DNA Damage Response/Repair in Cancer Stem Cells - Potential Vs. Controversies PDF Download
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Author: Maria Louka
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages :
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Book Description
DNA Damage Response/Repair in Cancer Stem Cells - Potential vs. Controversies.
Author: Maria Louka
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages :
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Book Description
DNA Damage Response/Repair in Cancer Stem Cells - Potential vs. Controversies.
Author: Lesley A Mathews
Publisher: Springer Science & Business Media
ISBN: 9400745907
Category : Medical
Languages : en
Pages : 180
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Book Description
The existence of ‘cancer stem cells’ (CSCs) has been a topic of heated debate for the last few years within the field of cancer biology. Their continuous characterization in a variety of solid tumors has lead to an abundance of evidence supporting their existence. CSCs are believed to be responsible for resistance against conventional treatment regimes of chemotherapy and radiation, ultimately, leading to metastasis and patient demise. To help aid clinicians, pharmaceutical companies and academic labs investigating how to better kill these highly aggressive cells we have summarized the DNA repair mechanism(s) and their role in the maintenance and regulation of both normal and cancer stem cells. Our book represents a comprehensive investigation into the highly effective DNA repair mechanisms of CSCs and what we need to understand in order to develop more advanced therapies to eradicate them from patients. Currently, there are no other published works entirely on DNA repair and Cancer Stem Cells. In addition, our book provides a comprehensive overview of CSC isolation and characterization from a variety of solid tumor types.
Author: Marcel van Vugt
Publisher: Frontiers Media SA
ISBN: 2889199495
Category : Genetics
Languages : en
Pages : 111
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Book Description
For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: ‘Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets’ we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the ‘DNA damage response (DDR)’ cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.
Author: Yitzhak Zimmer
Publisher: Frontiers Media SA
ISBN: 2889662152
Category : Medical
Languages : en
Pages : 114
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Book Description
Topic Editor Christian Reinhardt has received funding from companies Gilead, and lecture fees from Abbvie, Merck, and AstraZeneca. All other topic editors declare no competing interests with regards to the Research Topic subject.
Author: Srinivasan Madhusudan
Publisher: CRC Press
ISBN: 1466577436
Category : Medical
Languages : en
Pages : 720
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Book Description
DNA repair is a rapidly advancing field in biology and these systems represent a major defense mechanism against environmental and intracellular damaging agents such as sunlight, ionizing radiation, and reactive oxygen species. With contributions from eminent researchers, this book explores the basics and current trends in this critical field. Topics include carcinogenesis as a predictive and/or prognostic biomarker for cancer therapy, nucleotide excision repair, and tumor genetics and personalized medicine. The contributions provide essential information to scientists, pharmaceutical investigators, and clinicians interested in cancer therapy.
Author:
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
For this eBook, and the associated Research Topic in Frontiers in Genetics, entitled: 'Cancer-associated defects in the DNA damage response: drivers for malignant transformation and potential therapeutic targets' we have selected 10 papers that each discusses important, yet distinct aspects of the response to DNA damage in normal cells and cancer cells. Using an evolutionary conserved signaling network called the 'DNA damage response (DDR)' cells maintain the integrity of their genome, and thus safeguard cellular functioning and the ability to create viably progeny. Initially, the DDR appeared to consist of few linear kinase-driven pathways. However, research over the past decades in model organisms, as well as in the human system has revealed that the DDR is a complex signaling network, wired by multiple parallel pathways and displaying extensive crosstalk. Besides phosphorylation, multiple other post-translational modifications, including ubiquitination and sumoylation, are involved to achieve chromatin remodeling and initiation of DNA repair. Also, rather than being a cell-intrinsic phenomenon, we increasingly appreciate that cell-cell communication is involved. The recognition and repair of DNA damage is essential to maintain normal physiology. Multiple pathological conditions have been attributed to defective DNA repair, most notably accelerated aging, neurodegeneration and cancer. In the context of cancer, through repair of DNA damage or elimination of irreparably damaged cells, the DDR clearly has a tumor-suppressive role. Indeed, many tumor cells show partially inactivated DDR signaling, which allows proliferation in the context of DNA damage-inducing oncogenes. Simultaneously, loss of specific DDR signaling nodes creates a specific dependence of tumor cells on their remaining DDR components, and thus creates therapeutic opportunities. Especially in the context of cancer treatment, numerous targeted agents are under investigation, either to potentiate the cytotoxic effects of chemo-radiotherapy, or to induce synthetic lethality with cancer-specific alterations, with the treatment of BRCA1/2 mutant cancers with PARP1 inhibitors as a prototype example. We have selected four review articles that provide insight into the key components and the wiring of the DDR and DNA repair. Torgovnick and Schumacher review the involvement of DNA repair in the initiation and treatment of cancer, Brinkmann et al., describe the involvement of ubiquitination in DNA damage signaling and Jaiswal and Lindqvist discuss how cell-extrinsic signaling participates in communication of DNA damage to neighboring cells. In addition, Shatneyeva and colleagues review the connection between the cellular response to DNA damage and escape from immune surveillance. Concerning the therapeutic application of targeting the DDR and DNA repair, three articles were included. Krajewska and van Vugt review the wiring of homologous recombination and how this offers therapeutic opportunities. Additionally, Knittel and colleagues describe how genetic loss of the central DDR component ATM in chronic lymphocytic leukemia can be exploited therapeutically by targeting certain parallel DNA repair pathways. Syljuasen and colleagues report on how targeting of the DDR can be used as a therapeutic strategy in lung cancer. Finally, three chapters describe newly identified regulators of the cellular response to DNA damage. Von Morgen et al. describe the R2TP complex, Lezzi and Fanciluuli review the involvement of Che-1/AATF in the DDR, and Ohms and co-authors describe how retrotransposons are at the basis of increased genomic instability. Altogether, these articles describe how defective responses to DNA damage underlie disease - and especially in the context of cancer -can be exploited to better treat disease.
Author: Amar Bharat Desai
Publisher:
ISBN:
Category : Adult stem cells
Languages : en
Pages : 168
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Book Description
The DNA damage response is composed of multiple signaling and repair pathways which together constitute an important tool cells utilize to preserve genomic stability. Repair pathways have shown to be critical in many cell types, including in human cancers where upregulation of DNA repair is believed to contribute to therapy resistance. In normal human development it is vital to stem cell populations, including in the hematopoietic system, where maintenance of genomic stability is necessary for development and normal immune function. The precise proteins and pathways responsible for maintaining cellular damage responses are often cell type specific, and identification of critical repair enzymes continues to yield promising therapeutic targets for a plethora of human conditions.The 5'->3' nuclease Exonuclease 1 (Exo1) has been implicated in several cellular processes including DNA mismatch and double strand break repair. Its upregulation has been characterized in human cancers of the breast, lung, colon, bladder and others. Here we examine the role of Exo1 in multiple contexts, including in hematopoietic stem cells (HSC), where we describe Exo1 loss in the HSC damage response both in quiescent and active settings. We demonstrate that while Exo1 and homologous recombination (HR) are dispensable for HSCs at steady state, stress induced cell cycle entry results in an HSC reliance on Exo1 mediated HR. We also explore the importance of DNA repair pathways and Exo1 in human lung cancer stem cells using the CD133 marker, and characterize the potential for Exo1 silencing as a cancer stem cell specific therapy. We find that upon prior exposure to double-strand break therapy, CD133+ cells are activated and rely on multiple DNA repair proteins including Exo1, and that this reliance contributes to radiation resistance. Finally we mechanistically describe the role of Exo1 in DNA Mismatch Repair (MMR) and identify a compensatory Exo1 independent pathway that cells adopt to minimize genomic instability involving the additional 5'-->3' nucleases Artemis, Fan1, and Mre11.Collectively our findings provide deeper insight into the DNA repair dependence of multiple stem cell populations and characterize the importance of Exonuclease 1 both in stem cell maintenance and as a potential therapeutic target.
Author: Susie Nilsson
Publisher: Academic Press
ISBN: 0323853250
Category : Science
Languages : en
Pages : 246
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Book Description
The Cancer Stem Cell Niche, Volume Five in the Advances in Stem Cells and their Niches series, highlights new advances in the field, with this new volume presenting interesting chapters on a variety of timely topics, including Acute lymphoblastic leukemia and the bone marrow microenvironment, Stem cell niches in bone and their roles in cancer metastasis, The role of vasculature in cancer stem cell niches, The lung cancer stem cell niche, The prostate cancer stem cell niche: Genetic drivers and therapeutic approaches, Impact of prostate cancer stem cell niches on prostate cancer tumorigenesis and progression, The testicular cancer stem cell niche. Provides the authority and expertise of leading contributors from an international board of authors Presents the latest release in the Advances in Stem Cells and their Niches series Includes the latest information on the Cancer Stem Cell Niche
Author: Bo Lin
Publisher:
ISBN:
Category : Electronic dissertations
Languages : en
Pages :
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Book Description
The DNA mismatch repair (MMR) pathway is a very important DNA repair pathway to maintain genomic integrity. Germline mutations in the MMR genes can cause a hereditary cancer predisposition syndrome, Lynch Syndrome (LS). LS patients develop colorectal cancer as well as other extracolonic cancers at an early age. However, how the loss of DNA MMR leads to tumorigenesis remains unclear. The MMR mediated DNA damage response to the alkylating agent N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) observed in various cancer cell lines may contribute to preventing tumorigenesis by eliminating damaged cells. In the first part of this study, we examined the MMR dependent DNA damage response in the human pluripotent stem cell (hPSC) which is a nontransformed cell model. We found that hPSCs are hypersensitive to alkylation damage which triggers massive apoptosis. Interestingly, the nature of this alkylation response differs from that previously reported in somatic cells. In somatic cells, a permanent G2/M cell cycle arrest is induced in the second cell cycle after DNA damage. The hPSCs, however, directly undergo apoptosis in the first cell cycle. Furthermore, the signaling mechanisms of this damage response are also very different from somatic cells in that the checkpoint kinases Chk1 and Chk2 are not activated in hPSCs in response to alkylation damage, but rather p53 activation is responsible for inducing apoptosis. This response reveals that hPSCs rely on apoptotic cell death as an important defense to avoid mutation accumulation. Since LS patients predominantly develop colorectal cancer and human embryonic stem cells (hESCs) can be differentiated into intestinal organoids in vitro, in the second part of this study we generated both hESCs-derived human intestinal organoids (HIOs) and adult human intestinal enteroids (HIEs) from patient colon samples to study the damage responses to alkylation damage in intestinal cells specifically. We found that the MMR pathway can direct multiple responses to DNA damage in different intestinal cell types in HIOs. Intestinal stem cells (ISCs) appear more prone to undergo apoptosis in response to DNA damage whereas more differentiated cells such as the transient amplifying cells are more likely to senesce. Both mechanisms may play an important role in tumor suppression by eliminating or halting progression of damaged cells. Therefore loss of MMR pathway function might provide an immediate selective advantage at an early stage during tumorigenesis in LS patients. Taken together, this work further reveals the MMR-dependent DNA damage response in nontransformed cell types and cell types related to LS, and provides insights into how loss of these damage responses may contribute to tumorigenesis at an early stage in LS patients.
Author: Maria del Mar Vivanco
Publisher: Humana
ISBN: 9781493925186
Category : Science
Languages : en
Pages : 0
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Book Description
The identification of normal and breast cancer stem cells has offered a new vision of this heterogeneous disease and new hopes for its prognosis and treatment. This volume provides an overview of recent developments in mammary stem cell research and discusses the many varieties of approaches used by researchers to investigate the properties and functions of mammary stem cells. The beginning chapters provide readers with an introduction to mammary stem cells, and the processes used to characterize stem cells and isolate them via fluorescent activated cell sorting. The next few chapters discuss DNA and mRNA sequencing, proteomic techniques to help profile cells, lentiviral cell transduction for gene expression, and in vivo lineage tracing. The final few chapters are dedicated to following stem cells from their initial niche to the new microenvironment at their metastasis site, and to studying these cells using physical and mathematical approaches. Written in the highly successful Methods in Molecular Biology series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Authoritative and cutting-edge, Mammary Stem Cells: Methods and Protocols aims to help members of the scientific community explore the behavior of stem cells and how to work with them in order to guide the design of new and complimentary strategies to be applied in the clinic with the ultimate end goal of fighting breast cancer.
