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 Molecular Medicine' source. Sun, 21 Mar 2010 17:04:05 +0100 http://www.medworm.com/index.php?rid=3386104&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236050%26dopt%3DAbstract Authors: Fukami K, Yamagishi SI, Okuda S Pigment epithelium-derived factor (PEDF) is reported to play a protective role against diabetic vascular complications through its anti-oxidative properties. However, since a commercially available kit is not suitable for measurement of serum PEDF in humans, kinetics and regulation of serum PEDF are not known in these devastating disorders. Therefore, we developed a simple, specific and reliable method for measurement of serum PEDF in humans using a competitive enzyme-linked immunosorbent assay (ELISA) system. Assay linearity was shown intact with 50~300-fold dilution of urea-pretreated serum by phosphate-buffered saline. The recovery ratio of added recombinant human PEDF in serum was 94.2 +/- 1.7 %. Inter- and intra-assay coefficient of variati... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386104 Thu, 18 Mar 2010 00:00:00 +0100 3386104 http://www.medworm.com/index.php?rid=3386103&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236051%26dopt%3DAbstract Authors: Nakamura T, Yamagishi SI Septic shock is one of the leading causes of morbidity and mortality. Endotoxin plays an important role in the pathogenesis of septic shock. Lack of clinical success with anti-endotoxin or anti-cytokine therapies has shifted interest to extracorporeal therapies to reduce circulating levels of various mediators for septic shock patients. Polymyxin B -immobilized polystyrene fiber (PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption. Since 1994, PMX-F column has been available in Japan, and many investigators have reported that PMX-F treatment is safe and effective in patients with septic shock. Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF ind... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386103 Thu, 18 Mar 2010 00:00:00 +0100 3386103 http://www.medworm.com/index.php?rid=3386102&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236052%26dopt%3DAbstract Authors: Kawaguchi T, Yamagishi SI, Sata M Pigment epithelial-derived factor (PEDF) is a 50-kDa secreted glycoprotein that belongs to the noninhibitory serpin. It has an alpha/beta core serine-protease inhibitor domain, 3 major beta-sheets, and 10 alpha-helices. Although PEDF does not inhibit either serine or cysteine proteinases, PEDF exerts diverse physiological activities including anti-angiogenesis, anti-vasopermeability, anti-tumor, and neurotrophic activities. Recent studies have shown that a variety of peptides derived from PEDF possess activities similar to those of the parent molecule through interactions with the extracellular matrix, binding to PEDF receptors, nuclear localization and phosphorylation. Thus, peptides derived from PEDF have therapeutic potential for various di... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386102 Thu, 18 Mar 2010 00:00:00 +0100 3386102 http://www.medworm.com/index.php?rid=3386101&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236053%26dopt%3DAbstract Authors: Broadhead ML, Akiyama T, Choong PF, Dass CR First discovered in 1991 as a factor secreted by retinal pigment epithelial cells, the potency of pigment epithelium derived factor (PEDF) as an anti-angiogenic has led to examination of its role in active bone growth, repair and remodelling. In the musculoskeletal system, PEDF expression occurs particularly at sites of active bone formation. Expression has been noted in osteoblasts and to a lesser degree osteoclasts, the major classes of bone cells. In fact, PEDF is capable of inducing differentiation of precursor cells into mature osteoblasts. Expression and localisation are closely linked with that of vascular endothelial growth factor (VEGF). Studies at the epiphyseal plate have revealed that PEDF expression plays a key role in e... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386101 Thu, 18 Mar 2010 00:00:00 +0100 3386101 http://www.medworm.com/index.php?rid=3386100&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236054%26dopt%3DAbstract Authors: Hoshina D, Abe R, Yamagishi SI, Shimizu H Pigment epithelium-derived factor (PEDF), one of the non-inhibitory serpines, is widely expressed throughout the body. Although PEDF was initially identified as a neuronal differentiation factor, more attention has been paid to its anti-angiogenic activity. Additionally, recent researches have demonstrated that PEDF has an anti-tumor effect against several human neoplasms. This review focuses on the pathological role of PEDF in tumors, especially tumor growth and metastasis. PEDF is an endogenous anti-tumor factor and its clinical application seems quite promising, although there is much to be further investigated. PMID: 20236054 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386100 Thu, 18 Mar 2010 00:00:00 +0100 3386100 http://www.medworm.com/index.php?rid=3386099&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236055%26dopt%3DAbstract This article summarizes the pathophysiological role of PEDF in atherothrombosis and its potential therapeutic implication in CVD. We also discuss here the kinetics and regulation of PEDF in high-risk patients for atherothrombosis. PMID: 20236055 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386099 Thu, 18 Mar 2010 00:00:00 +0100 3386099 http://www.medworm.com/index.php?rid=3386098&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236056%26dopt%3DAbstract Authors: Ueda S, Yamagishi SI, Okuda S The vascular system has an important function of supplying tissues with oxygen and nutrients and clearing waste products. Therefore, the microvasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. It is well recognized that vascular endothelial growth factor (VEGF) can increase vascular permeability, thus playing important roles in variety of disorders, including diabetic retinopathy, nephrotic syndrome, brain edema, acute respiratory distress syndrome, and sepsis-associated hypotension. However, how vascular permeability is controlled by anti-permeable factors is not fully understood. We have recently found that pigment epitheliumderived factor ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386098 Thu, 18 Mar 2010 00:00:00 +0100 3386098 http://www.medworm.com/index.php?rid=3386097&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236057%26dopt%3DAbstract Authors: Tombran-Tink J Most diseases that cause blindness do so as a result of neovascularization. Angiogenesis is a complex process regulated in adult tissues by a large interacting network of molecules. In pathological conditions the checks and balances of the angiogenesis system go awry and endothelial cells of the microvasculature, proliferate, migrate, and form new but leaky vessels that invade the tissue. Hemorrhaging vessels cause edema and damage to surrounding tissues, particularly the retina. Microvascular lesions often cause severe retinal detachment and loss of vision. In this review, the value of an important endogenous anti angiogenic molecule, PEDF, is discussed in relationship to its ability to prevent retinal cell death and counter the abnormal vessel growth induced b... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386097 Thu, 18 Mar 2010 00:00:00 +0100 3386097 http://www.medworm.com/index.php?rid=3386096&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236058%26dopt%3DAbstract Authors: Yabe T, Sanagi T, Yamada H Neuronal degeneration is closely associated with cognitive, motor and visual dysfunctions. Neuroprotective strategies have been investigated with the view to being employed as potential therapy for patients with these disabilities. Pigment epithelium-derived factor (PEDF) is a 50-kDa secreted glycoprotein and a non-inhibitory member of the serine protease inhibitor (SERPIN) gene family. PEDF is detected in a broad range of human tissues, including almost all brain areas, and has been shown to have strong neuroprotective properties for various types of neurons including cerebellar granule neurons, hippocampal neurons, striatal neurons, retinal neurons and spinal cord motor neurons. These observations raise the possibility that application of PEDF may ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386096 Thu, 18 Mar 2010 00:00:00 +0100 3386096 http://www.medworm.com/index.php?rid=3336092&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196723%26dopt%3DAbstract Authors: Sikaroodi M, Galachiantz Y, Baranova A Tumor markers are the molecules that indicate the presence or prognosis of malignancy. Most often, tumor markers are produced by the cancer tissue itself. Many of them could be secreted into the body fluids in small quantities. Thus, tumor markers could be useful for early diagnostics of primary tumors and relapsed disease, as well as for determining tumor prognosis and predicting likely response of the tumor to therapy. Tumor markers are part of the clinical routine. Nevertheless, lack of sensitivity and specificity precludes routine usage of single tumor markers in population-based screening. Shortcomings of single tumor markers could be solved by parallel evaluation of multiple tumor markers that can perform with required certainty. Ge... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336092 Wed, 03 Mar 2010 00:00:00 +0100 3336092 http://www.medworm.com/index.php?rid=3336091&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196724%26dopt%3DAbstract Authors: Claus RA, Bockmeyer CL, Sossdorf M, Lösche W Purpose: This review investigates and highlights the activity of Willebrand factor (VWF) and its cleaving protease as biomarkers of the development of multiple organ dysfunction in infectious and noninfectious systemic inflammatory response syndrome. State of the Art: Ultra-large VWF (ULVWF) multimers activate platelets resulting in a prothrombotic situation. Systemic inflammation is associated with increased ULVWF plasma level and a decreased ADAMTS13 activity. The potential role of ADAMTS13 as a diagnostic and prognostic marker of disseminated intravascular coagulopathy is largely underestimated. Summary: VWF is an acute phase protein and its plasma level increases in systemic inflammation. When released from endothelial cell... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336091 Wed, 03 Mar 2010 00:00:00 +0100 3336091 http://www.medworm.com/index.php?rid=3336090&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196725%26dopt%3DAbstract In conclusion, there is an unmet medical need for identification and validation of reliable biomarkers of sepsis; the clinical information obtained from the use of novel biomarkers might contribute to transform sepsis from a physiologic syndrome to a group of distinct biochemical disorders, to improve diagnosis and therapeutic decision making for high-risk patients, to monitor the response to therapy and to ensure the enrollment of seriously characterized patients in clinical studies. PMID: 20196725 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336090 Wed, 03 Mar 2010 00:00:00 +0100 3336090 http://www.medworm.com/index.php?rid=3336089&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196726%26dopt%3DAbstract Authors: Koal T, Deigner HP The gap of the post-genomic era is increasingly being filled by the metabolomics approach, comprising a technology for analyzing small molecule endogenous metabolites (<1500 Dalton) in complex biological samples. This new analytical science has progressed within the last years particularly with regard to improvements in mass spectrometry based detection, now allowing highly robust, reproducible, selective and sensitive qualitative or quantitative analysis of endogenous metabolites. The precise and accurate quantitation of these metabolites via targeted metabolomics, now critically contributes to the quantitative analysis of endogenous compounds in biomarker discovery and validation thus to future personalized therapy. The analytical methods of choice in (... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336089 Wed, 03 Mar 2010 00:00:00 +0100 3336089 http://www.medworm.com/index.php?rid=3336088&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196727%26dopt%3DAbstract Authors: Aydiner F, Yetkin CE, Seli E A key step in assisted reproduction is the assessment of embryo viability in order to identify the embryo(s) most likely to result in pregnancy. Currently used embryo assessment systems are largely based on morphology and cleavage rate. While these systems have been pivotal in improving implantation and pregnancy rates and reducing multiple gestations, their precision is still insufficient. The limitations of strategies based on morphology have led to the investigation of adjunctive technologies for non-invasive assessment of embryo viability in assisted reproduction. These include the measurement of glucose, pyruvate, or amino acid levels in the embryo culture media, assessment of oxygen consumption by the embryo, genomic and proteomic profiling, ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336088 Wed, 03 Mar 2010 00:00:00 +0100 3336088 http://www.medworm.com/index.php?rid=3336087&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196728%26dopt%3DAbstract Authors: Bonaterra GA, Zügel S, Kinscherf R Motivated by the challenge of risk assessment in a heterogeneous population and guided by advances in our knowledge of the pathobiology of cardiovascular diseases (CVD), basic and clinical scientists have maintained substantial interest in the development and application of novel biomarkers for risk stratification of CVD. In particular, strategies to identify and combine multiple biomarkers, which may reflect diverse pathobiological contributors to the onset and complications of CVD, have been arising as an approach to improve more effectively the risk assessment and target therapy. Moreover, comparative evaluations of novel markers are necessary to estimate these candidates for integration into present and future strategies. In this rev... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336087 Wed, 03 Mar 2010 00:00:00 +0100 3336087 http://www.medworm.com/index.php?rid=3336086&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196729%26dopt%3DAbstract We describe the necessary development and validation steps including recent results of the second phase of the MAQC project (MAQC-II) and emphasise on potential pitfalls. PMID: 20196729 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336086 Wed, 03 Mar 2010 00:00:00 +0100 3336086 http://www.medworm.com/index.php?rid=3336085&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196730%26dopt%3DAbstract Authors: Estep JM, Birerdinc A, Younossi Z Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although simple or bland steatosis follows a relatively benign clinical course, NASH can potentially progress to cirrhosis (approximately 10 to 15 percent) and hepatocellular carcinoma. NAFLD occurs in an estimated 25 to 30 percent of the US general population, while NASH is reported in 2 to 3 percent of the population. Even though common explanation for the increased prevalence of NAFLD is the increased rate of obesity, the risk of developing NAFLD and NASH is not limited to overweight and obese individuals. Currently, the only way to diagnose NASH or to assess the stage of fibrosis is ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336085 Wed, 03 Mar 2010 00:00:00 +0100 3336085 http://www.medworm.com/index.php?rid=3336084&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196731%26dopt%3DAbstract Authors: Vlassov VV, Laktionov PP, Rykova EY Since the association of circulating DNA level changes with tumor growth was discovered many attempts have been made to develop the sensitive and robust blood-based tests for early tumor diagnostics. Both genomic as well as mitochondrial DNA quantification in the circulation have been extensively evaluated as a diagnostic and prognostic tool to monitor cancer therapy. Cell-free DNA bearing the same genetic and epigenetic changes as the tumor tissues were shown to be detectable in plasma / serum of cancer patients indicating the principal possibility to create the minimally invasive diagnostic tests based on tumor-specific DNA markers. Apart from circulating DNA, tumor-derived RNA in plasma / serum was found to be a promising approach for the... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336084 Wed, 03 Mar 2010 00:00:00 +0100 3336084 http://www.medworm.com/index.php?rid=3336083&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196732%26dopt%3DAbstract Authors: Luchini A, Fredolini C, Espina BH, Meani F, Reeder A, Rucker S, Petricoin EF, Liotta LA Clinically relevant biomarkers exist in blood and body fluids in extremely low concentrations, are masked by high abundance high molecular weight proteins, and often undergo degradation during collection and transport due to endogenous and exogenous proteinases. Nanoparticles composed of a Nisopropylacrylamide hydrogel core shell functionalized with internal affinity baits are a new technology that can address all of these critical analytical challenges for disease biomarker discovery and measurement. Coreshell, bait containing, nanoparticles can perform four functions in one step, in solution, in complex biologic fluids (e.g. blood or urine): a) molecular size sieving, b) complete exclusio... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336083 Wed, 03 Mar 2010 00:00:00 +0100 3336083 http://www.medworm.com/index.php?rid=3336082&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196733%26dopt%3DAbstract Authors: Shivapurkar N, Gazdar AF DNA methylation plays a critical role in the regulation of gene expression, differentiation and in the development of cancer and other diseases. Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is now firmly established as the most frequent mechanism for gene inactivation in cancers. Feasibility of using DNA methylation based biomarkers for early detection of cancer has been shown. Potential of using DNA methylation for prediction of therapeutic outcome and patient survival has also been shown. DNA originated from cancer cells has been routinely detected in clinical specimens (ex. Plasma/serum, sputum, urine etc.) from cancer patients. Presence of methylated DNA sequences in clinical specimens and potential of u... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336082 Wed, 03 Mar 2010 00:00:00 +0100 3336082 http://www.medworm.com/index.php?rid=3336081&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196734%26dopt%3DAbstract Authors: Belousov PV, Kuprash DV, Nedospasov SA, Shebzukhov YV Malignant tumors induce humoral immune response in cancer patients, although the incidence of such autoantibody responses against individual tumor-associated antigens (TAA) is rather low. To increase predictive value of TAA-recognizing autoantibodies as potential cancer biomarkers, TAAs should be combined into protein arrays. Here we review recent advances in the application of such arrays and summarize data concerning most promising antigens. We also review the methods of cloning TAA-recognizing autoantibodies, generation of human hybridomas and screening of recombinant human immunoglobulin libraries. PMID: 20196734 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336081 Wed, 03 Mar 2010 00:00:00 +0100 3336081 http://www.medworm.com/index.php?rid=3032489&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19938317%26dopt%3DAbstract Authors: Shinohara ET, Maity A Sensitivity to radiation and chemotherapy can be influenced by factors extrinsic to the cancer cell. For example, severely hypoxic cells require 2-3 times the radiation dose as do well-oxygenated cells to achieve similar cell killing. Apart from the tumor cells, neighboring cells such as endothelial cells may influence radiosensitivity. Irradiation can lead to expression of molecules that may increase radio/chemoresistance, for example vascular endothelial growth factor (VEGF), a secreted protein that regulates angiogenesis, or hypoxia inducible factor-1 alpha (HIF-1 alpha), a master transcription factor that regulates gene expression in hypoxia. Hence, response to cytotoxic therapy may be improved by modulating the tumor microenvironment (TME). Several a... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3032489 Fri, 27 Nov 2009 15:02:06 +0100 3032489 http://www.medworm.com/index.php?rid=3015731&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925404%26dopt%3DAbstract Authors: Cao Y PMID: 19925404 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015731 Sun, 01 Nov 2009 00:00:00 +0100 3015731 http://www.medworm.com/index.php?rid=3015730&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925405%26dopt%3DAbstract Authors: Arbiser JL, Bonner MY, Berrios RL Angiogenesis is a major factor in the development of benign, inflammatory, and malignant processes of the skin. Endothelial cells are the effector cells of angiogenesis, and understanding their response to growth factors and inhibitors is critical to understanding the pathogenesis and treatment of skin disease. Hemangiomas, benign tumors of endothelial cells, represent the most common tumor of childhood. In our previous studies, we have found that tumor vasculature in human solid tumors expresses similarities in signaling to that of hemangiomas, making the knowledge of signaling in hemangiomas widely applicable. These similarities include expression of reactive oxygen, NFkB and akt in tumor vasculature. Furthermore, we have studied malignant v... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015730 Sun, 01 Nov 2009 00:00:00 +0100 3015730 http://www.medworm.com/index.php?rid=3015729&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925406%26dopt%3DAbstract Authors: Moserle L, Amadori A, Indraccolo S Angiogenesis plays an established role in the growth promotion of dormant micrometastasis, because blood vessels deliver oxygen and nutrients into the tumor microenvironment. A discrete event termed "the angiogenic switch" has been recognized as key in promoting the transition towards a clinically aggressive tumor. This concept generally describes a permanent change in the angiogenic capacity of the tumor sustained by genetic events occurring in cancer cells. Recent evidence, however, indicates that a transient angiogenic switch delivered by components of the tumor microenvironment can also convey tumorigenic properties to tumor cells. Why is the angiogenic switch so fundamental in the promotion of tumor growth? In addition to the recognized ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015729 Sun, 01 Nov 2009 00:00:00 +0100 3015729 http://www.medworm.com/index.php?rid=3015728&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925407%26dopt%3DAbstract Authors: Kawai Y, Ohhashi T We have reviewed physiological significance of rhythmical spontaneous contractions of collecting lymphatics, which play an important role in lymph transport and seem to regulate lymph formation through changing the pacemaker sites of the rhythmic contractions and conractile patterns of lymphangions. Next, we reported experimental findings that the wall effective permeability of hydrophilic substances labelled with fluorescent dyes was evaluated in an isolated cannulated rat single lymphatic using a microscope system. With the experimental evidence, we have discussed physiological significance and crucial roles of the enrichment of albumin in lymph through the wall of small lymphatics in regulation of innate immunity. In addition, we have described the mode o... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015728 Sun, 01 Nov 2009 00:00:00 +0100 3015728 http://www.medworm.com/index.php?rid=3015727&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925408%26dopt%3DAbstract Authors: Ali AM, Toi M, Ueno T Anti-angiogenic therapy has fundamentally landmarked the clinical new era of anti-cancer therapy. It was demonstrated that the blockade of vascular endothelial growth factor results in regression of the disease and prolongation of survival. In contrast, it was clarified that the differential sensitivity of the therapeutic impact exists. Many thought-provoking questions have been raised in this field. Herein, we focus on the clinical data and attempt to summarize some clinical trials of anti-angiogenic treatment, highlighting the sparkling articles, the differential sensitivities to these agents beyond progression continuation, and how to individualize treatment according to validated biomarkers. PMID: 19925408 [PubMed - as supplied by publisher] (Sour... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015727 Sun, 01 Nov 2009 00:00:00 +0100 3015727 http://www.medworm.com/index.php?rid=3015726&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925409%26dopt%3DAbstract Authors: Cao Y The idea of delivery of proangiogenic factors to the ischemic region of myocardium or skeletal muscles was proposed more than 30 years ago and abundant preclinical data validate this concept. However, clinical experience with this approach has generally produced unfulfilled promises. Although reestablishment of functional collateral networks for improvement of blood perfusion in ischemic tissues is an undisputed concept for therapeutic intervention, the molecular mechanism underlying collaterogenesis under tissue hypoxia remains poorly understood. Critical issues including the therapeutic efficacy of monotherapy vs. combination with arteriogenic therapy, drug release, optimal dose, and time scale of delivery remain to be resolved. The aim of this review is to discuss mol... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015726 Sun, 01 Nov 2009 00:00:00 +0100 3015726 http://www.medworm.com/index.php?rid=3015725&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925410%26dopt%3DAbstract This article will summarize the emergence of vascular endothelial growth factor (VEGF) as a validated treatment target for and current understanding of the pathophysiology of ocular neovascularization. The article will then cover promising future strategies and therapeutic targets that are aimed at enhancing the efficacy and/or duration of effect of these clinically available anti-VEGF strategies. In particular molecules that target, VEGF, PDGF, Complement, Inflammation and Integrins that are entering or are currently in clinical trials will be reviewed. PMID: 19925410 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015725 Sun, 01 Nov 2009 00:00:00 +0100 3015725 http://www.medworm.com/index.php?rid=3015724&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925411%26dopt%3DAbstract Authors: Jensen LD, Cao R, Cao Y Angiogenesis research has become one of the most important areas in biomedical research. At the time of writing this review, there were approximately 3536 articles published in the year of 2008 alone on the topic of angiogenesis. The fast expansion of this research field demands development of rigorous, reliable, stable, convenient, and clinically relevant assay systems for disease diagnosis, prognosis, therapeutic evaluation, drug discovery, and mechanistic studies at the molecular level. Here, we discuss several commonly used in vivo angiogenesis models by systematically analyzing and pointing out pitfalls of each assay. Owing to existence of numerous assays and the limitation of text, it is impossible to discuss all these assays in this article. Here... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015724 Sun, 01 Nov 2009 00:00:00 +0100 3015724 http://www.medworm.com/index.php?rid=2797405&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747105%26dopt%3DAbstract Authors: Strand DW, Franco OE, Basanta D, Anderson AR, Hayward SW From the morphogenetic movements of the three germ layers during development to the reactive stromal microenvironment in cancer, tissue interactions are vital to maintaining healthy organ morphologic architecture and function. The stromal compartment is thought to be complicit in tumor progression and, as such, represents an opportune target for disease therapies. However, recent developments in our understanding of the diversity of the stromal compartment and the lack of appropriate models to study its relevance in human disease have limited our further understanding of the role of tissue interactions in tumor progression. The failure any model to fully recapitulate the complexities of systemic biology continue to creat... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797405 Sat, 12 Sep 2009 23:00:00 +0100 2797405 http://www.medworm.com/index.php?rid=2797404&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747106%26dopt%3DAbstract Authors: Sohns W, van Veen TA, van der Heyden MA Cardiovascular disease is the leading cause of death in the western world. The major contributor of all cardiovascular deaths is myocardial infarction, which often progresses into end-stage heart failure. The loss of cardiomyocytes is a key problem in the development of cardiovascular disease. Two main processes mediate cardiomyocyte loss: necrosis and apoptosis. In contrast to necrosis, apoptosis is a well regulated process essential in normal development and tissue homeostasis. Tight regulation of this process is crucial, especially in post mitotic cells lacking regenerative capacity, like cardiomyocytes. The ubiquitinproteasome system, accounting for 80 to 90% of intracellular protein degradation, appears to be involved in the regulat... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797404 Sat, 12 Sep 2009 23:00:00 +0100 2797404 http://www.medworm.com/index.php?rid=2797403&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747107%26dopt%3DAbstract Authors: Fierabracci A The incidence of autoimmune disorders is increasing worldwide. Several theories have been proposed to explain how the breakdown in the balance between autoregulatory immune pathways and pathogenic autoreactivity generate autoimmunity. On the basis of a large body of epidemiological, clinical and experimental evidence, it has been suggested that an unfortunate interplay of genetic susceptibility and environmental factors must play an important role in generating the abnormal autoimmune response. Although genetic factors have been well dissected, the environmental agents, that may be causative of disease are still under investigation. Their discovery is obviously relevant because enable us to device preventive and therapeutic strategies in trying to halt the progre... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797403 Sat, 12 Sep 2009 23:00:00 +0100 2797403 http://www.medworm.com/index.php?rid=2797402&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747108%26dopt%3DAbstract Authors: Torrentino-Madamet M, Desplans J, Travaillé C, James Y, Parzy D The Plasmodium falciparum mitochondrion is an organelle that presents structural and physiological characteristics different from mitochondria in other eukaryotes. Moreover, there are substantial differences in the properties of asexual and sexual mitochondria. One of the reasons is the adaptation of the parasite to different environments, in particular the great differences in oxygen tension between the host and the mosquito. In this review, we present a synthesis of the recent data on the ultrastructure, the genome and the physiology of the mitochondrion. We try to clarify the mitochondrial role in the intraerythrocytic environment and particularly focus on mitochondrial metabolic pathways that relate to ox... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797402 Sat, 12 Sep 2009 23:00:00 +0100 2797402 http://www.medworm.com/index.php?rid=2797401&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747109%26dopt%3DAbstract Authors: Trivedi R, Mithal A, Chattopadhyay N Anabolic therapy for osteoporosis has become the most desirable therapeutic option for menopausal osteoporosis. The anabolic agents currently in clinical use are reviewed. Teriparatide (recombinant human 1-34 parathyroid hormone) is used to treat women with menopausal osteoporosis and men at high risk for fractures. Despite PTH's clinical use, the mechanism underlying its anabolic action requires greater elucidation. Proteol (strontium ranelate) acts by inhibiting bone resorption and presumably promoting bone formation. Though clinical trials have shown that strontium ranelate reduces the frequency of both vertebral and non-vertebral fractures, its molecular target remains controversial. Lately, with the discontinuation of estrogen replacem... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797401 Sat, 12 Sep 2009 23:00:00 +0100 2797401 http://www.medworm.com/index.php?rid=2797400&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747110%26dopt%3DAbstract Authors: Marin JJ, Romero MR, Martinez-Becerra P, Herraez E, Briz O Primary malignancies of the liver and the gastrointestinal tract constitute one of the main health problems worldwide. Together, these types of tumour are the first cause of death due to cancer, followed by lung and breast cancer respectively. One important limitation in the treatment of these tumours is that, with a few exceptions, they exhibit marked resistance to currently available drugs. Moreover, most of them develop chemoresistance during treatment. The mechanisms responsible for drug refractoriness in gastrointestinal tumours include a reduction in drug uptake; enhanced drug export; intracellular inactivation of the effective agent; alteration of the molecular target; an increase in the activity of the target r... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797400 Sat, 12 Sep 2009 23:00:00 +0100 2797400 http://www.medworm.com/index.php?rid=2797399&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747111%26dopt%3DAbstract Authors: Saran A Medulloblastoma is a cerebellar tumor affecting children and young adults, and accounts for approximately one fifth of all pediatric brain tumors. Despite multimodal therapy that includes surgery, radiotherapy and chemotherapy, recurrence is frequent and overall mortality rate remains relatively high. Moreover, radiation therapy results in severe effects on intellect, and younger age of treatment correlates with larger deficits. Improvements in therapy of this childhood tumor will focus increasingly on the clarification of the exact cellular origin and the genetic mechanisms contributing to tumor formation, and on new targeted therapeutic options. Aberrant activation of the Hedgehog (Hh) and Wnt developmental pathways is associated with medulloblastoma, but deregulatio... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797399 Sat, 12 Sep 2009 23:00:00 +0100 2797399 http://www.medworm.com/index.php?rid=2797398&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747112%26dopt%3DAbstract Authors: Shevde LA, Das S, Clark DW, Samant RS Osteopontin (OPN) is a matricellular protein that is produced by multiple tissues in our body and is most abundant in bone. It is also produced by cancer cells and plays a determinative role in the growth, progression and metastasis of cancer. Clinically, OPN has been reported to be upregulated in tumor cells per se; this is also reflected by increased levels of OPN in the circulation. Thus, increased OPN levels the plasma are an effect of tumor growth and progression. Functionally, high OPN levels are determinative of higher incidence of bone metastases in mouse models and are clinically correlated with metastatic bone disease and bone resorption in advanced breast cancer patients. Several research efforts have been made to therapeuticall... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797398 Sat, 12 Sep 2009 23:00:00 +0100 2797398 http://www.medworm.com/index.php?rid=2797397&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747113%26dopt%3DAbstract Authors: Smith MQ, Staley CA, Kooby DA, Styblo T, Wood WC, Yang L Combining groundbreaking research and developments in cancer biomarkers, nanotechnology and molecular targeted medicine, a new realm of therapy is possible: personalized and predictive medicine. Developing a method to detect the overexpression of several tumor marker genes simultaneously, knowing that a single cell generally expresses more than one altered gene, should have a high predictive value for identifying cancer cells amidst the normal cellular background. Theoretically, a cancer's unique molecular profile can be used to predict its invasive and metastatic potential, its ability to evade immune surveillance, and its potential response to treatment. Fluorescent probes have been developed to detect the levels of ex... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797397 Sat, 12 Sep 2009 23:00:00 +0100 2797397 http://www.medworm.com/index.php?rid=2797396&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747114%26dopt%3DAbstract Authors: McCombe PA, Greer JM, Mackay IR We briefly survey the concept of autoimmunity and nominate the range of autoimmune diseases that include multisystemic and organ-specific disorders, and cite prevalences of autoimmune diseases in males and females, in humans and in experimental animals. Most human autoimmune diseases such as systemic lupus erythematosus (SLE), multiple sclerosis (MS) and autoimmune thyroid disease, have an increased incidence and prevalence in females, but a few others such as autoimmune diabetes, the Guillain Barré syndrome (GBS) and psoriasis are increased in males. Animal models of autoimmunity show an equivalent sexual dimorphism. The possible reasons for the differing incidence and prevalence of autoimmune diseases in females and males engage our atten... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797396 Sat, 12 Sep 2009 23:00:00 +0100 2797396 http://www.medworm.com/index.php?rid=2797395&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747115%26dopt%3DAbstract Authors: Puri M, Kaur I, Kanwar RK, Gupta RC, Chauhan A, Kanwar JR This review describes the nature and applications of ribosome inactivating proteins (RIPs) from Momordica charantia (bitter melon). RIPs from the plant kingdom have received much attention in biomedical research because they target conserved host protein synthesis machinery and show specificity towards human and animal cell targets. Recent studies aimed at unravelling the enzymatic activities of the M charantia RIPs provide a structural basis for their activities. It has been reported that RIPs are member of the single chain ribosome inactivating protein (SCRIP) family which act irreversibly on ribosome by removing adenine residue from eukaryotic ribosomal RNA. Various activities of RIPs include anti-tumor, broad anti-v... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797395 Sat, 12 Sep 2009 23:00:00 +0100 2797395 http://www.medworm.com/index.php?rid=2797394&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747116%26dopt%3DAbstract Authors: Mancuso M, Orsucci D, Coppedè F, Nesti C, Choub A, Siciliano G Mitochondrial diseases (MD) are disorders caused by impairment of the mitochondrial electron transport chain (ETC). Phenotypes are polymorphous and may range from pure myopathy to multisystemic disorders. The genetic defect can be located on mitochondrial or nuclear DNA. The ETC is needed for oxidative phosphorylation (which provides the cell with the most efficient energetic outcome in terms of ATP production), and consists of five multimeric protein complexes located in the inner mitochondrial membrane. The ETC also requires cytochrome c and a small electron carrier, coenzyme Q10. One of the pathogenic mechanisms of ETC disorders is excessive accumulation of reactive oxygen species (ROS). Mitochondrial dysfu... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797394 Sat, 12 Sep 2009 23:00:00 +0100 2797394 http://www.medworm.com/index.php?rid=2797393&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747117%26dopt%3DAbstract Authors: Zeidan YH, Hannun YA One of the most intriguing enzymes of sphingolipid biology is acid sphingomyelinase (ASMase). In a phospholipase C reaction, ASMase catalyzes the cleavage of the phosphocholine head group of sphingomyelin to generate ceramide. Cumulative efforts of various laboratories over the past 40 years have placed ASMase and its product ceramide at the forefront of lipid research. Activation of the ASMase/ceramide pathway is a shared response to an ever growing list of receptor and non receptor mediated forms of cellular stress including: death ligands (TNFalpha, TRAIL, Fas ligand), cytokines (IL-1, IFNgamma), radiation, pathogenic infections, cytotoxic agents and others. The strategic role of ASMase in lipid metabolism and cellular stress response has sparked intere... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797393 Sat, 12 Sep 2009 23:00:00 +0100 2797393 http://www.medworm.com/index.php?rid=2797392&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19747118%26dopt%3DAbstract Authors: Siatskas C, Bernard CC Multiple sclerosis is a disease of the central nervous system that predmoninantly affects young adults. The pathogenic mechanisms are complex, however numerous studies indicate that the disease is initiated by an autoimmune attack on protein targets present in the central nervous system. Given that a dysfunctional immune system perpetuates the pathophysiological mechanisms that characterize this inflammatory disorder, several therapeutic approaches that target immune cells or their secreted mediators have been generated and are currently used clinically. Although these strategies have been partially beneficial to a proportion of patients, current therapies are not particularly effective at preventing disease progression. As such there is a large and unme... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2797392 Sat, 12 Sep 2009 23:00:00 +0100 2797392 http://www.medworm.com/index.php?rid=2720381&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689292%26dopt%3DAbstract Authors: Joshi BH, Puri RK PMID: 19689292 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720381 Fri, 31 Jul 2009 23:00:00 +0100 2720381 http://www.medworm.com/index.php?rid=2720380&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689293%26dopt%3DAbstract Authors: Terabe M, Berzofsky JA NKT cells are true T cells that serve as a bridge between the innate and adaptive immune system, acting as first responders. They recognize lipid antigens rather than peptides, and respond to these when presented by a non-classical class I MHC molecule, CD1d. NKT cells can play a pathogenic role in asthma or a protective role against several autoimmune diseases, in part based on their cytokine profile. In cancer, they can play opposite roles, contributing to anti-tumor immunity or suppressing it. The protective NKT cells were found to be primarily type I NKT cells defined by use of a semi-invariant T cell receptor involving Valpha14Jalpha18 in mice and Valpha24Jalpha18 in humans and responding to alpha-galactosylceramide, and the most protective were amo... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720380 Fri, 31 Jul 2009 23:00:00 +0100 2720380 http://www.medworm.com/index.php?rid=2720379&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689294%26dopt%3DAbstract Authors: Petrausch U, Poehlein CH, Jensen SM, Twitty C, Thompson JA, Assmann I, Puri S, Lacelle MG, Moudgil T, Maston L, Friedman K, Church S, Cardenas E, Haley DP, Walker EB, Akporiaye E, Weinberg AD, Rosenheim S, Crocenzi TS, Hu HM, Curti BD, Urba WJ, Fox BA Since multiple lines of experimental and clinical data clearly identified regulatory T cells as an integral part of the immune response, these cells have become a major focus of investigation in tumor immunology. Regulatory T cells are in place to dampen ongoing immune responses and to prevent autoimmunity, but they also have profound effects in blocking therapeutic anti-tumor activity. Therefore regulatory T cells are seen as a major hurdle that must be overcome in order for cancer immunotherapy to reach its therapeutic potentia... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720379 Fri, 31 Jul 2009 23:00:00 +0100 2720379 http://www.medworm.com/index.php?rid=2720378&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689295%26dopt%3DAbstract Authors: Voskens CJ, Strome SE, Sewell DA In the vast majority of studies conducted to date, activation of cancer-specific T cell immunity through peptide-based immunization has failed to induce objective tumor regression. This failure is particularly troublesome given that these vaccines often stimulate T cell responses. In this review, we attempt to understand the relative failure of peptide cancer vaccines to achieve clinically meaningful responses. In the first part of the review, we discuss specific hurdles to successful application of synthetic peptide-based vaccines including patient variability and epitope selection. In the second part of this review, we summarize the importance of CD4(+) T cell help in peptide-based vaccine strategies and offer a potential strategy to improve ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720378 Fri, 31 Jul 2009 23:00:00 +0100 2720378 http://www.medworm.com/index.php?rid=2720377&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689296%26dopt%3DAbstract Authors: Varney ML, Singh S, Backora M, Chen Z, Singh RK Tumor-induced immunosuppression is a fundamental problem in cancer immunotherapy and can occur by a variety of cellular and molecular mechanisms, affecting all arms of the immune system. Tumor-produced or elicited factors have been shown to inhibit antigen-specific immune effector function as well as impairment of the development, recruitment and maturation of dendritic cells (DCs) and T cells. A better understanding of the cross-talk between tumors and tumor-associated DCs and T cells is necessary to develop novel approaches for cancer immunotherapy. The recruitment of DCs to tumors, antigen processing and presentation, and migration of antigen-loaded DCs to secondary lymphoid organs are perturbed in tumor-bearing hosts. The abi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720377 Fri, 31 Jul 2009 23:00:00 +0100 2720377 http://www.medworm.com/index.php?rid=2720376&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689297%26dopt%3DAbstract Authors: Johnson B, Osada T, Clay T, Lyerly H, Morse M Vascular endothelial growth factor (VEGF), known as a primary mediator of tumor-induced angiogenesis, is now understood to have a role in tumor-associated immunosuppression. Initially, VEGF was identified to alter the growth and maturation of the immature granulocyte-macrophage progenitors, and more recently it has been noted that it prevents dendritic cell (DC) precursors from developing into mature, antigen-presenting DC. VEGF is associated with recruitment of macrophages to the tumor stroma and VEGF inhibition of myeloid progenitor maturation is associated with the development tumor associated macrophages (TAM) which possess immunosuppressive capacity as well. Therapies intended to inhibit VEGF or VEGF receptors have demonstrate... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720376 Fri, 31 Jul 2009 23:00:00 +0100 2720376 http://www.medworm.com/index.php?rid=2720375&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689298%26dopt%3DAbstract Authors: Srivastava RM, Khar A DCs are recognized as the pivotal group of lymphocytes, which induce a variety of antitumor immune responses. Enduring professional antigen presenting cells, DCs eminence to induce adaptive antitumor immune response was exploited, which showed promising results in DCs-based phased clinical studies. Nevertheless, DCs also influence other immune cells to induce multiple arms of immune system to cure cancer. Recently, direct cytotoxic capacity of DCs has been demonstrated in several studies. Altogether DCs hold a strong link between innate and adaptive immune responses. DCs are known to kill tumor cells, phagocytose immunogenic substrates and present a wide variety of antigens to prime T cells to induce concerted antitumor responses. These functional aspects... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720375 Fri, 31 Jul 2009 23:00:00 +0100 2720375 http://www.medworm.com/index.php?rid=2720374&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689299%26dopt%3DAbstract Authors: Murthy V, Moiyadi A, Sawant R, Sarin R Since the first reported clinical trial of Dendritic Cell Vaccine (DCV) in cancer in the mid nineties, few hundred clinical trials have been initiated and it was projected that over 3000 patients would be treated in DCV clinical trials by 2008. Despite extensive data to establish its safety, DCV remains an investigational approach, highlighting the need to undertake more meaningful proof of principle studies and more importantly, well designed and well conducted large efficacy trials. As opposed to phase I and II trials of new chemical entities where pharmacokinetics, maximum tolerated dose, toxicity profile and dose response effects are the primary concerns, for DCV the pertinent issues are quite different. Based on a critical appraisal ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720374 Fri, 31 Jul 2009 23:00:00 +0100 2720374 http://www.medworm.com/index.php?rid=2720373&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689300%26dopt%3DAbstract Authors: Puri S, Puri S, Mahapatra AK, Hussain E, Sarkar C, Sinha S, Joshi BH Despite advances in biomedical sciences, the prognosis of patients with brain tumors remains poor. Effective treatment is lacking for these central nervous system (CNS) cancers. Targeted immunotoxins are a new class of therapeutic approaches that have emerged for the treatment of human cancers. In this approach, tumor antigen or cell surface receptor is targeted by a chimeric fusion protein consisting of an antibody or a ligand and a suicidal gene or toxin to kill tumor cells. In that regard, receptors for interleukin (IL)-4 (IL-4R) have been identified to be overexpressed on a variety of human CNS tumor cell lines and tissue samples including meningioma. In various studies, high grade brain tumor specimens a... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720373 Fri, 31 Jul 2009 23:00:00 +0100 2720373 http://www.medworm.com/index.php?rid=2720372&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689301%26dopt%3DAbstract Authors: Strober W, Kitani A, Fichtner-Feigl S, Fuss IJ The IL-13Ralpha2 receptor is a high affinity receptor for IL-13 that is used only by IL-13 and is quite distinct from the well known IL-13Ralpha1 receptor that IL-13 shares with IL-4. It was widely considered to be a secreted receptor that is devoid of signaling activity and functional only as a decoy receptor that retarded signaling via IL-13Ralpha1. In recent studies, however, it was shown to be capable of robust signaling that results in production of TGF-beta1 and through the latter cytokine, the induction of fibrosis occuring in various experimental inflammatory states. Thus, in initial studies, IL-13 signaling via IL-13Ralpha2 was shown to play an important role in the fibrosis developing in both oxazolone colitis and bleomy... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720372 Fri, 31 Jul 2009 23:00:00 +0100 2720372 http://www.medworm.com/index.php?rid=2720371&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689302%26dopt%3DAbstract Authors: Li X, Fasano R, Wang E, Marincola FM Several associations have been described between the frequency of human leukocyte antigen (HLA) class I genes in certain populations and the risk of developing nasopharyngeal carcinoma (NPC). Associations between ethnic background and geographic distribution, and relative disease incidence have been reported. Populations in geographical areas at higher risk of developing NPC display HLA distribution patterns different and sometimes opposite from areas of low incidence, whereas populations in areas with intermediate incidence display a totally independent pattern. Two main reasons may explain this association between HLA phenotype distribution and the risk of developing NPC in various populations. First, given the fact that expression of Eps... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720371 Fri, 31 Jul 2009 23:00:00 +0100 2720371 http://www.medworm.com/index.php?rid=2720370&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19689303%26dopt%3DAbstract Authors: Samara RN, Khleif SN HPV has been linked to many human malignancies and, as such, represents a major public health crisis. The understanding of HPV biology, however, has helped tremendously in developing prophylactic vaccines, which should help in decreasing mortality due to HPV infections. Understanding HPV biology has allowed researchers to use the virus as a model for the development of not only prophylactic vaccines, but also therapeutic ones. The advantages of HPV as a model stem from the limited number of proteins encoded by the HPV genome that can be targeted by vaccines, and also from the restricted expression of certain viral proteins during different stages of infection. In this review, we discuss how HPV can be used as a model for the development of both prophylacti... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2720370 Fri, 31 Jul 2009 23:00:00 +0100 2720370 http://www.medworm.com/index.php?rid=2611458&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601804%26dopt%3DAbstract Authors: Lindemans C, Kimpen J, Bont L Virus-induced respiratory disease accounts for the majority of hospitalizations of young children during the winter months. The major viral causes of lower respiratory tract disease in infants and children are respiratory syncytial virus (RSV), rhinovirus, metapneumovirus (hMPV), parainfluenza virus 3 (PIV-3), and influenza. The primary antiviral mechanism involves the activation of cytotoxic T cells and the clearance of virus-infected epithelial cells, and Toll-like receptors that recognize microbial molecular patterns are thought to initiate and orchestrate the immune response. Here, we review the role of Toll-like receptors in modulating the immune response to respiratory viral disease, including the role of maturation of the TLR system in earl... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611458 Tue, 30 Jun 2009 23:00:00 +0100 2611458 http://www.medworm.com/index.php?rid=2611457&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601805%26dopt%3DAbstract Authors: Yanamadala V, Negoro H, Denker BM Apoptosis, a programmed cell death mechanism, is a fundamental process during the normal development and somatic maintenance of all multicellular organisms and thus is highly conserved and tightly regulated through numerous signaling pathways. Apoptosis is of particular clinical importance as its dysregulation contributes significantly to numerous human diseases, primarily through changes in the expression and activation of key apoptotic regulators. Each of the four families of heterotrimeric G proteins (G(s), G(i/o), G(q/11) and G(12/13)) has been implicated in numerous cellular signaling processes, including proliferation, transformation, migration, differentiation, and apoptosis. Heterotrimeric G protein signaling is an important but not wi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611457 Tue, 30 Jun 2009 23:00:00 +0100 2611457 http://www.medworm.com/index.php?rid=2611456&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601806%26dopt%3DAbstract Authors: Hilgert N, Smith RJ, Van Camp G Hearing loss is the most common sensory disorder, present in 1 of every 500 newborns. To date, 46 genes have been identified that cause nonsyndromic hearing loss, making it an extremely heterogeneous trait. This review provides a comprehensive overview of the inner ear function and expression pattern of these genes. In general, they are involved in hair bundle morphogenesis, form constituents of the extracellular matrix, play a role in cochlear ion homeostasis or serve as transcription factors. During the past few years, our knowledge of genes involved in hair bundle morphogenesis has increased substantially. We give an up-to-date overview of both the nonsyndromic and Usher syndrome genes involved in this process, highlighting proteins that inte... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611456 Tue, 30 Jun 2009 23:00:00 +0100 2611456 http://www.medworm.com/index.php?rid=2611455&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601807%26dopt%3DAbstract Authors: Janakiram NB, Rao CV Recently, lipoxins (LXs) and resolvins (Rvs) have become the topic of intense interest because of expanding views of their action, particularly in chronic disorders where unresolved inflammation is a key factor leading to colon carcinogenesis. Rvs are biosynthesized from omega-3 fatty acids eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) via cyclooxygenase-2/lipoxygenase (COX-2/LOX) pathways; Rvs are shown to dramatically reduce dermal inflammation, peritonitis, dendritic cell migration, and interleukin production. This explains that dietary supplementation of omega-3 fatty acids generates potent local endogenous mediators that control inflammation. LXs are biosynthesized from COX-2/LOX pathways. Metabolites of 15-LOX-1 and 2 are anti-tumorigenic... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611455 Tue, 30 Jun 2009 23:00:00 +0100 2611455 http://www.medworm.com/index.php?rid=2611454&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601808%26dopt%3DAbstract Authors: de la Iglesia N, Puram SV, Bonni A Malignant gliomas are the most common primary brain tumors. Despite efforts to find effective treatments, these tumors remain incurable. The failure of malignant gliomas to respond to conventional cancer therapies may reflect the unique biology of these tumors, underscoring the need for new approaches in their investigation. Recently, progress has been made in characterization of the molecular pathogenesis of glioblastoma using a developmental neurobiological perspective, by exploring the role of signaling pathways that control the differentiation of neural stem cells along the glial lineage. The transcription factor STAT3, which has an established function in neural stem cell and astrocyte development, has been found to play dual tumor suppr... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611454 Tue, 30 Jun 2009 23:00:00 +0100 2611454 http://www.medworm.com/index.php?rid=2611453&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601809%26dopt%3DAbstract Authors: Holmøy T, Harbo H, Vartdal F, Spurkland A Although the aetiology of MS remains elusive, several genetic approaches have provided clues to the underlying molecular pathogensis. In addition to the well known association to HLA class II alleles, weak but highly significant association to the interleukin-7 receptor and interleukin-2 receptor genes has recently been established. A series of other promising candidate genes identified in large genome screens are under evaluation. The genetic predisposition to MS is so far shown to be mediated by common polymorphisms in genes encoding molecules involved in T cell activation and homeostasis, but only a small proportion of the potential susceptibility genes have yet been identified. Analyses of transcribed immune receptor genes hav... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611453 Tue, 30 Jun 2009 23:00:00 +0100 2611453 http://www.medworm.com/index.php?rid=2611452&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601810%26dopt%3DAbstract Authors: Renner O, Carnero A Deregulation of the PI3K pathway is common in human cancer. The basic players in this pathway are the kinases PI3K and AKT and the phosphatase PTEN. This review will summarize some of the key animal models that have helped us understand this signaling network and its contribution to tumorigenesis. Recently, great advances in cancer mouse models have been achieved [1]. While germline deletion often affects the development of the organism and can result in embryonic lethality, conditional knockout mouse models offer the possibility of inducing gene deletion in the adult organism. Another useful strategy involves the inactivation of enzyme function by introducing small mutations in the gene sequence, thereby maintaining the protein in an inactivated state and ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611452 Tue, 30 Jun 2009 23:00:00 +0100 2611452 http://www.medworm.com/index.php?rid=2611451&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601811%26dopt%3DAbstract Authors: Devarajan E, Huang S Metastasis is a major cause of morbidity and mortality in patients with cancer. The molecular mechanisms that control metastasis are related to alterations in various oncogenes, tumor suppressor genes, metastasis suppressor genes, and growth factors and their receptors. These abnormalities affect the downstream signal transduction pathways involved in the control of cell growth and other malignant properties. One of the most recognized signal transduction pathways involves the signal transducer and activator of transcription 3 (STAT3) protein. STAT3, known to be activated by numerous cytokines, growth factors, and oncogenic proteins, is constitutively phosphorylated in several clinical cancer specimens and cell lines, leading to cell transformation and tum... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611451 Tue, 30 Jun 2009 23:00:00 +0100 2611451 http://www.medworm.com/index.php?rid=2611450&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601812%26dopt%3DAbstract Authors: Larizza L, Gervasini C, Natacci F, Riva P Neurofibromatosis type 1 (NF1) is a developmental and cancer predisposing syndrome resulting from haploinsufficiency or alteration in neurofibromin, a multifunctional protein that acts in various signaling pathways affecting morphogenetic processes and cell proliferation. Neurofibromin deficiency deregulates Ras/Raf/MEK/ERK and Ras/PI3K/AKT/PKB/mTOR signaling networks and intersected pathways including the cAMP-dependent protein kinase A (PKA) and the Rho-cofillin which acts on actin cytoskeleton reorganization, cell motility and adhesion. As the neurofibromin-mediated pathways are associated with biological effects depending on the cell lineage, deregulation induced by NF1 mutation clearly has cell type-specific effects. This review s... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611450 Tue, 30 Jun 2009 23:00:00 +0100 2611450 http://www.medworm.com/index.php?rid=2611449&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19601813%26dopt%3DAbstract This article serves as an overview of the pre-clinical data and clinical trial data on HSP90 inhibitor 17-AAG in different malignancies. 17-AAG has shown significant anti-tumor activity against a spectrum of cancers in the pre-clinical studies and information from various phases of clinical trials is growing. The potential indication of 17-AGG for the treatment of refractory multiple myeloma now awaits for the results of two phase III studies. More work needs to be done before the broader oncological use of HSP90 inhibitors in the area of defining HSP90 client proteins, understanding the mechanism of HSP90 actions, identifying reliable surrogate markers for HSP90 inhibition in vivo and optimizing drug delivery and efficacy. PMID: 19601813 [PubMed - in process] (Source: Current Molecula... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2611449 Tue, 30 Jun 2009 23:00:00 +0100 2611449 http://www.medworm.com/index.php?rid=2548468&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519396%26dopt%3DAbstract Authors: Glazer PM, Bindra RS PMID: 19519396 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548468 Thu, 30 Apr 2009 23:00:00 +0100 2548468 http://www.medworm.com/index.php?rid=2548467&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519397%26dopt%3DAbstract Authors: Chan N, Koch CJ, Bristow RG Hypoxia is a common characteristic of many solid tumors and is associated with poor prognosis. Cells with low oxygen levels can have altered sensitivity to radiotherapy and chemotherapy secondary to changes in the incidence of DNA single- and double-strand breaks (DNA-ssb, DNA-dsb), DNA base damage, DNA-DNA cross-links and DNA-protein cross-links. Recent evidence also supports that cells exposed to chronic hypoxia have a decreased capacity of DNA-dsb repair. This review will examine the influence of short-term and prolonged hypoxia on the two major pathways of DNA-dsb repair: homologous recombination (HR) and non-homologous end-joining (NHEJ). Novel treatment strategies designed to exploit the hypoxic tumor microenvironment are also discussed. Modif... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548467 Thu, 30 Apr 2009 23:00:00 +0100 2548467 http://www.medworm.com/index.php?rid=2548466&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519398%26dopt%3DAbstract Authors: Ye J, Koumenis C Hypoxia/anoxia promotes tumor aggressiveness and negatively impacts tumor response to therapy. Coordinate regulation of HIF-dependent and HIF-independent pathways has been shown to contribute to cellular adaptation to hypoxic stress, and to couple macromolecular synthesis rates to reduced energy availability. An important component of this type of adaptation is the activation of the endoplasmic reticulum kinase PERK by acute or prolonged hypoxia. Activated PERK subsequently induces phosphorylation of the translation initiation factor eIF2alpha and translational upregulation of the transcription factor ATF4. ATF4 is a basic leucine-zipper (bZip) transcription factor, which regulates amino acid metabolism, cellular redox state, and anti-stress responses. ATF4 ex... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548466 Thu, 30 Apr 2009 23:00:00 +0100 2548466 http://www.medworm.com/index.php?rid=2548465&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519399%26dopt%3DAbstract Authors: Rouschop KM, Wouters BG The poorly developed vasculature in solid human tumors is responsible for a profound level of intra- and inter-tumor heterogeneity in oxygen concentration. High levels of hypoxia are associated with poor patient prognosis due in part to hypoxia-induced changes in cell metabolism, angiogenesis, invasiveness and resistance to therapy. Over the past decade several distinct oxygen sensing pathways that regulate the cellular response to hypoxia have been defined. These include transcriptional and translational responses initiated by oxygen-dependent stabilization of the HIF-1 transcription factor, activation of the unfolded protein response (UPR) and inhibition of the mTOR (mammalian target of rapamycin) kinase signaling pathway. Variations in the duration a... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548465 Thu, 30 Apr 2009 23:00:00 +0100 2548465 http://www.medworm.com/index.php?rid=2548464&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519400%26dopt%3DAbstract Authors: Kim Y, Lin Q, Glazer PM, Yun Z Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhibit tumor cell differentiation and thus plays a direct role in the maintenance of cancer stem cells. Studies have also shown that hypoxia blocks differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells. It is therefore likely that hypoxia may have a profound impact on the evolution of the tumor stromal microenvironment. These observations have led to the emergence of a novel paradigm ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548464 Thu, 30 Apr 2009 23:00:00 +0100 2548464 http://www.medworm.com/index.php?rid=2548463&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519401%26dopt%3DAbstract Authors: Hardee ME, Dewhirst MW, Agarwal N, Sorg BS Hypoxia is a common feature of solid tumors, and abnormal tumor oxygen transport is a key factor in the imbalance between tumor oxygen supply and demand. Novel advanced imaging techniques can enable new insights into the complexities of tumor oxygen transport and hypoxia that were not previously known or fully appreciated. In this paper, we document new insights into tumor oxygen transport enabled by spectral imaging of microvascular hemoglobin saturation. PMID: 19519401 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548463 Thu, 30 Apr 2009 23:00:00 +0100 2548463 http://www.medworm.com/index.php?rid=2548462&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519402%26dopt%3DAbstract We describe the importance of new technologies for measuring hypoxia in human tumors, which allow assessment of pretreatment tumor oxygen levels and changes in hypoxia over the course of prolonged treatment regimens. These offer the possibility of improving the design of clinical trials and the selection of patients who will benefit from hypoxia-directed therapies, as well as the possibility of facilitating the development of better agents and regimens for use in hypoxia-directed therapy. We also discuss how the improved understanding of the abnormal vascular beds in solid tumors and of the effects of hypoxia and related microenvironmental insults, resulting from recent and ongoing research, offers the potential for finding new therapeutic targets, that may lead to the development of new a... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548462 Thu, 30 Apr 2009 23:00:00 +0100 2548462 http://www.medworm.com/index.php?rid=2548461&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519403%26dopt%3DAbstract Authors: Cocco C, Pistoia V, Airoldi I Metastatic melanoma is a poor prognosis skin cancer. Since conventional treatments including surgery and chemotherapy often fail, novel therapeutic strategies are needed. In particular, identification of melanoma associated antigen has fostered the progress of both active (vaccines) and adoptive immunotherapy. Some promising results have been obtained, but most melanoma patients are not yet cured possibly because of different immune-escape mechanisms operated by tumor cells. Several studies have addressed the use of interleukin (IL)-12 for melanoma therapy due to its immunoregulatory function and anti-tumor activity mediated by stimulation of T and NK effector cells. Unfortunately, IL-12 has shown considerable toxicity. We [1] have recently demons... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548461 Thu, 30 Apr 2009 23:00:00 +0100 2548461 http://www.medworm.com/index.php?rid=2548460&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519404%26dopt%3DAbstract Authors: Wu Y, Brosh RM Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. Cells from FA patients exhibit spontaneous chromosomal instability and hypersensitivity to DNA interstrand cross-linking (ICL) agents. Although the precise mechanistic details of the FA/BRCA pathway of ICL-repair are not well understood, progress has been made in the identification of the FA proteins that are required for the pathway. Among the 13 FA complementation groups from which all the FA genes have been cloned, only a few of the FA proteins are predicted to have direct roles in DNA metabolism. One of the more recently identified FA proteins, shown to be responsible for complementation of the FA compl... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548460 Thu, 30 Apr 2009 23:00:00 +0100 2548460 http://www.medworm.com/index.php?rid=2548459&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519405%26dopt%3DAbstract Authors: Meinicke H, Darcan Y, Hamelmann E Allergic diseases emerge as a substantial health problem of the 21(st) century. Current therapies including combination therapies of corticosteroids and beta(2)-agonists are highly effective, inexpensive and relatively safe. However, these medicaments only relieve symptoms but are not curing disease. So the challenge has to be to develop new therapeutics which are as effective as present medicaments without any side effects and hopefully even heal the disease. It has become clear over the past years that Th2-cells and their cytokines have an outstanding role in the development of airway hyperresponsiveness, airway inflammation, airway remodelling and reversible airway obstruction, the cardinal symptoms of allergic asthma. There is legitimate h... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548459 Thu, 30 Apr 2009 23:00:00 +0100 2548459 http://www.medworm.com/index.php?rid=2548458&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519406%26dopt%3DAbstract Authors: Cummins N, Badley A Since the discovery of Tumor Necrosis Factor-Related Apoptosis Inducing Ligand (TRAIL) in 1995, much has been learned about the protein, its receptors and signaling cascade to induce apoptosis and the regulation of its expression. However, the physiologic role or roles that TRAIL may play in vivo are still being explored. The expression of TRAIL on effector T cells and the ability of TRAIL to induce apoptosis in virally infected cells provided early clues that TRAIL may play an active role in the immune defense against viral infections. However, increasing evidence is emerging that TRAIL may have a dual function in the immune system, both as a means to kill virally infected cells and in the regulation of cytokine production. TRAIL has been implicated in the... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548458 Thu, 30 Apr 2009 23:00:00 +0100 2548458 http://www.medworm.com/index.php?rid=2548457&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19519407%26dopt%3DAbstract Authors: Le Strat Y, Ramoz N, Gorwood P Schizophrenia is a multifactorial disease characterized by a high heritability. Several candidate genes have been suggested, with the strongest evidences for genes encoding dystrobrevin binding protein 1 (DTNBP1), neuregulin 1 (NRG1), neuregulin 1 receptor (ERBB4) and disrupted in schizophrenia 1 (DISC1), as well as several neurotrophic factors. These genes are involved in neuronal plasticity and play also a role in adult neurogenesis. Therefore, the genetic basis of schizophrenia could involve different factors more or less specifically required for neuroplasticity, including the synapse maturation, potentiation and plasticity as well as neurogenesis. Following the model of Knudson in tumors, we propose a two-hit hypothesis of schizophrenia. In ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2548457 Thu, 30 Apr 2009 23:00:00 +0100 2548457 http://www.medworm.com/index.php?rid=2327077&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355915%26dopt%3DAbstract Authors: Shah IM, Macrae IM, Di Napoli M Cerebrovascular disease is one of the commonest causes of disability and mortality worldwide. Over the past two decades, a tremendous amount of research has been undertaken into developing effective therapeutic strategies for the treatment of acute stroke. Unfortunately, many neuroprotective agents that have shown successful results in treating animal models of acute stroke have failed to translate into clinical treatments. Only tissue-plasminogen activator (t-PA) is currently licensed for use in the treatment of acute ischaemic stroke. One of the important pathophysiological mechanisms involved during the acute phase of stroke is neuroinflammation. This review article will discuss the molecular aspects of neuroinflammation in acute ischaemic st... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2327077 Wed, 01 Apr 2009 04:00:00 +0100 2327077 http://www.medworm.com/index.php?rid=2327024&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355916%26dopt%3DAbstract Authors: Lorz C, Segrelles C, Paramio JM The epidermis is the stratified epithelium that covers and protects the body from external damage. This tissue undergoes continuous cell renewal throughout the life of the individual at the expense of a pool of pluripotent cells, some of them lie in a well defined niche in the hair follicle known as the bulge. Epidermal tumours are the most frequent type of cancer in human populations, as a consequence, the development and progression of these tumours have been extensively characterised and a number of mouse models generated. Over the last years several findings suggest that a subset of cells, named cancer stem cells, could play an important role in tumour development; however, the identity of these cells remains unknown in most cases. Understan... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2327024 Wed, 01 Apr 2009 04:00:00 +0100 2327024 http://www.medworm.com/index.php?rid=2327018&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355917%26dopt%3DAbstract Authors: Li M, Zhou Y, Feng G, Su SB Toll-like receptors (TLRs) form a large family of pattern recognition receptors with at least 11 members in human and 13 in mouse. TLRs recognize a wide variety of microbial components and potential host-derived agonists that have emerged as key mediators of innate immunity. TLR signaling also plays an important role in the activation of the adaptive immune system by inducing proinflammatory cytokines and upregulating costimulatory molecules of antigen presenting cells. The dysregulation of TLR signaling may cause autoimmunity. This review discusses the contribution of TLR signaling to the initiation and progression of autoimmune diseases, such as rheumatoid arthritis, experimental autoimmune encephalitis, myocarditis, hepatitis, kidney disease, sys... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2327018 Wed, 01 Apr 2009 04:00:00 +0100 2327018 http://www.medworm.com/index.php?rid=2327015&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355918%26dopt%3DAbstract Authors: Cottet S, Schorderet DF Mutations in humans are associated with several forms of inherited retinal dystrophies, such as Retinitis Pigmentosa which lead to retinal cell death and irreversible loss of vision. Genes involved in affected patients mainly encode proteins related to vision physiology including visual cycle and light-dependent phototransduction cascade. As reported in spontaneous and genetically engineered mouse models, apoptosis is a common fate in retinal degeneration, although the triggered signals to retinal apoptosis remain largely unraveled. Several studies highlighted that many of the molecular pathways involved in ocular diseases rely on caspase-dependent or -independent apoptotic mitochondrial pathway involving the Bcl-2 family of proteins. Anti- and pro-apop... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2327015 Wed, 01 Apr 2009 04:00:00 +0100 2327015 http://www.medworm.com/index.php?rid=2327013&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355919%26dopt%3DAbstract Authors: Mehrotra AK, Henderson WR Asthma is an inflammatory disorder of the airways that has been typified by its bronchospastic component. New attention has been directed to the long-term changes in asthmatic airways as indicated by the accelerated rate of lung function decline occurring in these patients despite therapy with inhaled corticosteroids. These structural changes in the airway wall, termed airway remodeling, are now thought to be a key component in the pathophysiology of asthma. Airway remodeling is characterized by thickening of the lamina reticularis with deposition of collagen and other extracellular matrix proteins leading to subepithelial fibrosis and increased airway goblet cells causing mucus hypersecretion. Of note, there is myofibroblast proliferation and increas... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2327013 Wed, 01 Apr 2009 04:00:00 +0100 2327013 http://www.medworm.com/index.php?rid=2327006&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19355920%26dopt%3DAbstract Authors: Pellegrini M, Baldari CT p66Shc is the only known proapoptotic member of the Shc protein family of molecular adaptors. Through its redox activity, p66Shc oxidates cytochrome-c, leading to increased ROS production and, eventually, to apoptosis. p66Shc has been implicated in the control of oxidative stress and life span in mammals. In this review the multifaceted role of p66Shc in redox regulation will be discussed, with a focus on the mechanisms underlying p66Shc-dependent apoptosis and its role in oxidative stress-related diseases. PMID: 19355920 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2327006 Wed, 01 Apr 2009 04:00:00 +0100 2327006 http://www.medworm.com/index.php?rid=2258287&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275620%26dopt%3DAbstract Authors: Be NA, Kim KS, Bishai WR, Jain SK Central Nervous System (CNS) tuberculosis is a serious, often fatal form of tuberculosis, predominantly affecting young children. HIV co-infection and drug resistant strains of Mycobacterium tuberculosis are making the diagnosis and treatment of CNS tuberculosis more complicated. Current concepts about the pathogenesis of CNS tuberculosis are based on necropsy studies done in 1933, which suggest that tuberculous meningitis develops subsequent to the rupture into the cerebrospinal fluid of tuberculomas that form around M. tuberculosis deposited in the brain parenchyma and meninges during the initial hematogenous dissemination. Foreign antigens including pathogens deposited in the brain parenchyma are not detected efficiently by the immune syste... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258287 Sun, 01 Mar 2009 05:00:00 +0100 2258287 http://www.medworm.com/index.php?rid=2258285&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275621%26dopt%3DAbstract Authors: Deurenberg RH, Stobberingh EE Staphylococcus aureus can cause a wide variety of infections, ranging from minor skin infections to post-operative wound infections. Its adaptive power to antibiotics has resulted in the emergence of methicillin-resistant S. aureus (MRSA) in the beginning of the 1960s. Resistance to methicillin and all other beta-lactam antibiotics is caused by the mecA gene, which is situated on a mobile genomic island, the Staphylococcal Cassette Chromosome mec (SCCmec). Seven main SCCmec types, I to VII, have been distinguished. The most important methods used to study the molecular epidemiology of MRSA are pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST), spa typing and SCCmec typing. These methods have been used to investigate the ev... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258285 Sun, 01 Mar 2009 05:00:00 +0100 2258285 http://www.medworm.com/index.php?rid=2258283&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275622%26dopt%3DAbstract Authors: Ramirez JL, Garver LS, Dimopoulos G Malaria is one of today's most serious diseases with an enormous socioeconomic impact. While anti-malarial drugs have existed for some time and vaccines development may be underway, the most successful malaria eradication programs have thus far relied on attacking the mosquito vector that spreads the disease causing agent Plasmodium. Here we will review past, current and future perspectives of malaria vector control strategies and how these approaches have taken a promising turn thanks recent advances in functional genomics and molecular biology. PMID: 19275622 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258283 Sun, 01 Mar 2009 05:00:00 +0100 2258283 http://www.medworm.com/index.php?rid=2258282&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275623%26dopt%3DAbstract Authors: Michaelis M, Doerr HW, Cinatl J Highly pathogenic H5N1 avian influenza virus can infect humans and is currently the most deadly influenza virus that has crossed the species barrier. As of December 2007, the spread of H5N1 virus from human to human has been rare. Nobody can predict if H5N1 may cause a pandemic. However, the number of human cases is continuously increasing and changes in virulence and epidemiology have been detected. There are specific pathogenic features of H5N1 infection. In contrast to human-adapted influenza A strains, H5N1 preferentially infects cells of the lower respiratory tract and may spread to tissues outside the respiratory tract in humans. Moreover, H5N1 replication is prolonged in target organs and results in higher viral loads and increased tissue... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258282 Sun, 01 Mar 2009 05:00:00 +0100 2258282 http://www.medworm.com/index.php?rid=2258279&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275624%26dopt%3DAbstract Authors: Swaminathan S, Khanna N Dengue is a very rapidly growing public health problem being currently faced by approximately 40% of the global population living in more than a hundred tropical and sub-tropical countries. It is a viral disease, caused by four types of dengue viruses, transmitted by mosquitoes, to an estimated 50 million people each year. Vector control methods to contain transmission have not been successful and there is currently no useful diagnostic test, drug or vaccine to combat dengue disease. However, as a result of the heightened awareness of its magnitude and its potential to spread beyond the tropical world, dengue has begun to emerge out of the list of neglected diseases in recent years. New interest in this disease has drawn scientists from multiple discipl... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258279 Sun, 01 Mar 2009 05:00:00 +0100 2258279 http://www.medworm.com/index.php?rid=2258277&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275625%26dopt%3DAbstract Authors: Mohamadzadeh M The filoviruses, Ebola (EBOV) and Marburg (MARV), are among the deadliest of human pathogens, causing acute diseases typified by rapidly fatal hemorrhagic fevers. Upon filoviral infection, innate immune cells become paralyzed and lose the capacity to properly co-stimulate and activate filovirus-specific, T-cell responses. Deleterious inflammation and upregulation of co-inhibitory molecules expressed by monocytic lineage cells (e.g., dendritic cells) and their co-inhibitory receptors on T- and B-cells may lead to incomplete humoral and T-cell immunity, anergy, exhaustion, apoptosis, and subsequent immune subversion. Hence, the dysregulation of inflammatory and co-inhibitory molecules may be exploited by filoviruses to further deteriorate host immune responses, ul... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258277 Sun, 01 Mar 2009 05:00:00 +0100 2258277 http://www.medworm.com/index.php?rid=2258274&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275626%26dopt%3DAbstract Authors: Bargiotas P, Monyer H, Schwaninger M Hemichannels are transmembrane channels that represent the functional subunits of gap junctions. Each hemichannel is composed of a connexin or pannexin hexamer and, after being transported to the membrane, remains unpaired until it is incorporated in a gap junction. Several studies have already provided evidence that gap junction-mediated intercellular diffusion of ions and small molecules during ischemia represents an important mechanism through which necrotic, apoptotic, or even protective signals are transported between cells. Although initially hemichannels were supposed to be functional only in gap junctions, recent findings indicate that unpaired hemichannels also display a large array of activities that can be modulated under several... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258274 Sun, 01 Mar 2009 05:00:00 +0100 2258274 http://www.medworm.com/index.php?rid=2258272&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275627%26dopt%3DAbstract Authors: Urra X, Obach V, Chamorro A The interaction between the brain and immune system has been intensely studied in patients with several central nervous system (CNS) disorders including brain trauma and brain tumours. Pioneering studies described cellular immune changes after human stroke more than three decades ago but the potential existence of a CNS- mediated immunodepression syndrome has obtained renewed attention only recently. The CNS and the immune system are extensively interconnected through neural pathways, hormonal cascades and cell-to-cell interactions orchestrated primarily by cytokines. Indeed, the balance between pro- and anti-inflammatory cytokines determines the prowess of the immunological response but could also influence the fate of the injured brain tissue and ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258272 Sun, 01 Mar 2009 05:00:00 +0100 2258272 http://www.medworm.com/index.php?rid=2258271&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275628%26dopt%3DAbstract Authors: Godoy J, Mellado P, Tapia J, Santín J Obstructive Sleep Apnea (OSA) is a prevalent disease that has emerged as a new cerebrovascular disease (CVD) risk factor, which is independent of its association to hypertension, age and other known conditions that increase CVD. The mechanisms involved in this relation are most likely induced by the periodic hypoxia/reoxygenation that characteristically occurs in OSA, which results in oxidative stress, endothelial dysfunction and activation of the inflammatory cascade, all of which favor atherogenesis. Numerous markers of these changes have been reported in OSA patients, including increased circulating free radicals, increased lipid peroxidation, decreased antioxidant capacity, elevation of tumor necrosis factor and interleukines, inc... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258271 Sun, 01 Mar 2009 05:00:00 +0100 2258271 http://www.medworm.com/index.php?rid=2258270&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275629%26dopt%3DAbstract Authors: Grond-Ginsbach C, Debette S A predisposing weakness of the vessel wall has been assumed in patients with spontaneous cervical artery dissections (sCAD). Skin biopsies from many patients with sCAD show mild connective tissue alterations. However, their assessment depends on an invasive and highly specialized technique. Clinical signs of connective tissue disease are absent in the majority of CAD patients. In this review we document that only very few CAD patients are affected by known inherited connective tissue disorders like Ehlers-Danlos syndrome, Marfan syndrome or Osteogenesis Imperfecta. In a second part of this review we discuss the possible role of unrecognized or unknown forms of connective tissue disorders in the etiology of CAD. PMID: 19275629 [PubMed - in proces... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258270 Sun, 01 Mar 2009 05:00:00 +0100 2258270 http://www.medworm.com/index.php?rid=2258269&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275630%26dopt%3DAbstract Authors: Pezzini A, Del Zotto E, Giossi A, Volonghi I, Grassi M, Padovani A Strong epidemiological evidence indicates that migraine, especially migraine with aura, is associated with increased risk of ischemic stroke. However, the precise mechanisms of such a relation are currently not fully elucidated and are still a matter of speculation. Migraine may directly cause an ischemic event (i.e, migrainous infarct), by inducing cerebral microcirculatory vasoconstriction (cortical spreading depression-related oligemia), intracerebral large vessels spasm, and vascular endothelium-related hypercoagulability. On the other hand, migraine may predispose to cerebral ischemia outside of a migraine attack by affecting endothelial function, alone or in combination with traditional vascular risk fact... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258269 Sun, 01 Mar 2009 05:00:00 +0100 2258269 http://www.medworm.com/index.php?rid=2258268&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19275631%26dopt%3DAbstract Authors: Poli S, Veltkamp R Hyperbaric (HBO) or normobaric oxygen (NBO) therapy applied in acute ischemic stroke aims to increase oxygen supply to the ischemic tissue and to reduce the extent of irreversible tissue damage. Over the past decade, multiple studies have clarified the potential and limitations of oxygen therapy in preclinical stroke models. Considering that the reduction of the infarct size amounts to 30-40%, the cerebroprotection induced by HBO is moderate. In the experimental setting, the effective time window of HBO initiation is only a few hours. Higher pressures (2.5-3 ATA) are more effective. Even though oxygen therapy has some effectiveness in permanent cerebral ischemia without vascular recanalization, it appears more promising for bridging of a transient ischemic p... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2258268 Sun, 01 Mar 2009 05:00:00 +0100 2258268 http://www.medworm.com/index.php?rid=2233806&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199936%26dopt%3DAbstract Authors: Wong FS, Wen L PMID: 19199936 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2233806 Sun, 01 Feb 2009 05:00:00 +0100 2233806 http://www.medworm.com/index.php?rid=2233805&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199940%26dopt%3DAbstract Authors: Kim HS, Lee MS Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cells (APCs) to beta-cell antigens to almost total insulin deficiency due to islet destruction. Although it is established that the interaction of environmental factors with genetic traits plays a pivotal role in the pathogenesis of T1D, in most cases, the exact trigger of anti-islet autoimmunity and how genetic and environmental factors regulate its progression, ultimately leading to the development of T1D remain elusive. In this review, based on the r... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2233805 Sun, 01 Feb 2009 05:00:00 +0100 2233805 http://www.medworm.com/index.php?rid=2173418&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199936%26dopt%3DAbstract Authors: Wong FS, Wen L PMID: 19199936 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173418 Sun, 01 Feb 2009 05:00:00 +0100 2173418 http://www.medworm.com/index.php?rid=2173417&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199937%26dopt%3DAbstract Authors: Wu L, Van Kaer L Natural killer T (NKT) cells are an unusual subset of innate immune cells that express a surface receptor generated by somatic DNA rearrangement, a hallmark of cells of the adaptive immune system. NKT cells express a highly restricted repertoire of T cell receptors that recognize glycolipid antigens bound with the antigen-presenting molecule CD1d. A hallmark of NKT cells is their capacity to produce copious amounts of immunomodulatory cytokines upon antigenic stimulation, which endows these cells with potent immunoregulatory properties. Consequently, NKT cells have been implicated in regulating a wide variety of immune responses, including immune responses against autoantigens. In patients and mice with a variety of autoimmune diseases, numbers and functions o... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173417 Sun, 01 Feb 2009 05:00:00 +0100 2173417 http://www.medworm.com/index.php?rid=2173416&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199938%26dopt%3DAbstract Authors: Blink SE, Miller SD gammadelta T cells are a multifaceted group of cells which have both innate and adaptive characteristics and functions. Although they are most commonly known for their response to mycobacterium and their locations at mucosal sites, their roles in autoimmunity are still unclear. gammadelta T cells have been seen in the CSF and lesions of Multiple Sclerosis patients and although their function is not entirely understood, it is clear these cells may have roles in regulating autoimmune inflammation in the CNS. Recent studies have focused on the role of gammadelta T cells in MS and EAE as both pathogenic and protective, their functions within the CNS, the types of subsets and a possible role in Th17 inflammation. In this review we will examine the data acquired ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173416 Sun, 01 Feb 2009 05:00:00 +0100 2173416 http://www.medworm.com/index.php?rid=2173415&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199939%26dopt%3DAbstract Authors: Nicholson LB, Raveney BJ, Munder M In chronic inflammation, across a number of quite different pathological conditions, monocytes accumulate. In autoimmune disease, these cells are widely recognised to play an inflammatory and tissue destructive role. But these cells also inhibit T cell proliferation by a range of different mechanisms that are accompanied by the depletion of specific amino acids in the local microenvironment and the downregulation of the T cell receptor zeta chain. This occurs within the pro-inflammatory environment and in the presence of Th1 (IFNgamma) and Th17 (IL-17) cytokines. In tumours, related cells are part of a population called myeloid-derived suppressor cells (MDSC) and they are associated with immunosuppression. Their depletion can lead to clinical... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173415 Sun, 01 Feb 2009 05:00:00 +0100 2173415 http://www.medworm.com/index.php?rid=2173414&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199940%26dopt%3DAbstract Authors: Kim HS, Lee MS Type 1 diabetes (T1D) is an organ-specific autoimmune disease resulting from the specific destruction of insulin-producing pancreatic beta-cells, culminating in a state of hypoinsulinemia and hyperglycemia. Pathogenesis of T1D comprises complex series of events from the initial sensitization of antigen-presenting cells (APCs) to beta-cell antigens to almost total insulin deficiency due to islet destruction. Although it is established that the interaction of environmental factors with genetic traits plays a pivotal role in the pathogenesis of T1D, in most cases, the exact trigger of anti-islet autoimmunity and how genetic and environmental factors regulate its progression, ultimately leading to the development of T1D remain elusive. In this review, based on the r... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173414 Sun, 01 Feb 2009 05:00:00 +0100 2173414 http://www.medworm.com/index.php?rid=2173413&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199941%26dopt%3DAbstract Authors: Selmi C, Lleo A, Pasini S, Zuin M, Gershwin ME There has been a rapid growth in our understanding of the molecular bases of primary biliary cirrhosis (PBC). These efforts were initiated when the immunodominant mitochondrial autoantigen was cloned and sequenced. Using the recombinant cloned antigen as a tool, research has focused on the effector mechanisms of disease and the uniqueness of the primary target tissue, the intrahepatic bile ducts. Most recently, there have been experimental data suggesting that innate immunity changes may be critical to the initiation and perpetuation of the autoimmune injury, as in the case of the enhanced response of monocytes and memory B cells to infectious stimulation and environmental mimics. These observations are important as they help fill... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173413 Sun, 01 Feb 2009 05:00:00 +0100 2173413 http://www.medworm.com/index.php?rid=2173412&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199942%26dopt%3DAbstract Authors: Lien E, Zipris D Toll-like receptors (TLRs) and the innate immune system play a key role in sensing and eliminating microbial infections. Interactions between TLRs and their ligands expressed by microbial pathogens induce a cascade of intracellular signaling events, culminating in the upregulation of proinflammatory pathways. Over the past two decades, numerous studies have established the role of the acquired immune system in the mechanism triggering type 1 diabetes (T1D). The recent discovery of TLRs has led to the recognition that the innate immune system may act, under some circumstances, as a double-edged sword. In addition to its beneficial role in host defense, it may lead to upregulation of proinflammatory autoimmune responses, islet destruction and diabetes. Indeed, r... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173412 Sun, 01 Feb 2009 05:00:00 +0100 2173412 http://www.medworm.com/index.php?rid=2173411&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199943%26dopt%3DAbstract Authors: Page TH, Smolinska M, Gillespie J, Urbaniak AM, Foxwell BM The activity of tyrosine kinases is central to many cellular processes, and accumulating evidence suggests that their role in inflammation is no less profound. Three main tyrosine kinase families, the Src, Tec and Syk kinase families are intimately involved in TLR signalling, the critical first step in cellular recognition of invading pathogens and tissue damage. Their activity results in changes in gene expression in affected cells. Key amongst these genes are the cytokines, which orchestrate both the duration and extent of inflammation. Tyrosine kinases also play important roles in cytokine function, and are implicated in signalling through both pro- and anti-inflammatory cytokines such as TNF, IL-6 and IL-10. Thus, ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173411 Sun, 01 Feb 2009 05:00:00 +0100 2173411 http://www.medworm.com/index.php?rid=2173410&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19199944%26dopt%3DAbstract Authors: Patel M, McInnes IB, Graham G There is considerable interest in the therapeutic utility of inhibiting cellular trafficking in a variety of inflammatory diseases. Approaches including inhibition of adhesion molecule function and in particular of chemokine effector function have met with high levels of success in many models of disease but have been of less value in application to clinical disease states. Although this may in part be explained by pharmacokinetic and pharmacodynamic issues surrounding therapeutic agents tried thus far, it is also likely that functional redundancy in the chemokine network may pose significant problems for achieving potent inflammation suppression. The atypical chemokine receptors comprise a novel group of receptors capable of binding to several ch... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2173410 Sun, 01 Feb 2009 05:00:00 +0100 2173410 http://www.medworm.com/index.php?rid=2047602&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075669%26dopt%3DAbstract Authors: Asli NS, Pitulescu ME, Kessel M Large numbers and quantities of different, small RNA molecules are present in the cytoplasm of animal and plant cells. One subclass of these molecules is represented by the noncoding microRNAs. Since their discovery in the 1990s a multitude of basic information has accumulated, which has identified their function in post-transcriptional control, either via degradation or translational inhibition of target mRNAs. This function is in most of the cases a finetuning of gene expression, working in parallel with transcriptional regulatory processes. MicroRNA expression profiles are highly dynamic during embryonic development and in adulthood. Misexpression of microRNAs can perturb embryogenesis, organogenesis, tissue homeostasis and the cell cycle. Ev... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047602 Mon, 01 Dec 2008 05:00:00 +0100 2047602 http://www.medworm.com/index.php?rid=2047601&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075670%26dopt%3DAbstract Authors: Schaller BJ, Cornelius JF, Sandu N, Buchfelder M Non-invasive energy metabolism measurements in brain tumors in vivo are now performed widely as molecular imaging by positron emission tomography. This capability has developed from a large number of basic and clinical science investigations that have cross fertilized one another. Apart from precise anatomical localization and quantification, the most intriguing advantage of such imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, molecular imaging represents a key-technology in translational research, helping to develop experimental protocols that may later be applied to human patients. Common clinical indications for molecular imagi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047601 Mon, 01 Dec 2008 05:00:00 +0100 2047601 http://www.medworm.com/index.php?rid=2047600&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075671%26dopt%3DAbstract Authors: Shukla V, Coumoul X, Vassilopoulos A, Deng CX Hereditary breast cancers affect women who have an increased risk of developing tumors because of a familial history. In most cases, they can be attributed to mutations in the breast cancer associated gene 1 and 2 (BRCA1 and BRCA2). Recent studies have demonstrated a link between the insulin-like growth factor (IGF) signaling pathway and familial breast cancer incidence. IGF and IGF receptors represent a family of biological growth factors and transducers, which have been involved in both physiological and pathological processes. It has been shown that BRCA1 regulates expression of several members of the IGF family. Here, we will examine our understanding of the functions of IGF/IGF-receptor signaling, the development of new inhibi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047600 Mon, 01 Dec 2008 05:00:00 +0100 2047600 http://www.medworm.com/index.php?rid=2047599&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075672%26dopt%3DAbstract Authors: Gosens R, Mutawe M, Martin S, Basu S, Bos ST, Tran T, Halayko AJ Caveolae are flask-shaped invaginations of the plasma membrane that are present in most structural cells. They owe their characteristic Omega-shape to complexes of unique proteins, the caveolins, which indirectly tether cholesterol and sphingolipid-enriched membrane microdomains to the cytoskeleton. Caveolins possess a unique scaffolding domain that anchors receptors, ion channels, second messenger producing enzymes, and effector kinases, thereby sequestering them to caveolae, and modulating cellular signaling and vesicular transport. The lungs express numerous caveolae and high levels of caveolins; therefore they likely play an important role in lung physiology. Indeed, recent and ongoing studies indicate import... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047599 Mon, 01 Dec 2008 05:00:00 +0100 2047599 http://www.medworm.com/index.php?rid=2047598&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075673%26dopt%3DAbstract Authors: Hoenig MR, Bianchi C, Rosenzweig A, Sellke FW Ageing is associated with endothelial dysfunction, decreased endothelial progenitor cell (EPC) function and mobilization. These defects culminate in a decreased capacity for neovascularization in the aged. Multiple lines of evidence suggest that defective neovascularization with ageing is related to depressed signaling by hypoxia inducible factor-1 (HIF-1). HIF-1, the master regulator or neovascularization, regulates the expression of vascular endothelial growth factor (VEGF), stromal cell-derived factor-1 (SDF-1) and CXC chemokine Receptor-4 (CXCR4). Given that the SDF-1/CXCR4 axis is a crucial regulator of progenitor cell function and homing, the ramifications of depressed HIF-1 signaling with age include depressed vascular repai... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047598 Mon, 01 Dec 2008 05:00:00 +0100 2047598 http://www.medworm.com/index.php?rid=2047597&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075674%26dopt%3DAbstract Authors: Jankun J, Doerks T, Aleem AM, Lysiak-Szydłowska W, Skrzypczak-Jankun E Human lipoxygenases and products of their catalytic reaction have a well established connection to many human diseases. Despite their importance in inflammation, cancer, cardiorenal and other ailments the drug development is impaired by the lack of structural details to understand their intricate specificity and function in molecular and cellular signaling. The major effort so far has been directed towards understanding the determinants of their specificity and inhibition of their active site with the iron cofactor. Their structure is believed to consist of only two domains: one regulatory - a beta-sandwich, important for membrane binding, and one, mostly helical, catalytic domain. Although recently p... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047597 Mon, 01 Dec 2008 05:00:00 +0100 2047597 http://www.medworm.com/index.php?rid=2047596&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075675%26dopt%3DAbstract Authors: Mizuarai S, Irie H, Schmatz DM, Kotani H Various types of cancers are generated through mutations or dysregulations of oncogenes/tumor suppressor genes involved in cell cycles and signaling transduction pathways. To identify cancer therapeutic targets whose inhibition selectively kills cancer cells, synthetic lethal screening is being developed to identify genes whose intervention suppresses tumor progression only when combined with the dysregulation of the genes. The recent emergence of genomic technologies, including microarray, RNA interference and chemogenomics, provides platforms to realize this concept. This review introduces the research that could successfully identify synthetic lethal genes in cancer cells harboring major gene alterations such as p53, RB, K-Ras, or My... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047596 Mon, 01 Dec 2008 05:00:00 +0100 2047596 http://www.medworm.com/index.php?rid=2047595&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075676%26dopt%3DAbstract Authors: Marhaba R, Klingbeil P, Nuebel T, Nazarenko I, Buechler MW, Zoeller M Embryonic stem cells are immortal, can self renew, and differentiate into all cells of the body. The adult organism maintains adult stem cells in regenerative organs that can differentiate into all cells of the respective organ. Virchow's hypothesis that cancer may arise from embryonic-like cells has received strong support, as it was demonstrated that tumors contain few cells, known as cancer stem or cancer-initiating cells (CIC), that account for primary and metastatic tumor growth. CIC are mostly defined by expression of CIC-markers that are associated and correlated with the potential of CIC to grow in xenogeneic mice. CIC marker profiles have been elaborated for many tumors, with several markers as CD24... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047595 Mon, 01 Dec 2008 05:00:00 +0100 2047595 http://www.medworm.com/index.php?rid=2047594&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075677%26dopt%3DAbstract Authors: Wu X, Hua X Menin is a tumor suppressor encoded by the MEN1 gene that is mutated in patients with an inherited syndrome, multiple endocrine neoplasia type 1 (MEN1). Loss of menin has potent impact on proliferation of endocrine and non-endocrine cells. However, until recently little has been known as to how menin regulates cell proliferation. Rapid research progress in the past several years suggests that menin represses proliferation of endocrine cells yet promotes proliferation in certain types of leukemia cells via interacting with various transcriptional regulators. Menin interacts with histone H3 methyltransferases such as MLL (mixed lineage leukemia) protein. Increasing evidence has linked the biological function of menin to epigenetic histone modifications, control of th... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047594 Mon, 01 Dec 2008 05:00:00 +0100 2047594 http://www.medworm.com/index.php?rid=2047593&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075678%26dopt%3DAbstract Authors: Dandona P, Dhindsa S, Chaudhuri A, Bhatia V, Topiwala S, Mohanty P Recent work shows a high prevalence of low testosterone and inappropriately low LH and FSH concentrations in type 2 diabetes. This syndrome of hypogonadotrophic hypogonadism (HH) is associated with obesity, and other features of the metabolic syndrome (obesity and overweight, hypertension and hyperlipidemia) in patients with type 2 diabetes. However, the duration of diabetes or HbA1c were not related to HH. Furthermore, recent data show that HH is also observed frequently in patients with the metabolic syndrome without diabetes but is not associated with type 1 diabetes. Thus, HH appears be related to the two major conditions associated with insulin resistance: type 2 diabetes and the metabolic syndrome. CRP co... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047593 Mon, 01 Dec 2008 05:00:00 +0100 2047593 http://www.medworm.com/index.php?rid=2047592&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075679%26dopt%3DAbstract Authors: Planelles L, Medema JP, Hahne M, Hardenberg G Proteins of the tumour necrosis factor (TNF) family are implicated in the regulation of essential cell processes such as proliferation, differentiation, survival and cell death. Altered expression of TNF family members is often associated with pathological conditions such as autoimmune disease and cancer. The TNF-like ligand APRIL (A PRoliferation Inducing Ligand), first described in 1998, was named for its capacity to stimulate tumour cell proliferation in vitro. APRIL expression was initially reported in haematopoietic cells in physiological conditions, and it is overexpressed in certain tumour tissues. APRIL is now known to be involved in activation and immune responses of B cells, as well as in B cell malignancies. This review ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047592 Mon, 01 Dec 2008 05:00:00 +0100 2047592 http://www.medworm.com/index.php?rid=2047591&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19075680%26dopt%3DAbstract Authors: Zhang J, Chen X p53 tumor suppressor plays a pivotal role in maintaining genomic integrity and preventing cancer development. The importance of p53 in tumor suppression is illustrated by the observation that about 50% human tumor cells have a dysfunctional p53 pathway. Although it has been well accepted that the activity of p53 is mainly controlled through post-translational modifications, recent studies have revealed that posttranscriptional regulations of p53 by various RNA-binding proteins also play a crucial role in modulating p53 activity and its downstream targets. PMID: 19075680 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2047591 Mon, 01 Dec 2008 05:00:00 +0100 2047591 http://www.medworm.com/index.php?rid=2040381&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991654%26dopt%3DAbstract Authors: Sadelain M, Boulad F, Lisowki L, Moi P, Riviere I The beta-thalassemias and sickle cell anemia are severe congenital anemias for which there is presently no curative therapy other than allogeneic bone marrow transplantation. This therapeutic option, however, is not available to most patients due to the lack of an HLA-matched bone marrow donor. Emerging modalities based on cell engineering offer new prospects for potentially curative approaches that are applicable to more patients. The first is based on the transfer of a regulated globin gene in autologous hematopoietic stem cells (HSCs). This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid-specific, differentiation and stage-restricted, elev... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=2040381 Sat, 01 Nov 2008 04:00:00 +0100 2040381 http://www.medworm.com/index.php?rid=1961170&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991644%26dopt%3DAbstract Authors: Vichinsky E, Rodgers GP, Rachmilewitz E PMID: 18991644 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1961170 Sat, 01 Nov 2008 04:00:00 +0100 1961170 http://www.medworm.com/index.php?rid=1952384&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991644%26dopt%3DAbstract Authors: Vichinsky E, Rodgers GP, Rachmilewitz E PMID: 18991644 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952384 Sat, 01 Nov 2008 04:00:00 +0100 1952384 http://www.medworm.com/index.php?rid=1952383&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991645%26dopt%3DAbstract Authors: Weatherall DJ The genetic disorders of hemoglobin, the commonest monogenic diseases, occur at some of their highest frequencies in the developing countries, particularly those of Sub-Saharan Africa and Asia. Although progress towards their control and management continues to be made, the prospects for curing them, apart from marrow transplantation, remain uncertain. In many countries expertise and facilities for their control are extremely limited. Although a great deal can be done to help the situation by developing further North/South and South/South partnerships for disseminating better practice, the major problem for the future lies in the unwillingness of governments and international health agencies to accept that the hemoglobinopathies represent a health burden comparat... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952383 Sat, 01 Nov 2008 04:00:00 +0100 1952383 http://www.medworm.com/index.php?rid=1952382&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991646%26dopt%3DAbstract Authors: Rund D, Fucharoen S Hereditary anemias show considerable variation in their clinical presentation. In some cases, the causes of these variations are easily apparent. In thalassemia (or in HbE/thalassemia), genetic variation is primarily caused by the severity of the thalassemia mutation. However, not uncommonly, there is variation unexplained by the globin gene mutations themselves, which may be caused by genetic modifiers. In sickle cell disease, the primary mutation is the same in all patients. Therefore, variations in disease severity generally are due to genetic modifiers. In most genetic diseases involving beta globin, the most clearcut influence on phenotype results from elevated fetal hemoglobin levels. In addition, alpha globin gene number can influence disease phenoty... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952382 Sat, 01 Nov 2008 04:00:00 +0100 1952382 http://www.medworm.com/index.php?rid=1952381&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991647%26dopt%3DAbstract Authors: Fibach E, Rachmilewitz E The oxidative status of cells is determined by the balance between pro-oxidants and antioxidants. Pro-oxidants, referred to as reactive oxygen species (ROS), are classified into radicals and nonradicals. The radicals are highly reactive due to their tendency to accept or donate an electron and attain stability. When cells experience oxidative stress, ROS, which are generated in excess, may oxidize proteins, lipids and DNA - leading to cell death and organ damage. Oxidative stress is believed to aggravate the symptoms of many diseases, including hemolytic anemias. Oxidative stress was found in the beta-hemoglobinopathies (sickle cell anemia and thalassemia), glucose-6-phosphate dehydrogenase deficiency, hereditary spherocytosis, congenital dyserythropoi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952381 Sat, 01 Nov 2008 04:00:00 +0100 1952381 http://www.medworm.com/index.php?rid=1952380&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991648%26dopt%3DAbstract Authors: Morris CR, Gladwin MT, Kato GJ Secondary pulmonary hypertension (PH) is emerging as one of the leading causes of mortality and morbidity in patients with hemolytic anemias such as sickle cell disease (SCD) and thalassemia. Impaired nitric oxide (NO) bioavailability represents the central feature of endothelial dysfunction, and is a major factor in the pathophysiology of PH. Inactivation of NO correlates with hemolytic rate and is associated with the erythrocyte release of cell-free hemoglobin, which consumes NO directly, and the simultaneous release of the arginine-metabolizing enzyme arginase, which limits bioavailability of the NO synthase substrate arginine during the process of intravascular hemolysis. Rapid consumption of NO is accelerated by oxygen radicals that exists i... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952380 Sat, 01 Nov 2008 04:00:00 +0100 1952380 http://www.medworm.com/index.php?rid=1952379&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991649%26dopt%3DAbstract Authors: Kuypers FA The complex mixture of lipids and proteins of the red blood cell membrane is well maintained during the life of the cell. Lipid analysis of the red cell reveals hundreds of phospholipid molecular species and cholesterol that differ with respect to their (polar) head group, and (apolar) side chains. These molecules move rapidly in the plane, as well as across the lipid bilayer. This dynamic movement is highly organized. In the plane of the bilayer, areas enriched in certain lipids accommodate protein structure and modulate function. While lipids move across the bilayer, the organization is highly asymmetric. Amino phospholipids are mainly found on the inside and choline containing phospholipids on the outside. Both the composition and organization of the red cell mem... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952379 Sat, 01 Nov 2008 04:00:00 +0100 1952379 http://www.medworm.com/index.php?rid=1952378&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991650%26dopt%3DAbstract Authors: Singer ST, Ataga KI Sickle cell disease (SCD) and beta-thalassemia (also referred to as beta-thalassemia) are common hereditary hemoglobinopathies with differing pathophysiologies and clinical courses. However, patients with both diseases exhibit increased platelet and coagulation activation, as well as decreased levels of natural anticoagulant proteins. In addition, they are characterized by thrombotic complications that may share a similar pathogenesis. The pathogenesis of hypercoagulability is likely multifactorial, with contributions from the abnormal red blood cell (RBC) phospholipid membrane asymmetry, ischemia-reperfusion injury, and chronic hemolysis with resultant nitric oxide depletion. More studies are needed to better define the contribution of hemostatic activatio... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952378 Sat, 01 Nov 2008 04:00:00 +0100 1952378 http://www.medworm.com/index.php?rid=1952377&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991651%26dopt%3DAbstract Authors: Rechavi G, Rivella S Beta-thalassemia and sickle cell anemia (SCD) represent the most common hemoglobinopathies caused, respectively, by deficient production or alteration of the beta chain of hemoglobin (Hb). Patients affected by the most severe form of thalassemia suffer from profound anemia that requires chronic blood transfusions and chelation therapies to prevent iron overload. However, patients affected by beta-thalassemia intermedia, a milder form of the disease that does not require chronic blood transfusions, eventually also show elevated body iron content due to increased gastrointestinal iron absorption. Even SCD patients might require blood transfusions and iron chelation to prevent deleterious and painful vaso-occlusive crises and complications due to iron overloa... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952377 Sat, 01 Nov 2008 04:00:00 +0100 1952377 http://www.medworm.com/index.php?rid=1952376&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991652%26dopt%3DAbstract Authors: Cappellini MD, Piga A Although blood transfusions are important for patients with hemoglobinopathies, chronic transfusions inevitably lead to iron overload as humans cannot actively remove excess iron. The cumulative effects of iron overload lead to significant morbidity and mortality, if untreated. Desferrioxamine (DFO) is the reference-standard iron chelator whose safety and efficacy profile has been established through many years of clinical use. DFO side effects are acceptable and manageable however the prolonged subcutaneous infusion regimen of 5-7 days per week is very demanding and results in poor adherence to therapy. Deferiprone (Ferriprox, L1) is a bidentate molecule, orally administrable three-times/day, licensed in Europe and in other regions but in the USA and Can... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952376 Sat, 01 Nov 2008 04:00:00 +0100 1952376 http://www.medworm.com/index.php?rid=1952375&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991653%26dopt%3DAbstract Authors: Michlitsch JG, Walters MC Allogeneic hematopoietic cell transplantation (HCT) is currently the only treatment with curative potential for sickle cell disease (SCD) and beta-thalassemia. HCT was first used to treat SCD and thalassemia more than two decades ago, and with increasing experience this treatment modality has shifted from being an experimental intervention to one in which selected patient populations are targeted for treatment. Recent multicenter clinical studies show an event-free survival (EFS) of 85% after human leukocyte antigen (HLA)-identical sibling transplantation for SCD, using conventional myeloablative conditioning with a backbone of busulfan (BU) and cyclophosphamide (CY) [1-3]. Results of HCT for thalassemia show very similar outcomes, with EFS probabilit... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952375 Sat, 01 Nov 2008 04:00:00 +0100 1952375 http://www.medworm.com/index.php?rid=1952374&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18991654%26dopt%3DAbstract Authors: Sadelain M, Boulad F, Lisowki L, Moi P, Riviere I The beta-thalassemias and sickle cell anemia are severe congenital anemias for which there is presently no curative therapy other than allogeneic bone marrow transplantation. This therapeutic option, however, is not available to most patients due to the lack of an HLA-matched bone marrow donor. Emerging modalities based on cell engineering offer new prospects for potentially curative approaches that are applicable to more patients. The first is based on the transfer of a regulated globin gene in autologous hematopoietic stem cells (HSCs). This strategy, simple in principle, raises major challenges in terms of controlling transgene expression, which ideally should be erythroid-specific, differentiation and stage-restricted, elev... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1952374 Sat, 01 Nov 2008 04:00:00 +0100 1952374 http://www.medworm.com/index.php?rid=1782863&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781952%26dopt%3DAbstract Authors: Prochownik EV CMYC has long been known to be among the most frequently de-regulated oncogenes in human cancer. Only recently, however has a clear understanding begun to emerge of how it promotes transformation. Through its role as a transcription factor, c-Myc alters the expression of hundreds of target genes, many of which are themselves oncogenes or tumor suppressors. The deregulation of c-Myc is both necessary and sufficient for the "acute" type of rapid in vitro transformation that occurs in certain established rodent cell lines. Transformation of primary rodent cells in vitro is also rapid but requires the contribution of at least one additional cooperating oncogene such as Ras. In contrast, the "chronic" form of in vivo transformation by c-Myc is a rare event that requir... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782863 Mon, 01 Sep 2008 04:00:00 +0100 1782863 http://www.medworm.com/index.php?rid=1782862&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781953%26dopt%3DAbstract Authors: Georgescu MM, Morales FC, Molina JR, Hayashi Y This review summarizes the emerging roles of NHERF1/EBP50 adaptor protein in tumorigenesis. NHERF1/EBP50 (Na(+)/H(+) exchanger regulating factor 1; ezrin-radixin-moesin (ERM) binding phosphoprotein of 50 kDa) is a PDZ domain-containing protein with physiological localization at the plasma membrane. We discuss in this review the functions of NHERF1/EBP50 as a linker between membrane proteins and the cytoskeleton network, as well as its involvement in different types of cancer, such as breast and liver cancers. Recent evidence obtained from our laboratory and from other groups shows that NHERF1/EBP50 is an important player in cancer progression. It appears that, depending on its subcellular distribution, NHERF1/EBP50 may behave eith... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782862 Mon, 01 Sep 2008 04:00:00 +0100 1782862 http://www.medworm.com/index.php?rid=1782861&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781954%26dopt%3DAbstract Authors: Zhou HY, Pon YL, Wong AS Ovarian cancer is the leading cause of death from gynecological cancers in North America and Europe. Despite its clinical significance, the factors that regulate the development and progression of ovarian cancer are among the least understood of all major human malignancies. A growth factor with pleiotropic effects, which has attracted increasing attention in recent years, is the hepatocyte growth factor (HGF) and its receptor MET. While deregulated HGF/MET signaling is observed in many tumors, the consequences of MET activation are complex and context dependent. Recent observations have demonstrated a cross-talk of other signaling pathways with MET signaling. This review summarizes the key findings and recent advances in our understanding of HGF and M... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782861 Mon, 01 Sep 2008 04:00:00 +0100 1782861 http://www.medworm.com/index.php?rid=1782860&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781955%26dopt%3DAbstract Authors: Tóvári J, Pirker R, Tímár J, Ostoros G, Kovács G, Döme B Erythropoietin (EPO) has long been recognized as the major hematopoietic cytokine regulating normal erythropoiesis. Moreover, there is a growing interest in the non-erythropoietic, tissue-protective effects of EPO. Because of its potential to correct anemia, EPO has been increasingly prescribed to cancer patients. However, although recombinant human Epo (rHuEPO) significantly reduces the risk for red blood cell transfusions in cancer patients, recent clinical studies have reported decreased survival and disease control following rHuEPO treatment in patients with different cancer types. The issue of EPOR expression in tumor cells is critical in this respect. The expression of EPOR in tumor ce... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782860 Mon, 01 Sep 2008 04:00:00 +0100 1782860 http://www.medworm.com/index.php?rid=1782859&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781956%26dopt%3DAbstract Authors: Grigorian M, Ambartsumian N, Lukanidin E The role of S100A4 in tumor progression and metastasis is well documented in numerous research articles and summarized in several reviews [1-3]. Currently S100A4 is categorized as an essential metastasis-promoting factor whose production and secretion from "activated" stromal cells (fibroblasts, immunocytes and vascular cells) is initiated and stimulated by signals derived in tumor cells (cytokines, growth factors and others). However recent data gained from experimental and clinical studies significantly extend our knowledge on S100A4. Implications of S100A4 in various non-malignant pathological conditions have been demonstrated by number of research groups. In the mini-review we attempted to highlight the role of S100A4 in other than ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782859 Mon, 01 Sep 2008 04:00:00 +0100 1782859 http://www.medworm.com/index.php?rid=1782858&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781957%26dopt%3DAbstract Authors: Marriott HM, Mitchell TJ, Dockrell DH The cholesterol-dependent cytolysins are pore-forming toxins. Pneumolysin is the cytolysin produced by Streptococcus pneumoniae and is a key virulence factor. The protein contains 471 amino acids and four structural domains. Binding to cholesterol is followed by oligomerization and membrane pore formation. Pneumolysin also activates the classical pathway of complement. Mutational analysis of the toxin and knowledge of sequence variation in outbreak strains suggests that additional activities of biologic importance exist. Pneumolysin activates a large number of genes, some by epigenetic modification, in eukaryotic cells and multiple signal transduction pathways. Cytolytic effects contribute to lung injury and neuronal damage while pro-infla... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782858 Mon, 01 Sep 2008 04:00:00 +0100 1782858 http://www.medworm.com/index.php?rid=1782857&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781958%26dopt%3DAbstract Authors: Bonney KM, Engman DM Chagas heart disease (CHD), caused by the protozoan parasite Trypanosoma cruzi, is the leading cause of infectious myocarditis in the world. The etiology of CHD is unclear and multiple mechanisms have been proposed to explain the pathogenesis of the disease. This review describes the proposed mechanisms of CHD pathogenesis and evaluates the historical significance and evidence supporting each. Although the majority of CHD-related pathologies are currently attributed to parasite persistence in the myocardium and autoimmunity, there is strong evidence that CHD develops as a result of additive and even synergistic effects of several distinct mechanisms rather than one factor. PMID: 18781958 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782857 Mon, 01 Sep 2008 04:00:00 +0100 1782857 http://www.medworm.com/index.php?rid=1782856&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781959%26dopt%3DAbstract Authors: Qi L, Hu FB, Hu G Type 2 diabetes is one of the fastest growing public health problems worldwide. Both environmental (e.g. physical activity, obesity, and diet) and genetic factors are involved in the development of type 2 diabetes. The associations between physical activity and diabetes risk have been assessed by a number of prospective studies and clinical trials. The results from these studies consistently indicate that the regular physical activity during occupation, commuting, leisure time or daily life reduces the risk of type 2 diabetes by 15-60%; and lifestyle intervention, including counselling for physical activity, nutrition, and body weight, can reduce the risk of type 2 diabetes by 40-60% among adults with impaired glucose tolerance and by about 20% among general ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782856 Mon, 01 Sep 2008 04:00:00 +0100 1782856 http://www.medworm.com/index.php?rid=1782855&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781960%26dopt%3DAbstract Authors: Aso Y Diabetic nephropathy, which represents a major form of chronic kidney disease (CKD), is a leading cause of end-stage renal disease worldwide, and is also a risk factor for cardiovascular disease (CVD). Patients with diabetes and CKD have poorer outcomes after myocardial infarction. The underlying pathogenic mechanism that links diabetic nephropathy to a high risk of CVD remains unclear. In addition to traditional risk factors, including hypertension, hyperglycemia, and dyslipidemia, identification of novel modifiable risk factors is important in preventing CVD in people with diabetes. Inflammation/oxidative stress are known to be associated with an increased risk for CVD in patients with diabetic nephropathy. Moreover, homocysteine, advanced glycation end products, asymm... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782855 Mon, 01 Sep 2008 04:00:00 +0100 1782855 http://www.medworm.com/index.php?rid=1782854&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781961%26dopt%3DAbstract Authors: Martens K, Jaeken J, Matthijs G, Creemers JW Cystinuria type I is an autosomal recessive disorder with an exclusively renal phenotype caused by inactivating mutations in SLC3A1. Recently 3 similar but distinct syndromes associated with cystinuria type I have been described: 2p21 deletion syndrome, Hypotonia-Cystinuria Syndrome (HCS) and atypical HCS. Genetic analysis indicated that these are recessive contiguous gene deletion syndromes which differ in the number of genes affected. Patients with HCS are missing both alleles of SLC3A1 and PREPL. In atypical HCS an additional gene (C2orf34) is deleted, and finally, in the 2p21 deletion syndrome the open reading frame of PPM1B is also disrupted. With the exception of SLC3A1, the gene products have not been fully characterized. The... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782854 Mon, 01 Sep 2008 04:00:00 +0100 1782854 http://www.medworm.com/index.php?rid=1782853&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781962%26dopt%3DAbstract Authors: Gutierrez-Roelens I, Lauwerys BR Susceptibility to autoimmune disorders results from the interaction of multiple genetic factors that regulate the threshold of autoreactivity. Genome-wide microsatellite screens and large-scale single nucleotide polymorphism (SNP) association studies have identified chromosomal loci that are associated with specific disorders including systemic lupus erythematosus, rheumatoid arthritis, juvenile arthritis, multiple sclerosis, and diabetes. Numerous candidate gene association studies have in turn investigated the association of specific genes within these chromosomal regions, with susceptibility to autoimmune diseases (e.g. FcgammaReceptors, TYK2 and systemic lupus). More recently, large-scale differential gene expression studies performed on se... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782853 Mon, 01 Sep 2008 04:00:00 +0100 1782853 http://www.medworm.com/index.php?rid=1782852&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781963%26dopt%3DAbstract Authors: Giaginis C, Tsourouflis G, Theocharis S Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) ligands constitute important insulin sensitizers that have already been used for the treatment of human metabolic disorders, exerting also pleiotropic effects on inflammatory related diseases and cancer. Ischemia-reperfusion injury that is mainly associated with organ transplantation constitutes a serious complication with a great relevance in clinical practice. Accumulating experimental data have recently revealed that natural and synthetic PPAR-gamma ligands exert beneficial effects against ischemia-reperfusion injury. The present review summarizes the available information on the role of PPAR-gamma ligands in ischemia-reperfusion injury amongst the different organ systems. ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782852 Mon, 01 Sep 2008 04:00:00 +0100 1782852 http://www.medworm.com/index.php?rid=1782851&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781964%26dopt%3DAbstract Authors: Chiang PK, Lam MA, Luo Y The 'amyloid cascade hypothesis' links amyloid beta peptide (Abeta) with the pathological process of Alzheimer's disease (AD) and it still awaits universal acceptance. Amyloid precursor protein (APP), through the actions of the gamma-secretase complex, eventually becomes a different Abetaspecies. The various Abeta species have proven to be difficult to investigate under physiological conditions, and the species of Abeta responsible for neurotoxicity has yet to be unequivocally identified. The two important Abeta peptides involved are Abeta(1-40) and Abeta(1-42), and each has been ascribed both toxic and beneficial attributes. The ratio between the two species can be important in AD etiology. Additionally, shorter variants of Abeta peptides such as Abet... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782851 Mon, 01 Sep 2008 04:00:00 +0100 1782851 http://www.medworm.com/index.php?rid=1782850&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18781965%26dopt%3DAbstract Authors: Foster PS, Rosenberg HF, Asquith KL, Kumar RK Recruitment of eosinophils has long been recognized as a hallmark of the inflammatory response in asthma. However, the functions of this population of cells in host defense remain poorly understood. Eosinophils play an important part in the inflammatory response and have key regulatory roles in the afferent arm of the immune response. More recently, eosinophils have been demonstrated to participate in host defense against respiratory viruses. The specific contributions of eosinophils to the pathophysiology of asthma remain controversial. However, the balance of evidence indicates that they have a significant role in the disease, suggesting that they may be appropriate targets for therapy. Towards this end, a novel intervention of c... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1782850 Mon, 01 Sep 2008 04:00:00 +0100 1782850 http://www.medworm.com/index.php?rid=1701279&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691058%26dopt%3DAbstract Authors: Agrawal DK PMID: 18691058 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1701279 Fri, 01 Aug 2008 04:00:00 +0100 1701279 http://www.medworm.com/index.php?rid=1701278&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691059%26dopt%3DAbstract Authors: Barnes PJ GATA-3 is a transcription factor that is specifically expressed in T helper 2 (Th2) cells and plays a critical role in the differentiation of Th2 cells from uncommitted CD4(+) lymphocytes. In addition GATA-3 is essential for the gene expression of the cytokines IL-4, IL-5 and IL-13 that mediate allergic inflammation. In human T lymphocytes GATA-3 is normally localized to the cytoplasm, but on activation by antigen-presenting cells via the T cell receptor (CD3) and co-stimulatory receptor CD28 GATA-3 is phosphorylated by p38 MAP kinase and translocates to the nucleus via the nuclear import protein importin-alpha. Corticosteroids bound to glucocorticoid receptors inhibit GATA-3 function by competing for nuclear entry via importin-alpha and also by inhibiting p38 MAP ki... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1701278 Fri, 01 Aug 2008 04:00:00 +0100 1701278 http://www.medworm.com/index.php?rid=1701277&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691060%26dopt%3DAbstract Authors: Boyce JA Eicosanoids are diverse mediators of inflammation that derive from a single cell membrane phospholipid-associated precursor, arachidonic acid. This precursor is metabolized to several groups of lipid mediators, including (but not limited to) prostaglandins, leukotrienes, and lipoxins, in a tightly regulated, coordinated, cell- and context-specific manner. Each mediator serves regulatory and homeostatic functions in the onset and resolution of inflammation, immune responses, and tissue repair. The cloning of biosynthetic enzymes and G protein-coupled receptors for each of these mediators, the development of transgenic mice deficient in these molecules, and the availability of selective antagonists have permitted studies that have rapidly expanded our understanding of t... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1701277 Fri, 01 Aug 2008 04:00:00 +0100 1701277 http://www.medworm.com/index.php?rid=1701276&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D18691061%26dopt%3DAbstract Authors: Aceves SS, Broide DH Asthma is characterized by the presence of increased numbers of inflammatory cells in the airway in particular eosinophils and Th2 lymphocytes. In addition to the presence of inflammatory cells, the airways of patients with asthma exhibit varying levels of structural changes termed airway remodeling. These structural changes include subepithelial fibrosis, smooth muscle hypertrophy/hyperplasia, epithelial cell mucus metaplasia, and increased angiogenesis. This review focuses on the potential role of the eosinophil in promoting features of airway remodeling including fibrosis and neovascularization in chronic asthma. Eosinophils may potentially contribute to airway remodeling through release of eosinophil derived mediators such as TGFbeta which act directly... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=1701276 Fri, 01 Aug 2008 04:00:00 +0100 1701276