Download or read book Integrated Analysis of Breast Cancer Cell Lines Reveals Unique Signaling Pathways written by and published by . This book was released on 2009 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Cancer is a heterogeneous disease resulting from the accumulation of genetic defects that negatively impact control of cell division, motility, adhesion and apoptosis. Deregulation in signaling along the EGFR-MAPK pathway is common in breast cancer, though the manner in which deregulation occurs varies between both individuals and cancer subtypes. We were interested in identifying subnetworks within the EGFR-MAPK pathway that are similarly deregulated across subsets of breast cancers. To that end, we mapped genomic, transcriptional and proteomic profiles for 30 breast cancer cell lines onto a curated Pathway Logic symbolic systems model of EGFR-MEK signaling. This model was comprised of 539 molecular states and 396 rules governing signaling between active states. We analyzed these models and identified several subtype specific subnetworks, including one that suggested PAK1 is particularly important in regulating the MAPK cascade when it is over-expressed. We hypothesized that PAK1 overexpressing cell lines would have increased sensitivity to MEK inhibitors. We tested this experimentally by measuring quantitative responses of 20 breast cancer cell lines to three MEK inhibitors. We found that PAK1 over-expressing luminal breast cancer cell lines are significantly more sensitive to MEK inhibition as compared to those that express PAK1 at low levels. This indicates that PAK1 over-expression may be a useful clinical marker to identify patient populations that may be sensitive to MEK inhibitors. All together, our results support the utility of symbolic system biology models for identification of therapeutic approaches that will be effective against breast cancer subsets.
Download or read book Molecular Profiling Ofchemotherapy Acquired Resistance in Triple Negatice Breast Cancer Cell Lines written by Elaheh Ahmadzadeh and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: "Triple-negative breast cancer (TNBCs), characterized by tumors that do not express estrogen receptor (ER), progesterone receptor (PR), or HER-2 genes, shows one of the most aggressive clinical behaviors with distinctive metastatic patterns and very poor prognosis. Since no targeted therapy is available, chemotherapy and, in particular, taxane-based therapy (e.g. paclitaxel) is the treatment of choice for patients with TNBC. TNBCs are initially highly responsive to PTX, however the majority of advanced TNBC patients acquire resistance and develop progressive disease. Here we developed five in vitro models of resistance to better understand and characterize the biological mechanisms underlying resistance to PTX. We used an integrative analysis of array CGH and gene expression data to gain insights into the functional genomic changes in PTX-resistant TNBC cell lines. The results of integrative analysis of array CGH and gene expression identified ABCB1 as the most highly up-regulated gene in all 5 resistant cell lines. This up-regulation was accompanied by gene amplification in three resistant cell lines: BT20R, SUM149R and MDA-468 but not in 2 other lines, MDA-MB-231 and MDA-MB-436. Further analysis of the 7q21.12 chromosome fragment containing the ABCB1 gene in BT20R, SUM149R and MDA-468R revealed similar, but not identical, intra-genic breakpoints in ABCB1. RNAseq analysis identified novel inter-chromosomal translocations of ABCB1 in 2 drug resistance cell lines containing ABCB1 breakpoints. These genomic rearrangements occurred in the 5' un-translated region (UTR) of ABCB1. We hypothesize that the deletion of the 5'UTR of ABCB1 in these resistant cell lines may serve to overcome a translation initiation block, which would then favor the expression of ABCB1. The overexpression of ABCB1 at protein level was confirmed only in the three resistant cell lines with the ABCB1 genomic rearrangement, suggesting that the deletion of 5'UTR of ABCB1 may be a candidate biomarker to predict resistance to paclitaxel in triple negative breast cancers. In order to better understand the biological significance of the observed changes we performed pathway analysis and identified enriched molecular function of deregulated genes common in resistant cell lines. We found that the molecular function "growth factor activity", including several epidermal growth factor receptor (EGFR) ligands was consistently up-regulated in all 5 resistant cell line models. Considering the importance of EGFR ligands and given the up-regulation of EGFR signaling pathway, we examined the sensitivity of all five cell line models to two EGFR inhibitors, lapatinib and neratinib in combination with PTX. Our results revealed that the addition of 100nM of lapatinib or neratinib partially re-sensitized resistant cell lines to PTX to various degrees, with one exception: BT20R did not show sensitivity to the addition of 100nM lapatinib to increasing concentration of PTX. These results suggest that anti-EGFR therapies can re-sensitize PTX-resistant TNBC cells to PTX and that up-regulation of EGFR ligands in PTX resistant cell lines may be a biomarker of sensitivity to EGFR inhibitors." --
Download or read book Atlas of Cancer written by Maurie Markman and published by Current Medicine Group. This book was released on 2008-06-13 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: The second edition of the Atlas of Cancer highlights the major features of current cancer management, and clearly presents fundamental facts regarding our understanding of the etiology and pathophysiology of malignant disease.
Download or read book The OMICs written by Giovanni Coppola and published by Oxford University Press. This book was released on 2014 with total page 385 pages. Available in PDF, EPUB and Kindle. Book excerpt: The OMICs:Applications in Neuroscience summarizes the state of the art in OMICs applications in neurology and neuroscience, attracting neurologists who are interested in the progress of this field towards clinical applications, and neuroscientists who may be not familiar with the most recent advances in this ever-changing field. The book will include an overview of most relevant high-throughput approaches (collectively known as 'OMICs') and how they relate to neurology and neuroscience. The explosion of high-throughput assays has introduced large datasets, computational servers, and bioinformatics approaches to neuroscience and medicine in general. The reader will be provided with an overview of the application or method, a perspective on the current and future applications in neurology and neuroscience, and a few published examples illustrating possible practical use. Emerging topics such as ethical issues related to personal genome sequencing, epigenetics, network analysis, and role of peripheral biomarkers in disease diagnosis and follow-up will be covered as well.
Download or read book Epithelial Mesenchymal Plasticity in Cancer Metastasis written by Mohit Kumar Jolly and published by MDPI. This book was released on 2020-12-29 with total page 512 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recent studies have highlighted that epithelial-mesenchymal transition (EMT) is not only about cell migration and invasion, but it can also govern many other important elements such as immunosuppression, metabolic reprogramming, senescence-associated secretory phenotype (SASP), stem cell properties, therapy resistance, and tumor microenvironment interactions. With the on-going debate about the requirement of EMT for cancer metastasis, an emerging focus on intermediate states of EMT and its reverse process mesenchymal-epithelial transition (MET) offer new ideas for metastatic requirements and the dynamics of EMT/MET during the entire metastatic cascade. Therefore, we would like to initiate discussions on viewing EMT and its downstream signaling networks as a fulcrum of cellular plasticity, and a facilitator of the adaptive responses of cancer cells to distant organ microenvironments and various therapeutic assaults. We hereby invite scientists who have prominently contributed to this field, and whose valuable insights have led to the appreciation of epithelial-mesenchymal plasticity as a more comprehensive mediator of the adaptive response of cancer cells, with huge implications in metastasis, drug resistance, tumor relapse, and patient survival.
Download or read book Cancer Systems Biology Bioinformatics and Medicine written by Alfredo Cesario and published by Springer Science & Business Media. This book was released on 2011-08-21 with total page 496 pages. Available in PDF, EPUB and Kindle. Book excerpt: This teaching monograph on systems approaches to cancer research and clinical applications provides a unique synthesis, by world-class scientists and doctors, of laboratory, computational, and clinical methods, thereby establishing the foundations for major advances not possible with current methods. Specifically, the book: 1) Sets the stage by describing the basis of systems biology and bioinformatics approaches, and the clinical background of cancer in a systems context; 2) Summarizes the laboratory, clinical, data systems analysis and bioinformatics tools, along with infrastructure and resources required; 3) Demonstrates the application of these tools to cancer research; 4) Extends these tools and methods to clinical diagnosis, drug development and treatment applications; and 5) Finishes by exploring longer term perspectives and providing conclusions. This book reviews the state-of-the-art, and goes beyond into new applications. It is written and highly referenced as a textbook and practical guide aimed at students, academics, doctors, clinicians, industrialists and managers in cancer research and therapeutic applications. Ideally, it will set the stage for integration of available knowledge to optimize communication between basic and clinical researchers involved in the ultimate fight against cancer, whatever the field of specific interest, whatever the area of activity within translational research.
Download or read book Statistical Diagnostics for Cancer written by Matthias Dehmer and published by John Wiley & Sons. This book was released on 2012-11-28 with total page 301 pages. Available in PDF, EPUB and Kindle. Book excerpt: This ready reference discusses different methods for statistically analyzing and validating data created with high-throughput methods. As opposed to other titles, this book focusses on systems approaches, meaning that no single gene or protein forms the basis of the analysis but rather a more or less complex biological network. From a methodological point of view, the well balanced contributions describe a variety of modern supervised and unsupervised statistical methods applied to various large-scale datasets from genomics and genetics experiments. Furthermore, since the availability of sufficient computer power in recent years has shifted attention from parametric to nonparametric methods, the methods presented here make use of such computer-intensive approaches as Bootstrap, Markov Chain Monte Carlo or general resampling methods. Finally, due to the large amount of information available in public databases, a chapter on Bayesian methods is included, which also provides a systematic means to integrate this information. A welcome guide for mathematicians and the medical and basic research communities.
Download or read book Signal Transduction in Cancer written by David A. Frank and published by Springer Science & Business Media. This book was released on 2002-12-31 with total page 358 pages. Available in PDF, EPUB and Kindle. Book excerpt: One of the most exciting areas of cancer research now is the development of agents which can target signal transduction pathways that are activated inappropriately in malignant cells. The understanding of the molecular abnormalities which distinguish malignant cells from their normal counterparts has grown tremendously. This volume summarizes the current research on the role that signal transduction pathways play in the pathogenesis of cancer and how this knowledge may be used to develop the next generation of more effective and less toxic anticancer agents. Series Editor comments: "The biologic behavior of both normal and cancer cells is determined by critical signal transduction pathways. This text provides a comprehensive review of the field. Leading investigators discuss key molecules that may prove to be important diagnostic and/or therapeutic targets."
Download or read book Innovative Approaches in Drug Discovery written by Bhushan Patwardhan and published by Academic Press. This book was released on 2016-10-03 with total page 482 pages. Available in PDF, EPUB and Kindle. Book excerpt: Despite considerable technological advances, the pharmaceutical industry is experiencing a severe innovation deficit, especially in the discovery of new drugs. Innovative Approaches in Drug Discovery: Ethnopharmacology, Systems Biology and Holistic Targeting provides a critical review and analysis of health, disease and medicine, and explores possible reasons behind the present crisis in drug discovery. The authors illustrate the benefits of systems biology and pharmacogenomics approaches, and advocate the expansion from disease-centric discovery to person-centric therapeutics involving holistic, multi-target, whole systems approaches. This book lays a path for reigniting pharmaceutical innovation through a disciplined reemergence of pharmacognosy, embracing open innovation models and collaborative, trusted public-private partnerships. With unprecedented advances made in the development of biomedically-relevant tools and technologies, the need is great and the time is now for a renewed commitment towards expanding the repertoire of medicines. By incorporating real-life examples and state-of-the-art reviews, this book provides valuable insights into the discovery and development strategies for professionals, academicians, and students in the pharmaceutical sciences. Analyzes the reasons behind historical drug failures to provide valuable insights on lessons learned Uses current scientific research to promote learning from traditional knowledge systems and through the integration of traditional and western medicines Discusses advances in technologies and systems biology to support the transition from formulation discovery to therapeutic discovery
Download or read book Human Cell Transformation written by Johng S. Rhim and published by Springer Nature. This book was released on 2019-10-01 with total page 246 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, part contributed volume, part proceedings, discusses state-of-the-art advances on human cell transformation in cell models for the study of cancer and aging. Several of the chapters are from the Human Cell Transformation: Advances in Cell Models for the Study of Cancer and Aging conference that was held in June 2018 at McGill University. The authors represent international expertise on a wide variety of topics ranging from different types of cancer (prostate, bone, breast, etc.) to tumor microenvironment, tumor progression, homogeneity, and possible therapies and treatments.
Download or read book Gene Regulation in Eukaryotes written by Edgar Wingender and published by Wiley-Blackwell. This book was released on 1993 with total page 452 pages. Available in PDF, EPUB and Kindle. Book excerpt: A much-needed guide through the overwhelming amount of literature in the field. Comprehensive and detailed, this book combines background information with the most recentinsights. It introduces current concepts, emphasizing the transcriptional control of genetic information. Moreover, it links data on the structure of regulatory proteins with basic cellular processes. Both advanced students and experts will find answers to such intriguing questions as: - How are programs of specific gene repertoires activated and controlled? - Which genes drive and control morphogenesis? - Which genes govern tissue-specific tasks? - How do hormones control gene expression in coordinating the activities of different tissues? An abundant number of clearly presented glossary terms facilitates understanding of the biological background. Speacial feature: over 2200 (!) literature references.
Download or read book Reverse Phase Protein Arrays written by Tesshi Yamada and published by Springer. This book was released on 2021-01-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book provides practical guidance on all aspects of reverse phase protein array (RPPA) technology, which permits the quantification of protein levels in cell or tissue lysates. In addition, the latest results are presented from laboratories across the world where experts are successfully running the challenging RPPA data platform. After an introductory chapter by the inventor of the RPPA technique, the demanding task of lysate preparation is explained. Subsequent chapters review printing platforms and analytical platforms and discuss antibody screening in detail. The role of RPPA data in integrative analyses is thoroughly examined, and the various applications of RPPA, for example to identify molecular targeting drugs or evaluate cancer drug efficacy, are discussed with reference to the latest knowledge. It is hoped that the book will foster the implementation of RPPA by documenting the practical details of the technology and by revealing its great potential. It will be of high value for researchers who plan to build an RPPA platform in their institute and for researchers, clinicians, and companies who use RPPA through collaboration with an existing RPPA facility.
Download or read book Formal Modeling Actors Open Systems Biological Systems written by Gul Agha and published by Springer. This book was released on 2011-10-30 with total page 465 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Festschrift volume, published in honor of Carolyn Talcott on the occasion of her 70th birthday, contains a collection of papers presented at a symposium held in Menlo Park, California, USA, in November 2011. Carolyn Talcott is a leading researcher and mentor of international renown among computer scientists. She has made key contributions to a number of areas of computer science including: semantics and verification of progamming languages; foundations of actor-based systems; middleware, meta-architectures, and systems; Maude and rewriting logic; and computational biology. The 21 papers presented are organized in topical sections named: Essays on Carolyn Talcott; actors and programming languages; cyberphysical systems; middleware and meta-architectures; formal methods and reasoning tools; and computational biology.
Download or read book A First Course in Bayesian Statistical Methods written by Peter D. Hoff and published by Springer Science & Business Media. This book was released on 2009-06-02 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: A self-contained introduction to probability, exchangeability and Bayes’ rule provides a theoretical understanding of the applied material. Numerous examples with R-code that can be run "as-is" allow the reader to perform the data analyses themselves. The development of Monte Carlo and Markov chain Monte Carlo methods in the context of data analysis examples provides motivation for these computational methods.
Download or read book Network Pharmacology written by Shao Li and published by Springer Nature. This book was released on 2021-09-29 with total page 480 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book introduces “network pharmacology” as an emerging frontier subject of systematic drug research in the era of artificial intelligence and big data. Network Pharmacology is an original subject of fusion system biology, bioinformatics, network science and other related disciplines. It emphasizes on starting from the overall perspective of the system level and biological networks, the analysis of the laws of molecular association between drugs and their treatment objects, reveals the systematic pharmacological mechanisms of drugs, and guides the research and development of new drugs and clinical diagnosis and treatment. After it was proposed, network pharmacology has been paid attention by researchers, and it has been rapidly developed and widely used. In order to systematically reveal the biological basis of diagnosis and treatment in traditional Chinese medicine and modern medicine, we proposed a new concept of "network target" for the first time, which has become the core theory of "network pharmacology". The core principle of a network target is to construct a biological network that can be used to decipher complex diseases. The network is then used as the therapeutic target, to which multicomponent remedies are applied. This book mainly includes four parts: 1) The concept and theory of network pharmacology; 2) Common analysis methods, databases and software in network pharmacological research; 3) Typical cases of traditional Chinese medicine modernization and modern drug research based on network pharmacology; 4) Network pharmacology practice process based on drugs and diseases.
Download or read book Hybrid Systems Biology written by Alessandro Abate and published by Springer. This book was released on 2016-01-09 with total page 256 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book constitutes the thoroughly referred post-workshop proceedings of the 4th International Workshop on Hybrid Systems biology, HSB 2015, held as part of the Madrid Meet 2015 event, in Madrid, Spain in September 2015. The volume presents 13 full papers together with 2 abstracts of invited sessions from 18 submissions. The scope of the HSB workshop is the general area of dynamical models in Biology with an emphasis on hybrid approaches — by no means restricted to a narrow class of mathematical models — and taking advantage of techniques developed separately in different areas.
Download or read book Breast Cancer Metastasis and Drug Resistance written by Aamir Ahmad and published by Springer Nature. This book was released on 2019-08-27 with total page 427 pages. Available in PDF, EPUB and Kindle. Book excerpt: Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.
