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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 | Sodium glucose co-transporter 2 inhibition reduces succinate levels in diabetic mice显示文摘BACKGROUND Type 1 diabetes(T1D) is associated with major chronic microvascular complications which contribute significantly to diabetes associated morbidity.The protein primarily responsible for glucose reabsorption in the kidney is sodium glucose co-transporter 2(SGLT2). Presently, SGLT2 inhibitors are widely used in diabetic patients to improve blood glucose levels and prevent cardiovascular and renal complications. Given the broad therapeutic application of SGLT2 inhibitors, we hypothesised that SGLT2 inhibition may exert its protective effects via alterations of the gut microbiome and tested this in a type 1 diabetic mouse model of diabetic retinopathy.AIM To determine whether the treatment with two independent SGLT2 inhibitors affects gut health in a type 1 diabetic mouse model.METHODS The SGLT2 inhibitors empagliflozin or dapagliflozin(25 mg/kg/d) or vehicle dimethylsulfoxide(DMSO) were administered to C57 BL/6 J, Akita, Kimba and Akimba mice at 10 wk of age for 8 wk via their drinking water. Serum samples were collected and the concentration of succinate and the short chain fatty acid(SCFA) butyric acid was measured using gas chromatography-mass spectrometry. Enzyme-linked immunosorbent assay(ELISA) was performed to determine the concentration of insulin and leptin. Furthermore, the norepinephrine content in kidney tissue was determined using ELISA. Pancreatic tissue was collected and stained with haematoxylin and eosin and analysed using brightfield microscopy.RESULTS Due to the presence of the Akita allele, both Akita and Akimba mice showed a reduction in insulin production compared to C57 BL/6 J and Kimba mice.Furthermore, Akita mice also showed the presence of apoptotic bodies within the pancreatic islets. The acinar cells of Akita and Akimba mice showed swelling which is indicative of acute injury or pancreatitis. After 8 wk of SGLT2 inhibition with dapagliflozin, the intermediate metabolite of gut metabolism known as succinate was significantly reduced in Akimba mice when compared to DMSO treated mice. In addition, empagliflozin resulted in suppression of succinate levels in Akimba mice. The beneficial SCFA known as butyric acid was significantly increased in Akita mice after treatment with dapagliflozin when compared to vehicle treated mice. The norepinephrine content in the kidney was significantly reduced with both dapagliflozin and empagliflozin therapy in Akita mice and was significantly reduced in Akimba mice treated with empagliflozin.In non-diabetic C57 BL/6 J and Kimba mice, serum leptin levels were significantly reduced after dapagliflozin therapy.CONCLUSION The inhibition of SGLT2 reduces the intermediate metabolite succinate, increases SCFA butyric acid levels and reduces norepinephrine content in mouse models of T1 D. Collectively, these improvements may represent an important mechanism underlying the potential benefits of SGLT2 inhibition in T1 D and its complications. | Lakshini Y Herat Natalie C Ward Aaron L Magno Elizabeth P Rakoczy Marcio G Kiuchi Markus P Schlaich Vance B Matthews | 2020 | World Journal of Gastroenterology2020，26，23： | 3 |
| 3 | Cloning and mapping of variety-speeific rice genomic DNA sequences:amplifled fragment length polymorphisms(AFLP)from silver-stained Polyaerylamide gels显示文摘 | Yong G C MattheW w B OliVier P et a1 | 1996 | Genome1996，39，： | 1 |
| 4 | Microwave Land Surface Em- issivities Estimated from SSM/I Observations 显示文摘 | Prigent C Rossow W B Matthews E | 1997 | ] Geophys Res1997，102，21： | 1 |
| 5 | Adaptation of HIV-1to human leukocyte antigen class I显示文摘 | Kawashima Y Pfafferott K Frater J Matthews P Payne R Addo M Gatanaga H Fujiwara M Hachiya A Koizumi H Kuse N Oka S Duda A Prendergast A Crawford H Leslie A Brumme Z Brumme C Allen T Brander C Kaslow R Tang J Hunter E Allen S Mulenga J Branch S Roach T John M Mallal S Ogwu A Shapiro R Prado J G Fidler S Weber J Pybus O G Klenerman P Ndung'u T Phillips R Heckerman D Harrigan P R Walker B D Takiguchi M Goulder P | 2009 | Nature2009，458，7238： | 1 |
| 6 | Host plant evaluation behaviour of Bemisia tabaci and its modification by external uptake of imidacloprid显示文摘 | RUFUS I MATTHEW C DAVID N B | 1999 | Physiol Entomol1999，24，： | 1 |
| 7 | SCL-90-R and 16PF Profiles of senior high school students with excessive internet use显示文摘 | Chang-Kong Y Byeong-Moo C Matthew B | 2005 | Canada J Psychiatry2005，50，： | 1 |
| 8 | Extraction and characterisation of lipids from Antarctic krill (Euphausia superba)显示文摘 | JOSEPH C G MATTHEW P D SARAH K B | 2010 | Food Chemistry2010，125，3： | 1 |
| 9 | Transparent conducting Nnc oxide thin films doped with aluminum and molybdenum显示文摘 | JOEL N D TIMOTHY A G DAVID M W TERESA M B MATTHEW Y BOBBY T TIMOTHY J C | 2007 | Journal V-acuum Society Technology2007，25，4： | 1 |
| 10 | Laser capture microdissection (LCM) and comparative microarray expression analysis of syncytial cells isolated from incompatible and compatible soybean (Glycine max) roots infected by soybean cyst nematode (Heterodera glycines)显示文摘 | Klink V P Overall C C Alkharouf N MacDonald M H Matthews B F | | 0，，06： | 1 |
| 11 | Excitation-emission-matrix fluorescence spectroscopy applied to humic acid bands in coral reefs显示文摘 | Matthews B J H Jones A C Theodorou N K | 1996 | Mar Chem1996，55，34： | 1 |
| 12 | Rapid evolution of animal mitochondrial DNA显示文摘 | Wesley M B Matthew G JR Allen C W | 1979 | Proc Natl Acad Sci USA1979，76，4： | 1 |
| 13 | Angel-dependent XPS study of functional group orientation for aminosilicone polymers adsorbed onto cellulose surfaces显示文摘 | Michael C B Matthew D B Daniel Derr | 2004 | Appl Surf Sci2004，，227： | 1 |
| 14 | The influence o{ socioeconomic, environmental, and demographic factors on municipality scale land-cover change in Mexico显示文摘 | MARTHA B MITCHELL A T MATTHEW L C | 2012 | Regional Environmental Change2012，12，： | 1 |
| 15 | Strepto- myces competition and co-evolution in relation to plant disease suppression 显示文摘 | Linda L K Daniel C S Matthew G B | 2012 | Research in Microbiology2012，163，8： | 1 |
| 16 | Wild type and innate immune-deficient mice are not susceptible to the middle east respiratory syndrome eoronavirus显示文摘 | Coleman C M Matthews K L Goicochea L Frieman M B | 2014 | J Gen Virol2014，95，2： | 1 |
| 17 | Extraction and characterization of lipids from Antarctic krill(Euphausia superba)显示文摘 | Joseph C G Matthew P D Sarah K B | 2011 | Food Chemistry2011，，125： | 1 |
| 18 | Determination of halogenated mono-alcohols and diols in water by gas chromatography with electron-capture detection显示文摘 | Matthew B M Anastasio C | | 0，，： | 1 |
| 19 | Efficacy of SSH PCR in isolating differentially expressed genes显示文摘 | WAN J MATTHEW B W LI C | 2002 | BMC Genomics2002，3，1： | 1 |
| 20 | Global Maps of Micro-wave Land Surface Emissivities:Potential for Land SurfaceCharacterization显示文摘 | Prigent C Rossow W B Matthews E | 1998 | Radio Science1998，33，： | 1 |
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