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 'Cell Research' source. Fri, 19 Mar 2010 18:00:47 +0100 http://www.medworm.com/index.php?rid=3374615&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231860%26dopt%3DAbstract Authors: Bradford JW, Li S, Li XJ The neurodegenerative polyglutamine diseases are caused by an expansion of unstable polyglutamine repeats in various disease proteins. Although these mutant proteins are expressed ubiquitously in neuronal and non-neuronal cells, they cause selective degeneration of specific neuronal populations. Recently, increasing evidence shows that polyglutamine disease proteins also affect non-neuronal cells. However, it remains unclear how the expression of polyglutamine proteins in non-neuronal cells contributes to the course of the polyglutamine diseases. Here, we discuss recent findings about the expression of mutant polyglutamine proteins in non-neuronal cells and their influence on neurological symptoms. Understanding the contribution of non-neuronal polyglu... Cell Research journals http://www.medworm.com/rss/comments.php?id=3374615 Tue, 16 Mar 2010 00:00:00 +0100 3374615 http://www.medworm.com/index.php?rid=3374614&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20231861%26dopt%3DAbstract Authors: Zhang J, Yang Y, Wu J PMID: 20231861 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3374614 Tue, 16 Mar 2010 00:00:00 +0100 3374614 http://www.medworm.com/index.php?rid=3374613&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20232362%26dopt%3DAbstract Authors: Joo KI, Tai A, Lee CL, Wong C, Wang P Membrane fusion plays an essential role in the entry of enveloped viruses into target cells. The merging of viral and target cell membranes is catalyzed by viral fusion proteins, which involves multiple sequential steps in the fusion process. However, the fusion mechanisms mediated by different fusion proteins involve multiple transient intermediates that have not been well characterized. Here, we report a synthetic virus platform that allows us to better understand the different fusion mechanisms driven by the diverse types fusion proteins. The platform consists of lentiviral particles coenveloped with a surface antibody, which serves as the binding protein, along with a fusion protein derived from either influenza virus (HAmu) or Sindbis... Cell Research journals http://www.medworm.com/rss/comments.php?id=3374613 Mon, 15 Mar 2010 00:00:00 +0100 3374613 http://www.medworm.com/index.php?rid=3374612&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20232363%26dopt%3DAbstract Authors: Manojlović-Stojanoski M, Nestorović N, Ristić N, Trifunović S, Filipović B, Sošić-Jurjević B, Sekulić M Glucocorticoids have an inhibitory influence on proliferation activity of the pituitary cells while stimulating apoptosis. Therefore, it was hypothesized that the synthetic glucocorticoid, dexamethasone (DX), has an inhibitory influence on the number of thyroid-stimulating hormone (TSH) cells during fetal development. The effects of maternal administration of DX on stereological parameters of TSH cells, and TSH serum concentration were investigated in 21-day-old rat fetuses. On day 16 of pregnancy, the experimental dams received 1.0 mg DX/kg b.w. subcutaneously, followed by 0.5 mg DX/kg b.w./day on days 17 and 18 of gesta... Cell Research journals http://www.medworm.com/rss/comments.php?id=3374612 Mon, 15 Mar 2010 00:00:00 +0100 3374612 http://www.medworm.com/index.php?rid=3374611&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20232466%26dopt%3DAbstract Authors: Canale C, Jacono M, Diaspro A, Dante S Solid supported lipid bilayers (SLB) are extensively used as a model for the investigation of cell membranes in a variety of spectroscopic and biophysical methods. It is nevertheless well known that the interaction with the solid substrate, such as mica or silicon, influences the properties of the membranes. In this article we have employed atomic force microscopy (AFM) in force spectroscopy mode (FS) to investigate the local mechanical properties of lipid membranes supported on mica and on polymer cushion. The lipid double layers were obtained by fusion of unilamellar vesicle of phospholipids. The polymer support was created by self-assembly of charged polyelectrolytes. Force spectroscopy provided information about the breakthrough force... Cell Research journals http://www.medworm.com/rss/comments.php?id=3374611 Mon, 15 Mar 2010 00:00:00 +0100 3374611 http://www.medworm.com/index.php?rid=3374616&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20229523%26dopt%3DAbstract Authors: Khan S, Newaz G This comprehensive literature review covers recent studies on patterning neuronal cells by topographical modifications on material surfaces targeted for neural prostheses. We explore different materials that are used as the candidate surface for neuronal cell adhesion. Cell-material interactions are identified in both cases where the material surface was in direct contact with cells and where the materials were coated to facilitate cell adhesion. Commonly used coating materials and coating methods are discussed. The existing hypotheses behind mechanism of the response of neuronal cells to a specific topography are presented briefly. A few selected important studies have been presented to show the range of techniques employed and the extent of the research area.... Cell Research journals http://www.medworm.com/rss/comments.php?id=3374616 Fri, 12 Mar 2010 00:00:00 +0100 3374616 http://www.medworm.com/index.php?rid=3362899&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20221799%26dopt%3DAbstract Authors: Thyssen M, Beker B, Ediger D, Yilmaz D, Garcia N, Denis M Automated in situ flow cytometry, high-pressure liquid chromatography (HPLC), optical microscopy and fluorometry were combined to monitor phytoplankton over two summer periods (2005 and 2006). In 2006, temperature was higher and nutrients lower than in 2005, generating differences in the phytoplankton assemblages (i.e., abundance and structure). Pigment-size classes based on daily HPLC analysis provided evidence for higher proportions of picoplankton and nanoplankton with higher biomass in 2005 and a dominance of microplankton with lower biomass in 2006, the latter with lower specific diversity, as evidenced by weekly microscopy analyses. Total chlorophyll a estimations from fluorometry measurements recorded every 30 mi... Cell Research journals http://www.medworm.com/rss/comments.php?id=3362899 Thu, 11 Mar 2010 00:00:00 +0100 3362899 http://www.medworm.com/index.php?rid=3362898&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20221894%26dopt%3DAbstract This study laid the foundation of nanochemoprevention by bioactive food components. Since oral consumption is the most desirable and acceptable form of delivery of bioactive food components, it will be important to develop nanoparticles containing bioactive food components that are suitable for oral consumption for which experiments are underway in this laboratory. PMID: 20221894 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3362898 Thu, 11 Mar 2010 00:00:00 +0100 3362898 http://www.medworm.com/index.php?rid=3362897&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20225211%26dopt%3DAbstract Authors: Anbharasi V, Cao N, Feng SS This research developed a prodrug strategy to conjugate doxorubicin (DOX) to D-alpha-tocopheryl polyethylene glycol succinate (TPGS) and folic acid (FOL) for targeted chemotherapy to enhance the therapeutic effects and reduce the side effects of the drug. We synthesized two conjugates, TPGS-DOX and TPGS-DOX-FOL, to quantitatively evaluate the advantages of TPGS conjugation and FOL conjugation through passive and active targeting effects. The successful conjugation was confirmed by (1)H nuclear magnetic resonance spectroscopy and Fourier transform infrared spectroscopy. The in vitro drug release was found pH dependent, which is in favor of cancer treatment. The in vitro cellular uptake and cytotoxicity were evaluated with MCF-7 breast cancer cells. I... Cell Research journals http://www.medworm.com/rss/comments.php?id=3362897 Thu, 11 Mar 2010 00:00:00 +0100 3362897 http://www.medworm.com/index.php?rid=3362896&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20225212%26dopt%3DAbstract In conclusions, these results suggest that removing residual protein contamination may decrease the immunogenicity of certain alginate preparations. The measurement of proteins could be used as a screening method for evaluating alginate preparations. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010. PMID: 20225212 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3362896 Thu, 11 Mar 2010 00:00:00 +0100 3362896 http://www.medworm.com/index.php?rid=3362895&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20225216%26dopt%3DAbstract Authors: Haberstroh K, Ritter K, Kuschnierz J, Bormann KH, Kaps C, Carvalho C, Mülhaupt R, Sittinger M, Gellrich NC The aim of this study was to investigate the osteogenic effect of three different cell-seeded 3D-bioplotted scaffolds in a ovine calvarial critical-size defect model. The choice of scaffold-materials was based on their applicability for 3D-bioplotting and respective possibility to produce tailor-made scaffolds for the use in cranio-facial surgery for the replacement of complex shaped boneparts. Scaffold raw-materials are known to be osteoinductive when being cell-seeded [poly(L-lactide-co-glycolide) (PLGA)] or having components with osteoinductive properties as tricalciumphosphate (TCP) or collagen (Col) or chitosan. The scaffold-materials PLGA, TCP/Col, and HYDR (TC... Cell Research journals http://www.medworm.com/rss/comments.php?id=3362895 Thu, 11 Mar 2010 00:00:00 +0100 3362895 http://www.medworm.com/index.php?rid=3362894&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20225285%26dopt%3DAbstract Authors: Han HS, Lee S, Kim JH, Seong SC, Lee MC We undertook this study to characterize changes in the proliferative capacities, chondrogenic phenotypes, and gene expression profiles of human synovium-derived progenitor cells from osteoarthritic patients during in vitro expansion. Cells isolated from osteoarthritic synovia were cultured, and growth rates during serial passages were evaluated. Surface molecule expressions were determined by flow cytometry and cytogenetic analyses were performed. After chondrogenic differentiation in cell pellets, we evaluated type II collagen and glycosaminoglycan (GAG) synthesis. To assess whether the in vitro expansion of synovium-derived cells affects gene expression, we performed microarray analyses on cells at passage 0, 1, 2, 4, 6, and 8. Synoviu... Cell Research journals http://www.medworm.com/rss/comments.php?id=3362894 Thu, 11 Mar 2010 00:00:00 +0100 3362894 http://www.medworm.com/index.php?rid=3362893&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20225313%26dopt%3DAbstract This study aims to explore these mechanisms by using a mouse treadmill running model to examine the effects of exercise on newly discovered tendon stem cells (TSCs). After treadmill running, patellar TSCs (PTSCs) and Achilles TSCs (ATSCs) were isolated from the mice, and their proliferation was measured in vitro. We found that treadmill running nearly doubled proliferation rates of both PTSCs and ATSCs compared to cage control mice. Moreover, using a mixed tendon cell culture consisting of TSCs and tenocytes, cellular production of collagen was found to increase by 70% and 200% in PTSCs and ATSCs, respectively, from the treadmill running group over cells from the cage control group. These findings suggest that exercise exerts its anabolic effects on tendons at least in part by increasing p... Cell Research journals http://www.medworm.com/rss/comments.php?id=3362893 Thu, 11 Mar 2010 00:00:00 +0100 3362893 http://www.medworm.com/index.php?rid=3362892&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20225321%26dopt%3DAbstract The objective of this study was to investigate the association of aggregation (condensation) of mesenchymal stem cell (MSCs) and chondrogenesis in vitro. Previous work with chondrocytes indicated that the cross-link density and related cell-mediated contraction of collagen scaffolds significantly affects cartilaginous tissue formation within the cell-seeded construct. Based on this finding, we hypothesized that the cell-aggregating effect of the contraction of MSC-seeded collagen scaffolds of lower cross-link density favors chondrogenesis; scaffolds of higher cross-link density, which resist cell-mediated contraction, would demonstrate a lower cell number density (i.e., subcritical packing density) and less cartilage formation. Type II collagen-GAG scaffolds, chemically cross-linked to ach... Cell Research journals http://www.medworm.com/rss/comments.php?id=3362892 Thu, 11 Mar 2010 00:00:00 +0100 3362892 http://www.medworm.com/index.php?rid=3347426&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205869%26dopt%3DAbstract CONCLUSIONS: This study predicts that crucial hydrogen bonding between N-sh2 domain of Shp-1 and Kit activation loop can modulate the negative regulation of c-Kit kinase by Shp-1. Thus, this finding is expected to play a significant role in designing suitable gain-of-function c-Kit mutants for inducing conditional proliferation of hematopoietic stem cells. PMID: 20205869 [PubMed - in process] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3347426 Wed, 10 Mar 2010 10:24:03 +0100 3347426 http://www.medworm.com/index.php?rid=3338158&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20122228%26dopt%3DAbstract CONCLUSION: The above-mentioned virtual screening procedures helped in the identification of several potent candidates that possess inhibitory activity against Mtb DHDPS. Therefore, these novel scaffolds/candidates which could have the potential to inhibit Mtb DHDPS enzyme would represent promising starting points as lead compounds and certainly aid the experimental designing of antituberculars in lesser time. PMID: 20122228 [PubMed - in process] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3338158 Sat, 06 Mar 2010 16:40:03 +0100 3338158 http://www.medworm.com/index.php?rid=3338156&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20204826%26dopt%3DAbstract Authors: Sakai H, Sou K, Horinouchi H, Kobayashi K, Tsuchida E Hb-vesicles (HbV) are artificial O(2) carriers encapsulating concentrated Hb solution (35 g/dL) with a phospholipid bilayer membrane (liposome). The concentration of the HbV suspension is extremely high ([Hb] = 10 g/dL) and it has an O(2) carrying capacity that is comparable to that of blood. HbV is much smaller than RBC (250 vs. 8000 nm), but it recreates the functions of RBCs; (i) the slower rate of O(2) unloading than Hb solution; (ii) colloid osmotic pressure is zero; (iii) the viscosity of a HbV suspension is adjustable to that of blood; (iv) HbV is finally captured by and degraded in RES; (v) co-encapsulation of an allosteric effector to regulate O(2) affinity; (vi) the lipid bilayer membrane prevents direct contact o... Cell Research journals http://www.medworm.com/rss/comments.php?id=3338156 Sat, 06 Mar 2010 16:40:03 +0100 3338156 http://www.medworm.com/index.php?rid=3338155&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20205237%26dopt%3DAbstract This study describes the preparation of semi-Interpenetrated Networks (semi-IPNs) of crosslinked poly(N-isopropylacrylamide), or PNIPAam, with collagen type I. The collagen-PNIPAam networks with varying collagen content were characterized using Fourier transform infrared spectroscopy techniques and their thermal responsiveness was evaluated by swelling experiments, differential scanning calorimetric (DSC) analysis. Rheological studies were performed at constant frequency and oscillating stress. PNIPAam and semi-IPNs were preloaded with nerve growth factor (NGF), and the NGF releasing profiles at different temperatures were studied using Enzyme-Linked ImmunoSorbent Assay (ELISA). The growth and differentiation of PC12 cells on NGF PNIPAam and collagen-PNIPAam scaffolds were investigated in ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3338155 Thu, 04 Mar 2010 00:00:00 +0100 3338155 http://www.medworm.com/index.php?rid=3338157&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20199106%26dopt%3DAbstract Authors: He H, Nilsson CL, Emmett MR, Marshall AG, Kroes RA, Moskal JA, Ji Y, Lang FF, Priebe W, Colman H, Conrad CA A glioblastoma stem cell (GSC) line, GSC11, grows as neurospheres in serum-free media supplemented with EGF (epidermal growth factor) and bFGF (basic fibroblast growth factor), and if implanted in nude mice brains, will recapitulate high-grade glial tumors. Treatment with a STAT3 (signal transducer and activator of transcription 3) phosphorylation inhibitor (WP1193) or 10% FBS (fetal bovine serum) both led to a decrease in expression of the stem cell marker CD133 in GSC11 cells, but differed in phenotype changes. Altered glycolipid profiles were associated with some differentially expressed glycogenes. In serum treated cells, an overall increase in glycosphingolipids may... Cell Research journals http://www.medworm.com/rss/comments.php?id=3338157 Wed, 03 Mar 2010 00:00:00 +0100 3338157 http://www.medworm.com/index.php?rid=3331614&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20195295%26dopt%3DAbstract In this study, we found that a protein encoded by the antisense gene ADF1 acts as a transcription suppressor, regulating the expression of sense gene MDF1 in Saccharomyces cerevisiae. Based on the evolutionary, genetic, cytological and biochemical evidence, we show that the protein-coding sense gene MDF1 most likely originated de novo from a previously non-coding sequence and can significantly suppress the mating efficiency of baker's yeast in rich medium by binding MATalpha2 and thus promote vegetative growth. These results shed new light on several important issues, including a new sense-antisense interaction mechanism, the de novo origination of a functional gene, and the regulation of yeast mating pathway.Cell Research advance online publication 2 March 2010; doi: 10.1038/cr.2010.31. ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331614 Tue, 02 Mar 2010 00:00:00 +0100 3331614 http://www.medworm.com/index.php?rid=3331610&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197379%26dopt%3DAbstract In this study, we show that the reduction of PDK1 by RNAi in melanoma and colon cancer cell lines activated in the MAPK pathway results in significant cell growth inhibition and apoptosis. Furthermore, PDK1 reduction in tumor cells resulted in impaired PAK kinase signaling, altered actin polymerization, and reduced cell migration. These studies show that PDK1 plays a pivotal role in MAPK and PI3K signaling in tumor cells. Mol Cancer Res; 8(3); 421-32. PMID: 20197379 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3331610 Tue, 02 Mar 2010 00:00:00 +0100 3331610 http://www.medworm.com/index.php?rid=3331609&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197380%26dopt%3DAbstract Authors: Huck JJ, Zhang M, McDonald A, Bowman D, Hoar KM, Stringer B, Ecsedy J, Manfredi MG, Hyer ML Aurora A Kinase is a serine/threonine protein kinase responsible for regulating several mitotic processes including centrosome separation, spindle assembly, and chromosome segregation. Small molecule inhibitors of Aurora A kinase are being pursued as novel anticancer agents, some of which have entered clinical trials. Despite the progress in developing these agents, terminal outcomes associated with Aurora A inhibition are not fully understood. Although evidence exists that Aurora A inhibition leads to apoptosis, other therapeutically relevant cell fates have not been reported. Here, we used the small molecule inhibitor MLN8054 to show that inhibition of Aurora A induces tumor cell sene... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331609 Tue, 02 Mar 2010 00:00:00 +0100 3331609 http://www.medworm.com/index.php?rid=3331608&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197381%26dopt%3DAbstract We examined whether these two angiogenic factors cooperate in regulation of endothelial cell migratory responses. VEGF stimulated expression of ATX and LPA1, a receptor for the ATX enzymatic product lysophosphatidic acid (LPA), in human umbilical vein endothelial cells. Knockdown of ATX expression significantly decreased mRNA levels for the receptors LPA1, LPA2, S1P1, S1P2, S1P3, and VEGFR2 and abolished cell migration to lysophosphatidylcholine, LPA, recombinant ATX, and VEGF. Migration to sphingosylphosphorylcholine and sphinogosine-1-phosphate was also reduced in ATX knockdown cells, whereas migration to serum remained unchanged. Furthermore, ATX knockdown decreased Akt2 mRNA levels, whereas LPA treatment strongly stimulated Akt2 expression. We propose that VEGF stimulates LPA productio... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331608 Tue, 02 Mar 2010 00:00:00 +0100 3331608 http://www.medworm.com/index.php?rid=3331607&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197383%26dopt%3DAbstract Authors: Ben Shachar B, Feldstein O, Hacohen D, Ginsberg D The E2F1 transcription factor is a critical downstream target of the tumor suppressor RB. When activated, E2F1 can induce cell proliferation and/or apoptosis. In addition, E2F1 overexpression sensitizes cancer cells to chemotherapeutic drugs. In a screen for genes that are regulated synergistically by E2F1 and chemotherapy in cancer cells, we identified the proapoptotic tumor suppressor gene maspin (mammary serine protease inhibitor) as a novel E2F1-regulated gene. In line with being an E2F-regulated gene, maspin expression is inhibited by short hairpin RNA directed against E2F1 and increases upon activation of endogenous E2F. Furthermore, maspin mRNA and protein levels are elevated upon activation of exogenous E2F1. Importantl... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331607 Tue, 02 Mar 2010 00:00:00 +0100 3331607 http://www.medworm.com/index.php?rid=3331605&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197384%26dopt%3DAbstract Authors: Vidal LJ, Perry JK, Vouyovitch CM, Pandey V, Brunet-Dunand SE, Mertani HC, Liu DX, Lobie PE Deregulated PAX5 expression has been associated with metastatic mammary carcinoma, although the precise role of PAX5 in cancer progression is unclear. Stable forced expression of PAX5alpha in the mammary carcinoma cell lines MCF-7 and MDA-MB-231 reduced cell cycle progression, cell survival, and anchorage-independent cell growth. In xenograft studies, forced expression of PAX5alpha was associated with a significant reduction in tumor volume. Furthermore, forced expression of PAX5alpha in mammary carcinoma cells resulted in altered cell morphology with resultant enhancement of epithelial cell characteristics. Morphologic changes were associated with localization of beta-CATENIN at cell-c... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331605 Tue, 02 Mar 2010 00:00:00 +0100 3331605 http://www.medworm.com/index.php?rid=3331598&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197385%26dopt%3DAbstract Authors: Fritz RD, Radziwill G Hallmarks of cancer cells are uncontrolled proliferation, evasion of apoptosis, angiogenesis, cell invasion, and metastasis, which are driven by oncogenic activation of signaling pathways. Herein, we identify the scaffold protein CNK1 as a mediator of oncogenic signaling that promotes invasion in human breast cancer and cervical cancer cells. Downregulation of CNK1 diminishes the invasiveness of cancer cells and correlates with reduced expression of matrix metalloproteinase 9 (MMP-9) and membrane-type 1 MMP (MT1-MMP). Ectopic expression of CNK1 elevates MT1-MMP promoter activity in a NF-kappaB-dependent manner. Moreover, CNK1 cooperates with the NF-kappaB pathway, but not with the extracellular signal-regulated protein kinase pathway, to promote cell inva... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331598 Tue, 02 Mar 2010 00:00:00 +0100 3331598 http://www.medworm.com/index.php?rid=3331596&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197461%26dopt%3DAbstract Authors: Xu Y, Stamenkovic I, Yu Q Glioblastoma multiforme (GBM) is the most aggressive brain tumor that, by virtue of its resistance to chemotherapy and radiotherapy, is currently incurable. Identification of molecules whose targeting may eliminate GBM cells and/or sensitize glioblastoma cells to cytotoxic drugs is therefore urgently needed. CD44 is a major cell surface hyaluronan receptor and cancer stem cell marker that has been implicated in the progression of a variety of cancer types. However, the major downstream signaling pathways that mediate its protumor effects and the role of CD44 in the progression and chemoresponse of GBM have not been established. Here we show that CD44 is upregulated in GBM and that its depletion blocks GBM growth and sensitizes GBM cells to cytotoxic d... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331596 Tue, 02 Mar 2010 00:00:00 +0100 3331596 http://www.medworm.com/index.php?rid=3331593&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197462%26dopt%3DAbstract This study further elucidates the molecular loop between p53 and Ras in the transformation process. Cancer Res; 70(6); 2274-84. PMID: 20197462 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3331593 Tue, 02 Mar 2010 00:00:00 +0100 3331593 http://www.medworm.com/index.php?rid=3331592&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197463%26dopt%3DAbstract Authors: Zoubeidi A, Zardan A, Wiedmann RM, Locke J, Beraldi E, Fazli L, Gleave ME Hsp27 is highly expressed in castrate-resistant prostate cancer. Although its overexpression confers resistance to androgen ablation and chemotherapy, the mechanisms by which Hsp27 inhibits treatment-induced apoptosis are incompletely defined. Castrate-resistance often correlates with increased activity of autocrine and/or paracrine growth/survival stimulatory loops including the mitogen-activated protein kinase (MAPK) and Akt pathways and insulin-like growth factor (IGF) axis components. Because Hsp27 can be activated by both MAPK and Akt pathways, it is possible that interactions between IGF-I signaling and Hsp27 phosphoactivation function to promote castrate-resistant progression. Here, we report that... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331592 Tue, 02 Mar 2010 00:00:00 +0100 3331592 http://www.medworm.com/index.php?rid=3331591&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197464%26dopt%3DAbstract In this study, we developed an IgG-like fusion protein molecule [vascular endothelial growth factor (VEGF) receptor 31-immunoglobulin (VEGFR31-Ig)] which could simultaneously bind the angiogenic growth factor VEGF-A and the lymphangiogenic growth factor VEGF-C. Importantly, VEGFR31-Ig exhibited VEGF-A-binding affinity similar to that of VEGFTrap, the most potent VEGF-A binder, and VEGF-C-binding affinity comparable with that of the soluble fusion protein VEGFR3-Ig (sVEGFR3). Pharmacokinetic analysis in mice showed that VEGFR31-Ig had improved pharmacokinetic properties compared with either VEGFTrap or sVEGFR3. In a highly metastatic human hepatocellular carcinoma (HCCLM3) model in severe combined immunodeficient mice, VEGFR31-Ig potently blocked both tumor angiogenesis and lymphangiogenesi... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331591 Tue, 02 Mar 2010 00:00:00 +0100 3331591 http://www.medworm.com/index.php?rid=3331590&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197465%26dopt%3DAbstract Authors: Yan TD, Wu H, Zhang HP, Lu N, Ye P, Yu FH, Zhou H, Li WG, Cao X, Lin YY, He JY, Gao WW, Zhao Y, Xie L, Chen JB, Zhang XK, Zeng JZ Retinoic acid receptors (RAR; alpha, beta, and gamma), members of the nuclear receptor superfamily, mediate the pleiotropic effects of the vitamin A metabolite retinoic acid (RA) and derivatives (retinoids) in normal and cancer cells. Abnormal expression and function of RARs are often involved in the growth and development of cancer. However, the underlying molecular mechanisms remain largely elusive. Here, we report that levels of RARgamma were significantly elevated in tumor tissues from a majority of human hepatocellular carcinoma (HCC) and in HCC cell lines. Overexpression of RARgamma promoted colony formation by HCC cells in vitro and the growt... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331590 Tue, 02 Mar 2010 00:00:00 +0100 3331590 http://www.medworm.com/index.php?rid=3331589&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197466%26dopt%3DAbstract Authors: Yogev O, Goldberg R, Anzi S, Yogev O, Shaulian E The growing number of biological functions affected by autophagy ascribes a special significance to identification of factors regulating it. The activator protein-1 (AP-1) transcription factors are involved in most aspects of cellular proliferation, death, or survival, yet no information regarding their involvement in autophagy is available. Here, we show that the AP-1 proteins JunB and c-Jun, but not JunD, c-Fos, or Fra-1, inhibit autophagy. JunB inhibits autophagy induced by starvation, overexpression of a short form of ARF (smARF), a potent inducer of autophagy, or even after rapamycin treatment. In agreement, acute repression of JunB expression, by JunB knockdown, potently induces autophagy. As expected from autophagy-inhibi... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331589 Tue, 02 Mar 2010 00:00:00 +0100 3331589 http://www.medworm.com/index.php?rid=3331588&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197467%26dopt%3DAbstract In this study, we use an ERBB2-transgenic mouse model of breast cancer (neuT) to show that Notch signaling plays a critical role in tumor maintenance. Inhibition of the Notch pathway with a gamma-secretase inhibitor (GSI) decreased both the Notch and the mammalian target of rapamycin/AKT pathways. Antitumor activity resulting from GSI treatment was associated with decreased cell proliferation as measured by Ki67 and decreased expression of glucose transporter Glut1. Positron emission tomography (PET) imaging showed that the functional consequences of decreased Glut1 translated to reduced glucose uptake and correlated with antitumor effects as measured by micro-computed tomography imaging. The decrease of Glut1 in neuT tumors was also observed in several human breast cancer cell lines follo... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331588 Tue, 02 Mar 2010 00:00:00 +0100 3331588 http://www.medworm.com/index.php?rid=3331587&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197468%26dopt%3DAbstract We report the development of a genetically engineered mouse model of BSG using the RCAS/tv-a system and its implementation in preclinical trials. Using immunohistochemistry, we found that platelet-derived growth factor (PDGF) receptor alpha is overexpressed in 67% of pediatric BSGs. Based on this observation, we induced low-grade BSGs by overexpressing PDGF-B in the posterior fossa of neonatal nestin tv-a mice. To generate high-grade BSGs, we overexpressed PDGF-B in combination with Ink4a-ARF loss, given that this locus is commonly lost in high-grade pediatric BSGs. We show that the likely cells of origin for these mouse BSGs exist on the floor of the fourth ventricle and cerebral aqueduct. Irradiation of these high-grade BSGs shows that although single doses of 2, 6, and 10 Gy significant... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331587 Tue, 02 Mar 2010 00:00:00 +0100 3331587 http://www.medworm.com/index.php?rid=3331586&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197469%26dopt%3DAbstract Authors: Hashizume H, Falcón BL, Kuroda T, Baluk P, Coxon A, Yu D, Bready JV, Oliner JD, McDonald DM Inhibition of angiopoietin-2 (Ang2) can slow tumor growth, but the underlying mechanism is not fully understood. Because Ang2 is expressed in growing blood vessels and promotes angiogenesis driven by vascular endothelial growth factor (VEGF), we asked whether the antitumor effect of Ang2 inhibition results from reduced sprouting angiogenesis and whether the effect is augmented by inhibition of VEGF from tumor cells. Using Colo205 human colon carcinomas in nude mice as a model, we found that selective inhibition of Ang2 by the peptide-Fc fusion protein L1-7(N) reduced the number of vascular sprouts by 46% and tumor growth by 62% over 26 days. Strikingly, when the Ang2 inhibitor was ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331586 Tue, 02 Mar 2010 00:00:00 +0100 3331586 http://www.medworm.com/index.php?rid=3331585&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197470%26dopt%3DAbstract Authors: Ouyang M, Huang H, Shaner NC, Remacle AG, Shiryaev SA, Strongin AY, Tsien RY, Wang Y Both Src kinase and membrane type 1 matrix metalloproteinase (MT1-MMP) play critical roles in cancer invasion and metastasis. It is not clear, however, how the spatiotemporal activation of these two critical enzymes is coordinated in response to an oncogenic epithelial growth factor (EGF) stimulation. Here, we have visualized the activities of Src and MT1-MMP concurrently in a single live cell by combining two fluorescence resonance energy transfer (FRET) pairs with distinct spectra: (a) cyan fluorescent protein (CFP) and yellow FP (YFP), and (b) orange FP (mOrange2) and red FP (mCherry). The new FRET pair, mOrange2 and mCherry, was first characterized in vitro and in cultured mammalian cells.... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331585 Tue, 02 Mar 2010 00:00:00 +0100 3331585 http://www.medworm.com/index.php?rid=3331584&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197482%26dopt%3DAbstract Authors: Wiezorek J, Holland P, Graves J Apoptosis is integral to normal, physiologic processes that regulate cell number and results in the removal of unnecessary or damaged cells. Apoptosis is frequently dysregulated in human cancers, and recent advancements in our understanding of the regulation of programmed cell death pathways has led to the development of novel agents to reactivate apoptosis in malignant cells. The activation of cell surface death receptors by tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) and death receptor agonists represent an attractive therapeutic strategy to promote apoptosis of tumor cells through the activation of the extrinsic pathway. The observation that Apo2L/TRAIL can eliminate tumor cells preferentially over normal cells has r... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331584 Tue, 02 Mar 2010 00:00:00 +0100 3331584 http://www.medworm.com/index.php?rid=3331583&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20197483%26dopt%3DAbstract CONCLUSIONS: 5-ASA increases replication fidelity in mononucleotide, dinucleotide, and tetranucleotide repeats and reduces mutations in tumor suppressor genes TGFBR2 and ACVR2, a finding that may provoke in vivo studies for the prevention of colorectal cancer in hereditary nonpolyposis colorectal cancer. Clin Cancer Res; 16(6); 1950-6. PMID: 20197483 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3331583 Tue, 02 Mar 2010 00:00:00 +0100 3331583 http://www.medworm.com/index.php?rid=3331582&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198690%26dopt%3DAbstract This study aims to optimize the immobilization of EGF on 11-mercapto-1-undecyl-tetra(ethylene)glycol (EG4)-self-assembled monolayers (SAMs) and to establish a new model surface to study EGF-mediated signaling. Gold substrates were modified with a monolayer of EG4 and N,N'-carbonyldiimidazole (CDI) was used to activate hydroxyl terminated groups of EG4-SAMs. EGF was then immobilized on activated EG4-SAMs at pH 7.4, 4 degrees C, and 100 rpm. Different immobilization reaction times were tested as well as different CDI concentrations to optimize the reaction conditions and obtain a range of immobilized EGF concentrations on the surfaces. Surface characterization of EGF-SAMs was performed using radiolabeling, water contact angle measurements, X-ray photoelectron spectroscopy, and ELISA. Phospho... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331582 Tue, 02 Mar 2010 00:00:00 +0100 3331582 http://www.medworm.com/index.php?rid=3331581&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198692%26dopt%3DAbstract In this study, we investigated this concept by loading porous hydroxyapatite-poly(lactide-co-glycolide) (HA-PLAGA) scaffolds with a model protein, cytochrome c, and then studying its release in a phosphate-buffered saline solution. The HA-PLAGA scaffold has previously been shown to be bioactive, osteoconductive, and to have appropriate physical properties for tissue engineering applications. The loading experiments demonstrated that the HA-PLAGA scaffold could also function effectively as a substrate for protein adsorption and release. Scaffold protein adsorptive loading (as opposed to physical entrapment within the matrix) was directly related to levels of scaffold HA-content. The HA phase of the scaffold facilitated protein retention in the matrix following incubation in aqueous buffer f... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331581 Tue, 02 Mar 2010 00:00:00 +0100 3331581 http://www.medworm.com/index.php?rid=3331580&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198693%26dopt%3DAbstract This study was conducted to investigate whether in vitro chondrogenic differentiated human adipose-derived stem cells (hASCs) can maintain the chondrogenic phenotype in (3-hydroxybutrate-co-3-hydroxyvalerate) (PHBV) scaffolds and whether differentiated hASCs/PHBV construct can produce neocartilage in a heterotopic animal model. hASCs were cultured with or without chondrogenic media in vitro and then seeded on PHBV foams. Differentiated cell/PHBV constructs were subcutaneously implanted in nude mice for 8 or 16 weeks; nondifferentiated cell/PHBV constructs were implanted in the control group. The results in the control group showed no cartilage formation and the disappearance of the scaffold at 8 weeks. Conversely, all differentiated hASCs/PHBV implants kept their original shape throughout ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331580 Tue, 02 Mar 2010 00:00:00 +0100 3331580 http://www.medworm.com/index.php?rid=3331579&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198694%26dopt%3DAbstract In this study, osteogenic MC3T3-E1 cells were cultured and differentiation-induced on bulk and sputter-deposited titanium specimens, and the osteogenesis were investigated. For the preparation of bulk specimens, titanium discs were mirror-polished. On the other hand, titanium was sputter-deposited on smooth and clean cover glasses as sputter-deposited specimens. As a result, no significant difference was observed in the cell morphology and attached number. On the other hand, the time showing maximum activity in the alkaline phosphatase and gene expressions, which are related to bone differentiation on the bulk titanium, were superior to those on the sputter-deposited titanium. From the surface observation of the specimens with a scanning electron microscope and a scanning probe microscope,... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331579 Tue, 02 Mar 2010 00:00:00 +0100 3331579 http://www.medworm.com/index.php?rid=3331578&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198695%26dopt%3DAbstract Authors: d'Ayala GG, Calarco A, Malinconico M, Laurienzo P, Petillo O, Torpedine A, Peluso G The major aim of nonviral delivery systems for gene therapy is to mediate high levels of gene expression with low toxicity. Nowadays, one of the most successful synthetic polycations used in gene delivery research is poly(ethylenimine) (PEI) in its high-molecular weight (HMW) branched form. However, PEI is not the ideal transfection agent in vivo because of its overwhelming cytotoxicity. To overcome its toxic effects with a minimal impact on transfection efficiency, PEI has been conjugated with several nonionic biocompatible polymers. Here, we describe the synthesis of nanosized particles consisting of HMW PEI (25 kDa) crosslinked with poly(epsilon-caprolactone) (PCL, 50-60 kDa), a biodegradabl... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331578 Tue, 02 Mar 2010 00:00:00 +0100 3331578 http://www.medworm.com/index.php?rid=3331577&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198696%26dopt%3DAbstract In this study, the PBAE library was assessed for candidate materials that met design criteria (e.g., physical properties such as degradation and mechanical strength and in vitro cell viability and osteoconductive behavior) for scaffolding in mineralized tissue repair. The most promising candidate, A6, was then processed into three-dimensional porous scaffolds and implanted subcutaneously and only presented a mild inflammatory response. The scaffolds were then implanted intramuscularly and into a critical-sized cranial defect either alone or loaded with bone morphogenetic protein-2 (BMP-2). The samples in both locations displayed mineralized tissue formation in the presence of BMP-2, as evident through radiographs, micro-computed tomography, and histology, whereas samples without BMP-2 show... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331577 Tue, 02 Mar 2010 00:00:00 +0100 3331577 http://www.medworm.com/index.php?rid=3331573&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198698%26dopt%3DAbstract Authors: Zhang W, Shao J The biomedical properties of novel biodegradable copoly(amino acid)s based on 6-aminocaproic acid and L-proline were analyzed in this article. The cytotoxicity of the copolymer films was tested in vitro using human embryonic kidney (HEK) 293 cells. The cell proliferation, cell cycle, cell apoptosis, and hemolysis of the polymers were also investigated. No significant cytotoxic response was detected statistically by cytotoxicity assay, and the results of cell apoptosis and cell cycle showed that there were no statistically significant differences in them. Generally, the cells spread and grew well on polymer film. Meanwhile, the extent of hemolysis on the polymers was acceptable. Evaluation of cytotoxicity by cell cycle and apoptosis as a supplementary assay is c... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331573 Tue, 02 Mar 2010 00:00:00 +0100 3331573 http://www.medworm.com/index.php?rid=3331572&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20198699%26dopt%3DAbstract This study compares the behavior of osteoblastic cells seeded on three structurally distinct collagen-based materials. Adhesion and long-term behavior were evaluated in vitro in regard to collagen scaffolds forming loose or dense fibrillar networks or exempt of fibrils. In this purpose collagen solutions at concentrations of 5 and 40 mg/mL were processed by freeze-drying or by sol/gel fibrillogenesis to form either sponges or hydrogels. Macroscopic and microscopic images of sponges showed a light material exhibiting large pores surrounded by dense collagen walls made of thin unstriated microfibrils of 20 nm in diameter. In comparison collagen hydrogels are more homogeneous materials, at 5 mg/mL the material consists of a regular network of cross-striated collagen fibrils of 100 nm in diame... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331572 Tue, 02 Mar 2010 00:00:00 +0100 3331572 http://www.medworm.com/index.php?rid=3331612&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196102%26dopt%3DAbstract Authors: Karthigeyan D, Prasad SB, Shandilya J, Agrawal S, Kundu TK The Aurora A kinase belongs to serine/threonine group of kinases, well known for its role in cell cycle, especially in the regulation of mitosis. Numerous substrates of Aurora A kinase have been identified, which are predominantly related to cell cycle progression while some of them are transcription factors. Aurora A-mediated phosphorylation can either directly or indirectly regulate the function of its substrates. There are overwhelming evidences which report overexpression and gene amplification of Aurora A in several human cancers, and suggest that Aurora A could be a bona fide oncogene involved in tumorigenesis. Hence, Aurora A plays wide-ranging roles in both mitosis and its deregulation manifests in cancer progr... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331612 Mon, 01 Mar 2010 00:00:00 +0100 3331612 http://www.medworm.com/index.php?rid=3331611&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196106%26dopt%3DAbstract This study was aimed to establish an efficient xeno-feeder free limbal culture system towards ocular surface regeneration. To study the effect of initial dispase treatment and culture system used, migratory distance of cells from explants was analyzed from phase contrast images using "interactive measurements" of Qwin software (Leica). Expression of p63 in different culture systems was studied by immunofluorescent staining, followed by quantitative confocal microscopy (Carl Zeiss). Results showed dispase treatment was not necessary for establishing limbal explant culture. A combination of Iscove's modified Dulbecco's medium and Panserin 801 resulted in formation of autofeeder layer with maintenance of progenitor characteristics, thus mimicking natural tissue architecture. Further analysis ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3331611 Mon, 01 Mar 2010 00:00:00 +0100 3331611 http://www.medworm.com/index.php?rid=3322826&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20190773%26dopt%3DAbstract Authors: Norman KL, Sarnow P PMID: 20190773 [PubMed - in process] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3322826 Mon, 01 Mar 2010 00:00:00 +0100 3322826 http://www.medworm.com/index.php?rid=3322825&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20190774%26dopt%3DAbstract Authors: Zou J, Cochran R, Cheng L PMID: 20190774 [PubMed - in process] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3322825 Mon, 01 Mar 2010 00:00:00 +0100 3322825 http://www.medworm.com/index.php?rid=3322824&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20190775%26dopt%3DAbstract Authors: Agarwal S, Daley GQ PMID: 20190775 [PubMed - in process] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3322824 Mon, 01 Mar 2010 00:00:00 +0100 3322824 http://www.medworm.com/index.php?rid=3189559&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20078792%26dopt%3DAbstract Conclusion - One can demonstrate that the Masel elastic induced less cell lysis compared with other elastics, but all trademarks were found to be clinically biocompatible. Clinical relevance - Separating orthodontic elastics are used in the interdental subgingival region with the aim to separate the teeth for placement of orthodontic bands. However, latex has been known to cause allergy. As these materials are widely used in clinical orthodontics, care regarding the cytotoxicity of orthodontic elastics should be taken. Thus, clinically proven biocompatible materials should be acquired whenever possible. PMID: 20078792 [PubMed - in process] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3189559 Wed, 20 Jan 2010 19:36:17 +0100 3189559 http://www.medworm.com/index.php?rid=3189558&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20084082%26dopt%3DAbstract Authors: Huang C, Xiang Y, Wang Y, Li X, Xu L, Zhu Z, Zhang T, Zhu Q, Zhang K, Jing N, Chen CD Dimethylations of histone H3 lysine 9 and lysine 27 are important epigenetic marks associated with transcription repression. Here, we identified KIAA1718 (KDM7A) as a novel histone demethylase specific for these two repressing marks. Using mouse embryonic stem cells, we demonstrated that KIAA1718 expression increased at the early phase of neural differentiation. Knockdown of the gene blocked neural differentiation and the effect was rescued by the wild-type human gene, and not by a catalytically inactive mutant. In addition, overexpression of KIAA1718 accelerated neural differentiation. We provide the evidence that the pro-neural differentiation effect of KDM7A is mediated through direct tran... Cell Research journals http://www.medworm.com/rss/comments.php?id=3189558 Tue, 19 Jan 2010 00:00:00 +0100 3189558 http://www.medworm.com/index.php?rid=3189557&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20084083%26dopt%3DAbstract Authors: Qian G, Qin X, Zang YQ, Ge B, Guo TB, Wan B, Fang L, Zhang JZ alpha-Galactosylceramide (alpha-GC) is widely known to activate invariant natural killer T (iNKT) cells to suppress myelin antigen-specific Th1 responses, protecting susceptible mice against experimental autoimmune encephalomyelitis (EAE). Here, we demonstrate an unexpected finding that high doses of alpha-GC exacerbated, rather than ameliorated, EAE. Similar results were observed when MOG(35-55)-specific T cells treated with high-dose alpha-GC were transferred into naïve syngeneic recipient mice. Further study showed that high doses of alpha-GC directly enhance the Th17 and Th1 response by activation of CD4(+)CD44(+) memory T cells through phosphorylation of STAT3 and activation of NF-kappaB. Unlike the activa... Cell Research journals http://www.medworm.com/rss/comments.php?id=3189557 Tue, 19 Jan 2010 00:00:00 +0100 3189557 http://www.medworm.com/index.php?rid=3189556&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20084084%26dopt%3DAbstract Authors: Chen H, Wei Q, Zhang J, Xu C, Tan T, Ji W PMID: 20084084 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3189556 Tue, 19 Jan 2010 00:00:00 +0100 3189556 http://www.medworm.com/index.php?rid=3179337&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20073508%26dopt%3DAbstract Authors: Benoit DS, Henry SM, Shubin AD, Hoffman AS, Stayton P Small interfering RNA (siRNA)-based therapies have great potential for the treatment of debilitating diseases such as cancer, but an effective delivery strategy for siRNA is elusive. Here, pH-responsive complexes were developed for the delivery of siRNA in order to sensitize drug-resistant ovarian cancer cells (NCI/ADR-RES) to doxorubicin. The electrostatic complexes consisted of a cationic micelle used as a nucleating core, siRNA, and a pH-responsive endosomolytic polymer. Cationic micelles were formed from diblock copolymers of dimethylaminoethyl methacrylate (pDMAEMA) and butyl methacrylate (pDbB). The hydrophobic butyl core mediated micelle formation while the positively-charged pDMAEMA corona enabled siRNA condensation... Cell Research journals http://www.medworm.com/rss/comments.php?id=3179337 Thu, 14 Jan 2010 00:00:00 +0100 3179337 http://www.medworm.com/index.php?rid=3179336&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20077575%26dopt%3DAbstract CONCLUSIONS: These studies show that the embryo/fetal development effects observed following CNTO 530 treatment during organogenesis are qualitatively similar to those seen with other erythropoietin agonists and are likely a secondary consequence of increased hematocrit in the dams. Unlike other erythropoietin receptor agonists, CNTO 530 was able to cross the placental barrier, which was considered likely the result of FcRn-mediated transcytosis. Birth Defects Res (Part B), 2010. (c) 2010 Wiley-Liss, Inc. PMID: 20077575 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3179336 Thu, 14 Jan 2010 00:00:00 +0100 3179336 http://www.medworm.com/index.php?rid=3172776&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20066008%26dopt%3DAbstract Authors: Wang C, Huang Z, Du Y, Cheng Y, Chen S, Guo F Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4-deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 (UCP2) and beta-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172776 Tue, 12 Jan 2010 00:00:00 +0100 3172776 http://www.medworm.com/index.php?rid=3172775&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20066009%26dopt%3DAbstract Authors: Zhu M, Xin T, Weng S, Gao Y, Zhang Y, Li Q, Li M PMID: 20066009 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172775 Tue, 12 Jan 2010 00:00:00 +0100 3172775 http://www.medworm.com/index.php?rid=3172774&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20066010%26dopt%3DAbstract Authors: Teng L, Zhao J, Wang F, Ma L, Pei G Dysregulation of beta-site APP-cleaving enzyme (BACE) and/or gamma-secretase leads to anomalous production of amyloid-beta peptide (Abeta) and contributes to the etiology of Alzheimer's disease (AD). Since these secretases mediate proteolytic processing of numerous proteins, little success has been achieved to treat AD by secretase inhibitors because of inevitable undesired side effects. Thus, it is of importance to unravel the regulatory mechanisms of these secretases. Here, we show that delta-opioid receptor (DOR) promotes the processing of Abeta precursor protein (APP) by BACE1 and gamma-secretase, but not that of Notch, N-cadherin or APLP. Further investigation reveals that DOR forms a complex with BACE1 and gamma-secretase, and activati... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172774 Tue, 12 Jan 2010 00:00:00 +0100 3172774 http://www.medworm.com/index.php?rid=3172773&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068066%26dopt%3DAbstract In conclusion, SDF-1 binding receptors CXCR4 and CXCR7 are differently regulated in RMS cells. The upregulation of CXCR4 and downregulation of CXCR7 expression by PAX3-FKHR or hypoxia may give SDF-1 an advantage to better engage the CXCR4 receptor, thus increasing RMS motility. Mol Cancer Res; 8(1); 1-14. PMID: 20068066 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172773 Tue, 12 Jan 2010 00:00:00 +0100 3172773 http://www.medworm.com/index.php?rid=3172772&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068068%26dopt%3DAbstract In this study, we report that continuous IFN-alpha stimulation of the human Jurkat variant H123 led to resistance to type I IFN-induced apoptosis due to a loss of signal transducers and activators of transcription 2 (STAT2) expression. The apoptotic effects of IFN-alpha were hampered as STAT2-deficient cells were defective in activating the mitochondrial-dependent death pathway and ISGF3-mediated gene activation. Reconstitution of STAT2 restored the apoptotic effects of IFN-alpha as measured by the loss of mitochondrial membrane potential, cytochrome c release from mitochondria, caspase activation, and ultimately cell death. Nuclear localization of STAT2 was a critical event as retention of tyrosine-phosphorylated STAT2 in the cytosol was not sufficient to activate apoptosis. Furthermore, ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172772 Tue, 12 Jan 2010 00:00:00 +0100 3172772 http://www.medworm.com/index.php?rid=3172771&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068069%26dopt%3DAbstract We report that sCLU increases NF-kappaB nuclear translocation and transcriptional activity by serving as a ubiquitin-binding protein that enhances COMMD1 and I-kappaB proteasomal degradation by interacting with members of the SCF-betaTrCP E3 ligase family. Knockdown of sCLU in prostate cancer cells stabilizes COMMD1 and I-kappaB, thereby sequestrating NF-kappaB in the cytoplasm and decreasing NF-kappaB transcriptional activity. Comparative microarray profiling of sCLU-overexpressing and sCLU-knockdown prostate cancer cells confirmed that the expression of many NF-kappaB-regulated genes positively correlates with sCLU levels. We propose that elevated levels of sCLU promote prostate cancer cell survival by facilitating degradation of COMMD1 and I-kappaB, thereby activating the canonical NF-k... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172771 Tue, 12 Jan 2010 00:00:00 +0100 3172771 http://www.medworm.com/index.php?rid=3172770&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068070%26dopt%3DAbstract Authors: Kwok JM, Peck B, Monteiro LJ, Schwenen HD, Millour J, Coombes RC, Myatt SS, Lam EW The transcription factor Forkhead box M1 (FOXM1) is a key regulator of cell proliferation and is overexpressed in many forms of primary cancers, leading to uncontrolled cell division and genomic instability. To address the role of FOXM1 in chemoresistance, we generated a cisplatin-resistant breast cancer cell line (MCF-7-CIS(R)), which had an elevated level of FOXM1 protein and mRNA expression relative to the parental MCF-7 cells. A close correlation was observed between FOXM1 and the expression of its proposed downstream targets that are involved in DNA repair; breast cancer-associated gene 2 (BRCA2) and X-ray cross-complementing group 1 (XRCC1) were expressed at higher levels in the resistant ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172770 Tue, 12 Jan 2010 00:00:00 +0100 3172770 http://www.medworm.com/index.php?rid=3172769&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068071%26dopt%3DAbstract Authors: Tang JB, Goellner EM, Wang XH, Trivedi RN, St Croix CM, Jelezcova E, Svilar D, Brown AR, Sobol RW Base excision repair (BER) protein expression is important for resistance to DNA damage-induced cytotoxicity. Conversely, BER imbalance [DNA polymerase beta (Polbeta) deficiency or repair inhibition] enhances cytotoxicity of radiation and chemotherapeutic DNA-damaging agents. Whereas inhibition of critical steps in the BER pathway result in the accumulation of cytotoxic DNA double-strand breaks, we report that DNA damage-induced cytotoxicity due to deficiency in the BER protein Polbeta triggers cell death dependent on poly(ADP-ribose) (PAR) polymerase activation yet independent of PAR-mediated apoptosis-inducing factor nuclear translocation or PAR glycohydrolase, suggesting that c... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172769 Tue, 12 Jan 2010 00:00:00 +0100 3172769 http://www.medworm.com/index.php?rid=3172768&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068072%26dopt%3DAbstract CONCLUSIONS: These results show that pharmacologic doses of ascorbate, easily achievable in humans, may have potential for therapy in pancreatic cancer. Clin Cancer Res; 16(2); 509-20. PMID: 20068072 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172768 Tue, 12 Jan 2010 00:00:00 +0100 3172768 http://www.medworm.com/index.php?rid=3172767&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068073%26dopt%3DAbstract CONCLUSIONS: Gene transfer allows the reliable generation of HER2-specific T cells from GBM patients, which have potent antitumor activity against autologous HER2-positive tumors including their putative stem cells. Hence, the adoptive transfer of HER2-redirected T cells may be a promising immunotherapeutic approach for GBM. Clin Cancer Res; 16(2); 474-85. PMID: 20068073 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172767 Tue, 12 Jan 2010 00:00:00 +0100 3172767 http://www.medworm.com/index.php?rid=3172766&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068074%26dopt%3DAbstract CONCLUSIONS: A two-pronged approach confirmed that SLPI overcomes paclitaxel in part through activation of ERK1/2. These results credential SLPI as a molecular target for ovarian cancer and suggest CR012 as a tool for proof of concept. Clin Cancer Res; 16(2); 600-9. PMID: 20068074 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172766 Tue, 12 Jan 2010 00:00:00 +0100 3172766 http://www.medworm.com/index.php?rid=3172765&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068076%26dopt%3DAbstract CONCLUSIONS: We identified a miR expression profile that strongly differentiated adenocarcinoma from SQ and had prognostic implications. These findings may lead to histology-based therapeutic approaches. Clin Cancer Res; 16(2); 430-41. PMID: 20068076 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172765 Tue, 12 Jan 2010 00:00:00 +0100 3172765 http://www.medworm.com/index.php?rid=3172764&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068077%26dopt%3DAbstract CONCLUSIONS: Collectively, these results suggest that cigarette smoke-induced methylation of HtrA3 could contribute to the etiology of chemoresistant disease in smoking-related lung cancer. Clin Cancer Res; 16(2); 398-409. PMID: 20068077 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172764 Tue, 12 Jan 2010 00:00:00 +0100 3172764 http://www.medworm.com/index.php?rid=3172763&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068080%26dopt%3DAbstract CONCLUSIONS: Collectively, these data strongly suggest that HDACI such as romidepsin or belinostat in combination with a proteasome inhibitor could represent a novel and rationale platform for the treatment of MCL. Clin Cancer Res; 16(2); 554-65. PMID: 20068080 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172763 Tue, 12 Jan 2010 00:00:00 +0100 3172763 http://www.medworm.com/index.php?rid=3172762&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068082%26dopt%3DAbstract Authors: Dai Y, Grant S The DNA damage response (DDR) represents a complex network of multiple signaling pathways involving cell cycle checkpoints, DNA repair, transcriptional programs, and apoptosis, through which cells maintain genomic integrity following various endogenous (metabolic) or environmental stresses. In cancer treatment, the DDR occurs in response to various genotoxic insults by diverse cytotoxic agents and radiation, representing an important mechanism limiting chemotherapeutic and radiotherapeutic efficacy. This has prompted the development of agents targeting DDR signaling pathways, particularly checkpoint kinase 1 (Chk1), which contributes to all currently defined cell cycle checkpoints, including G1/S, intra-S-phase, G2/M, and the mitotic spindle checkpoint. Although... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172762 Tue, 12 Jan 2010 00:00:00 +0100 3172762 http://www.medworm.com/index.php?rid=3172761&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068083%26dopt%3DAbstract The objective of this study was to identify novel genes that potentially regulate tumor growth, to target these gene products with monoclonal antibodies, and to examine the therapeutic potential of these antibodies. EXPERIMENTAL DESIGN: Using cDNA microarray analysis, we identified genes overexpressed in several solid malignancies. We generated a mouse monoclonal antibody, 19.2.1, and its humanized counterpart, PDL192, to one such target, TweakR (TWEAK receptor, Fn14, TNFRSF12A, CD266), and characterized the antitumor activities in vitro and in mouse xenograft models. RESULTS: Both 19.2.1 (mouse IgG2a) and PDL192 (human IgG1), like TWEAK, the natural ligand of TweakR, inhibited the growth of several TweakR-expressing cancer cell lines in anchorage-dependent and anchorage-independent assays... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172761 Tue, 12 Jan 2010 00:00:00 +0100 3172761 http://www.medworm.com/index.php?rid=3172760&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068086%26dopt%3DAbstract CONCLUSIONS: Three conceptually different predictors performed similarly in this validation study and tended to identify the same patients as responders. A genomic predictor that relied solely on a composite of individual drug sensitivity predictions from cell lines did not show any predictive value. Clin Cancer Res; 16(2); 711-8. PMID: 20068086 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172760 Tue, 12 Jan 2010 00:00:00 +0100 3172760 http://www.medworm.com/index.php?rid=3172759&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068089%26dopt%3DAbstract CONCLUSION: There are many important immune cell subsets in the microenvironment of follicular lymphoma. Each of these is independently associated with outcome. This is the first study showing the effect of the balance of the entire microenvironment, not only of individual subsets. Clin Cancer Res; 16(2); 637-50. PMID: 20068089 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172759 Tue, 12 Jan 2010 00:00:00 +0100 3172759 http://www.medworm.com/index.php?rid=3172758&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068090%26dopt%3DAbstract CONCLUSION: DRC is an independent susceptibility biomarker for SCCHN risk but not a tumor marker. Clin Cancer Res; 16(2); 764-74. PMID: 20068090 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172758 Tue, 12 Jan 2010 00:00:00 +0100 3172758 http://www.medworm.com/index.php?rid=3172757&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068092%26dopt%3DAbstract CONCLUSIONS: Our study documents that PTGS2/COX-2 is part of a cyclic hypoxia gene signature and largely accounts for the unique phenotype of endothelial and tumor cells exposed to fluctuations in pO(2), thereby offering new perspectives for the clustering of tumors expressing COX-2 together with other cyclic hypoxia-responsive genes. Clin Cancer Res; 16(2); 410-9. PMID: 20068092 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172757 Tue, 12 Jan 2010 00:00:00 +0100 3172757 http://www.medworm.com/index.php?rid=3172756&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068094%26dopt%3DAbstract CONCLUSIONS: NVP-BEZ235 displays the features to be considered for sarcoma therapy to potentiate the activity of other anticancer agents. The drug is currently undergoing phase I/II clinical trials in advanced cancer patients. Clin Cancer Res; 16(2); 530-40. PMID: 20068094 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172756 Tue, 12 Jan 2010 00:00:00 +0100 3172756 http://www.medworm.com/index.php?rid=3172755&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068096%26dopt%3DAbstract CONCLUSIONS: AR-67 is a novel, blood-stable camptothecin with a predictable toxicity profile and linear pharmacokinetics. The recommended phase II dosage is 7.5 mg/m(2)/d five times every 21 days. Clin Cancer Res; 16(2); 673-80. PMID: 20068096 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172755 Tue, 12 Jan 2010 00:00:00 +0100 3172755 http://www.medworm.com/index.php?rid=3172754&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068098%26dopt%3DAbstract CONCLUSIONS: These findings support further clinical exploration of kinesin spindle protein inhibitors for the treatment of breast cancer. Clin Cancer Res; 16(2); 566-76. PMID: 20068098 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172754 Tue, 12 Jan 2010 00:00:00 +0100 3172754 http://www.medworm.com/index.php?rid=3172753&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068099%26dopt%3DAbstract CONCLUSIONS: MiRNA profiling is a highly reliable strategy for classifying NSCLCs. Indeed, classification is consistently accurate even in small biopsies/aspirates of poorly differentiated tumors. Confirmation of its reliability across the full range of tumor grades and specimen types represents an important step toward broad application. Clin Cancer Res; 16(2); 610-9. PMID: 20068099 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172753 Tue, 12 Jan 2010 00:00:00 +0100 3172753 http://www.medworm.com/index.php?rid=3172752&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068100%26dopt%3DAbstract CONCLUSIONS: Altogether, expression of the IGHV3-23 gene characterizes a CLL subset with distinct clinical and biological features. Clin Cancer Res; 16(2); 620-8. PMID: 20068100 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172752 Tue, 12 Jan 2010 00:00:00 +0100 3172752 http://www.medworm.com/index.php?rid=3172751&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068102%26dopt%3DAbstract CONCLUSION: We show the utility of molecular profiling of pretreatment biopsies to discover markers of response. Our results suggest the potential use of immune signaling molecules such as DEFA as well as MAP2, a microtubule-associated protein, as tumor markers that associate with response to neoadjuvant taxane-based therapy. Clin Cancer Res; 16(2); 681-90. PMID: 20068102 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172751 Tue, 12 Jan 2010 00:00:00 +0100 3172751 http://www.medworm.com/index.php?rid=3172750&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068103%26dopt%3DAbstract CONCLUSIONS: These data suggest that bortezomib has significant single agent activity in patients with FL, and that longer durations of treatment may improve overall response. Clin Cancer Res; 16(2); 719-26. PMID: 20068103 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172750 Tue, 12 Jan 2010 00:00:00 +0100 3172750 http://www.medworm.com/index.php?rid=3172749&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068104%26dopt%3DAbstract CONCLUSIONS: These data suggest that the novel oncolytic mutant AdDeltaDelta is a promising candidate for targeting of solid tumors specifically in combination with chemotherapeutics. Clin Cancer Res; 16(2); 541-53. PMID: 20068104 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172749 Tue, 12 Jan 2010 00:00:00 +0100 3172749 http://www.medworm.com/index.php?rid=3172748&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068105%26dopt%3DAbstract CONCLUSION: Cancer-initiating cells contribute to tumor evasion of the immunosurveillance and approaches that alter the differentiation state may have immunotherapeutic potential. Clin Cancer Res; 16(2); 461-73. PMID: 20068105 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172748 Tue, 12 Jan 2010 00:00:00 +0100 3172748 http://www.medworm.com/index.php?rid=3172747&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068106%26dopt%3DAbstract CONCLUSIONS: Thus, SYK inhibition predicts cellular response to dasatinib. SYK, together with phospholipase Cgamma2, may serve as potential biomarkers to predict dasatinib therapeutic response in patients. From the pathogenic perspective, our study suggests the existence of alternative mechanisms or pathways that activate SYK, independent of SRC kinase activities. The study further implicates that SYK might serve as a more effective therapeutic target in CLL treatment. Clin Cancer Res; 16(2); 587-99. PMID: 20068106 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172747 Tue, 12 Jan 2010 00:00:00 +0100 3172747 http://www.medworm.com/index.php?rid=3172746&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068107%26dopt%3DAbstract Authors: Bühler A, Zenz T, Stilgenbauer S Increasing evidence supports the prognostic relevance of specific immunoglobulin heavy chain variable (IGHV) genes or stereotyped B-cell receptors (BCR) in chronic lymphocytic leukemia (CLL). The clonotypic BCRs differ in their specificity and affinity toward classical antigens and/or superantigens. The BCR-triggered mechanisms are distinct but could explain in part the different clinical behavior among CLL subgroups. Clin Cancer Res; 16(2); 373-5. PMID: 20068107 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172746 Tue, 12 Jan 2010 00:00:00 +0100 3172746 http://www.medworm.com/index.php?rid=3172745&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068108%26dopt%3DAbstract CONCLUSIONS: These results indicate that IL-13Ralpha2 is a functional receptor as IL-13 mediates signaling in human pancreatic cancer cell lines. IL-13 causes transforming growth factor-beta activation via AP-1 pathway, which may cause tumor induced immunosuppression in the host. In addition, IL13-PE cytotoxin may be an effective therapeutic agent for the treatment of pancreatic cancer. Clin Cancer Res; 16(2); 577-86. PMID: 20068108 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172745 Tue, 12 Jan 2010 00:00:00 +0100 3172745 http://www.medworm.com/index.php?rid=3172744&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068110%26dopt%3DAbstract CONCLUSIONS: This study indicates that PTCH1 gene alternation may play a significant role in the pathogenesis of NBCCS and the related sporadic tumors. Not only the standard two-hit model, but also haploinsufficiency or dominant-negative isoforms may be implicated in the inactivation of the PTCH1 gene. Clin Cancer Res; 16(2); 442-50. PMID: 20068110 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172744 Tue, 12 Jan 2010 00:00:00 +0100 3172744 http://www.medworm.com/index.php?rid=3172743&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068111%26dopt%3DAbstract CONCLUSION: This study shows the potent biological activity of rhIL-7 in humans over a well-tolerated dose range and allows further exploration of its possible therapeutic applications. Clin Cancer Res; 16(2); 727-35. PMID: 20068111 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172743 Tue, 12 Jan 2010 00:00:00 +0100 3172743 http://www.medworm.com/index.php?rid=3172742&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068146%26dopt%3DAbstract Authors: Holterman CE, Franovic A, Payette J, Lee S Inappropriate expression of Ets-1 is observed in a variety of human cancers, and its forced expression in cultured cells results in transformation, autonomous proliferation, and tumor formation. The basis by which Ets-1 confers autonomous growth, one of the primary hallmarks of cancer cells and a critical component of persistent proliferation, has yet to be fully explained. Using a variety of cancer cell lines, we show that inhibition of Ets-1 blocks tumor formation and cell proliferation in vivo and autonomous growth in culture. A screen of multiple diffusible growth factors revealed that inhibition of Ets-1 results in the specific downregulation of transforming growth factor alpha (TGFalpha), the proximal promoter region of which co... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172742 Tue, 12 Jan 2010 00:00:00 +0100 3172742 http://www.medworm.com/index.php?rid=3172741&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068147%26dopt%3DAbstract Authors: Davis IJ, McFadden AW, Zhang Y, Coxon A, Burgess TL, Wagner AJ, Fisher DE Clear cell sarcoma (CCS), a childhood tumor of the tendons and aponeuroses, is uniformly fatal once it has metastasized because of its profound therapeutic resistance. CCS is characterized by production of a chimeric transcription factor, EWS-ATF1, which is formed as the result of a disease-specific chromosomal translocation. EWS-ATF1 activates the melanocyte transcription factor MITF, which in turn activates transcription of c-Met, an oncogenic receptor tyrosine kinase recently shown to be activated in CCS. Based on this connection, we hypothesized that c-Met inhibition may offer a strategy to treat CCS, as an indirect tactic to defeat a transforming pathway downstream of EWS-ATF1. Here, we show that pr... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172741 Tue, 12 Jan 2010 00:00:00 +0100 3172741 http://www.medworm.com/index.php?rid=3172740&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068148%26dopt%3DAbstract Authors: Kimura Y, Morita T, Hayashi K, Miki T, Sobue K Myocardin is an important transcriptional regulator in smooth and cardiac muscle development. We noticed that the expression of myocardin was markedly downregulated in human uterine leiomyosarcoma cells. Restoration of myocardin expression induced the reexpression of smooth muscle marker proteins and the formation of well-developed actin fibers. A concomitant increase in the expression of a cyclin-dependent kinase inhibitor, p21, led to significantly reduced cell proliferation, via p21's inhibition of the G(1)-S transition. A p21 promoter-reporter assay showed that myocardin markedly increased p21's promoter activity. Furthermore, a serum response factor (SRF)-binding cis-element CArG box in the p21 promoter region was required fo... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172740 Tue, 12 Jan 2010 00:00:00 +0100 3172740 http://www.medworm.com/index.php?rid=3172739&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068150%26dopt%3DAbstract Authors: Kool J, Uren AG, Martins CP, Sie D, de Ridder J, Turner G, van Uitert M, Matentzoglu K, Lagcher W, Krimpenfort P, Gadiot J, Pritchard C, Lenz J, Lund AH, Jonkers J, Rogers J, Adams DJ, Wessels L, Berns A, van Lohuizen M The cyclin dependent kinase (CDK) inhibitors p15, p16, p21, and p27 are frequently deleted, silenced, or downregulated in many malignancies. Inactivation of CDK inhibitors predisposes mice to tumor development, showing that these genes function as tumor suppressors. Here, we describe high-throughput murine leukemia virus insertional mutagenesis screens in mice that are deficient for one or two CDK inhibitors. We retrieved 9,117 retroviral insertions from 476 lymphomas to define hundreds of loci that are mutated more frequently than expected by chance. Many of t... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172739 Tue, 12 Jan 2010 00:00:00 +0100 3172739 http://www.medworm.com/index.php?rid=3172738&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068153%26dopt%3DAbstract Authors: Kemper K, Sprick MR, de Bree M, Scopelliti A, Vermeulen L, Hoek M, Zeilstra J, Pals ST, Mehmet H, Stassi G, Medema JP Colon cancer stem cells (CSC) can be identified with AC133, an antibody that detects an epitope on CD133. However, recent evidence suggests that expression of CD133 is not restricted to CSCs, but is also expressed on differentiated tumor cells. Intriguingly, we observed that detection of the AC133 epitope on the cell surface decreased upon differentiation of CSC in a manner that correlated with loss of clonogenicity. However, this event did not coincide with a change in CD133 promoter activity, mRNA, splice variant, protein expression, or even cell surface expression of CD133. In contrast, we noted that with CSC differentiation, a change occured in CD133 glycos... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172738 Tue, 12 Jan 2010 00:00:00 +0100 3172738 http://www.medworm.com/index.php?rid=3172737&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068154%26dopt%3DAbstract Authors: Seitzer N, Mayr T, Streit S, Ullrich A In the growth factor receptor gene FGFR4 the presence of the common single nucleotide polymorphism Arg388 has been associated with progression of various types of cancer including breast cancer. However, a causative relationship is not readily assigned due to genetic heterogeneity in different patient cohorts. To address this issue, we compared the effects of this allele on malignant progression in the WAP-TGFalpha transgenic mouse model of breast cancer. A knock-in strain was generated to introduce an analogous Arg385 allele into the murine FGFR4 gene. Mouse embryonic fibroblasts derived from this strain displayed accelerated cell transformation, with transformed cells exhibiting greater motility and invasive behavior. In the in vivo con... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172737 Tue, 12 Jan 2010 00:00:00 +0100 3172737 http://www.medworm.com/index.php?rid=3172736&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068155%26dopt%3DAbstract Authors: Li Y, Li X, Guo B 3,3'-Diindolylmethane (DIM) is an anticancer agent that induces cell cycle arrest and apoptosis through unknown mechanisms. Here, we report that DIM can selectively induce proteasome-mediated degradation of class I histone deacetylases (HDAC1, HDAC2, HDAC3, and HDAC8) without affecting the class II HDAC proteins. DIM induced downregulation of class I HDACs in human colon cancer cells in vitro and in vivo in tumor xenografts. HDAC depletion relieved HDAC-mediated transcriptional inhibition of the cyclin-dependent kinase inhibitors p21WAF1 and p27KIP2, significantly increasing their expression and triggering cell cycle arrest in the G(2) phase of the cell cycle. Additionally, HDAC depletion was associated with an induction of DNA damage that triggered apoptosis... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172736 Tue, 12 Jan 2010 00:00:00 +0100 3172736 http://www.medworm.com/index.php?rid=3172735&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068156%26dopt%3DAbstract We report that E2F8 is strongly upregulated in human hepatocellular carcinoma (HCC), where it was evidenced to contribute to oncogenesis and progression. Ectopic overexpression of E2F8 promoted cell proliferation, colony formation, and tumorigenicity, whereas E2F8 knockdown inhibited these phenotypes, as documented in Huh-7, Focus, Hep3B, and YY-8103 HCC cell lines. Mechanistic analyses indicated that E2F8 could bind to regulatory elements of cyclin D1, regulating its transcription and promoting accumulation of S-phase cells. Together, our findings suggest that E2F8 contributes to the oncogenic potential of HCC and may constitute a potential therapeutic target in this disease. Cancer Res; 70(2); 782-91. PMID: 20068156 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3172735 Tue, 12 Jan 2010 00:00:00 +0100 3172735 http://www.medworm.com/index.php?rid=3172734&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068157%26dopt%3DAbstract In this study, we examined alterations in the structure or expression of SLIT2, its receptor ROBO1, and beta-catenin, along with the AKT/glycogen synthase kinase 3beta (GSK3beta)/beta-transducin repeat-containing protein (betaTrCP) pathway in lung cancer cell lines and patients. Low SLIT2 expression correlated with an upward trend of pathological stage and poorer survival in lung cancer patients. Importantly, SLIT2, betaTrCP, and beta-catenin expression levels predicted postoperative recurrence of lung cancer in patients. Stimulating SLIT2 expression by various methods increased the level of E-cadherin caused by attenuation of its transcriptional repressor SNAI1. Conversely, knocking down SLIT2 expression increased cell migration and reduced cell adhesion through coordinated deregulation o... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172734 Tue, 12 Jan 2010 00:00:00 +0100 3172734 http://www.medworm.com/index.php?rid=3172733&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068158%26dopt%3DAbstract Authors: Lun X, Alain T, Zemp FJ, Zhou H, Rahman MM, Hamilton MG, McFadden G, Bell J, Senger DL, Forsyth PA Oncolytic myxoma virus (MYXV) is being developed as a novel virotherapeutic against human brain cancer and has promising activity against human brain tumor models in immunocompromised hosts. Because an intact immune system could reduce its efficacy, the purpose of this study was to evaluate the oncolytic potential of MYXV in immunocompetent racine glioma models. Here, we report that MYXV infects and kills all racine cell glioma lines and that its effects are enhanced by rapamycin. Intratumoral administration of MYXV with rapamycin improved viral replication in the tumor and significantly prolonged host survival. Similarly, coadministration via a method of convection-enhanced deli... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172733 Tue, 12 Jan 2010 00:00:00 +0100 3172733 http://www.medworm.com/index.php?rid=3172732&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068160%26dopt%3DAbstract Authors: Zhang D, Li J, Costa M, Gao J, Huang C Hypoxia-inducible factor-1alpha (HIF-1alpha) is a master transcription factor that is critical for the regulation of a variety of cellular functions. HIF-1alpha is rapidly degraded under normoxic conditions by ubiquitin-mediated proteasome pathway controlled by the tumor suppressor von Hippel Lindau (VHL). Several recent studies reveal that heat-shock proteins (Hsp) can regulate HIF-1alpha protein degradation by a VHL-independent pathway. Here, we demonstrate that the stress kinase c-Jun NH(2)-terminal kinase 1 (JNK1) is required for Hsp-dependent regulation of HIF-1alpha. Stabilization of HIF-1alpha was impaired in JNK1-/- cells but could be rescued by JNK1 reconstitution under hypoxic conditions. These effects could be phenocopied in ot... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172732 Tue, 12 Jan 2010 00:00:00 +0100 3172732 http://www.medworm.com/index.php?rid=3172731&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068161%26dopt%3DAbstract Authors: Harrison H, Farnie G, Howell SJ, Rock RE, Stylianou S, Brennan KR, Bundred NJ, Clarke RB Notch receptor signaling pathways play an important role not only in normal breast development but also in breast cancer development and progression. We assessed the role of Notch receptors in stem cell activity in breast cancer cell lines and nine primary human tumor samples. Stem cells were enriched by selection of anoikis-resistant cells or cells expressing the membrane phenotype ESA(+)/CD44(+)/CD24(low). Using these breast cancer stem cell populations, we compared the activation status of Notch receptors with the status in luminally differentiated cells, and we evaluated the consequences of pathway inhibition in vitro and in vivo. We found that Notch4 signaling activity was 8-fold high... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172731 Tue, 12 Jan 2010 00:00:00 +0100 3172731 http://www.medworm.com/index.php?rid=3172730&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068162%26dopt%3DAbstract Authors: Schaaf G, Hamdi M, Zwijnenburg D, Lakeman A, Geerts D, Versteeg R, Kool M RAS oncogenes are among the most frequently mutated genes in human cancer, but effective strategies for therapeutic inhibition of the RAS pathway have been elusive. Sprouty1 (SPRY1) is an upstream antagonist of RAS that is activated by extracellular signal-related kinase (ERK), providing a negative feedback loop for RAS signaling, and other evidence suggests that SPRY1 may have a tumor suppressor function. Studies of RAS status in the human childhood tumor rhabdomyosarcoma (RMS) indicated mutations in approximately half of the tumors of the embryonal rhabdomyosarcoma subtype (ERMS) but not the alveolar subtype (ARMS). ERMS tumors also showed overexpression of SPRY1, which was indeed upregulated by mutant... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172730 Tue, 12 Jan 2010 00:00:00 +0100 3172730 http://www.medworm.com/index.php?rid=3172729&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068165%26dopt%3DAbstract In this study, we define a critical mechanism in this process by showing that the prometastatic adapter protein human enhancer of filamentation 1 (HEF1; NEDD9) links PGE(2) to the cell cycle machinery in colorectal cancer cells. PGE(2) rapidly induced expression of HEF1 mRNA and protein in colorectal cancer cells. HEF1 overexpression elicited the same effects as PGE(2) treatment on cell proliferation, cell cycle progression, and tumor growth. Conversely, HEF1 knockdown suppressed PGE(2)-driven cell proliferation and cell cycle progression. Cell cycle alterations involved HEF1 fragmentation as well as co-distribution of HEF1 and cell cycle kinase Aurora A along spindle asters during cell division. Moreover, Aurora A co-immunoprecipitated with HEF1 and was activated by HEF1. Consistent with ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172729 Tue, 12 Jan 2010 00:00:00 +0100 3172729 http://www.medworm.com/index.php?rid=3172728&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068166%26dopt%3DAbstract Authors: Pantuck AJ, An J, Liu H, Rettig MB The critical downstream signaling consequences contributing to renal cancer as a result of loss of the tumor suppressor gene von Hippel-Lindau (VHL) have yet to be fully elucidated. Here, we report that VHL loss results in an epithelial to mesenchymal transition (EMT). In studies of paired isogenic cell lines, VHL silencing increased the levels of N-cadherin and vimentin and reduced the levels of E-cadherin relative to the parental VHL(+) cell line, which displayed the opposite profile. VHL(+) cells grew as clusters of cuboidal and rhomboid cells, whereas VHL-silenced cells took on an elongated, fibroblastoid morphology associated with a more highly invasive character in Matrigel chamber assays. Based on earlier evidence that VHL loss can act... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172728 Tue, 12 Jan 2010 00:00:00 +0100 3172728 http://www.medworm.com/index.php?rid=3172727&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068167%26dopt%3DAbstract Authors: Ashiru O, Boutet P, Fernández-Messina L, Agüera-González S, Skepper JN, Valés-Gómez M, Reyburn HT The MHC class I-related chain (MIC) A and MICB ligands for the activating receptor NKG2D can be shed from tumor cells, and the presence of these soluble molecules in sera is related with compromised immune response and progression of disease. Recently, thiol disulphide isomerases and members of the ADAM (a disintegrin and metalloproteinase) gene family were identified as key enzymes in mediating MICA/B shedding from cells. Here, we report shedding of the most frequently expressed MICA allele in human populations (MICA*008) into exosomes, small membrane vesicles that are secreted upon fusion with the plasma membrane. Although similar to other MICA/B molecul... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172727 Tue, 12 Jan 2010 00:00:00 +0100 3172727 http://www.medworm.com/index.php?rid=3172726&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068168%26dopt%3DAbstract Authors: Cerovac V, Monteserin-Garcia J, Rubinfeld H, Buchfelder M, Losa M, Florio T, Paez-Pereda M, Stalla GK, Theodoropoulou M Rapamycin and its analogues have significant antiproliferative action against a variety of tumors. However, sensitivity to rapamycin is reduced by Akt activation that results from the ablative effects of rapamycin on a p70 S6K-induced negative feedback loop that blunts phosphoinositide 3-kinase (PI3K)-mediated support for Akt activity. Thus, sensitivity to rapamycin might be increased by imposing an upstream blockade to the PI3K/Akt pathway. Here, we investigated this model using the somatostatin analogue octreotide as a tool to decrease levels of activated Ser(473)-phosphorylated Akt (pAkt-Ser(473)) in pituitary tumor cells that express somatostatin receptor... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172726 Tue, 12 Jan 2010 00:00:00 +0100 3172726 http://www.medworm.com/index.php?rid=3172725&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068170%26dopt%3DAbstract In this study, we documented functional relevance and mechanism of activation of HOXA9 in glioblastoma (GBM), the most common malignant brain tumor. Expression of HOXA genes was investigated using reverse transcription-PCR in primary gliomas and glioblastoma cell lines and was validated in two sets of expression array data. In a subset of GBM, HOXA genes are aberrently activated within confined chromosomal domains. Transcriptional activation of the HOXA cluster was reversible by a phosphoinostide 3-kinase (PI3K) inhibitor through an epigenetic mechanism involving histone H3K27 trimethylation. Functional studies of HOXA9 showed its capacity to decrease apoptosis and increase cellular proliferation along with tumor necrosis factor-related apoptosis-including ligand resistance. Notably, aberr... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172725 Tue, 12 Jan 2010 00:00:00 +0100 3172725 http://www.medworm.com/index.php?rid=3172724&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068171%26dopt%3DAbstract Authors: Wilson AJ, Chueh AC, Tögel L, Corner GA, Ahmed N, Goel S, Byun DS, Nasser S, Houston MA, Jhawer M, Smartt HJ, Murray LB, Nicholas C, Heerdt BG, Arango D, Augenlicht LH, Mariadason JM Histone deacetylase inhibitors (HDACi) induce growth arrest and apoptosis in colon cancer cells and are being considered for colon cancer therapy. The underlying mechanism of action of these effects is poorly defined with both transcription-dependent and -independent mechanisms implicated. We screened a panel of 30 colon cancer cell lines for sensitivity to HDACi-induced apoptosis and correlated the differences with gene expression patterns induced by HDACi in the five most sensitive and resistant lines. A robust and reproducible transcriptional response involving coordinate induction of mult... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172724 Tue, 12 Jan 2010 00:00:00 +0100 3172724 http://www.medworm.com/index.php?rid=3172723&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068172%26dopt%3DAbstract In this study, we investigated a role of p38 mitogen-activated protein kinase (MAPK) in this process, using bladder cancer cell lines HTB9 and HTB5 that were derived from different tumor stages. p38 MAPK modulated MMP-2/9 mRNA levels at the levels of transcript stability and MMP-2/9 activity along with invasive capacity. We defined a downstream effector of p38 MAPK, MAPK-activated protein kinase 2 (MAPKAPK2), that was associated with MMP-2/9 activation. Ectopic expression of wild-type or constitutively active forms of MAPKAPK2 increased MMP-2/9 activities and invasive capacity. Conversely, p38 MAPK inhibition blocked the MAPKAPK2-mediated increase in MMP-2/9 activities and the invasive capacity of the cancer cells. Our findings implicate p38 MAPK and MAPKAPK2 in mediating bladder cancer in... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172723 Tue, 12 Jan 2010 00:00:00 +0100 3172723 http://www.medworm.com/index.php?rid=3172722&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068174%26dopt%3DAbstract Authors: Du W, Takuwa N, Yoshioka K, Okamoto Y, Gonda K, Sugihara K, Fukamizu A, Asano M, Takuwa Y Sphingosine-1-phosphate (S1P) has been implicated in tumor angiogenesis by acting through the G(i)-coupled chemotactic receptor S1P(1). Here, we report that the distinct receptor S1P(2) is responsible for mediating the G(12/13)/Rho-dependent inhibitory effects of S1P on Akt, Rac, and cell migration, thereby negatively regulating tumor angiogenesis and tumor growth. By using S1P(2)(LacZ/+) mice, we found that S1P(2) was expressed in both tumor and normal blood vessels in many organs, in both endothelial cells (EC) and vascular smooth muscle cells, as well as in tumor-associated, CD11b-positive bone marrow-derived cells (BMDC). Lewis lung carcinoma or B16 melanoma cells implanted in S1P(2)-... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172722 Tue, 12 Jan 2010 00:00:00 +0100 3172722 http://www.medworm.com/index.php?rid=3172721&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068175%26dopt%3DAbstract Authors: Schatton T, Schütte U, Frank NY, Zhan Q, Hoerning A, Robles SC, Zhou J, Hodi FS, Spagnoli GC, Murphy GF, Frank MH Highly immunogenic cancers such as malignant melanoma are capable of inexorable tumor growth despite the presence of antitumor immunity. Thus, only a restricted minority of tumorigenic malignant cells may possess the phenotypic and functional characteristics needed to modulate tumor-directed immune activation. Here we provide evidence supporting this hypothesis. Tumorigenic ABCB5(+) malignant melanoma initiating cells (MMICs) possessed the capacity to preferentially inhibit IL-2-dependent T-cell activation and to support, in a B7.2-dependent manner, induction of CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs). Compared with melanoma bulk cell populations, ABC... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172721 Tue, 12 Jan 2010 00:00:00 +0100 3172721 http://www.medworm.com/index.php?rid=3172720&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068176%26dopt%3DAbstract Authors: Lin L, Mernaugh R, Yi F, Blum D, Carbone DP, Dang TP Like many signaling pathways in development, the Notch receptor pathway plays an important role in cancer pathobiology when it is dysregulated. Potential ligand-binding sites within the epidermal growth factor (EGF)-like repeats of Notch1 have been identified, but the ligand-binding domains in Notch3, which is implicated in lung cancer, are not known. In screening a library of 155 peptides representing all 34 EGF-like repeats in Notch3, we discovered two distinct ligand-binding regions involving the 7-10 and 21-22 repeats that are distinct from the putative ligand-binding domain of Notch1. In cell-based assays, peptides from these regions induced apoptosis and reduced expression of the Notch3-dependent gene Hey1. They also b... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172720 Tue, 12 Jan 2010 00:00:00 +0100 3172720 http://www.medworm.com/index.php?rid=3172719&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068177%26dopt%3DAbstract Authors: Yu K, Shi C, Toral-Barza L, Lucas J, Shor B, Kim JE, Zhang WG, Mahoney R, Gaydos C, Tardio L, Kim SK, Conant R, Curran K, Kaplan J, Verheijen J, Ayral-Kaloustian S, Mansour TS, Abraham RT, Zask A, Gibbons JJ The mammalian target of rapamycin (mTOR) is a major component of the phosphoinositide 3-kinase (PI3K)/AKT signaling pathway that is dysregulated in 50% of all human malignancies. Rapamycin and its analogues (rapalogs) partially inhibit mTOR through allosteric binding to mTOR complex 1 (mTORC1) but not mTOR complex 2 (mTORC2), an emerging player in cancer. Here, we report WYE-125132 (WYE-132), a highly potent, ATP-competitive, and specific mTOR kinase inhibitor (IC(50): 0.19 +/- 0.07 nmol/L; >5,000-fold selective versus PI3Ks). WYE-132 inhibited mTORC1 and mTORC2 in dive... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172719 Tue, 12 Jan 2010 00:00:00 +0100 3172719 http://www.medworm.com/index.php?rid=3172718&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068178%26dopt%3DAbstract Authors: García-Olmo DC, Domínguez C, García-Arranz M, Anker P, Stroun M, García-Verdugo JM, García-Olmo D It has been proposed that cell-free nucleic acids in the plasma participate in tumorigenesis and the development of metastases via transfection-like uptake of such nucleic acids by susceptible cells. This putative phenomenon is tentatively referred to as "genometastasis." In the present study, we examined the effects on cultured cells of plasma from healthy individuals and from patients with colon cancer. Cultures of NIH-3T3 cells and human adipose-derived stem cells (hASC) were supplemented with samples of plasma from patients with K-ras-mutated colorectal tumors or from healthy subjects using two different protocols: direct addition of plasma to cultures... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172718 Tue, 12 Jan 2010 00:00:00 +0100 3172718 http://www.medworm.com/index.php?rid=3172717&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068180%26dopt%3DAbstract Authors: Huang Z, Mayr NA, Yuh WT, Lo SS, Montebello JF, Grecula JC, Lu L, Li K, Zhang H, Gupta N, Wang JZ Applications of mathematical modeling can improve outcome predictions of cancer therapy. Here we present a kinetic model incorporating effects of radiosensitivity, tumor repopulation, and dead-cell resolving on the analysis of tumor volume regression data of 80 cervical cancer patients (stages 1B2-IVA) who underwent radiation therapy. Regression rates and derived model parameters correlated significantly with clinical outcome (P < 0.001; median follow-up: 6.2 years). The 6-year local tumor control rate was 87% versus 54% using radiosensitivity (2-Gy surviving fraction S(2) < 0.70 vs. S(2) >/= 0.70) as a predictor (P = 0.001) and 89% vs. 57% using dead-cell resolving time ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172717 Tue, 12 Jan 2010 00:00:00 +0100 3172717 http://www.medworm.com/index.php?rid=3172716&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068181%26dopt%3DAbstract In this study, we illustrate how the immunostimulatory and immunosuppressive effects of this agent can be uncoupled to therapeutic advantage. We took advantage of two TLR3-expressing tumor models that produced large amounts of CCL5 (a CCR5 ligand) and CXCL10 (a CXCR3 ligand) in response to type I IFN and poly(A:U), both in vitro and in vivo. Conventional chemotherapy or in vivo injection of poly(A:U), alone or in combination, failed to reduce tumor growth unless an immunochemotherapeutic regimen of vaccination against tumor antigens was included. CCL5 blockade improved the efficacy of immunochemotherapy, whereas CXCR3 blockade abolished its beneficial effects. These findings show how poly(A:U) can elicit production of a range of chemokines by tumor cells that reinforce immunostimulatory or... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172716 Tue, 12 Jan 2010 00:00:00 +0100 3172716 http://www.medworm.com/index.php?rid=3172715&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068183%26dopt%3DAbstract Authors: Schiffman JD, Hodgson JG, Vandenberg SR, Flaherty P, Polley MY, Yu M, Fisher PG, Rowitch DH, Ford JM, Berger MS, Ji H, Gutmann DH, James CD Malignant astrocytomas are a deadly solid tumor in children. Limited understanding of their underlying genetic basis has contributed to modest progress in developing more effective therapies. In an effort to identify such alterations, we performed a genome-wide search for DNA copy number aberrations (CNA) in a panel of 33 tumors encompassing grade 1 through grade 4 tumors. Genomic amplifications of 10-fold or greater were restricted to grade 3 and 4 astrocytomas and included the MDM4 (1q32), PDGFRA (4q12), MET (7q21), CMYC (8q24), PVT1 (8q24), WNT5B (12p13), and IGF1R (15q26) genes. Homozygous deletions of CDKN2A (9p21), PTEN (10q26), and ... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172715 Tue, 12 Jan 2010 00:00:00 +0100 3172715 http://www.medworm.com/index.php?rid=3172714&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068185%26dopt%3DAbstract Authors: Wang J, Ying G, Wang J, Jung Y, Lu J, Zhu J, Pienta KJ, Taichman RS Tumor and stromal interactions in the tumor microenvironment are critical for oncogenesis and cancer progression. Our understanding of the molecular events by which reactive stromal fibroblasts-myofibroblast or cancer-associated fibroblasts (CAF)-affect the growth and invasion of prostate cancer remains unclear. Laser capture microdissection and cDNA microarray analysis of CAFs in prostate tumors revealed strong upregulation of phosphoglycerate kinase-1 (PGK1), an ATP-generating glycolytic enzyme that forms part of the glycolytic pathway and is directly involved in CXCL12-CXCR4 signaling. Normal fibroblasts overexpressing PGK1 resembled myofibroblasts in their expression of smooth muscle alpha-actin, vimentin,... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172714 Tue, 12 Jan 2010 00:00:00 +0100 3172714 http://www.medworm.com/index.php?rid=3172713&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068187%26dopt%3DAbstract In this study, we investigated whether MMP-9 is critical for colitis-associated colon cancer (CAC). Mice that are wild type (WT) or MMP-9 nullizygous (MMP-9(-/-)) were used for in vivo studies and the human enterocyte cell line Caco2-BBE was used for in vitro studies. CAC was induced in mice using an established carcinogenesis protocol that involves exposure to azoxymethane followed by treatment with dextran sodium sulfate. MMP-9(-/-) mice exhibited increased susceptibility to CAC relative to WT mice. Elevations in tumor multiplicity, size, and mortality were associated with increased proliferation and decreased apoptosis. Tumors formed in MMP-9(-/-) mice exhibited expression of p21(WAF1/Cip1) and increased expression of beta-catenin relative to WT mice. In vitro studies of MMP-9 overexpre... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172713 Tue, 12 Jan 2010 00:00:00 +0100 3172713 http://www.medworm.com/index.php?rid=3172712&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20068188%26dopt%3DAbstract Authors: Pedersen MW, Jacobsen HJ, Koefoed K, Hey A, Pyke C, Haurum JS, Kragh M Epidermal growth factor receptor (EGFR) is a validated therapeutic target in cancer and EGFR antagonists with greater effectiveness than existing clinical agents remain of interest. Here, we report a novel approach based on Sym004, a mixture of two anti-EGFR monoclonal antibodies directed against distinct nonoverlapping epitopes in EGFR extracellular domain III. Like anti-EGFR monoclonal antibodies in current clinical use, Sym004 inhibits cancer cell growth and survival by blocking ligand-binding receptor activation and phosphorylation and downstream receptor signaling. However, unlike the other antibodies, Sym004 induces rapid and efficient removal of the receptor from the cancer cell surface by triggering... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172712 Tue, 12 Jan 2010 00:00:00 +0100 3172712 http://www.medworm.com/index.php?rid=3172711&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20069568%26dopt%3DAbstract Authors: Stratos I, Graff J, Rotter R, Mittlmeier T, Vollmar B Insufficiency of skeletal muscle regeneration is often accompanied with functional deficiencies. The goal of our study was to assess the restoration of peripheral muscle upon injury of different severity. Blunt crush injury of the soleus muscle in rats was induced by a clamp and stepwise amplified in severity by rising the locking level of the clamp, resulting in three different groups (1x lock; 2x lock; 3x lock; n = 30 animals per group). After assessment of the fast twitch and tetanic contraction capacity at days 1, 4, 7, 14, and 42 postinjury sampling of muscle tissue served for analysis of cell proliferation, including satellite cells, apoptosis, and leukocyte infiltration. Contraction force analysis demonstrated signif... Cell Research journals http://www.medworm.com/rss/comments.php?id=3172711 Tue, 12 Jan 2010 00:00:00 +0100 3172711 http://www.medworm.com/index.php?rid=3164672&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20063378%26dopt%3DAbstract Authors: Ryu K, Choy E, Yang C, Susa M, Hornicek FJ, Mankin H, Duan Z Stat3 expression in cancer may have important prognostic and therapeutic value, but there has been no reports correlating Stat3 expression with prognosis in patients with osteosarcoma. The goal of this study is to correlate patient prognosis with the expression of Stat3 in osteosarcoma tissue and determine the effectiveness of blocking this pathway in osteosarcoma cell lines by Stat3 inhibitor, CDDO-Me. We examine the expression levels of Stat3 and pStat3 in osteosarcoma cell lines and primary tissues by Western blot analysis. We also evaluate the levels of pStat3 expression in osteosarcoma tissue microarray (TMA) by immunohistochemistry. We use clinical data to determine the impact of levels of Stat3 expression on p... Cell Research journals http://www.medworm.com/rss/comments.php?id=3164672 Fri, 08 Jan 2010 00:00:00 +0100 3164672 http://www.medworm.com/index.php?rid=3164671&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20063383%26dopt%3DAbstract Authors: Savarino L, Avnet S, Greco M, Giunti A, Baldini N In a cohort study, the role of the active tartrate-resistant acid phosphatase (TRACP 5b), a marker of bone-resorbing osteoclasts, for the assessment of loosening after total hip arthroplasty (THA), was analyzed, as well as its correlation with osteolysis and multinucleated cell appearance in the retrievals. Eighty THA patients, who went consecutively to the orthopedic department, were asked to participate, and 54 accepted and were enrolled in the study. Finally, 46 subjects were analyzed, clinical-radiographic evaluation was considered the gold standard, serum TRACP 5b was blindly measured, and a cut-off was obtained, by performing a ROC Curve. Based on the gold standard, patients were split by 19 stable and 27 loosened subject... Cell Research journals http://www.medworm.com/rss/comments.php?id=3164671 Fri, 08 Jan 2010 00:00:00 +0100 3164671 http://www.medworm.com/index.php?rid=3149480&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20047504%26dopt%3DAbstract Authors: Antonarakis ES, Carducci MA Prostate GVAX((R)) is an allogeneic cell-based prostate cancer vaccine engineered to secrete GM-CSF. The release of GM-CSF by this immunotherapy serves to recruit dendritic cells, which then present tumor antigens to T cells, thus initiating antitumor immune responses. However, preclinical data show that, when used alone, cell-based immunotherapy is generally unable to break specific T-cell tolerance in tumor-bearing hosts. The study by Wada and colleagues employed an autochthonous prostate cancer mouse model to demonstrate that low-dose cyclophosphamide given prior to a cell-based GM-CSF-secreting vaccine (T-GVAX) abrogated immune tolerance, augmented prostatic CD8(+) T-cell infiltration, mediated depletion of regulatory T cells (Tregs), and increa... Cell Research journals http://www.medworm.com/rss/comments.php?id=3149480 Tue, 05 Jan 2010 00:00:00 +0100 3149480 http://www.medworm.com/index.php?rid=3149479&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20052708%26dopt%3DAbstract Authors: Lyakhov I, Zielinski R, Kuban M, Kramer-Marek G, Fisher R, Chertov O, Bindu L, Capala J The human epidermal growth factor receptors, EGFR and HER2, are members of the EGFR family of cell-surface receptors/tyrosine kinases. EGFR- and HER2-positive cancers represent a more aggressive disease with greater likelihood of recurrence, poorer prognosis, and decreased survival rate, compared to EGFR- or HER2-negative cancers. The details of HER2 proto-oncogenic functions are not deeply understood, partially because of a restricted availability of tools for EGFR and HER2 detection (A. Sorkin and L. K. Goh, Exp. Cell Res. 2009, 315, 683-696). We have created photostable and relatively simple-to-produce imaging probes for in vitro staining of EGFR and HER2. These new reagents, called affi... Cell Research journals http://www.medworm.com/rss/comments.php?id=3149479 Tue, 05 Jan 2010 00:00:00 +0100 3149479 http://www.medworm.com/index.php?rid=3143088&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20046199%26dopt%3DAbstract Authors: Masson F, Belz GT PMID: 20046199 [PubMed - in process] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=3143088 Fri, 01 Jan 2010 00:00:00 +0100 3143088 http://www.medworm.com/index.php?rid=3115581&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20021204%26dopt%3DAbstract Authors: Michalski CW, Erkan M, Friess H, Kleeff J Evaluation of: Komar G, Kauhanen S, Liukko K et al.: Decreased blood flow with increased metabolic activity: a novel sign of pancreatic tumor aggressiveness. Clin. Cancer Res. 15(17), 5511-5517 (2009). Novel methods in assessing pancreas cancer vascularization and metabolism are urgently needed for pretherapeutic patient stratification. Recently, noninvasive quantification of blood flow and metabolic activity of pancreatic tumors using [(15)O]H(2)O and [(18)F] fluorodeoxyglucose positron emission tomography/computed tomography imaging has been demonstrated to be a promising approach to assess these parameters. This also implied that high tumor metabolism and low blood flow (and thus probably also low tissue oxygenation) are linked with... Cell Research journals http://www.medworm.com/rss/comments.php?id=3115581 Wed, 23 Dec 2009 22:56:06 +0100 3115581 http://www.medworm.com/index.php?rid=2992969&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19907983%26dopt%3DAbstract Authors: Goldstein RS, Pomp O, Brokhman I, Ziegler L Peripheral somatic sensory neurons (PSNs) are responsible for the critical function of transmitting multiple modalities of information from the outside world, including heat, touch, and pain, as well as the position of muscles required for coordinated voluntary movement to the central nervous system. Many peripheral neuropathies exist, including hereditary neurodegeneration in Familial Dysautonomia, infections of PSNs by viruses such as Varicella zoster and damage to PSNs and/or their process resulting from other disease conditions such as diabetes. Understanding of the etiology of these diseases and development of treatments is hampered by the lack of normal and healthy human PSNs for study, which are only available from abortuses o... Cell Research journals http://www.medworm.com/rss/comments.php?id=2992969 Sun, 15 Nov 2009 01:14:04 +0100 2992969 http://www.medworm.com/index.php?rid=2985663&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903766%26dopt%3DAbstract Authors: Zhao J, Xin M, Wang T, Zhang Y, Deng X Lung cancer has a strong etiologic association with cigarette smoking. Nicotine, a major component in tobacco smoke, functions as a survival agonist that inhibits apoptosis following various stresses. However, the mechanism of action remains elusive. Mcl-1, a major antiapoptotic protein of the Bcl2 family, is extensively expressed in both small cell and non-small cell lung cancer cells, suggesting that Mcl-1 may be a therapeutic target of patients with lung cancer. Here, we found that nicotine induces Mcl-1 phosphorylation through activation of extracellular signal-regulated kinase 1/2 in association with increased chemoresistance of human lung cancer cells. Since nicotine stimulates Mcl-1 phosphorylation and survival in cells expressing ... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985663 Tue, 10 Nov 2009 00:00:00 +0100 2985663 http://www.medworm.com/index.php?rid=2985662&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903768%26dopt%3DAbstract Authors: Hillion J, Wood LJ, Mukherjee M, Bhattacharya R, Di Cello F, Kowalski J, Elbahloul O, Segal J, Poirier J, Rudin CM, Dhara S, Belton A, Joseph B, Zucker S, Resar LM Although lung cancer is the leading cause of cancer death worldwide, the precise molecular mechanisms that give rise to lung cancer are incompletely understood. Here, we show that HMGA1 is an important oncogene that drives transformation in undifferentiated, large-cell carcinoma. First, we show that the HMGA1 gene is overexpressed in lung cancer cell lines and primary human lung tumors. Forced overexpression of HMGA1 induces a transformed phenotype with anchorage-independent cell growth in cultured lung cells derived from normal tissue. Conversely, inhibiting HMGA1 expression blocks anchorage-independent cell growth... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985662 Tue, 10 Nov 2009 00:00:00 +0100 2985662 http://www.medworm.com/index.php?rid=2985661&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903769%26dopt%3DAbstract Authors: Gueron G, De Siervi A, Ferrando M, Salierno M, De Luca P, Elguero B, Meiss R, Navone N, Vazquez ES Prostate cancer (PCa) is the second leading cause of cancer-associated death in men. Inflammation has been recognized as a risk factor for this disease. Heme oxygenase 1 (HO-1), the inducible isoform of the rate-limiting enzyme in heme degradation, counteracts oxidative and inflammatory damage. Here, we investigated the regulated expression of HO-1 and its functional consequences in PCa. We studied the effect of genetic and pharmacologic disruption of HO-1 in the growth, invasion, and migration in androgen-sensitive (MDA PCa2b and LNCaP) and androgen-insensitive (PC3) PCa cell lines. Our results show that HO-1 levels are markedly decreased in PC3 compared with MDA PCa2b and LNCaP... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985661 Tue, 10 Nov 2009 00:00:00 +0100 2985661 http://www.medworm.com/index.php?rid=2985660&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903772%26dopt%3DAbstract In this study, we describe a novel function of the p34(SEI-1) protein, which is both an oncogenic protein and a positive regulator of the cell cycle. The p34(SEI-1) protein was found to inhibit doxorubicin-induced senescence. We investigated the molecular mechanisms of the inhibitory effect of p34(SEI-1) on senescence. First, we found that the activation of protein kinase C-delta (PKC-delta), which is cleaved into a 38 kDa active form from a 78 kDa pro-form, induced after doxorubicin treatment, was inhibited by p34(SEI-1). Furthermore, p34(SEI-1) induced the ubiquitination of PKC-delta. Yet, there is no interaction between p34(SEI-1) and PKC-delta. We also found that the phosphorylation of c-Jun-NH(2)-kinase 1 (JNK1) induced after doxorubicin treatment was suppressed by p34(SEI-1), but not... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985660 Tue, 10 Nov 2009 00:00:00 +0100 2985660 http://www.medworm.com/index.php?rid=2985659&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903777%26dopt%3DAbstract CONCLUSION: These data suggest that GM-CSF is not helpful as an immune adjuvant in this dose and schedule and raise concern that it may be harmful. Based on the discordant findings of an immune endpoint and clinical outcome, the use of such surrogate endpoints in selecting treatments for further evaluation must be done with a great deal of caution. (Clin Cancer Res 2009;15(22):7029-35). PMID: 19903777 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985659 Tue, 10 Nov 2009 00:00:00 +0100 2985659 http://www.medworm.com/index.php?rid=2985658&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903779%26dopt%3DAbstract Authors: Eggermont AM Three articles in this issue of Clinical Cancer Research show how multiple vaccinations can lead to immunosuppression. Moreover, two studies in patients show that granulocyte macrophage colony-stimulating factor (GM-CSF) as an adjuvant immunostimulant to different kind of vaccines can lead to adverse outcome in terms of relapse-free and overall survival. Modulation of regulatory T-cell activity may be required to overcome this outcome and may be crucial for the successful development of therapeutic vaccines. (Clin Cancer Res 2009;15(22):6745-7). PMID: 19903779 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985658 Tue, 10 Nov 2009 00:00:00 +0100 2985658 http://www.medworm.com/index.php?rid=2985657&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903780%26dopt%3DAbstract CONCLUSIONS: High immune response rates for this multipeptide vaccine were achieved, but CD8(+) and CD4(+) T-cell responses were lower when administered with GM-CSF. These data challenge the value of local GM-CSF as a vaccine adjuvant in humans. (Clin Cancer Res 2009;15(22):7036-44). PMID: 19903780 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985657 Tue, 10 Nov 2009 00:00:00 +0100 2985657 http://www.medworm.com/index.php?rid=2985656&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903784%26dopt%3DAbstract CONCLUSION: These results suggest that CD4+ T(reg) cells limit the efficacy of multiple vaccinations and that timed partial depletion of CD4+ T cells may reduce suppression and "tip-the-balance" in favor of therapeutic antitumor immunity. The recent failure of large phase III cancer vaccine clinical trials, wherein patients received multiple vaccines, underscores the potential clinical relevance of these findings. (Clin Cancer Res 2009;15(22):6881-90). PMID: 19903784 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985656 Tue, 10 Nov 2009 00:00:00 +0100 2985656 http://www.medworm.com/index.php?rid=2985655&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903785%26dopt%3DAbstract CONCLUSION: This is the first clinical use of carfilzomib that shows tolerability and clinical activity in multiple hematologic malignancies using consecutive-day dosing. (Clin Cancer Res 2009;15(22):7085-91). PMID: 19903785 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985655 Tue, 10 Nov 2009 00:00:00 +0100 2985655 http://www.medworm.com/index.php?rid=2985654&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903789%26dopt%3DAbstract CONCLUSION: The results indicate that deregulated GSK3beta sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. (Clin Cancer Res 2009;15(22):6810-19). PMID: 19903789 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985654 Tue, 10 Nov 2009 00:00:00 +0100 2985654 http://www.medworm.com/index.php?rid=2985653&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903791%26dopt%3DAbstract CONCLUSIONS: We showed a cooperative effect of IMO plus trastuzumab in trastuzumab-resistant breast cancers due to IMO direct antitumor and antiangiogenic activity and antibody-dependent cell-mediated cytotoxicity enhancement. Moreover, we provided first evidence of a toll-like receptor 9/HER interaction at membrane level as novel mechanism of action. Altogether, we propose IMO plus trastuzumab as an effective strategy in trastuzumab-resistant breast cancers. (Clin Cancer Res 2009;15(22):6921-30). PMID: 19903791 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985653 Tue, 10 Nov 2009 00:00:00 +0100 2985653 http://www.medworm.com/index.php?rid=2985652&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903839%26dopt%3DAbstract Authors: Kamat AM, Tharakan ST, Sung B, Aggarwal BB Although Bacillus Calmette-Guerin (BCG) intravesical therapy is a standard treatment for bladder cancer, eventual failure of response is a major problem. Treatments that can augment BCG therapy are urgently needed. We investigated whether curcumin, a component of Curcuma longa (also called turmeric), has potential to improve the current therapy using in vitro and in vivo MBT-2 murine tumor models. We found that curcumin potentiated BCG-induced apoptosis of human bladder cancer cells. BCG stimulated the release of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from peripheral mononuclear neutrophils in a dose- and time-dependent manner, whereas curcumin enhanced the upregulation of TRAIL receptors. Electrophoretic mobi... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985652 Tue, 10 Nov 2009 00:00:00 +0100 2985652 http://www.medworm.com/index.php?rid=2985651&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903840%26dopt%3DAbstract Authors: Brown CE, Starr R, Martinez C, Aguilar B, D'Apuzzo M, Todorov I, Shih CC, Badie B, Hudecek M, Riddell SR, Jensen MC Solid tumors contain a subset of stem-like cells that are resistant to the cytotoxic effects of chemotherapy/radiotherapy, but their susceptibility to cytolytic T lymphocyte (CTL) effector mechanisms has not been well characterized. Using a panel of early-passage human brain tumor stem/initiating cell (BTSC) lines derived from high-grade gliomas, we show that BTSCs are subject to immunologic recognition and elimination by CD8(+) CTLs. Compared with serum-differentiated CD133(low) tumor cells and established glioma cell lines, BTSCs are equivalent with respect to expression levels of HLA class I and ICAM-1, similar in their ability to trigger degranulation and cyt... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985651 Tue, 10 Nov 2009 00:00:00 +0100 2985651 http://www.medworm.com/index.php?rid=2985650&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903841%26dopt%3DAbstract In this report, we identify two miRNAs, miR-15a and miR-16, that are underexpressed in ovarian cell lines and in primary ovarian tissues. We show that these miRNAs directly target the Bmi-1 3' untranslated region and significantly correlate with Bmi-1 protein levels in ovarian cancer patients and cell lines. Furthermore, Bmi-1 protein levels are downregulated in response to miR-15a or miR-16 expression and lead to significant reduction in ovarian cancer cell proliferation and clonal growth. These findings suggest the development of therapeutic strategies by restoring miR-15a and miR-16 expression in ovarian cancer and in other cancers that involve upregulation of Bmi-1. [Cancer Res 2009;69(23):OF1-6]. PMID: 19903841 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985650 Tue, 10 Nov 2009 00:00:00 +0100 2985650 http://www.medworm.com/index.php?rid=2985649&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903843%26dopt%3DAbstract Authors: Kiyono K, Suzuki HI, Matsuyama H, Morishita Y, Komuro A, Kano MR, Sugimoto K, Miyazono K Transforming growth factor-beta (TGF-beta) is a multifunctional cytokine that regulates cell growth, differentiation, and apoptosis of various types of cells. Autophagy is emerging as a critical response of normal and cancer cells to environmental changes, but the relationship between TGF-beta signaling and autophagy has been poorly understood. Here, we showed that TGF-beta activates autophagy in human hepatocellular carcinoma cell lines. TGF-beta induced accumulation of autophagosomes and conversion of microtubule-associated protein 1 light chain 3 and enhanced the degradation rate of long-lived proteins. TGF-beta increased the mRNA expression levels of BECLIN1, ATG5, ATG7, and death-asso... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985649 Tue, 10 Nov 2009 00:00:00 +0100 2985649 http://www.medworm.com/index.php?rid=2985648&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903845%26dopt%3DAbstract Authors: Pang H, Flinn R, Patsialou A, Wyckoff J, Roussos ET, Wu H, Pozzuto M, Goswami S, Condeelis JS, Bresnick AR, Segall JE, Backer JM Class IA (p85/p110) phosphoinositide 3-kinases play a major role in regulating cell growth, survival, and motility. Activating mutations in the p110alpha isoform of the class IA catalytic subunit (PIK3CA) are commonly found in human cancers. These mutations lead to increased proliferation and transformation in cultured cells, but their effects on cell motility and tumor metastasis have not been evaluated. We used lentiviral-mediated gene transfer and knockdown to produce stable MDA-MB-231 cells in which the endogenous human p110alpha is replaced with either wild-type bovine p110alpha or the two most common activating p110alpha mutants, the helical do... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985648 Tue, 10 Nov 2009 00:00:00 +0100 2985648 http://www.medworm.com/index.php?rid=2985647&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903846%26dopt%3DAbstract In conclusion, persistent betaPV infections in this population were associated with an increased occurrence of actinic keratosis. Additional studies are needed to determine the possible association of betaPV persistence with SCC. [Cancer Res 2009;69(23):OF1-6]. PMID: 19903846 [PubMed - as supplied by publisher] (Source: Cell Research) Cell Research journals http://www.medworm.com/rss/comments.php?id=2985647 Tue, 10 Nov 2009 00:00:00 +0100 2985647 http://www.medworm.com/index.php?rid=2985646&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903848%26dopt%3DAbstract Authors: Weige CC, Allred KF, Allred CD Numerous clinical and animal studies show that hormone replacement therapy reduces the risk of colon tumor formation. However, the majority of experiments have shown that estradiol (E(2)) does not inhibit the growth of malignantly transformed colon epithelia. As such, the presented studies focused on evaluating the effects of E(2) in noncancerous colonocytes. E(2) treatments (0-10 nmol/L) reduced cell growth and increased apoptotic activity in young adult mouse colonocytes (YAMC), a nonmalignant cell line, in a dose-responsive manner. These effects were lost in the YAMC-Ras cells, an isogenic cell line with a single malignant transformation. Cotreatment with an estrogen receptor (ER) antagonist inhibited the physiologic effects of E(2) in YAMC ce... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985646 Tue, 10 Nov 2009 00:00:00 +0100 2985646 http://www.medworm.com/index.php?rid=2985645&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903849%26dopt%3DAbstract Authors: Arafa ES, Zhu Q, Barakat BM, Wani G, Zhao Q, El-Mahdy MA, Wani AA Combination of innocuous dietary components with anticancer drugs is an emerging new strategy for cancer chemotherapy to increase antitumor responses. Tangeretin is a citrus flavonoid known to inhibit cancer cell proliferation. Here, we show an enhanced response of A2780/CP70 and 2008/C13 cisplatin-resistant human ovarian cancer cells to various combination treatments of cisplatin and tangeretin. Pretreatment of cells with tangeretin before cisplatin treatment synergistically inhibited cancer cell proliferation. This combination was effective in activating apoptosis via caspase cascade as well as arresting cell cycle at G(2)-M phase. Moreover, phospho-Akt and its downstream substrates, e.g., NF-kappaB, phospho-G... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985645 Tue, 10 Nov 2009 00:00:00 +0100 2985645 http://www.medworm.com/index.php?rid=2985644&cid=s_30451_171_f&fid=30451&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19903850%26dopt%3DAbstract Authors: Ochs MF, Rink L, Tarn C, Mburu S, Taguchi T, Eisenberg B, Godwin AK Cell signaling plays a central role in the etiology of cancer. Numerous therapeutics in use or under development target signaling proteins; however, off-target effects often limit assignment of positive clinical response to the intended target. As direct measurements of signaling protein activity are not generally feasible during treatment, there is a need for more powerful methods to determine if therapeutics inhibit their targets and when off-target effects occur. We have used the Bayesian Decomposition algorithm and data on transcriptional regulation to create a novel methodology, Differential Expression for Signaling Determination (DESIDE), for inferring signaling activity from microarray measurements. We ... Cell Research journals http://www.medworm.com/rss/comments.php?id=2985644 Tue, 10 Nov 2009 00:00:00 +0100 2985644