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Emerging Target (emerging + target)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Emerging targets and novel strategies in the treatment of AIDS-related Kaposi's sarcoma: Bidirectional translational science

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 3 2006
Bruce J. Dezube
Through the mentorship process, Dr. Arthur Pardee emphasized the critical importance of bidirectional translational research,not only advancing drug development from bench to bedside, but also bringing back precious clinical material to the laboratory to assess the biologic effects of therapeutic agents on their targets. This mini-review focuses on the signal transduction pathways of Kaposi's sarcoma (KS) and on how the knowledge of such pathways has led to the rational development of molecularly targeted pathogenesis-driven therapies. Acquired immune deficiency syndrome (AIDS) related-KS results from co-infection with human immunodeficiency virus and KS herpesvirus/human herpesvirus-8 (KSHV/HHV8), which leads to the development of an angiogenic-inflammatory state that is critical in the pathogenesis of KS. KS is driven by KSHV/HHV8-specific pathways, which include viral G protein-coupled receptor (vGPCR), viral interleukin-6 (vIL-6), and viral chemokine homologues. In addition, cellular growth/angiogenic pathways, such as vascular endothelial growth factor (VEGF), insulin-like growth factor, platelet-derived growth factor (PDGF), angiopoietin and matrix metalloproteinases (MMPs) are "pirated" by KSHV/HHV8. As a very tangible example of how translational research has led to a marked improvement in patient outcome, the signal transduction inhibitor imatinib (a tyrosine kinase inhibitor of c-kit and PDGF) was administered to patients with KS whose tumors were serially biopsied. Not only did the patients' tumors regress, but also the regression was correlated with the inhibition of PDGF receptor (PDGFR) in the biopsy samples. Recent and future clinical trials of molecularly targeted therapy for the treatment of KS are a prelude to a shift in the paradigm of how KS is managed. J. Cell. Physiol. 209: 659,662, 2006. © 2006 Wiley-Liss, Inc. [source]

Peroxisome proliferator-activated receptor-, as emerging target in liver disease

DRUG DEVELOPMENT RESEARCH, Issue 2 2010
Bernd Schnabl
Abstract Liver fibrosis is characterized by an excessive deposition of extracellular matrix (ECM) proteins that occurs in chronic liver disease of any origin, including nonalcoholic steatohepatitis (NASH), alcohol abuse, and viral hepatitis. Cirrhosis occurs with the development of regenerating nodules of hepatocytes and is a major health burden worldwide. Patients with decompensated liver cirrhosis have a poor prognosis, with liver transplantation often being necessary. The current treatment paradigm for patients with hepatic fibrosis is to treat the underlying liver disease. However, if this cannot be achieved, there are currently no effective antifibrotic treatments for patients with chronic liver diseases. With the advent of basic molecular technology providing insight into the mechanisms of the development of hepatic fibrosis, there is now an opportunity to develop therapeutic interventions for human clinical use. In this review, the function of peroxisome proliferator-activated receptor-, (PPAR ,) will be summarized with a special emphasis on ligand activation as potential use in liver disease. Drug Dev Res 2009. © 2009 Wiley-Liss, Inc. [source]

MRI of atherosclerosis in clinical trials

NMR IN BIOMEDICINE, Issue 6 2006
Chun Yuan
Abstract Magnetic resonance imaging (MRI) of the arterial wall has emerged as a viable technology for characterizing atherosclerotic lesions in vivo, especially within carotid arteries and other large vessels. This capability has facilitated the use of carotid MRI in clinical trials to evaluate therapeutic effects on atherosclerotic lesions themselves. MRI is specifically able to characterize three important aspects of the lesion: size, composition and biological activity. Lesion size, expressed as a total wall volume, may be more sensitive than maximal vessel narrowing (stenosis) as a measure of therapeutic effects, as it reflects changes along the entire length of the lesion and accounts for vessel remodeling. Lesion composition (e.g. lipid, fibrous and calcified content) may reflect therapeutic effects that do not alter lesion size or stenosis, but cause a transition from a vulnerable plaque composition to a more stable one. Biological activity, most notably inflammation, is an emerging target for imaging that is thought to destabilize plaque and which may be a systemic marker of vulnerability. The ability of MRI to characterize each of these features in carotid atherosclerotic lesions gives it the potential, under certain circumstances, to replace traditional trials involving large numbers of subjects and hard end-points , heart attacks and strokes , with smaller, shorter trials involving imaging end-points. In this review, the state of the art in MRI of atherosclerosis is presented in terms of hardware, image acquisition protocols and post-processing. Also, the results of validation studies for measuring lesion size, composition and inflammation will be summarized. Finally, the status of several clinical trials involving MRI of atherosclerosis will be reviewed. Copyright © 2006 John Wiley & Sons, Ltd. [source]

Report on the Second Asia Autoimmunity Forum, Hong Kong, 3,5 March 2006

INTERNATIONAL JOURNAL OF RHEUMATIC DISEASES, Issue 3 2006
S. KAVIKONDALA
Abstract The Second Asia Autoimmunity Forum was jointly organized by the Hong Kong Society of Rheumatology, the University of Hong Kong, and the Singapore National Arthritis Foundation, and was attended by over 200 delegates from around Asia. More than 20 invited international and regional experts in the field of autoimmune rheumatic diseases from China, Greece, Hong Kong, Israel, Italy, the Netherlands, Singapore, and South Korea attended the meeting. A total of eight plenary lectures and four clinical symposia covered topics ranging from the role of dendritic cells and various genes in the pathogenesis of systemic lupus erythematosus, the changes in disease manifestations during pregnancy in lupus, advances on genetic studies in ankylosing spondylitis (AS), the role of dendritic cells and cytokines in the pathogenesis of rheumatoid arthritis (RA) to the novel emerging targets for treatment of RA, systemic sclerosis (SSc) and primary Sjogren's syndrome (pSS). It was an excellent avenue promoting the co-ordination and exchange of knowledge in the area of autoimmune rheumatic diseases in Asia. [source]