Checkpoint Controls And Cancer

Author : Axel H. Schönthal
Publisher : Springer Science & Business Media
Page : 362 pages
File Size : 46,8 Mb
Release : 2008-02-03
Category : Medical
ISBN : 9781592598113

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Checkpoint Controls and Cancer by Axel H. Schönthal Pdf

Intracellular checkpoint controls constitute a network of signal transd- tion pathways that protect cells from external stresses and internal errors. Ext- nal stresses can be generated by the continuous assault of DNA-damaging agents, such as environmental mutagens, ultraviolet (UV) light, ionizing radiation, or the reactive oxygen species that can arise during normal cellular metabolism. In response to any of these assaults on the integrity of the genome, the activation of the network of checkpoint control pathways can lead to diverse cellular responses, such as cell cycle arrest, DNA repair, or elimination of the cell by cell death (apoptosis) if the damage cannot be repaired. Moreover, internal errors can occur during the highly orchestrated replication of the cellular genome and its distribution into daughter cells. Here, the temporal order of these cell cycle events must be strictly enforced—for example, to ensure that DNA replication is c- plete and occurs only once before cell division, or to monitor mitotic spindle assembly, and to prevent exit from mitosis until chromosome segregation has been completed. Thus, well functioning checkpoint mechanisms are central to the maintenance of genomic integrity and the basic viability of cells and, the- fore, are essential for proper development and survival. The importance of proper functioning of checkpoints becomes plainly obvious under conditions in which this control network malfunctions and fails. Depending on the severity and timing, failure of this machinery can lead to embryonic lethality, genetic diseases, and cancer.

Author : Zahid H. Siddik
Publisher : Springer Science & Business Media
Page : 274 pages
File Size : 52,8 Mb
Release : 2010-03-12
Category : Medical
ISBN : 9781607611783

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Checkpoint Controls and Targets in Cancer Therapy by Zahid H. Siddik Pdf

Much work over the last two decades has firmly established that loss of cell cycle checkpoint regulation, and resultant unabated cellular proliferation, is an inherent characteristic of cancer. This loss may occur through aberration in any single component involved in signal transduction pathways that orchestrate checkpoint regulation, which may manifest through either a failure to activate the checkpoint or a failure to respond to the activated checkpoint. In normal cells, checkpoint pathways are activated when genetic or cellular homeostasis is compromised, and signals are then transduced to re-stabilize homeostasis, and, failing this, to activate the apoptotic machinery to induce a cellular suicidal response. This implies that both survival and cell death pathways are induced following checkpoint activation, and that the final decision is dependant on the net result of integrating the two sets of signals. It is intriguing that checkpoint pathways are also critical in cancer therapy to provide an apoptotic stimulus when cellular damage induced by the therapeutic agent is detected by the sensor system. Therefore, it is not surprising that failure in pro-survival checkpoint response will render tumor cells hypersensitive to cytotoxics and, conversely, failure in pro-apoptotic checkpoint response will induce genetic instability and/or therapeutic resistance. Understanding the intricacies of checkpoint response is, therefore, central to the design of therapeutic regimen that will enhance antitumor effects. Although early versions of this design entail combination of cytotoxic agents with cell cycle or checkpoint inhibitors, a greater understanding of the concepts could make such combinations clinically more effective. The contributions in this book will consolidate the current state of knowledge on checkpoint responses that may lay the foundation for hypothesis-driven rational approaches in advancing the management of cancer. The immediate attraction of the book to the scientific community is that it represents a timely opportunity to build upon existing concepts of checkpoints to expand our understanding of the inner workings of the critical checkpoint machinery. The present understanding has provided ample appreciation that response to checkpoint activation is manifested through coordinated inhibition of cyclin-dependent kinase (CDK) complexes in G1, S and/or the G2 phase in order to arrest the cell cycle. Kinase inhibition can occur through several mechanisms, including inhibitory phosphorylation of CDK, destruction of the cognate cyclins, and recruitment of CDK inhibitors from the INK and WAF1/CIP1 families. However, the wealth of information from recent discoveries needs to be examined critically to consolidate our conceptual knowledge of checkpoints. At the same time, there is acute awareness in the diversity of checkpoint response between cytotoxic agents, and this serves as a reminder of the magnitude of complexity that is inherent in checkpoint regulation. This volume is intended to bring the cancer research community closer toward an improved understanding of this regulation, how checkpoint abnormalities can impact negatively on cancer therapy, and emerging strategies to target checkpoint response as a therapeutic end-point.

Author : Axel H. Schönthal
Publisher : Springer Science & Business Media
Page : 328 pages
File Size : 52,6 Mb
Release : 2008-02-05
Category : Medical
ISBN : 9781592597888

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Checkpoint Controls and Cancer by Axel H. Schönthal Pdf

Intracellular checkpoint controls constitute a network of signal transd- tion pathways that protect cells from external stresses and internal errors. Ext- nal stresses can be generated by the continuous assault of DNA-damaging agents, such as environmental mutagens, ultraviolet (UV) light, ionizing radiation, or the reactive oxygen species that can arise during normal cellular metabolism. In response to any of these assaults on the integrity of the genome, the activation of the network of checkpoint control pathways can lead to diverse cellular responses, such as cell cycle arrest, DNA repair, or elimination of the cell by cell death (apoptosis) if the damage cannot be repaired. Moreover, internal errors can occur during the highly orchestrated replication of the cellular genome and its distribution into daughter cells. Here, the temporal order of these cell cycle events must be strictly enforced—for example, to ensure that DNA replication is c- plete and occurs only once before cell division, or to monitor mitotic spindle assembly, and to prevent exit from mitosis until chromosome segregation has been completed. Thus, well functioning checkpoint mechanisms are central to the maintenance of genomic integrity and the basic viability of cells and, the- fore, are essential for proper development and survival. The importance of proper functioning of checkpoints becomes plainly obvious under conditions in which this control network malfunctions and fails. Depending on the severity and timing, failure of this machinery can lead to embryonic lethality, genetic diseases, and cancer.

Author : Axel H. Schönthal
Publisher : Unknown
Page : 128 pages
File Size : 49,9 Mb
Release : 2004
Category : Electronic
ISBN : OCLC:456507251

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Checkpoint Controls and Cancer by Axel H. Schönthal Pdf

Author : Howard B. Lieberman
Publisher : Springer Science & Business Media
Page : 366 pages
File Size : 53,8 Mb
Release : 2008-02-02
Category : Science
ISBN : 9781592596461

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Cell Cycle Checkpoint Control Protocols by Howard B. Lieberman Pdf

The field of cell cycle regulation is based on the observation that the life cycle of a cell progresses through several distinct phases, G1, M, S, and G2, occurring in a well-defined temporal order. Details of the mechanisms involved are rapidly emerging and appear extraordinarily complex. Furthermore, not only is the order of the phases important, but in normal eukaryotic cells one phase will not begin unless the prior phase is completed successfully. Che- point control mechanisms are essentially surveillance systems that monitor the events in each phase, and assure that the cell does not progress prematurely to the next phase. If conditions are such that the cell is not ready to progress—for example, because of incomplete DNA replication in S or DNA damage that may interfere with chromosome segregation in M—a transient delay in cell cycle progression will occur. Once the inducing event is properly handled— for example, DNA replication is no longer blocked or damaged DNA is repaired—cell cycle progression continues. Checkpoint controls have recently been the focus of intense study by investigators interested in mechanisms that regulate the cell cycle. Furthermore, the relationship between checkpoint c- trol and carcinogenesis has additionally enhanced interest in these cell cycle regulatory pathways. It is clear that cancer cells often lack these checkpoints and exhibit genomic instability as a result. Moreover, several tumor suppressor genes participate in checkpoint control, and alterations in these genes are as- ciated with genomic instability as well as the development of cancer.

Author : Jie Xu
Publisher : Springer Nature
Page : 657 pages
File Size : 52,5 Mb
Release : 2020-03-17
Category : Medical
ISBN : 9789811532665

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Regulation of Cancer Immune Checkpoints by Jie Xu Pdf

This book systematically reviews the most important findings on cancer immune checkpoints, sharing essential insights into this rapidly evolving yet largely unexplored research topic. The past decade has seen major advances in cancer immune checkpoint therapy, which has demonstrated impressive clinical benefits. The family of checkpoints for mediating cancer immune evasion now includes CTLA-4, PD-1/PD-L1, CD27/CD70, FGL-1/LAG-3, Siglec-15, VISTA (PD-1L)/VSIG3, CD47/SIRPA, APOE/LILRB4, TIGIT, and many others. Despite these strides, most patients do not show lasting remission, and some cancers have been completely resistant to the therapy. The potentially lethal adverse effects of checkpoint blockade represent another major challenge, the mechanisms of which remain poorly understood. Compared to the cancer signaling pathways, such as p53 and Ras, mechanistic studies on immune checkpoint pathways are still in their infancy. To improve the responses to checkpoint blockade therapy and limit the adverse effects, it is essential to understand the molecular regulation of checkpoint molecules in both malignant and healthy cells/tissues. This book begins with an introduction to immune checkpoint therapy and its challenges, and subsequently describes the regulation of checkpoints at different levels. In closing, it discusses recent therapeutic developments based on mechanistic findings, and outlines goals for future translational studies. The book offers a valuable resource for researchers in the cancer immunotherapy field, helping to form a roadmap for checkpoint regulation and develop safer and more effective immunotherapies.

Author : Axel H. Schönthal
Publisher : Unknown
Page : 128 pages
File Size : 49,6 Mb
Release : 2004
Category : Electronic
ISBN : OCLC:456507251

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Checkpoint Controls and Cancer by Axel H. Schönthal Pdf

Author : Michael B. Kastan
Publisher : Unknown
Page : 375 pages
File Size : 48,8 Mb
Release : 1997
Category : Electronic
ISBN : 0598027939

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Checkpoint Controls and Cancer by Michael B. Kastan Pdf

Author : Wei Dai
Publisher : Springer Science & Business Media
Page : 314 pages
File Size : 44,8 Mb
Release : 2008-05-01
Category : Medical
ISBN : 9781597452748

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Checkpoint Responses in Cancer Therapy by Wei Dai Pdf

Extensive research has uncovered a set of molecular surveillance mechanisms – commonly called “checkpoints” – which tightly monitor cell-cycle processes. Today’s anticancer drug development has identified many of these cell-cycle checkpoint molecules as effective targets. Research now promises to uncover a new generation of anticancer drugs with improved therapeutic indices based on their ability to target emerging checkpoint components. Checkpoint Responses in Cancer Therapy summarizes the advances made over the past 20 years, identifying components of cell-cycle checkpoints and their molecular regulation during checkpoint activation and validating the use of checkpoint proteins as targets for the development of anticancer drugs. This book’s distinguished panel of authors takes a close look at topics ranging from the major molecular players affecting DNA synthesis and the response to DNA damage to advances made in the identification of chemical compounds capable of inhibiting individual mitotic kinases. Illuminating and authoritative, Checkpoint Responses in Cancer Therapy offers a critical summary of findings for researchers in the pharmaceutical and biotechnology industries and a valuable resource for academic scientists in cancer research and the study of cell-cycle regulation, signal transduction and apoptosis.

Author : Philipp Kaldis
Publisher : Springer
Page : 0 pages
File Size : 51,5 Mb
Release : 2010-11-18
Category : Science
ISBN : 3642070930

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Cell Cycle Regulation by Philipp Kaldis Pdf

This book is a state-of-the-art summary of the latest achievements in cell cycle control research with an outlook on the effect of these findings on cancer research. The chapters are written by internationally leading experts in the field. They provide an updated view on how the cell cycle is regulated in vivo, and about the involvement of cell cycle regulators in cancer.

Author : Mikhail V. Blagosklonny
Publisher : Unknown
Page : 276 pages
File Size : 51,8 Mb
Release : 2001
Category : Cancer cells
ISBN : CORNELL:31924095087510

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Cell Cycle Checkpoints and Cancer by Mikhail V. Blagosklonny Pdf

Author : Bruce Alberts
Publisher : Unknown
Page : 0 pages
File Size : 52,8 Mb
Release : 2002
Category : Cytology
ISBN : 0815332181

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Molecular Biology of The Cell by Bruce Alberts Pdf

Author : Steven Grant
Publisher : Academic Press
Page : 290 pages
File Size : 40,8 Mb
Release : 2012-11
Category : Business & Economics
ISBN : 9780123943873

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Histone Deacetylase Inhibitors as Cancer Therapeutics by Steven Grant Pdf

Provides information on the exciting and fast-moving field of cancer research.

Author : Mikhail V. Blagosklonny
Publisher : Unknown
Page : 268 pages
File Size : 46,7 Mb
Release : 2002
Category : Electronic
ISBN : 1597341800

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Cell Cycle Checkpoints in Cancer by Mikhail V. Blagosklonny Pdf

This book addresses mechanisms of normal and cancer cell cycling, checkpoint control, the link of mitogenic signaling and cell cycle machinery. Considerable attention is devoted to the analysis of checkpoint mechanisms from yeast to man allowing us to understand the logic of the cell cycle.

Author : Sam Thiagalingam
Publisher : Cambridge University Press
Page : 597 pages
File Size : 50,6 Mb
Release : 2015-04-09
Category : Mathematics
ISBN : 9780521493390

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Systems Biology of Cancer by Sam Thiagalingam Pdf

An overview of the current systems biology-based knowledge and the experimental approaches for deciphering the biological basis of cancer.