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| 1 | c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1显示文摘AIM: To investigate the effect of stable c-Fos overexpression on immortalized human hepatocyte (IHH) proliferation. METHODS: IHHs stably transfected with c-Fos (IHH-Fos) or an empty vector (IHH-C) were grown in medium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and fl ow cytometry analyses. The levels of cell cycle regulatory proteins (Cyclin D1, E, A) cyclin dependent kinases (cdk) cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, to- tal and phosphorylated GSK-3β and epidermal growth factor receptor (EGF-R) were assayed by Western blot- ting. Analysis of Cyclin D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction (PCR) analysis. Stability of Cyclin D1 was studied by cycloheximide blockade experiments. RESULTS: Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora- tion following serum addition. Cell cycle analysis by fl ow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpressing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein compared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH- Fos by treatment with AG1478, a specif ic EGF-R tyrosine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION: Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate a new mechanism by which c-Fos could contribute to hepatocarcinogenesis through stabilization of Cyclin D1 within the nucleus, evoking a new feature to c-Fos implication in hepatocellular carcinoma. | Meryem Güller Kahina Toualbi-Abed Agnès Legrand Laurence Michel Alain Mauviel Dominique Bernuau Fanny Daniel | 2008 | World Journal of Gastroenterology2008,14,41: | 6 |
| 2 | The human application of gene therapy to re-program T-cell specificity using chimeric antigen receptors显示文摘The adoptive transfer of T cells is a promising approach to treat cancers. Primary human T cells can be modified using viral and non-viral vectors to promote the specific targeting of cancer cells via the introduction of exogenous T-cell receptors(TCRs) or chimeric antigen receptors(CARs). This gene transfer displays the potential to increase the specificity and potency of the anticancer response while decreasing the systemic adverse effects that arise from conventional treatments that target both cancerous and healthy cells. This review highlights the generation of clinical-grade T cells expressing CARs for immunotherapy, the use of these cells to target B-cell malignancies and, particularly, the first clinical trials deploying the Sleeping Beauty gene transfer system, which engineers T cells to target CD19+ leukemia and non-Hodgkin's lymphoma. | Alan D Guerrero Judy S Moyes Laurence JN Cooper | 2014 | Chinese Journal of Cancer2014,33,9: | 4 |
| 3 | Miniature gastrointestinal endoscopy: Now and the future显示文摘Since its original application,gastrointestinal(GI)endoscopy has undergone many innovative transformations aimed at expanding the scope,safety,accuracy,acceptability and cost-effectiveness of this area of clinical practice.One method of achieving this has been to reduce the caliber of endoscopic devices.We propose the collective term“Miniature GI Endoscopy”.In this Opinion Review,the innovations in this field are explored and discussed.The progress and clinical use of the three main areas of miniature GI endoscopy(ultrathin endoscopy,wireless endoscopy and scanning fiber endoscopy)are described.The opportunities presented by these technologies are set out in a clinical context,as are their current limitations.Many of the positive aspects of miniature endoscopy are clear,in that smaller devices provide access to potentially all of the alimentary canal,while conferring high patient acceptability.This must be balanced with the costs of new technologies and recognition of device specific challenges.Perspectives on future application are also considered and the efforts being made to bring new innovations to a clinical platform are outlined.Current devices demonstrate that miniature GI endoscopy has a valuable place in investigation of symptoms,therapeutic intervention and screening.Newer technologies give promise that the potential for enhancing the investigation and management of GI complaints is significant. | John J McGoran Mark E McAlindon Prasad G Iyer Eric J Seibel Rehan Haidry Laurence B Lovat Sarmed S Sami | 2019 | World Journal of Gastroenterology2019,25,30: | 4 |
| 4 | Risk for emerging bipolar disorder, variants, and symptoms in children with attention deficit hyperactivity disorder, now grown up显示文摘AIM: To determine the prevalence of bipolar disorder(BD) and sub-threshold symptoms in children with attention deficit hyperactivity disorder(ADHD) through 14 years' follow-up, when participants were between 21-24 years old.METHODS: First, we examined rates of BD type Ⅰ?and Ⅱ diagnoses in youth participating in the NIMH-funded Multimodal Treatment Study of ADHD(MTA). We used the diagnostic interview schedule for children(DISC), administered to both parents(DISC-P) and youth(DISCY). We compared the MTA study subjects with ADHD(n = 579) to a local normative comparison group(LNCG, n = 289) at 4 different assessment points: 6, 8, 12, and 14 years of follow-ups. To evaluate the bipolar variants, we compared total symptom counts(TSC) of DSM manic and hypomanic symptoms that were generated by DISC in ADHD and LNCG subjects. Then we sub-divided the TSC into pathognomonic manic(PM) and non-specific manic(NSM) symptoms. We compared the PM and NSM in ADHD and LNCG at each assessment point and over time. We also evaluated the irritability as category A2 manic symptom in both groups and over time. Finally, we studied the irritability symptom in correlation with PM and NSM in ADHD and LNCG subjects.RESULTS: DISC-generated BD diagnosis did not differ significantly in rates between ADHD(1.89%) and LNCG 1.38%). Interestingly, no participant met BD diagnosis more than once in the 4 assessment points in 14 years. However, on the symptom level, ADHD subjects reported significantly higher mean TSC scores: ADHD 3.0; LNCG 1.7; P < 0.001. ADHD status was associated with higher mean NSM: ADHD 2.0 vs LNCG 1.1; P < 0.0001. Also, ADHD subjects had higher PM symptoms than LNCG, with PM means over all time points of 1.3 ADHD; 0.9 LNCG; P = 0.0001. Examining both NSM and PM, ADHD status associated with greater NSM than PM. However, Over 14 years, the NSM symptoms declined and changed to PM over time(df 3, 2523; F = 20.1; P < 0.0001). Finally, Irritability(BD DSM criterion-A2) rates were significantly higher in ADHD than LNCG(χ2 = 122.2, P < 0.0001), but irritability was associated more strongly with NSM than PM(df 3, 2538; F = 43.2; P < 0.0001).CONCLUSION: Individuals with ADHD do not appear to be at significantly greater risk for developing BD, but do show higher rates of BD symptoms, especially NSM. The greater linkage of irritability to NSM than to PM suggests caution when making BD diagnoses based on irritability alone as one of 2(A-level) symptoms for BD diagnosis, particularly in view of its frequent presentation with other psychopathologies. | Ahmed Z Elmaadawi Peter S Jensen L Eugene Arnold Brooke SG Molina Lily Hechtman Howard B Abikoff Stephen P Hinshaw Jeffrey H Newcorn Laurence Lee Greenhill James M Swanson Cathryn A Galanter | 2015 | World Journal of Psychiatry2015,5,4: | 3 |
| 5 | Stereotactic body radiation therapy for management of spinal metastases in patients without spinal cord compression: a phase 1–2 trial显示文摘 | Xin Shelley Wang Laurence D Rhines Almon S Shiu James N Yang Ugur Selek Ibrahima Gning Ping Liu Pamela K Allen Syed S Azeem Paul D Brown Hadley J Sharp David C Weksberg Charles S Cleeland Eric L Chang | 2012 | Lancet Oncology2012,,4: | 2 |
| 6 | Age-related macular degeneration显示文摘 | Laurence S Lim Paul Mitchell Johanna M Seddon Frank G Holz Tien Y Wong | 2012 | The Lancet . 2012 (9827)2012,,9827: | 2 |
| 7 | Interleukin - 2 sig -naling via STAT5 constrains T helper 17 cell generation显示文摘 | Laurence A Tato C M Davidson T S | 2007 | Im- munity2007,26,3: | 1 |
| 8 | Fingolimod potentiates the effects of sunitinib malate in a rat breast cancer model显示文摘 | Yoanne Mousseau Séverine Mollard Karine Faucher-Durand Laurence Richard Angélique Nizou Jeanne Cook-Moreau Yasser Baaj Hao Qiu Xavier Plainard Laurent Fourcade Benoit Funalot Franck G. Sturtz | 2012 | Breast Cancer Research and Treatment2012,,1: | 1 |
| 9 | Regulated hypothermia reduces brain oxidative stress after hypoxic-ischemia显示文摘 | Laurence M Katz Amanda S Young Jonathan E Frank Yuanfan Wang Kyunam Park | 2004 | Brain Research2004,,1: | 1 |
| 10 | Real- time intrauperative ureteral guidance using invisible near-in- frared fluorescence 显示文摘 | TANAKA E OHNISHI S LAURENCE R G | 2007 | The Journal of Urology2007,178,5: | 1 |
| 11 | Shock-wave surfing 显示文摘 | Laurence S J Deiterding R | 2011 | Journal of Fluid Mechanics2011,676,3: | 1 |
| 12 | Equipment investment and economic growth 显示文摘 | Long D Bradford J Laurence H S | 1991 | Quarterly Journal of Economics1991,,106: | 1 |
| 13 | Dynamical separation of spherical bodies in super-sonic flow显示文摘 | Laurence S J Parziale N J Deiterding R | 2012 | Journal of Fluid Mechanics2012,713,12: | 1 |
| 14 | Mitochontrial DNA and RNA isolation from small amounts of potato tissue显示文摘 | Nunzia S Teodoro C Laurence M | 2001 | Plant molecular biology reporter2001,19,: | 1 |
| 15 | LES coarse LES,and transient RANS comparisons on the ? ow across a tube bundle显示文摘 | Benharnadouche S Laurence D | 2003 | International Journal of Heat and Fluid Flow2003,24,: | 1 |
| 16 | Interleukin - 2 signaling via STATS constrains T helper 17 cell generation显示文摘 | LAURENCE A TATO C M DAVIDSON T S | 2007 | Immunity2007,26,3: | 1 |
| 17 | STAT3 Transcription Factor Promotes Instability of nTreg Cells and Limits Generation of iTreg Cells during Acute Murine Graft-versus-Host Disease显示文摘 | Laurence A Amarnath S Mariotti J | | 0,,03: | 1 |
| 18 | Optimising monitoring in the management of Crohn’s disease: A physician’s perspective显示文摘 | Pavol Papay Ana Ignjatovic Konstantinos Karmiris Heda Amarante Pal Milheller Brian Feagan Geert D’Haens Philippe Marteau Walter Reinisch Andreas Sturm Flavio Steinwurz Laurence Egan Julián Panés Edouard Louis Jean-Frédéric Colombel Remo Panaccione | 2013 | Journal of Crohn’s and Colitis2013,,: | 1 |
| 19 | A fully adaptive distance-dependent thresholding search (FADTS) algorithm for performance management motion estimation 显示文摘 | Golam Sorwar Manzur Murshed Laurence S Dooley | 2007 | IEEE Trans on Circuits and Systems for Video Technology2007,17,4: | 1 |
| 20 | Niosomes and Polymeric Chitosan Based Vesicles Bearing Transferrin and Glucose Ligands for Drug Targeting显示文摘 | CHRISTINE D ANDREAS G S LAURENCE T | 2000 | Pharmaceutical Research(S0724-8741)2000,17,10: | 1 |