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| 1 | Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer显示文摘AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS: A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS: Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed localrecurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fi stula. CONCLUSION: Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome. | Shu-Lian Wang Zhongxing Liao Helen Liu( Jaffer Ajani Stephen Swisher James D Cox Ritsuko Komaki | 2006 | World Journal of Gastroenterology2006，12，34： | 27 |
| 2 | 应用最大似然率及随机效应模型探讨非小细胞肺癌放化疗中急性放射性食管炎与照射剂量和疗程的关系显示文摘背景与目的:局部晚期非小细胞肺癌的治疗疗效差,增加治疗强度如同期放化疗是提高疗效的方法,但毒性反应较大。本研究探讨非小细胞肺癌同期放化疗的治疗方式中,应用最大似然率及随机效应模型探讨非小细胞肺癌放化疗中急性放射性食管炎的发生率与照射剂量和疗程时间因素的关系。方法:本研究中的39例病例资料来自于1998年3月-2000年11月间在M.D.Anderson癌症治疗中心进入随机临床Ⅲ期的同期放化疗治疗研究不能手术的Ⅱ期和Ⅲ期非小细胞肺癌患者。所有的患者在放疗前均接受顺铂和口服依托泊苷(VP-16)的化疗。放疗方案为每次1.2Gy,bid,前后野对照治疗至肿瘤剂量达40~50Gy后,采用避开脊髓的斜野放疗至总剂量69.6Gy。病例分布为amifostine治疗组,19例;非amifostine治疗组,20例。还原三维治疗计划设计并计算了剂量-体积直方图(DVHs)。治疗开始后每周对急性放射性食管炎程度评估1次,在放疗结束后1个月再随访评估1次。评分的标准是根据美国放射治疗研究组(RTOG)的急性反应的标准。采用了多因素的随机效应模型及最大似然率的分析以研究在这39例病例中急性放射性食管炎的严重程度与照射剂量和疗程时间因素的关系,并考虑了不同病例个体间的敏感性差异。结果:在amifostine治疗组有11%(2/19),非amifostine治疗组有30%(6/20)的患者发生Ⅲ度的急性食管炎。在这两组中,急性食管炎的发生率在开始治疗后第4周(累计剂量为48Gy)达高峰并呈一稳定状态。随治疗后期剂量的进一步增加,急性食管炎发生的危险性并不明显增加。原因可能是食管粘膜上皮组织的修复和在治疗后的上皮细胞加速再增殖。疗程中的周剂量或累计周剂量要比整个疗程的总剂量更好地预测急性食管炎的发生。结论:肿瘤累积剂量和患者的内在敏感性与Ⅲ度急性放射性食管炎的发生率有关。欲将发生急性食管炎的危险性降低至10%以下,需限制第4周的累计剂量在36Gy以下,或9Gy/周。这可能为开展IMRT等新技术的治疗提供有用的参考信息。 | 章真 Helen Liu Zhongxing Liao Ritsuko Komaki James D Cox | 2006 | 中国癌症杂志2006，16，12： | 5 |
| 3 | Costimulation of resting B lymphocytes alters the IL-4-activated IRS2 signaling pathway in a STAT6 independent manner: implications for cell survival and proliferation显示文摘IL-4 is an important B cell survival and growth factor. IL-4 induced the tyrosine phosphorylation of IRS2 in resting B lymphocytes and in LPS- or CD40L-activated blasts. Phosphorylated IRS2 coprecipitated with the p85 subunit of PI 3’ kinase in both resting and activated cells. By contrast, association of phosphorylated IRS2 with GRB2 was not detected in resting B cells after IL-4 treatment although both proteins were expressed. However, IL-4 induced association of IRS2 with GRB2 in B cell blasts. The pattern of IL-4- induced recruitment of p85 and GRB2 to IRS2 observed in B cells derived from STAT6 null mice was identical to that observed for normal mice. While IL-4 alone does not induce activation of MEK, a MEKI inhibitor suppressed the IL-4-induced proliferative response of LPS-activated B cell blasts. These results demonstrate that costimulation of splenic B cells alters IL-4-induced signal transduction independent of STAT6 leading to proliferation. Furthermore, proliferation induced by IL-4 in LPS-activated blasts is dependent upon the MAP kinase pathway. | ZAMORANO JOSE,Unidad de Investigacion, Hospital San Pedro de Alcantara, Avda Millan Astray, 10003 Caceres ANN E KELLY, JONATHAN AUSTRIAN, HELEN Y WANG, ACHSAH D KEEGAN (Department of Immunology, Jerome Holland Labs, American Red Cross, Rockville, MD, USA | 2001 | Cell Research2001，11，1： | 4 |
| 4 | Nat Genet:单基因突变导致过敏性皮炎的发生显示文摘最近,研究者们鉴定出了一类导致神经性皮炎发生的关键基因突变:CARDll。来自美国NIH过敏与传染病研究所的研究者们通过对四个没有血缘关系的患病家庭进行分析,发现了这一导致疾病产生的基因、 | Chi A Ma, Yuan Zhang, Michael A Weinreich, Jonathan J Lyons, Celeste G Nelson, Thomas DiMaggio, Kelly D Stone, Joshua D Milner Jeffrey R Stinson, Elisa Ruffo, Batsukh Dorjbal, Swadhinya Arjunaraja, Kelsey Voss, Andrew L Snow Jordan K Abbott, Pia J Hauk, Paul R Reynolds, Erwin W Gelfand Elisa Ruffo Salomé Glauzy, Natsuko Yamakawa, Eric Meffre Jennifer Stoddard, Julie Niemela, Sergio D Rosenzweig Yu Zhang, Helen F Matthews Joshua J McElwee Nina Jones Alejandro Palma, Matías Oleastro, Emma Prieto, Andrea R Bernasconi, Geronimo Dubra, Silvia Danielian, Jonathan Zaiat, Marcelo A Marti Brian Kim Megan A Cooper Neil Romberg | 2017 | 现代生物医学进展2017，17，27： | 3 |
| 5 | Macrophage secretory products induce an inflammatory phenotype in hepatocytes显示文摘AIM:To investigate the influence of macrophages on hepatocyte phenotype and function.METHODS:Macrophages were differentiated from THP-1 monocytes via phorbol myristate acetate stimulation and the effects of monocyte or macrophageconditioned medium on HepG2 mRNA and protein expression determined.The in vivo relevance of these findings was confirmed using liver biopsies from 147 patients with hepatitis C virus(HCV)infection.RESULTS:Conditioned media from macrophages,but not monocytes,induced a transient morphological change in hepatocytes associated with upregulation of vimentin(7.8±2.5-fold,P=0.045)and transforming growth factor(TGF)-β1(2.6±0.2-fold,P<0.001)and downregulation of epithelial cadherin(1.7±0.02-fold,P=0.017)mRNA expression.Microarray analysis revealed significant upregulation of lipocalin-2(17-fold,P <0.001)and pathways associated with inflammation,and substantial downregulation of pathways related to hepatocyte function.In patients with chronic HCV,realtime polymerase chain reaction and immunohistochemistry confirmed an increase in lipocalin-2 mRNA(F0 1.0 ±0.3,F1 2.2±0.2,F2 3.0±9.3,F3/4 4.0±0.8,P= 0.003)and protein expression(F1 1.0±0.5,F2 1.3± 0.4,F3/4 3.6±0.4,P=0.014)with increasing liver injury.High performance liquid chromatography-tandem mass spectrometry analysis identified elevated levels of matrix metalloproteinase(MMP)-9 in macrophageconditioned medium,and a chemical inhibitor of MMP-9 attenuated the change in morphology and mRNA expression of TGF-β1(2.9±0.2 vs 1.04±0.1,P<0.001) in macrophage-conditioned media treated HepG2 cells.In patients with chronic HCV infection,hepatic mRNA expression of CD163(F0 1.0±0.2,F1/2 2.8±0.3,F3/4 5.3±1.0,P=0.001)and MMP-9(F0 1.0±0.4,F1/2 2.8±0.3,F3/4 4.1±0.8,P=0.011)was significantly associated with increasing stage of fibrosis.CONCLUSION:Secreted macrophage products alter the phenotype and function of hepatocytes,with increased expression of inflammatory mediators,suggesting that hepatocytes actively participate in liver injury. | Michelle Melino Victoria L Gadd Gene V Walker Richard Skoien Helen D Barrie Dinesh Jothimani Leigh Horsfall Alun Jones Matthew J Sweet Gethin P Thomas Andrew D Clouston Julie R Jonsson Elizabeth E Powell | 2012 | World Journal of Gastroenterology2012，18，15： | 3 |
| 6 | 雄激素受体的目标基因在骨骼肌的表达显示文摘本文通过研究体外和体内模型中潜在的雄激素受体调节基因来确定骨骼肌中雄激素的合成代谢作用机制。睾酮治疗组的去势雄性小鼠与对照组去势雄性小鼠比较,其骨骼肌中肌源性调节因子肌细胞生成素的表达显著下降,而缺乏DNA结合活性的雄性雄激素受体敲除小鼠(AR^△ZF2)与野生型小鼠比较,其骨骼肌中肌源性调节因子肌细胞生成素的表达显著升高,证明了肌细胞生成素是通过雄激素/雄激素受体通路被抑制。通过12小时的骨骼肌细胞(SkMC)的成肌细胞联合双氢睾酮治疗,睾酮治疗组的去势雄性小鼠肌肉中的泛素连接酶Fbxo32被抑制,而肌肉中c—Myc表达较对照组去势雄性小鼠降低,在△R^△ZF2组小鼠肌肉中c-Myc表达升高。调节成肌细胞由增殖向分化转变的一组基因如Tceal7,p57^Kip2,Igf2和钙调磷酸酶Aa的表达在AR^△ZF2组小鼠肌肉中升高,除p57^Kip2外的上述所有基因在睾酮治疗组去势雄性小鼠肌肉中的表达均较对照组降低。因此得出结论,雄激素通过雄激素受体在雄性小鼠体内发挥作用,它在肌肉生长和发展过程中可维持成肌细胞处于增殖状态并推迟成肌细胞向分化状态转变,另外还可抑制泛素连接酶介导的导致肌肉萎缩的通路来保持小鼠肌肉质量,从而一定程度上促进肌肉不断生长达到顶峰。 | Kesha Rana Nicole KL Lee Jeffrey D Zajac Helen E MacLean | 2014 | Asian Journal of Andrology2014，16，5： | 3 |
| 7 | Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial显示文摘 | A David Mendelow Barbara A Gregson Helen M Fernandes Gordon D Murray Graham M Teasdale D Terence Hope Abbas Karimi M Donald M Shaw David H Barer | 2005 | 2005 (9457)2005，，9457： | 2 |
| 8 | From the archives of the AFIP gastrointestinal stromal tumors: radiologic features with pathologic correlation 显示文摘 | Angela D Helen E William M | 2003 | Radio Graphics2003，23，： | 1 |
| 9 | Endothelial dysfunction caused by circulating microparticles from patients with metabolic syndrome 显示文摘 | Abdelali A Anne Helene LL Pierre-Henri D | 2008 | Am J Pathnl2008，173，4： | 1 |
| 10 | Protracted release of the LHRH agonist avorelin (MF 6001) from two depot formulations in dogs and men显示文摘 | FRANGOIS B HELENE T SANDRINE D | 1997 | Lett Pept Sci1997，4，46： | 1 |
| 11 | Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the International Surgical Trial in Intracerebral Haemorrhage (STICH): a randomised trial显示文摘 | A David Mendelow Barbara A Gregson Helen M Fernandes Gordon D Murray Graham M Teasdale D Terence Hope Abbas Karimi M Donald M Shaw David H Barer | 2005 | The Lancet2005，，9457： | 1 |
| 12 | Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial显示文摘 | Helen M Colhoun D John Betteridge Paul N Durrington Graham A Hitman H Andrew W Neil Shona J Livingstone Margaret J Thomason Michael I Mackness Valentine Charlton-Menys John H Fuller | 2004 | The Lancet . 2004 (9435)2004，，9435： | 1 |
| 13 | 基于G-蛋白偶联受体激酶2抑制剂治疗心力衰竭的合理药物设计(英文)显示文摘G protein-coupled receptors(GPCRs)convert extracellular stimuli in the form of hormones,odorants and light into profound changes in cell homeostasis.Their timely desensitization is critical for cells to rapidly respond to changes in their environment and to avoid damage from sustained signaling.Seven GPCR kinases(GRKs)phosphorylate and regulate the activity of most of the^800 GPCRs in the human genome.Although GRKs normally play an adaptive role,in conditions such as chronic heart failure they are overexpressed and linked to disease progression.GRK2 and GRK5 have thus become important targets for the treatment of heart failure and pathological cardiac hypertrophy,respectively.Our lab has determined atomic structures representing all three vertebrate GRK subfamilies,and is now in the midst of a campaign to develop selective inhibitors of these enzymes using structure-based rational design.We have identified the FDA approved drug paroxetine as a selective GRK2 inhibitor,determined the crystal structure of the GRK2·paroxetine complex and,in collaboration with the Koch lab,showed that the drug improves contractility in myocytes and,most impressively,recovery in postmyocardial infarcted mice.Since then,we have identified additional chemical scaffolds that exhibit even higher potency and/or selectivity for GRK5.Using a'hybrid'inhibitor design approach we have generated GRK selective chemical probes that exhibit improved potency and stability and are able to increase inotropy and dampen the hypertrophic response in cardiomyocytes and small animal models.Structural analysis has revealed the molecular basis for selectivity and potency in many of these compounds,allowing for the design of future generations of GRK chemical probes. | John J TESMER Helen V WALDSCHMIDT Marie C CATO Renee BOULEY Osvaldo CRUZ-RODRIGUEZ Scott D LARSEN | 2017 | 中国药理学与毒理学杂志2017，31，10： | 1 |
| 14 | Trehalose biosynthesis in Rhizobium leguminosarum:trifolii and its role in desiccation tolerance显示文摘 | Helen J M Holiday D Timothy A | 2007 | Applied and Environmental Microbiology2007，73，12： | 1 |
| 15 | several kinds of Chiral mobile phase additional in Capillary Zone Electrophoresis 显示文摘 | Ekberg-OTT Helen K Armstrong D W | 1998 | Chirality1998，，10： | 1 |
| 16 | Cytokines, insulin-like growth factor 1, sarcopenia, and mortality in very old community-dwelling men and women: the Framingham Heart Study显示文摘 | Ronenn Roubenoff Helen Parise Hélène A Payette Leslie W Abad Ralph D’Agostino Paul F Jacques Peter W.F Wilson Charles A Dinarello Tamara B Harris | 2003 | The American Journal of Medicine2003，，6： | 1 |
| 17 | Pharmacokinetics of Micafuungin in healthy volunteers, volunteers with modertate liver disease, and volunteers with renal dysfunction 显示文摘 | Mary FH Pharm D Helen ES | 2005 | J Clin Pharmacol2005，45，： | 1 |
| 18 | Cotton (Gossypium hirsutum) MatP6 and MatP7 Oleosin Genes 显示文摘 | D Wayne Hughes Helen Y C Wang Clenn A Calau | 1993 | Plant Physiology1993，101，： | 1 |
| 19 | Increased nuclear factor кB activation critically ill patients who die 显示文摘 | Ross L P Helen F G Jatinde K D | 2000 | Crit Care Med2000，28，： | 1 |
| 20 | Mosaic SCN1A mutation in famlial severe myoclonic epilepsy of infancy显示文摘 | Marini C Mei D Helen Cross J | 2006 | Epilepsia2006，47，10： | 1 |
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