阿帕替尼对卵巢癌术后复发铂类耐药的影响

目的 探讨阿帕替尼治疗卵巢癌术后复发铂类耐药的临床价值.方法 选择2017年10月至2019年3月期间邢台市人民医院66例卵巢癌术后复发铂类耐药的病人作为研究对象,采用随机数字表法分为阿帕替尼联合化疗组、化疗组及阿帕替尼单药组,各22例.其中联合化疗组给予阿帕替尼+多西他赛(或吉西他滨)治疗,4个周期后阿帕替尼单药维持...     

Parp inhibitors as maintenance treatment in platinum sensitive recurrent ovarian cancer: An updated meta-analysis of randomized clinical trials according to BRCA mutational status

ObjectiveThis meta-analysis investigated the effectiveness of PARP inhibitors (PARPis) as maintenance treatment in platinum sensitive recurrent ovarian cancer (ROC), stratifying results based on BRCA mutational status into five different categories: whole population, germ-line BRCA mutated patients, somatic BRCA mutated patients, HRD patients and wild type population.MethodsPubMed, Medline, Scopus, EMBASE and clinicaltrials.gov, as well as meeting proceedings were searched for eligible studies that described RCTs testing the efficacy of PARPis as maintenance treatment in platinum sensitive ROC. Data were extracted independently and analysed using RevMan statistical software version 5.3. Primary end-point was progression free survival (PFS).ResultsThe analysis confirmed the positive effect of PARPis in patients with platinum sensitive ROC in case of germinal or somatic BRCA mutations. Specifically, HR for PFS was 0.26, 95% CI 0.21–0.31, p < 0.00001 for the mutation of BRCA gene and 0.24, 95%, CI 0.12–0.48, p < 0.0001 for the somatic alteration. In addition, in the HRD population, studies that analysed the efficacy of PARPis  reported a PFS improvement with HR 0.34, 95% CI 0.26–0.43, p < 0.00001. Finally, our analysis confirms the role of these drugs in prolonging PFS in the whole population with HR 0.36, 95% CI 0.32–0.42, p < 0.00001, although to a lesser extent, with a significant improvement even in wild type cancers with HR 0.49, 95%, CI 0.41–0.59, p < 0.00001).ConclusionsPARPis are effective regardless of BRCA mutational status. Future investigations are necessary to explore the use of different PARPis as monotherapy, comparing them among each other in terms of efficacy and toxicity, and exploring their potential re-use.     

Efficacy and Safety of Carboplatin Plus Paclitaxel as the First-, Second-, and Third-line Chemotherapy in Men With Castration-resistant Prostate Cancer

IntroductionCarboplatin and paclitaxel (CP) had shown moderate efficacy in treating castration-resistant prostate cancer (CRPC) before standard first-line docetaxel chemotherapy became available. Currently, for patients with homology-directed repair gene defects as well as for unselected patients, platinum chemotherapy is administered after all standard treatments have been ineffective. Here, we retrospectively studied the efficacy and safety of CP administered as the first-, second-, and third-line chemotherapy in patients with CRPC.Patients and MethodsA retrospective chart review was performed for 58 patients with CRPC who received CP between 2001 and 2018 in a single institution. Twenty-seven patients received CP as the first-line chemotherapy, 21 as the second-line after docetaxel, and 10 as the third-line after docetaxel and cabazitaxel. Prostate-specific antigen (PSA) responses (> 50% decline of PSA from baseline), progression-free survival, overall survival, and adverse events were examined.ResultsPSA responses at any time were 55.6%, 19.0%, and 10.0%; PSA responses at 12 weeks were 48.1%, 14.3%, and 10.0%; the median progression-free survival was 3, 1, and 1 month; and the median overall survival was 19, 11, and 6 months, respectively, for the first-, second-, and third-line settings. The only patient who achieved exceptional and durable PSA response in the third-line setting had a deleterious germline BRCA2 mutation (5645C>A). The adverse event profile was favorable.ConclusionCP shows moderate efficacy against CRPC in the first-line setting, but shows little effect in the third-line setting. CP after docetaxel and cabazitaxel may be recommended in selected patients with CRPC with homology-directed repair gene defects.     

铂金弹簧圈与 HydroCoil 治疗未破裂颅内动脉瘤的疗效比较

目的 评价铂金弹簧圈与 HydroCoil 治疗未破裂颅内动脉瘤的疗效。方法 选择2011年4月～2015年4月在本院就诊的未破裂脑动脉瘤患者78例,随机分为水凝胶弹簧圈(HES)组40例和铂金弹簧圈(BPC)组38例,分别采用HES和BPC进行血管栓塞术,评价2组术后动脉瘤栓塞程度、栓塞密度弹簧圈使用数量和12个月后动脉瘤复发情况,并记录相关并发症。结果 HES组和BPC组完全栓塞率分别为84.21%(32/38)和75.00%(30/40),栓塞密度为0.329±0.143和0.668±0.227,组间比较均无明显差异(P>0.05); HES组达到完全栓塞所需要的弹簧圈少于BPC组(P<0.05); 2组并发症发生率分别为13.16%(5/38)和5.00%(2/40),组间比较无明显差异(χ²=1.588,P=0.208); 随访12个月后2组分别有35例和37例患者完成随访,复发率为14.29%(5/35)和18.92%(7/37),组间比较无明显差异(P>0.05); logistic回归分析表明只有血管瘤直径是复发的独立相关因素(P<0.05)。结论 HES治疗未破裂脑动脉瘤的完全栓塞率和远期复发率不能优于BPC组,而且价格高于BPC,不推荐HES作为首选方法。     

Interleukins as new prognostic genetic biomarkers in non-small cell lung cancer

Background

Surgery is the standard treatment for early-stage NSCLC, and platinum-based chemotherapy remains as the treatment of choice for advanced-stage NSCLC patients with naïve EGFR status. However, overall 5-years relative survival rates are low. Interleukins (ILs) are crucial for processes associated with tumor development. In NSCLC, IL1B, IL6, IL12A, IL13 and IL16 gene polymorphisms may contribute to individual variation in terms of patient survival. The purpose of this study was to evaluate the association between IL gene polymorphisms and survival in NSCLC patients.

晚期非小细胞肺癌中SOD2基因多态性与含铂方案化疗敏感性的研究

目的 探讨超氧化物歧化酶2（SOD2）基因多态性与晚期非小细胞肺癌（NSCLC）患者含铂方案化疗疗效的关系。方法 采用直接测序法检测162例以含铂方案化疗的晚期NSCLC患者外周血DNA中SOD2 rs7855、rs5746151、rs5746136、rs2758331和rs4880的基因多态性;162例患者中,43例接受多西他赛联合顺铂方案,63例接受吉西他滨联合顺铂方案,56例接受培美曲塞联合顺铂方案化疗,2个周期后采用RECIST 1.0版标准评价疗效并将患者分为化疗敏感组（CR+PR）和不敏感组（SD+PD）,分析疗效与临床病理特征及以上多态性位点的关系。结果 162例晚期NSCLC患者SOD2 rs7855、rs5746151、rs5746136、rs2758331和rs4880位点基因型频率均符合Hardy-Weinberg平衡（P>0.05）。162例患者经2个周期化疗后,获PR 43例、SD 68例、PD 51例,分为化疗敏感组43例和不敏感组119例,化疗敏感率为265%。年龄、性别、病理类型、分期、ECOG评分和化疗方案与化疗敏感性均无关。SOD2 rs7855、rs5746151、rs5746136和rs2758331位点中,各基因型及等位基因化疗敏感率的差异无统计学意义,且突变型等位基因相对于野生型等位基因及携带突变等位基因的基因型相对于野生型纯合子化疗不敏感的风险未升高（P>0.05）;SOD2 rs4880 TT、TC、CC基因型的敏感率依次为42.1%、19.6%和16.7%,差异有统计学意义（P<0.05）;T、C等位基因的敏感率分别为35.2%和17.6%,差异有统计学意义（P<0.05）;以野生型TT型为参照,TC、CC基因型化疗不敏感的风险升高,且C等位基因相对于T等位基因化疗不敏感的风险亦升高,差异均有统计学意义（P<0.05）。 结论 SOD2 rs4880多态性与晚期NSCLC患者含铂方案的疗效有关,且携带突变等位基因者化疗不敏感的风险较高,SOD2 rs4880多态性可用于预测晚期NSCLC患者对含铂方案的疗效。     

ERCC1在局部区域晚期鼻咽癌中的表达及临床意义

目的 探讨核苷酸切除修复交叉互补基因1（excision repair cross complementing 1,ERCC1）在局部区域晚期鼻咽癌（nasopharyngeal carcinoma,NPC）组织中的表达及其临床意义。方法 收集2013年1月至2015年6月收治的以接受顺铂为基础化疗的102例局部区域晚期NPC癌组织标本作为观察组,同时选取其中31例局部区域晚期NPC癌旁上皮组织为对照组。采用免疫组化法检测两组组织中ERCC1的表达,并分析ERCC1表达与局部区域晚期NPC患者临床病理参数及化疗疗效的关系。结果 观察组和对照组ERCC1的阳性表达率分别为62.7%和90.3%,差异有统计学意义（P<0.05）。ERCC1表达与局部区域晚期NPC患者年龄有关（P<0.05）,与性别、T分期、N分期无关（P>0.05）。ERCC1表达阳性的患者化疗有效率为35.9%,ERCC1表达阴性患者为63.2%,差异有统计学意义（P＝0.019）。结论 ERCC1在局部区域晚期鼻咽癌癌组织中低表达,ERCC1表达与化疗疗效呈负相关,检测ERCC1有助于预测局部区域晚期NPC患者对顺铂化疗的敏感性。     

Synthesis of 4-aminoquinoline analogues and their platinum(II) complexes as new antileishmanial and antitubercular agents

A series of 4-amino-7-chloroquinoline derivatives were synthesized by the reaction of 4,7-dichloro-quinoline with the corresponding diamine and then with propargyl bromide. In addition, platinum(II) complexes were obtained by reacting some of the organic derivatives with K₂PtCl₄. Several of the synthesized compounds displayed antituberculosis activities. Compound 3 was 47.5 times more active than amphotericin B against Leishmania chagasi (IC₅₀ = 0.04 μg/mL). Compounds 5, 6, 7, 9, 10, 11 and 13 presented promising results against Mycobacterium tuberculosis, with MIC values ranging from 12.5 to 15.6 μg/mL, comparable to the “first and second line” drugs used to treat tuberculosis.     

用于脑动脉瘤血管内栓塞治疗的涂层弹簧圈

自电解可脱性弹簧圈应用于临床以来,脑动脉瘤的血管内栓塞治疗被越来越多的医生和患者所接受.然而,相对较高的复发率仍然是介入治疗中引人关注的问题.新型弹簧圈的研发和应用已取得一定的进展.文章综述了新型涂层弹簧圈及其临床应用进展.     

ERCC1codon118基因表达对预测三代含铂方案治疗晚期非小细胞肺癌疗效的影响

目的探讨ERCClcodon118基因表达对预测三代含铂方案治疗晚期非小细胞肺癌疗效的影响。方法对240例晚期非小细胞肺癌患者进行ERCClcodon118基因多样性检测,并对各基因型对三代含铂方案治疗晚期非小细胞肺癌疗效进行比较。结果C／C型组与C／T型组＋T／T型组患者的肿瘤分化程度、临床分期、肿瘤大小、血管侵犯等基本资料无明显的相关性（P〉0．05）。C／C型组患者的无进展生存时间为（13．2±5．4）个月,生存时间为（25．4±4．3）个月,1年、2年和3年生存率分别为62．9％、23．5％和14．4％;C／T型＋T／T型组患者无进展生存时间和生存时间分别为（6．2±4．3）个月和（10．5±3．2）个月,其1、2和3年生存率分别为26．9％、8．3％和1．9％。结论ERCClcodon118基因表达可能与预测三代含铂方案治疗晚期非小细胞肺癌敏感性有关。