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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 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.
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.
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 Small Molecules in Oncology by : Uwe M. Martens
Download or read book Small Molecules in Oncology written by Uwe M. Martens and published by Springer Science & Business Media. This book was released on 2010-01-14 with total page 242 pages. Available in PDF, EPUB and Kindle. Book excerpt: Extensive research into the molecular mechanisms of cancer disease has heralded a new age of targeted therapy. In malignant cells, key proteins that are crucial to tumor growth and survival are now being targeted directly with rationally designed inhibitors. Apart from monoclonal antibodies, small molecule therapeutics such as oncogenic protein kinase inhibitors are attracting a vast amount of investigational attention. This textbook, written by acknowledged experts, provides a broad overview of the small molecules currently used for the treatment of malignant diseases and discusses interesting novel compounds that are in the process of clinical development to combat cancer.
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:
Download or read book Telomere written by Marcelo Larramendy and published by BoD – Books on Demand. This book was released on 2016-11-23 with total page 228 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book, Telomere - A Complex End of a Chromosome, is organized into nine chapters containing the latest aspects of the current knowledge about the structure of telomeres and the crucial role that telomerase plays not only in maintaining chromosomal stability but also in relation to cell immortality, cell instability, and cancer biology. We now appreciate that these unusual complexes of DNA and proteins we all know as "telomeres" are dynamic and key structures that depend on telomerase and other cellular factors for continuance. Regulation of telomere activity is a dynamic area of current research, and new insights into telomeres and their role in aging and cancer, among other biological functions and pathologies, appear regularly in the scientific world. However, one fact is more than understandable in this difficult biological conundrum: the end of the telomere story is far from being totally unraveled.
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 Biomarkers in Cancer by : Victor R. Preedy
Download or read book Biomarkers in Cancer written by Victor R. Preedy and published by . This book was released on with total page pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Cancer Drug Design and Discovery by : Stephen Neidle
Download or read book Cancer Drug Design and Discovery written by Stephen Neidle and published by Elsevier. This book was released on 2011-04-28 with total page 517 pages. Available in PDF, EPUB and Kindle. Book excerpt: The ultimate source of information on the design of new anticancer agents, emphasizing small molecules, this newest work covers recent notable successes resulting from the human genome and cancer genomics projects. These advances have provided information on targets involved in specific cancers that are leading to effective medicines for at least some of the common solid tumors. Unique sections explain the basic underlying principles of cancer drug development and provide a practical introduction to modern methods of drug design. Appealing to a broad audience, this is an excellent reference for translational researchers interested in cancer biology and medicine as well as students in pharmacy, pharmacology, or medicinal and biological chemistry and clinicians taking oncology options. * Covers both currently available drugs as well as those under development * Provides a clinical perspective on trials of new anticancer agents * Presents drug discovery examples through the use of case histories
