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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 | The wonders of BMP9:From mesenchymal stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism to regenerative medicine显示文摘Although bone morphogenetic proteins(BMPs)initially showed effective induction of ectopic bone growth in muscle,it has since been determined that these proteins,as members of the TGF-b superfamily,play a diverse and critical array of biological roles.These roles include regulating skeletal and bone formation,angiogenesis,and development and homeostasis of multiple organ systems.Disruptions of the members of the TGF-b/BMP superfamily result in severe skeletal and extra-skeletal irregularities,suggesting high therapeutic potential from understanding this family of BMP proteins.Although it was once one of the least characterized BMPs,BMP9 has revealed itself to have the highest osteogenic potential across numerous experiments both in vitro and in vivo,with recent studies suggesting that the exceptional potency of BMP9 may result from unique signaling pathways that differentiate it from other BMPs.The effectiveness of BMP9 in inducing bone formation was recently revealed in promising experiments that demonstrated efficacy in the repair of critical sized cranial defects as well as compatibility with bone-inducing bio-implants,revealing the great translational promise of BMP9.Furthermore,emerging evidence indicates that,besides its osteogenic activity,BMP9 exerts a broad range of biological functions,including stem cell differentiation,angiogenesis,neurogenesis,tumorigenesis,and metabolism.This review aims to summarize our current understanding of BMP9 across biology and the body. | Sami Mostafa Mikhail Pakvasa Elam Coalson Allen Zhu Alex Alverdy Hector Castillo Jiaming Fan Alex Li Yixiao Feng Di Wu Elliott Bishop Scott Du Mia Spezia Alissa Li Ofir Hagag Alison Deng Winny Liu Mingyang Li Sherwin S·Ho Aravind Athiviraham Michael J·Lee Jennifer Moriatis Wolf Guillermo A·Ameer Hue H·Luu Rex C·Haydon Jason Strelzow Kelly Hynes Tong-Chuan He Russell R·Reid | 2019 | Genes & Diseases2019，6，3： | 15 |
| 3 | Plecanatide and dolcanatide, novel guanylate cyclase-C agonists, ameliorate gastrointestinal inflammation in experimental models of murine colitis显示文摘AIM: To evaluate the effect of orally administeredplecanatide or dolcanatide, analogs of uroguanylin, on amelioration of colitis in murine models.METHODS: The cyclic guanosine monophosphate(cG MP) stimulatory potency of plecanatide and dolcanatide was measured using a human colon carcinoma T84 cellbased assay. For animal studies all test agents were formulated in phosphate buffered saline. Sulfasalazine or 5-amino salicylic acid(5-ASA) served as positive controls. Effect of oral treatment with test agents on amelioration of acute colitis induced either by dextran sulfate sodium(DSS) in drinking water or by rectal instillation of trinitrobenzene sulfonic(TNBS) acid, was examined in BALB/c and/or BDF1 mice. Additionally, the effect of orally administered plecanatide on the spontaneous colitis in T-cell receptor alpha knockout(TCRα-/-) mice was also examined. Amelioration of colitis was assessed by monitoring severity of colitis, disease activity index and by histopathology. Frozen colon tissues were used to measure myeloperoxidase activity.RESULTS: Plecanatide and dolcanatide are structurally related analogs of uroguanylin, which is an endogenous ligand of guanylate cyclase-C(GC-C). As expected from the agonists of GC-C, both plecanatide and dolcanatide exhibited potent cG MP-stimulatory activity in T84 cells. Once-daily treatment by oral gavage with either of these analogs(0.05-0.5 mg/kg) ameliorated colitis in both DSS and TNBS-induced models of acute colitis, as assessed by body weight, reduction in colitis severity(P < 0.05) and disease activity index(P < 0.05). Amelioration of colitis by either of the drug candidates was comparable to that achieved by orally administered sulfasalazine or 5-ASA. Plecanatide also effectively ameliorated colitis in TCRα-/- mice, a model of spontaneous colitis. As dolcanatide exhibited higher resistance to proteolysis in simulated gastric and intestinal juices, it was selected for further studies. CONCLUSION: This is the first-ever study reporting the therapeutic utility of GC-C agonists as a new class of orally delivered and mucosally active drug candidates for the treatment of inflammatory bowel diseases. | Kunwar Shailubhai Vaseem Palejwala Krishna Priya Arjunan Sayali Saykhedkar Bradley Nefsky John A Foss Stephen Comiskey Gary S Jacob Scott E Plevy | 2015 | World Journal of Gastrointestinal Pharmacology and Therapeutics2015，6，4： | 5 |
| 4 | Guanylyl cyclase C signaling axis and colon cancer prevention显示文摘Colorectal cancer(CRC) is a major cause of cancerrelated mortality and morbidity worldwide. While improved treatments have enhanced overall patient outcome, disease burden encompassing quality of life, cost of care, and patient survival has seen little benefit. Consequently, additional advances in CRC treatments remain important, with an emphasis on preventative measures. Guanylyl cyclase C(GUCY2C), a transmembrane receptor expressed on intestinal epithelial cells, plays an important role in orchestrating intestinal homeostatic mechanisms. These effects are mediated by the endogenous hormones guanylin(GUCA2A) and uroguanylin(GUCA2B), which bind and activate GUCY2 C to regulate proliferation, metabolism and barrier function in intestine. Recent studies have demonstrated a link between GUCY2 C silencing and intestinal dysfunction, including tumorigenesis. Indeed, GUCY2 C silencing by the near universal loss of its paracrine hormone ligands increases colon cancer susceptibility in animals and humans. GUCY2C's role as a tumor suppressor has opened the door to a new paradigm for CRC prevention by hormone replacement therapy using synthetic hormone analogs, such as the FDA-approved oral GUCY2 C ligand linaclotide(Linzess^(TM)). Here we review the known contributions of the GUCY2 C signaling axis to CRC, and relate them to a novel clinical strategy targeting tumor chemoprevention. | Amanda M Pattison Dante J Merlino Erik S Blomain Scott A Waldman | 2016 | World Journal of Gastroenterology2016，22，36： | 2 |
| 5 | Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders显示文摘 | E Joanna Baxter Linda M Scott Peter J Campbell Clare East Nasios Fourouclas Soheila Swanton George S Vassiliou Anthony J Bench Elaine M Boyd Natasha Curtin Mike A Scott Wendy N Erber Anthony R Green | 2005 | The Lancet . 2005 (9464)2005，，： | 2 |
| 6 | Transformation of wheat with the gene encoding the coat protein of barley yellow mosaic virus显示文摘 | Karunaratne S Sohn A Mouradov A Scott J Steinbi H Scott K J | 1996 | Aust J Plant Physiol1996，23，： | 2 |
| 7 | 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 |
| 8 | Human apolipoprotein A-gene expression increase high-density lipoprotein and suppresses atherosclerosis in the apoprotein E-deficientmouse 显示文摘 | Plump A S Scott C J Breslow J L | 1994 | Proc Natal Acad Sci USA1994，91，： | 2 |
| 9 | Spring-dashpot models for the Dynamics of radially rotating beam with impact显示文摘 | Ulsoy A G Scott R A | 1990 | Journal of Sound and Vibration1990，142，3： | 1 |
| 10 | Genetic and Mechanistic Exploration of the Two Pathways of Vitamin B12 Biosynthesis显示文摘 | Scott A I Roessner C A Patricio J S | 2003 | The Porphyrin Handbook2003，，12： | 1 |
| 11 | Toward a unifying framework for exploring fit and flexibility in strategic human resource management显示文摘 | Patrick M W & Scott A S | 1998 | Academy of management review1998，23，： | 1 |
| 12 | Scrapie injected murine neuroblastoma cells produce proteaseresistant prion proteins 显示文摘 | Butler D A Scott M R D Prusiner S B | 1988 | J Virol1988，62，： | 1 |
| 13 | Randomized and non - ran- domized evidence for the effect of compulsory community involun- tary out -patient treatment on health service use:systematic review and meta - analysis显示文摘 | Kisely S Campbell LE Scott A | 2007 | Psychological Medicine2007，37，1： | 1 |
| 14 | In Situ Gasfication of Coal Using Steam with Chemical Looping:a Technique for Load- ing COz from Burning a Solid Fuel显示文摘 | Dennis J S Scott S A Hayhurst A N | 2006 | Journal of the Energy Institute2006，97，3： | 1 |
| 15 | Cross-validation of multivariate densities显示文摘 | SAIN S R BAGGERLYB K A SCOTT A D | 1994 | Journal of the American Statistical As- sociation1994，89，8： | 1 |
| 16 | Fatty acid composition of adipose tissue from lean and obese swine 显示文摘 | SCOTT R A CORNELIUS S G MERSMANN H J | 1981 | Journal of Animal Science1981，53，： | 1 |
| 17 | Total knee arthroplasty with the PFC system results at a minimum of ten years and survivorship analysis 显示文摘 | Schai P A Thornhill T S Scott R D | 1998 | J Bone Joint Surg Br1998，80，5： | 1 |
| 18 | Reexpression of epigenetically silenced AML tumor suppressor genes by SUV39H1 inhibition显示文摘 | Lakshmikuttyamma A S A Scott DeCoteau J F | 2010 | Oncogene2010，29，： | 1 |
| 19 | Changes in growth factor and cytokine mRNA levels after hepatectomy in rat with CCL4-induced cirrhosis显示文摘 | Masson S Scotte M Francois A | 1999 | Am J Physiol1999，277，41： | 1 |
| 20 | Validation of real-time three-dimensional echocardiography for quantifying left ventricular volumes in the presence of a left ventricular aneurysm: in vitro and in vivo studies显示文摘 | Jian Xin Qin Michael Jones Takahiro Shiota Neil L Greenberg Hiroyuki Tsujino Michael S Firstenberg Pankaj C Gupta Arthur D Zetts Yong Xu Jing Ping Sun Lisa A Cardon Jill A Odabashian Scott D Flamm Richard D White Julio A Panza James D Thomas | 2000 | Journal of the American College of Cardiology2000，，3： | 1 |
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