【摘要】 目的 研究腫瘤壞死因子相關凋亡誘導配體（TRAIL）蛋白對SKOV3移植瘤細胞半胱天冬氨酸蛋白酶-3（Caspase-3）表達的影響及其與腫瘤細胞凋亡的關系。 方法 建立雌性裸小鼠SKOV3移植瘤24只，隨機分為4組，每組6只。TRAIL組單用重組人TRAIL蛋白（10 μg/kg），順鉑（DDP）組單用DDP（3 mg/kg），TRAIL+DDP組聯合使用TRAIL蛋白（10 μg/kg）和DDP（3 mg/kg），空白對照組給予0.5 mL生理鹽水。經處理后，各組的組織切片用免疫組織化學染色檢測Caspase-3的表達和末端脫氧核苷酸轉移酶介導核苷酸缺口標記技術（TUNEL）檢測腫瘤細胞凋亡指數。 結果 Caspase-3的表達水平在TRAIL組（171.67±14.38）、DDP組（172.50±14.75）、聯合組（230.00±40.99）中均明顯高于對照組（135.83±16.25）（Plt;0.05）。SKOV3移植瘤細胞凋亡指數在空白對照組、TRAIL組、DDP組和聯合組分別為16.67±5.43、33.17±8.42、24.33±4.59和40.50±6.16，TRAIL組和聯合組細胞凋亡指數較空白對照組和DDP組明顯增高（Plt;0.05）。 結論 TRAIL蛋白使卵巢癌移植瘤細胞的Caspase-3表達增強，TRAIL蛋白促進腫瘤細胞凋亡發生。【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.
ObjectiveTo systematically review the prognostic efficacy and safety of patients with ovarian cancer treated with systemic lymphadenectomy (SL). MethodsPubMed, The Cochrane Library, Web of Science, CNKI, WanFang Data, and CBM databases were electronically searched to collect randomized controlled trials (RCTs) and cohort studies on the prognostic outcomes of patients with ovarian cancer treated with SL from inception to December 16th, 2020. Six reviewers independently screened literature, extracted data, and assessed the risk of bias of included studies. Meta-analysis was then performed using RevMan 5.4 software. ResultsA total of 5 RCTs and 23 cohort studies involving 6 166 patients were included. The results of meta-analysis showed that there were no significant differences in the 3-year survival rate, 5-year survival rate, 3-year progression-free survival rate, and 5-year progression-free survival rate between SL group and the no systemic lymphadenectomy (NSL) group. The results of the subgroup analysis showed that pelvic and para-aortic lymph node dissection combined with large omentum resection had a better prognosis for patients. ConclusionsCurrent evidence shows that SL has no significant efficacy on survival and progression-free survival in patients with ovarian cancer. Due to limited quality and quantity of the included studies, more high-quality studies are required to verify the above conclusions.
ObjectiveTo systematically review the effectiveness and safety of intraperitoneal hyperthermic perfusion chemotherapy (IHPC) for ovarian cancer, so as to provide references for clinical practice and studies. MethodsWe electronically searched PubMed, EMbase, The Cochrane Library (Issue 6, 2013), Web of Science, WanFang Data, CBM, VIP and CNKI for randomized controlled trials (RCTs) about IHPC vs. intravenous chemotherapy (IC) for ovarian cancer from the inception of the databases to June 2013. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality. Then meta-analysis was performed using RevMan 5.1 software. ResultsA total of 10 RCTs involving 723 patients were included. The results of meta-analysis showed that the IHPC group was superior to the IC group in clinical efficiency (OR=4.02, 95%CI 2.85 to 5.68, P < 0.000 01), clinical benefit response (OR=3.41, 95%CI 2.13 to 5.45, P < 0.000 01), recurrence and metastasis rates (OR=0.29, 95%CI 0.20 to 0.42, P < 0.000 1), and overall survival rates (OR=3.30, 95%CI 1.82 to 5.99, P < 0.000 1). In the aspect of safety, no significant difference was found in bone marrow suppression, hemoglobin reduction, nausea and vomiting between two groups. ConclusionIHPC for ovarian cancer can improve clinical efficiency, clinical benefit response and overall survival rates, and reduce recurrence and metastasis rates; and it is also safe for patients.
Objective To systematically review the prognostic value of progesterone receptor (PR) for survival in ovarian cancer. Methods PubMed, EMbase, MEDLINE, The Cochrane Library (Issue 1, 2016), CNKI, VIP, CBM and WanFang Data databases were searched for cohort studies on the correlation between PR expression and prognosis of ovarian cancer from inception to June 1st 2016. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was performed by using RevMan 5.3 software. Results A total of 12 studies involving 1 881 patients were included. The results of meta-analysis showed that the PR positive patients was superior than the PR negative patients on overall survival (OS) (HR=0.64, 95%CI 0.44 to 0.93,P=0.02), disease free survival (DFS) (HR=0.64, 95%CI 0.48 to 0.85,P=0.002), progression free survival (PFS) (HR=0.62, 95%CI 0.47 to 0.82,P=0.000 9) and remission rate of chemotherapy (OR=1.91, 95%CI 1.28 to 2.86,P=0.002). When analysis based on the clinical pathogesis stages, PR expression was higher in clinical stages Ⅰ-Ⅱ than stage Ⅲ-Ⅳ (OR=2.38, 95%CI 1.71 to 3.32,P<0.000 01), and was higher in cell differentiation G1-G2 than G3 (OR=2.48, 95%CI 1.72 to 3.56,P<0.000 01), while no significant difference was found in groups of serous ovarian cancervs. non serous ovarian cancer (OR=1.28, 95%CI 0.89 to 1.83,P=0.18). Conclusion The current evidence shows that the expression of PR protein have predictive value for the prognosis of ovarian cancer. Due to limited quantity and quality of included studies, the above conclusions are still needed to verified by more high quality studies.
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.
至2002年2月,有關晚期卵巢癌的手術治療效果和細胞毒性化療效果的臨床證據如下:⑴在改進生活質量方面的任何治療效果的證據都不充分. ⑵晚期卵巢癌的手術治療: ①先行手術加化療與單用化療相比較:缺乏相關RCT. ②先行手術與不手術比較:缺乏相關RCT. ③在初次手術加化療后一定間隔期的縮瘤術:1個RCT發現,初次手術加化療后一定間隔期的縮瘤術提高總的存活年限為3.5年;另1個RCT則認為該方法對存活率沒有顯著性作用,但可能系檢驗效能不夠而沒有發現潛在的臨床重要作用. ④常規二次手術:2個RCT認為,在晚期卵巢癌初次手術后常規進行二探手術的存活率并不優于術后只進行化療的對照組. ⑶晚期卵巢癌的細胞毒性藥物化療: ①鉑劑+紫杉醇方案:1篇系統評價和另1個RCT認為,晚期卵巢癌初次手術后,以鉑劑+紫杉醇為基礎的化療能延長存活時間和總存活率. ②含鉑劑的化療方案:1篇系統評價發現,鉑劑加入任何不含鉑劑的方案都能顯著提高存活率,尤其是鉑劑加入聯合治療方案. ③卡鉑+紫杉醇與卡鉑+多烯紫杉醇比較:未找到比較這兩種方案療效的高質量RCT. ④含鉑劑的聯合方案與不含鉑劑的聯合方案比較:7個RCT比較了這兩種方案;大多數RCT發現含鉑劑的方案能改善結局,其益處和危害依賴于具體方案;沒有研究顯示鉑劑能顯著減少存活時間和總存活率. ⑤聯用鉑劑與單用鉑劑比較:1篇系統評價和另3個RCT認為沒有證據表明,延長存活時間和總存活率上,聯用鉑劑優于單用鉑劑. ⑥紫杉醇+順鉑與紫杉醇+卡鉑比較:1個RCT表明在延長存活時間和總存活率上兩者無顯著性差異,雖然不足以排除臨床上的重要作用.
ObjectivesTo systematically review the efficacy of Chinese herbal medicine (CHM) combined with chemotherapy for ovarian cancer.MethodsCNKI, VIP, WanFang Data and PubMed databases were searched to collect randomized controlled trials on the CHM combined with chemotherapy for ovarian cancer from inception to March 31st, 2018. Two reviewers independently screened literature, extracted data and evaluated the risk bias of included studies. Meta-analysis was then performed using RevMan 5.3 software.ResultsThirteen studies were included. Meta-analysis showed that, CHM combined with chemotherapy group was superior to the chemotherapy alone group in effective rate of TCM syndrome (RR=1.72, 95%CI 1.46 to 2.03, P<0.00.000 1), effective rate of tumor change (RR=1.40, 95%CI 1.21 to 1.63,P<0.000 01), physical condition score (MD=9.19, 95%CI 5.89 to 12.48,P<0.000 01), tumor markers (MD=–18.00, 95%CI –20.62 to –1.538,P<0.000 01), leukocyte reduction (RR=0.67, 95%CI 0.58 to 0.77,P<0.000 01), granulocy tedepletion (RR=0.67, 95%CI 0.55 to 0.81,P<0.000 1), thrombocytopenia (RR=0.55, 95%CI 0.45 to 0.69,P<0.000 01), and digestive tract reaction (RR=0.66, 95%CI 0.50 to 0.87,P=0.004).ConclusionsThe current evidence shows that CHM combined with chemotherapy is superior to chemotherapy alone in the treatment of ovarian cancer. Due to limited quality and quantity of included studies, the above conclusions are required to be verified by more high-quality studies.
ObjectiveTo explore the relationship between p53 mutation in 5-8 exons and type of epithelial ovarian cancer (EOC) pathogenesis of Han nationality women. MethodsFrom August 2011 to December 2012, 45 patients with primary EOC (Han nationality women from Sichuan Province) diagnosed surgically and pathologically were selected. Using direct DNA sequencing, we analyzed the mutations of p53 in 5-8 exons of all cases, and the EOC patients were divided into two types according dualism and the pathogenesis results. The p53 mutation of the different types in EOC patients were analyzed. ResultsThe frequency and efficiency of p53 mutation in type-ⅡEOC patients were significantly higher than that in typeⅠ(P < 0.01). And the codon 175 might be a mutational hotspot of type-ⅡEOC. The malignant degree and oviduct involved frequency of type-ⅡEOC were obviously higher than that of type-I EOC; p53 mutation frequency in high malignant patients increased significantly. Conclusionsp53 mutation plays an important role in the development of type-ⅡEOC. The codon 175 might be a mutational hotspot of type-ⅡEOC.