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| 1 | Subcurative radiation significantly increases cell proliferation, invasion, and migration of primary glioblastoma multiforme in vivo显示文摘Tumor cell proliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme(GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77(baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation(n = 8), or underwent no radiation(n = 8). Brain tissues were obtained on day 112(nonirradiated) or day 133(irradiated). Immunohistochemistry was performed to determine tumor cell proliferation(Ki-67) and to assess the expression of infiltration marker(matrix metalloproteinase-2, MMP-2) and cell migration marker(CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor(vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was(71 ± 15)% compared with(25 ± 12)% in the nonirradiated group(P = 0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance following radiation therapy for GBM. | Adarsh Shankar Sanath Kumar Asm Iskander Nadimpalli RS Varma Branislava Janic Ana deCarvalho Tom Mikkelsen Joseph A Frank Meser M Ali Robert A Knight Stephen Brown Ali S Arbab | 2014 | Chinese Journal of Cancer2014，33，3： | 5 |
| 2 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 3 | Campylobacter concisus and inflammatory bowel disease显示文摘Investigation of the possible role of Campylobacter concisus(C. concisus) in inflammatory bowel disease(IBD) is an emerging research area. Despite the association found between C. concisus and IBD, it has been difficult to explain how C. concisus, a bacterium that is commonly present in the human oral cavity, may contribute to the development of enteric diseases. The evidence presented in this review shows that some C. concisus strains in the oral cavity acquired zonula occludens toxin(zot) gene from a virus(prophage) and that C. concisus Zot shares conserved motifs with both Vibrio cholerae Zot receptor binding domain and human zonulin receptor binding domain. Both Vibrio cholerae Zot and human zonulin are known to increase intestinal permeability by affecting the tight junctions. Increased intestinal permeability is a feature of IBD. Based on these data, we propose that a primary barrier function defect caused by C. concisus Zot is a mechanism by which zot-positive C. concisus strains may trigger the onset and relapse of IBD. | Li Zhang Hoyul Lee Michael C Grimm Stephen M Riordan Andrew S Day Daniel A Lemberg | 2014 | World Journal of Gastroenterology2014，20，5： | 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 | A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010显示文摘 | Stephen S Lim Theo Vos Abraham D Flaxman Goodarz Danaei Kenji Shibuya Heather Adair-Rohani Mohammad A AlMazroa Markus Amann H Ross Anderson Kathryn G Andrews Martin Aryee Charles Atkinson Loraine J Bacchus Adil N Bahalim Kalpana Balakrishnan John Balmes S | 2012 | 2012 (9859)2012，，9859： | 3 |
| 6 | Th1 cytokines promote T-cell binding to antigen-presenting cells via enhanced hyaluronan production and accumulation at the immune synapse显示文摘Hyaluronan(HA)production by dendritic cells(DCs)is known to promote antigen presentation and to augment T-cell activation and proliferation.We hypothesized that pericellular HA can function as intercellular‘glue’directly mediating T cell–DC binding.Using primary human cells,we observed HA-dependent binding between T cells and DCs,which was abrogated upon pre-treatment of the DCs with 4-methylumbelliferone(4-MU),an agent which blocks HA synthesis.Furthermore,T cells regulate HA production by DCs via T cell-derived cytokines in a T helper(Th)subset-specific manner,as demonstrated by the observation that cell-culture supernatants from Th1 but not Th2 clones promote HA production.Similar effects were seen upon the addition of exogenous Th1 cytokines,IL-2,interferon c(IFN-c)and tumor necrosis factor a(TNF-a).The critical factors which determined the extent of DC–T cell binding in this system were the nature of the pre-treatment the DCs received and their capacity to synthesize HA,as T-cell clones which were pre-treated with monensin,added to block cytokine secretion,bound equivalently irrespective of their Th subset.These data support the existence of a feedforward loop wherein T-cell cytokines influence DC production of HA,which in turn affects the extent of DC–T cell binding.We also document the presence of focal deposits of HA at the immune synapse between T-cells and APC and on dendritic processes thought to be important in antigen presentation.These data point to a pivotal role for HA in DC–T cell interactions at the IS. | Paul L Bollyky Stephen P Evanko Rebecca P Wu Susan Potter-Perigo S Alice Long Brian Kinsella Helena Reijonen Kelly Guebtner Brandon Teng Christina K Chan Kathy R Braun John A Gebe Gerald T Nepom Thomas N Wight | 2010 | Cellular & Molecular Immunology2010，7，3： | 3 |
| 7 | 光动力疗法治疗非小细胞肺癌显示文摘光动力疗法被越来越多地应用于治疗胸部恶性肿瘤。对于早期非小细胞肺癌(如支气管腔内肺癌)、X线检查阴性或同时性原发癌,光动疗法可作为主要治疗手段进行腔内根治性治疗。作为单一根治疗法,光动力疗法是治疗支气管镜可见≤1 cm且无软骨外浸润的肺部肿瘤的最有效方法。对于晚期非小细胞癌患者,光动力治疗可以作为综合根治疗法的一部分,用于减轻阻塞性支气管内病变,增加可手术性或缩小所需手术范围。本文对现有发表的应用光动力疗法治疗至少10例以上非小细胞肺癌病例的研究文献进行综述,提出了光动力疗法应用的治疗建议并进行了总结。 | Charles B Simone II Joseph S Friedberg Eli Glatstein James P Stevenson Daniel H Sterman Stephen M Hahn Keith A Cengel 袁光金 李金銮 朱宇熹 凌扬 | 2013 | 国际病理科学与临床杂志2013，33，3： | 3 |
| 8 | Labeling of influenza viruses with synthetic fluorescent and biotin-labeled lipids显示文摘Direct labeling of virus particles is a powerful tool for the visualization of virus–cell interaction events. However, this technique involves the chemical modification of viral proteins that affects viral biological properties. Here we describe an alternative approach of influenza virus labeling that utilizes Function-Spacer-Lipid(FSL) constructs that can be gently inserted into the virus membrane. We assessed whether labeling with fluorescent(fluo-Ad-DOPE) or biotin-labeled(biot-CMG2-DOPE) probes has any deleterious effect on influenza virus hemagglutinin(HA) receptor specificity, neuraminidase(NA) activity, or replicative ability in vitro. Our data clearly show that neither construct significantly affected influenza virus infectivity or viral affinity to sialyl receptors. Neither construct influenced the NA activities of the influenza viruses tested, except the A/Puerto Rico/8/34(H1N1) strain. Our data indicate that lipid labeling provides a powerful tool to analyze influenza virus infection in vitro. | Natalia A Ilyushina Evgeny S Chernyy Elena Y Korchagina Aleksra S Gambaryan Stephen M Henry Nicolai V Bovin | 2014 | Virologica Sinica2014，29，4： | 2 |
| 9 | The safety of tenofovir disoproxil fumarate for the treatment of HIV infection in adults: the first 4 years显示文摘 | Mark R Nelson Christine Katlama Julio S Montaner David A Cooper Brian Gazzard Bonaventura Clotet Adriano Lazzarin Knud Schewe Joep Lange Christina Wyatt Sue Curtis Shan-Shan Chen Stephen Smith Norbert Bischofberger James F Rooney | 2007 | AIDS2007，，10： | 2 |
| 10 | A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990–2010: a systematic analysis for the Global Burden of Disease Study 2010显示文摘 | Stephen S Lim Theo Vos Abraham D Flaxman Goodarz Danaei Kenji Shibuya Heather Adair-Rohani Mohammad A AlMazroa Markus Amann H Ross Anderson Kathryn G Andrews Martin Aryee Charles Atkinson Loraine J Bacchus Adil N Bahalim Kalpana Balakrishnan John Balmes S | 2012 | The Lancet2012，，9859： | 2 |
| 11 | The zygomatic-sphenoid fracture line in malar reduction显示文摘 | James A Stephen S | 1997 | Arch Otolaryngol Head Neck Surg1997，123，12： | 1 |
| 12 | Stability and composition of terrestrially derived dissolved organic nitrogen in continental shelf surface waters 显示文摘 | GARDNER W S STEPHENS J A | 1978 | Marine Chemistry1978，6，4： | 1 |
| 13 | Chemokine receptors CCR6 and CXCR3 are necessary for CD4 + T cell mediated ocular surface disease in experimen- tal dry eye disease显示文摘 | TERRY G NIRAL B EUGENE A STEPHEN C CINTIA S | 2013 | PLoS One2013，8，78： | 1 |
| 14 | Controlled-root formulation for digital phase-locked loops显示文摘 | Stephens S A Thomas J B | 1995 | IEEE Transactions on Aerospace and Electronic Systems1995，3，1： | 1 |
| 15 | The effect of temperature varia- tion on spontaneous potential production from explants of brain tissue in culture 显示文摘 | Cunningham A W B Stephens S G | 1962 | Experientia1962，18，1： | 1 |
| 16 | Mossbauer and NMR characterization of tin octoate: Neat and residues in RTV foams 显示文摘 | LABOURIAU A TAYLOR D STEPHENS T S | 2006 | Polym Degrad Stab2006，91，： | 1 |
| 17 | Drivers display anger-congruent attention to potential traffic hazards显示文摘 | STEPHENS A N TRAWLEY S L MADIGAN R | 2013 | Applied Cognitive Psychology2013，27，2： | 1 |
| 18 | SPH for High Velocity Impact Computations显示文摘 | Gordon R J Robert A S Stephen R B | 1996 | Computer Methods in Applied Mechanics and Engineering1996，139，14： | 1 |
| 19 | Laboratory studies of faceors affecting egg hatch of triops longicaudatus显示文摘 | STEPHEN R S ALBERT A G | 1979 | Hydrobiologia1979，63，： | 1 |
| 20 | Genotyping of peach and nectarine cultivars with SSR and SRAP molecular marker显示文摘 | Riaz A Dan P Stephen M S | 2004 | Journal of the American Society for Horticultural Science2004，129，2： | 1 |
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