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Author: Stephen B. Howell Publisher: Springer Science & Business Media ISBN: 030644027X Category : Medical Languages : en Pages : 563
Book Description
Taken together the data presented in this review, and work by many other investigators, support the notion that DNA excision repair is important in a tumor cell's resistance to platinum compounds. Inhibition of this repair system by combination chemotherapy with the excision repair inhibitors HU and Ara-C produces synergistic cell kills and increased levels and persistance of DNA interstrand crosslinks. The studies with cis-DDP and ~-DDP in combination with UV induced thymine dimers suggest that there may be competition for DNA repair enzymes between the dimer and the platinum lesion. Whether the competing lesion is an intrastrand crosslink, interstrand crosslink, or platinum monoadduct (or all of these lesions) cannot be determined. The similarity between an intrastrand crosslink and a cyclobutane dimer suggests that these lesions may compete for repair. However, the increased peak levels of interstrand crosslinks, and increased persistence of these lesions at later time points suggest that this lesion may also be a substrate for the repair system. These observations may be of clinical relevance. Recently Dr. Kathy Albain of our institution has completed a Phase III I study using a 12 hour pretreatment with HU and Ara-C in patients prior to their cis-DDP therapy. She observed a significant number of responders in this trial (54). She is currently completing a second Phase IIII study substituting IV HU for the oral formulation. We anticipate initiating other clinical trials based upon these observations.
Author: Stephen B. Howell Publisher: Springer Science & Business Media ISBN: 030644027X Category : Medical Languages : en Pages : 563
Book Description
Taken together the data presented in this review, and work by many other investigators, support the notion that DNA excision repair is important in a tumor cell's resistance to platinum compounds. Inhibition of this repair system by combination chemotherapy with the excision repair inhibitors HU and Ara-C produces synergistic cell kills and increased levels and persistance of DNA interstrand crosslinks. The studies with cis-DDP and ~-DDP in combination with UV induced thymine dimers suggest that there may be competition for DNA repair enzymes between the dimer and the platinum lesion. Whether the competing lesion is an intrastrand crosslink, interstrand crosslink, or platinum monoadduct (or all of these lesions) cannot be determined. The similarity between an intrastrand crosslink and a cyclobutane dimer suggests that these lesions may compete for repair. However, the increased peak levels of interstrand crosslinks, and increased persistence of these lesions at later time points suggest that this lesion may also be a substrate for the repair system. These observations may be of clinical relevance. Recently Dr. Kathy Albain of our institution has completed a Phase III I study using a 12 hour pretreatment with HU and Ara-C in patients prior to their cis-DDP therapy. She observed a significant number of responders in this trial (54). She is currently completing a second Phase IIII study substituting IV HU for the oral formulation. We anticipate initiating other clinical trials based upon these observations.
Author: Angela Casini Publisher: Royal Society of Chemistry ISBN: 1788017676 Category : Science Languages : en Pages : 370
Book Description
Metal-based anticancer drugs are among the most successful therapeutic agents, as evidenced by the frequent prescription of selected platinum and arsenic compounds to patients. Metal-based Anticancer Agents covers the interdisciplinary world of inorganic drug discovery and development by introducing the most prominent compound classes based on different transition metals, discussing emerging concepts and enabling methods, as well as presenting key pre-clinical and clinical aspects. Recent progress on the unique features of next-generation targeted metal-based anticancer agents, including supramolecular coordination complexes used for both therapy and drug delivery, promise a bright future beyond the benefits of pure cytotoxic activity. With contributions from global leaders in the field, this book will serve as a useful reference to established researchers as well as a practical guide to those new to metallodrugs, and postgraduate students of medicinal chemistry and metallobiology.
Author: Astrid Sigel Publisher: Walter de Gruyter GmbH & Co KG ISBN: 311047073X Category : Science Languages : en Pages : 588
Book Description
Volume 18, entitled Metallo-Drugs: Development and Action of Anticancer Agents of the series Metal Ions in Life Sciences centers on biological, medicinal inorganic chemistry. The serendipitous discovery of the antitumor activity of cis-diamminodichloroplatinum(II) (cisplatin) by Barnett Rosenberg in the 1960s is a landmark in metallodrug-based chemotherapy. The success of cisplatin in the clinic, followed by oxaliplatin and carboplatin, along with their drawbacks relating mainly to resistance development and severe toxicity, initiated research on polynuclear platinum complexes and on Pt(IV) complexes as prodrugs. Furthermore, the indicated shortcomings led to the exploration of other transition and main group metal ions, among them Ru(II/III), Au(I/III), Ti(IV), V(IV/V), and Ga(III) including also the essential metal ions Fe(II/III), Cu(I/II), and Zn(II). Ionic as well as covalent and non-covalent interactions between structurally very different complexes and biomolecules like nucleic acids, proteins, and carbohydrates are studied and discussed with regard to their possible anticancer actions. Hence, MILS-18 summarizes the research at the forefront of medicinal inorganic chemistry, including studies on the next-generation, tailor-made anticancer drugs. All this and more is treated in an authoritative and timely manner in the 17 stimulating chapters of this book, written by 39 internationally recognized experts from 10 nations (from the US via Europe to China and Australia). The impact of this vibrant research area is manifested by more than 2700 references, nearly 150 illustrations (more than half in color) and several comprehensive tables. Metallo-Drugs: Development and Action of Anticancer Agents is an essential resource for scientists working in the wide range from enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine including the clinic ... not forgetting that it also provides excellent information for teaching.
Author: Shahid Ul Islam Publisher: John Wiley & Sons ISBN: 1119640423 Category : Science Languages : en Pages : 432
Book Description
This book is organized into 12 important chapters that focus on the progress made by metal-based drugs as anticancer, antibacterial, antiviral, anti-inflammatory, and anti-neurodegenerative agents, as well as highlights the application areas of newly discovered metallodrugs. It can prove beneficial for researchers, investigators and scientists whose work involves inorganic and coordination chemistry, medical science, pharmacy, biotechnology and biomedical engineering.
Author: Astrid Sigel Publisher: CRC Press ISBN: 9780824799847 Category : Science Languages : en Pages : 826
Book Description
"Volume 35 covers the biological cycling of iron in oceans; the transport of iron in microorganisms, fungi, and plants; the roles and properties of siderophores; the regulation of iron transport and uptake in animals, plants, and microorganisms, and more. "
Author: Peggy L. Carver Publisher: Walter de Gruyter GmbH & Co KG ISBN: 3110526980 Category : Science Languages : en Pages : 640
Book Description
Volume 19, entitled Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic of the series Metal Ions in Life Sciences centers on the role of metal ions in clinical medicine. Metal ions are tightly regulated in human health: while essential to life, they can be toxic as well. Following an introductory chapter briefly discussing several important metal-related drugs and diseases and a chapter about drug development, the focus is fi rst on iron: its essentiality for pathogens and humans as well as its toxicity. Chelation therapy is addressed in the context of thalassemia, its relationship to neurodegenerative diseases and also the risks connected with iron administration are pointed out. A subject of intense debate is the essentiality of chromium and vanadium. For example, chromium(III) compounds are taken as a nutritional supplement by athletes and bodybuilders; in contrast, chromate, Cr(VI), is toxic and a carcinogen for humans. The benefi cial and toxic effects of manganese, cobalt, and copper on humans are discussed. The need for antiparasitic agents is emphasized as well as the clinical aspects of metal-containing antidotes for cyanide poisoning. In addition to the essential and possibly essential ones, also other metal ions play important roles in human health, causing harm (like the metalloid arsenic, lead or cadmium) or being used in diagnosis or treatment of human diseases, like gadolinium, gallium, lithium, gold, silver or platinum. The impact of this vibrant research area on metals in the clinic is provided in 14 stimulating chapters, written by internationally recognized experts from the Americas, Europe and China, and is manifested by approximately 2000 references, and about 90 illustrations and tables. Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic is an essential resource for scientists working in the wide range from pharmacology, enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine ... not forgetting that it also provides excellent information for teaching.
Author: S.P. Fricker Publisher: Springer Science & Business Media ISBN: 9401112525 Category : Medical Languages : en Pages : 269
Book Description
The discovery of the antitumour activity of cisplatin in 1965 and its subsequent introduction into clinical trials in 1971 was the catalyst for a major international research effort investigating the potential of metal compounds in cancer therapy. Cisplatin now occupies an important place in the armamentarium of the oncologist due to its effectiveness in the treatment of testicular cancer. A second generation analogue, carbo platin, offers reduced toxicity together with therapeutic activity, which gives it a place in the front-line therapy of genitourinary cancers. These and other successes have encouraged the search for novel metal-based drugs for cancer therapy. Research has shown that metal compounds have potential for activity not only as cytotoxic antitumour agents, but also in areas such as adjuvant therapy, diagnosis and immunotherapy. The aim of this book is to review and describe the major achievements and developments arising from this international research effort. The contributing authors come from labora tories throughout Europe and America and represent the many disci plines characteristic of this research, such as clinical research, pharmacology, tumour biology and inorganic medicinal chemistry.
Author: Toshiyuki Fukada Publisher: Springer Nature ISBN: 9811505578 Category : Medical Languages : en Pages : 412
Book Description
This book, now in an extensively revised second edition, describes the crucial role of zinc signaling in biological processes on a molecular and physiological basis. Global leaders in the field review the latest knowledge, including the very significant advances in understanding that have been achieved since publication of the first edition. Detailed information is provided on all the essentials of zinc signaling, covering molecular aspects and the roles of zinc transporters, the zinc sensing receptor, and metallothioneins. Detection techniques for zinc signals, involving genetically encoded and chemical probes, are also described. The critical contributions of the zinc signal in maintaining health and the adverse consequences of any imbalance in the signal are then thoroughly addressed. Here, readers will find up-to-date information on the significance of the zinc signal in a wide range of conditions, including cardiovascular disorders, neurodegenerative diseases, diabetes, autoimmune diseases, inflammatory conditions, skin disease, osteoarthritis, and cancer. The book will be of value for researchers, clinicians, and advanced students.
Author: Marcel Gielen Publisher: John Wiley & Sons ISBN: 0470864044 Category : Science Languages : en Pages : 638
Book Description
There are an astonishing number and variety of roles that metals play in contemporary medicine. This book contains information on the medicinal uses of inorganics, that is, of elements such as boron, lithium, selenium, to name a few, as well as metal-containing species. In keeping with the notion that healthy mammals rely on (bio-essential) metals for the normal functioning of approximately a third of their proteins and enzymes, a large number of drugs are metal-based and considerable effort is being devoted to developing both second- and third-generation drugs as well as generating novel metal-based drugs. While there is no doubt that there is an emphasis on 'Metallotherapeutics' throughout the volume, the use of metals in medicine is not restricted to metal-based drugs. The following are also covered: non-invasive radiopharmaceuticals Magnetic Resonance Imaging (MRI) mineral supplements From the foregoing and, more importantly, from the contents of the various Chapters, the reader will gain an appreciation of the very real role metal-based drugs play in modern medicine and of the considerable effort being devoted to the development of novel complexes with greater efficacy as therapeutic and diagnostic agents.
Author: Stephen B. Howell
Author: Stephen B. Howell
Author: Angela Casini
Author: Astrid Sigel
Author: Shahid Ul Islam
Author: Astrid Sigel
Author: Peggy L. Carver
Author: Etienne Baulieu
Author: S.P. Fricker
Author: Toshiyuki Fukada
Author: Marcel Gielen