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260 records returned

Advances in Allergen-Specific Immunotherapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
After several decades of controversies, allergen specific immunotherapy (SIT) was recognized as an effective treatment for respiratory and hymenoptera allergy by the World Health Organization in 1998. SIT involves the administration (usually subcutaneous) of increasing doses of allergen in order to achieve a hyposensitization. Moreover, SIT is the only allergen-specific treatment capable of modifying the natural history of the disease. During the last 25 years, there was an impressive development of basic and clinical research in the field of SIT, with the goal of improving the safety, the efficacy and ameliorating the...
Source: Current Drug Targets - November 19, 2009 Category: Drugs & Pharmacology Authors: Passalacqua G, Compalati E, Canonica GW Tags: Curr Drug Targets Source Type: journals

Targeting Matrix Metalloproteinases in Inflammatory Conditions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The matrix metalloproteinases (MMPs) and their endogenous regulators, the tissue inhibitors of MMPs (TIMPs) are responsible for the physiological remodelling of the extracellular matrix (ECM) in healthy connective tissues. MMPs are also involved in the regulation of cell behaviour via the release of growth factors and cytokines from the substrates they cleave, increasing the magnitude of their effects. Excess MMP activity is associated with ECM destruction in various inflammatory conditions, such as osteoarthritis (OA), while MMP under-activity potentially impairs healing by promoting fibrosis and preventing the effect...
Source: Current Drug Targets - November 19, 2009 Category: Drugs & Pharmacology Authors: Clutterbuck AL, Asplin KE, Harris P, Allaway D, Mobasheri A Tags: Curr Drug Targets Source Type: journals

Molecular Targets in Malignant Pleural Mesothelioma Treatment.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Malignant mesothelioma is an aggressive tumour of the serosal surfaces with poor prognosis and increasing incidence due to widespread previous asbestos exposure. Relative chemotherapeutic and radiotherapeutic resistance makes malignant pleural mesothelioma (MPM) difficult to manage, even though encouraging results were achieved with multimodality treatment. Better knowledge of angiogenesis and molecular pathways involved in MPM seems to be the right way to define new targets for systemic treatment. Neoangiogenesis may be considered as a critical step in the development of mesothelioma. Vascular endothelial growth facto...
Source: Current Drug Targets - November 19, 2009 Category: Drugs & Pharmacology Authors: Pasello G, Favaretto A Tags: Curr Drug Targets Source Type: journals

Targeting Toll-like Receptors in Autoimmunity.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the past few years there has been an increasing appreciation of the importance of Toll-like receptors (TLRs), not just in immunity, but also in autoimmune diseases. TLRs were first identified as sensors of viral and bacterial pathogens that form an integral part of the innate immune response. It was later discovered that these receptors can also respond to endogenous ligands that are produced as a result of tissue damage. This lead to the hypothesis that TLRs may be key contributors to the pathogenesis of chronic inflammatory conditions. A large body of data supporting the role of TLRs in autoimmunity has emerged fr...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Midwood KS, Piccinini AM, Sacre S Tags: Curr Drug Targets Source Type: journals

The Bioartificial Kidney in the Treatment of Acute Kidney Injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute kidney injury (AKI) continues to have an exceedingly high mortality rate, despite advances in dialysis technology. Current dialysis therapies replace only the filtration function of the kidney, not the critical transport, metabolic, and endocrine functions of renal tubule cells. Replacement of these additional functions would provide more complete AKI therapy and thereby change the natural history of this disease process. A renal tubule assist device (RAD) containing living renal proximal tubule cells has been successfully engineered and has demonstrated differentiated absorptive, metabolic, and endocrine functio...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Song JH, Humes HD Tags: Curr Drug Targets Source Type: journals

Novel Therapeutic Targets for Prevention and Therapy of Sepsis Associated Acute Kidney Injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Sepsis associated Acute Kidney Injury (SA-AKI) is the leading cause of AKI in the hospital setting and its incidence is increasing. Although the exact pathophysiology and phenotype of SA-AKI are not known, it is widely accepted that SA-AKI has a multi-injury pathway. This form of AKI has components of ischemia-reperfusion injury, direct inflammatory injury, coagulation and endothelial cell dysfunction, and apoptosis. As such, multiple agents have been shown in pre-clinical studies to ameliorate SA-AKI, but there are no interventions currently available for the treatment of SA-AKI. Promising agents that are in developme...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Pelte CH, Chawla LS Tags: Curr Drug Targets Source Type: journals

Activated Protein C and Acute Kidney Injury: Selective Targeting of PAR-1.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Protein C is a plasma serine protease that when activated plays a central role in modulating the function of the vascular endothelium and its interface with the innate immune system. Activated protein C (APC) has a dual mechanism of action via the feedback inhibition of thrombin generation, and as an agonist of protease activated receptor-1 (PAR-1). Through different cofactor interactions, this dual mechanism of antithrombotic and cytoprotective activity results in the ability of APC to modulate endothelial dysfunction by blocking cytokine signaling, functional cell adhesion expression, vascular permeability, apoptosis...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Gupta A, Williams MD, Macias WL, Molitoris BA, Grinnell BW Tags: Curr Drug Targets Source Type: journals

Immune Mechanisms and Novel Pharmacological Therapies of Acute Kidney Injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and both innate and adaptive immunity contribute to the pathogenesis. Kidney resident cells promote inflammation after IRI by increasing endothelial cell adhesion molecule expression and vascular permeability. Kidney epithelial cells bind complement and express toll-like receptors and resident and infiltrating cells produce cytokines/chemokines. Early activation of kidney dendritic cells (DCs) initiates a cascade of events leading to accumulation of interferon-gamma-producing neutrophils, infiltrating macrophages, CD4(+) T cells, B cells an...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Bajwa A, Kinsey GR, Okusa MD Tags: Curr Drug Targets Source Type: journals

Clinical Trials for Acute Kidney Injury: Design Challenges and Possible Solutions.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute kidney injury is associated with significant morbidity and mortality in hospitalized patients. Clinical trials for acute kidney injury have been hampered not only by a paucity of appropriate potential therapeutic agents, but also by several clinical trial design challenges. First, for novel therapies to have the best chance at efficacy, early patient identification is critical. Second, for certain novel therapies with a mechanism of action directed at the underlying disease state (e.g., sepsis) or a specific pathogenic process, careful disease phenotyping may be required. Third, even among patients with AKI, risk...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Liu KD, Glidden DV Tags: Curr Drug Targets Source Type: journals

Novel Imaging Techniques in Acute Kidney Injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Imaging of the kidneys can provide valuable information in the work up and management of acute kidney injury. Several different imaging modalities are used to gather information on anatomy of the kidney, to rule out obstruction, differentiate acute kidney injury (AKI) and chronic kidney disease and to obtain information on renal blood flow and GFR. Ultrasound is the most widely used imaging modality used in the initial work up of AKI. The utility of contrast enhanced computerized tomography and magnetic resonance imaging is limited because of toxicities associated with contrast agents used. In this review the basics of...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Kalantarinia K Tags: Curr Drug Targets Source Type: journals

Pathogenesis of Acute Kidney Injury during Sepsis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Septic acute kidney injury (AKI) occurs between 15% and 20% of all intensive care unit admissions and its mortality ranges from 20% to 60%. The incidence and mortality of septic AKI has remained high throughout the last 10 years, whereas our understanding of septic AKI pathogenesis has remained limited. Current evidence about the pathophysiology of septic AKI will be reviewed and areas that require further investigation will be discussed. Improvement of knowledge about this condition seems to be most important in order to find valid diagnostic exams to exactly identify septic AKI and effective therapies to treat it: bo...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Ricci Z, Ronco C Tags: Curr Drug Targets Source Type: journals

Epidemiology of Septic Acute Kidney Injury.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The incidence of sepsis and acute kidney injury (AKI) are increasing in critically ill patients and both portend a higher risk of morbidity and death. Sepsis has consistently been shown to be a key contributing factor for the development of AKI. Numerous observational studies have found septic AKI to be highly common among the critically ill. Septic AKI patients are characterized by important differences in baseline demographics, acuity of illness and treatment intensity when compared with non-septic AKI. In particular, these patients are often older, have a higher prevalence of co-morbid illnesses, and are admitted fo...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Parmar A, Langenberg C, Wan L, May CN, Bellomo R, Bagshaw SM Tags: Curr Drug Targets Source Type: journals

Acute Kidney Injury: Turning the Tide.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Acute kidney injury (AKI) associated with sepsis remains an all too common occurrence with an associated high mortality rate. However, recent developments bring hope that this scenario may be changing. This change is being brought about by a multi-pronged approach that highlights several different but inter-related aspects of AKI. These include: (1) defining a standard definition for AKI; (2) understanding the importance of early recognition of AKI; (3) improving imaging techniques for the diagnosis of AKI; (4) improved understanding of the complex pathogenesis of AKI, especially in sepsis; (5) the development of targe...
Source: Current Drug Targets - September 2, 2009 Category: Drugs & Pharmacology Authors: Rosner MH Tags: Curr Drug Targets Source Type: journals

The 5-HT(1B) Receptor: A Novel Target for the Pathophysiology of Depression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The serotonergic (5-HT) system has been widely implicated in the pathophysiology of Major Depressive Disorder (MDD). Although the 5-HT system is a popular target for drug therapy in MDD the role that serotonin plays in MDD is not clearly understood. An abundance of research suggests that several 5-HT receptor subtypes may be dysfunctional in patients with MDD including the 5-HT(1B) receptor. Evidence implicating 5-HT(1B) receptors in the pathophysiology of depression comes from a number of converging lines of research. Two common genetic polymorphisms of 5-HT(1B) receptors, G861C and C129T, have been implicated in affe...
Source: Current Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Ruf BM, Bhagwagar Z Tags: Curr Drug Targets Source Type: journals

Therapeutic Potential of 5-HT(7) Receptors in Mood Disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Serotonin (5-HT) exerts its diverse physiological and pharmacological effects through the activation of multiple receptor subtypes. One of the newest members of this family is the 5-HT(7) receptor. Increasing investigations on this receptor are currently undertaken to highlight its physiological and physiopathological significance. With the development of selective 5-HT(7) receptor ligands, preclinical studies have started to elucidate the functions of this receptor subtype in more details. Hence, growing body of evidence suggests that the 5-HT(7) receptor is involved in biological processes such as circadian rhythm an...
Source: Current Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Mnie-Filali O, Lambas-Señas L, Scarna H, Haddjeri N Tags: Curr Drug Targets Source Type: journals

The beta-Endorphin Role in Stress-Related Psychiatric Disorders.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Long known for its anti-nociceptive effects, the opioid beta-endorphin is also reported to have rewarding and reinforcing properties and to be involved in stress response. In this manuscript we summarize the present neurobiological and behavioral evidence regarding the role of beta-endorphin in stress-related psychiatric disorders, depression and PTSD. There is existing data that support the importance of beta-endorphin neurotransmission in mediating depression. As for PTSD, however, the data is thus far circumstantial. The studies described herein used diverse techniques, such as biochemical measurements of beta-endor...
Source: Current Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Merenlender-Wagner A, Dikshtein Y, Yadid G Tags: Curr Drug Targets Source Type: journals

Serotonin Receptors, Type 4: A New Hope?Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Serotonin(4) (5-HT(4)) receptors have been shown to be involved in several peripheral and central functions, including control of the gastro-intestinal tract, modulation of memory and food intake, as well as positive regulation of the release of various neurotransmitters. Recently, we have proposed that the study of these receptors may also bring a new hope for treating depression, their agonists possibly acting as fast-acting antidepressants. This hypothesis was based on several studies showing that 5-HT(4) receptors play an important role in the modulation of central 5-HT neurotransmission, both at pre- and postsynap...
Source: Current Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Lucas G Tags: Curr Drug Targets Source Type: journals

Prospect of a Dopamine Contribution in the Next Generation of Antidepressant Drugs: The Triple Reuptake Inhibitors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Biogenic amine transporters for serotonin and norepinephrine (5-HT and NE respectively), are major targets for currently available antidepressant drugs, particularly those inhibiting the reuptake of 5-HT and/or NE. Compelling evidence suggest that dopamine (DA) is also involved in the pathophysiology and treatment of depression, leading to the development of a new class of antidepressants: the triple reuptake inhibitors that simultaneously inhibit 5-HT, NE and DA reuptake thereby prolonging their duration of action at postsynaptic levels. Although preclinical studies strongly suggest that triple reuptake inhibitors dis...
Source: Current Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Guiard BP, El Mansari M, Blier P Tags: Curr Drug Targets Source Type: journals

Brain Norepinephrine System as a Target for Antidepressant and Mood Stabilizing Medications.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
There are numerous lines of evidence pointing to norepinephrine being of crucial importance in pathophysiology of anxiety and mood disorders. First, norepinephrine projections innervate the limbic system, suggesting the involvement of norepinephrine in the regulation of emotions and cognition. Second, norepinephrine closely interacts with serotonin and dopamine systems, which also play very important roles in the regulation of mood. Third, it has been shown that various agents which increase norepinephrine availability, such as norepinephrine reuptake inhibitors, are also effective antidepressant drugs. And fourth, the...
Source: Current Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Dremencov E, El Mansari M, Blier P Tags: Curr Drug Targets Source Type: journals

The Role of Sodium Channels in the Mechanism of Action of Antidepressants and Mood Stabilizers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Antidepressant drugs modify in different ways the activity of neurons, by increasing monoamines levels and by modulating ion channels. Sodium channels are molecular targets for antiepileptic drugs, which can also be mood stabilizers (i.e. lamotrigine, topiramate, phenytoin, carbamazepine, valproic acid). After a short overview on the sodium channels and the interaction with antidepressants and mood stabilizers, a comparison of the activity of both antidepressants and mood stabilizers with the addition of veratrine (sodium channel opener) on the forced swimming test (FST) in mice was presented. By comparing the antidepr...
Source: Current Drug Targets - August 27, 2009 Category: Drugs & Pharmacology Authors: Bourin M, Chenu F, Hascoët M Tags: Curr Drug Targets Source Type: journals

Reducing Perioperative Myocardial Infarction with Anesthetic Drugs and Techniques.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
CONCLUSIONS: Volatile agents and levosimendan consistently reduce perioperative myocardial infarction and mortality in cardiac surgery but they have not been properly studied in non-cardiac surgery. Minor (epidural analgesia, statins, calcium antagonists and alfa agonists) or doubtful (beta-blockers) results were found in non-cardiac surgery. PMID: 19538174 [PubMed - as supplied by publisher] (Source: Current Drug Targets)
Source: Current Drug Targets - June 27, 2009 Category: Drugs & Pharmacology Authors: Landoni G, Zambon M, Zangrillo A Tags: Curr Drug Targets Source Type: journals

Proteasome Inhibitors in Cancer Therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The ubiquitin-proteasome pathway is involved in intracellular protein turnover and plays an essential function in many cellular processes, thus contributing to cellular homeostasis. The observation that proteasome inhibitors are able to induce apoptosis preferentially in tumor cells opened the way to their use as potential drugs. One of these drugs, bortezomib, was introduced in cancer therapy and its use was approved for the treatment of multiple myeloma and mantle cell lymphoma. The investigation of the mechanisms through which bortezomib causes cell death of cancer cells showed that this drug affects many cellular p...
Source: Current Drug Targets - June 27, 2009 Category: Drugs & Pharmacology Authors: Testa U Tags: Curr Drug Targets Source Type: journals

Structure, expression, and regulation of UDP-GlcNAc: dolichol phosphate GlcNAc-1-phosphate transferase (DPAGT1).Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Glycosylation of proteins on asparagine amino acids (N-linked) in proteins of eukaryotic cells is initiated by the biosynthesis of dolichol-pyrophosphate-N-acetylglucosamine from dolichol-phosphate and UDP-N-acetylglucosamine. The enzyme catalyzing this reaction, UDP-GlcNAc:Dolichol Phosphate GlcNAc-1-Phosphate Transferase (DPAGT1), has been further characterized in several cell types with respect to its gene, gene products, membrane topology, functional sites, lipid dependence, and metabolic regulation. This review summarizes these properties as an update from an earlier detailed and critical review by Lehrman (Lehrma...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Bretthauer RK Tags: Curr Drug Targets Source Type: journals

Comparative sequence analysis in the sialyltransferase protein family: analysis of motifs.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The sialyltransferase family represents a group of enzymes that transfers sialic acid from its common nucleotide sugar donor, CMP-NeuAc, to the terminal carbohydrates group of various glycoproteins and glycolipids. Cloning of these enzymes from mammalian sources indicated these are all type II membrane proteins with topological features common to other glycosyltransferases. To date, 20 cloned enzymes with distinct substrate specificity have been obtained for mammalian sialyltransferases. These account for four subfamilies according to the carbohydrate linkages synthesized, namely, ST3Gal, ST6Gal, ST6GalNAc, and ST8Sia....
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Datta AK Tags: Curr Drug Targets Source Type: journals

Insulin therapy for improving cardiac surgical outcomes.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
In the current era, more complex cardiac surgical procedures are being performed on elderly patients with variety of co-morbid conditions, which increases the demand to further improve the outcome of cardiac surgery. The role of insulin therapy in improving cardiac surgical outcomes has long been studied. However, the more recent evidence suggests that the entire potential of the insulin therapy has not yet been fully disclosed. The aim of this paper is to review different aspects of insulin therapy including different protocols used, timing of therapy and the objective glycemic target levels with its effect on improvi...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Albacker T, Lachapelle K Tags: Curr Drug Targets Source Type: journals

Liver fibrosis and therapeutic strategies: the goal for improving metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PURPOSE OF REVIEW: This review summarizes the current state of knowledge on non-alcoholic fatty liver disease (NAFLD) and the hepatitis C virus (HCV)-associated liver fibrosis, and provides insight into the role of dysmetabolism in hepatic fibrogenesis. Clinical relevance of drugs correcting these metabolic disturbances in the reversion of liver fibrosis will also be discussed. RECENT FINDINGS: Liver fibrosis affects more than ten millions of people worldwide and may lead to cirrhosis, liver failure, and death. Recent epidemiological data indicate that the incidence of liver fibrosis is expected to triple during the ne...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Balsano C, Alisi A, Nobili V Tags: Curr Drug Targets Source Type: journals

Toll-like receptors: link between "danger" ligands and plaque instability.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Myocardial infarction and stroke are exaggerated by rupture of atherosclerotic lesions. Rupture-sensitive plaques have a specific composition which renders them vulnerable, but additional factors (acute infection, higher sympathetic activity, excessive increase of blood pressure or exposure to a variety of drugs) are needed to set off the event. Toll-like receptors are important components of the innate and adaptive immune system and seem to be a potential link between inflammation, infectious disease and atherosclerosis. In addition to classical bacterial and viral antigens, several endogenous ligands (HSP, ox-LDL, ap...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Balogh S, Kiss I, Csaszar A Tags: Curr Drug Targets Source Type: journals

Deciphering dual antiplatelet therapy in the era of drug-eluting coronary stents.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article reviews the current data on coronary stents, in-stent restenosis and stent thrombosis and role of antiplatelet medication post percutaneous coronary intervention (PCI) to provide a concise and clear algorithm for managing perioperative antiplatelet therapy in patients having undergone recent PCI. The algorithm encourages a multidisciplinary approach and is based on the surgical bleeding risk, operative risk of adverse cardiac events and stent thrombosis risk to guide safe practice. Challenging areas including aspirin and clopidogrel hypersensitivity, clopidogrel resistance and concomitant vitamin K antagonist ...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Bell B, Walters D, Spaulding C Tags: Curr Drug Targets Source Type: journals

Nilotinib therapy in chronic myelogenous leukemia: the strength of high selectivity on BCR/ABL.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Imatinib mesylate is currently the standard therapy for chronic myeloid leukemia (CML) patients. Despite the remarkable results achieved with imatinib, the emergence of resistance to this drug has become a significant problem. Several strategies have been developed to overcome imatinib resistance, including dose escalation of the drug, combination treatments or novel targeted agents. Nilotinib is a second-generation tyrosine kinase inhibitor 30-50 fold more potent than imatinib with high affinity and selectivity on BCR/ABL, active against a wide range of mutant clones, except T315I mutation. Phase II trials of nilotini...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Breccia M, Alimena G Tags: Curr Drug Targets Source Type: journals

HER2 targeted therapies for cancer and the gastrointestinal tract.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
HER2 (v-erb-b2 erythroblastic leukemia viral oncogene) is a member of the epidermal growth factor (EGF) receptor family of receptor tyrosine kinases. Since the discovery of a role for HER2 and other EGF receptors in the development and progression of cancer, they have become targets for a number of targeted anti-cancer drugs. These drugs have proven to be effective in treating and managing a range of cancers, however, recent observations in the clinic have suggested that their administration causes many toxicities, including gastrointestinal toxicity. Drugs with HER2 inhibitory activity fall into two categories; the mo...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Al-Dasooqi N, Gibson R, Bowen J, Keefe D Tags: Curr Drug Targets Source Type: journals

The role of proteomics in osteoarthritis pathogenesis research.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Osteoarthritis (OA) is the most common rheumatic pathology. It is related to aging, and is characterized mainly by cartilage degradation. Despite its high prevalence, currently available therapy is limited and focused on treating pain, which is the principal symptom of OA. Therefore, new treatments for OA that slow the progression of the disease are urgently needed. Because the progression of OA involves different tissues and complex biological processes, ongoing research is attempting to increase our knowledge of OA pathogenesis. New approaches for the characterization of molecules that play a role in OA have recently...
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Ruiz-Romero C, Blanco FJ Tags: Curr Drug Targets Source Type: journals

Immunosuppression in liver transplantation.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
This article will review currently used immunosuppressants in liver transplantation, novel therapies in development and the impact of these medications of the recurrence of hepatitis C after liver transplantation. PMID: 19519358 [PubMed - in process] (Source: Current Drug Targets)
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Mukherjee S, Botha JF, Mukherjee U Tags: Curr Drug Targets Source Type: journals

Novel tyrosine kinase inhibitors in the treatment of cancer.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19519359 [PubMed - in process] (Source: Current Drug Targets)
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Ocana A, Serrano R, Calero R, Pandiella A Tags: Curr Drug Targets Source Type: journals

Terlipressin continuous infusion: please mind the solvent!Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19526638 [PubMed - in process] (Source: Current Drug Targets)
Source: Current Drug Targets - May 31, 2009 Category: Drugs & Pharmacology Authors: Rodriguez-Nunez A, Martínez V, Lopez-Herce J Tags: Curr Drug Targets Source Type: journals

ING family of tumor suppressors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19442110 [PubMed - in process] (Source: Current Drug Targets)
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Kutateladze TG Tags: Curr Drug Targets Source Type: journals

Signaling pathways of the ING proteins in apoptosis.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Members of the ING family of type II tumor suppressors reside in different chromatin regulatory complexes and are stoichiometeric members of histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes. It has been frequently observed that expressing ING proteins promotes apoptosis in both normal and transformed cells of different species. They have also been reported to either rely upon p53, or to add to its ability to promote programmed cell death (apoptosis) although whether ING proteins require p53 to induce apoptosis is now questionable based upon observations using knockout cell lines and animal model...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Shah S, Riabowol K Tags: Curr Drug Targets Source Type: journals

Modulators of inhibitor of growth (ING) family expression in development and disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The inhibitor of growth (ING) gene family proteins regulate many critical cellular processes such as cell proliferation and growth, apoptosis, DNA repair, senescence, angiogenesis, and drug resistance. Their transcripts and proteins are differentially expressed in health and disease and there is evidence for developmental regulation. The vast majority of studies have characterized ING levels in the context of cancer. However, relatively little attention has been paid to the expression of ING family members in other contexts. This review summarizes the findings from human and animal model systems that provide insight in...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Maher SK, Helbing CC Tags: Curr Drug Targets Source Type: journals

ING proteins in cellular senescence.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Cellular senescence is an effective anti-tumor barrier that acts by restraining the uncontrolled proliferation of cells carrying potentially oncogenic alterations. ING proteins are putative tumor suppressor proteins functionally linked to the p53 pathway and to chromatin regulation. ING proteins exert their tumor-protective action through different types of responses. Here, we review the evidence on the participation of ING proteins, mainly ING1 and ING2, in the implementation of the senescent response. The currently available data support an important role of ING proteins as regulators of senescence, in connection wit...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Menéndez C, Abad M, Gómez-Cabello D, Moreno A, Palmero I Tags: Curr Drug Targets Source Type: journals

The return of the INGs, histone mark sensors and phospholipid signaling effectors.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Since their discovery, the members of the ING (inhibitor of growth) family of tumor suppressors have emerged as essential and core components of chromatin modifying complexes. Recent work has identified the ING family as histone mark sensors that orchestrate cellular responses to genotoxic insults and regulate chromatin homeostasis. Dysregulation of chromatin homeostasis is implicated in tumorigenesis through mechanisms such as silencing of tumor suppressor genes, inappropriate activation of oncogenes, and genomic instability due to failure to repair DNA damage. This review will concentrate on the chromatin signaling a...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Bua DJ, Binda O Tags: Curr Drug Targets Source Type: journals

Structural insight into histone recognition by the ING PHD fingers.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Inhibitor of Growth (ING) tumor suppressors are implicated in oncogenesis, control of DNA damage repair, cellular senescence and apoptosis. All members of the ING family contain unique amino-terminal regions and a carboxy-terminal plant homeodomain (PHD) finger. While the amino-terminal domains associate with a number of protein effectors including distinct components of histone deacetylase (HDAC) and histone acetyltransferase (HAT) complexes, the PHD finger binds strongly and specifically to histone H3 trimethylated at lysine 4 (H3K4me3). In this review we describe the molecular mechanism of H3K4me3 recognition by...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Champagne KS, Kutateladze TG Tags: Curr Drug Targets Source Type: journals

ING proteins as potential anticancer drug targets.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Recent emerging evidence suggests that ING family proteins play roles in carcinogenesis both as oncogenes and tumor suppressor genes depending on the family members and on cell status. Previous results from non-physiologic overexpression experiments showed that all five family members induce apoptosis or cell cycle arrest, thus it had been thought until very recently that all of the family members function as tumor suppressor genes. Therefore restoration of ING family proteins in cancer cells has been proposed as a treatment for cancers. However, ING2 knockdown experiments showed unexpected results: ING2 knockdown led ...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Unoki M, Kumamoto K, Harris CC Tags: Curr Drug Targets Source Type: journals

The role of ING tumor suppressors in UV stress response and melanoma progression.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The INhibitor of Growth (ING) genes were discovered during the past decade and identified as type II tumor suppressor genes. Previous studies demonstrated that ING family members participate in various cellular stress responses and thus play important roles in the pathogenesis of various types of cancers, including melanoma. Epidemiological studies showed that UV radiation is the primary etiological factor in melanoma development. Here we review the studies on the role of ING proteins in cellular responses to UV irradiation, melanoma cell motility, and melanoma progression. PMID: 19442117 [PubMed - in process] (Sou...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Li J, Wang Y, Wong RP, Li G Tags: Curr Drug Targets Source Type: journals

Potential usage of ING family members in cancer diagnostics and molecular therapy.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The Inhibitor of Growth (ING) gene family is an emerging putative type II tumor suppressor gene (TSG). Proteins of INGs (ING1-5), critical modulator of the histone code via PHD fingers, are able to suppress cell growth and proliferation, induce apoptosis, and modulate cell cycle progression. ING proteins are involved in transcriptional regulation of genes, such as the p53-inducible gene p21. ING proteins also serve as shuttling proteins between nucleus and cytoplasm, and dysregulation of this nucleocytoplasmic traffic has been shown in some cancer cells. In cancer cells, ING mRNA levels are often lost or suppressed but...
Source: Current Drug Targets - April 30, 2009 Category: Drugs & Pharmacology Authors: Gunduz M, Demircan K, Gunduz E, Katase N, Tamamura R, Nagatsuka H Tags: Curr Drug Targets Source Type: journals

One century of triglycerides, but there is still lots to learn!Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
PMID: 19355854 [PubMed - in process] (Source: Current Drug Targets)
Source: Current Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Anagnostopoulou K, Kolovou G, Mikhailidis DP Tags: Curr Drug Targets Source Type: journals

Triacylglycerol metabolism.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Apart from being the main energy reserves of the human body, triacylglycerols take part in metabolic processes that determine the rate of fatty acid oxidation, the plasma levels of free fatty acids, the biosynthesis of other lipid molecules and the metabolic fate of lipoproteins. Allosteric, hormonal, nutritional and transcriptional signals activate short-term and long-term regulatory mechanisms that assure the storage of triacylglycerols (TAGs) under states of excess energy and their mobilization under conditions of metabolic stress. New enzymes and novel regulatory mechanisms, involved in triacylglycerol metabolism, ...
Source: Current Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Karantonis HC, Nomikos T, Demopoulos CA Tags: Curr Drug Targets Source Type: journals

Triglycerides and vascular risk: insights from epidemiological data and interventional studies.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
The role of elevated triglyceride (TG) levels in the pathogenesis of atherosclerosis is controversial. Some studies suggest that TG might play a direct role in the development of vascular disease. Elevated TG levels are also associated with other vascular risk factors and may therefore represent an indirect marker of a high risk state. Another issue is that laboratory measurements of TG levels frequently show a substantial variability. Accumulating epidemiological data show that there is an independent association of TG levels with vascular risk. Some interventional studies also suggested that lowering TG levels might ...
Source: Current Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Tziomalos K, Athyros VG, Karagiannis A, Kolovou GD, Mikhailidis DP Tags: Curr Drug Targets Source Type: journals

Nonfasting hyperlipidemia and cardiovascular disease.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Most humans are in the nonfasting or postprandial state in the majority of a 24 hour cycle; however, lipids, lipoproteins, and apolipoproteins are usually measured in the fasting state. Recent studies demonstrate that these values at most change minimally in response to normal food intake, changes that are clinically unimportant. Also, elevated levels of nonfasting triglycerides as a marker of elevated remnant lipoprotein cholesterol associate strongly with increased risk of myocardial infarction, ischemic stroke, and early death. The mechanism behind these findings likely involves entrance of remnant lipoproteins into...
Source: Current Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Nordestgaard BG, Langsted A, Freiberg JJ Tags: Curr Drug Targets Source Type: journals

Primary and secondary hypertriglyceridaemia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Familial hypertriglyceridaemia is inherited in an autosomal dominant manner. The responsible genetic abnormality is unknown but recently, a novel gene encoding apolipoprotein AV has been linked to familial hypertriglyceridaemia. All patients develop the same phenotype with elevated levels of very low density lipoproteins (VLDL) in plasma. The main disorder of this dyslipidaemia is decreased intestinal absorption of biliary acids, leading to a compensatory increase of VLDL production. In familial hypertriglyceridaemia, a marked increase in plasma triglyceride (TG) levels can cause acute pancreatitis. Moreover, patients ...
Source: Current Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Kolovou GD, Anagnostopoulou KK, Kostakou PM, Bilianou H, Mikhailidis DP Tags: Curr Drug Targets Source Type: journals

Influence of lifestyle measures on hypertriglyceridaemia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypertriglyceridaemia is a common dyslipidaemia encountered in clinical practice. People with hypertriglyceridaemia are frequently obese, insulin-resistant, hypertensive or diabetic, all of which are risk factors for cardiovascular diseases. Hypertriglyceridaemia also contributes to metabolic syndrome, in which an atherogenic diet, sedentary lifestyle, overweight/obesity and genetic factors interact. A multi-factorial intervention for all risk factors is necessary, including weight reduction, dietary modification and increased physical exercise. This review focuses on the influence of diet, sedentary lifestyle and nega...
Source: Current Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Manfredini F, D'Addato S, Laghi L, Malagoni AM, Mandini S, Boari B, Borghi C, Manfredini R Tags: Curr Drug Targets Source Type: journals

Potential options to treat hypertriglyceridaemia.Email this article to a colleague. Save this article to My Clippings. Discuss or comment on this article.
Hypertriglyceridaemia is associated with insulin resistance, hypertension, obesity and diabetes. The management of hypertriglyceridaemia and atherogenic dyslipidaemias increasingly involves the use of several drugs for different aspects of the metabolic syndrome. This review highlights the agents for treatment of blood pressure, weight and blood pressure that reduce triglycerides as a number of drugs used to treat these co-morbidities also lower triglycerides as additional effects beyond their primary actions. Lipid-lowering drugs particularly fibrates and niacin and to a lesser degree statins and omega-3 fatty acids r...
Source: Current Drug Targets - March 31, 2009 Category: Drugs & Pharmacology Authors: Viljoen A, Wierzbicki AS Tags: Curr Drug Targets Source Type: journals