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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 | miR-182参与调节胶质母细胞瘤的凋亡、生长和分化(英文)显示文摘Glioblastoma multiforme(GBM)is a lethal,therapy-resistant brain cancer consisting of numerous tumor cell subpopulations,including stem-like glioma-initiating cells(GICs),which contribute to tumor recurrence following initial response to therapy.Here,we identified miR-182 as a regulator of apoptosis,growth,and differentiation programs whose expression level is correlated with GBM patient survival.Repression of Bcl2-like12(Bcl2L12),c-Met,and hypoxia-inducible factor 2α(HIF2A)is of central importance to miR-182 anti-tumor activity,as it results in enhanced therapy susceptibility,decreased GIC sphere size,expansion,and stemness in vitro.To evaluate the tumor-suppressive function of miR-182 in vivo,we synthesized miR-182-based spherical nucleic acids(182-SNAs);i.e.,gold nanoparticles covalently functionalized with mature miR-182 duplexes.Intravenously administered 182-SNAs penetrated the bloodbrain/blood-tumor barriers(BBB/BTB)in orthotopic GBM xenografts and selectively disseminated throughout extravascular glioma parenchyma,causing reduced tumor burden and increased animal survival.Our results indicate that harnessing the anti-tumor activities of miR-182 via safe and robust delivery of 182-SNAs represents a novel strategy for therapeutic intervention in GBM. | Kouri FM Hurley LA Daniel WL Day ES Hua Y Hao L Peng CY Merkel TJ Queisser MA Ritner C Zhang H James CD Sznajder JI Chin L Giljohann DA Kessler JA Peter ME Mirkin CA Stegh AH | 2015 | 中华神经外科疾病研究杂志2015，14，2： | 14 |
| 3 | Retrograde-viewing device improves adenoma detection rate in colonoscopies for surveillance and diagnostic workup显示文摘AIM:To determine which patients might benefit most from retrograde viewing during colonoscopy through subset analysis of randomized,controlled trial data.METHODS:The Third Eye Retroscope Randomized Clinical Evaluation(TERRACE) was a randomized,controlled,multicenter trial designed to evaluate the efficacy of a retrograde-viewing auxiliary imaging device that is used during colonoscopy to provide a second video image which allows viewing of areas on the proximal aspect of haustral folds and flexures that are difficult to see with the colonoscope's forward view.We performed a post-hoc analysis of the TERRACE data to determine whether certain subsets of the patient population would gain more benefit than others from use of the device.Subjects were patients scheduled for colonoscopy for screening,surveillance or diagnostic workup,and each underwent same-day tandem examinations with standard colonoscopy(SC) and Third Eye colonoscopy(TEC),randomized to SC followed by TEC or vice versa.RESULTS:Indication for colonoscopy was screening in 176/345 subjects(51.0%),surveillance after previous polypectomy in 87(25.2%) and diagnostic workup in 82(23.8%).In 4 subjects no indication was specified.Previously reported overall results had shown a net additional adenoma detection rate(ADR) with TEC of 23.2% compared to SC.Relative risk(RR) of missing adenomas with SC vs TEC as the initial procedure was 1.92(P = 0.029).Post-hoc subset analysis shows additional ADRs for TEC compared to SC were 4.4% for screening,35.7% for surveillance,55.4% for diagnostic and 40.7% for surveillance and diagnostic combined.The RR of missing adenomas with SC vs TEC was 1.11(P = 0.815) for screening,3.15(P = 0.014) for surveillance,8.64(P = 0.039) for diagnostic and 3.34(P = 0.003) for surveillance and diagnostic combined.Although a multivariate Poisson regression suggested gender as a possibly significant factor,subset analysis showed that the difference between genders was not statistically significant.Age,bowel prep quality and withdrawal time did not significantly affect the RR of missing adenomas with SC vs TEC.Mean sizes of adenomas detected with TEC and SC were similar at 0.59 cm and 0.56 cm,respectively(P = NS).CONCLUSION:TEC allows detection of significantly more adenomas compared to SC in patients undergoing surveillance or diagnostic workup,but not in screening patients(ClinicalTrials.gov Identifier:NCT01044732). | Peter D Siersema Amit Rastogi Anke M Leufkens Paul A Akerman Kassem Azzouzi Richard I Rothstein Frank P Vleggaar Alessandro Repici Giacomo Rando Patrick I Okolo Olivier Dewit Ana Ignjatovic Elizabeth Odstrcil James East Pierre H Deprez Brian P Saunders Anthony N Kalloo Bradley Creel Vikas Singh Anne Marie Lennon Daniel C DeMarco | 2012 | World Journal of Gastroenterology2012，18，26： | 6 |
| 4 | Nat Med:靶向两分子或有助于彻底治愈白血病显示文摘科学家在癌细胞内发现两个信号蛋白能够让癌细胞抵抗化疗。研究表明阻断这两种蛋白能够增强化疗对人类白血病小鼠模型的治疗效果。相关研究结果发表在国际学术期刊NatureMedicine上。研究人员发现在治疗中阻断c-Fos和Dusp1这两个蛋白能够治愈一些受激酶驱动且抵抗治疗的白血病和实体瘤。 | Meenu Kesarwani, Zachary Kincaid, Ahmed Gomaa, Erika Huber, Sara Rohrabaugh, Zain Siddiqui, Muhammad F Bouso, Kakajan Komurov, James C Mulloy, Jose A Cancelas, H Leighton Grimes Mohammad Azam Tahir Latif Ming Xu H Leighton Grimes Mohammad Azam | 2017 | 现代生物医学进展2017，17，17： | 4 |
| 5 | Inhibition of the G9a/GLP histone methyltransferase complex modulates anxiety-related behavior in mice显示文摘Epigenetic 基因规定畸形包括精神分裂症和消沉在各种各样的 neuropsychiatric 混乱,以及在心情和焦虑的规定被含有。另外, epigenetic 机制涉及精神病学的药的行动。当前的 anxiolytic 药有新药的重要缺点,和开发被保证。二蛋白质, G9a (也作为 EHMT2 或 KMT1C 知道) 并且 GLP (象 G9a 一样蛋白质,也作为 EHMT1 或 KMT1D 知道) ,它甲醇化物离氨酸 9 histone H3 (H3K9 ) ,能正在答应 anxiolytic 目标。G9a 的出生后的基因大美人减少焦虑相关的行为,与由过去常对待焦虑(amitriptyline, imipramine 和 paroxetine ) 的一些药的 G9a 层次的减小一致。相反地,在有 GLP haplodeficiency 的老鼠有增加的像焦虑的行为。我们寻求了决定是否 G9a/GLP, UNC0642 和 A-366 的二个药理学禁止者,将有类似的效果到基因 G9a/GLP 不足。当予成年老鼠以时,我们发现有任何一个化合物的 G9a/GLP 抑制减少了像焦虑的行为,与在大脑的减少的 H3K9 methylation 一起。相反,到这些的暴露从胚胎的白天加重(E9.5 ) 9.5 增加了像焦虑的行为直到出生并且减少在成人生活的社会相互作用,当 H3K9 methylation 在在成年老鼠的大脑的正常层次时。这些调查结果增强 G9a/GLP 在大脑开发的不同阶段在像焦虑的行为上有不同效果的基因证据,并且建议指向这条 histone methyltransferase 小径能为开发新 anxiolytic 药是有用的。这些数据也建议在 utero 的抗抑郁剂暴露能在成人生活有否定效果,并且这些效果的进一步的调查被保证。 | Dong-yao WANG Joel KOSOWAN James SAMSOM Laura LEUNG Kai-lai ZHANG Ying-xiang LI Yan XIONG Jian JIN Arturas PETRONIS Gabriel OH Albert H C WONG | 2018 | Acta Pharmacologica Sinica2018，39，5： | 4 |
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