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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 | VEGF-D expression correlates with colorectal cancer aggressiveness and is downregulated by cetuximab显示文摘AIM:To gain mechanistic insights into the role played by epidermal growth factor receptor (EGFR) in the regulation of vascular endothelial growth factors (VEGFs) in colorectal cancer (CRC). METHODS:The impact of high-level expression of the growth factor receptors EGFR and VEGF receptor (VEGFR)3 and the VEGFR3 ligands VEGF-C and VEGF-D on disease progression and prognosis in human CRC was investigated in 108 patients using immunohistochemistry. Furthermore, the expression of the lymphangiogenic factors in response to the modulation of EGFR signalling by the EGFR-targeted monoclonal antibody cetuximab was investigated at the mRNA and protein level in human SW480 and SW620 CRC cell lines and a mouse xenograft model. RESULTS: Human CRC specimens and cell lines displayed EGFR, VEGF-C and VEGF-D expression with varying intensities. VEGF-C expression was associated with histological grade. Strong expression of VEGF-D was significantly associated with lymph node metastases and linked to a trend for decreased survival in lymph node-positive patients. EGFR blockade with cetuximab resulted in a significant decrease of VEGF-D expression in vitro and in vivo. CONCLUSION:In conclusion, the expression of VEGF-D in colorectal tumours is significantly associated with lymphatic involvement in CRC patients and such expression might be blocked effectively by cetuximab. | Markus Moehler Christian Frings Annett Mueller Ines Gockel Carl C Schimanski Stefan Biesterfeld Institute of Pathology Johannes Gutenberg University Mainz 55101 Germany Peter R Galle Martin H Holtmann | 2008 | World Journal of Gastroenterology2008，14，26： | 15 |
| 3 | Predicting Protein Subcellular Localization: Past, Present, and Future显示文摘Functional characterization of every single protein is a major challenge of the postgenomic era. The large-scale analysis of a cell's proteins, proteomics, seeks to provide these proteins with reliable annotations regarding their interaction partners and functions in the cellular machinery. An important step on this way is to determine the subcellular localization of each protein. Eukaryotic cells are divided into subcellular compartments, or organelles. Transport across the membrane into the organelles is a highly regulated and complex cellular process. Predicting the subcellular localization by computational means has been an area of vivid activity during recent years. The publicly available prediction methods differ mainly in four aspects: the underlying biological motivation, the computational method used, localization coverage, and reliability, which are of importance to the user.This review provides a short description of the main events in the protein sorting process and an overview of the most commonly used methods in this field. | Pierre Dnnes Annette Hglund | 2004 | Genomics, Proteomics & Bioinformatics2004，2，4： | 4 |
| 4 | Immunisation against PCV2 structural protein by DNA vaccination of mice显示文摘 | Ren S K Annette M B Tine H F | 2004 | Vaccine2004，22，： | 1 |
| 5 | Predictors of survival for esophageal cancer patients with and without celiac axis lymphadenopathy: impact of staging endosonography显示文摘 | Mohamad A Eloubeidi Michael B Wallace Brenda J Hoffman Margaret B Leveen Annette Van Velse Robert H Hawes Carolyn E Reed | 2001 | The Annals of Thoracic Surgery2001，，1： | 1 |
| 6 | Solar Energy Assess-ment Using Remote Sensing Technologies显示文摘 | Annette H Detlev H Carsten H | 2003 | Remote Sens-ing of Environment2003，86，3： | 1 |
| 7 | Impact of pollen on hu- man health: more than allergen carriers 显示文摘 | Claudia T H Anna K Annette M | 2003 | Allergy Immunol2003，131，： | 1 |
| 8 | Organochlorine exposure and risk of breast cancer显示文摘 | Annette P H Philippe G Torben J | 1998 | Lancet1998，352，： | 1 |
| 9 | Pressure ulcer treatment strategies :A systematic comparative effec- tiveness review显示文摘 | ME Beth Smith Annette Totten David H | 2013 | Annals of Internal Medicine2013，159，1： | 1 |
| 10 | A study on reducing substrates of manganese-oxidizing peroxidases from Pleurotus eryngii and Bjerkandera adusta 显示文摘 | Annette H Francisco J R D Maria J M | 1998 | FEBS Lett1998，428，3： | 1 |
| 11 | An ethics core curriculum for Australasian medical schools, A Working Group, on behalf of the Association of Teachers of Ethics and Law in Australian and New Zealand Medical Schools (ATEAM) 显示文摘 | ANNETTE J B LYNN H G EDWINA F V | 2001 | MJA2001，，175： | 1 |
| 12 | The molecular basis of cancer immunotherapy by cytotoxic T lymphocytes显示文摘 | M. Lindauer T. Stanislawski Annett H?u?ler Edith Antunes Anne Cellary Christoph Huber M. Theobald | 1998 | Journal of Molecular Medicine1998，，1： | 1 |
| 13 | Large-scale evaluation ofenzyme-linked immunospot assay and skin test for diagnosis ofMycobactefium tuberculosis infection against a gradient of exposurein the Gambia显示文摘 | Philip C Roger H Annette F | 2004 | Clin Infect Dis2004，38，7： | 1 |
| 14 | Position of horse- shoe crabs in estuarine food webs: N and C stable isotopic study of foraging ranges and diet composition 显示文摘 | Carmichael R H Rutecki D Annett B | 2004 | Journal of Experimental Marine Biology and Ecology2004，299，2： | 1 |
| 15 | Secretory expression and characterization of insulin in Pichia pastoris显示文摘 | Annette F P Morten H | 1999 | Biotechnol Appl Biochem1999，29，： | 1 |
| 16 | Laccase-induced cross-coupling of 4-aminobenzoic acid with para-dihydroxylated compounds 2,5-dihydroxy-N-(2-hydroxyethyl)-benzamide and 2,5-dthydroxybenzoic acid methyl ester显示文摘 | Katrin M Elke H Annett M T | 2005 | Journal of Molecular Catalysis B: Enzymatic2005，，35： | 1 |
| 17 | Reversal of Multidrug Resistance in Chinese Hamster Ovary Cells by the Immunosuppressive Agent Rapamycin显示文摘 | Torsten H Annette D Uwe C | 1993 | Eur J Pharmacology1993，246，： | 1 |
| 18 | Cell cultures as tools in biopharmacy显示文摘 | Annette B Sibylle H Kayosh I S | 2000 | Eur J Pharm Sci2000，11，2： | 1 |
| 19 | Differential regulation of the Fe-hydrogenase during anaerobic adaptation in the green alga Chlamydomonas reinhardtii显示文摘 | THOMAS H ANNETTE K | 2002 | Eur J Biochem2002，269，： | 1 |
| 20 | Reesttabish in freshwater wetlands in Denmark显示文摘 | CARL C H ANNETTE B P | 2006 | Ecological Engineering2006，，9： | 1 |
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