Lawrence J. Marnett – författare

One of the significant developments explored within this collection of articles is the expression of the novel isoform of cyclooxygenase, which may play a large role in the development of anti-inflammatory drugs. Over one hundred contributions detail advances in the molecular and cellular biology of eicosanoid production, as well as their role in signal transduction.

This volume constitutes, in part, the proceedings of the Hong Kong Conference on "Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Radiation Injury" held in Hong Kong in October 1995. It contains papers by the symposium speakers, as well as poster contributions from researchers in this field. Since the discovery of "PROSTAGLANDIN-LIKE' substances 60 years ago. much has been learned. EICOSANOID is the new term that is used to include prostaglandins. thromboxanes, leukotrienes, lipoxins, isoprostanes, depoxilins, hydroxy acids, epoxy and hydroperoxy fatty acids. The conference focussed on recent development in underatanding the role of EICOSANOIDS in inflammation, cancer, and radiation damage. At the confer- ence, we also highlighted advances in newly developing areas such as "NO," "A POP- TOSIS and "ANANDAMIDE." The discovery of the structures of genes that encode several key enzymes and receptors of the Eicosanoid cascade, has allowed us to include reports in the "Alteration of the Gene Expression" section that reflects the most recent de- velopments in regulation for PGH-synthase and lipoxygenases.The editors are convinced that this volume will be an up-to-date and useful reference for investigators in both basic and clinical research.

Since their discovery over 60 years ago, eicosanoids have come to represent a diverse family of bioactive lipid modulators, including prostaglandins, thromboxanes, leukotrienes, lipoxins, isoprostanes, hepoxilins, hydroxy acids, epoxy and hydroxy fatty acids. This book contains conference presentations regarding the regulation of eicosanoid enzymes and, in particular, cyclooxygenases, lipoxygenases, and phospholipases. In addition, the latest evidence over the last seven years has led to the identification of a number of receptors for these bioactive lipids. The new field of isoprostanes is also represented. It has become increasingly evident that eicosanoids play a critical role in signal transduction, both in normal cells and in pathological processes. These aspects are discussed in relation to cellular events, such as apoptosis, angiogenesis, and cancer prevention and treatment.

This volume represents a collection of manuscripts dealing with the roles and actions of lipid mediators and their impact on human physiology and disease pathogenesis. In particular these contributions focus on cancer, inflammation and cardiovascular disease. The most recent advances in the formation and actions of lipid mediators is discussed at the molecular and cellular level. The synthesis of novel inhibitors is discussed relevant to their potential impact on cancer and inflammatory disease therapy. In addition to the "classical" lipid mediators, this volume contains presentations of exciting new developments in anandamides, nitric oxide and isoeicosanoids. The data and concepts presented in this volume should be of interest to both clinicians and basic researchers in the fields of cancer and inflammation.

This volume contains the proceedings of the First International Conference on Eicosanoids and Other Bioactive Lipids in Cancer and Radiation Injury held in Detroit, Michigan on October 11-14, 1989. The conference was unique in its forging of a link between the eicosanoid and lipid researchers in the disciplines of radiobiology and cancer. The diverse roles that eicosanoids and other bioactive lipids play in these biological phenomena, including the participation of lipid oxidation in conversion of procarcinogens, positive and negative modulation of tumor growth, immunomodulation, tissue injury, and yet protection and enhancement of cancer therapy, necessitated a scientific interaction to sort out and understand these complex and sometimes contradictory observations. The scope of this volume encompasses the complete range of eicosanoid studies in these two fields, beginning with discussions of improved means of detecting eicosanoids using radioimmunoassays, high performance liquid chromatography, and GC-mass spectrometry and including specialized assays of the enzyme system involved in the metabolism of the bioactive lipids.Studies on the mechanistic basis of bioactive lipids in carcinogenesis and radiation injury have been conducted in vitro in biochemical assays and cell culture, culminating in observations in vivo, including applications in the treatment of cancer patients.

In recent decades, eicosanoids have been attracting an increasing amount of attention as a result of their important physiological roles in many areas of biology and medicine. The eicosanoids comprise the prostaglandins, thromboxanes and leukotrienes and are products of arachidonic acid, an essential polyunsaturated fatty acid stored in tissue phospholipids. Disturbances of eicosanoids and their metabolic products play a regulatory role in many types of cell injuries and diseases. One of the most exciting areas of eicosanoid research pinpoints their participation in the control of cell proliferation and differentiation. Eicosanoids form a link between different fields of research into such areas as cancer, inflammation and radiation-induced injury. This link provided the impetus for the development of the conference series of which this volume represents the proceedings of the Second International Conference, held in Berlin in October 1991.

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series that will focus on an emerging area of cancer research. In 1968, R.H. Williams first reported that elevated prostaglandin levels are present in human medullary car- cinoma. Since that time, the concept that arachidonic acid metabolites may be in- volved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family of bioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respec- tively. Cyclooxygenase products consist of diverse products such as prosta- glandin E2 (POE ), prostacyclin (POI ) and thromboxane A2 (TXA ), whereas 2 2 2 lipoxygenase products consist of hydroperoxy fatty acids and mono-, di- and tri-hydroxy acids including leukotrienes. The precursor fatty acids for the cyclooxygenase and lipoxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis-the release of substrate.This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengl Samuelsson's extensive study of the metabolism of pros- taglandins indicated that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in or in the vicinity of target tissues leading to the concept that prostaglandins are local hormones or autocoids.

Prostaglandins, Leukotrienes, and Cancer is a multi-volume series that will focus on an emerging area of cancer research. In 1968, R.H. Williams first reported that elevated prostaglandin levels are present in human medullary car- cinoma. Since that time, the concept that arachidonic acid metabolites may be in- volved in cancer has expanded to include every aspect of the disease from cell transformation through metastasis. Prostaglandins and leukotrienes are generic terms used to describe a family of bioactive lipids produced from unsaturated fatty acids (principally from arachidonic acid) via the cyclooxygenase and lipoxygenase pathways, respec- tively. Cyclooxygenase products consist of diverse products such as prosta- glandin E2 (POE ), prostacyclin (POI ) and thromboxane A2 (TXA ), whereas 2 2 2 lipoxygenase products consist of hydroperoxy fatty acids and mono-, di- and tri-hydroxy acids including leukotrienes. The precursor fatty acids for the cyclooxygenase and lipoxygenase pathways are present in cellular phospholipids. This finding established an important control point in their biosynthesis-the release of substrate.This occurs in response to numerous stimuli that act at the cell surface. Dr. Bengl Samuelsson's extensive study of the metabolism of pros- taglandins indicated that they are rapidly inactivated on a single pass through pulmonary circulation. Thus, they cannot act as circulating hormones and appear to be made on demand in or in the vicinity of target tissues leading to the concept that prostaglandins are local hormones or autocoids.

This volume represents a collection of contributions from the 6th International Conference on Eicosanoids and Other Bioactive Lipids in Cancer, Inflammation, and Related Diseases held in Boston from September 12-15, 1999. The mission of this meeting was to bring together senior and junior investigators to both announce and examine their recent advancements in cutting-edge research on the roles and actions of lipid mediators and their impact in human physiology and disease pathogenesis. The meeting focused on new concepts in these areas of interest to both clinicians and researchers. The program included several outstanding plenary lectures and presentations by leading experts in the fields of cancer and inflammation. In addition, the Boston meeting presented three Young Investigator awards, one in each of the major focus areas. The meeting was exciting and proved to be very memorable. The program was developed with an emphasis on recent advances in molecular and of lipid mediators relevant in cellular mechanisims involved in the formation and actions inflammation and cancer. Plenary lectures were presented by Prof. Bengt Sammuelsson (Karolinska Institute, Stockholm; 1982 Nobel Laureate in Physiology or Medicine) and Prof. E. 1. Corey (Harvard University; 1990 Nobel Laureate in Chemistry). Both of these plenary lectures were held on Day 1, which set an exciting tone for this meeting. Immediately following these plenary lectures, three simultaneous breakout sessions were held, one of inflammation, a second on cancer and synthesis of novel inhibitors, and a third on enzymes-lipoxygenases/cyclooxygenases and inhibitors.

In recent decades eicosanoids have been attracting an increasing amount of attention as a result of their important physiological roles in many areas of biology and medicine. Eicosanoids form a link between different fields of research into such areas as cancer, inflammation and radiation-induced injury.

This volume contains the proceedings of the First International Conference on Eicosanoids and Other Bioactive Lipids in Cancer and Radiation Injury held in Detroit, Michigan on October 11-14, 1989. The program consisted of 83 oral and 29 poster presentations, 74 of which are included in these proceedings. The major sponsors of the conference were the Armed Forces Radiobiology Research Institute, located in Bethesda, Maryland, the Radiation Oncology Research and Development Center of the Gershenson Radiation Oncology Center, Harper Hospital in Detroit, Michigan, and Schering AG of West Germany. Eighteen other organizations provided additional support. The conference was unique in its attempt to link the eicosanoid and lipid researchers in the radiobiology and cancer disciplines. The diverse roles that eicosanoids and other bioactive lipids play in these biological phenomena including the participation of lipid oxidation in conversion of procarcinogens, positive and negative modulation of tumor growth, immunomodulation, tissue injury, and yet protection and enhancement of cancer therapy, necessitated scientific interaction to sort out and understand these complex and sometimes contradictory observations. The success of this effort is reflected not only through these proceedings, but also through the decision to continue the conference series with a second meeting to be held in Berlin between September 17-21, 1991.

This book contains conference presentations regarding the regulation of eicosanoid enzymes and, in particular, cyclooxygenases, lipoxygenases, and phospholipases. The new field of isoprostanes is also represented.

Over one hundred contributions detail advances in the molecular and cellular biology of eicosanoid production, as well as their role in signal transduction. One of the most exciting developments explored within this collection of articles is the expression of the novel isoform of cyclooxygenase (cox-2), which may play a large role in the development of anti-inflammatory drugs.