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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 | Methionine adenosyltransferases in liver cancer显示文摘Methionine adenosyltransferases(MATs)are essential enzymes for life as they produce S-adenosylmethionine(SAMe),the biological methyl donor required for a plethora of reactions within the cell.Mammalian systems express two genes,MAT1A and MAT2A,which encode for MATα1 and MATα2,the catalytic subunits of the MAT isoenzymes,respectively.A third gene MAT2B,encodes a regulatory subunit known as MATβwhich controls the activity of MATα2.MAT1A,which is mainly expressed in hepatocytes,maintains the differentiated state of these cells,whilst MAT2A and MAT2B are expressed in extrahepatic tissues as well as non-parenchymal cells of the liver(e.g.,hepatic stellate and Kupffer cells).The biosynthesis of SAMe is impaired in patients with chronic liver disease and liver cancer due to decreased expression and inactivation of MATα1.A switch from MAT1A to MAT2A/MAT2B occurs in multiple liver diseases and during liver growth and dedifferentiation,but this change in the expression pattern of MATs results in reduced hepatic SAMe level.Decades of study have utilized the Mat1a-knockout(KO)mouse that spontaneously develops non-alcoholic steatohepatitis(NASH)and hepatocellular carcinoma(HCC)to elucidate a variety of mechanisms by which MAT proteins dysregulation contributes to liver carcinogenesis.An increasing volume of work indicates that MATs have SAMe-independent functions,distinct interactomes and multiple subcellular localizations.Here we aim to provide an overview of MAT biology including genes,isoenzymes and their regulation to provide the context for understanding consequences of their dysregulation.We will highlight recent breakthroughs in the field and underscore the importance of MAT’s in liver tumorigenesis as well as their potential as targets for cancer therapy. | Ben Murray Lucia Barbier-Torres Wei Fan JoséM Mato Shelly C Lu | 2019 | World Journal of Gastroenterology2019，25，31： | 10 |
| 3 | Is autoimmune hepatitis a frequent finding among HCV patients with intense interface hepatitis?显示文摘AIM:To evaluate the overlap of autoimmune hepatitis in hepatitis C virus(HCV)-infected patients with intense interface hepatitis.METHODS:Among 1759 patients with hepatitis C submitted to liver biopsy,92(5.2%) presented intense interface hepatitis.These patients were evaluated regarding the presence of antinuclear antibody(ANA),anti-smooth muscle antibody(SMA) and anti-liver/kidney microsomal antibody(LKM-1),levels of γ-globulin and histological findings related to autoimmune hepatitis(plasma cell infiltrate and presence of rosettes).RESULTS:Among patients with hepatitis C and intense interface hepatitis there was a low prevalence of autoantibodies(ANA=12%,SMA=5%,LKM-1=0%) and the median γ-globulin level was within the normal range.Typical histological findings of autoimmune disease were observed in only two cases(2%).After applying the score for diagnosis of autoimmune hepatitis,only one patient was classified with a definitive diagnosis of autoimmune hepatitis.Since overlap with autoimmune hepatitis was not the explanation for the intense necroinflammatory activity in patients with chronic hepatitis C we sought to identify the variables associated with this finding.The presence of intense interface hepatitis was associated with more advanced age,both at the time of infection and at the time of the biopsy,and higher prevalence of blood transfusion and alcohol abuse.CONCLUSION:Although possible,overlap with autoimmune hepatitis is a very rare association in HCV-infected patients with intense interface hepatitis,an unusual presentation which seems to be related to other host variables. | Rosilene G Badiani Vitória Becker Renata M Perez Carla AL Matos Lara B Lemos Valéria P Lanzoni Luis Eduardo C Andrade Alessandra Dellavance Antonio Eduardo B Silva Maria Lucia G Ferraz | 2010 | World Journal of Gastroenterology2010，16，29： | 7 |
| 4 | Acid-promoted reaction of the stilbene antioxidant resveratrol with nitrite ions : mild phenolic oxidation at the 4' -hydroxystiryl sector triggering nitration, dimerization, and aldehyde-forming routes显示文摘 | Panzella L De Lucia M Amalfitano C | 2006 | J Org Chem2006，71，11： | 1 |
| 5 | Analysis of continuous glucose monitoring data from non-diabetic and diabetic children: A tale of two algorithms 显示文摘 | WEINZIMER S A DE Lucia M C BOLAND E A | 2003 | Diabetes Technology & Therapeutics2003，5，3： | 1 |
| 6 | Clinical haemorheology and microcirculation显示文摘 | Lucia M Emanuele C Cinzia F | 2007 | Ann Ist Super Sanita2007，43，： | 1 |
| 7 | Family cohesion and chidren’sbehavior problems:a longitudinal investigation显示文摘 | LUCIA V C BRESLAU M | 2006 | PsychiatryRes2006，141，2： | 1 |
| 8 | Pulmonary function test: its correlation with pulmonary high-resolution computed tomography in patients with rheumatoid arthritis 显示文摘 | Leonel D Lucia C A M | 2012 | Rheumatol Irtt2012，32，7： | 1 |
| 9 | Comparing ICA-based and single-trial topographic ERP analyses显示文摘 | Lucia M D Michel C M Murray M M | 2010 | Brain Topogra- phy2010，23，2： | 1 |
| 10 | Catching up trajectories in the wine sector:a comparative study of Chile,Italy,and South Africa显示文摘 | LUCIA C ANDREA M ROBERTA R | 2010 | World Development2010，38，11： | 1 |
| 11 | The Pros- tate Cancer Prevention Trial and the future of chemo- prevention显示文摘 | Thompson I M Tangen C M Lucia M S | 2008 | BJU Int2008，101，8： | 1 |
| 12 | Comparison of two different doses of iodide in the prevention of gestational goiter in marginal iodine deficiency: a longitudinal study显示文摘 | Lucia A Doretta M Rossana C | 2002 | Eur J Endocrinol2002，147，： | 1 |
| 13 | Cancer-related Fatigue: Can Exercise Physiology Assist Oncologists?显示文摘 | Lucia A Earnest C P:rez M | 2003 | Lancet Oncol2003，4，10： | 1 |
| 14 | Generalized B-splines as a tool in isogeometric analysis显示文摘 | MANNI C PELOSI F LUCIA S M | 2011 | Comput Methods Appl Mech & Eng2011，200，58： | 1 |
| 15 | Food security and public agricultural spending in bolivia: putting money where your mouth is? 显示文摘 | JOSE C SVETLANA E LUCIA M | 2013 | Food Policy2013，，1： | 1 |
| 16 | Induction of CD69 antigen on normal CD4+ and CD8+ lymphocyte subsets and its relationship with the phenotype of responding T-cells显示文摘 | Rutella S Rumi C Lucia M B | 1999 | Cytometry1999，38，： | 1 |
| 17 | The prostate cancer preven tion trial and the future of chemoprevention显示文摘 | Thompson I M Tang C M Lucia M S | 2008 | BJU Int2008，10，1： | 1 |
| 18 | Dominant oncogenes,tumor suppressors,and radiosensitivity显示文摘 | Vincenzo C Lucia M Mavina C | 1995 | Cell Mol Biol Res1995，41，3： | 1 |
| 19 | Evaluation of pain during posture change in patients with invasive mechanical ventilation显示文摘 | V6zquez C M Pardavila B M Lucia M M | 2009 | Enfermlntensiva2009，20，1： | 1 |
| 20 | Clinical haemorheology and microcirculation显示文摘 | Lucia M Emanuele C Cinzia F | 2007 | Ann Ist Super Sanita2007，43，： | 1 |
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