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| 1 | 帕博利珠单抗治疗伴脑转移NSCLC患者的一项非随机、开放Ⅱ期试验的长期随访结果和生物标志物分析显示文摘背景与目的我们开展了一项帕博利珠单抗用于伴未治疗脑转移的非小细胞肺癌(non-small cell lung cancer,NSCLC)或黑色素瘤患者的疗效和安全性的II期试验,旨在评估程序性死亡受体1(programmed cell death 1,PD-1)抑制剂在中枢神经系统(central nervous system,CNS)中的疗效。中期结果已发表,现报道对NSCLC队列的更新分析结果。方法这是一项开放性、单中心、II期试验。纳入标准:年龄≥18岁,诊断为晚期NSCLC并伴有≥1个5 mm-20 mm脑转移病灶,既往从未治疗或之前放疗后进展,无神经系统症状,不需要激素治疗且美国东部肿瘤协作组(Eastern Cooperative Oncology Group,ECOG)<2分。患者每2周接受一次帕博利珠单抗(10 mg/kg)治疗。队列1为程序性死亡配体1(programmed cell death ligand 1,PD-L1)≥1%的患者,队列2为PD-L1<1%或未评估的患者。主要终点是脑转移患者缓解比例。所有经治患者均纳入疗效与安全性终点的分析。该研究已结束入组,并于Clinicaltrials.gov登记注册,注册号为NCT02085070。结果2014年3月31日-2018年5月21日,共42例患者接受治疗。中位随访时间为8.3个月(IQR:4.5个月-26.2个月)。队列1的37例患者中11例有脑转移缓解[29.7%(95%CI:15.9%-47.0%)]。队列2未观察到缓解。治疗相关的3级-4级不良事件(adverse events,AEs)包括2例肺炎、1例全身症状、1例结肠炎、1例肾上腺皮质功能不全、1例高血糖症和1例低钾血症。6例(14%)患者发生了治疗相关的严重不良事件,包括肺炎、急性肾损伤、低钾血症和肾上腺皮质功能不全。没有观察到治疗相关死亡病例。结论帕博利珠单抗治疗PD-L1≥1%的NSCLC伴脑转移患者有效,且对所有纳入的未经治疗的脑转移患者安全。需要进一步探索免疫治疗用于NSCLC合并CNS转移。 | Sarah B GOLDBERG Kurt A SCHALPER Scott N GETTINGER Amit MAHAJAN Roy S HERBST Anne C CHANG Rogerio LILENBAUM Frederick H WILSON Sacit Bulent OMAY James B YU Lucia JILAVEANU Thuy TRAN Kira PAVLIK Elin ROWEN Heather GERRSH Annette KOMLO Richa GUPTA Hailey WYATT Matthew RIBEIRO Yuval KLUGER Geyu ZHOU Wei WEI Veronica L CHANG Harriet M KLUGER 董晓荣(翻译/校对) | 2021 | 中国肺癌杂志2021，24，9： | 34 |
| 2 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 3 | Cadmium, Environmental Exposure, and Health Outcomes显示文摘 | Satarug Soisungwan Garrett Scott H Sens Mary Ann Sens Donald A | 2010 | Environmental Health Perspectives2010，，2： | 3 |
| 4 | Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma显示文摘BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in HCC.AIM To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to RO7070179.METHODS In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of RO7070179.RESULTS Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased toxicity.This study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes in either m RNA level or DCE-MRI within 1 cycle of therapy. | Jennifer Wu Merly Contratto Krishna P Shanbhogue Gulam A Manji Bert H O'Neil Anne Noonan Robert Tudor Ray Lee | 2019 | World Journal of Clinical Oncology2019，10，3： | 2 |
| 5 | B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: Application to autoimmune disease therapy显示文摘 | Vijay K Kuchroo Mercy Prabhu Das Julia A Brown Ann M Ranger Scott S Zamvil Raymond A Sobel Howard L Weiner Nasrin Nabavi Laurie H Glimcher | 1995 | Cell1995，，5： | 2 |
| 6 | Ziprasidone: a novel antipsychotic agent with a unique human receptor binding profile显示文摘 | Anne W Schmidt Lorraine A Lebel Harry R Howard Stevin H Zorn | 2001 | European Journal of Pharmacology2001，，： | 1 |
| 7 | Examining Ni- laterite leach mineralogy & chemistry-a holistic multi-scale approach 显示文摘 | Hunter H M A Herrington R J Anne O E | 2013 | Minerals Engineering2013，54，： | 1 |
| 8 | An innovative approach to enhance dermatology competencies for advanced practice nurses: Service-learning with a migrant farm worker health clinic显示文摘 | Elizabeth A Ann C Maeve H | 2014 | J Nurs Educ2014，53，12： | 1 |
| 9 | Antecedents and sex/gender differences in youth suicidal behavior显示文摘Suicide is the second leading cause of death in youth globally; however, there is uncertainty about how best to intervene. Suicide rates are typically higher in males than females, while the converse is true for suicide attempts. We review this 'gender paradox' in youth, and in particular, the age-dependency of these sex/gender differences and the developmental mechanisms that may explain them. Epidemiologic, genetic,neurodevelopmental and psychopathological research have identified suicidal behaviour risks arising from genetic vulnerabilities and sex/gender differences in early adverse environments, neurodevelopment, mental disorder and their complex interconnections. Further, evolving sex-/gender-defined social expectations and norms have been thought to influence suicide risk. In particular, how youth perceive and cope with threats and losses(including conforming to others' or one's own expectations of sex/gender identity) and adapt to pain(through substance use and helpseeking behaviours). Taken together, considering brain plasticity over the lifespan, these proposed antecedents to youth suicide highlight the importance of interventions that alter early environment(s)(e.g., childhood maltreatment) and/or one's ability to adapt to them. Further, such interventions may have more enduring protective effects, for the individual and for future generations, if implemented in youth. | Anne E Rhodes Michael H Boyle Jeffrey A Bridge Mark Sinyor Paul S Links Lil Tonmyr Robin Skinner Jennifer M Bethell Corine Carlisle Sarah Goodday Travis Salway Hottes Amanda Newton Kathryn Bennett Purnima Sundar Amy H Cheung Peter Szatmari | 2014 | World Journal of Psychiatry2014，4，4： | 1 |
| 10 | Phytoremediation of contaminated soils and groundwater: lessons from the field显示文摘 | Jaco V Rolf H Nele W Jana B Kristin A Ann R | 2009 | Environmental Science and Pollution Research2009，16，7： | 1 |
| 11 | Attitudes towards organic foods among Swedish consumers显示文摘 | MARIA K M ANNE A ULLA-KAISA K H | 2001 | British Food Journal2001，103，： | 1 |
| 12 | 早期乳腺癌最佳辅助化疗方案与人类表皮生长因子受体2阳性乳腺癌辅助靶向治疗选择:依据 ASCO 对 CCO临床实践指南的改编显示文摘目的研究加拿大安大略癌症治疗中心(CCO)关于早期乳腺癌最佳辅助化疗方案,包括人类表皮生长因子受体2(HER2)阳性乳腺癌辅助靶向治疗方案,并对其进行改编。方法按照美国临床肿瘤协会(ASCO)对其他组织临床实践指南改编的策略和程序,对CCO临床实践指南的严谨性与内容适用性进行回顾。结果基于对CCO临床实践指南内容的回顾,ASCO小组认为,CCO临床实践指南在整体上清晰全面,以最确切的科学证据为基础,为患者提供可接受的治疗选项。推荐关于辅助化疗方案的决定,应考虑到基线复发风险、毒性、利益可能性和宿主因素(如合并症)。对于高风险HER2阴性的身体状况良好的人群,蒽环类和紫杉烷治疗方案是标准治疗方案。4个周期的多西他赛和环磷酰胺治疗方案是可接受的非蒽环类治疗方案。对于高风险HER2阳性患者,推荐蒽环类与紫杉烷序贯疗法联合曲妥单抗或多西他赛、卡铂、曲妥单抗进行6个周期的治疗。对于低风险、非淋巴结转移、HER2阳性人群,推荐每周一次的紫杉醇和曲妥单抗连续进行12个周期的替代治疗。曲妥单抗应持续使用1年。不应采用铂复合盐对三阴性人群进行常规的辅助管理,除非出现有效的生存数据加以支持。 | Neelima Denduluri Mark R Somerfield Andrea Eisen Jamie N Holloway Arti Hurria Tari A King Gary H Lyman Ann H Partridge Melinda L Telli Maureen E Trudeau Antonio C Wolff 本刊编辑部 | 2016 | 中国全科医学2016，19，18： | 1 |
| 13 | Extraction and analysis of low concentrations of DDT,DDE and DDD in small volumes of sediment pore water显示文摘 | Anne M C Patricia A K Robert A H | 1996 | Chemosphere1996，33，7： | 1 |
| 14 | Classical swine fever virus is genetically stable in vitro and in vivo 显示文摘 | Vanderhallen H Mittelhozer C hofm ann M A | 1999 | Arch Virol1999，，： | 1 |
| 15 | Texture Fusion and Feature Se- lection Applied to SARImagety 显示文摘 | Anne H Solberg S Jain A K | 1997 | IEEE Transaction on Geo- science and Remote Sensing1997，35，2： | 1 |
| 16 | Increased dietary intake of co-3 polyunsaturated fatty acidsreduces pathological retinal angiogenesis显示文摘 | Kip M C San Giovanni J P Lofqvist C Christopher M A Chen J HiguchiA Hong S Elke A P Majchrzak S Carper D Ann H Kang J X Emily Y C Norman S Charles N S | 2007 | Nature Medicine2007，13，： | 1 |
| 17 | Changes in male reproductive health and effects of endocrine disruptor in Scandinavian countries 显示文摘 | Jorma T Anne M H Markku A | 2002 | Cad Satide P6blica Riode Janeiro2002，18，2： | 1 |
| 18 | Producers' perceptions and attitudes toward precision agriculture technologies显示文摘 | Anne M A Shannon H N | | 0，，48： | 1 |
| 19 | The importance of vacA, cagA, and iceA genotypes of Helicobacter pylori infection in peptic ulcer disease and gastroesophageal reflux disease显示文摘 | Nicolaas L.A Arents Anton A van Zwet Jacob C Thijs Anne M.D Kooistra-Smid Kornelis R van Slochteren John E Degener Jan H Kleibeuker Leen-Jan van Doorn | 2001 | The American Journal of Gastroenterology2001，，9： | 1 |
| 20 | Increased lipolysis in transgenic animals overexpressing the epithelial fatty acid binding protein in adipose cells 显示文摘 | ANN V H ASSUMPTA B E DAVID A B | 2002 | Journal of Lipid Research2002，43，： | 1 |
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