Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Publication Date: 2011-08-23
    Description: The human mind and body respond to stress, a state of perceived threat to homeostasis, by activating the sympathetic nervous system and secreting the catecholamines adrenaline and noradrenaline in the 'fight-or-flight' response. The stress response is generally transient because its accompanying effects (for example, immunosuppression, growth inhibition and enhanced catabolism) can be harmful in the long term. When chronic, the stress response can be associated with disease symptoms such as peptic ulcers or cardiovascular disorders, and epidemiological studies strongly indicate that chronic stress leads to DNA damage. This stress-induced DNA damage may promote ageing, tumorigenesis, neuropsychiatric conditions and miscarriages. However, the mechanisms by which these DNA-damage events occur in response to stress are unknown. The stress hormone adrenaline stimulates beta(2)-adrenoreceptors that are expressed throughout the body, including in germline cells and zygotic embryos. Activated beta(2)-adrenoreceptors promote Gs-protein-dependent activation of protein kinase A (PKA), followed by the recruitment of beta-arrestins, which desensitize G-protein signalling and function as signal transducers in their own right. Here we elucidate a molecular mechanism by which beta-adrenergic catecholamines, acting through both Gs-PKA and beta-arrestin-mediated signalling pathways, trigger DNA damage and suppress p53 levels respectively, thus synergistically leading to the accumulation of DNA damage. In mice and in human cell lines, beta-arrestin-1 (ARRB1), activated via beta(2)-adrenoreceptors, facilitates AKT-mediated activation of MDM2 and also promotes MDM2 binding to, and degradation of, p53, by acting as a molecular scaffold. Catecholamine-induced DNA damage is abrogated in Arrb1-knockout (Arrb1(-/-)) mice, which show preserved p53 levels in both the thymus, an organ that responds prominently to acute or chronic stress, and in the testes, in which paternal stress may affect the offspring's genome. Our results highlight the emerging role of ARRB1 as an E3-ligase adaptor in the nucleus, and reveal how DNA damage may accumulate in response to chronic stress.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628753/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3628753/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Hara, Makoto R -- Kovacs, Jeffrey J -- Whalen, Erin J -- Rajagopal, Sudarshan -- Strachan, Ryan T -- Grant, Wayne -- Towers, Aaron J -- Williams, Barbara -- Lam, Christopher M -- Xiao, Kunhong -- Shenoy, Sudha K -- Gregory, Simon G -- Ahn, Seungkirl -- Duckett, Derek R -- Lefkowitz, Robert J -- HL16037/HL/NHLBI NIH HHS/ -- HL70631/HL/NHLBI NIH HHS/ -- R01 HL016037/HL/NHLBI NIH HHS/ -- R01 HL070631/HL/NHLBI NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2011 Aug 21;477(7364):349-53. doi: 10.1038/nature10368.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21857681" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/deficiency/genetics/*metabolism ; Catecholamines/pharmacology ; Cell Line ; Cell Nucleus/enzymology/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; *DNA Damage ; Fibroblasts ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Protein Processing, Post-Translational/drug effects ; Proto-Oncogene Proteins c-akt/metabolism ; Proto-Oncogene Proteins c-mdm2/metabolism ; Receptors, Adrenergic, beta-2/*metabolism ; Signal Transduction/drug effects ; Stress, Physiological/*physiology ; Testis/metabolism ; Thymus Gland/metabolism ; Tumor Suppressor Protein p53/chemistry/metabolism
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Publication Date: 2014-04-11
    Description: The BRAF kinase is mutated, typically Val 600--〉Glu (V600E), to induce an active oncogenic state in a large fraction of melanomas, thyroid cancers, hairy cell leukaemias and, to a smaller extent, a wide spectrum of other cancers. BRAF(V600E) phosphorylates and activates the MEK1 and MEK2 kinases, which in turn phosphorylate and activate the ERK1 and ERK2 kinases, stimulating the mitogen-activated protein kinase (MAPK) pathway to promote cancer. Targeting MEK1/2 is proving to be an important therapeutic strategy, given that a MEK1/2 inhibitor provides a survival advantage in metastatic melanoma, an effect that is increased when administered together with a BRAF(V600E) inhibitor. We previously found that copper (Cu) influx enhances MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interaction. Here we show decreasing the levels of CTR1 (Cu transporter 1), or mutations in MEK1 that disrupt Cu binding, decreased BRAF(V600E)-driven signalling and tumorigenesis in mice and human cell settings. Conversely, a MEK1-MEK5 chimaera that phosphorylated ERK1/2 independently of Cu or an active ERK2 restored the tumour growth of murine cells lacking Ctr1. Cu chelators used in the treatment of Wilson disease decreased tumour growth of human or murine cells transformed by BRAF(V600E) or engineered to be resistant to BRAF inhibition. Taken together, these results suggest that Cu-chelation therapy could be repurposed to treat cancers containing the BRAF(V600E) mutation.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138975/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138975/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Brady, Donita C -- Crowe, Matthew S -- Turski, Michelle L -- Hobbs, G Aaron -- Yao, Xiaojie -- Chaikuad, Apirat -- Knapp, Stefan -- Xiao, Kunhong -- Campbell, Sharon L -- Thiele, Dennis J -- Counter, Christopher M -- 092809/Wellcome Trust/United Kingdom -- 092809/Z/10/Z/Wellcome Trust/United Kingdom -- CA094184/CA/NCI NIH HHS/ -- CA172104/CA/NCI NIH HHS/ -- CA178145/CA/NCI NIH HHS/ -- DK074192/DK/NIDDK NIH HHS/ -- HL075443/HL/NHLBI NIH HHS/ -- K01 CA178145/CA/NCI NIH HHS/ -- P01 HL075443/HL/NHLBI NIH HHS/ -- P30 CA014236/CA/NCI NIH HHS/ -- P30 CA016086/CA/NCI NIH HHS/ -- R01 CA089614/CA/NCI NIH HHS/ -- R01 CA094184/CA/NCI NIH HHS/ -- R01 DK074192/DK/NIDDK NIH HHS/ -- R21 CA172104/CA/NCI NIH HHS/ -- T32 GM007184/GM/NIGMS NIH HHS/ -- T32 GM008570/GM/NIGMS NIH HHS/ -- England -- Nature. 2014 May 22;509(7501):492-6. doi: 10.1038/nature13180. Epub 2014 Apr 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. ; Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Nuffield Department of Clinical Medicine, Target Discovery Institute and Structural Genomics Consortium, University of Oxford, Oxford OX3 7DQ, UK. ; 1] Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24717435" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Cation Transport Proteins/deficiency/genetics ; Cell Line, Tumor ; *Cell Transformation, Neoplastic/drug effects ; Chelating Agents/pharmacology/therapeutic use ; Copper/*metabolism/pharmacology ; Disease Models, Animal ; Drug Repositioning ; Drug Resistance, Neoplasm/drug effects ; Female ; Hepatolenticular Degeneration/drug therapy ; Humans ; Indoles/pharmacology ; Lung Neoplasms/drug therapy/genetics/metabolism/pathology ; *MAP Kinase Signaling System/drug effects ; Mice ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Mitogen-Activated Protein Kinase Kinases/antagonists & ; inhibitors/genetics/metabolism ; Phosphorylation/drug effects ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors/genetics/*metabolism ; Sulfonamides/pharmacology ; Survival Analysis
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Publication Date: 2013-04-23
    Description: The functions of G-protein-coupled receptors (GPCRs) are primarily mediated and modulated by three families of proteins: the heterotrimeric G proteins, the G-protein-coupled receptor kinases (GRKs) and the arrestins. G proteins mediate activation of second-messenger-generating enzymes and other effectors, GRKs phosphorylate activated receptors, and arrestins subsequently bind phosphorylated receptors and cause receptor desensitization. Arrestins activated by interaction with phosphorylated receptors can also mediate G-protein-independent signalling by serving as adaptors to link receptors to numerous signalling pathways. Despite their central role in regulation and signalling of GPCRs, a structural understanding of beta-arrestin activation and interaction with GPCRs is still lacking. Here we report the crystal structure of beta-arrestin-1 (also called arrestin-2) in complex with a fully phosphorylated 29-amino-acid carboxy-terminal peptide derived from the human V2 vasopressin receptor (V2Rpp). This peptide has previously been shown to functionally and conformationally activate beta-arrestin-1 (ref. 5). To capture this active conformation, we used a conformationally selective synthetic antibody fragment (Fab30) that recognizes the phosphopeptide-activated state of beta-arrestin-1. The structure of the beta-arrestin-1-V2Rpp-Fab30 complex shows marked conformational differences in beta-arrestin-1 compared to its inactive conformation. These include rotation of the amino- and carboxy-terminal domains relative to each other, and a major reorientation of the 'lariat loop' implicated in maintaining the inactive state of beta-arrestin-1. These results reveal, at high resolution, a receptor-interacting interface on beta-arrestin, and they indicate a potentially general molecular mechanism for activation of these multifunctional signalling and regulatory proteins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654799/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3654799/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shukla, Arun K -- Manglik, Aashish -- Kruse, Andrew C -- Xiao, Kunhong -- Reis, Rosana I -- Tseng, Wei-Chou -- Staus, Dean P -- Hilger, Daniel -- Uysal, Serdar -- Huang, Li-Yin -- Paduch, Marcin -- Tripathi-Shukla, Prachi -- Koide, Akiko -- Koide, Shohei -- Weis, William I -- Kossiakoff, Anthony A -- Kobilka, Brian K -- Lefkowitz, Robert J -- GM072688/GM/NIGMS NIH HHS/ -- GM087519/GM/NIGMS NIH HHS/ -- HL 075443/HL/NHLBI NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- HL70631/HL/NHLBI NIH HHS/ -- NS028471/NS/NINDS NIH HHS/ -- P41 RR011823/RR/NCRR NIH HHS/ -- R01 HL016037/HL/NHLBI NIH HHS/ -- R01 HL070631/HL/NHLBI NIH HHS/ -- R01 NS028471/NS/NINDS NIH HHS/ -- U01 GM094588/GM/NIGMS NIH HHS/ -- U54 GM074946/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2013 May 2;497(7447):137-41. doi: 10.1038/nature12120. Epub 2013 Apr 21.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/23604254" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*chemistry/immunology/*metabolism ; Crystallography, X-Ray ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology/metabolism ; Models, Molecular ; Phosphopeptides/*chemistry/*metabolism ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Stability ; Rats ; Receptors, Vasopressin/*chemistry ; Rotation
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Publication Date: 2014-07-22
    Description: G-protein-coupled receptors (GPCRs) are critically regulated by beta-arrestins, which not only desensitize G-protein signalling but also initiate a G-protein-independent wave of signalling. A recent surge of structural data on a number of GPCRs, including the beta2 adrenergic receptor (beta2AR)-G-protein complex, has provided novel insights into the structural basis of receptor activation. However, complementary information has been lacking on the recruitment of beta-arrestins to activated GPCRs, primarily owing to challenges in obtaining stable receptor-beta-arrestin complexes for structural studies. Here we devised a strategy for forming and purifying a functional human beta2AR-beta-arrestin-1 complex that allowed us to visualize its architecture by single-particle negative-stain electron microscopy and to characterize the interactions between beta2AR and beta-arrestin 1 using hydrogen-deuterium exchange mass spectrometry (HDX-MS) and chemical crosslinking. Electron microscopy two-dimensional averages and three-dimensional reconstructions reveal bimodal binding of beta-arrestin 1 to the beta2AR, involving two separate sets of interactions, one with the phosphorylated carboxy terminus of the receptor and the other with its seven-transmembrane core. Areas of reduced HDX together with identification of crosslinked residues suggest engagement of the finger loop of beta-arrestin 1 with the seven-transmembrane core of the receptor. In contrast, focal areas of raised HDX levels indicate regions of increased dynamics in both the N and C domains of beta-arrestin 1 when coupled to the beta2AR. A molecular model of the beta2AR-beta-arrestin signalling complex was made by docking activated beta-arrestin 1 and beta2AR crystal structures into the electron microscopy map densities with constraints provided by HDX-MS and crosslinking, allowing us to obtain valuable insights into the overall architecture of a receptor-arrestin complex. The dynamic and structural information presented here provides a framework for better understanding the basis of GPCR regulation by arrestins.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134437/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉   〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4134437/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shukla, Arun K -- Westfield, Gerwin H -- Xiao, Kunhong -- Reis, Rosana I -- Huang, Li-Yin -- Tripathi-Shukla, Prachi -- Qian, Jiang -- Li, Sheng -- Blanc, Adi -- Oleskie, Austin N -- Dosey, Anne M -- Su, Min -- Liang, Cui-Rong -- Gu, Ling-Ling -- Shan, Jin-Ming -- Chen, Xin -- Hanna, Rachel -- Choi, Minjung -- Yao, Xiao Jie -- Klink, Bjoern U -- Kahsai, Alem W -- Sidhu, Sachdev S -- Koide, Shohei -- Penczek, Pawel A -- Kossiakoff, Anthony A -- Woods, Virgil L Jr -- Kobilka, Brian K -- Skiniotis, Georgios -- Lefkowitz, Robert J -- DK090165/DK/NIDDK NIH HHS/ -- GM072688/GM/NIGMS NIH HHS/ -- GM087519/GM/NIGMS NIH HHS/ -- GM60635/GM/NIGMS NIH HHS/ -- HL075443/HL/NHLBI NIH HHS/ -- HL16037/HL/NHLBI NIH HHS/ -- HL70631/HL/NHLBI NIH HHS/ -- MOP-93725/Canadian Institutes of Health Research/Canada -- NS028471/NS/NINDS NIH HHS/ -- R01 DK090165/DK/NIDDK NIH HHS/ -- R01 GM060635/GM/NIGMS NIH HHS/ -- R01 GM072688/GM/NIGMS NIH HHS/ -- R01 HL016037/HL/NHLBI NIH HHS/ -- R01 HL070631/HL/NHLBI NIH HHS/ -- R01 NS028471/NS/NINDS NIH HHS/ -- UL1 TR000430/TR/NCATS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Aug 14;512(7513):218-22. doi: 10.1038/nature13430. Epub 2014 Jun 22.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Biological Sciences and Bioengineering, Indian Institute of Technology, Kanpur 208016, India. [3]. ; 1] Life Sciences Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA [2]. ; 1] Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA [2]. ; Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Chemistry, University of California at San Diego, La Jolla, California 92093, USA. ; Life Sciences Institute and Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA. ; School of Pharmaceutical &Life Sciences, Changzhou University, Changzhou, Jiangsu 213164, China. ; Terrence Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, Ontario M5S 3E1, Canada. ; Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA. ; Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, USA. ; Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas 77054, USA. ; 1] Department of Chemistry, University of California at San Diego, La Jolla, California 92093, USA [2]. ; Department of Molecular and Cellular Physiology, Stanford University School of Medicine, 279 Campus Drive, Stanford, California 94305, USA. ; 1] Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA [2] Department of Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA [3] Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25043026" target="_blank"〉PubMed〈/a〉
    Keywords: Animals ; Arrestins/*chemistry/*metabolism ; GTP-Binding Proteins/chemistry/metabolism ; *Models, Molecular ; Protein Structure, Quaternary ; Receptors, Adrenergic, beta-2/chemistry/metabolism ; Receptors, G-Protein-Coupled/*chemistry/*metabolism ; Sf9 Cells
    Print ISSN: 0028-0836
    Electronic ISSN: 1476-4687
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Publication Date: 2018-01-06
    Description: A magnetoresistance (MR) effect induced by the Rashba spin-orbit interaction was predicted, but not yet observed, in bilayers consisting of normal metal and ferromagnetic insulator. We present an experimental observation of this new type of spin-orbit MR (SOMR) effect in the Cu[Pt]/Y 3 Fe 5 O 12 (YIG) bilayer structure, where the Cu/YIG interface is decorated with nanosize Pt islands. This new MR is apparently not caused by the bulk spin-orbit interaction because of the negligible spin-orbit interaction in Cu and the discontinuity of the Pt islands. This SOMR disappears when the Pt islands are absent or located away from the Cu/YIG interface; therefore, we can unambiguously ascribe it to the Rashba spin-orbit interaction at the interface enhanced by the Pt decoration. The numerical Boltzmann simulations are consistent with the experimental SOMR results in the angular dependence of magnetic field and the Cu thickness dependence. Our finding demonstrates the realization of the spin manipulation by interface engineering.
    Electronic ISSN: 2375-2548
    Topics: Natural Sciences in General
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Electrochimica Acta 38 (1993), S. 459-464 
    ISSN: 0013-4686
    Keywords: dye photocell ; organic dyes. ; photoelectrochemical cells ; photovoltage
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Publication Date: 2018-08-30
    Description: An improved method was applied for remediating cadmium and copper co-contaminated soil and reducing the metal concentration in Rhizoma chuanxiong . Pot experiments were conducted with six amendments (composed with bentonite, phosphate, humic acid, biochar, sepiolite powder, etc.). The results showed that soil pH, biological activities (soil enzymatic activities and microbial counts) and R. chuanxiong biomass were greatly improved with the addition of amendments in all treatments, especially in T3 and T6. Also, amendments effectively decreased the concentration of malondialdehyde and H 2 O 2 in R. chuanxiong . In the T3 treatment, the bio-available Cd and Cu in soil were significantly decreased by 0.53 and 0.41 mg kg –1 , respectively. Meanwhile, the amendment in T3 reduced Cd and Cu accumulation in R. chuanxiong about 45.83 and 39.37%, respectively, compared to T0. Moreover, the Fourier transform infrared spectroscopy spectra showed the surface functional groups of every amendment. To conclude, this study offers an effective and environmental method to reduce metal accumulation in R. chuanxiong on heavy metal co-contaminated soil.
    Keywords: environmental science
    Electronic ISSN: 2054-5703
    Topics: Natural Sciences in General
    Published by Royal Society
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Publication Date: 2018-12-15
    Description: Purpose: Circular RNAs (circRNAs), a novel class of noncoding RNAs, have recently drawn lots of attention in the pathogenesis of human cancers. However, the role of circRNAs in cancer cells epithelial–mesenchymal transition (EMT) remains unclear. In this study, we aimed to identify novel circRNAs that regulate urothelial carcinoma of the bladder (UCB) cells’ EMT and explored their regulatory mechanisms and clinical significance in UCBs. Experimental Design: We first screened circRNA expression profiles using a circRNA microarray in paired UCB and normal tissues, and then studied the clinical significance of an upregulated circRNA, circPRMT5, in a large cohort of patients with UCB. We further investigated the functions and underlying mechanisms of circPRMT5 in UCB cells’ EMT. Moreover, we evaluated the regulation effect of circPRMT5 on miR-30c, and its target genes, SNAIL1 and E-cadherin , in two independent cohorts from our institute and The Cancer Genome Atlas (TCGA). Results: We demonstrated that upregulated expression of circPRMT5 was positively associated with advanced clinical stage and worse survival in patients with UCB. We further revealed that circPRMT5 promoted UCB cell's EMT via sponging miR-30c. Clinical analysis from two independent UCB cohorts showed that the circPRMT5/miR-30c/SNAIL1/E-cadherin pathway was essential in supporting UCB progression. Importantly, we identified that circPRMT5 was upregulated in serum and urine exosomes from patients with UCB, and significantly correlated with tumor metastasis. Conclusions: CircPRMT5 exerts critical roles in promoting UCB cells’ EMT and/or aggressiveness and is a prognostic biomarker of the disease, suggesting that circPRMT5 may serve as an exploitable therapeutic target for patients with UCB.
    Print ISSN: 1078-0432
    Electronic ISSN: 1557-3265
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Publication Date: 2018-03-06
    Description: Background/Aim: Prostate cancer (PCa) diagnosis using patient urine samples represents a non-invasive and more convenient method than the conventional biopsy and prostate-specific antigen (PSA) test. This study intended to identify a biomarker panel to distinguish PCa from benign prostate using urine samples. Materials and Methods: We identified six biomarkers with differential gene expression in 154 PCa and benign prostate specimens. We then determined mRNA expression signature and the diagnostic performance of the 6-biomarker panel in 156 urine samples from patients with PCa and benign disease. Results: The 6-biomarker panel distinguished PCa from benign prostate cases with sensitivity of 80.6%, specificity of 62.9% and area under the curve (AUC) of 0.803 (p〈0.0001), whereas serum PSA at 4 ng/ml cutoff had sensitivity of 95.5%, specificity of 20.2% and AUC of 0.521 (p〈0.0001). Conclusion: The 6-biomarker panel for use in urine samples was able to distinguish PCa from benign prostate with higher specificity and accuracy than PSA and may be useful in clinical settings.
    Print ISSN: 0250-7005
    Electronic ISSN: 1791-7530
    Topics: Medicine
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...