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| 1 | 帕博利珠单抗联合以铂类为基础的化疗治疗非小细胞肺癌合并稳定性脑转移患者的结局:KEYNOTE-021、-189和-407研究的汇总分析显示文摘背景与目的此项探索性分析回顾评价了晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)患者的结局,旨在确定基线时合并脑转移是否会影响一线应用帕博利珠单抗联合化疗(pembrolizumab plus chemotherapy,PC)比对单用化疗的疗效。患者和方法对KEYNOTE-021队列G(非鳞癌)、KEYNOTE-189(非鳞癌)和KEYNOTE-407(鳞癌)三项研究晚期NSCLC患者的数据进行汇总分析。患者接受含铂两药化疗和/或35个周期帕博利珠单抗治疗(每3周200 mg)。所有研究均纳入了经治或初治的稳定性脑转移患者(KEYNOTE-189与KEYNOTE-407研究纳入初治脑转移患者)。经治的脑转移患者已处于病情稳定的状态≥2周(KEYNOTE-021队列G患者≥4周),无新发或脑转移病灶扩大的证据且入组前至少3天以上未使用激素。初治的无症状脑转移患者需定期接受脑部影像学检查。结果共纳入1298例患者,其中171例有基线脑转移,1127例无脑转移。两组的中位随访时间(范围)在数据截止时分别为10.9(0.1-35.1)个月和11.0(0.1-34.9)个月。合并脑转移和无脑转移患者的总生存期[0.48(95%CI:0.32-0.70)和0.63(95%CI:0.53-0.75)]和无进展生存期[0.44(95%CI:0.31-0.62)和0.55(95%CI:0.48-0.63)]的风险比(PC/化疗)相似。合并脑转移的患者中,PC组和单用化疗组患者的中位总生存期分别为18.8个月和7.6个月,中位无进展生存期分别为6.9个月和4.1个月。无论是否合并脑转移,PC组患者的客观缓解率都高于单用化疗组,且缓解持续时间有显著延长。合并脑转移的患者中,PC组与单用化疗组的治疗相关不良事件发生率分别为88.2%和82.8%;而无脑转移的患者中,两组治疗相关不良事件的发生率分别为94.5%和90.6%。结论无论是否合并脑转移,与单用化疗相比,帕博利珠单抗联合以铂类为基础的组织学特异性化疗可改善所有PD-L1亚组的临床结局,其中包括PD-L1肿瘤比例评分<1%的患者,并且在晚期NSCLC患者中安全性良好。该方案是晚期NSCLC初治患者的标准方案,并可用于合并稳定性脑转移的患者。 | 周清(翻译校对) Steven F Powell Delvys Rodríguez-Abreu Corey J Langer Ali Tafreshi Luis Paz-Ares Hans-Georg Kopp Jeronimo Rodríguez-Cid Dariusz M Kowalski Ying Cheng Takayasu Kurata Mark M Awad Jinaxin Lin Bin Zhao M Catherine Pietanza Bilal Piperdi Marina C Garassino | 2022 | 中国肺癌杂志2022，25，1： | 6 |
| 2 | Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial显示文摘 | JY Douillard D Cunningham AD Roth M Navarro RD James P Karasek P Jandik T Iveson J Carmichael M Alakl G Gruia L Awad P Rougier | 2000 | The Lancet2000，，9209： | 4 |
| 3 | Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice显示文摘Stress during prenatal development is correlated with detrimental cognitive and behavioral outcomes in offspring. However, the long-term impact of prenatal stress(PS) and disrupted glucocorticoid signaling on bone mass and strength is not understood. In contrast, the detrimental effect of lead(Pb) on skeletal health is well documented. As stress and Pb act on common biological targets via glucocorticoid signaling pathways and co-occur in the environment, this study first sought to assess the combined effect of stress and Pb on bone quality in association with alterations in glucocorticoid signaling. Bone parameters were evaluated using microCT, histomorphometry, and strength determination in 8-month-old male mouse offspring subjected to PS on gestational days 16 and 17, lifetime Pb exposure(100 p.p.m. Pb in drinking water), or to both. Pb reduced trabecular bone mass and, when combined with PS, Pb unmasked an exaggerated decrement in bone mass and tensile strength. Next, to characterize a mechanism of glucocorticoid effect on bone, prednisolone was implanted subcutaneously(controlled-release pellet, 5 mg·kg^(-1) per day) in 5-month-old mice that decreased osteoblastic activity and increased sclerostin and leptin levels. Furthermore, the synthetic glucocorticoid dexamethasone alters the anabolic Wnt signaling pathway. The Wnt pathway inhibitor sclerostin has several glucocorticoid response elements, and dexamethasone administration to osteoblastic cells induces sclerostin expression. Dexamethasone treatment of isolated bone marrow cells decreased bone nodule formation, whereas removal of sclerostin protected against this decrement in mineralization.Collectively, these findings suggest that bone loss associated with steroid-induced osteoporosis is a consequence of sclerostin-mediated restriction of Wnt signaling, which may mechanistically facilitate glucocorticoid toxicity in bone. | Eric E Beier Tzong-Jen Sheu Emily A Resseguie Masahiko Takahata Hani A Awad Deborah A Cory-Slechta J Edward Puzas | 2017 | Bone Research2017，5，2： | 3 |
| 4 | Expression of anglogenesis factors and selected vascular wall matrix proteins in intracranial saccular aneurysms 显示文摘 | Skirgaudas M Awad IA Kim J | 1996 | Neurosurgery1996，39，3： | 1 |
| 5 | Prolonged pumpless arteriovenous perfusion for carbon dioxide extraction显示文摘 | Deslauriers J Major D | 1991 | Ann Thorac Surg1991，51，： | 1 |
| 6 | Tuning Soft-ware Phase- locked Loop for Series-connected Converters 显示文摘 | AWAD H SVENSSON J BOLLEN M J | 2005 | IEEE Transactions on Power Delivery2005，21，1： | 1 |
| 7 | Ischemic preconditioning in immature myocardium 显示文摘 | Awad W I Shattock M J Chambers D J | 1998 | Circulation1998，98，11： | 1 |
| 8 | Spinal epidural hematoma causing acute cauda equina syndrome显示文摘 | Kebaish K M Awad J N | 2004 | Neurosurg Focus2004，16，6： | 1 |
| 9 | Homozygous mutations in ARIX (PHOX2A) result in congenital fibrosis of the extraocular muscles type 2 显示文摘 | Nakano M Yamada K Fain J Sener EC Selleck CJ Awad AH | 2001 | Nature Genet2001，29，3： | 1 |
| 10 | Effectiveness and complications of mitomycin C use during pediatric glaucoma surgery 显示文摘 | A1 - Hazmi A Zwaan J Awad A | 1998 | Ophthalmology1998，105，10： | 1 |
| 11 | The safety and efficacy of combined phacoemulsification and trabeculec- tomy with releasable sutures显示文摘 | Stark W J Goyal R K Awad O | 2006 | Br J Ophthalmol2006，90，2： | 1 |
| 12 | Intractable epilepsy and structural lesions of the brain, mapping, resection strategies, and seizure outcome显示文摘 | Awad IA Rosenfeid J Ahl J et sl | 1991 | Epilepsia1991，32，： | 1 |
| 13 | Analysis of the risk factors for the development of post-operative spinal epidural haematoma显示文摘 | Awad K N Kebaish K M Donigan J | 2005 | J Bone Joint Surg Br2005，87，9： | 1 |
| 14 | Tuning software phase-locked loop for series-connectedconverters显示文摘 | Awad Hilmy Svensson Jan Bollen M J | 2005 | IEEE Transactions on Power Delivery2005，20，1： | 1 |
| 15 | Expermental measure ment of the vortex development downstream of a lobed forced mixer显示文摘 | Eckerie W A Sheibani H Awad J | 1992 | Journal of Engineering for Gas Turbines and Power1992，114，1： | 1 |
| 16 | Orthodromic median and ulnar fourth digit sensory conductions in mild carpal tunnel syndrome显示文摘 | Uncini A Di Muzio A Cutarella R Awad J Gambi D | 1990 | Neurophysiol Clin1990，20，1： | 1 |
| 17 | Effects of luminal deoxynivalenol and L-proline on eleetrophysiologieal parameters in the jejunums of lay- ing hens 显示文摘 | Awad W A Rehman H Bohm J | 2005 | Poultry Science2005，84，6： | 1 |
| 18 | Experimental measurement of the vortex development downstream of a lobed forced mixer 显示文摘 | Eckerle J K Sheibani H Awad J | 1992 | ASME Journal of Engineering for Gas Turbines and Power1992，114，： | 1 |
| 19 | Ischemic preconditioning: a protential role for constitutive low molular weight stress protein translation phosphorylation显示文摘 | Eata P Awad W Miller J | 2000 | J Mol Cell Cardiol2000，32，： | 1 |
| 20 | Preliminary studies of a newly developed subunit vaccine for channel cat- fish virus disease 显示文摘 | AWAD M A NUSBAUM K E BRADY Y J | 1989 | Journal of Aquatic Animal Health1989，1，7： | 1 |
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