RUNX Proteins in Development and Cancer

2018-06-09
 |  Medical
RUNX Proteins in Development and Cancer

Author: Yoram Groner

Publisher: Springer

ISBN: 9811098220

Category: Medical

Page: 515

View: 719

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This volume provides the reader with an overview of the diverse functions of the RUNX family of genes. As highlighted in the introduction and several of the 29 chapters, humans and other mammals have three RUNX genes that are known to play specific roles in blood, bone and neuronal development. However, their evolutionary history has recently been traced back to unicellular organisms and their involvement in many well-known signaling pathways (Wnt, TGFb, Notch, Hippo) is indicative of a more general function in cell biology. Their documented roles in cell fate decisions include control of proliferation, differentiation, survival, senescence and autophagy. The pleiotropic effects of RUNX in development are mirrored in cancer, where RUNX genes can function as oncogenes that collaborate strongly with Myc family oncogenes or as tumour suppressor genes. In the latter role, they display hallmarks of both ‘gatekeepers’ that modulate p53 responses and ‘caretakers’ that protect the genome from DNA damage. Several chapters focus on the importance of these genes in leukemia research, where RUNX1 and CBFB are frequently affected by chromosomal translocations that generate fusion oncoproteins, while recent studies suggest wider roles for RUNX modulation in solid cancers. Moreover, RUNX genes are intimately involved in the development and regulation of the immune system, while emerging evidence suggests a role in innate immunity to infectious agents, including HIV. At the biochemical level, the RUNX family can serve as activators or repressors of transcription and as stable mediators of epigenetic memory through mitosis. Not surprisingly, RUNX activity is controlled at multiple levels, this includes miRNAs and a plethora of post-translational modifications. Several chapters highlight the interplay between the three mammalian RUNX genes, where cross-talk and partial functional redundancies are evident. Finally, structural analysis of the RUNX/CBFB interaction has led to the development of small molecule inhibitors that provide exciting new tools to decipher the roles of RUNX in development and as targets for therapy. This volume provides a compendium and reference source that will be of broad interest to cancer researchers, developmental biologists and immunologists.

RUNX Proteins in Development and Cancer

2017-03-15
 |  Medical
RUNX Proteins in Development and Cancer

Author: Yoram Groner

Publisher: Springer

ISBN: 9789811032332

Category: Medical

Page: 515

View: 357

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This volume provides the reader with an overview of the diverse functions of the RUNX family of genes. As highlighted in the introduction and several of the 29 chapters, humans and other mammals have three RUNX genes that are known to play specific roles in blood, bone and neuronal development. However, their evolutionary history has recently been traced back to unicellular organisms and their involvement in many well-known signaling pathways (Wnt, TGFb, Notch, Hippo) is indicative of a more general function in cell biology. Their documented roles in cell fate decisions include control of proliferation, differentiation, survival, senescence and autophagy. The pleiotropic effects of RUNX in development are mirrored in cancer, where RUNX genes can function as oncogenes that collaborate strongly with Myc family oncogenes or as tumour suppressor genes. In the latter role, they display hallmarks of both ‘gatekeepers’ that modulate p53 responses and ‘caretakers’ that protect the genome from DNA damage. Several chapters focus on the importance of these genes in leukemia research, where RUNX1 and CBFB are frequently affected by chromosomal translocations that generate fusion oncoproteins, while recent studies suggest wider roles for RUNX modulation in solid cancers. Moreover, RUNX genes are intimately involved in the development and regulation of the immune system, while emerging evidence suggests a role in innate immunity to infectious agents, including HIV. At the biochemical level, the RUNX family can serve as activators or repressors of transcription and as stable mediators of epigenetic memory through mitosis. Not surprisingly, RUNX activity is controlled at multiple levels, this includes miRNAs and a plethora of post-translational modifications. Several chapters highlight the interplay between the three mammalian RUNX genes, where cross-talk and partial functional redundancies are evident. Finally, structural analysis of the RUNX/CBFB interaction has led to the development of small molecule inhibitors that provide exciting new tools to decipher the roles of RUNX in development and as targets for therapy. This volume provides a compendium and reference source that will be of broad interest to cancer researchers, developmental biologists and immunologists.

Advances in Cancer Research

2007-12-17
 |  Science
Advances in Cancer Research

Author: George F. Vande Woude

Publisher: Elsevier

ISBN: 9780080556512

Category: Science

Page: 450

View: 150

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The Advances in Cancer Research series provides invaluable information on the exciting and fast-moving field of cancer research. This volume presents outstanding and original reviews on a variety of topics including RUNX Genes in Development and Cancer; The RNA Continent; The c-myc Promoter; Designer Self-Assembling Peptide Nanofiber Scaffolds for Study of 3-D Cell Biology and Beyond; and Dendritic Cells in Cancer. Immunotherapy

Investigating the RUNX1-CBF[beta] Transcription Factor Complex as a Mitotic Gene Bookmark to Maintain the Normal Mammary Epithelial Phenotype

2020
 |  Breast
Investigating the RUNX1-CBF[beta] Transcription Factor Complex as a Mitotic Gene Bookmark to Maintain the Normal Mammary Epithelial Phenotype

Author: Eliana Moskovitz

Publisher:

ISBN: OCLC:1195968478

Category: Breast

Page: 222

View: 934

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Disruption of normal mammary epithelial cell homeostasis through acquisition of deleterious somatic and/or germline mutations leads to breast cancer development. Breast cancer is the most commonly diagnosed cancer among women worldwide, and is associated with the second highest amount of cancer-related deaths. Breast cancer mortality rates are decreasing, likely through increased methods of detection and development of targeted therapies. However, due to the complexity and heterogeneity of the disease, the incidence rate remains high and the molecular events that lead to breast cancer initiation and progression are poorly understood. The epithelial-to-mesenchymal transition (EMT) is an essential molecular process involved in the initiation and progression of epithelial-based tumors. Loss of cell-cell connections, altered extracellular matrix interactions, and dramatic cytoskeletal changes promote cell individuality and development of a migratory and often invasive phenotype. Under normal physiological conditions, EMT is involved in processes such as embryonic development and wound healing. EMT is tightly regulated by a combination of signaling pathways and epigenetic factors. However, the molecular mechanisms that suppress EMT within the normal epithelium to prevent tumorigenesis remain understudied. Mitotic gene bookmarking -- retention of cell lineage-specific transcription factors with target genes, together with histone modifications, specific DNA methylation patterns, and components of transcriptional machinery on mitotic chromosomes -- is an epigenetic mechanism that maintains cellular identity throughout successive cell divisions. Mitotic occupancy and post-mitotic transcription regulation of target genes involved in proliferation, growth, and cellular identity by transcription factors, reestablishes epithelial-specific transcriptional programs in newly formed progeny cells. The RUNX1-CBF[Beta] heterodimeric transcription factor complex is essential for normal mammary gland development. Mutations in both subunits have been identified in breast cancers. Studies by our group have shown that RUNX proteins act as mitotic bookmarks in a variety of tissue types and depletion of RUNX1 in normal mammary epithelial cells leads to EMT. Findings reported in this study show that inhibition of the RUNX1-CBF[Beta] interaction disrupts the normal mammary epithelial phenotype, alters cell cycle regulation, and initiates EMT. Furthermore, results demonstrate RUNX1 is maintained on mitotic chromosomes during all topologically identifiable stages of mitosis in live MCF10A cells. Conditions and methods have been optimized to study the specific function of the RUNX1-CBF[Beta] transcription factor complex as a mitotic bookmark, essential for mitotic and post-mitotic transcriptional regulation of genes involved in proliferation, cell growth, and epithelial cell identity throughout successive cell divisions. Further studies utilizing these conditions and methods are required to address the functional role of the RUNX1-CBF[Beta] transcription factor complex as an essential mitotic bookmark involved in phenotypic maintenance in the normal mammary epithelium.

Epigenetics in Psychiatry

2021-08-16
 |  Science
Epigenetics in Psychiatry

Author: Jacob Peedicayil

Publisher: Academic Press

ISBN: 9780128235782

Category: Science

Page: 846

View: 114

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Epigenetics in Psychiatry, Second Edition covers all major areas of psychiatry in which extensive epigenetic research has been performed, fully encompassing a diverse and maturing field, including drug addiction, bipolar disorder, epidemiology, cognitive disorders, and the uses of putative epigenetic-based psychotropic drugs. Uniquely, each chapter correlates epigenetics with relevant advances across genomics, transcriptomics, and proteomics. The book acts as a catalyst for further research in this growing area of psychiatry. This new edition has been fully revised to address recent advances in epigenetic understanding of psychiatric disorders, evoking data consortia (e.g., CommonMind, ATAC-seq), single cell analysis, and epigenome-wide association studies to empower new research. The book also examines epigenetic effects of the microbiome on psychiatric disorders, and the use of neuroimaging in studying the role of epigenetic mechanisms of gene expression. Ongoing advances in epigenetic therapy are explored in-depth. Fully revised to discuss new areas of research across neuronal stem cells, cognitive disorders, and transgenerational epigenetics in psychiatric disease Relates broad advances in psychiatric epigenetics to a modern understanding of the genome, transcriptome, and proteins Catalyzes knowledge discovery in both basic epigenetic biology and epigenetic targets for drug discovery Provides guidance in research methods and protocols, as well how to employ data from consortia, single cell analysis, and epigenome-wide association studies (EWAS) Features chapter contributions from international leaders in the field

The Hereditary Basis of Rheumatic Diseases

2006-07-02
 |  Medical
The Hereditary Basis of Rheumatic Diseases

Author: Rikard Holmdahl

Publisher: Springer Science & Business Media

ISBN: 9783764374198

Category: Medical

Page: 182

View: 915

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Rheumatoid Arthritis (RA) represents a complex disease where the inheritable component has been estimated to be up to 60%. This PIR volume deals with the genetic basis and regulation of rheumatic diseases. The first part of the book describes genetic studies on rheumatic diseases. The second part deals with the shared heredity of rheumatic diseases, e.g., RA, lupus and ankylosing spondylitis. The third part of the volume describes tools for analysing genetic complexity, ranging from animal models to new molecular tools. The volume is essential reading for researchers and clinicians from rheumatology, inflammation research, immunology, and cell and molecular biology.

Nuclear Signaling Pathways and Targeting Transcription in Cancer

2013-08-23
 |  Medical
Nuclear Signaling Pathways and Targeting Transcription in Cancer

Author: Rakesh Kumar

Publisher: Springer Science & Business Media

ISBN: 9781461480396

Category: Medical

Page: 439

View: 432

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At the moment, there is no dedicated book to summarize the roles, the significance, and potential therapeutic targeting of transcriptional factors from the perspective of signaling cascade, and thus, directly impacting the functionality of transcriptional factors in cancer. In addition, this book will offer a comprehensive basic and clinical science behind the functions of representative core transcriptional factors. These chapters will serve as a treasure for all those who have an interest in the basis, progression, and targeting of human cancer. Each chapter will be intended to provide comprehensive, up-to-date information by the leaders about the physiologic and pathologic roles of TFs in specific representative organ systems of prime importance. The book will consist of chapters that will give biomedical students, under and graduate students, basic sciences and clinical cancer fellows, residents and researchers, and oncology educators will get a thorough summary of the overall subject. The readers will be able to understand the important current information and views on specific TFs and its role in cancer in areas outside their own expertise or experience. A special emphasis will be also placed on the "classic" papers as well as perspectives on future directions for the field.

Molecular Targeting and Signal Transduction

2006-04-18
 |  Medical
Molecular Targeting and Signal Transduction

Author: Rakesh Kumar

Publisher: Springer Science & Business Media

ISBN: 9781402078477

Category: Medical

Page: 331

View: 499

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Our limited understanding of cellular regulatory signal-transduction-networks has been a barrier to progress in improving the overall cure-rate of human cancers. Delineation of the physiologic roles of the specific regulatory signaling components, with known association with metastatic phenotypes, is a highly promising area which will likely provide the next generation of targeted strategies in the future of molecular cancer medicine. These signaling components are likely to be used in diagnosis, prognosis, and as novel targets for therapeutic development. This book brings together up-to-date summaries by leading cancer researchers on the major principles of cancer cell biology: survival, apoptosis, adhesion, and cell cycle deregulation. It is directed at clinicians and scientists working in the areas of experimental and molecular therapeutics, molecular medicine, translational cancer research, and bio-medical sciences in general.

Fusion Genes And Cancer

2017-04-07
 |  Medical
Fusion Genes And Cancer

Author: Kunnumakkara Ajaikumar B

Publisher: World Scientific

ISBN: 9789813200951

Category: Medical

Page: 432

View: 140

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Development of cancer, a dreadful disease of mankind, is a multi-stage process involving numerous molecular alterations at both genomic and proteomic levels. Immense research for the past several decades in the field of cancer identified many such mutations and their role in carcinogenesis. Concept of 'fusion genes' seeded way back in 20th century has now grown into a new field of cancer research. However, there is a lack of knowledge among scientists about these fusion genes and their importance in cancer, which can be mainly attributed to unavailability of a comprehensive book on this topic. Therefore, this book is first of its kind and aims at giving a detailed idea on the formation of gene fusions and their importance in the development and progression of cancer; techniques to identify novel gene fusions; and therapeutics available to target various fusion proteins and their impact in cancer therapy by compiling the information from the literature available till date. Contents:Cancer — An Overview and Molecular Alterations in Cancer (Nand K Roy, Devivasha Bordoloi, Javadi Monisha, Anand Anip, Ganesan Padmavathi and Ajaikumar B Kunnumakkara)Basic Concepts of Fusion Genes and Their Classification (Ganesan Padmavathi, Nand K Roy, Devivasha Bordoloi, Javadi Monisha and Ajaikumar B Kunnumakkara)Techniques to Identify Novel Fusion Genes and to Detect Known Fusion Genes (Nand K Roy, Ganesan Padmavathi, Devivasha Bordoloi and Ajaikumar B Kunnumakkara)The Receptor Tyrosine Kinase ALK — Its Fusion Partners and Their Implication in Various Cancers(Ganesan Padmavathi, Krishan Kumar Thakur, Anand Anip, Devivasha Bordoloi and Ajaikumar B Kunnumakkara)Role of BCR-ABL Fusion Kinase in the Development of Leukemia (Ganesan Padmavathi, Kishore Banik, Nand K Roy, Javadi Monisha and Ajaikumar B Kunnumakkara)BRD4-NUT Fusion Oncoprotein and Its Significance in the Initiation and Progression of NUT Midline Carcinoma (Ganesan Padmavathi, Devivasha Bordoloi, Kishore Banik and Ajaikumar B Kunnumakkara)Importance of CBFB-MYH11 — A Chimeric Transcriptional Regulator in Leukemia (Ganesan Padmavathi, Choudhary Harsha, Devivasha Bordoloi, Krishan Kumar Thakur and Ajaikumar B Kunnumakkara)Rearrangements Involving ETS Family of Genes and Their Role in Different Cancers (Ganesan Padmavathi, Javadi Monisha, Kishore Banik, Choudhary Harsha, Devivasha Bordoloi and Ajaikumar B Kunnumakkara)Translocation of FET Family Members with Various Partner Genes and Their Role in Cancer Development (Ganesan Padmavathi, Devivasha Bordoloi, Anand Anip, Krishan Kumar Thakur and Ajaikumar B Kunnumakkara)Translocations of FGF and FGFR Proteins and Their Effect in Cancer (Ganesan Padmavathi, Javadi Monisha, Choudhary Harsha and Ajaikumar B Kunnumakkara)IG/MYC and Its Implication in Cancer (Ganesan Padmavathi, Kishore Banik, Krishan Kumar Thakur and Ajaikumar B Kunnumakkara)Chimeric RAF Kinases in the Development of Cancer (Ganesan Padmavathi, Kishore Banik, Devivasha Bordoloi, Choudhary Harsha and Ajaikumar B Kunnumakkara)Mucoepidermoid Carcinoma (MEC) and Associated MAML2 Fusion Genes (Ganesan Padmavathi, Choudhary Harsha, Devivasha Bordoloi, Kishore Banik and Ajaikumar B Kunnumakkara)Mixed Lineage Leukemia/AF9 Fusion and Associated Leukemia (Ganesan Padmavathi, Choudhary Harsha and Ajaikumar B Kunnumakkara)MYB-NFIB Fusion Gene — Hallmark of Adenoid Cystic Carcinoma (ACC) (Ganesan Padmavathi, Krishan Kumar Thakur and Ajaikumar B Kunnumakkara)Translocations Involving PAX Family Genes and Their Effect in Cancer (Ganesan Padmavathi, Krishan Kumar Thakur and Ajaikumar B Kunnumakkara)Retinoic Acid Receptor Alpha (RARα) Fusion Genes in Leukemia (Ganesan Padmavathi, Javadi Monisha, Anand Anip, Krishan Kumar Thakur and Ajaikumar B Kunnumakkara)RET/PTC Translocations and Thyroid Malignancies (Ganesan Padmavathi, Devivasha Bordoloi, Anand Anip, Choudhary Harsha and Ajaikumar B Kunnumakkara)RUNX1 or AML1 Fusion Genes in Leukemia and Other Cancers (Ganesan Padmavathi, Javadi Monisha, Kishore Banik, Choudhary Harsha, Devivasha Bordoloi and Ajaikumar B Kunnumakkara)Recently Discovered Fusion Genes and Their Implications in Cancer (Ganesan Padmavathi, Devivasha Bordoloi, Javadi Monisha, Nand K Roy, Choudhary Harsha and Ajaikumar B Kunnumakkara)Targeting Fusion Genes for Cancer Therapy (Nand K Roy, Devivasha Bordoloi, Ganesan Padmavathi and Ajaikumar B Kunnumakkara) Readership: Scientists working in the field of cancer biology, cancer genomics and proteomics. Also specialists and researchers in diverse fields of disease pathogenesis as it provides collective information about fusion genes and cancer from the basics to the targeted therapies.

Encyclopedia of Cancer

2011-10-14
 |  Medical
Encyclopedia of Cancer

Author: Manfred Schwab

Publisher: Springer Science & Business Media

ISBN: 9783642164828

Category: Medical

Page: 4071

View: 409

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The merging of different basic and clinical science disciplines towards the common goal of fighting against cancer has long ago called for the establishment of a comprehensive reference source both as a tool to close the language gap between clinical and basic science investigators and as a platform of information for students and informed laymen alike. The Encyclopedia of Cancer provides rapid access to focused information on all topics of cancer research for clinicians, research scientists and advanced students. Given the overwhelming success of the Second Edition, which appeared in 2009, and fast recent development in the different fields of cancer research, it has been decided to publish a third fully revised and expanded edition, following the principal concept of the first edition that has proven so successful. Recent developments are seeing a dynamic progress in basic and clinical cancer science, with translational research increasingly becoming a new paradigm in cancer research. In particular, new approaches to both Personalized Cancer Medicine and Targeted Therapies have made promising progress. While the Second Edition featured scholarly contributions from approximately 1.000 scientists/clinicians in four Volumes, the Third Edition includes 1.300 contributors in 7 Volumes with an A-Z format of approx. 7000 entries. It provides definitions of common acronyms and short definitions of related terms and processes in the form of keyword entries. In addition, there are detailed essays, which provide comprehensive information on syndromes, genes and molecules, and processes and methods. Each essay is well-structured, with extensive cross-referencing between all entries. In the Third Edition, topical Essays present a comprehensive picture of major cancers, such as Breast Cancer, Colorectal Cancer, Prostate Cancer, Ovarian Cancer, Renal Cancer, Lung Cancer, and Hematological Maligancies, Leukemias and Lymphomas. For each of these cancers, different authoritative Essays are included that cover topics ranging from Pathology, to Clinical Oncology and Targeted Therapies. This new feature should meet the expectance that a wide community has towards a major cancer reference works. The Encyclopedia of Cancer will be accessible both in print and online, and this information source should be of value to both the clinical and basic scientific community as well as to the public.