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Telomerase Inhibition
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Book Synopsis Telomerase Inhibition by : Lucy Andrews
Download or read book Telomerase Inhibition written by Lucy Andrews and published by Springer Science & Business Media. This book was released on 2007-11-29 with total page 197 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume presents a compendium of the most recent and advanced methods applied to the rapidly expanding field of telomerase inhibition. The techniques described provide the researcher with a diverse and comprehensive set of tools for the study of telomerase inhibition. The volume is aimed at biochemists, molecular biologists, cancer researchers, and geneticists.
Book Synopsis Telomeres and Telomerase in Cancer by : Keiko Hiyama
Download or read book Telomeres and Telomerase in Cancer written by Keiko Hiyama and published by Springer Science & Business Media. This book was released on 2009-03-18 with total page 375 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.
Book Synopsis Telomeres and Telomerase by : Predrag Slijepcevic
Download or read book Telomeres and Telomerase written by Predrag Slijepcevic and published by S. Karger AG (Switzerland). This book was released on 2008 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomeres are essential functional elements of eukaryotic chromosomes. Their fundamental biological role as protectors of chromosome stability was identified for the first time in the 1930s by Hermann Muller and Barbara McClintock based on pioneering cytological experiments. Modern molecular research carried out more recently revealed that telomeres and telomerase play important roles in processes such as carcinogenesis and cellular senescence. This special issue presents the most recent developments in this highly active field of research. It is becoming increasingly clear that molecular pathways involved in regulation of telomere length and structure are functionally linked with pathways involved in DNA damage response, cellular stress response, chromatin organization and perhaps even pathways that regulate evolutionary chromosome rearrangements. The above functional link is explored by the leading experts in the field of telomere biology. Cell biologists, molecular biologists, oncologists, gerontologists, and radiobiologists with an interest in the role of telomeres/telomerase will appreciate the up-to-date information in this publication.
Book Synopsis Inhibition of Human Telomerase by Targeting Its Transitory RNA/DNA Heteroduplex by : Rawle Francis
Download or read book Inhibition of Human Telomerase by Targeting Its Transitory RNA/DNA Heteroduplex written by Rawle Francis and published by . This book was released on 2005 with total page 708 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase is a target of intense scientific interest largely because of its implicated role in human carcinogenesis. The inactivation of this enzyme is widely believed to be a promising method to selectively destroy neoplastic cells, while leaving normal cells mostly unaffected. In this dissertation work, the inactivation of human telomerase by molecules based on nucleic acid intercalator structures is presented. The process of cell division shortens the distal portion of linear chromosomes (the telomere). Human telomerase, a special DNA polymerase which functions to maintain telomere length, is composed of RNA and protein subunits. Upon binding to its telomeric DNA substrate, a RNA/DNA heteroduplex is formed. The working hypothesis pursued here is that molecules which target this specific RNA/DNA heteroduplex will stabilize this structure and effectively stall telomerase polymerase activity. Since telomere maintenance is paramount for the survival of rapidly dividing cancer cells, the prevention of telomere maintenance, via inhibition of the telomerase enzyme, is a promising approach to cancer treatment. There are several other approaches to telomerase inhibition presented in the literature. However, targeting the RNA/DNA heteroduplex with the use of modified DNA intercalating agents is a novel and attractive approach to telomerase inhibition. A multifaceted methodology was undertaken to achieve the goal of producing specific inhibitors of human telomerase. First, commercially available nucleic acid intercalators were tested to obtain lead compounds with good inhibitory effect on telomerase activity. Secondly, utilizing techniques of enzyme kinetics, investigations were carried out to determine whether the telomerase RNA/DNA heteroduplex was the target of these lead compounds. Finally, the generation of more potent inhibitors of telomerase was attempted through the use of combinatorial peptide synthesis using lead intercalator(s) as the base structure. It was demonstrated in vitro, that more potent inhibitors of human telomerase could be developed by this approach. Using previously existing assay methods, in addition to original methods developed, relevant experiments were carried out to investigate the stated working hypothesis. During the course of these experiments many interesting observations were made, some of which were pursued and dealt with in these chapters.
Book Synopsis Inhibition of Telomerase from Human Ovarian Cancer Cells Via the Stabalization of G-quadruplex Structures by Various Chemotheraputic Agents by : Paul Edrick Schutt
Download or read book Inhibition of Telomerase from Human Ovarian Cancer Cells Via the Stabalization of G-quadruplex Structures by Various Chemotheraputic Agents written by Paul Edrick Schutt and published by . This book was released on 2001 with total page 74 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Telomerase Inhibition and Chemosensitization of Prostate Cancer Cells by :
Download or read book Telomerase Inhibition and Chemosensitization of Prostate Cancer Cells written by and published by . This book was released on 2004 with total page 17 pages. Available in PDF, EPUB and Kindle. Book excerpt: We hypothesize that telomerase inhibition (telomere shortening) can sensitize human tumor cells to existing anticancer drugs. During the period of the grant we made the following findings-: 1) 2'-methoxy ethyl oligonucleotides inhibit - -telomerase in prostate cancer cells, cause telomeres to shorten, and cause cell- proliferation to decrease; -2) Cell proliferation in culture is -more pronounced when cells are grown under conditions that mimic tumor growth; 3) Cell proliferation is dramatically reduced in a xenograft model using LNCAP cells, and 4) We did not observe significant synergy with standard chemotherapy agents. The ability of relatively short-term treatments with telomerase inhibitors to slow tumor growth in vivo suggests that telomerase inhibitors are a reasonable approach to prostate cancer therapy.
Download or read book Telomerases written by Neal F. Lue and published by John Wiley & Sons. This book was released on 2012-05-22 with total page 334 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a comprehensive and up-to-date review and evaluation of the contemporary status of telomerase research. Chapters in this volume cover the basic structure, mechanisms, and diversity of the essential and regulatory subunits of telomerase. Other topics include telomerase biogenesis, transcriptional and post-translational regulation, off-telomere functions of telomerase and the role of telomerase in cellular senescence, aging and cancer. Its relationship to retrotransposons, a class of mobile genetic elements that shares similarities with telomerase and serves as telomeres in selected organisms, are also reviewed.
Book Synopsis Telomeres and Telomerase by : John A. Double
Download or read book Telomeres and Telomerase written by John A. Double and published by Springer Science & Business Media. This book was released on 2008-02-02 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: The fundamental problem that dividing cells have to ov- come is that of end-replication. Chromosomes shorten by many bases during DNA replication and so this presents a major hurdle that a cell has to overcome both to enable it to proliferate and for the larger organism to survive and reproduce. The enzyme telomerase provides a mechanism to ensure chromosome stability in both normal and neoplastic cells. The demonstration of telomerase expression in a majority of tumors and the realization of the potential role of telomerase in aging has opened up the potential for telomerase to be used as a target for therapeutic intervention. There is therefore great interest in the expression and activity of telomerase in a wide range of biological disciplines. Telomeres and Telomerase: Methods and Protocols has been produced as a tool for the many researchers in different areas of cell biology who are interested in following research in the area of telomerase and telomere maintenance, either in the area of fundamental mec- nisms or perhaps in the area of more applied drug discovery work.
Book Synopsis Enzyme Inhibitors and Activators by : Murat Şentürk
Download or read book Enzyme Inhibitors and Activators written by Murat Şentürk and published by BoD – Books on Demand. This book was released on 2017-03-29 with total page 270 pages. Available in PDF, EPUB and Kindle. Book excerpt: Over the recent years, medicinal chemistry has become responsible for explaining interactions of chemical molecule processes such that many scientists in the life sciences from agronomy to medicine are engaged in medicinal research. This book contains an overview focusing on the research area of enzyme inhibitor and activator, enzyme-catalyzed biotransformation, usage of microbial enzymes, enzymes associated with programmed cell death, natural products as potential enzyme inhibitors, protease inhibitors from plants in insect pest management, peptidases, and renin-angiotensin system. The book provides an overview on basic issues and some of the recent developments in medicinal science and technology. Especially, emphasis is devoted to both experimental and theoretical aspect of modern medicine. The primary target audience for the book includes students, researchers, chemists, molecular biologists, medical doctors, pharmacologists, and professionals who are interested in associated areas. The textbook is written by international scientists with expertise in biochemistry, enzymology, molecular biology, and genetics, many of which are active in biochemical and pharmacological research. I would like to acknowledge the authors for their contribution to the book. We hope that the textbook will enhance the knowledge of scientists in the complexities of some medical approaches; it will stimulate both professionals and students to dedicate part of their future research in understanding relevant mechanisms and applications of pharmacology.
Book Synopsis Mechanism of Telomerase Inhibition Using Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization by :
Download or read book Mechanism of Telomerase Inhibition Using Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization written by and published by . This book was released on 2005 with total page 15 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, a ribonucleoprotein enzyme composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeres after cell divisions and is obligatory for continuous tumor cell proliferation as well as malignant progression of breast cancer cells. Telomerase is an attractive anti-cancer therapeutic agent because telomerase activity is present in over 90% of human breast cancers but is undetectable in most normal somatic cells. Traditional therapies (surgery, chemotherapy, radiotherapy, etc.) lack the ability to effectively control and cure breast cancer, primarily because residual cells are or become resistant to DNA damaging modalities including standard chemo- and radio-therapies. Since telomerase requires its associated hTR for repeat synthesis, we have chosen to use RNA interference as a method to inactivate hTR and hence telomerase. RNA interference (RNAI) has become a powerful tool for the analysis of gene function in that RNAI allows sequence specific inhibition of gene expression. Another protein we targeted is p21, which has long been established as a requirement for senescence. We wanted to further examine its relationship to senescence and apotosis, in an attempt to sensitize breast tumor cells more effectively.
Book Synopsis Telomeres and Telomerase in Aging, Disease, and Cancer by : K. Lenhard Rudolph
Download or read book Telomeres and Telomerase in Aging, Disease, and Cancer written by K. Lenhard Rudolph and published by Springer Science & Business Media. This book was released on 2007-11-07 with total page 332 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomere shortening represents one of the basic aspects of ageing and telomere dysfunction could contribute to the accumulation of DNA damage during ageing. This book summarizes evidence and data indicating that telomere dysfunction influences human ageing, diseases and cancer. The book describes our current knowledge on checkpoints that limit cellular lifespan and survival in response to telomere dysfunction. There is special focus on adult stem cells.
Book Synopsis Mechanism of Telomerase Inhibition Using Small Inibitory RNAs and Induction of Breast Tumor Cell Sensitivity by :
Download or read book Mechanism of Telomerase Inhibition Using Small Inibitory RNAs and Induction of Breast Tumor Cell Sensitivity written by and published by . This book was released on 2007 with total page 21 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, a ribonucleoprotein enzyme composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeres after cell divisions and is obligatory for continuous tumor cell proliferation as well as malignant progression of breast cancer cells. Telomerase is an attractive anti-cancer therapeutic agent because telomerase activity is present in over 90% of human breast cancers but is undetectable in most normal somatic cells. Traditional therapies (surgery, chemotherapy, radiotherapy, etc.) lack the ability to effectively control and cure breast cancer, primarily because residual cells are or become resistant to DNA damaging modalities including standard chemo- and radio-therapies. Since telomerase requires its associated hTR for repeat synthesis, we have chosen to use RNA interference as a method to inactivate hTR and hence telomerase. RNA interference (RNAi) has become a powerful tool for the analysis of gene function in that RNAi allows sequence specific inhibition of gene expression. Another protein we targeted is p21, which has long been established as a requirement for senescence. We wanted to further examine its relationship to senescence and apotosis, in an attempt to sensitize breast tumor cells more effectively.
Book Synopsis The Molecular Regulation of Telomeres and Telomerase by : Craig Daniel Nicholls
Download or read book The Molecular Regulation of Telomeres and Telomerase written by Craig Daniel Nicholls and published by . This book was released on 2011 with total page 562 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomeres are nucleoprotein caps present at each chromosomal end that play a key role in maintaining genomic stability. Telomeres shorten with each cell division, eventually reaching a critical length at which cellular senescence or death pathways are activated. The enzyme telomerase overcomes this shortening through de novo synthesis of telomeric DNA, and telomerase activity is present at high levels in cancer and stem cells. Telomerase is highly regulated by extracellular and intracellular signals, with this regulation having important consequences for telomere homeostasis. This thesis primarily focuses on the novel role of the glycolytic enzyme glyceraldehyde-3- phosphate dehydrogenase (GAPDH) in the regulation of telomeres and telomerase. Chapter 3 demonstrates an interaction between single-stranded 3' C-rich telomeric overhangs and the N-terminal Rossman fold-containing NAD+ binding region of GAPDH. GAPDH is further revealed to inhibit telomerase activity in vitro and in cultured cells. This inhibition has been found to be dependent upon the C-terminal catalytic region of GAPDH. Furthermore, this chapter also demonstrates that nitric oxide modification of GAPDH impairs telomerase inhibition. Chapter 4 examines the relationship between the telomeric DNA binding activity of GAPDH and its telomerase inhibitory function. Several residues critical for mediating telomeric DNA binding were identified by site-directed mutagenesis and gel-shift assays. Expression of these GAPDH mutants in MCF7 breast cancer cells revealed that they retained the ability to inhibit telomerase, suggesting that telomeric DNA binding plays a role in positioning GAPDH on telomeres rather than inhibiting telomerase. However, the mutation K259N - located in a known protein-protein interaction region - abolishes telomerase inhibition and telomere shortening, demonstrating a critical role in telomerase inhibition for this region.This chapter also demonstrates for the first time an interaction between GAPDH and the telomerase RNA component hTERC, suggesting a switch between GAPDH binding of telomeric DNA and telomerase RNA. GAPDH specifically binds hTERC using identical components to those needed for the interaction with telomeric DNA. Furthermore, increased exogenous hTERC eliminates GAPDH-mediated telomerase inhibition. Recent studies from our laboratory have demonstrated that exogenous provision of several TGF[beta] superfamily cytokines can inhibit hTERT expression and telomerase activity. Chapter 5 focuses on the role in telomerase regulation played by the TGF[beta] superfamily type II receptors by inhibiting their action with siRNA or expression of dominant-negative (DN) proteins. Up-regulation of hTERT and telomerase activity resulted from receptor knockdown, confirming the telomerase inhibitory role for these receptors. However, longterm disruption of receptor signalling by stable expression of DN receptors resulted in telomerase inhibition in three of the four receptors examined. This data clearly demonstrates a role for TGF[beta] superfamily receptor signalling in telomerase regulation, though this regulation is likely complex in nature. In summary, this thesis investigates a new mechanismof telomere and telomerase regulation in GAPDH, while also furthering the understanding of the influence on telomerase activity by the TGF[beta] superfamily. The control of telomerase is important in the context of stem cell biology, cancer, and aging research and the findings from this thesis therefore have implications for all these fields.
Book Synopsis Telomeres and Telomerase by : Derek J. Chadwick
Download or read book Telomeres and Telomerase written by Derek J. Chadwick and published by John Wiley & Sons. This book was released on 2008-04-30 with total page 250 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomeres and Telomerase Chairman: Sydney Brenner, 1997 Telomeres are the protective genetic elements located at the ends of chromosomes and are essential for correct chromosomal structure and function. They are not fully replicated by the conventional DNA polymerase system because DNA synthesis occurs only in the 5' to 3' direction and requires an RNA primer for initiation. Consequently, cells require a special enzyme to maintain the telomeric ends of chromosomes during each round of replication. This enzyme, telomerase, is a ribonucleoprotein that extends chromosome ends by adding short stretches of nucleotide repeats using a portion of its integral RNA component as the template. Recently, much excitement has been generated by the suggestion that telomerase, or rather the absence of telomerase and the resultant loss of terminal DNA, is a cause of human ageing. The evidence for this is twofold: the telomeres of certain cells in culture shorten during their lifespan; and immortalization of cells is associated, at least in some cases, with the maintenance of telomeres and telomerase activity. The latter observation prompted the analysis of clinical samples from patients with cancer and the demonstration that, in contrast to normal somatic cells, malignant cells possess telomerase activity. This is a unique book. Not only does it contain the latest experimental results from an international group of experts, but it also includes critical examinations of the current evidence, and discussions that attempt to identify the central and underlying concepts of this rapidly expanding field.
Book Synopsis Mechanism of Telomerase Inhibition Using a Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization by :
Download or read book Mechanism of Telomerase Inhibition Using a Small Inhibitory RNAs and Induction of Breast Tumor Cell Sensitization written by and published by . This book was released on 2007 with total page 53 pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomerase, a ribonucleoprotein enzyme minimally composed of an RNA template (hTR) and a catalytically active protein subunit (hTERT), synthesizes telomeric repeats onto chromosome ends and is obligatory for continuous tumor cell proliferation, as well as malignant progression of breast cancer cells. Telomerase is an attractive anti-cancer therapeutic target because its activity is present in over 90% of human cancers, including more than 95% of breast carcinomas, but undetectable in most somatic cells. Traditional chemo- and radiotherapies lack the ability to effectively control and cure breast cancer, in part because residual cells are or become resistant to DNA damaging modalities. While various telomerase inhibition strategies cause cancer cells to undergo apoptosis or senescence, there is often a lag period between administration and biologic effect (Corey, 2002). Our goal in this study was to compare the efficacy of different telomerase inhibition strategies in concert with standard chemotherapeutic agents at triggering senescence and/or apoptosis in cultures of breast cancer cells. We hypothesized that telomerase inhibition strategies will sensitize breast cancer cells to traditional chemotherapies, potentially reducing the lag phase, allowing for more potent anti-tumor effects at lower doses, and therefore ultimately imparting less toxicity to the patient.
Download or read book Enzyme Kinetics written by Irwin H. Segel and published by . This book was released on 2014 with total page 957 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Telomerase Inhibitors and Activators: Pharmaceutical Importance by : Ayse Gul Mutlu
Download or read book Telomerase Inhibitors and Activators: Pharmaceutical Importance written by Ayse Gul Mutlu and published by . This book was released on 2017 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Telomeres are specialized functional complexes that protect the ends of eukaryotic chromosomes. The telomeric DNA sequences are tandem repeats of a short hexameric sequence unit. The inability to DNA polymerase to replicate the end of the chromosome during lagging strand synthesis results in the loss of telomeric repeats when cell divides. Telomere shortening provides a barrier to cancer progression and the majority of the cancer cells depend on the activation of telomerase to gain proliferative immortality. Thus, telomerase is a molecular target for diseases since its discovery. Telomerase inhibition enables more specific ground for cancer therapy because the telomerase is not detected in most normal tissues. Some of the synthetic and natural telomerase inhibitors were tried on various cancer cells and there was a decrease in the number of cancer cells. But on the other hand, telomere shortening correlates with cellular aging. Some evidence suggests that the progressive loss of telomeric repeats of chromosomes may function as a molecular clock that triggers senescence. Telomerase-related gene mutations also result in some diseases. Because of this, telomerase activators are important for antiaging and telomerase-dependent disease treatments. This chapter summarizes the pharmaceutical importance of telomeres, telomerase structure, telomerase activators, and inhibitors.
