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Author: Thomas John Hayman
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Current approaches aimed at improving the efficacy of radiation as a cancer treatment modality involve the development and application of molecularly targeted radiosensitizers, a strategy that requires a thorough understanding of the fundamental processes comprising the cellular radioresponse. Recent data indicating that radiation modifies gene expression primarily through translational control rather than transcriptional events suggests that mRNA translation contributes to cell survival after irradiation. The overall goal of this project is to determine whether the regulatory/rate-limiting components of the translational machinery provide targets for tumor cell radiosensitization. The majority of translation in mammalian cells occurs in a cap-dependent manner and is highly dependent on eIF4E. As such, we investigated a regulatory role for eIF4E in cellular radiosensitivity. eIF4E knockdown enhanced the radiosensitivity of tumor but not normal cells. eIF4E knockdown inhibited the dispersal of radiation-induced [gamma]H2AX foci. Furthermore, radiation was found to increase the binding of >1000 unique mRNAs to eIF4E, many involved in DNA replication, recombination, and repair. S6 kinase 1 (S6K1), also an important regulatory component of the translational machinery, enhances the translation of specific mRNA subpopulations, independent from eIF4E, and mediates ribosome biogenesis. The role of S6K1 in determing cell survival after radiation was determined in several tumor cell lines and one normal cell line. S6K1 knockdown enhanced the radiosensitivity of all 3 tumor lines. In contrast S6K1 knockdown had no effect on the cellular radiosensitivity of the one normal line tested. The mechanistic target of rapamycin (mTOR) is a critical kinase in the regulation of gene translation and has been suggested as a potential target for radiosensitization. Importantly, it plays a major role in regulating eIF4E availability as well as S6K1 activity.
Author: Thomas John Hayman
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Book Description
Current approaches aimed at improving the efficacy of radiation as a cancer treatment modality involve the development and application of molecularly targeted radiosensitizers, a strategy that requires a thorough understanding of the fundamental processes comprising the cellular radioresponse. Recent data indicating that radiation modifies gene expression primarily through translational control rather than transcriptional events suggests that mRNA translation contributes to cell survival after irradiation. The overall goal of this project is to determine whether the regulatory/rate-limiting components of the translational machinery provide targets for tumor cell radiosensitization. The majority of translation in mammalian cells occurs in a cap-dependent manner and is highly dependent on eIF4E. As such, we investigated a regulatory role for eIF4E in cellular radiosensitivity. eIF4E knockdown enhanced the radiosensitivity of tumor but not normal cells. eIF4E knockdown inhibited the dispersal of radiation-induced [gamma]H2AX foci. Furthermore, radiation was found to increase the binding of >1000 unique mRNAs to eIF4E, many involved in DNA replication, recombination, and repair. S6 kinase 1 (S6K1), also an important regulatory component of the translational machinery, enhances the translation of specific mRNA subpopulations, independent from eIF4E, and mediates ribosome biogenesis. The role of S6K1 in determing cell survival after radiation was determined in several tumor cell lines and one normal cell line. S6K1 knockdown enhanced the radiosensitivity of all 3 tumor lines. In contrast S6K1 knockdown had no effect on the cellular radiosensitivity of the one normal line tested. The mechanistic target of rapamycin (mTOR) is a critical kinase in the regulation of gene translation and has been suggested as a potential target for radiosensitization. Importantly, it plays a major role in regulating eIF4E availability as well as S6K1 activity.
Author: N. B. Strazhevskaya
Publisher: John Wiley & Sons
ISBN:
Category : Science
Languages : en
Pages : 232
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Book Description
Author: Henning Willers
Publisher: Springer Nature
ISBN: 3030497011
Category : Medical
Languages : en
Pages : 370
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Book Description
Molecular Targeted Radiosensitizers: Opportunities and Challenges provides the reader with a comprehensive review of key pre-clinical research components required to identify effective radiosensitizing drugs. The book features discussions on the mechanisms and markers of clinical radioresistance, pre-clinical screening of targeted radiosensitizers, 3D radiation biology for studying radiosensitizers, in vivo determinations of local tumor control, genetically engineered mouse models for studying radiosensitizers, targeting the DNA damage response for radiosensitization, targeting tumor metabolism to overcome radioresistance, radiosensitizers in the era of immuno-oncology, and more. Additionally, the book features discussions on high-throughput drug screening, predictive biomarkers, pre-clinical tumor models, and the influence of the tumor microenvironment and the immune system, with a specific focus on the challenges radiation oncologists and medical oncologists currently face in testing radiosensitizers in human cancers. Edited by two acclaimed experts in radiation biology and radiosensitizers, with thirteen chapters contributed by experts, this new volume presents an in-depth look at current developments within a rapidly moving field, with a look at where the field will be heading and providing comprehensive insight into the framework of targeted radiosensitzer development. Essential reading for investigators in cancer research and radiation biology.
Author: Mario D. Cordero
Publisher: Springer
ISBN: 3319435892
Category : Medical
Languages : en
Pages : 519
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Book Description
AMPK has emerged as an important integrator of signals that control energy balance through the regulation of multiple biochemical pathways in eukaryotes. This book focuses on the implications of AMPK as a master metabolic regulator in diseases, including new methods and animal models. The contributions are written by leading experts in the field and give an extensive overview of the current knowledge of AMPK biology and the role of AMPK in health and disease.
Author: Søren M. Bentzen
Publisher: Springer Science & Business Media
ISBN: 0387367446
Category : Medical
Languages : en
Pages : 347
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Book Description
This book provides an up-to-date comprehensive overview of the exciting new developments shaping the current and future practice of radiation oncology. Advances in treatment planning and delivery, in biological targeted therapies combined with radiation and in functional and molecular imaging are all covered in a single volume. All of these advances are discussed by leading experts in the field and with a critical evaluation of their clinical relevance throughout.
Author: Valerio Voliani
Publisher: Walter de Gruyter GmbH & Co KG
ISBN: 1501511459
Category : Medical
Languages : en
Pages : 113
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Book Description
Gold nanoparticles provide a platform for the development of new and efficient diagnostic and therapeutic tools.This book offers a general guide to the synthesis and coating of gold nanoparticles. It describes the links between optical features and geometries of gold nanoparticles and provides a readily comprehensible connection in all the chapters between the geometry of gold nanoparticles and their final applications.
Author: Qiang Zhang
Publisher: Frontiers Media SA
ISBN: 2832533841
Category : Medical
Languages : en
Pages : 155
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Book Description
Author: Adam Eltorai
Publisher: Elsevier
ISBN: 0323884245
Category : Science
Languages : en
Pages : 736
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Book Description
Translational Radiation Oncology covers the principles of evidence-based medicine and applies them to the design of translational research. The book provides valuable discussions on the critical appraisal of published studies and recent developments in radiation oncology, allowing readers to learn how to evaluate the quality of such studies with respect to measuring outcomes and make effective use of all types of evidence. By reading this book, researchers have access to a practical approach to help them navigate challenging considerations in study design and implementation. It is a valuable resource for researchers, oncologists and members of biomedical field who want to understand more about translational research applied to the field of radiation oncology. Translational medicine serves as an indispensable tool in grant writing and funding efforts, so understanding how to apply its principles to research is necessary to guarantee that results will be impactful to patients. Provides a clear process for understanding, designing, executing and analyzing clinical and translational research Presents practical, step-by-step guidance to help readers take ideas from the lab to the bedside Written by a team of oncologists, radiologists and clinical research experts that fully cover translational research in radiation oncology
Author: Martin J. Brown
Publisher: Springer Science & Business Media
ISBN: 3540356622
Category : Medical
Languages : en
Pages : 346
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Book Description
The first part of this book summarizes the rationale and the preclinical data for combined treatment with ionizing radiation and pharmaceutical agents. Individual chapters focus on forms of combined treatment, with due consideration being given to a range of drugs and to emerging combinations with small molecules and antibodies. The second part comprises a series of disease-specific chapters in which the clinical results of combined modality treatment are presented.
Author: Kelly K. Hunt
Publisher: Springer Science & Business Media
ISBN: 159745222X
Category : Medical
Languages : en
Pages : 469
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Book Description
The three sections of this volume present currently available cancer gene therapy techniques. Part I describes the various aspects of gene delivery. In Part II, the contributors discuss strategies and targets for the treatment of cancer. Finally, in Part III, experts discuss the difficulties inherent in bringing gene therapy treatment for cancer to the clinic. This book will prove valuable as the volume of preclinical and clinical data continues to increase.
