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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 | Coexpression of receptor-tyrosine-kinases in gastric adenocarcinoma-a rationale for a molecular targeting strategy?显示文摘AIM: To define the (co-)expression pattern of target receptor-tyrosine-kinases (RTK) in human gastric adenocarcinoma. METHODS: The (co-)expression pattern of VEGFR1-3,PDGFRα/b and EGFR1 was analyzed by RT-PCR in 51 human gastric adenocarcinomas. In addition,IHC staining was applied for confirmation of expression and analysis of RTK localisation. RESULTS: The majority of samples revealed a VEGFR1 (98%),VEGFR2 (80%),VEGFR3 (67%),PDGFRα (82%) and PDGFRβ(82%) expression,whereas only 62% exhibited an EGFR1 expression. 78% of cancers expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRα revealed a predominantly cytoplasmatic staining in tumor cells,accompanied by an additional nuclear staining for VEGFR3 ,EGFR1 was almost exclusively detected on the membrane of tumor cells. PDGFRβ was restricted to stromal pericytes,which also depicted a PDGFRα expression.receptor-tyrosine-kinases coexpression in gastric adenocarcinoma and might therefore encourage an application of multiple-target RTK-inhibitors within a combination therapy. | Daniel Drescher Markus Moehler Ines Gockel Kirsten Frerichs Annett Müller Friedrich Dünschede Thomas Borschitz Stefan Biesterfeld Martin Holtmann Thomas Wehler Andreas Teufel Kerstin Herzer Thomas Fischer Martin R Berger Theodor Junginger Peter R Galle Carl C Schimanski | 2007 | World Journal of Gastroenterology2007，13，26： | 4 |
| 4 | 无明显移位的髋臼骨折可以保守治疗吗?显示文摘对髋臼骨折保守治疗的长期随访结果研究甚少。作者对104例保守治疗的髋臼骨折患者进行平均随访12.1年(9-20年)的研究。结果发现,保守治疗髋臼骨折患者的10年生存率为94%,89%患者Harris评分优良,88%患者Merle-Postel评分优良,最主要的负面影响因素是闭孔斜位片上骨折台阶〉2mm。 | John C J Annette K B Olav R 李军 荆珏华 | 2017 | 临床骨科杂志2017，20，1： | 2 |
| 5 | Exogenous cytokinin application to Actinidia chinensis var. deliciosa ‘Hayward’ fruit promotes fruit expansion through water uptake显示文摘Exogenous application of a cytokinin-like compound forchlorfenuron(CPPU)can promote fruit growth,although often at the expense of dry matter(DM),an important indicator of fruit quality.Actinidia chinensis var.deliciosa‘Hayward’fruit are very responsive to CPPU treatments,but the mechanism underlying the significant fruit weight increase and associated decrease in DM is unclear.In this study,we hypothesised that CPPU-enhanced growth increases fruit carbohydrate demand,but limited carbohydrate supply resulted in decreased fruit DM.During fruit development,CPPU effects on physical parameters,metabolites,osmotic pressure and transcriptional changes were assessed under conditions of both standard and a high carbohydrate supply.We showed that CPPU increased fruit fresh weight but the dramatic DM decrease was not carbohydrate limited.Enhanced glucose and fructose concentrations contributed to an increase in soluble carbohydrate osmotic pressure,which was correlated with increased water accumulation in CPPU-treated fruit and up-regulation of water channel aquaporin gene PIP2.4 at 49 days after anthesis.Transcipt analysis suggested that the molecular mechanism contributing to increased glucose and fructose concentrations was altered by carbohydrate supply.At standard carbohydrate supply,the early glucose increase in CPPU fruit was associated with reduced starch synthesis and increased starch degradation.When carbohydrate supply was high,the early glucose increase in CPPU fruit was associated with a general decrease in starch synthesis but up-regulation of vacuolar invertase and fructokinase genes.We conclude that CPPU affected fruit expansion by increasing the osmotically-driven water uptake and its effect was not carbohydrate supply-limited. | Simona Nardozza Helen L Boldingh Mark W Wohlers Andrew P Gleave Zhiwei Luo Guglielmo Costa Elspeth A MacRae Michael J Clearwater Annette C Richardson | 2017 | Horticulture Research2017，4，1： | 2 |
| 6 | Employee Involvement and Participation:Developing the Concept of Institutional Embeddedness Using WERS2004显示文摘 | Annette C Mick M Suterc J | | 0，，10： | 1 |
| 7 | Mixed-species plantations of Eucalyptus with nitrogen-fixing trees:A review显示文摘 | Forrester J B Annette L C | 2006 | Forest Ecology and Management2006，233，： | 1 |
| 8 | Solid lipod nanoparticles (SLN) for controlled drug delivery-drug release and release mechanism显示文摘 | Annette M Schwarz C Mehnert W | 1998 | Eur J Pharm Biopharm1998，45，2： | 1 |
| 9 | Oxidation of^6-to^5 by peroxomonosulfate in strong and weak acid solutions,an example of zero-order kinetics显示文摘 | Annette L N Robert C B Geoffrey A L | 1998 | J Chem Soc Dalton Trans1998，，5： | 1 |
| 10 | The solubility of calcium zincate (CaZn2(OH)6 · 2H2O)显示文摘 | Felix Ziegler Annette C Johnson | 2001 | Cement and Concrete Research2001，31，： | 1 |
| 11 | Computer modeling and intraoperative navigation in maxillofacial surgery 显示文摘 | Annette M Pham Amir A Rafii Marc C | 2007 | Otolaryngology-Head and Neck Surgery (S1043-1810)2007，137，4： | 1 |
| 12 | Crystal structures and enzymatic properties of three formyltransferases from archaea:Environmental adaptation and evolutionary relationship显示文摘 | Bjorn Mamat Annette Roth Clemens Grimm C | 2002 | Protein Science2002，11，9： | 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 | Nigrostriatal alpha- synueleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein: a new primate model of Parkinson' s disease显示文摘 | Kirik D Annett LE Burger C | 2003 | Proc Natl Aead Sci U S A2003，100，5： | 1 |
| 15 | High miR‐21 expression from FFPE tissues is associated with poor survival and response to adjuvant chemotherapy in colon cancer显示文摘 | Naohide Oue Katsuhiro Anami Aaron J. Schetter Markus Moehler Hirokazu Okayama Mohammed A. Khan Elise D. Bowman Annett Mueller Arno Schad Manabu Shimomura Takao Hinoi Kazuhiko Aoyagi Hiroki Sasaki Masazumi Okajima Hideki Ohdan Peter R. Galle Wataru Yasui C | 2014 | Int. J. Cancer2014，，： | 1 |
| 16 | Nigrostriatal alpha-synucleinopathy induced by viral vector-mediated overexpression of human alpha-synuclein:a new primate model of Parkinson's disease显示文摘 | Kirik D Annett LE Burger C | 2003 | Proc Natl Acad Sci USA2003，100，5： | 1 |
| 17 | Performance of children and adolescents with asperger syndrome or high-functioning autism on advanced theory of mind tasks 显示文摘 | Nils K Kirsten C Annette MN | 2008 | J Autism Dev Dis- ord2008，38，6： | 1 |
| 18 | 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 |
| 19 | Multichannel CT:evaluating the spine in postoperative patients with orthopedic hardware显示文摘 | Annette C Douglas A Kenneth A | 2006 | Radiographics2006，26，1： | 1 |
| 20 | Assessing the potential long-term behavior of the landfill fraction of sorted demolition waste显示文摘 | C Annette Johnson Hermann Moench Sandro Brandenberger | 1999 | Journal of Environmental Quality1999，28，： | 1 |
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