Investigation Into the Role of the Par-4 Tumor Suppressor Pathway in B Cell Biology and Chronic Lymphocytic Leukemia PDF Download
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Author: Joseph Thomas Greene
Publisher:
ISBN:
Category : B cells
Languages : en
Pages : 132
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Book Description
The Eμ-TCL1 mouse is a B cell leukemia model commonly used to test the efficacy of experimental therapeutics and interrogate the functions of oncogenes and tumor suppressors. The CLL-like disease in this mouse shares similar pathology and molecular etiology with the human variant. We therefore hypothesized that overexpression of the human isoform of Par-4 in the B cells of this mouse would impede disease progression through either an anti-proliferative or pro-apoptotic mechanism. Consistent with this hypothesis, results indicated that B cell-specific overexpression of human Par-4 reduced the rate of T Cell Leukemia/Lymphoma 1 (TCL1)-induced leukemogenesis. In addition, B cell-specific knockout of endogenous Par-4 increased the rate of TCL1-induced leukemogenesis. Par-4 activity is regulated through a variety of mechanisms, which seem to give it a pleiotropic property. It is generally thought to act as either an anti-proliferative or pro-apoptotic tumor suppressor. In our study, TCL1 mice overexpressing human Par-4 were found to harbor malignant B cell clones that proliferated at reduced rates when compared to their Par-4 wild-type (WT) littermates. This indicated that Par-4 was reducing the expansion of overexpressing cells; which we found interesting, because Par-4 overexpressing mice null for the TCL1 oncogene exhibited no phenotype when examined in various immune response assays.
Author: Joseph Thomas Greene
Publisher:
ISBN:
Category : B cells
Languages : en
Pages : 132
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Book Description
The Eμ-TCL1 mouse is a B cell leukemia model commonly used to test the efficacy of experimental therapeutics and interrogate the functions of oncogenes and tumor suppressors. The CLL-like disease in this mouse shares similar pathology and molecular etiology with the human variant. We therefore hypothesized that overexpression of the human isoform of Par-4 in the B cells of this mouse would impede disease progression through either an anti-proliferative or pro-apoptotic mechanism. Consistent with this hypothesis, results indicated that B cell-specific overexpression of human Par-4 reduced the rate of T Cell Leukemia/Lymphoma 1 (TCL1)-induced leukemogenesis. In addition, B cell-specific knockout of endogenous Par-4 increased the rate of TCL1-induced leukemogenesis. Par-4 activity is regulated through a variety of mechanisms, which seem to give it a pleiotropic property. It is generally thought to act as either an anti-proliferative or pro-apoptotic tumor suppressor. In our study, TCL1 mice overexpressing human Par-4 were found to harbor malignant B cell clones that proliferated at reduced rates when compared to their Par-4 wild-type (WT) littermates. This indicated that Par-4 was reducing the expansion of overexpressing cells; which we found interesting, because Par-4 overexpressing mice null for the TCL1 oncogene exhibited no phenotype when examined in various immune response assays.
Author: Mary Kathryn McKenna
Publisher:
ISBN:
Category :
Languages : en
Pages : 196
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Book Description
Author: Vivek M. Rangnekar
Publisher: Springer
ISBN: 9783030805579
Category : Medical
Languages : en
Pages : 331
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Book Description
Par-4 is a naturally occurring tumor suppressor. Studies have indicated that overexpression of Par-4 selectively induces apoptosis in cancer cells while leaving normal, health, cells unaffected. Mechanisms contributing to this cancer-selective action of Par-4 have been associated with PKA activation of intracellular Par-4 in cancer cells or GRP78 expression primarily on the surface of cancer cells. On the other hand, endogenous Par-4 sensitizes cells to the action of a broad range of apoptotic inducers acting via the extrinsic and intrinsic pathways. A number of binding partners of Par-4 have been identified and shown to regulate Par-4 function in cancer and other diseases, such as Alzheimer’s and major depression. Recent studies have recognized a number of natural products, dietary supplements, synthetic molecules and FDA-approved drugs that induce the secretion of Par-4 protein to cause apoptosis in primary or metastatic tumors, one of which is in clinical trials. More than 50 different laboratories worldwide are involved in Par-4 based research of this unique protein that has progressed from the bench to clinical trials. This second, companion volume will provide a comprehensive overview of Par-4’s role in cancer and other diseases. Chapters are written by leading researchers, and will be useful for a broad audience across the scientific community, particularly students and trainees, who are the next generation of scientists and clinicians to participate in new studies and discoveries on Par-4.
Author: Vivek M. Rangnekar
Publisher: Springer
ISBN: 9783030735715
Category : Medical
Languages : en
Pages : 323
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Book Description
Par-4 is a tumor suppressor protein first discovered and identified in 1993 by Dr. Vivek Rangnekar’s laboratory in prostate cancer cells undergoing apoptosis. Par-4 (later also known as PAWR) is a naturally occurring tumor suppressor. Studies have indicated that Par-4 selectively induces apoptosis in cancer cells while leaving normal, healthy, cells unaffected. Mechanisms contributing to the cancer-selective action of Par-4 have been associated with protein kinase A activation of intracellular Par-4 in cancer cells or GRP78 expression primarily on the surface of cancer cells. Par-4 is downregulated, inactivated or mutated in diverse cancers. This first of two volumes will be the first on the market on the topic of Par-4, and will provide the opportunity for researchers to discuss the future direction of studies, broaden the scope of research, and contribute a more complete understanding of the molecule’s structural features, key functional domains, regulation and relevant basic and clinical/translational facets.
Author: Vivek M. Rangnekar
Publisher: Springer Nature
ISBN: 3030805581
Category : Medical
Languages : en
Pages : 329
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Book Description
Par-4 is a naturally occurring tumor suppressor. Studies have indicated that overexpression of Par-4 selectively induces apoptosis in cancer cells while leaving normal, health, cells unaffected. Mechanisms contributing to this cancer-selective action of Par-4 have been associated with PKA activation of intracellular Par-4 in cancer cells or GRP78 expression primarily on the surface of cancer cells. On the other hand, endogenous Par-4 sensitizes cells to the action of a broad range of apoptotic inducers acting via the extrinsic and intrinsic pathways. A number of binding partners of Par-4 have been identified and shown to regulate Par-4 function in cancer and other diseases, such as Alzheimer’s and major depression. Recent studies have recognized a number of natural products, dietary supplements, synthetic molecules and FDA-approved drugs that induce the secretion of Par-4 protein to cause apoptosis in primary or metastatic tumors, one of which is in clinical trials. More than 50 different laboratories worldwide are involved in Par-4 based research of this unique protein that has progressed from the bench to clinical trials. This second, companion volume will provide a comprehensive overview of Par-4’s role in cancer and other diseases. Chapters are written by leading researchers, and will be useful for a broad audience across the scientific community, particularly students and trainees, who are the next generation of scientists and clinicians to participate in new studies and discoveries on Par-4.
Author: Tasuku Honjo
Publisher: Academic Press
ISBN: 9780123979339
Category : Science
Languages : en
Pages : 0
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Book Description
Molecular Biology of B Cells, Second Edition is a comprehensive reference to how B cells are generated, selected, activated and engaged in antibody production. All of these developmental and stimulatory processes are described in molecular, immunological, and genetic terms to give a clear understanding of complex phenotypes. Molecular Biology of B Cells, Second Edition offers an integrated view of all aspects of B cells to produce a normal immune response as a constant, and the molecular basis of numerous diseases due to B cell abnormality. The new edition continues its success with updated research on microRNAs in B cell development and immunity, new developments in understanding lymphoma biology, and therapeutic targeting of B cells for clinical application. With updated research and continued comprehensive coverage of all aspects of B cell biology, Molecular Biology of B Cells, Second Edition is the definitive resource, vital for researchers across molecular biology, immunology and genetics.
Author: Marie-Caroline Dieu-Nosjean
Publisher: Humana Press
ISBN: 9781493987085
Category : Medical
Languages : en
Pages : 289
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Book Description
This volume explores the various methods used to study tertiary lymphoid structures (TLS) in pathological situations. Pre-clinical models are also discussed in detail to show how TLS structure, development, and maintenance can be targeted and studied in vivo. The chapters in this book cover topics such as humans and mice; strategies to quantify TLS in order to use it in stained tissue sections; classifying a gene signature form fixed and paraffin-embedded tissues; and development of murine inflammatory models to help look at TLS in the context of infection or malignancy. 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 thorough, Tertiary Lymphoid Structures: Methods and Protocols is a valuable resource that increases the reader’s knowledge on immune functions and how they will pave the way to future therapeutic applications.
Author: Tomohiro Kurosaki
Publisher: Springer
ISBN: 3319261339
Category : Medical
Languages : en
Pages : 231
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Book Description
This volume details our current understanding of the architecture and signaling capabilities of the B cell antigen receptor (BCR) in health and disease. The first chapters review new insights into the assembly of BCR components and their organization on the cell surface. Subsequent contributions focus on the molecular interactions that connect the BCR with major intracellular signaling pathways such as Ca2+ mobilization, membrane phospholipid metabolism, nuclear translocation of NF-kB or the activation of Bruton’s Tyrosine Kinase and MAP kinases. These elements orchestrate cytoplasmic and nuclear responses as well as cytoskeleton dynamics for antigen internalization. Furthermore, a key mechanism of how B cells remember their cognate antigen is discussed in detail. Altogether, the discoveries presented provide a better understanding of B cell biology and help to explain some B cell-mediated pathogenicities, like autoimmune phenomena or the formation of B cell tumors, while also paving the way for eventually combating these diseases.
Author: David A. Frank
Publisher: Springer Science & Business Media
ISBN: 1402073402
Category : Medical
Languages : en
Pages : 358
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Book Description
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."
Author: Ajay Vora
Publisher: Springer
ISBN: 3319397087
Category : Medical
Languages : en
Pages : 345
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Book Description
This book provides a comprehensive and up-to-date review of all aspects of childhood Acute Lymphoblastic Leukemia, from basic biology to supportive care. It offers new insights into the genetic pre-disposition to the condition and discusses how response to early therapy and its basic biology are utilized to develop new prognostic stratification systems and target therapy. Readers will learn about current treatment and outcomes, such as immunotherapy and targeted therapy approaches. Supportive care and management of the condition in resource poor countries are also discussed in detail. This is an indispensable guide for research and laboratory scientists, pediatric hematologists as well as specialist nurses involved in the care of childhood leukemia.
