MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Current Drug Targets' source. Wed, 08 Feb 2012 14:04:08 +0100 http://www.medworm.com/index.php?rid=5662834&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300022%26dopt%3DAbstract In conclusion, α7-nAChR in roughly 100 years of life, instead to be an old actor it became an important player in regulating cell signalling. PMID: 22300022 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662834 Thu, 02 Feb 2012 05:00:00 +0100 5662834 http://www.medworm.com/index.php?rid=5662833&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300025%26dopt%3DAbstract Authors: Brust P, Peters D, Deuther-Conrad W, Barbarroja N Abstract Molecular imaging of brain structures by highly sensitive non-invasive techniques offers unique possibilities in the understanding of physiological and pathological processes in the central nervous system. In particular, the quantitative analysis by positron emission tomography (PET) of a7 nicotinic acetylcholine receptors (a7 nAChR), which are involved in different signalling pathways in the brain, is assumed to provide important information on the relation between receptor dysfunction and the pathogeneses of neuropsychiatric brain diseases, but the applicability of this imaging approach is still hampered due to insufficient imaging agents. This paper presents the recent efforts made to develop PET radiotracers ta... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662833 Thu, 02 Feb 2012 05:00:00 +0100 5662833 http://www.medworm.com/index.php?rid=5662832&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300029%26dopt%3DAbstract Authors: Neri M, Bonassi S, Russo P Abstract The presence of memory impairment and cognitive deficits in the Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and Pick's disease (PiD) has been associated to dysfunction of cholinergic transmission, possibly due to the loss of cholinergic neurons and to the elimination of nAChR in dementia patients. Alternative hypotheses take into account molecular interactions of the β-amyloid peptide Aβ with nAChR, which may lead to deregulation of the receptor function. Genetic polymorphisms of CHRNA7 and CHRFAM7A, a fusion gene containing a partial CHRNA7 duplication, have been investigated as possible susceptibility traits to dementia, potentially useful either to identify high risk individuals or as therapeutic targets. To summarize... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662832 Thu, 02 Feb 2012 05:00:00 +0100 5662832 http://www.medworm.com/index.php?rid=5662831&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300030%26dopt%3DAbstract Authors: Kawamata J, Suzuki S, Shimohama S Abstract Parkinson's disease (PD) is characterized by relatively selective degeneration of dopaminergic neurons in the substantia nigra and loss of dopamine in the striatum. More than 50 epidemiological studies confirmed the low incidence of PD in smokers. Examining the distribution of subtypes of nicotinic acetylcholine receptors (nAChRs) in dopaminergic neurons of nigrostriatal system and its change in PD patients is quite important to elucidate possible neuroprotective cascade triggered by nicotine. Evidences of nAChR-mediated protection against neurotoxicity induced by rotenone, 6-hydroxydopamine (6-OHDA), and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are briefly reviewed. In rotenone- and 6-OHDA-induced PD models, nAChR-medi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662831 Thu, 02 Feb 2012 05:00:00 +0100 5662831 http://www.medworm.com/index.php?rid=5662830&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300031%26dopt%3DAbstract Authors: Kelso ML, Oestreich JH Abstract Traumatic brain injury (TBI) is a significant public health concern worldwide for which there is no cure. Once trauma has occurred, multiple biochemical pathways are set into motion that leads to a chronic, neurodegenerative condition. Two of the most widely studied pathological pathways are excitotoxicity and inflammatory, processes that are influenced by α7 nicotinic acetylcholine receptors (nAChR). Previous studies have found a bilateral decrease in α7 nAChR expression in regions of the cortex and hippocampus occurring in relation to injury severity. Subsequent studies showed that this decrease was evident in some parts of the hippocampus as early as 1 hour post-injury and remained decreased through 21 days. Other ligand-gated ion chann... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662830 Thu, 02 Feb 2012 05:00:00 +0100 5662830 http://www.medworm.com/index.php?rid=5662829&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300032%26dopt%3DAbstract Authors: Lin W, Hirata N, Sekino Y, Kanda Y Abstract The α7-nicotinic acetylcholine receptor (α7-nAChR) is widely known as a neurotransmitter receptor in nervous systems. α7-nAChR is also present in a variety of non-neuronal tissues, where it has been implicated in the regulation of essential cellular functions including proliferation, survival, differentiation and communication. We have recently found in breast cancer that α7-nAChR is involved in the proliferation of cancer stem cells, which constitute a minor subpopulation responsible for tumor development and metastasis. Since growing evidence suggests that α7-nAChR is present not only in mature tissues and organs but also in undifferentiated stem cells and progenitor cells, α7-nAChR emerges as a key mediator in the regula... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662829 Thu, 02 Feb 2012 05:00:00 +0100 5662829 http://www.medworm.com/index.php?rid=5662828&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300035%26dopt%3DAbstract Authors: Schuller HM Abstract Exposure to tobacco products is responsible for the majority of all human cancers. Nicotinic acetylcholine receptors (nAChRs) were identified as early as 1989 as important regulators of cancer cells. In analogy to its function in the brain, the homomeric a7nAChR has "accelerator function" on the most common human cancers by stimulating the synthesis and release of excitatory neurotransmitters (serotonin in small cell lung cancer, noradrenaline/adrenaline in most other cancers) that drive cell proliferation, migration, angiogenesis, neurogenesis and metastasis while inhibiting apoptosis. These effects are not only caused by a7nAChRs expressed in cancer cells but also by a7nAChRs in ganglia and nerves of the sympathetic part of the autonomic nervous syst... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662828 Thu, 02 Feb 2012 05:00:00 +0100 5662828 http://www.medworm.com/index.php?rid=5662827&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300039%26dopt%3DAbstract Authors: Filippini P, Cesario A, Fini M, Locatelli F, Rutella S Abstract The alkaloid nicotine, a major addictive component of tobacco, exerts anti-inflammatory and immune-modulating activities on multiple cell types, such as T cells, B cells, dendritic cells, mononuclear phagocytes and polymorphonuclear leukocytes, in lung, spleen, liver, kidney and gastrointestinal tract. In addition, nicotine may blunt pro-inflammatory cytokine release, with prominent effects on T helper type 1 (Th1) and Th17 cytokines. The non-neuronal α7-nicotinic cholinergic receptors are a primary target for nicotine through the JAK2 and STAT3/NF-κB pathways, ultimately mediating the inhibition of pro-inflammatory gene transcription. The present paper reviews the growing evidence in favor of detrimental as... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662827 Thu, 02 Feb 2012 05:00:00 +0100 5662827 http://www.medworm.com/index.php?rid=5662826&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300040%26dopt%3DAbstract A new "era" for ∝7- nAChR. Curr Drug Targets. 2012 Feb 2; Authors: Russo P, Cardinale A, Shuller H Abstract The role played by a7-nAChR is critical in nature, but it strictly dependent on the organism and/or cellular type and cellular function. In this special issue different Authors have been contributed to clarify the different roles played by a7-nAChR. Post-translational process such as receptor "underactivation" or "overactivation" are associated in the central nervous system with brain disorders including neurodegeneration, as well as in non-neuronal cells in cancer. Current advances in the knowledge of a7-nAChR biology encourage the exploitation of a7-nAChR as a target for different diseases (i.e. Alzheimer's and Parkinson's disease, cognitive decline, pain and canc... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5662826 Thu, 02 Feb 2012 05:00:00 +0100 5662826 http://www.medworm.com/index.php?rid=5643820&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280342%26dopt%3DAbstract Authors: Yang QY PMID: 22280342 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5643820 Thu, 19 Jan 2012 05:00:00 +0100 5643820 http://www.medworm.com/index.php?rid=5643819&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280343%26dopt%3DAbstract Authors: Arakane Y, Taira T, Ohnuma T, Fukamizo T Abstract Plants utilized for agricultural productions interact with insects, fungi, and bacteria under the field conditions, affecting thereby their productivity. Since chitin and its derivatives play important roles in the interactions between these organisms, chitin-related enzymes are effective tools or drug targets for controlling the interactions. Thus, the molecular biology, protein chemistry, and enzymology of the chitin-related enzymes have been intensively studied by many investigators. Identifications and classifications of the genes encoding chitin synthetases, chitinases, chitosanases, and chitin deacetylases in these organisms were conducted, and their physiological functions were defined by knockdown, knockout, or over... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5643819 Thu, 19 Jan 2012 05:00:00 +0100 5643819 http://www.medworm.com/index.php?rid=5643818&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280344%26dopt%3DAbstract Authors: Pang YP, Brimijoin S, Ragsdale DW, Zhu KY, Suranyi R Abstract Insect pests are responsible for human suffering and financial losses worldwide. New and environmentally safe insecticides are urgently needed to cope with these serious problems. Resistance to current insecticides has resulted in a resurgence of insect pests, and growing concerns about insecticide toxicity to humans discourage the use of insecticides for pest control. The small market for insecticides has hampered insecticide development; however, advances in genomics and structural genomics offer new opportunities to develop insecticides that are less dependent on the insecticide market. This review summarizes the literature data that support the hypothesis that an insect-specific cysteine residue located at t... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5643818 Thu, 19 Jan 2012 05:00:00 +0100 5643818 http://www.medworm.com/index.php?rid=5643817&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280345%26dopt%3DAbstract Authors: Weinreb OR, Amit TJ, Bar-Am OK, Youdim MB Abstract Ladostigil [(N-propargyl-(3R) aminoindan-5yl)-ethyl methyl carbamate] is a dual acetylcholine-butyrylcholine-esterase and brain selective monoamine oxidase (MAO)-A and -B inhibitor in vivo (with little or no MAO inhibitory effect in the liver and small intestine), intended for the treatment of dementia co-morbid with extrapyramidal disorders and depression (presently in a Phase IIb study). This suggests that the drug should not cause significant potentiation of the cardiovascular response to tyramine, thereby making it a potentially safer antidepressant than other irreversible MAO-A inhibitors. Ladostigil was shown to antagonize scopolamine-induced impairment in spatial memory, indicating that it can cause significant incr... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5643817 Thu, 19 Jan 2012 05:00:00 +0100 5643817 http://www.medworm.com/index.php?rid=5643816&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280346%26dopt%3DAbstract Authors: Lang GJ, Zhu KY, Zhang CX Abstract Acetylcholinesterase (AChE; EC 3.1.1.7) is a primary target of many insecticides including organophosphates (OP) and carbamates (CB). Because AChE is expressed in all invertebrate and vertebrate animals as a key enzyme of the cholinergic system, the toxicity of anticholinesterase insecticides to mammals and non-target species such as beneficial insects has been a great concern. In addition, the intensive use of OP and CB insecticides has resulted in the development of resistance in many insect pests, which has limited the use of anticholinesterase insecticides. Many aces encoding AChEs have been sequenced from a variety of vertebrates, insects and other invertebrates, and crystal structures of four AChEs have been determined in the past 2... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5643816 Thu, 19 Jan 2012 05:00:00 +0100 5643816 http://www.medworm.com/index.php?rid=5643815&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280347%26dopt%3DAbstract Authors: Chu H, Wang J, Shen H, Yang Y, Zhu W, Li G Abstract Chitinases belong to family 18 glycosyl hydrolases that can hydrolyze chitin by cleaving β-1,4-glycosidic bond, and are at key points in the life cycles of organism. The inhibitors of chitinases not only have chemotherapeutic potential against fungi, insects, but also hold anti-inflammatory efficacy against asthma and allergic disease in human. This review summarizes the structural characters of chitinases, the proposed catalytic mechanism, furthermore, also gives descriptions of currently existing inhibitors. In addition, computational studies of the interaction modes of chitinases with different inhibitors and substrates, as well as the inhibitor design of chitinases, are summarized so as to obtain an overall understan... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5643815 Thu, 19 Jan 2012 05:00:00 +0100 5643815 http://www.medworm.com/index.php?rid=5643814&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280348%26dopt%3DAbstract Authors: Liu T, Yan J, Yang Q Abstract Glycosyl hydrolase family 3, 20 and 84 β-N-acetyl-D-hexosaminidases are widely distributed enzymes that function in energy metabolism, cell proliferation, signal transduction as well as in pathogen-related inflammation and autoimmune diseases. Sharing the same retaining catalytic mechanism, they are distinguished from each other in terms of structure rather than substrate-enzyme transition state. Selective inhibition of each of these enzymes that exploits the structural differences would appear promising in the regulation and investigation of their corresponding life functions within the organism. Thanks to molecular structural biology, detailed structures of GH3, 20 and 84 β-N-acetyl-D-hexosaminidases have become available at the atomic lev... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5643814 Thu, 19 Jan 2012 05:00:00 +0100 5643814 http://www.medworm.com/index.php?rid=5606212&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250649%26dopt%3DAbstract Authors: Yap FY, Kantharidis P, Coughlan MT, Slattery R, Forbes JM Abstract The globally rising incidence of Type 1 diabetes (T1D) is no longer restricted to individuals with higher risk genotypes, but is now significantly increasing in a population with lower risk genotypes, likely as the result of environmental factors. In this review, we discuss the potential of advanced glycation end products (AGEs) as environmental contributors to the development of T1D. AGEs are nonenzymatically formed protein modifications found in the body, as well as, consumed in our daily diets. To date, many studies have provided evidence of AGE involvement in β cell dysfunction, whether by AGE modification itself or via interaction with AGE receptors. The receptor for AGE (RAGE) and AGE-receptor-1 (AGE... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5606212 Tue, 17 Jan 2012 05:00:00 +0100 5606212 http://www.medworm.com/index.php?rid=5606211&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250650%26dopt%3DAbstract This article reviews current data on the role played by ADA in the regulation of immune system activity through its modulation of adenosine pathways. Particular attention has been paid to the involvement of ADA in the pathophysiology of relevant inflammatory diseases. In addition, the interest in designing and developing novel ADA inhibitors, as new tools potentially useful for the therapeutic management of inflammatory disorders, has been discussed. PMID: 22250650 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5606211 Tue, 17 Jan 2012 05:00:00 +0100 5606211 http://www.medworm.com/index.php?rid=5606210&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250651%26dopt%3DAbstract Authors: Liu J, Li S, Dunker AK, Uversky VN Abstract Breast cancer is the most common non-cutaneous cancer diagnosed in women in the United States and the second most common cause of cancer-related mortality. Over the past two decades, the progress in screening and adjuvant systemic therapies noticeably improved the survival rate. However, traditional methods of characterizing tumors are imprecise and create heterogeneous groupings of tumors and patients. As a result, despite the important medical advances in diagnosis and treatment of breast cancer, one-third of the patients with initial breast tumor have recurrence of the disease 10 years after the diagnosis. Therefore, novel tools for discovery of strong prognostic and predictive markers that can be used to identify patients at ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5606210 Tue, 17 Jan 2012 05:00:00 +0100 5606210 http://www.medworm.com/index.php?rid=5606209&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250652%26dopt%3DAbstract Authors: Lopez-Pedrera C, Ruiz-Limón P, Valverde-Estepa A, Barbarroja N, Rodriguez-Ariza A Abstract Statins have been successfully used in patients with hypercholesterolemia and cardiovascular diseases, but there is increasing evidence that they exert effects by much exceeding the lowering of cholesterol levels. Statins have antiatherosclerotic, antiinflammatory, antioxidant, immunomodulatory and antithrombotic effects. These "pleiotropic" effects stem from their inhibition of prenylation of the small GTP-binding proteins Ras and Rho, and to the disruption, or depletion, of cholesterol rich membrane micro-domains (membrane rafts). Through these pathways statins modulate immune responses by altering cytokine levels and by affecting the function of cells involved in both innate and ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5606209 Tue, 17 Jan 2012 05:00:00 +0100 5606209 http://www.medworm.com/index.php?rid=5606208&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250653%26dopt%3DAbstract Authors: Chen BY, Wang X, Chen LW, Luo ZJ Abstract The bone marrow-derived mesenchymal stem cells or mesenchymal stromal cells (MSCs), with pluripotent differentiation capacity, present an ideal source for cell transplantation or tissue engineering therapies, but exact understanding of regulating mechanism underling MSC proliferation and differentiation remains a critical issue in securing their safe and efficient clinical application. This review outlines current knowledge regarding MSC cell surface biomarkers and molecular mechanisms of MSC differentiation and proliferation with emphasis on Wnt/β-catenin signaling, Notch signaling pathway, bone morphogenesis proteins and various growth factors functioning in regulation of differentiation and proliferation of MSCs. Possible relat... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5606208 Tue, 17 Jan 2012 05:00:00 +0100 5606208 http://www.medworm.com/index.php?rid=5606207&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250654%26dopt%3DAbstract Authors: Baweja R, Sedky K, Lippmann S Abstract Antipsychotic medicines are the cornerstone pharmacotherapy for patients with psychotic disorders. Early and continuous management of psychoses improves the quality of life, decreases hospitalization and reduces medical costs. However, many psychotic patients are not fully compliant with treatment, and thus they more often experience a relapsing course with a suboptimal clinical outcome. Long-term parenteral antipsychotic agents may improve compliance by offering clear evidence of medication non-compliance and documented drug administration monitoring. Using injection therapy might be especially beneficial to poorly compliant individuals with their first-psychotic episode and those with severe psychopathology or comorbid substance abu... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5606207 Tue, 17 Jan 2012 05:00:00 +0100 5606207 http://www.medworm.com/index.php?rid=5606206&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22250655%26dopt%3DAbstract Authors: Agrawal R, Jain P, Dikshit SN Abstract Apixaban (BMS-562247-01) is a compound being investigated as an anticoagulant. Apixaban molecule is developed in a joint venture by Pfizer and Bristol-Myers Squibb. Apixaban, a coagulation factor Xa inhibitor, approved in the E.U. in 2011 for the prevention of venous thromboembolic events in adult patients, who have undergone elective hip or knee replacement. The Apixaban based drug will be marketed under the brand name Eliquis® and is expected to rack up annual sales of over $2.5 billion. Apixaban is expected to provide stiff competition to warfarin, a popular blood thinner used in Europe. Warfarin is known to cause some serious side effects in patients. Apixaban, as compared with aspirin, reduced the risk of stroke or systemic embo... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5606206 Tue, 17 Jan 2012 05:00:00 +0100 5606206 http://www.medworm.com/index.php?rid=5567141&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206248%26dopt%3DAbstract Authors: Conway EM PMID: 22206248 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567141 Thu, 29 Dec 2011 05:00:00 +0100 5567141 http://www.medworm.com/index.php?rid=5567140&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206249%26dopt%3DAbstract Authors: Valdez Y, Maia M, Conway EM Abstract CD248, also known as endosialin or tumor endothelial marker-1 (TEM-1), is a C-type lectin-like domain (CTLD) containing cell surface glycoprotein that is expressed by stromal cells of proliferating tissues during embryogenesis and postnatally in tumors and inflammatory lesions. Loss-of-function studies in mice support the notion that CD248 promotes tumor growth and inflammation, observations that are stimulating interest in evaluating this molecule as a therapeutic target. In spite of these advances, the mechanisms by which CD248 modulates cancer and inflammation remain largely enigmatic. This review highlights our current understanding of CD248, its structure, pattern of expression, regulation and function in various disease processes.... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567140 Thu, 29 Dec 2011 05:00:00 +0100 5567140 http://www.medworm.com/index.php?rid=5567139&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206250%26dopt%3DAbstract Authors: Morser J Abstract Thrombomodulin (TM) is a type 1 membrane bound glycoprotein that has a C-type lectin domain at its N-terminus, 6 copies of the epidermal growth factor-like (EGF) domain and serine/threonine rich domain carrying a glycosoaminoglycan external to the membrane. TM binds thrombin changing thrombin's substrate specificity from pro-coagulant and pro-inflammatory to anti-coagulant and anti-inflammatory because of the activation of protein C (PC) and thrombin-activatable fibrinolysis inhibitor (TAFI). Thrombin's anion binding site 1 binds to TM's EGF domains 5 and 6. EGF4 is required for PC activation and EGF3 and 4 for TAFI activation in addition to EGF56. The X-ray structure of thrombin bound to TM has been solved and shows few major alterations in the active si... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567139 Thu, 29 Dec 2011 05:00:00 +0100 5567139 http://www.medworm.com/index.php?rid=5567138&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206251%26dopt%3DAbstract Authors: Greenlee-Wacker MC, Galvan M, Bohlson SS Abstract While it has been known for some time that CD93 regulates several processes involved in innate immunity and inflammation including phagocytosis and adhesion, the function of CD93 in disease progression is only now being elucidated. Recent in vivo studies in mice, and genome wide studies in mice and humans, have provided clues about its molecular function. Following a comprehensive review of CD93 expression patterns, this review will focus on recent findings over the last three years that address the putative function of CD93 in inflammation and innate immunity. PMID: 22206251 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567138 Thu, 29 Dec 2011 05:00:00 +0100 5567138 http://www.medworm.com/index.php?rid=5567137&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206252%26dopt%3DAbstract Authors: Sun H PMID: 22206252 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567137 Thu, 29 Dec 2011 05:00:00 +0100 5567137 http://www.medworm.com/index.php?rid=5567136&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206253%26dopt%3DAbstract Authors: McArthur JD, Cook SM, Venturini C, Walker MJ Abstract Streptococcus pyogenes is a major human pathogen responsible for numerous diseases ranging from uncomplicated skin and throat infections to severe, life threatening invasive disease such as necrotising fasciitis and streptococcal toxic shock syndrome. These severe invasive infections progress rapidly and produce high rates of morbidity and mortality despite the implementation of aggressive treatment plans. The activation of plasminogen and the acquisition of plasmin activity at the bacterial cell surface is critical for the invasive pathogenesis of this organism. To facilitate this process, S. pyogenes secrete streptokinase, a potent plasminogen activating protein. Here, we describe the role of streptokinase in invasive... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567136 Thu, 29 Dec 2011 05:00:00 +0100 5567136 http://www.medworm.com/index.php?rid=5567135&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206254%26dopt%3DAbstract Authors: Thomas C, Lee SW Abstract Group A Streptococcus (GAS) is a leading human pathogen that causes a multitude of diseases from pharyngitis, and impetigo, to more severe outcomes such as rheumatoid arthritis and necrotizing fasciitis. GAS remains a global burden as currently no vaccine exists that is completely effective. In this review we highlight recent studies on the virulence of GAS and present several approaches that have extended those findings into aims at combating GAS disease. These and other studies such as recent genome-wide efforts into host-pathogen relationships of GAS disease will likely reveal new targets of intervention. Given the recent rise in GAS strains that have acquired resistance to several types of antibiotics, it is crucial that we continue to increas... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567135 Thu, 29 Dec 2011 05:00:00 +0100 5567135 http://www.medworm.com/index.php?rid=5567134&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206255%26dopt%3DAbstract Authors: Gámez G, Hammerschmidt S Abstract Streptococcus pneumoniae (pneumococcus) is an asymptomatic colonizer of the upper respiratory tract in humans. However, these apparently harmless bacteria have also a high virulence potential and are known as the etiologic agent of respiratory and life-threatening invasive diseases. Dissemination of pneumococci from the nasopharynx into the lungs or bloodstream leads to community-acquired pneumonia, septicaemia and meningitis. Traditionally, pneumococcal diseases are treated with antibiotics and prevented with polysaccharide-based vaccines. However, due to the dramatic increase in antibiotic resistance and limitations of the current available vaccines, the burden of diseases remains high. Thus, combating pneumococcal transmission and infe... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567134 Thu, 29 Dec 2011 05:00:00 +0100 5567134 http://www.medworm.com/index.php?rid=5567133&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206256%26dopt%3DAbstract Authors: Kline T, Felise HB, Sanowar S, Miller SI Abstract Type III Secretion Systems (T3SSs) are highly organized multi-protein nanomachines which translocate effector proteins from the bacterial cytosol directly into host cells. These systems are required for the pathogenesis of a wide array of Gram-negative bacterial pathogens, and thus have attracted attention as potential antibacterial drug targets. A decade of research has enabled the identification of natural products, conventional small molecule drug-like structures, and proteins that inhibit T3SSs. The mechanism(s) of action and molecular target(s) of the majority of these inhibitors remain to be determined. At the same time, structural biology methods are providing an increasingly detailed picture of the functional arrang... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567133 Thu, 29 Dec 2011 05:00:00 +0100 5567133 http://www.medworm.com/index.php?rid=5567132&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206257%26dopt%3DAbstract Authors: Robinson A, Causer RJ, Dixon NE Abstract New antibiotics with novel modes of action are required to combat the growing threat posed by multi-drug resistant bacteria. Over the last decade, genome sequencing and other high-throughput techniques have provided tremendous insight into the molecular processes underlying cellular functions in a wide range of bacterial species. We can now use these data to assess the degree of conservation of certain aspects of bacterial physiology, to help choose the best cellular targets for development of new broad-spectrum antibacterials. DNA replication is a conserved and essential process, and the large number of proteins that interact to replicate DNA in bacteria are distinct from those in eukaryotes and archaea; yet none of the antibiotics... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567132 Thu, 29 Dec 2011 05:00:00 +0100 5567132 http://www.medworm.com/index.php?rid=5567131&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206258%26dopt%3DAbstract This article will first review commonly used screening strategies used to identify potential new antibiotics and then discuss novel screening methods. In addition, new assays, methods, biological targets and compounds with novel modes of action in that are in pre-clinical or clinical development are briefly discussed. PMID: 22206258 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567131 Thu, 29 Dec 2011 05:00:00 +0100 5567131 http://www.medworm.com/index.php?rid=5567130&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22206259%26dopt%3DAbstract Authors: Lahiri S, Kazmirski S, Kern G, Sanyal G Abstract New antibacterial drugs are urgently needed to combat the growing problem of multidrug resistant bacterial infections. Major advances in bacterial genomics have uncovered many unexploited targets, leading to the possibility of discovering new antibacterials with novel mechanisms that would circumvent resistance. Many of these targets are soluble enzymes that vary in their degrees of mechanistic complexity. Protein crystallography as well as solution based biophysical methods are playing an increasingly important role in selecting, characterizing and validating promising targets as well as identifying and optimizing lead compounds that inhibit their functions. Advances made in recent years in sensitivity, resolution and throu... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5567130 Thu, 29 Dec 2011 05:00:00 +0100 5567130 http://www.medworm.com/index.php?rid=5552412&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204314%26dopt%3DAbstract Authors: Ying W PMID: 22204314 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552412 Thu, 29 Dec 2011 05:00:00 +0100 5552412 http://www.medworm.com/index.php?rid=5552410&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204315%26dopt%3DAbstract Authors: Liu C, Ge P, Sun L, Wu J, Sun KF, Hu B Abstract There are two major routes for clearance of aberrant cellular components: (i) the ubiquitin-proteasomal system (UPS); and (ii) the autophagy pathway. The UPS degrades individual abnormal proteins, whereas the autophagy pathway is the chief route for bulk degradation of large abnormal protein aggregates and aberrant organelles. Impairments of the protein degradation pathways are closely tied with many human diseases. For example, brain ischemia leads to protein misfolding and aggregation, resulting in overproduction of protein aggregate-associated organelles. Brain ischemia also damages protein degradation pathways. As a result, damaged organelles overproduced in postischemic neurons are unable to be eliminated. This chapter w... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552410 Thu, 29 Dec 2011 05:00:00 +0100 5552410 http://www.medworm.com/index.php?rid=5552409&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204316%26dopt%3DAbstract Authors: Wang Y, Huang J, Li Y, Yang GY Abstract Chemokine CXC ligand 12 (CXCL12), originally named stromal cell-derived factor-1 (SDF-1), is a member of the CXC chemokine subfamily. CXCL12 is found to be expressed by all cell types that are presented in the central nervous system (CNS). It works in conjunction with the G-protein coupled receptor CXCR4, which is found at the surface of a variety of cells including neurons, astrocytes, microglia, bone marrow-derived cells, as well as other progenitor cells. Recent studies revealed that CXCL12 could also bind and signal through receptor CXCR7. CXCL12 and CXCR4 are constitutively expressed in the brain but are up-regulated in the ischemic penumbra regions following ischemic stroke. CXCL12/CXCR4 play important roles in multiple process... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552409 Thu, 29 Dec 2011 05:00:00 +0100 5552409 http://www.medworm.com/index.php?rid=5552408&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204317%26dopt%3DAbstract Authors: Zhao H, Ren C, Chen X, Shen J Abstract Ischemic postconditioning is a concept originally defined to contrast with that of ischemic preconditioning. While both preconditioning and postconditioning confer a neuroprotective effect on brain ischemia, preconditioning is a sublethal insult performed in advance of brain ischemia, and postconditioning, which conventionally refers to a series of brief occlusions and reperfusions of the blood vessels, is conducted after ischemia/reperfusion. In this article, we first briefly review the history of preconditioning, including the experimentation that initially uncovered its neuroprotective effects and later revealed its underlying mechanisms-of-action. We then discuss how preconditioning research evolved into that of postconditioning -... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552408 Thu, 29 Dec 2011 05:00:00 +0100 5552408 http://www.medworm.com/index.php?rid=5552406&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204318%26dopt%3DAbstract Authors: Shao B, Cheng Y, Jin K Abstract Stroke is the third most common cause of death, particularly of the elderly. Despite considerable advances in knowledge about the mechanisms of cell death after stroke, a treatment for stroke remains exclusive. For a long time, estrogen was thought of only as a "sex hormone". Studies have documented that estrogen plays an important role in regulating behavioral and physiological events beyond the reproductive system. Most animal studies have shown that estrogens exert neuroprotective and neurogenesis effects in vivo and in vitro after ischemic stroke. However, clinical and epidemiological evidence shows that estrogen increases the risk of coronary heart disease, stroke, and breast cancer. The discrepancy between animal studies and clinical d... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552406 Thu, 29 Dec 2011 05:00:00 +0100 5552406 http://www.medworm.com/index.php?rid=5552404&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204319%26dopt%3DAbstract Authors: Cairns B, Kim JY, Tang XN, Yenari MA Abstract NADPH oxidase was originally identified in immune cells as playing an important microbicidal role. In neurodegenerative and cerebrovascular diseases, inflammation is increasingly being recognized as contributing negatively to neurological outcome, with NADPH-oxidase as an important source of superoxide. Recently, several forms of this oxidase have been found in a variety of non-immune cells. Neuronal NADPH oxidase is thought to participate in long-term potentiation and intercellular signaling. However, excessive superoxide production is damaging and has been shown to play an important role in the progression of brain injury. NADPH oxidase is a multisubunit complex composed of membrane-associated gp91phox and p22phox subunits an... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552404 Thu, 29 Dec 2011 05:00:00 +0100 5552404 http://www.medworm.com/index.php?rid=5552403&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204320%26dopt%3DAbstract Authors: Li ST, Ju JG Abstract The N-methyl-D-aspartate (NMDA) receptor is a major type of ionotropic glutamate receptor. Many studies have shown that NMDA receptors play a pivotal role in the central nervous system (CNS) under both physiological and pathological conditions. The functional diversity of NMDA receptors can be mainly attributed to their different subunit compositions that perform multiple functions in various situations. Furthermore, recent reports have indicated that synaptic and extrasynaptic NMDA receptors have distinct compositions and couple with different signaling pathways: while synaptic NMDA receptors tend to promote cell survival, extrasynaptic NMDA receptors promote cell death. Currently, intensive efforts are being made to study the pathological role of ex... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552403 Thu, 29 Dec 2011 05:00:00 +0100 5552403 http://www.medworm.com/index.php?rid=5552402&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204321%26dopt%3DAbstract Authors: Ma Y, Chen H, He X, Nie H, Sheng C, Wang Q, Xia W, Ying W Abstract Numerous studies have indicated that four interacting factors, including oxidative stress, mitochondrial alterations, calcium dyshomeostasis and inflammation, play crucial pathological roles in multiple major neurological diseases, including stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Increasing evidence has also indicated that NAD+ plays important roles in not only mitochondrial functions and energy metabolism, but also calcium homeostasis and inflammation. The key NAD+-consuming enzyme - poly(ADP-ribose) polymerase-1 (PARP-1) and sirtuins - have also been shown to play important roles in cell death and aging， which are two key factors in the pathology of multiple major age-dependent n... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552402 Thu, 29 Dec 2011 05:00:00 +0100 5552402 http://www.medworm.com/index.php?rid=5552401&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204322%26dopt%3DAbstract Authors: Feng Y, He X, Yang Y, Chao D, Lazarus LH, Xia Y Abstract The use of opioid analgesics has a long history in clinical settings, although the comprehensive action of opioid receptors is still less understood. Nonetheless, recent studies have generated fresh insights into opioid receptor-mediated functions and their underlying mechanisms. Three major opioid receptors (μ-opioid receptor, MOR; δ-opioid receptor, DOR; and κ-opioid receptor, KOR) have been cloned in many species. Each opioid receptor is functionally sub-classified into several pharmacological subtypes, although, specific gene corresponding each of these receptor subtypes are still widely unidentified as only a single gene has been isolated for each opioid receptor. In addition to pain modulation and addiction,... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552401 Thu, 29 Dec 2011 05:00:00 +0100 5552401 http://www.medworm.com/index.php?rid=5552400&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204323%26dopt%3DAbstract Authors: Dornbos D, Ding Y Abstract The effects of exercise pre-conditioning on lessening the impact of ischemia/reperfusion injury provide pivotal information and potential targets for future pharmacological intervention. Exercise induces increased expression of neurotrophic factors, the extracellular matrix (ECM) proteins, integrins, angiogenic factors, as well as tumor necrosis factor (TNF-α) and heat shock proteins (Hsp-70). These factors all directly enhance the neurovascular unit and alleviate the harmful effects following ischemia/reperfusion injury. Furthermore, pre-conditioning decreases expression of matrix metalloproteinase (MMP-9) and Toll-like receptor-4, which ameliorates the inflammatory response and apoptosis following ischemic insult. Perhaps most importantly, exe... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552400 Thu, 29 Dec 2011 05:00:00 +0100 5552400 http://www.medworm.com/index.php?rid=5552399&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204324%26dopt%3DAbstract Authors: Chu XP, Xiong ZG Abstract Protons are important signals for neuronal function. In the central nervous system (CNS), proton concentrations change locally when synaptic vesicles release their acidic contents into the synaptic cleft, and globally in ischemia, seizures, traumatic brain injury, and other neurological disorders due to lactic acid accumulation. The finding that protons gate a distinct family of ion channels, the acid-sensing ion channels (ASICs), has shed new light on the mechanism of acid signaling and acidosis-associated neuronal injury. Accumulating evidence has suggested that ASICs play important roles in physiological processes such as synaptic plasticity, learning/memory, fear conditioning, and retinal integrity, and in pathological conditions such as brain... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552399 Thu, 29 Dec 2011 05:00:00 +0100 5552399 http://www.medworm.com/index.php?rid=5552398&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22204325%26dopt%3DAbstract Authors: Molyneux R, Seymour AM, Bhandari S Abstract Cardiovascular complications are the leading cause of mortality, accounting for 50% of all deaths among patients with end-stage renal disease (ESRD). The majority of these deaths are from cardiac causes. The mechanisms underlying the enhanced susceptibility to myocardial ischaemia and subsequent morbidity in ESRD remain ill-defined. Numerous metabolic derangements accompany myocardial ischaemia and reperfusion and play a pivotal role in the development of concurrent myocardial dysfunction. Carnitine plays a critical role in myocardial energy metabolism, as the transporter of long chain fatty acyl intermediates across the inner mitochondrial membrane for β oxidation and as a central regulator of carbohydrate metabolism. Myocardia... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5552398 Thu, 29 Dec 2011 05:00:00 +0100 5552398 http://www.medworm.com/index.php?rid=5363079&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22023404%26dopt%3DAbstract Authors: Yamagishi SI Abstract Recent meta-analyses have revealed that the risk of bone fracture is increased in both type 1 and type 2 diabetic patients. Low bone mineral density (BMD) can not necessarily explain the link, because BMD is increased rather than decreased in type 2 diabetes, while it is consistently low in type 1 diabetes subjects. Although multiple factors could influence the quality of bone and increase the bone fragility in diabetes, there is accumulating evidence for the association between osteoporosis and vascular calcification, which is an independent predictor of cardiovascular disease morbidity and mortality. Advanced glycation end products (AGEs) are formed by a non-enzymatic reaction between aldehydes of reducing sugars and the amino groups of proteins, li... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363079 Fri, 21 Oct 2011 04:00:00 +0100 5363079 http://www.medworm.com/index.php?rid=5363078&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22023405%26dopt%3DAbstract Authors: Tao RR, Ji YL, Lu YM, Fukunaga K, Han F Abstract Nitric oxide/peroxynitrite signaling is associated with manifold neurovascular pathogenic cascades that lead to neurodegenerative diseases, including ischemic stroke, Alzheimer's disease, and vascular dementia. Considerable evidence suggests that reactive nitrogen species as mediators of nitrosative stress could damage biomolecules and subsequently facilitate the breakdown of the highly-structured cellular machinery. Herein, we focus on nitrosative stress signaling, which is intimately associated with endothelial cell injury and blood-brain barrier damage in stroke and neurodegenerative diseases. Unraveling the detrimental role of nitrosative stress signaling in initiating and driving neurovascular pathogenesis may lead to t... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363078 Fri, 21 Oct 2011 04:00:00 +0100 5363078 http://www.medworm.com/index.php?rid=5363077&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22023406%26dopt%3DAbstract Authors: Bonet ML, Granados N, Palou A Abstract Obesity and degenerative joint disease (osteoarthritis, OA) are two multifactorial pathologies that are becoming major medical issues with the aging of the world population. The relationship of OA with obesity is complex, involving both biomechanical and metabolic links. Dysregulated production of adipose tissue-derived inflammatory mediators, hyperlipidemia, and increased systemic oxidative stress are conditions frequently associated with obesity that may favor joint degeneration. In addition, it is remarkable that many regulatory factors have been implicated in the development, maintenance and function of both adipose tissues and cartilage and other articular joint tissues. Disturbances in these factors may underlie additional links... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363077 Tue, 18 Oct 2011 04:00:00 +0100 5363077 http://www.medworm.com/index.php?rid=5363076&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22023407%26dopt%3DAbstract Authors: Borroto-Escuela DO, Agnati LF, Fuxe K, Ciruela F Abstract Muscarinic acetylcholine receptors comprise a large family of G protein-coupled receptors that are involved in the regulation of many important functions of the central and peripheral nervous system. To achieve such a large range of physiological effects, these receptors interact, in addition to the canonical heterotrimeric G proteins, with a large array of accessory proteins including scaffold molecules, ion channels and enzymes which operate as molecular transducers of muscarinic function. Interestingly, as demonstrated for others G protein-coupled receptors this type of receptors are also able to oligomerize, a fact that has been shown to play a critical role in their subcellular distribution, trafficking, and fi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363076 Tue, 18 Oct 2011 04:00:00 +0100 5363076 http://www.medworm.com/index.php?rid=5363075&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22023408%26dopt%3DAbstract Authors: Luján R, Ciruela F Abstract γ-aminobutyric acid type B (GABAB) receptors play a critical role in neuronal excitability and modulation of synaptic neurotransmission in the central nervous system. They are G protein-coupled receptors that signal primarily through activation of G proteins (i.e. pertussis toxin sensitive Gαi/o family) to modulate the function of inwardly-rectifying K(+) and voltage-gated Ca(2+) channels, and to trigger cyclic adenosine monophosphate cascades. Functional GABAB receptors are obligated heterodimers formed by the co-assembly of two subunits, the GABAB1 and the GABAB2, which interact via coiled-coil domains in their C-terminal tails. It is now quite well established that GABAB receptors interact not only with heterotrimeric G proteins and effect... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5363075 Tue, 18 Oct 2011 04:00:00 +0100 5363075 http://www.medworm.com/index.php?rid=5108670&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777181%26dopt%3DAbstract Authors: Georgoussi Z, Georganta EM, Milligan G Opiate drugs mediate their analgesic, euphoriant, and rewarding effects by activating opioid receptors. Pharmacological and molecular studies have demonstrated the existence of three opioid receptor subtypes, μ, δ, and κ- that couple predominantly to Gi/Go types of G proteins to regulate the activity of a diverse array of effector systems. Ample experimental evidence has demonstrated that these receptors can physically interact with a variety of accessory proteins, confirming that signal transduction of the opioid receptors is not restricted to heterotrimeric G protein activation. Such interactions can alter the effectiveness of agonist-driven cell signalling, determine the signals generated and alter the trafficking, targeting, fine t... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108670 Wed, 20 Jul 2011 23:00:00 +0100 5108670 http://www.medworm.com/index.php?rid=5108668&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777182%26dopt%3DAbstract Authors: Couvineau A, Laburthe M G protein coupled receptors (GPCRs) play a crucial role in physiology and pathophysiology in humans. Beside the large family A (rhodopsin-like receptors) and family C GPCR (metabotropic glutamate receptors), the small family B1 GPCR (secretin-like receptors) includes important receptors such as vasoactive intestinal peptide receptors (VPAC), pituitary adenylyl cyclase activating peptide receptor (PAC1R), secretin receptor (SECR), growth hormone releasing factor receptor (GRFR), glucagon receptor (GCGR), glucagon like-peptide 1 and 2 receptors (GLPR), gastric inhibitory peptide receptor (GIPR), parathyroid hormone receptors (PTHR), calcitonin receptors (CTR) and corticotropin-releasing factor receptors (CRFR). They represent very promising targets for th... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108668 Wed, 20 Jul 2011 23:00:00 +0100 5108668 http://www.medworm.com/index.php?rid=5108666&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777183%26dopt%3DAbstract Authors: Yanamala N, Gardner E, Riciutti A, Klein-Seetharaman J The mammalian dim-light photoreceptor rhodopsin is a prototypic G protein coupled receptor (GPCR), interacting with the G protein, transducin, rhodopsin kinase, and arrestin. All of these proteins interact with rhodopsin at its cytoplasmic surface. Structural and modeling studies have provided in-depth descriptions of the respective interfaces. Overlap and thus competition for binding surfaces is a major regulatory mechanism for signal processing. Recently, it was found that the same surface is also targeted by small molecules. These ligands can directly interfere with the binding and activation of the proteins of the signal transduction cascade, but they can also allosterically modulate the retinal ligand binding pocket. ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108666 Wed, 20 Jul 2011 23:00:00 +0100 5108666 http://www.medworm.com/index.php?rid=5108664&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777184%26dopt%3DAbstract Authors: Cotecchia S, Stanasila L, Diviani D The adrenergic receptors are among the best characterized G protein-coupled receptors (GPCRs) and knowledge on this receptor family has provided several important paradigms about GPCR function and regulation. One of the most recent paradigms initially supported by studies on adrenergic receptors is that both βarrestins and G protein-coupled receptors themselves can act as scaffolds binding a variety of proteins and this can result in growing complexity of the receptor-mediated cellular effects. In this review we will briefly summarize the main features of βarrestin binding to the adrenergic receptor subtypes and we will review more in detail the main proteins found to selectively interact with distinct AR subtype. At the end, we will revie... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108664 Wed, 20 Jul 2011 23:00:00 +0100 5108664 http://www.medworm.com/index.php?rid=5108661&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777185%26dopt%3DAbstract This article first describes our current knowledge of the nature of GIPs that bind to the different metabotropic 5-HT receptor categories. It then focuses on their impact on receptor functional status at the cellular level and illustrates how GIPs permit G protein-independent signal transduction at G protein-coupled 5-HT receptors. Finally, it reports recent data dealing with the roles of GIPs in 5-HT-related behaviours and highlights the potential of manipulating 5-HT receptor-GIP interactions to design new treatments in psychiatric disorders related to perturbations of serotonergic systems. PMID: 21777185 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108661 Wed, 20 Jul 2011 23:00:00 +0100 5108661 http://www.medworm.com/index.php?rid=5108657&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777186%26dopt%3DAbstract Authors: Mahon MJ The parathyroid hormone 1 receptor (PTH1R) is activated by parathyroid hormone (PTH) and parathyroid hormone related protein (PTHrP), hormones that mediate mineral ion homeostasis and tissue development, respectively. These diverse actions mediated by one receptor are likely due to the formation of cell-specific receptorsome complexes with cytosolic constituents. Through the second and third intracellular loops, the PTH1R couples to several G protein sub-classes, including G(s), G(q/11), G(i/o) and G(12/13), resulting in the activation of many pathways. The PTH1R carboxy-terminal tail directs interactions with a plethora of binding partners. The WD1 and WD7 repeats of the G protein β subunit directly bind to a novel interaction domain located near the amino-terminal ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108657 Wed, 20 Jul 2011 23:00:00 +0100 5108657 http://www.medworm.com/index.php?rid=5108653&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777187%26dopt%3DAbstract Authors: Kabbani N, Woll MP, Nordman JC, Levenson R D2 dopamine receptors (D2Rs) represent an important class of receptors in the pharmacological development of novel therapeutic drugs for the treatment of schizophrenia. Recent research into D2R signaling suggests that receptor properties are dependent on interaction with a cohort of dopamine receptor interacting proteins (DRIPs) within a macromolecular structure termed the signalplex. One component of this signalplex is neuronal calcium sensor 1 (NCS-1) a protein found to regulate the phosphorylation, trafficking, and signaling profile of the D2R in neurons. It has also been found that NCS-1 can contribute to the pathology of schizophrenia and may play a role in the efficacy of antipsychotic drug medication in the brain. In this revie... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108653 Wed, 20 Jul 2011 23:00:00 +0100 5108653 http://www.medworm.com/index.php?rid=5108649&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777188%26dopt%3DAbstract Authors: Enz R The correct targeting, localization, regulation and signaling of metabotropic glutamate receptors (mGluRs) represent major mechanisms underlying the complex function of neuronal networks. These tasks are accomplished by the formation of synaptic signal complexes that integrate functionally related proteins such as neurotransmitter receptors, enzymes and scaffold proteins. By these means, proteins interacting with mGluRs are important regulators of glutamatergic neurotransmission. Most described mGluR interaction partners bind to the intracellular C-termini of the receptors. These domains are extensively spliced and phosphorylated, resulting in a high variability of binding surfaces offered to interacting proteins. Malfunction of mGluRs and associated proteins are linked ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108649 Wed, 20 Jul 2011 23:00:00 +0100 5108649 http://www.medworm.com/index.php?rid=5108644&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777189%26dopt%3DAbstract Authors: Ciruela F PMID: 21777189 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108644 Wed, 20 Jul 2011 23:00:00 +0100 5108644 http://www.medworm.com/index.php?rid=5108625&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777190%26dopt%3DAbstract Authors: Spear MA, Lorusso P, Mita A, Mita M Vascular Disrupting Agents (VDA) are a potential new class of oncology drugs that have garnered attention recently as a number of these agents have entered into Phase 2-3 studies. Currently available data suggest how the subsequent evolution of these agents into clinical practice may proceed, with new therapeutic paradigms based on similarities, differences and interactions with current standard of care agents. In particular, the broadly successful group of agents targeting angiogenesis through the Vascular Endothelial Growth Factor (VEGF) pathway, can be contrasted to the VDAs that principally disrupt established tumor vasculature through a different set of molecular targets. Although the angiogenesis inhibitors may benchmark where other va... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108625 Wed, 20 Jul 2011 23:00:00 +0100 5108625 http://www.medworm.com/index.php?rid=5108614&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777191%26dopt%3DAbstract Authors: Mahalingam D, Oldenhuis CN, Szegezdi E, Giles FJ, de Vries EG, de Jong S, Nawrocki ST Tumor necrosis factor-related apoptosis-inducing ligand or Apo2 ligand (TRAIL/Apo2L) is a member of the tumor necrosis factor (TNF) superfamily that induces apoptosis upon binding to its death domain-containing transmembrane receptors. The preferential toxicity of TRAIL to cancer cells and the sparing of normal cells make it an ideal cancer therapeutic agent. TRAIL induces apoptosis via the extrinsic death receptor apoptotic pathway and activates the JNK, ERK, Akt and NF-кB signaling cascades. However, not all cancer cells are sensitive to TRAIL therapy. This may limit its efficacy in the clinic, although ways have already been identified to overcome resistance by combining TRAIL with chemot... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108614 Wed, 20 Jul 2011 23:00:00 +0100 5108614 http://www.medworm.com/index.php?rid=5108601&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777192%26dopt%3DAbstract Authors: Rowinsky EK, Schwartz JD, Zojwalla N, Youssoufian H, Fox F, Pultar P, Ludwig DL Insulin-like growth factor type-1 receptor (IGF-1R) plays a central role in cell proliferation and survival and is overexpressed in many tumor types. Notably, IGF-1R-mediated signaling confers resistance to diverse cytotoxic, hormonal, and biologic agents, suggesting that therapies targeting IGF-1R may be effective against a broad range of human malignancies. Cixutumumab (IMC-A12; ImClone Systems) is a fully human immunoglobulin G1 (IgG1) monoclonal antibody that specifically inhibits IGF-1R signaling. Binding of cixutumumab to IGF-1R results in receptor internalization and degradation. Because cixutumumab is an IgG1 monoclonal antibody, it may induce additional cytotoxicity via immune effector mec... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108601 Wed, 20 Jul 2011 23:00:00 +0100 5108601 http://www.medworm.com/index.php?rid=5108591&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777193%26dopt%3DAbstract Authors: Swords R, Kelly K, Carew J, Nawrocki S, Mahalingam D, Sarantopoulos J, Bearss D, Giles F The three Pim kinases are a small family of serine/threonine kinases regulating several signaling pathways that are fundamental to cancer development and progression. They were first recognized as pro-viral integration sites for the Moloney Murine Leukemia virus. Unlike other kinases, they possess a hinge region which creates a unique binding pocket for ATP. Absence of a regulatory domain means that these proteins are constitutively active once transcribed. Pim kinases are critical downstream effectors of the ABL (ableson), JAK2 (janus kinase 2), and Flt-3 (FMS related tyrosine kinase 1) oncogenes and are required by them to drive tumorigenesis. Recent investigations have established that ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108591 Wed, 20 Jul 2011 23:00:00 +0100 5108591 http://www.medworm.com/index.php?rid=5108579&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777194%26dopt%3DAbstract Authors: Sandhu SK, Yap TA, de Bono JS Poly(ADP-ribose) polymerase (PARP) is a critical DNA repair enzyme involved in DNA single-strand break repair via the base excision repair pathway. PARP inhibitors have been shown to sensitize tumors to DNA-damaging agents and to also selectively kill homologous recombination repair-defective cancers, such as those arising in BRCA1 and BRCA2 mutation carriers. Recent proof-of-concept clinical studies have demonstrated the safety and substantial antitumor activity of the PARP inhibitor, olaparib in BRCA1/2 mutation carriers, highlighting the wide therapeutic window that can be achieved with this synthetic lethal strategy. Likewise, the PARP inhibitor, BSI-201, in combination with carboplatin and gemcitabine have produced promising results in "tripl... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108579 Wed, 20 Jul 2011 23:00:00 +0100 5108579 http://www.medworm.com/index.php?rid=5108553&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777195%26dopt%3DAbstract Authors: Yap TA, Sandhu SK, Alam SM, de Bono JS The hepatocyte growth factor/mesenchymal-epithelial transition factor (HGF/c-MET) receptor tyrosine kinase (RTK) pathway plays a pleotropic role in cell proliferation, migration, invasion, angiogenesis and survival. Although it has critical physiological functions in embryonic development and tissue repair, this signaling cascade is frequently deregulated in a wide range of tumors. Aberrant HGF/c-MET signaling, driven by various mechanisms, including constitutive activation and over-expression, has multifunctional effects in oncogenesis and is implicated in the acquisition of an aggressive phenotype with metastatic potential. The central role of c-MET activity in cancer progression, as well as disparities between quiescent HGF/c-MET signa... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108553 Wed, 20 Jul 2011 23:00:00 +0100 5108553 http://www.medworm.com/index.php?rid=5108544&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777196%26dopt%3DAbstract Authors: Sankhala KK, Mita MM, Mita AC, Takimoto CH Heat shock proteins (Hsp) are highly conserved proteins and their expression is dependent on the level of various cellular stresses. Hsp work as a molecular chaperon for several cellular proteins and have cytoprotective roles. Their function is essential for normal cell viability and growth. Hsp90 interacts with proteins mediating cell signaling involved in essential processes such as proliferation, cell cycle control, angiogenesis and apoptosis. The naturally occurring Hsp90 inhibitor geldanamycin (GA) was the first to demonstrate anticancer activity but its significant toxicity profile in pre-clinical models precluded its clinical development. Subsequently, several Hsp90 inhibitors have been developed and underwent clinical developm... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108544 Wed, 20 Jul 2011 23:00:00 +0100 5108544 http://www.medworm.com/index.php?rid=5108531&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777197%26dopt%3DAbstract Authors: Weiss GJ, Mita AC, Von Hoff DD Contrary to the Classical Greek poet Archilochus' phrase "The fox knows many things but the hedgehog knows one big thing", the Hedgehog (HH) signaling pathway knows at least 3 ways to promote or support carcinogenesis. In this review, we provide a summary of the HH signaling pathway, and detail the clinical relevance and treatment of patients. Finally, future directions in exploiting this promising pathway will be addressed. PMID: 21777197 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108531 Wed, 20 Jul 2011 23:00:00 +0100 5108531 http://www.medworm.com/index.php?rid=5108528&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777198%26dopt%3DAbstract Authors: Kelly KR, Ecsedy J, Mahalingam D, Nawrocki ST, Padmanabhan S, Giles FJ, Carew JS The Aurora family of serine/threonine kinases is essential for chromosome alignment, segregation, centrosomal maturation, mitotic spindle formation, and cytokinesis during mitosis. Their fundamental role in cell cycle regulation and aberrant expression in a broad range of malignancies prompted the development of small molecules that selectively inhibit their activity. Recent studies have revealed new insights into the cellular effects of Aurora kinase inhibition. Moreover, early phase clinical studies have shown that these agents have therapeutic efficacy. In this review, we will outline the functions of Aurora kinases in normal cell division and in malignancy. We will focus on recent preclinical ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108528 Wed, 20 Jul 2011 23:00:00 +0100 5108528 http://www.medworm.com/index.php?rid=5108515&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21777199%26dopt%3DAbstract Authors: Giles FJ PMID: 21777199 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108515 Wed, 20 Jul 2011 23:00:00 +0100 5108515 http://www.medworm.com/index.php?rid=5108673&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21756223%26dopt%3DAbstract Authors: Prabhu P, Patravale V Malaria has emerged as one of the most debilitating parasitic infection with about 500 million cases reported annually and one million deaths worldwide. Currently, Plasmodium falciparum has developed resistance to almost all classes of antimalarials, thus precluding the use of those agents which once formed the cornerstone of malaria therapy. In lieu of this phenomenon, and taking into consideration the absence of an effective vaccine for malaria, the only way to combat the deadly parasite is to enrich the antimalarial cache with new molecules acting on fresh targets in the parasite. After potential targets have been validated, these targets can be used as basis for screening compounds to identify new leads followed by lead optimization. This review discu... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5108673 Wed, 13 Jul 2011 23:00:00 +0100 5108673 http://www.medworm.com/index.php?rid=5012265&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718233%26dopt%3DAbstract Authors: Oestreich JH Numerous genetic variants have been studied in the context of antiplatelet responsiveness, particularly for aspirin and clopidogrel. The majority of these variants have failed to demonstrate any measurable level of clinical validity with the exception of the CYP2C19*2 allele. Several studies have identified a link between CYP2C19*2 carriers and decreased clopidogrel responsiveness as assessed by platelet function testing and clinical outcomes. The FDA black box warning and strong evidence of the CYP2C19*2 allele provide a compelling indication to alter treatment when genotype information is available. However, several questions remain and universal genotyping cannot be recommended at this time without further studies that prospectively establish the clinical utili... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012265 Wed, 29 Jun 2011 23:00:00 +0100 5012265 http://www.medworm.com/index.php?rid=5012264&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718234%26dopt%3DAbstract Authors: Sibbing D, Byrne RA, Kastrati A Oral antiplatelet therapy is routinely administered to ACS patients as well as to patients undergoing percutaneous coronary intervention (PCI) with the primary aim of inhibiting platelet-mediated thrombus formation and subsequent abrupt vessel occlusion. Individual platelet response to aspirin and especially to clopidogrel is highly variable and evidence has grown in recent years linking an attenuated response to therapy with the occurrence of ischemic events. At present, the antiplatelet therapy landscape is changing with the emergence of prasugrel and ticagrelor as alternative and more potent treatment options. In addition, tests for near-patient monitoring of platelet function in clinical practice are available and are being increasingly empl... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012264 Wed, 29 Jun 2011 23:00:00 +0100 5012264 http://www.medworm.com/index.php?rid=5012263&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718235%26dopt%3DAbstract Authors: Halim SA, Rao SV Acute coronary syndromes (ACS) continue to have a large impact on morbidity and mortality in the United States. Over the last two decades, there have been several advancements in the care of patients with ACS. The use of combined antiplatelet and anticoagulants and early invasive risk stratification in high risk patients has improved the rates of major adverse cardiovascular events. However, this treatment strategy increases the risk for bleeding. Studies have found an association between bleeding and subsequent mortality and morbidity in ACS patients; therefore, minimizing bleeding risk has become a priority. This review describes the prevalence of bleeding during ACS management, risk for bleeding, and strategies to reduce bleeding risk. PMID: 21718235 [P... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012263 Wed, 29 Jun 2011 23:00:00 +0100 5012263 http://www.medworm.com/index.php?rid=5012262&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718236%26dopt%3DAbstract Authors: Holly SP, Parise LV Platelets are dynamic blood cells that form life-threatening thrombi in response to a variety of pathological conditions such as atherosclerosis, diabetes, metastatic cancer, sickle cell disease and obesity. These thrombi can lead directly to myocardial infarction (MI), stroke and other thrombotic events that contribute to over a million deaths every year in the United States. Even though multiple, effective drugs have been developed to combat these pathologies by antagonizing platelet receptors and their ligands, clinical use of these drugs can result in serious bleeding consequences. With the advent of increasingly powerful and accessible systems biology approaches, however, new opportunities are available to identify novel platelet targets and elucidate ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012262 Wed, 29 Jun 2011 23:00:00 +0100 5012262 http://www.medworm.com/index.php?rid=5012261&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718237%26dopt%3DAbstract Authors: Bigalke B, Elvers M, Schönberger T, Gawaz M One of the key receptors involved in the prothrombotic stage of an acute coronary syndrome (ACS) is platelet glycoprotein VI (GPVI). This constitutively expressed collagen receptor is platelet-specific and has shown to be a useful biomarker tool for the early detection of atheroslerotic diseases such as ACS and ischemic stroke. In a multimarker panel of several biomarkers, platelet GPVI may contribute to risk stratification and prediction of clinical outcome in patients with symptomatic atherosclerotic diseases. Moreover, the soluble receptor of GPVI may also be an interesting and prospective target for molecular imaging to identify sites of vulnerable plaques as the results of preclinical studies suggest. Apart from the diagnostic ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012261 Wed, 29 Jun 2011 23:00:00 +0100 5012261 http://www.medworm.com/index.php?rid=5012260&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718238%26dopt%3DAbstract Authors: Schneider DJ The development of glycoprotein (GP) IIb-IIIa antagonists is reviewed with particular emphasis on the characteristics of each agent, the pharmacodynamic profile of each agent, results in pivotal clinical trials, and the associated implications. GP IIb-IIIa antagonists have greatest benefit when used as adjunctive therapy during percutaneous coronary intervention (PCI) when the patient has intra-coronary thrombosis. These agents appear to provide greatest benefit when used in combination with heparin. The clinical niche for parenteral GP IIb-IIIa antagonists is evolving but appears to be for patients in transition, such as individuals requiring emergent PCI before oral agents are fully active and for unstable patients requiring transport to PCI centers. Subsequent ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012260 Wed, 29 Jun 2011 23:00:00 +0100 5012260 http://www.medworm.com/index.php?rid=5012259&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718239%26dopt%3DAbstract Authors: Bailey AL, Campbell CL The platelet is central to the pathophysiology of ACS via its direct participation in the formation of the thrombotic occlusion and its participation in the coagulation cascade that results in the formation of thrombin. Antiplatelet therapy is a cornerstone of therapy in the setting of ACS. Unfortunately, many patients who receive intensive antiplatelet therapy remain at high risk for recurrent events. Current efforts to reduce this "residual risk" include lifestyle modifications, cardiac rehabilitation and intensive therapy for dyslipidemia. Also being investigated are methods of individualizing and intensifying antiplatelet therapy. Novel compounds that promise to reduce recurrent ischemic events without an increase in bleeding events are being evaluat... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012259 Wed, 29 Jun 2011 23:00:00 +0100 5012259 http://www.medworm.com/index.php?rid=5012258&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718240%26dopt%3DAbstract Authors: Steinhubl SR An understanding of the historical paths that have lead to our current state of knowledge in the field of platelet studies can be both illuminating and inspiring. Considering that the existence and function of platelets were initially described just barely over 100 years ago it is exciting to recognize how far our knowledge has advanced in such a relatively short period of time. Within 20 years of Giulio Bizzozero's definitive description of blood platelets investigators began to develop tests that could quantitate the relationship between platelets, hemostasis and bleeding, and these tests have continued to be refined ever since. At the same time, and well before the role of platelets and antiplatelet agents in cardiovascular disease was appreciated, several clin... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012258 Wed, 29 Jun 2011 23:00:00 +0100 5012258 http://www.medworm.com/index.php?rid=5012257&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21718241%26dopt%3DAbstract Authors: Smyth SS PMID: 21718241 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012257 Wed, 29 Jun 2011 23:00:00 +0100 5012257 http://www.medworm.com/index.php?rid=5012272&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707474%26dopt%3DAbstract Authors: Ploplis VA Plasminogen Activator Inhibitor-1 (PAI-1) is a multifunctional protein with the ability to not only regulate fibrinolysis through inhibition of plasminogen activation, but also cell signaling events which have direct downstream effects on cell function. Elevated plasma levels of this protein have been shown to have profound effects on the development and progression of cardiovascular diseases. However, results from a number of studies, especially those using PAI-1 deficient mouse models, have demonstrated that its function is ambiguous, with evidence of both preventing and enhancing various disease states. A number of lifestyle changes and pharmacological reagents have been identified that can regulate PAI-1 levels or function. Those reagents that target function ar... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012272 Sun, 26 Jun 2011 23:00:00 +0100 5012272 http://www.medworm.com/index.php?rid=5012271&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707475%26dopt%3DAbstract Authors: Medcalf R The plasminogen activating enzyme system has been exploited and harnessed for therapeutic, mainly thrombolytic benefit for many years. While plasminogen activator-based thrombolysis turned out to be a resounding success, it has become apparent that the "plasminogen activating system" per se is not only designed to simply remove fibrin and some other matrix proteins. Indeed, the plasminogen activators and the plasminogen activator inhibitors have important effects on cell signalling through both proteolytic and non-proteolytic means and can promote unwanted side effects, particularly in the brain. Tissue type plasminogen activator (t-PA) was heralded as a fibrin-selective plasminogen activator and subjected to clinical development in the early 1980's initially for the... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012271 Sun, 26 Jun 2011 23:00:00 +0100 5012271 http://www.medworm.com/index.php?rid=5012270&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707476%26dopt%3DAbstract Authors: Carriero MV, Franco P, Votta G, Longanesi-Cattani I, Vento MT, Masucci MT, Mancini A, Caputi M, Iaccarino I, Stoppelli MP Urokinase (uPA) is a 411 residues serine protease originally identified for its ability to activate plasminogen and generate plasmin, a broad-spectrum matrix- and fibrin-degrading enzyme. Later, this protease has been shown to possess also a clear-cut ability to stimulate cell migration and survival in a catalytic-independent manner. This activity turned out to be exerted through the growth factor-like domain (GFD-like, residues 1-49) of the protease binding to a GPI-anchored membrane receptor (uPAR), in complex with transmembrane receptors such as integrins, the epidermal growth factor and the formyl-peptide receptors. Direct binding of uPA to integrins th... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012270 Sun, 26 Jun 2011 23:00:00 +0100 5012270 http://www.medworm.com/index.php?rid=5012269&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707477%26dopt%3DAbstract Authors: Lund IK, Illemann M, Thurison T, Christensen IJ, Høyer-Hansen G Degradation of proteins in the extracellular matrix is crucial for the multistep process of cancer invasion and metastasis. Compelling evidence has demonstrated the urokinase receptor (uPAR) and its cognate ligand, the urokinase plasminogen activator (uPA), to play critical roles in the concerted action of several proteolytic systems in generation of a high proteolytic potential required for tissue remodeling processes. uPAR is additionally cleaved by uPA on the cell surface, liberating domain I, resulting in abrogated pericellular proteolysis. The expression of both uPAR and uPA is significantly up-regulated during cancer progression and is primarily confined to the tumor-associated stromal compartment. Furtherm... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012269 Sun, 26 Jun 2011 23:00:00 +0100 5012269 http://www.medworm.com/index.php?rid=5012268&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707478%26dopt%3DAbstract Authors: Ngo JC, Jiang L, Lin Z, Yuan C, Chen Z, Zhang X, Yu H, Wang J, Lin L, Huang M Urokinase-type plasminogen activator (uPA) is one of the two physiological serine proteases responsible for the activation of plasminongen to plasmin. uPA activity is regulated by its inhibitors (PAI-1 and PAI-2) and its receptor (uPAR), and an expanding list of their interacting proteins. In addition to plasminogen activation, this system also plays important roles in the regulation of many cellular processes including cell proliferation, adhesion and migration. It is beyond reasonable doubt that this enzyme system plays a central role in tumor biology and represents a high potential target for therapeutic intervention of tumor growth and metastasis. During the past fifteen years, crystal structures... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012268 Sun, 26 Jun 2011 23:00:00 +0100 5012268 http://www.medworm.com/index.php?rid=5012267&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707479%26dopt%3DAbstract Authors: Kriegbaum MC, Persson M, Haldager L, Alpizar-Alpizar W, Jacobsen B, Gårdsvoll H, Kjær A, Ploug M In the last two decades, the urokinase-type plasminogen activator has been implicated in a number of human pathologies such as cancer, bacterial infections, and paroxysmal nocturnal hemoglobinuria. The primary function of this glycolipid-anchored receptor is to focalize uPA-mediated plasminogen activation at the cell surface, which is accomplished by its high-affinity interaction with the growth factor-like domain of uPA. Detailed insights into the molecular basis underlying the interactions between uPAR and its two bona fide ligands, uPA and vitronectin, have been obtained recently by X-ray crystallography and surface plasmon resonance studies. Importantly, these structural stud... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012267 Sun, 26 Jun 2011 23:00:00 +0100 5012267 http://www.medworm.com/index.php?rid=5012266&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707480%26dopt%3DAbstract Authors: Ranson M PMID: 21707480 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=5012266 Sun, 26 Jun 2011 23:00:00 +0100 5012266 http://www.medworm.com/index.php?rid=4969223&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21675944%26dopt%3DAbstract Authors: Papaetis GS, Orphanidou D, Panagiotou TN The prevalence of type 2 diabetes is evolving globally at an alarming rate. This fact is mainly the result of our global lifestyle "modernization" that has resulted in overweight and obesity. Dysfunction of peroxisome proliferator activated receptor-gamma (PPAR-γ) has been implicated in the development of insulin resistance, while a reduce expression of many PPAR-γ regulated genes has been observed in an obese diabetic state. Thiazolidinediones (TZDs) are potent exogenous agonists of PPAR-γ, which augment the effects of insulin to its cellular targets and mainly at the level of adipose tissue. Preclinical and clinical studies have demonstrated that apart from their glucose-lowering activity, these drugs also regulate the production o... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4969223 Tue, 14 Jun 2011 23:00:00 +0100 4969223 http://www.medworm.com/index.php?rid=4876656&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561413%26dopt%3DAbstract Authors: Babcock JT, Quilliam LA mTOR exists in two distinct complexes. mTOR complex 1 (mTORC1) is potently inhibited by the immunosupressive macrolide rapamycin; whereas, mTORC2 is insensitive to this durg. These mTOR complexes play an integral role in the regulation of many cellular processes including protein synthesis, autophagy, lipid synthesis, mitochondrial metabolism/biogenesis, and cell cycle. Both mTOR complexes are important for maintaining cellular homeostasis and the growth of many types of cancer. Rapamycin and rapalogs have been effective in treating only a small number of these cancers, and other methods are being developed in order to address the short-comings of these drugs. The most direct of these approaches include ATP-competitive inhibitors of the mTOR kinase or d... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876656 Tue, 10 May 2011 23:00:00 +0100 4876656 http://www.medworm.com/index.php?rid=4876655&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561414%26dopt%3DAbstract Authors: Pellon-Cardenas O, Schweitzer J, D'Souza-Schorey C Several mechanisms function in the endocytic regulation of the Wnt/β-catenin signaling pathway to promote or interrupt the progression of critical cellular processes during embryonic development or disease progression. Endocytosis was initially associated with the formation of a morphogen gradient of Wnt/β-catenin signaling, but current studies have documented its role in defining signal intensity and propagation. Although the exact parameters that define and dictate the internalization of Wnt receptors and co-receptors via clathrin- or caveolae-mediated endocytosis remain unclear, new studies indicate that the trafficking of the signaling pool of the dual-function protein β-catenin from sites of cell-cell contacts serve as... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876655 Tue, 10 May 2011 23:00:00 +0100 4876655 http://www.medworm.com/index.php?rid=4876654&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561415%26dopt%3DAbstract Authors: Antoine-Bertrand J, Villemure JF, Lamarche-Vane N The establishment of neural connectivity implicates tight regulation of the intracellular signaling pathways mediated by axon guidance molecules. The Rho family of small GTPases, in particular Rho, Rac, and Cdc42, are important regulators of the cytoskeleton in neuronal cells acting, downstream of most, if not all, guidance cue receptors. Furthermore, recent studies using in vivo knockout mouse models provide new evidence of the primary role played by Rho GTPase signaling during the development of the nervous system. Here, we review our recent understanding of Rho GTPase signaling in response to classical axon guidance cues in mammalian cells. We also describe how in vivo knockout mouse models have been useful to implicate Rho ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876654 Tue, 10 May 2011 23:00:00 +0100 4876654 http://www.medworm.com/index.php?rid=4876653&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561416%26dopt%3DAbstract Authors: Baranwal S, Alahari SK Rho GTPases (Ras homologous family) comprise the largest subfamily cluster of the Ras-homology superfamily. Rho GTPases exist in inactive GDP and active GTP forms. The active forms of the Rho family members bind with numerous effector proteins that are crucial for various biological processes. Accumulating evidence exemplifies the importance of Rho effector proteins in various steps of cancer progression. Here, we highlight the actions of various effectors of Rho members in cancer invasion and metastasis. PMID: 21561416 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876653 Tue, 10 May 2011 23:00:00 +0100 4876653 http://www.medworm.com/index.php?rid=4876652&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561417%26dopt%3DAbstract Authors: Li G The Rab family of GTPases contains over 60 genes in the human genome and contributes to regulation of intracellular membrane trafficking along endocytic and exocytic pathways as well as specialized pathways in specific cell types. It has become increasingly clear that disruption of the intracellular membrane trafficking system at different stages can cause various diseases. In the past decade, altered expression levels and mutations of Rab GTPases have been associated with such diseases as cancer, Alzheimer's disease, and various genetic disorders. This review discusses the specific Rab GTPases and their involvement in the diseases. PMID: 21561417 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876652 Tue, 10 May 2011 23:00:00 +0100 4876652 http://www.medworm.com/index.php?rid=4876651&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561418%26dopt%3DAbstract Authors: D'Souza-Schorey C PMID: 21561418 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876651 Tue, 10 May 2011 23:00:00 +0100 4876651 http://www.medworm.com/index.php?rid=4876650&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561419%26dopt%3DAbstract Authors: Chlipala GE, Mo S, Orjala J Cyanobacteria are considered a promising source for new pharmaceutical lead compounds and a large number of chemically diverse and bioactive metabolites have been obtained from cyanobacteria over the last few decades. This review highlights the structural diversity of natural products from freshwater and terrestrial cyanobacteria. The review is divided into three areas: cytotoxic metabolites, protease inhibitors, and antimicrobial metabolites. The first section discusses the potent cytotoxins cryptophycin and tolytoxin. The second section covers protease inhibitors from freshwater and terrestrial cyanobacteria and is divided in five subsections according to structural class: aeruginosins, cyanopeptolins, microviridins, anabaenopeptins, and microgini... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876650 Tue, 10 May 2011 23:00:00 +0100 4876650 http://www.medworm.com/index.php?rid=4876649&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561420%26dopt%3DAbstract Authors: Nilsson J, Sterner O Nature provides science and society with a virtually unlimited supply of structurally diverse and biologically active molecules; the natural products. While some are directly useful in commercial applications, others are valuable for studying and understanding biological phenomena at the molecular level. An example is the signaling of nerve cells, which has been explored in considerable detail using a number of bioactive natural products. This review concerns primarily a part of the GABA inhibitory system of the central nervous system, the GABA(A) receptors, and natural products that have been reported to affect GABA(A) receptors in various ways. As the major inhibitory neurotransmittor, GABA plays a central role in the function of the central nervous syst... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876649 Tue, 10 May 2011 23:00:00 +0100 4876649 http://www.medworm.com/index.php?rid=4876648&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561421%26dopt%3DAbstract Identification of Novel Anti-inflammatory Agents from Ayurvedic Medicine for Prevention of Chronic Diseases: "Reverse Pharmacology" and "Bedside to Bench" Approach. Curr Drug Targets. 2011 May 11; Authors: Aggarwal BB, Prasad S, Reuter S, Kannappan R, Yadev VR, Park B, Kim JH, Gupta SC, Phromnoi K, Sundaram C, Prasad S, Chaturvedi MM, Sung B Inflammation, although first characterized by Cornelius Celsus, a physician in first Century Rome, it was Rudolf Virchow, a German physician in nineteenth century who suggested a link between inflammation and cancer, cardiovascular diseases, diabetes, pulmonary diseases, neurological diseases and other chronic diseases. Extensive research within last three decades has confirmed these observations and identified the molecular basis for most ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876648 Tue, 10 May 2011 23:00:00 +0100 4876648 http://www.medworm.com/index.php?rid=4876647&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561422%26dopt%3DAbstract Authors: Ramesha BT, Jürg G, Ravikanth G, Priti V, Ganeshaiah KN, Uma Shaanker R Biological diversity and its constituent chemical diversity have served as one of the richest sources of bioprospecting leading to the discovery of some of the most important bioactive molecules for mankind. Despite this excellent record, in the recent past, however, bioprospecting of biological resources has met with little success; there has been a perceptible decline in the discovery of novel bioactive compounds. Several arguments have been proposed to explain the current poor success in bioprospecting. Among them, it has been argued that to bioprospect more biodiversity may not necessarily be productive, considering that chemical and functional diversity might not scale with biological diversity. In t... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876647 Tue, 10 May 2011 23:00:00 +0100 4876647 http://www.medworm.com/index.php?rid=4876646&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561423%26dopt%3DAbstract Authors: Schneekloth JS, Crews CM Natural products continue to be a source of inspiration for chemists and biologists alike. The search for biologically active natural prodcuts has provided troves of information about biological processes, and natural products continue to be some of the most powerful and useful probes of biological processes available. Complex and unusual molecular architectures provide the impetus for new reaction development and push the limits of known synthetic chemistry. In addition to serving as tools for basic research, natural products represent starting points for drug discovery efforts in many cases. This review details the impressive chemical diversity present in the family of molecules that inhibit the proteasome and other aspects of the ubiquitin-proteasom... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876646 Tue, 10 May 2011 23:00:00 +0100 4876646 http://www.medworm.com/index.php?rid=4876645&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561424%26dopt%3DAbstract Authors: Gademann K Many proteins are transported from the nucleus to the cytoplasm by the exportin CRM1, which recognizes cargo proteins through a leucine rich nuclear export signal (NES). This nuclear export process can be inhibited by several small molecules, both natural products and fully synthetic compounds. The structural basis for the inhibition of nuclear export by leptomycin (LMB) based on disruption of the protein/protein interaction between CRM1 and cargo proteins is discussed. The chemistry and inhibition of nucleocytoplasmic transport of leptomycin, anguinomycin and derivatives, goniothalamin, JBIR-02, valtrate, dihydrovaltrate, ACA, peumusolide A and several synthetic compounds is presented. Consequences for the design of nuclear export inhibitors are discussed, and the ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876645 Tue, 10 May 2011 23:00:00 +0100 4876645 http://www.medworm.com/index.php?rid=4876644&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561425%26dopt%3DAbstract Authors: Merfort I Sesquiterpene lactones are a large group of secondary plant metabolites mostly known from the Asteraceae family. They exert a broad variety of different biological activities. This review attempts to critically summarise the knowledge on the anti-inflammatory and cytotoxic activity of SLs, with a special focus on parthenolide and helenalin. Recent advances on their molecular modes of action, allergic potential and also QSAR studies with SLs are presented. Therapeutic areas are highlighted in which SLs may play a role in the future. Thus, SLs may possess therapeutic relevance as single components for the local treatment of inflammation, such as rheumatoid complaints. In cancer therapy, SLs may be favourable in dual therapy or in the inhibition of leukaemia cell growth... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876644 Tue, 10 May 2011 23:00:00 +0100 4876644 http://www.medworm.com/index.php?rid=4876643&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561426%26dopt%3DAbstract Authors: Eberhardt L, Kumar K, Waldmann H Small bioactive molecules are pre-requisite for any discovery discipline. Aware of the fact that bioactivity is not randomly dispersed in the vast chemical space, chemists have been developing hypothesis that can lead them to the islands of bioactivities. Natural products have always been a source of inspiration and their structural motifs provide biologically relevant starting points for library synthesis. In addition to that, Diversity Oriented Synthesis (DOS) and Biology Oriented Synthesis (BIOS) have emerged as tools to guide synthesis design and help enrich compound collections in biological activities. Coherent developments in chem- and bioinformatic tools and in organic synthesis methods targeting efficient generation of compound collect... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876643 Tue, 10 May 2011 23:00:00 +0100 4876643 http://www.medworm.com/index.php?rid=4876642&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561427%26dopt%3DAbstract Authors: Witting K, Süssmuth RD After decades of neglect in industrial research the comeback of natural products is due since improved screening approaches are at disposal, yielding a multitude of new compounds from natural sources. Besides traditional compound libraries peptides are characterized by an enormous structural complexity, thus increasing the chance of finding a hit in a screening. Emphasizing antibacterial compounds structural complexity is a prerequisite for their success. This review focuses on the screening approaches employed for the discovery of mostly antibacterial, non-ribosomal peptides derived from natural sources. Traditional screening methodologies as well as genetic approaches are discussed in this context. Utilizing genetic engineering methods e.g., precursor... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876642 Tue, 10 May 2011 23:00:00 +0100 4876642 http://www.medworm.com/index.php?rid=4876641&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561428%26dopt%3DAbstract Authors: Kumar R, Khan S, Chauhan PM This review provides a detailed account on the biological activities of structurally diverse secondary metabolites from marine sponges having 2-aminoimidazole, glycociamidine and/or 2-thiohydantoin ring functions. This review will complement two previous short reviews which did however not address the potential of these natural products for drug discovery. We will discuss the naturally occurring alkaloids and give an account on their structure activity relationships. PMID: 21561428 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876641 Tue, 10 May 2011 23:00:00 +0100 4876641 http://www.medworm.com/index.php?rid=4823918&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561429%26dopt%3DAbstract Authors: Gertsch J PMID: 21561429 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4823918 Tue, 10 May 2011 23:00:00 +0100 4823918 http://www.medworm.com/index.php?rid=4876672&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466484%26dopt%3DAbstract Authors: Spinelli A, Sampietro GM, Bazzi P, Sacchi M, Montorsi M Ulcerative colitis (UC) is a chronic inflammatory condition of the mucosa affecting the rectum and extending up the colon in a continuous manner. Its etiology is unknown, but is most probably the result of the interaction of genetic and environmental factors. Approximately 30% of UC patients will need to undergo surgery at some point during their lifetime, despite progresses made in medical therapies. Indications for surgery include acute severe colitis with its complications, steroid-or antiTNF-refractory colitis (or growth impairment in children), and the onset of colorectal dysplasia/cancer. Recently, the introduction of biologic agents has provided a rationale for prolonging medical therapy before considering surgery ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876672 Mon, 04 Apr 2011 23:00:00 +0100 4876672 http://www.medworm.com/index.php?rid=4876671&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466485%26dopt%3DAbstract Authors: Fabro M, Szabo H, Terrosu G, Avellini C, Tabuso M, Sorrentino D Acute severe ulcerative colitis is a serious condition that requires early hospitalization, with intensive monitoring and treatment. Despite the recent progress in the medical approach of Inflammatory Bowel Diseases acute severe ulcerative colitis remains a clinical challenge, with a mortality rate of nearly 1%. As of today, I.V. corticosteroids remain the 1(st)-line therapy for this complication. For non-responders (up to one-third of patients) possible options are surgery - whose timing is a critical point in the overall management of the disease - or rescue therapy with 2(nd)- line agents such as Cyclosporine and Infliximab. Here we will review the published studies dealing with the use of these medications in ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876671 Mon, 04 Apr 2011 23:00:00 +0100 4876671 http://www.medworm.com/index.php?rid=4876670&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466486%26dopt%3DAbstract Authors: Filippi J, Allen PB, Hébuterne X, Peyrin-Biroulet L Infliximab has demonstrated its efficacy in moderate to severe ulcerative colitis. The Active Ulcerative Colitis Trial (ACT) -1 and 2 have demonstrated the beneficial impact of infliximab on the short-term colectomy rate. However, data evaluating this outcome beyond one year remains scarce. To provide evidence on the potential impact of infliximab on the long-term colectomy rate in patients suffering from ulcerative colitis, data was reviewed from randomized and controlled studies, referral centre studies and population-based studies, in adult and pediatric populations. In the pre-biologic era, 9-33%, 50% and 29% of adult patients with ulcerative colitis underwent colectomy in clinical trials, referral center studies and pop... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876670 Mon, 04 Apr 2011 23:00:00 +0100 4876670 http://www.medworm.com/index.php?rid=4876669&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466487%26dopt%3DAbstract Authors: Magro F, Lopes S, Rodrigues S, Azevedo I It is estimated that 50% of patients who have undergone ileal pouch-anal anastomosis (IPAA) surgery for UC will develop at least one episode of pouchitis. The risk of developing pouchitis is much higher in patients with preoperative extraintestinal manifestations and primary sclerosing cholangitis. In acute pouchtis metronidazole or ciprofloxacin have shown efficacy, however there is some evidence that ciprofloxacin may have better and has less toxic. In patients with chronic pouchitis antibiotics are less effective, and maintenance therapy may be required. In cases of refractoriness to conventional therapy a combination of two antibiotics for a prolonged period or infliximab may be effective. Starting maintenance treatment with highly ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876669 Mon, 04 Apr 2011 23:00:00 +0100 4876669 http://www.medworm.com/index.php?rid=4876668&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466488%26dopt%3DAbstract Authors: Kiss LS, Lakatos PL The clinical presentation at the time of diagnosis and the disease course of ulcerative colitis (UC) are heterogeneous and variable over time. In population-based epidemiological follow-up studies from the last decades, the extent of UC has shown only slight variation. At diagnosis, the initial extent is evenly distributed among proctitis, left-sided, and extensive colitis with some exceptions. The disease course may vary from a single attack to chronic symptoms that reduce the quality of life as well as lead to disease extension, colectomy or even to the development of colitis-associated colorectal cancer in some cases. Important predictive clinical factors and biomarkers of disease course have been under increasing scrutiny. Those identified may eventuall... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876668 Mon, 04 Apr 2011 23:00:00 +0100 4876668 http://www.medworm.com/index.php?rid=4876667&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466489%26dopt%3DAbstract Authors: Fries W, Comunale S The pathogenesis of ulcerative is still poorly understood. With the introduction of new culture-independent techniques the research on the intestinal microbiota has revealed an important reduction of Bacteroidetes and Firmicutes leading to a reduced biodiversity and dysbiosis in these patients. Going in depth, the intestinal barrier is covered under physiologic conditions by a mostly sterile mucus layer. Besides a reduction of mucus thickness or an alteration in mucus composition hypothesized for human ulcerative colitis, new evidence coming from mouse models has introduced a novel concept based on cellular stress due to misfolded mucus-associated proteins opening a new research area for the epithelial cell lining. A dysregulated immune response involving t... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876667 Mon, 04 Apr 2011 23:00:00 +0100 4876667 http://www.medworm.com/index.php?rid=4876666&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466490%26dopt%3DAbstract Authors: Fiorino G, Cesarini M, Indriolo A, Malesci A Ulcerative colitis (UC) is an inflammatory bowel disease (IBD) characterized by chronic inflammation affecting the colonic mucosa, that can extend to the whole large bowel. The severity of mucosal lesions directly reflects the disease activity and severity and may be prognostic for an aggressive behavior of the pathology. Remission, is usually defined as resolution of symptoms. Recently, mucosal healing (MH) has emerged as an important end point of any short-term medical therapy for IBD. It may predict long-term remission and may impact on the natural history of the disease in Crohn's disease (CD), while data in UC patients are still limited. This review of the literature is focused on the recent evidence on the impact of medication... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876666 Mon, 04 Apr 2011 23:00:00 +0100 4876666 http://www.medworm.com/index.php?rid=4876665&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466491%26dopt%3DAbstract Authors: Affendi R, Ali R, Egan LJ There is a strong association between chronic inflammation and cancer formation. This correlation has been well observed in patients with long standing inflammatory bowel disease (IBD) who are at high risk of colorectal cancer (CRC). At present, there is a lack of good markers for predicting the progression from normal to neoplastic mucosa in patients with IBD. IBD patients who are 'at-risk' of CRC should be identified, evaluated and should also be enrolled in surveillance program, regardless of their disease activity. Early identification of dysplasia and its appropriate management using endoscopic techniques or surgery are essential in patients with long-standing IBD, to minimize CRC morbidity and mortality. Gastroenterologists should work along wit... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876665 Mon, 04 Apr 2011 23:00:00 +0100 4876665 http://www.medworm.com/index.php?rid=4876664&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466492%26dopt%3DAbstract Authors: Fiorino G, Cesarini M, Danese S Ulcerative Colitis (UC) is an idiopathic chronic inflammation. Its etiology is still largely unknown. Environmental and genetic factors in combination with the microbial flora or specific microorganisms are thought to trigger the gut inflammation, leading to the activation of the intestinal immune response. Immune and non-immune cells create a cross talk via the secretion of soluble mediators and expression of cell adhesion molecules, resulting in further cell activation. Mediators such as cytokines and chemokines play a key role in cell recruitment and polarization, intercellular signal amplification or activation and differentiation. Lack of balance between pro-inflammatory and anti-inflammatory cytokines is crucial in the pathogenesis of IBD.... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876664 Mon, 04 Apr 2011 23:00:00 +0100 4876664 http://www.medworm.com/index.php?rid=4876663&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466493%26dopt%3DAbstract Authors: Cottone M, Renna S, Modesto I, Orlando A 5-Amino-salacylic acid (5-ASA) is up to now the treatment of choice in the induction and maintenance of remission of mild-to-moderate ulcerative colitis (UC). Sulfasalazine, despite similar efficacy, is hampered by more side effects, but in presence of peripheral arthopaties it remains the treatment of choice. The new delayed release MMX formulation seems to be promising in reducing compliance problems, but further studies are warranted to show the superiority of new MMX formulation compared with the older formulations of 5-ASA. Some trials evaluated also the efficacy and safety of once-daily dosing of older 5-ASA formulations in maintenance of remission, finding a greater adherence to therapy in the group given the once daily regimen, ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876663 Mon, 04 Apr 2011 23:00:00 +0100 4876663 http://www.medworm.com/index.php?rid=4876662&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466494%26dopt%3DAbstract Authors: Carbonnel F Ulcerative colitis (UC) is a chronic inflammatory bowel disease that is thought to affect 1780000 patients in USA and Europe. Its incidence is increasing rapidly in Asia. Drugs with proven clinical activity that are currently used in UC patients include salicylates, steroids, azathioprine and infliximab. None of them is active in every patient and all carry significant side effects. There is a need for other active drugs in UC. Low dose methotrexate has been used for decades in psoriasis, rheumatoid arthritis and Crohn's disease. In these diseases, it is an active, well tolerated and cheap drug. In UC there have been several open series, most of which are retrospective. Overall, these studies have shown promising results, with response rates of 50 to 72 p. cent. Th... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876662 Mon, 04 Apr 2011 23:00:00 +0100 4876662 http://www.medworm.com/index.php?rid=4876661&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466495%26dopt%3DAbstract Authors: Jáuregui-Amézaga A, Ricart E, Panés J The perception that Crohn's disease is a more severe process than ulcerative colitis, led to the initial development of a majority drugs, and testing of treatment strategies, in the former. In the absence of similar studies in ulcerative colitis, information of Crohn's disease studies may help the clinician in decision making in UC. Studies on aminosalicylates show that drugs with a topical effect which are not effective in Crohn's disease may still have efficacy in ulcerative colitis, and this should be considered in future drug development. The best efficacy of corticorteroids is achieved with high doses of 1 mg/kg/day, and reaching remission may be delayed by several weeks, although non-response in the initial days should lead to tre... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876661 Mon, 04 Apr 2011 23:00:00 +0100 4876661 http://www.medworm.com/index.php?rid=4876660&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466496%26dopt%3DAbstract Authors: La Nauze RJ, Sparrow MP The goals of treatment for ulcerative colitis (UC) are to induce and maintain corticosteroid-free remission, thereby reducing hospitalizations and surgeries and preventing longer-term disease complications including colorectal cancer. Despite an incomplete evidence base, thiopurine immunomodulators remain a principle therapeutic option for patients failing aminosalicylate monotherapy and requiring multiple courses of corticosteroids. In this review, we outline the current evidence supporting the role of thiopurines in achieving these treatment goals in UC, including discussions of the important safety issues regarding their use. We also explore some of the recent evidence emerging in regards to the risks of lymphoproliferative disease, dosage optimizati... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876660 Mon, 04 Apr 2011 23:00:00 +0100 4876660 http://www.medworm.com/index.php?rid=4876659&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466497%26dopt%3DAbstract Authors: Latiano A, Annese V Substantial progress has been made in the last years in characterizing the susceptibility genes involved in IBD pathogenesis, especially for Crohn's disease. Although some genetic factors associated with Crohn's disease also predispose individuals to ulcerative colitis, markers specific only for ulcerative colitis have been found. Recent genome-wide association studies in ulcerative colitis have identified several new loci, and suggested many new potential pathways. The identified susceptibility genes and their variants could be useful to predict disease course and to improve stratification of patients, when correlated with other subphenotypes. Moreover, understanding the biological pathways involved in the disease could lead to the development of new treat... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876659 Mon, 04 Apr 2011 23:00:00 +0100 4876659 http://www.medworm.com/index.php?rid=4876658&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21466498%26dopt%3DAbstract Authors: Danese S PMID: 21466498 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876658 Mon, 04 Apr 2011 23:00:00 +0100 4876658 http://www.medworm.com/index.php?rid=4876657&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21504070%26dopt%3DAbstract Authors: Saffar AS, Ashdown H, Gounni AS Neutrophil-dominated inflammation plays an important role in many airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis and cystic fibrosis. In cases of asthma where neutrophil-dominated inflammation is a major contributing factor to the disease, treatment with corticosteroids can be problematic as corticosteroids have been shown to promote neutrophil survival which, in turn, accentuates neutrophilic inflammation. In light of such cases, novel targeted medications must be developed that could control neutrophilic inflammation while still maintaining their antibacterial/anti-fungal properties, thus allowing individuals to maintain effective innate immune responses to invading pathogens. The aim of this revi... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4876657 Thu, 31 Mar 2011 23:00:00 +0100 4876657 http://www.medworm.com/index.php?rid=4664831&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443460%26dopt%3DAbstract Authors: Monsalve M, Olmos Y FOXO transcription factors control proliferation, apoptosis, differentiation and metabolic processes. Loss of FOXO function has been identified in several human cancers, and results in increased cellular survival and a predisposition to neoplasia, especially in epithelial cancer. FOXO factors are therefore bona fide tumor suppressors, and their potential use as therapeutic targets in cancer has been a matter of debate. Importantly, FOXO factors can also positively regulate cell survival through the activation of several detoxification genes, complicating its putative therapeutic potential. Targeting of FOXO factors has also been proposed for the treatment of metabolic dysfunctions such as diabetes mellitus, immunological disorders and neurodegeneration, as ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664831 Sun, 27 Mar 2011 23:00:00 +0100 4664831 http://www.medworm.com/index.php?rid=4664830&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443461%26dopt%3DAbstract Authors: Boccitto M, Kalb RG The Forkhead Box O (Foxo) proteins represent an evolutionarily conserved family of transcription factors that play an important role in regulating processes including metabolism, longevity, and cell death/survival. How is it that a single transcription factor can initiate such divergent cellular responses? We will review the evidence that specific patterns of post-translational modifications play a key role in directing Foxo into various transcriptional readouts. This regulation appears to take on a two tiered regulatory model; with a group of well defined post-translational modifications regulating nuclear localization and transcriptional activity while a second set of modifications regulate the transcriptional specificity of Foxo. PMID: 21443461 [PubM... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664830 Sun, 27 Mar 2011 23:00:00 +0100 4664830 http://www.medworm.com/index.php?rid=4664829&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443462%26dopt%3DAbstract Authors: Yang JY, Hung MC Forkhead O transcription factors (FOXO) are critical for the regulation of cell cycle arrest, cell death, and DNA damage repair. Inactivation of FOXO proteins may be associated with tumorigenesis, including breast cancer, prostate cancer, glioblastoma, rhabdomyosarcoma, and leukemia. Accumulated evidence shows that activation of oncogenic pathways such as phosphoinositide-3-kinase/AKT/IKK or RAS/mitogen-activated protein kinase suppresses FOXO transcriptional activity through the phosphorylation of FOXOs at different sites that ultimately leads to nuclear exclusion and degradation of FOXOs. In addition, posttranslational modifications of FOXOs such as acetylation, methylation and ubiquitination also contribute to modulating FOXO3a functions. Several anti-cance... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664829 Sun, 27 Mar 2011 23:00:00 +0100 4664829 http://www.medworm.com/index.php?rid=4664828&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443463%26dopt%3DAbstract Authors: Ghaffari S, Yalcin S, Rielland M, Zhang X Forkhead FoxO transcription factors exert critical biological functions in response to genotoxic stress. In mammals four FoxOs proteins are known. FoxOs induce cell cycle arrest, repair damaged DNA, or initiate apoptosis by modulating genes that control these processes. In particular, FoxO proteins are critical regulators of oxidative stress by modulating the expression of several anti-oxidant enzyme genes. This function of FoxO is essential for the regulation of stem and progenitor cell pool in the hematopoietic system and possibly other stem cells. Overall functions of FoxOs are consistent with their role as tumor suppressors as has been shown in animal models. As such, FoxOs are suppressed in various cancer cells. However, recent re... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664828 Sun, 27 Mar 2011 23:00:00 +0100 4664828 http://www.medworm.com/index.php?rid=4664827&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443464%26dopt%3DAbstract Authors: Singh A, Plati J, Khosravi-Far R The promotion of cellular survival, dedifferentiation, and uncontrolled proliferation via the suppression of apoptotic effectors is a fundamental characteristic of tumor cells. As substrates that are negatively regulated by oncogenic signaling cascades driven by AKT, SGK (serum- and glucocorticoid-inducible kinase), IkB kinase (IKK), ERK, and cyclin-dependent kinases (CDK), forkhead box-class O (FOXO) transcription factors have emerged as bona fide tumor suppressors. These transcription factors indeed regulate a variety of cellular responses and themselves are regulated by reversible phosphorylation, acetylation, ubiquitination and miRNAs. This review will discuss our current understanding of mechanisms for FOXO regulation and the potential imp... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664827 Sun, 27 Mar 2011 23:00:00 +0100 4664827 http://www.medworm.com/index.php?rid=4664826&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443465%26dopt%3DAbstract Authors: Kim DH, Zhang T, Ringquist S, Dong HH Hypertriglyceridemia is characterized by increased production and decreased clearance of triglyceride-rich lipoproteins including very low-density lipoprotein (VLDL) and chylomicron. Due to its proatherogenic profile, hypertriglyceridemia contributes to the development of atherosclerosis and coronary artery disease. While the pathophysiology of hypertriglyceridemia remains poorly understood, its close association with obesity and type 2 diabetes implicates insulin resistance in the pathogenesis of hypertriglyceridemia. However, the molecular basis linking insulin resistance to hypertriglyceridemia remains elusive. Preclinical studies show that FoxO1 plays a pivotal role in controlling insulin-dependent regulation of microsomal triglyceride... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664826 Sun, 27 Mar 2011 23:00:00 +0100 4664826 http://www.medworm.com/index.php?rid=4664825&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443466%26dopt%3DAbstract Authors: Lu H, Huang H The forkhead box O (FoxO) transcription factors are known to be involved in many physiological and pathological processes including apoptosis, cell cycle arrest, stress resistance, glucose metabolism, cellular differentiation and development, and tumor suppression. The environmental cues, such as growth factors, nutrients, oxidative stress and irradiation, can either positively or negatively modulate FoxO proteins' activities, thereby ensuring distinctive transcription programs in the cell. The potent activities of FoxOs are tightly controlled by multiple mechanisms, which include posttranslational modification such as phosphorylation, acetylation, methylation and ubiquitination, subcellular localization, and direct protein-protein interaction. Mounting evidence ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664825 Sun, 27 Mar 2011 23:00:00 +0100 4664825 http://www.medworm.com/index.php?rid=4664824&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443467%26dopt%3DAbstract Authors: Wilson MS, Brosens JJ, Schwenen HD, Lam EW FOXO transcription factors, functioning downstream of the PI3K-PTEN-AKT (PKB) signalling cascade, are essential for cell proliferation, differentiation, DNA damage repair, and apoptosis. Recent research indicates that the related transcription factor FOXM1 is a direct target of repression by FOXO proteins. Inactivation of FOXO or overexpression of FOXM1 is associated with tumorigenesis and cancer progression. In addition, the cytostatic and cytotoxic effects of a diverse spectrum of anti-cancer drugs, such as paclitaxel, doxorubicin, lapatinib, gefitinib, imatinib, and cisplatin, are mediated through the activation of FOXO3a and/or the inhibition of its target FOXM1. Paradoxically, FOXO proteins also contribute to drug resistance by d... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664824 Sun, 27 Mar 2011 23:00:00 +0100 4664824 http://www.medworm.com/index.php?rid=4664823&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443468%26dopt%3DAbstract Authors: Christian M, Lam EW, Wilson MS, Brosens JJ All fundamental reproductive events in the human ovary and uterus, including ovulation, implantation and menstruation, are dependent upon profound tissue remodelling, characterized by cyclical waves of cell proliferation, differentiation, recruitment of inflammatory cells, apoptosis, tissue breakdown and regeneration. Although the rise and fall in ovarian hormones, estradiol and progesterone, orchestrate these reproductive events, FOXO transcription factors, an evolutionary conserved subfamily of forkhead transcription factors, have emerged major downstream effector molecules, capable of integrating hormonal cues with a variety of stress, growth factor and cytokine signal transduction pathways. The ability of FOXOs to regulate seeming... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664823 Sun, 27 Mar 2011 23:00:00 +0100 4664823 http://www.medworm.com/index.php?rid=4664822&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443469%26dopt%3DAbstract Authors: Link W PMID: 21443469 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664822 Sun, 27 Mar 2011 23:00:00 +0100 4664822 http://www.medworm.com/index.php?rid=4664821&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443470%26dopt%3DAbstract Authors: Khan Z, Khan N, Tiwari RP, Sah NK, Prasad GB, Bisen PS Cyclooxygenase-2 (Cox-2) is an inducible enzyme involved in the conversion of arachidonic acid to prostaglandin and other eicosanoids. Molecular pathology studies have revealed that Cox-2 is over-expressed in cancer and stroma cells during tumor progression, and anti-cancer chemo-radiotherapies induce expression of Cox-2 in cancer cells. Elevated tumor Cox-2 is associated with increased angiogenesis, tumor invasion and promotion of tumor cell resistance to apoptosis. Several experimental and clinical studies have established potent anti-cancer activity of NSAID (Non-steroidal anti-inflammatory drugs) and other Cox-2 inhibitors such as celecoxib. Much attention is being focused on Cox-2 inhibitors as beneficial target for c... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664821 Sun, 27 Mar 2011 23:00:00 +0100 4664821 http://www.medworm.com/index.php?rid=4664820&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443471%26dopt%3DAbstract Authors: Kesharwani P, Gajbhiye V, Tekade RK, Jain NK Dendrimers, by virtue of their therapeutic value, have recently generated enormous interest among biomedical scientists. Advancement of dendrimeric nano-architecture with well defined size, shape and controlled exterior functionality embraces promise in biomedical and pharmaceutical applications such as drug delivery, solubilization, DNA transfection and diagnosis. Highly branched, monodisperse, stable molecular level and low polydispersity with micelle-like behavior possessing nano-scale container property distinguish these structures as inimitable and optimum carrier for those applications. Dendrimers has been evaluated for delivery of different types of bioactives inside the cells. Different types of techniques are being used for... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664820 Sun, 27 Mar 2011 23:00:00 +0100 4664820 http://www.medworm.com/index.php?rid=4664819&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443472%26dopt%3DAbstract Authors: Bonanno L, Jirillo A, Favaretto A EGFR somatic mutations define a subset of NSCLCs that are most likely to benefit from EGFR tyrosine kinase inhibitors (TKIs). These tumors are dependent on EGFR-signaling for survival. Recently, tyrosine kinase domain somatic mutations have been approved as criterion to decide first-line therapy in this group of advanced NSCLCs. Anyway, all patients ultimately develop resistance to these drugs. Acquired resistance is linked to a secondary EGFR mutation in about a half of patients. Uncontrolled activation of MET, another tyrosine kinase receptor, has been implicated in neoplastic invasive growth. MET is overexpressed, activated and sometimes mutated in NSCLC cell lines and tumor tissues. MET increased gene copy number has also been documented i... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664819 Sun, 27 Mar 2011 23:00:00 +0100 4664819 http://www.medworm.com/index.php?rid=4664818&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443473%26dopt%3DAbstract Authors: Rocha BS, Gago B, Pereira C, Barbosa RM, Bartesaghi S, Lundberg JO, Radi R, Laranjinha J Until recently, nitrite has been considered a stable oxidation inert metabolite of nitric oxide (•NO) metabolism. This view is now changing as it has been shown that nitrite can be reduced back to •NO and thus one may consider a reversible interaction regarding •NO:nitrite couple. Not only physiological regulatory actions have been assigned to nitrite but also may represent, in addition to nitrate, the largest •NO reservoir in the body. This notion has obvious importance when considering that •NO is a ubiquitous regulator of cell functions, ranging from neuromodulation to the regulation of vascular tone. Particularly in the stomach, following ingestion of nitrate and food or beverages... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664818 Sun, 27 Mar 2011 23:00:00 +0100 4664818 http://www.medworm.com/index.php?rid=4664817&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443474%26dopt%3DAbstract Authors: Rosenholm JM, Sahlgren C, Lindén M The main objective in the development of nanomedicine is to obtain delivery platforms for targeted delivery of drugs or imaging agents for improved therapeutic efficacy, reduced side effects and increased diagnostic sensitivity. A (nano)material class that has been recognized for its controllable properties on many levels is ordered mesoporous inorganic materials, typically in the form of amorphous silica (SiO(2)). Characteristics for this class of materials include mesoscopic order, tunable pore dimensions in the (macro)molecular size range, a high pore volume and surface area, the possibility for selective surface functionality as well as morphology control. The robust but biodegradable ceramic matrix moreover provides shelter for incorpor... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664817 Sun, 27 Mar 2011 23:00:00 +0100 4664817 http://www.medworm.com/index.php?rid=4664816&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443475%26dopt%3DAbstract Authors: Arias JL, Clares B, Morales ME, Gallardo V, Ruiz MA It is a fact that chemotherapy agents have little specificity for cancer cells, this leading to low concentrations into the tumor interstititum and severe side effects on healthy tissues. The formulation of lipid-based nanomedicines against cancer has been hypothesized to improve drug localization into the tumor tissue and to increase the anticancer efficacy of concentional drugs, while minimizing their systemic adverse effects. In this review, special attention is devoted to the analysis of the state-of-the-art in the development of lipid-based drug carriers against cancer. Specifically, the most significant in vitro and in vivo results on the use of niosomes, liposomes, and solid lipid nanoparticles are revised. It is concl... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664816 Sun, 27 Mar 2011 23:00:00 +0100 4664816 http://www.medworm.com/index.php?rid=4664815&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443476%26dopt%3DAbstract Authors: Gou M, Wei X, Men K, Wang B, Luo F, Zhao X, Wei Y, Qian Z Nanotechnology provides researchers with new tools for cancer treatment. Biodegradable polymeric nanoparticles, as an advanced drug delivery system, have promising applications in cancer treatment. Poly(ε-caprolactone)/poly(ethylene glycol) (PCL/PEG) copolymers are biodegradable and amphiphilic, and show potential application in drug delivery. In recent years, PCL/PEG copolymeric nanoparticles, as a potential nanoplatform for anticancer agent delivery, received increasing attention. This paper reviews PCL/PEG copolymer nanoparticles for anticancer agent delivery, including overcoming water insolubility of hydrophobic drug, targeting chemotherapeutic drug to tumor, and delivering genes, vaccines, and diagnostic agents. ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664815 Sun, 27 Mar 2011 23:00:00 +0100 4664815 http://www.medworm.com/index.php?rid=4664814&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443477%26dopt%3DAbstract Authors: Alvarez-Lorenzo C, Sosnik A, Concheiro A Drug carriers tailored to fit the physicochemical properties of anticancer agents and the therapeutic peculiarities of tumor management are envisioned for improving the effectiveness/toxicity ratio of the current treatments. Polymeric micelles are attracting much attention owing to their unique beneficial features: i) core-shell structure capable to host hydrophobic drugs, raising the apparent solubility in aqueous medium; ii) size adequate for a preferential accumulation (passive targeting) within the tumor, exhibiting enhanced permeability and retention (EPR effect), and iii) unimers that modulate the activity of efflux pumps involved in multidrug resistance (MDR). This review focuses on amphiphilic poly(ethylene oxide) (PEO) and poly... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664814 Sun, 27 Mar 2011 23:00:00 +0100 4664814 http://www.medworm.com/index.php?rid=4664813&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443478%26dopt%3DAbstract Authors: Holgado MA, Alvarez-Fuentes J, Fernández-Arévalo M, Arias JL Due to a very poor specificity, many chemotherapy agents generate a low antitumor effect and important severe side effects. Poly(D,L-lactide-co-glycolide) (PLGA)-based nanomedicines are under investigation to assure a very efficient anticancer activity in chemotherapy. In this work, we analyze the major applications of this FDA-approved biodegradable polymer in the formulation of nanomedicines against cancer. Despite conventional PLGA colloids could be only used to target tumors located into the mononuclear phagocyte system (MPS), special strategies are under intensive research to enhance the accumulation of anticancer drugs into any given tumor site. These are passive targeting (through the enhanced permeability a... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664813 Sun, 27 Mar 2011 23:00:00 +0100 4664813 http://www.medworm.com/index.php?rid=4664812&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21443479%26dopt%3DAbstract Authors: Arias JL PMID: 21443479 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4664812 Sun, 27 Mar 2011 23:00:00 +0100 4664812 http://www.medworm.com/index.php?rid=4605478&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366516%26dopt%3DAbstract Authors: Herrero L, Nelson M, Bettadapura J, Gahan ME, Mahalingam S Animal models, which mimic human disease, are invaluable tools for understanding the mechanisms of disease pathogenesis and development of treatment strategies. In particular, animal models play important roles in the area of infectious arthritis. Alphaviruses, including Ross River virus (RRV), o'nyong-nyong virus, chikungunya virus (CHIKV), mayaro virus, Semliki Forest virus and sindbis virus, are globally distributed and cause transient illness characterized by fever, rash, myalgia, arthralgia and arthritis in humans. Severe forms of the disease result in chronic incapacitating arthralgia and arthritis. The mechanisms of how these viruses cause musculoskeletal disease are ill defined. In recent years, the use of a mo... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605478 Wed, 02 Mar 2011 00:00:00 +0100 4605478 http://www.medworm.com/index.php?rid=4605477&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366517%26dopt%3DAbstract Authors: Hickey AJ The guinea pig model of disease has been considered synonymous with the experimental laboratory animal since the nineteenth century. Recently we have reviewed the use of this species in models of bacterial infectious disease. The present review extends to viral diseases for which the guinea pig is less frequently considered the relevant animal model. The use of the guinea pig as a laboratory animal, aspects of immunology, viral pathogens and host-pathogen models are discussed. As a small and relatively inexpensive model for infection and immunity the guinea pig has a significant future but there are substantial requirements for development of validated quantitative analytical methods for immunological and disease biomarkers if it is to reach its potential. PMID: ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605477 Wed, 02 Mar 2011 00:00:00 +0100 4605477 http://www.medworm.com/index.php?rid=4605476&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366518%26dopt%3DAbstract Authors: Meijer AH, Spaink HP The zebrafish holds much promise as a high-throughput drug screening model for immune-related diseases, including inflammatory and infectious diseases and cancer. This is due to the excellent possibilities for in vivo imaging in combination with advanced tools for genomic and large scale mutant analysis. The context of the embryo's developing immune system makes it possible to study the contribution of different immune cell types to disease progression. Furthermore, due to the temporal separation of innate immunity from adaptive responses, zebrafish embryos and larvae are particularly useful for dissecting the innate host factors involved in pathology. Recent studies have underscored the remarkable similarity of the zebrafish and human immune systems, whic... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605476 Wed, 02 Mar 2011 00:00:00 +0100 4605476 http://www.medworm.com/index.php?rid=4605475&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366519%26dopt%3DAbstract Authors: Limmer S, Quintin J, Hetru C, Ferrandon D To gain an in-depth grasp of infectious processes one has to know the specific interactions between the virulence factors of the pathogen and the host defense mechanisms. A thorough understanding is crucial for identifying potential new drug targets and designing drugs against which the pathogens might not develop resistance easily. Model organisms are a useful tool for this endeavor, thanks to the power of their genetics. Drosophila melanogaster is widely used to study host-pathogen interactions. Its basal immune response is well understood and is briefly reviewed here. Considerations relevant to choosing an adequate infection model are discussed. This review then focuses mainly on infections with two categories of pathogens, the well... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605475 Wed, 02 Mar 2011 00:00:00 +0100 4605475 http://www.medworm.com/index.php?rid=4605474&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366520%26dopt%3DAbstract Authors: Squiban B, Kurz CL One approach to identify new drugs with antimicrobial activities is to screen large libraries of molecules directly for their capacity to block the growth of bacterial or fungal monocultures. A more relevant way to assess both a product's efficacy and its potential cytotoxicity is undoubtedly to use an in vivo infection system. Testing banks containing thousands of natural or chemically synthesized molecules with rodents is generally neither desirable nor feasible. Therefore, invertebrate model organisms could represent a valuable alternative. In this review, we present the worm C. elegans as a suitable host model for the evaluation and characterization of drug effects in a pathogenesis context. This simple organism has been of great value in many fields of ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605474 Wed, 02 Mar 2011 00:00:00 +0100 4605474 http://www.medworm.com/index.php?rid=4605473&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366521%26dopt%3DAbstract Authors: Schlaich NL In the last twenty years, the use of Arabidopsis as a model plant sped up discoveries at the molecular levels in different plant-parasite interactions. Nowadays, we know of probably hundreds of genes that are involved in the one or the other defence reaction, offering hundreds of targets for drug development. Even more interesting, identifying crucial regulatory components might allow to influence the various defence pathways as needed. Moreover, since some pathogenic strategies are conserved between animal and plant pathogens, results obtained with one system might be applicable to the other. PMID: 21366521 [PubMed - as supplied by publisher] (Source: Current Drug Targets) Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605473 Wed, 02 Mar 2011 00:00:00 +0100 4605473 http://www.medworm.com/index.php?rid=4605472&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366522%26dopt%3DAbstract Authors: Bozzaro S, Eichinger L The use of simple hosts such as Dictyostelium discoideum in the study of host pathogen interactions offers a number of advantages and has steadily increased in recent years. Infection-specific genes can often only be studied in a very limited way in man and even in the mouse model their analysis is usually expensive, time consuming and technically challenging or sometimes even impossible. In contrast, their functional analysis in D. discoideum and other simple model organisms is often easier, faster and cheaper. Because host-pathogen interactions necessarily involve two organisms, it is desirable to be able to genetically manipulate both the pathogen and its host. Particularly suited are those hosts, like D. discoideum, whose genome sequence is known and... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605472 Wed, 02 Mar 2011 00:00:00 +0100 4605472 http://www.medworm.com/index.php?rid=4605471&cid=s_37009_13_f&fid=37009&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21366523%26dopt%3DAbstract Authors: Sandström G, Saeed A, Abd H Acanthamoebae are free-living amoebae distributed worldwide. They are among the most prevalent protozoa found in the environment, and have been isolated from a wide variety of public water supplies, swimming pools, bottled water, ventilation ducts, soil, air, surgical instruments, contact lenses, dental treatment units and hospitals. Acanthamoebae feed on bacteria by phagocytosis, but some bacteria are able to survive and sometimes multiply in the host, resulting in new properties of the bacteria. The intracellular growth of bacteria has been associated with enhanced environmental survival of the bacteria, increased virulence and increased resistance against antibiotic substances. The advantage of utilising free-living amoebae is that research can ... Current Drug Targets journals http://www.medworm.com/rss/comments.php?id=4605471 Wed, 02 Mar 2011 00:00:00 +0100 4605471