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Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy
Cisplatin, the first member of the family of platinum-containing chemotherapeutic agents, was discovered by Barnett Rosenberg in 1965 and approved by the FDA for marketing in 1978. After 30 years of use in the clinic, cisplatin remains a central element of many treatment regimens. Cisplatin is still an irreplaceable component of a regimen that produces high cure rates in even advanced nonseminomatous germ-cell cancers, and is widely used in the treatment of ovarian cancers and other gynecologic cancers, head and neck, and numerous other tumor types. The development of carboplatin has reduced some of the adverse events associated with cisplatin treatment, and the introduction of the DACH plat...
Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations
Membrane transporters are of vital importance for cells. They mediate the flux of many substances through the plasma membrane. In this book, the transporters for organic cations, a special class of membrane transporters, are presented. Transporters belonging to this class are important because they allow many neurotransmitters (e.g., histamine and serotonin) and many drugs (e.g., trospium and tofacitinib) to permeate the plasma membrane. Therefore, transporters for organic cations can modulate the action of neurotransmitters and drugs, having in this way important physiological and pharmacological implications. These aspects are illustrated in original works and reviews presented in this boo...
Organic Cation Transporters
This innovative text explores the cellular transport of organic cations, from functional and structural properties to pharmacological implications and psychiatric developments. The authoritative chapters introduce organic cation transporters and then proceed to discuss their mechanisms such as binding of substrates and inhibitors; their drug dispositions and toxicity; their relationships to genetic and pathophysiological variability; and their roles in endocrine, metabolic, and neurological systems. The final chapters delve into the use of animal models for the study of organic cation transporter function and their possible use in environmental cycling of pharmaceutical residues. This comprehensive volume unites integrative transporter physiology with structural and molecular biology, genetics, pharmacology and pathophysiology, offering a holistic approach to utilizing this novel technique in physiological contexts. It will prove invaluable reading for researchers and students in various areas of integrative, organ, cell and molecular physiology as well as pharmacologists and neurologists.
Organic Cation Transporter 1 (OCT1): Not Vital for Life, but of Substantial Biomedical Relevance
Around one third of all biologically relevant small molecules are organic cations. These include endogenous substances like catecholamines and other neurotransmitters, toxins and drugs designed to affect signaling processes. The organic cation transporter 1 (OCT1) is among the strongest expressed membrane transporters at the sinusoidal (blood-facing) side of liver cells and contributes substantially to the clearance of the blood from numerous organic cations. A most striking feature of OCT1 is its pronounced genetic diversity. Between 1 and 10% of all human populations have little to no OCT1 activity. With several of the OCT1 substrates up to 10% of Europeans are functionally OCT1 deficient....
Membrane Transporters and Channels as Targets for Drugs
Transporters and channels are membrane proteins that mediate the traffic of metabolites, water and ions across biological membranes. Membrane transport proteins are crucial to maintain homeostasis and assure cell survival upon intracellular or environmental stress. A failure of any of these transport systems may have dramatic consequences for cell function. There is increasing evidence that membrane transport proteins play important functions in healthy conditions and that their absence or dysfunction may cause diseases. In recent years much attention has been paid to diseases resulting from defective transporters (“carrier diseases”) and ion channels (“channelopathies”). Very intere...
Transportome Malfunction in the Cancer Spectrum
This is the first of three volumes in the "Ion Channels & Transporters in Tumor Biology" collection, which discusses the function of ion transport proteins in cellular and systemic homeostasis. The authors highlight the role of the so-called transportome, which is defined by the entirety of ion transporters and ion channels. Thereby, readers will get a better understanding of the impact dysregulated ion transport has on the whole spectrum of cancer types. Cancers display deficiencies in several, sometimes interdependent members of the transportome. Clinicians will be interested in the fact that controlled expression of ion transport proteins dramatically impacts the life span of cancer patients, as shown in recent studies. These observations offer a promising outlook for biomedical scientists, as members of the transportome could be the tumor markers of tomorrow - both for diagnostic and therapeutic purposes. As part of a three-volume collection, this book will fascinate members of the active research community, as well as clinicians from the cancer field.
Adverse Effects of Cancer Chemotherapy: Anything New to Improve Tolerance and Reduce Sequelae?
Advances in anti-cancer chemotherapy over recent years have led to improved efficacy in curing or controlling many cancers. Some chemotherapy-related side-effects are well recognized and include: nausea, vomiting, bone marrow suppression, peripheral neuropathy, cardiac and skeletal muscle dysfunction and renal impairment. However, it is becoming clearer that some chemotherapy-related adverse effects may persist even in long term cancer survivors. Problems such as cognitive, cardiovascular and gastrointestinal dysfunction, and neuropathy may lead to substantial long term morbidity. Despite improvements in treatments to counteract acute chemotherapy-induced adverse effects, they are often incompletely effective. Furthermore, counter-measures for some acute side-effects and many potential longer term sequelae of anti-cancer chemotherapy have not been developed. Thus, new insights into prevalence and mechanisms of cancer chemotherapy-related side effects are needed and new approaches to improving tolerance and reduce sequelae of cancer chemotherapy are urgently needed. The present Research Topic focuses on adverse effects and sequelae of chemotherapy and strategies to counteract them.
