至2002年2月,有关晚期卵巢癌的手术治疗效果和细胞毒性化疗效果的临床证据如下:⑴在改进生活质量方面的任何治疗效果的证据都不充分. ⑵晚期卵巢癌的手术治疗: ①先行手术加化疗与单用化疗相比较:缺乏相关RCT. ②先行手术与不手术比较:缺乏相关RCT. ③在初次手术加化疗后一定间隔期的缩瘤术:1个RCT发现,初次手术加化疗后一定间隔期的缩瘤术提高总的存活年限为3.5年;另1个RCT则认为该方法对存活率没有显著性作用,但可能系检验效能不够而没有发现潜在的临床重要作用. ④常规二次手术:2个RCT认为,在晚期卵巢癌初次手术后常规进行二探手术的存活率并不优于术后只进行化疗的对照组. ⑶晚期卵巢癌的细胞毒性药物化疗: ①铂剂+紫杉醇方案:1篇系统评价和另1个RCT认为,晚期卵巢癌初次手术后,以铂剂+紫杉醇为基础的化疗能延长存活时间和总存活率. ②含铂剂的化疗方案:1篇系统评价发现,铂剂加入任何不含铂剂的方案都能显著提高存活率,尤其是铂剂加入联合治疗方案. ③卡铂+紫杉醇与卡铂+多烯紫杉醇比较:未找到比较这两种方案疗效的高质量RCT. ④含铂剂的联合方案与不含铂剂的联合方案比较:7个RCT比较了这两种方案;大多数RCT发现含铂剂的方案能改善结局,其益处和危害依赖于具体方案;没有研究显示铂剂能显著减少存活时间和总存活率. ⑤联用铂剂与单用铂剂比较:1篇系统评价和另3个RCT认为没有证据表明,延长存活时间和总存活率上,联用铂剂优于单用铂剂. ⑥紫杉醇+顺铂与紫杉醇+卡铂比较:1个RCT表明在延长存活时间和总存活率上两者无显著性差异,虽然不足以排除临床上的重要作用.
Extracellular matrix (ECM) has been implicated in tumor progress and chemosensitivity. Ovarian cancer brings a great threat to the health of women with a significant feature of high mortality and poor prognosis. However, the potential significance of matrix stiffness in the pattern of long non-coding RNAs (lncRNAs) expression and ovarian cancer drug sensitivity is still largely unkown. Here, based on RNA-seq data of ovarian cancer cell cultured on substrates with different stiffness, we found that a great amount of lncRNAs were upregulated in stiff group, whereas SNHG8 was significantly downregulated, which was further verified in ovarian cancer cells cultured on polydimethylsiloxane (PDMS) hydrogel. Knockdown of SNHG8 led to an impaired efficiency of homologous repair, and decreased cellular sensitivity to both etoposide and cisplatin. Meanwhile, the results of the GEPIA analysis indicated that the expression of SNHG8 was significantly decreased in ovarian cancer tissues, which was negatively correlated with the overall survival of patients with ovarian cancer. In conclusion, matrix stiffening related lncRNA SNHG8 is closely related to chemosensitivity and prognosis of ovarian cancer, which might be a novel molecular marker for chemotherapy drug instruction and prognosis prediction.
Objective To use a meta-analysis method to establish quantitatively the association between the HER-2/neu gene amplification/enhanced protein expression status and the 5-year post-operative survival rate or median survival time in women with epithelial ovarian carcinoma. Methods We searched and screened Chinese and English literature published since 1989 to collect all retrospective cohort studies on the prognostic significance of HER-2/neu status in this population. The survival data were analyzed using Ludwig’s centered signed rank and the DerSimonian-Laird method. Results In total, 25 studies involving 3 251 patients were included. HER-2/neu was positive in 27.1% (95%CI 0 to 54.8%) of patients, which was not related to the pathological stage, type or grade of epithelial ovarian carcinoma. In HER-2/neu positive cases, the median survival time was shortened by 0.65 years, and the 5-year survival rate was lowered. The hazard ratio (HR) for mortality was 1.22 (95%C 1.09 to 1.36). By subgroup analysis, HER-2/neu protein expression was found to be most significant in prognostic assessment. Patients with a b positive value of HER-2/neu had an increased HR for the 5-year survival; and platinum-based chemotherapy was demonstrated to be less effective in HER-2/neu positive ovarian carcinoma. Conclusion In gynecological oncology, it is reasonable to measure HER-2/neu as a routine pathological marker to predict a patient’s prognosis and to determine the most appropriate adjuvant chemotherapy regimen.
【摘要】 目的 研究肿瘤坏死因子相关凋亡诱导配体（TRAIL）蛋白对SKOV3移植瘤细胞半胱天冬氨酸蛋白酶-3（Caspase-3）表达的影响及其与肿瘤细胞凋亡的关系。 方法 建立雌性裸小鼠SKOV3移植瘤24只，随机分为4组，每组6只。TRAIL组单用重组人TRAIL蛋白（10 μg/kg），顺铂（DDP）组单用DDP（3 mg/kg），TRAIL+DDP组联合使用TRAIL蛋白（10 μg/kg）和DDP（3 mg/kg），空白对照组给予0.5 mL生理盐水。经处理后，各组的组织切片用免疫组织化学染色检测Caspase-3的表达和末端脱氧核苷酸转移酶介导核苷酸缺口标记技术（TUNEL）检测肿瘤细胞凋亡指数。 结果 Caspase-3的表达水平在TRAIL组（171.67±14.38）、DDP组（172.50±14.75）、联合组（230.00±40.99）中均明显高于对照组（135.83±16.25）（Plt;0.05）。SKOV3移植瘤细胞凋亡指数在空白对照组、TRAIL组、DDP组和联合组分别为16.67±5.43、33.17±8.42、24.33±4.59和40.50±6.16，TRAIL组和联合组细胞凋亡指数较空白对照组和DDP组明显增高（Plt;0.05）。 结论 TRAIL蛋白使卵巢癌移植瘤细胞的Caspase-3表达增强，TRAIL蛋白促进肿瘤细胞凋亡发生。【Abstract】 Objective To investigate the effects of Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) on the expression of Cysteine/aspartic acid specific protease- 3 (Caspase-3) in SKOV3 ovarian tumor cells and its relationship with the apoptosis of the ovarian tumor xenografts in nude mice. Methods Twenty-four nude mice with SKOV3 cell line ovarian tumor were randomly divided into four groups with 6 in each group. TRAIL (10 μg/kg) was given to the mice in the TRAIL group; DDP (3 μg/kg) was given to the mice in the DDP group; TRAIL (10 μg/kg) and DDP (3 μg/kg) were given to the mice in the TRAIL+DDP group; and 0.5 mL of saline solution was give to the mice in the control group. The expression of Caspase-3 was detected with immunohistochemistry. The apoptosis index (AI) of cells was determined by Terminal deoxynucleotidyl transferase mediated-dUTP nick end labeling (TUNEL). Results The expression of Caspase-3 in the TRAIL group (171.67±14.38), DDP group (172.50±14.75), and TRAIL+DDP group (230.00±40.99) was significantly higher than that in the control group (135.83±16.25) (Plt;0.05). The apoptosis index for the control group, TRAIL group, DDP group and TRAIL+DDP group was 16.67±5.43, 33.17±8.42, 24.33±4.59, and 40.50±6.16, respectively. The apoptosis index for the TRAIL group and the TRAIL+DDP group was significantly higher than that in the control group and the DDP group (Plt;0.05). Conclusion Soluble TRAIL has an effect on enhancing the expression of Caspase-3 in implanted tumor in nude mice. TRAIL protein can inhibit the growth of SKOV3 cells in nude mice by inducing cell apoptosis.
Objective To assess the clinical effectiveness and safety of paclitaxel liposomes and carboplatin for ovarian cancer. Methods The databases such as The Cochrane Library, PubMed, EMBASE, CNKI and CBM were searched to collect all randomized control trials (RCTs) about the clinical effectiveness and safety of paclitaxel liposomes and carboplatin for ovarian cancer. Literatures were screened according to the inclusive and exclusive criteria, the data were extracted, the methodological quality of the included studies was assessed in line with Cochrane Handbook 5.0.1, and Meta-analysis was performed by using RevMan 5.0.24 software. Results Three RCTs involving 214 patients were included. Meta-analysis showed that compared with the paclitaxel plus carboplatin group, the paclitaxel liposomes plus carboplatin group didn’t show significant differences in the total effective rate (P=0.62), while it was obviously superior in reducing the adverse events, such as muscle and joint pain (Plt;0.000 01), peripheral neurotoxicity (P=0.04), nausea or vomiting (P=0.000 2), facial blushing (P=0.03) and rashes (P=0.003). But there were no significant differences between the two groups in trichomadesis, dyspnea, diarrhea, bellyache and blood system abnormalities. Conclusion As current clinical evidences shows, the paclitaxel liposomes and carboplatin in treating ovarian cancer is as effective as the paclitaxel and carboplatin, and it can reduce some of the adverse reactions. Therefore, the paclitaxel liposomes and carboplatin is available for ovarian cancer as a new, safe and effective treatment. Due to small scale and low quality of the included studies, this conclusion has to be further proved with more high-quality, large-scale, and double-blind RCTs.
Objective To estimate the diagnostic value of mesothelin in ovarian cancer. Methods PubMed, The Cochrane Library, CBM, CNKI and WanFang Data databases were searched from inception to October 2016 to collect relevant diagnostic accuracy studies of mesothelin in ovarian cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Statistical analysis was performed using Meta-Disc 1.4, Stata 12.0 and RevMan 5.2 softwares. The pooled sensitivity, specificity and diagnostic odds ratio were calculated, the summary receiver operating characteristic curve (SROC) was drawn and the area under the curve (AUC) was calculated. Results Seventeen studies involving 2 052 patients were included. The pooled sensitivity, specificity, DOR were 0.63 (95%CI 0.60 to 0.67), 0.92 (95%CI 0.90 to 0.93) and 26.62 (95%CI 14.96 to 47.38), respectively. The AUC and Q index were 0.915 1 and 0.847 8, respectively. Conclusion The current evidence indicates that mesothelin has high specificity and low sensitivity, which can’t be used alone as a biomarker for the detection of ovarian cancer, but should be combined with other biomarkers.
ObjectiveTo systematiclly review the correlation between physical activity and the risk of ovarian cancer. MethodsSuch databases as CBM, CNKI, WanFang Data, VIP, The Cochrane Library (Issue 10, 2013), PubMed, EMbase were searched from database establishment to October 2013 to collect prospective cohort studies about physical activities and the risk of ovarian cancer. Relevant magazines and references of included studies were also retrieved. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies. Then meta-analysis was performed using RevMan 5.2 software. ResultsA total of 8 cohort studies involving 580 581 subjects, of which there were 2 444 cases of patients with ovarian cancer. The results of meta-analysis showed that, women who participated in moderate level physical activities tended to have a lower incidence of ovarian cancer, compared with those who participated in low level physical activities (age-adjusted:RR=0.87, 95%CI 0.75 to 1.01, P=0.06; multivariate-adjusted:RR=0.97, 95%CI 0.83 to 1.14, P=0.71) but with no significant difference; while women who participated in high level physical activities tended to have a higher incidence of ovarian cancer with a significant difference found in the multivariate-adjusted results (age-adjusted:RR=1.19, 95%CI 0.91 to 1.56, P=0.21; multivariate-adjusted:RR=1.35, 95%CI 1.08 to 1.67, P=0.008). Along with the increase of sedentariness, the incidence of ovarian cancer rose, but with no significant difference. ConclusionCurrent evidence shows that, compared with low level physical activities, high level ones increase the risk of ovarian caner; while the effects of moderate level ones and sedentariness on the risk of ovarian caner still remain uncertain. However, more high-quality studies are required to verify the conclusion of this study because of the limited quantity of the included studies as well as many confounding factors.