy. Advances in technologies to interrogate these changes on a genome-wide scale have reshaped our understanding of this disease and rapidly expanded the field of cancer genomics. The objective of the projects described herein was to adapt high-throughput methods to discover and characterize novel genetic and epigenetic events in gastrointestinal cancers with the intention of translational application. Three primary studies comprise the body of this thesis. In the first, we identify recurrent mutations in the oncogene GNAS found by sequencing of the colorectal cancer genome. Targeted pyrosequencing of GNAS in a colon cancer tumor cohort established a mutation frequency in colorectal cancer of around 2%. By comparing GNAS mutation status with clinical and pathologic data, we found that GNAS mutations associate with a distinct class of colon cancers that are characterized by concomitant KRAS or BRAF mutations, by location in the proximal colon, and by a unique association with a villous morphology. The second study applied a targeted next generation sequencing approach, whole exome sequencing, to identify a germ-line susceptibility variant in a familial syndrome of Barrett's esophagus and esophageal adenocarcinoma. Sequencing revealed a private variant in the uncharacterized gene VSIG10L that segregated with disease in a large familial Barrett's esophagus family and functional studies suggested the discovered variant disrupted maturation of the normal esophageal epithelium. Lastly, we describe using reduced representation bisulfite sequencing to examine the colon cancer methylome for candidate methylated biomarker loci. Preliminary data from this work has identified 3 candidate methylated DNA biomarkers for potential use in detection of colorectal cancer in patient plasma. Cumulatively, these studies have identified a rare mutation in colon cancer associated with a unique molecular phenotype, a private germ-line variant predisposing to familial Barrett's esophagus and adenocarcinoma, and candidate methylated biomarkers for detection and monitoring of colon cancer, all of which are of potential clinical importance.
Download or read book Discovery of Novel Molecular Targets in Cancer Using Bioinformatics written by Maurice Phillip De Young and published by . This book was released on 2003 with total page 288 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Advances in Cancer Research written by and published by Elsevier. This book was released on 2011-07-29 with total page 429 pages. Available in PDF, EPUB and Kindle. Book excerpt: The Advances in Cancer Research series provides invaluable information on the exciting and fast-moving field of cancer research. This volume stands as the first ever thematic volume in the series, focusing on the topic of genomics in cancer drug development. The chapters included in this book represent the cutting-edge information in the field and span such topics as Mass Spectrometry: Uncovering the Cancer Proteome for Diagnostics; Biomarker Discovery in Epithelial Ovarian Cancer by Genomic Approaches; The Application of siRNA Technology to Cancer Biology Discovery; Ribozyme Technology for Cancer Gene Target Identification and Validation; Cancer Cell-Based Genomic and Small Molecule Screens; Tumour Antigens as Surrogate Markers and Targets for Therapy and Vaccines; Practices and Pitfalls of Mouse Cancer Models in Drug Discovery; Biomarker Assay Translation from Discovery to Clinical Studies in Cancer Drug Development – Quantification of Emerging Protein Biomarkers; Molecular Optical Imaging of Therapeutic Targets of Cancer; Cancer Drug Approval in the United States, Europe and Japan.
Download or read book Hereditary Colorectal Cancer written by Laura Valle and published by Springer. This book was released on 2018-05-04 with total page 494 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides information on a wide variety of issues ranging from genetics to clinical description of the syndromes, genetic testing and counseling, and clinical management including surveillance, surgical and prophylactic interventions, and chemoprevention. Moreover, current hot issues, such as the identification of novel causal genes and the challenges we face, and the relevance of cancer risk modifiers, both genetic and environmental, are also discussed. This reference book is great for geneticists, oncologists, genetic counselors, researchers, clinicians, surgeons and nurses dedicated to, or interested in, hereditary cancer. The best and most recognized experts in the field have contributed to this project, guaranteeing updated information, accuracy and the discussion of topical issues.
Download or read book Testing a Candidate Gene Conserved in Early Colon Cancer Among Three Mammalian Species for a Role in Field Cancerization written by and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Colorectal cancer is the third most common cancer in both incidence and mortality worldwide. The ability to identify disease in its early stages through screening colonoscopy and effectively treat individuals, exemplifies the importance of early detection. However, low compliance and continued high mortality rates demonstrate the importance of less invasive screening methods and a deeper understanding of early disease. The Dove Lab has undertaken a comparative approach, utilizing both a mouse and a rat model of early intestinal tumorigenesis for identification of genetic changes important for early tumorigenesis in humans. The ultimate goal of these studies is to translate laboratory findings to human patients. Whole genome microarray analysis in the mouse, the rat, and the human has identified a number of genomic changes between normal colonic epithelium and adenoma. My thesis work has focused on understanding genomic changes in common between these two model species and the human. Approaches of comparison between species has identified a strength of comparison using Boolean logic as well as higher-level GO Category comparison to overcome technical and biological variation between microarray studies. This comparison of species has identified one novel gene, Pde4b, that was previously unknown to play a role in early tumorigenesis. Work on Pde4b in the mouse has focused on its functional role in field cancerization and early tumorigenesis in spontaneous and inflammatory tumors. Pde4b plays a protective role in early tumor formation. We identified Pde4b as overrepresented in normal colonic epithelium in animals with colon tumors and further overrepresented in tumors. We have shown that removing Pde4b results in a dosage-dependent increase in colon tumors. This is the first time Pde4b has been shown to play a role in colon tumor formation. In work on Pde4b in an inflammatory mouse model, we showed that Pde4b plays a protective role in tumor formation and response to inflammation. Animals null for Pde4b demonstrate a Apc mutant-dependent lethality. Together, my work on overlap between species with a focus on Pde4b shows the potential of using multiple species to identify novel candidates. These discoveries may be used as a way to identify biomarkers and provides useful information to identify candidates with therapeutic application.
Download or read book Genetics of Colorectal Cancer written by John D. Potter and published by Springer. This book was released on 2008-12-08 with total page 309 pages. Available in PDF, EPUB and Kindle. Book excerpt: Genetic susceptibility refers to how variations in a person’s genes increase or decrease his or her susceptibility to environmental factors, such as chemicals, radiation and lifestyle (diet and smoking). This volume will explore the latest findings in the area of genetic susceptibility to gastrointestinal cancers, focusing on molecular epidemiology, DNA repair, and gene-environment interactions to identify factors that affect the incidence of GI cancers. Topics will include germline susceptibility, including Mendelian patterns of inheritance and gene-environment interactions that lead to cancer etiology.
Download or read book The Genetics of Cancer in Pharmacological Drug Development written by Benjamin Hoffman and published by . This book was released on 2011 with total page 121 pages. Available in PDF, EPUB and Kindle. Book excerpt: The field of cancer therapeutic development has been dominated by two research and discovery paradigms, the cytotoxicity-based or phenotype driven strategy and the target-based rational approach. This thesis describes the standardization of novel assays used in both approaches and the discoveries made using these processes. Rational drug design or the target-based approach to discovering novel anti-cancer agents requires a basic understanding of the oncogenic signals that induce uncontrolled cellular proliferation. c-MET is a proto-oncogene, linked to a number of different cancers, that encodes a receptor tyrosine kinase. As an oncogene, c-MET has been shown to transform cells in the laboratory setting and is dysregulated in number of malignancies. Thus, we sought to discover a small molecule inhibitor of c-MET kinase activity by screening a novel library of small molecules. In the second part of this dissertation, we describe the standardization of a high-throughput assay to identify putative c-MET inhibitors and the results of our screening attempt. Cytotoxicity-based screening is another validated approach that is used to discover anti-cancer agents. As a parallel program to our c-MET discovery effort, we designed a high-throughput cytotoxicity assay to identify a novel small molecule with high cytotoxic activity towards tumor cells. The result of this screen was the identification of ON015640, a novel anti-cancer therapeutic with tubulin-depolymerizing activity. Throughout the course of this project, we tried to discern the advantages and disadvantages of the two predominant paradigms in cancer therapeutic research. Both strategies require careful assay design and an acute understanding of the molecular and genetic underpinnings of cancer. While it is clear that structure-based rational drug design has its merits and its success stories, it has become increasingly clear that seeking out a desired biological effect may serve as a more effective staring point when dealing with cancers for which no clear oncogene addiction phenotype has been observed.
Download or read book Identification of Novel Candidate Tumor Suppressor Genes at 5q and 14q for Multiple Carcinomas by Integrative Genomics and Epigenetics written by Ka Man Ng and published by . This book was released on 2007 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Computational Determination of Novel Biomarkers of Colon Cancer written by Ashok Palaniappan and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Download or read book Tumor Suppressor Genes written by Wafik S. El-Deiry and published by Humana Press. This book was released on 2003-03-03 with total page 520 pages. Available in PDF, EPUB and Kindle. Book excerpt: It has become clear that tumors arise from excessive cell proliferation and a c- responding reduction in cell death. Tumors result from the successive accumulation of mutations in key regulatory target genes over time. During the 1980s, a number of oncogenes were characterized, whereas from the 1990s to the present, the emphasis shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and tumor suppressor genes function in the same pathways, providing positive and ne- tive growth regulatory activities. The signaling pathways controlled by these genes involve virtually every process in cell biology, including nuclear events, cell cycle, cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Tumor suppressor genes are mutated in hereditary cancer syndromes, as well as somatically in nonhereditary cancers. In their normal state, TSGs control cancer development and p- gression, as well as contribute to the sensitivity of cancers to a variety of therapeutics. Understanding the classes of TSGs, the biochemical pathways they function in, and how they are regulated provides an essential lesson in cancer biology. We cannot hope to advance our current knowledge and to develop new and more effective therapies without understanding the relevant pathways and how they influence the present approaches to therapy. Moreover, it is important to be able to access the powerful tools now available to discover these genes, as well as their links to cell biology and growth control.
Download or read book Molecular Pathogenesis of Colorectal Cancer written by Kevin M. Haigis, Ph.D. and published by Springer. This book was released on 2016-08-23 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Colorectal cancer has for more than two decades served as the paradigm for the multi-step concept of cancer initiation and progression. Perhaps more than any other organ site, cancer of the colon is extensively characterized at the molecular level. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. The book will focus on the progression from the identification of mutations that drive colorectal cancer initiation and progression to the search for novel therapies to treat the disease.
Download or read book Characterizing and Selectively Targeting RNF20 Defects Within Colorectal Cancer Cells written by Brent Guppy and published by . This book was released on 2016 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: By 2030, the global colorectal cancer burden is projected to approximately double. This highlights the immediate need to expand our understanding of the etiological origins of colorectal cancer, so that novel therapeutic strategies can be identified and validated. The putative tumor suppressor gene RNF20 encodes a histone H2B mono-ubiquitin ligase and has been found altered/mutated in colorectal and numerous other cancer types. Several studies suggest that RNF20, and by extension mono-ubiquitinated histone H2B (H2Bub1), play important roles in maintaining genome stability in human cells. Indeed, hypomorphic RNF20 expression and/or function have been shown to underlie several phenotypes consistent with genome instability, making aberrant RNF20 biology a potential driver in oncogenesis. Through an evolutionarily conserved trans-histone pathway, RNF20 and H2Bub1 have been shown to modulate downstream di-methylation events at lysines 4 (H3K4me2) and 79 (H3K79me2) of histone H3. Accordingly, understanding the biology associated with RNF20, H2Bub1, H3K4me2, and H3K79me2 is an essential preliminary step towards understanding the etiological origins of cancer-associated RNF20 alterations and identifying a novel therapeutic strategy to selectively kill RNF20-deficient cancers. In this thesis, I employ single-cell imaging, and multiple biochemical techniques to investigate the spatial and temporal patterning and characterize the biology of RNF20, H2Bub1, H3K4me2 and H3K79me2 throughout the cell cycle. In addition, I employ the CRISPR-Cas9 genome editing system to generate RNF20-deficient HCT116 cells. Finally, I employ synthetic lethal strategies to selectively kill RNF20-depleted cells. In conclusion, the research chapters contained within this thesis have characterized putative drivers in cancer (Chapter 3), generated a valuable research reagent for CRISPR-Cas9 ii genome editing experiments (Chapter 4), and identified a novel therapeutic strategy to selectively kill certain cancer cells (Chapter 5). This thesis has increased our understanding of the etiological origins of cancer and generated novel reagents and treatments strategies that after further validation and clinical studies, could be employed to reduce morbidity and mortality rates associated with cancer.
Download or read book Tumor Organoids written by Shay Soker and published by Humana Press. This book was released on 2017-10-20 with total page 225 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.
Download or read book Prevention and Early Detection of Colorectal Cancer written by Graeme P. Young and published by W.B. Saunders Company. This book was released on 1996 with total page 410 pages. Available in PDF, EPUB and Kindle. Book excerpt: This is an overview of the issues involved in prevention and early detection of colorectal cancer providing up-to-date, practical advice for clinicians. Possible management strategies for those at risk are provided, taking into account the biological principles of colorectal cancer development, epidemiological data and emerging genetic information, as well as social and environmental factors.
