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Author: Bruce D. Cheson
Publisher: CRC Press
ISBN: 1000148661
Category : Medical
Languages : en
Pages : 494
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Book Description
Offering the most current and complete coverage of nucleoside analog activity in oncology and hematology, this single-source volume includes topics from pharmacology to previously unpublished clinical findings on the pivotal role of fludarabine, cladribine, and pentostatin in the management of diseases, such as chronic lymphocytic and hairy cell leukemia, non-Hodgkin's lymphoma, membranous nephropathy, and rheumatoid and psoriatic arthritis.
Author: Bruce D. Cheson
Publisher: CRC Press
ISBN: 1000148661
Category : Medical
Languages : en
Pages : 494
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Book Description
Offering the most current and complete coverage of nucleoside analog activity in oncology and hematology, this single-source volume includes topics from pharmacology to previously unpublished clinical findings on the pivotal role of fludarabine, cladribine, and pentostatin in the management of diseases, such as chronic lymphocytic and hairy cell leukemia, non-Hodgkin's lymphoma, membranous nephropathy, and rheumatoid and psoriatic arthritis.
Author: Godefridus J Peters
Publisher: Springer Science & Business Media
ISBN: 1597451487
Category : Medical
Languages : en
Pages : 482
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Book Description
Successful cancer chemotherapy relies heavily on the application of various deoxynucleoside analogs. Since the very beginning of modern cancer chemotherapy, a number of antimetabolites have been introduced into the clinic and subsequently applied widely for the treatment of many malignancies, both solid tumors and hematological disorders. In the latter diseases, cytarabine has been the mainstay of treatment of acute myeloid leukemia. Although many novel compounds were synthesized in the 1980s and 1990s, no real improvement was made. However, novel technology is now capable of elucidating the molecular basis of several inborn errors as well as some specific malignancies. This has enabled the synthesis of several deoxynucleoside analogs that could be applied for specific malignancies, such as pentostatin and subsequently chlorodeoxyadenosine (cladribine) for the treatment of hairy cell leukemia. Already in the early stage of deoxynucleoside analog development, it was recognized that several of these compounds were very effective in the treatment of various viral infections, such as for the treatment of herpes infections. This formed the basis initially for the design of azidothymidine and subsequently many other analogs, which are currently successfully used for the treatment of HIV infections. As a spin-off of these research lines, some compounds not eligible for development as antiviral agents appeared to be very potent anticancer agents. The classical example is gemcitabine, now one of the most widely applied deoxynucleoside analogs, used for the (combination) treatment of non-small cell lung cancer, pancreatic cancer, bladder cancer, and ovarian cancer.
Author: IARC Working Group on the Evaluation of Carcinogenic Risks to Humans
Publisher: World Health Organization
ISBN:
Category : Health & Fitness
Languages : en
Pages : 536
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Book Description
Evaluates the carcinogenic risks to humans posed by the use of four antiretroviral agents four DNA topoisomerase II inhibitors used in the treatment of cancer and an additional three pharmaceutical agents (hydroxyures phenolphthalein and vitamin K substances). The volume marks the first IARC evaluation of nucleoside analogs that act as antiviral agents. The evaluation responds in part to recent findings that zidovudine (AZT) an effective antiretroviral agent now being given to pregnant HIV-infected women to prevent maternal-to-fetal transmission of the virus is a transplacental carcinogen in mice. The opening monograph evaluates the carcinogenicity to humans of the antiretroviral nucleoside analogs zidovudine (AZT) zalcitabine (ddC) and didanosine (ddI) and the antiherpesvirus drug aciclovir. Of these aciclovir and didanosine could not be classified on the basis of available data. For zidovudine transplacental administration to mice resulted in an increased incidence and multiplicity of lung and liver tumours and in an increased incidence of female reproductive tract tumours in one study but not in another involving treatment at a lower dose. Despite observation of toxic effects in some studies of humans human carcinogenicity data were judged to provide inadequate evidence of carcinogenicity in humans. Zidovudine was classified as possibly carcinogenic to humans. Similar weaknesses in human carcinogenicity data for zalcitabine which consistently induces thymic lymphomas in mice resulted in its classification as possibly carcinogenic to humans. The second monograph evaluates four DNA topoisomerase II inhibitors: etoposide teniposide mitoxantrone and amsacrine. Of these etoposide - one of the most widely used and effective cytotoxic drugs in combination therapy - was classified as probably carcinogenic to humans and etoposide in combination with cisplatin and bleomycin was judged to be carcinogenic to humans. Teniposide was classified as probably carcinogenic to humans and mitoxantrone and amsacrine were classified as possibly carcinogenic to humans. Of the three pharmaceutical agents evaluated in the final monograph hydroxyurea which is widely used in cancer treatment and increasingly in combination with didanosine in HIV infection could not be classified. Phenolphthalein a widely used laxative now being withdrawn from the market in many countries because of toxicological concerns was classified as possibly carcinogenic. Vitamin K substances could not be classified on the basis of available evidence.
Author: Yuen-Ting Lin
Publisher: Open Dissertation Press
ISBN: 9781361301807
Category :
Languages : en
Pages :
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Book Description
This dissertation, "Pharmacological Control of Human Nucleoside Transporters in Endothelial and Cancer Cells by Emodin" by Yuen-ting, Lin, 林婉婷, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Nucleosides possess many physiological and pharmacological properties. Among nucleosides, adenosine is a particularly important as it regulates many physiological functions in cardiovascular system. For instance, adenosine possesses anti-inflammatory effect through its action on endothelial cells. The functions of adenosine are indirectly controlled by the human equilibrative nucleoside transporters (hENTs). These transporters mediate the uptake of adenosine, thereby reducing the amount of extracellular adenosine available for the adenosine receptors and hence reducing its vascular protective effects. Nucleoside analogs such as gemcitabine, are commonly used as anti-cancer drugs in chemotherapy. Most of the anti-cancer nucleoside drugs require human concentrative nucleoside transporters (hCNTs) for their transport into cancer cells. On the other hand, hENTs is supposed to be responsible for the efflux of anti-cancer nucleoside drugs out of the cancer cells. In theory, hENT inhibitors should reduce the removal of adenosine from extracellular compartment by endothelial cells and hence increase and prolong the cardioprotective effect of adenosine. hENT inhibitors should also inhibit the efflux of anti-cancer nucleoside drugs, that in turn increases the drug accumulation in the cancer cells, resulting in a higher efficacy. Some typical and clinically used hENT inhibitors have side effects which limit their uses. Emodin, an active ingredient in many herbs, has been proven to have cardioprotective and anti-tumor properties. However, the mechanisms are not fully understood. We hypothesized that these properties may relate to its interaction with nucleoside transporters. The aims of this study were to investigate the pharmacological effects of emodin on hENTs and its implications on vascular functions and anti-cancer therapy. Our result showed that emodin inhibited both hENT-1 and hENT-2 dose-dependently with no priority to any subtypes of hENTs. The inhibitory effect of emodin on hENTs was reversible and non-competitive, indicating that emodin may interact with the allosteric sites on hENTs. 1,8-dihdroxy-3-methyl anthraquinone, which is similar to emodin in terms of chemical structure but it lacks hydroxyl group at position 3, did not inhibit hENTs. It implied that the presence of 3-hydroxyl group was critical for the inhibitory effect of emodin. Our result also demonstrated that emodin reduced the lipopolysaccharide-induced expression of adhesion molecule in human umbilical vein endothelial cells, reflecting its anti-inflammatory effect. Emodin also enhanced the cytotoxic effect of gemcitabine in HepG2, a liver cancer cell line. Nevertheless, these effects may not be due to the inhibitory effect of emodin on hENTs and further investigation is required. DOI: 10.5353/th_b4852188 Subjects: Endothelial Nucleosides Cancer - Chemotherapy
Author: R. T. Walker
Publisher: Springer Science & Business Media
ISBN: 1461591376
Category : Science
Languages : en
Pages : 463
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Book Description
This publication contains the Review Lectures given at a joint NATO Advanced Study Institute and a FEB S Advanced Study Course, held at Sogesta (Nr. Urbino), Italy from the 7th - 18th May 1979. The Course entitled "Nucleoside Analogues : Chemistry, Biology and Medical Applications" was held for several reasons. In the past few years, many useful and potentially-useful nucleoside analogues have either reached the stage of clinical use or are undergoing clinical trials. Many more compounds have been synthesised by the organic chemist and little more has been done with them other than possibly a few perfunctory biological tests. This is often due to either a lack of interest or an inadequate knowledge of the testing proced ures available or a lack of communication between the chemist, biochemist, pharmacologist and the clinician such that few compounds receive the testing and evaluation which they deserve. The aim of this meeting was to gather together many of the experts in the different scientific disciplines which are involved in the design, synthesis, testing and clinical use of nucleoside analogues, primarily as anti-viral and anti-cancer agents, and to discuss in depth the fundamental principles of each discipline so that participants could understand each other's problems and be more aware of the information required and that which can be obtained.
Author: Robert C. Bast, Jr.
Publisher: John Wiley & Sons
ISBN: 111900084X
Category : Medical
Languages : en
Pages : 2004
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Book Description
Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
Author: Bruce D. Cheson
Publisher: CRC Press
ISBN: 9780824705435
Category : Medical
Languages : en
Pages : 664
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Book Description
Written by over 50 internationally distinguished experts, 30 more than the first edition, and contains nine new chapters! Continuing in the esteemed tradition and heralded success of the first edition, Chronic Lymphoid Leukemias, Second Edition offers a full overview of chronic lymphocytic leukemia (CLL) from multiple perspectives-covering all major developments since the previous edition was published eight years ago. Chronicling the complete history and variations of CLL-type leukemia, the Second Edition reviews the origin, nature, and molecular differences between B-CLL and T-CLL/PLL leukemias analyzes core constituents of apoptosis and causes for dysregulation of programmed cell death (PCD) in B-CLL examines recent research on the role cytokines and regulatory molecules may play in cross-cell communication profiles commonly used vectors for somatic gene therapy, as well as the latest advances in genetic engineering and vector design and production utilizes up-to-the-minute techniques such as fluorescence in-situ hybridization (FISH) and comparative genomic hybridization (CGH) to detect genetic abnormalities and aberrations explores current measures of supportive care with splenectomy, cytokine proteins, and intravenous immunoglobulin applications identifies how to manage infectious and psychiatric complications in patients with CLL and much more! Provides contemporary results on the efficacy of nucleoside analog combinations such as ara-C with fludarabine and cladribine and on the emerging nucleosides nelarabine and clofarabine! Copiously supplemented with over 2500 literature references-1000 more than the first edition-Chronic Lymphoid Leukemias, Second Edition fulfills the reference needs of oncologists, hematologists, immunologists, pathologists, infectious disease specialists, internists, molecular biologists, and medical school students in these disciplines.
Author: Miriam Christine Poirier
Publisher: World Scientific
ISBN: 981323721X
Category : Medical
Languages : en
Pages : 391
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Book Description
As chemical exposures and cancer rates increase worldwide, there is a need for students, researchers, public health professionals, and physicians to understand the mechanisms connecting exposure with human cancer risk. This new book is an essential reference, as well as introduction to the field of chemical carcinogenesis, with particular focus on DNA damage as a critical link between exposure and disease, and emphasis on biomarkers associated with cancer risk in humans. In addition to DNA damage, related topics covered include metabolism of selected chemical carcinogens, exposure-induced epigenetic changes, cancer-associated mutations and reduction of DNA damage and cancer risk by chemoprevention. The book is designed to be a comprehensive guide to basic principles, a teaching tool for academics, and a map for the development of protective mechanisms to reduce human cancer risk.
Author: Moshe Szyf
Publisher: Springer Science & Business Media
ISBN: 9780306478482
Category : Medical
Languages : en
Pages : 264
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Book Description
NA methylation has bewildered molecular biologists since Hotchkiss discovered it almost six decades ago (Hotchkiss RDJ. Biol Cem 1948; 175:315-332). The fact that the chemical structure of our D genome consists of two components that are covalently bound, the genetic information that is replicated by the DNA replication machinery ana DNA methylation that is maintainea by independent enzymatic machinery, has redictably stimulated the imagination and curiosity of generations of mo Edular biologists. An obvious question was whether DNA methylation was a bearer of additional information to the genetic information and what was the nature of this information? It was tempting to speculate that DNA me thylation applied some form of control over programming of the genome s expression profile. Once techniques to probe the methylation profile of whole genomes as well as specific genes became available, it became clear that DNA methylation patterns are gene and tissue specific and that patterns of gene expression correlate with patterns of methylation. DNA methylation pat terns emerged as the only component of the chemical structure of DNA that exhibited tissue and cell specificity. This data seemingly provided an attrac tively simple explanation for the longstanding dilemma of how could one identical genome manifest itself in so many different forms in multicellular organisms? The DNA methylation pattern has thus become the only known factor to confer upon DNA a unique cellular identity.
Author: John Jeffrey McAtee
Publisher:
ISBN:
Category : Antiviral agents
Languages : en
Pages : 352
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Book Description
