Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy

Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy

Author: Stephen B. Howell

Publisher: Springer Science & Business Media

Published: 2013-11-11

Total Pages: 535

ISBN-13: 1489907386

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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.


Alternative Mechanisms of Multidrug Resistance in Cancer

Alternative Mechanisms of Multidrug Resistance in Cancer

Author: John A. Kellen

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 288

ISBN-13: 1461598524

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Nullius in verba. . . Truth will be tested not by words. Horace (Epistles) Few read introductions except for book reviewers, who want to take a shortcut and avoid reading the book itself. However, tradition requires that the preface make public why the book was written at all (this is not supposed to include powerful reasons such as augmenting the ego of the editor and authors). Frequently, the inflationary tendency to publish in verbose length is in conflict with market forces and interest. No doubt, multidrug resistance is a "fashionable" topic, but there are many fashions displayed on the cat-walk of scientific literature. One can rationalize that the forces driving our concern with multi drug resistance reflect the frustration of pharmaceutical companies and oncologists alike: as soon as a new anticancer drug enters clinical trials, cancer cells start eluding extinction with their elaborate and successful mechanisms. Many grants have been awarded and spent, only to confirm the futility of our efforts to defeat this cellular Darwinism. Our medical and scientific training makes it hard, if not impossible, to accept that the survival of a malignant cell, alone or as part of a tissue, is part of the continuance of life. Since exposure to noxious and lethal substances is unavoidable, cells have been forced to develop a multitude of mechanisms to prevent entry or accelerate exit of such materials from intracellular space.


Current Catalog

Current Catalog

Author: National Library of Medicine (U.S.)

Publisher:

Published: 1992

Total Pages: 666

ISBN-13:

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First multi-year cumulation covers six years: 1965-70.


New Approaches in Cancer Pharmacology: Drug Design and Development

New Approaches in Cancer Pharmacology: Drug Design and Development

Author: Paul Workman

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 240

ISBN-13: 3642790887

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The European School of Oncology came into existence to respond to a need for information, education and training in the field of the diagnosis and treatment of cancer. There are two main reasons why such an initiative was considered necessary. Firstly, the teaching of oncology requires a rigorously multidisciplinary approach which is difficult for the Universities to put into practice since their system is mainly disciplinary orientated. Secondly, the rate of technological development that impinges on the diagnosis and treatment of cancer has been so rapid that it is not an easy task for medical faculties to adapt their curricula flexibly. With its residential courses for organ pathologies and the seminars on new techniques (laser, monoclonal antibodies, imaging techniques etc.) or on the principal therapeutic controversies (conservative or mutilating surgery, primary or adjuvant chemotherapy, radiotherapy alone or integrated), it is the ambition of the European School of Oncology to fill a cultural and scientific gap and, thereby, create a bridge between the University and Industry and between these two and daily medical practice. One of the more recent initiatives of ESO has been the institution of permanent study groups, also called task forces, where a limited number of leading experts are invited to meet once a year with the aim of defining the state of the art and possibly reaching a consensus on future developments in specific fields of oncology.