Rucaparib in the landscape of PARP inhibition in ovarian cancer

Introduction: The landscape of poly (ADP-ribose) polymerase (PARP) inhibition in ovarian cancer is rapidly evolving and becoming increasingly complex. Ovarian cancer is leading therapeutic innovation by providing the proof of concept for DNA repair as a target. Three different PARP inhibitors have now received approvals in the US and Europe in different indications. Subtle but crucial differences can be found among the licensed indications for each PARP inhibitor in terms of histology, type of BRCA mutation (germline and/or somatic), number of prior lines of chemotherapy and whether the indication is in the treatment or maintenance settings.

Areas covered: We review the latest clinical data regarding the PARP inhibitor rucaparib in ovarian cancer, provide an update on the evolving landscape of PARP inhibition in ovarian cancer, and summarize avenues of ongoing and future research.

Expert opinion: All eligible patients should be offered a PARP inhibitor. SOLO1 trial results demonstrated an unprecedented benefit maintenance with PARP inhibitors in first line. Results from trials evaluating PARP inhibitors as maintenance in first line regardless of BRCA status and from trials evaluating combinatorial strategies are eagerly awaited.     

“阳化气，阴成形”：卵巢癌的中医证治

卵巢癌属于妇科恶性肿瘤之一,其发病率逐年上升趋势,属中医的"癥瘕"范畴。秉承《素问》"阳化气,阴成形"之旨来探讨卵巢癌的病机及治疗,认为"阳化气"不足,"阴成形"太过为卵巢癌发病的一个重要原因,并由此提出温补阳气的卵巢癌治疗原则,指出该原则应贯穿整个卵巢癌治疗的始终。     

Recurrent BRCA1 Mutation,but no BRCA2 Mutation,in Vietnamese Patients with Ovarian Carcinoma Detected with Next Generation Sequencing

Background: Identification of germline and somatic BRCA1/2 mutations in ovarian cancer is important for genetic counseling and treatment decision making with poly ADP ribose polymerase inhibitors. Unfortunately, data on the frequency of BRCA1/2 mutations in Vietnamese patients are scare. Methods: We aim to explore the occurrence of BRCA1/2 mutations in 101 Vietnamese patients with ovarian cancer including serous (n = 58), endometrioid (n = 14), mucinous (n = 24), and clear cell (n = 5) carcinomas. BRCA1/2 mutations were detected from formalin-fixed parafin-embedded tumor samples using the OncomineTM BRCA Research Assay on Personal Genome Machine Platform with Ion Reporter Software for sequencing data analysis. The presence of pathogenic mutations was confirmed by Sanger sequencing. Results: We found no BRCA2 mutation in the entire cohort. Four types of pathogenic mutations in BRCA1 (Ser454Ter, Gln541Ter, Arg1751Ter, and Gln1779AsnfsTer14) were detected in 8 unrelated patients (7.9%) belonging to serous and endometrioid carcinoma groups. Except for the c.1360_1361delAG (Ser454Ter) mutation in BRCA1 exon 11 that was somatic, the other mutations in exons 11, 20, and 22 were germline.  Interestingly, the recurrent Arg1751Ter mutation in BRCA1 exon 20 appeared in 4 patients, suggesting that this is a founder mutation in Vietnamese patients. Conclusion: Mutational analysis of tumor tissue using next generation sequencing allowed the detection of both germline and somatic BRCA1/2 mutations.     

miR-590-5p介导lncRNA SNHG1信号影响卵巢癌细胞增殖的实验研究

目的:探讨miR-590-5p在卵巢癌组织中的表达情况以及其对卵巢癌细胞增殖的影响及作用机制。方法:Real-time PCR和双荧光素酶实验确定miR-590-5p与lncRNA SNHG1之间的调控作用。Real-time PCR检测卵巢癌、癌旁组织以及卵巢癌细胞中miR-590-5p的表达。分别采用NC mimic或者miR-590-5p mimic转染两株卵巢癌细胞，CCK-8检测各组细胞的增殖情况。此外，Real-time PCR检测两株细胞中SOX2、RECK和YAP1的表达。结果:Real-time PCR结果显示下调SNHG1后miR-590-5p的表达显著升高。双荧光素酶结果显示转染miR-590-5p mimic和野生型SNHG1片段的细胞中荧光素酶的活性显著降低。此外，Real-time PCR结果显示miR-590-5p在卵巢癌组织中的表达水平显著低于癌旁组织。CaOV3、OV-90细胞中miR-590-5p的表达水平明显低于其他卵巢癌细胞。转染miR-590-5p mimic显著上调了CaOV3、OV-90细胞中miR-590-5p的表达并且抑制了这两株细胞的增殖，同时抑制了两株细胞中SOX2、RECK和YAP1的表达。结论:miR-590-5p的低表达与卵巢癌的进展密切相关，miR-590-5p能够介导SNHG1信号并且通过对其下游靶基因的调控抑制卵巢癌细胞的增殖。     

PEG-rhG-CSF预防卵巢癌、宫颈癌化疗中性粒细胞缺乏的临床研究

目的:探讨应用聚乙二醇化重组人粒细胞集落刺激因子(PEG-rhG-CSF)对卵巢癌、宫颈癌化疗患者粒细胞减少的影响，并观察不良反应。方法:选择本院2015年4月至2017年6月卵巢癌、宫颈癌患者136例，随机分为对照组（68例）和研究组（68例），对照组应用rhG-CSF，研究组应用PEG-rhG-CSF，两组均化疗两个周期，评估患者两个周期不同时间血常规绝对中性粒细胞计数值（ANC）水平、ANC不同数量发生率和持续时间以及不良反应。结果:研究组患者第一个化疗周期第5 d、第7 d、第10 d和第14 d 及第二个化疗周期第3 d、第5 d、第7 d、第10 d和第14 d血ANC分别为（3.19±0.32）×109/L、（1.93±0.35）×109/L、（2.08±0.39）×109/L、（2.11±0.36）×109/L和（2.79±0.40）×109/L、（2.44±0.33）×109/L、（1.68±0.34）×109/L、（1.71±0.37）×109/L、（1.92±0.34）×109/L，均高于对照组，差异具有统计学意义(P＜0.05)。研究组患者第一个和第二个化疗周期ANC＜1.5×109/L、ANC＜1.0×109/L和ANC＜0.5×109/L发生率分别为23.53%（16/68）、8.82%（6/68）、2.94%（2/68）和29.41%（20/68）、10.29%（7/68）、5.88%（4/68），均低于对照组，差异具有统计学意义(P＜0.05)。研究组患者第一个和第二个化疗周期ANC＜1.5×109/L、ANC＜1.0×109/L和ANC＜0.5×109/L持续时间分别为（3.50±0.18）d、（2.17±0.23)d、（2.06±0.29）d和（4.08±0.22）d、（4.62±0.29）d、（4.11±0.24）d，均短于对照组，差异具有统计学意义(P＜0.05)。研究组中、重度不良反应总发生率为10.29%（7/68），低于对照组23.53%（16/68），差异有统计学意义(P＜0.05)。结论:应用PEG-rhG-CSF能够有效预防卵巢癌、宫颈癌化疗患者粒细胞减少，不良反应显著降低，值得临床推广应用。     

E-cadherin在妇科三大恶性肿瘤中表达的意义及研究进展

E-钙黏蛋白（E-cadherin）是一种主要存在于人和动物上皮的黏附分子，主要功能是维持正常上皮细胞形态和结构完整性。现已在多种肿瘤研究中发现，E-cadherin表达的下调，极易造成肿瘤细胞向外周组织发生浸润和远端转移，但与E-cadherin相关研究在妇科恶性肿瘤中进展缓慢，E-cadherin在子宫内膜癌、卵巢癌和宫颈癌病变过程的调控机制尚不完全清楚，而且肿瘤的发生和发展是多因素作用的过程，需要进一步加强研究，该文章就 E-cadherin在妇科三大妇科恶性肿瘤中表达的意义及研究进展进行综述。     

D-二聚体和中性粒细胞/淋巴细胞比值评估卵巢癌预后的临床价值

目的:研究D-二聚体（D-dimer,D-D）和中性粒细胞/淋巴细胞比值（neutrophil to lymphocyte ratio,NLR）与卵巢癌临床病理特征及预后的关系。方法:回顾性分析2012年1月至2015年12月于我院妇科行手术治疗的卵巢恶性肿瘤患者387例和卵巢良性肿瘤患者250例临床资料。比较血清D-D和外周血NLR在卵巢良、恶性肿瘤中的表达水平；确定D-D和NLR临界值，D-D+NLR=0（D-D≤0.555 mg/L和NLR≤2.792）,D-D+NLR=1（D-D>0.555 mg/L或NLR>2.792），D-D+NLR=2（D-D>0.555 mg/L和NLR>2.792），分析两者联合的评分系统与卵巢癌临床病理特征和预后的关系。结果:血清D-D和外周血NLR在卵巢良、恶性肿瘤患者中的表达水平有统计学差异（P＜0.001）。D-D高水平组与低水平组相比，患者的分期、分级、淋巴结转移、腹水、CA125水平、残余瘤大小有统计学差异（P＜0.05）。NLR高水平组与低水平组相比，患者的年龄、分期、淋巴结转移、腹水、CA125水平、残余瘤大小有统计学差异（P＜0.05）。D-D+NLR为0、1、2分的平均总生存期（OS）分别为70个月、58个月、40个月。D-D+NLR评分是影响OS的独立预后因素。结论:术前血清D-D和外周血NLR与卵巢癌临床病理特征和OS相关，D-D+NLR评分可以作为评估卵巢癌预后的指标。     

从湿论治慢性静脉功能不全刍见

慢性静脉功能不全是常见的周围血管疾病。文章在梳理历代中医辨证思路的基础上,结合现代医学的认识和临床观察,分别从湿的来源、湿在慢性功能不全疾病中的具体体现和治疗3个方面来探讨本类疾病与湿的关系。认为湿作为本病的重要致病因素和病理产物,贯穿于本病的始终,与本病的形成密不可分,在治疗上应注重对湿的辨析,明确其性质、来源、病证特点等,选用多法以祛湿。     

Analysis of early mortality and related risk factors in maintenance hemodialysis patients

Objective To analyze the early mortality and related risk factors of new hemodialysis patients in Zhejiang province, and provide basis for reducing the death risk of hemodialysis patients. Methods The early mortality and related factors of new hemodialysis patients from January 1, 2010 to June 30, 2018 were retrospectively analyzed using the database of Zhejiang province hemodialysis registration. The early mortality was defined as death within 90 days of dialysis. Cox regression model was used to analyze the related risk factors of the early mortality in hemodialysis patients. Results The mortality was the highest in the first month after dialysis (46.40/100 person year), and gradually stabilized after three months. The early mortality was 25.33/100 person year. The mortality within 120 days and 360 days were 21.40/100 person year and 11.37/100 person year, respectively. The elderly (≥65 years old, HR=1.981, 95%CI 1.319-2.977, P＜0.001), primary tumor (HR=3.308, 95%CI 1.137-5.624, P=0.028), combined with tumors (not including the primary tumor, HR=2.327, 95%CI 1.200-4.513, P=0.012), temporary catheter (the initial dialysis pathway, HR=3.632, 95%CI 1.806-7.307, P＜0.001), lower albumin (＜30 g/L, HR=2.181, 95%CI 1.459-3.260, P＜0.001), lower hemoglobin (every 0.01 g/L increase, HR=0.861, 95%CI 0.793-0.935, P=0.001), lower high density lipoprotein (＜0.7 mmol/L, HR=1.796, 95%CI 1.068-3.019, P=0.027) and higher C reactive protein (≥40 mg/L, HR=1.889, 95%CI 1.185-3.012, P=0.008) were the risk factors of early death for hemodialysis patients. Conclusions The early mortality of hemodialysis patients is high after dialysis, and gradually stable after 3 months. The elderly, primary tumor, combined with tumors, the initial dialysis pathway, lower albumin, lower hemoglobin, lower high density lipoprotein and higher C reactive protein are the risk factors of early death for hemodialysis patients.