The mortality rate of ovarian cancer is the highest among female reproductive tract malignancies. Although most patients have undergone recurrent treatments such as surgery, chemotherapy, and targeted therapy, the recurrence rate is still high. The exploration of scholars in this field has never stopped. In recent years, remarkable achievements have been made in the medical treatment of ovarian cancer. The research of poly adenosinediphosphate-ribose polymerase, immunotherapy (immunocheckpoint inhibitor monotherapy, immune checkpoint inhibitor combined with other drugs) and anti-angiogenic drugs have provided new methods for the treatment of this disease, and throughout the whole process of ovarian cancer treatment. This paper summarizes this, and aims to provide a reference for the clinical treatment of ovarian cancer.
Objective To investigate the effects and underlying mechanisms of human pituitary tumor-transforming gene 1 (hPTTG1) small interfering RNA (siRNA) on apoptosis of ovarian cancer cell line A2780. Methods hPTTG1 siRNA was transfected into A2780 with lipofectamine (the hPTTG1 siRNA group), and the normal group and the negative control group were set up. Detections were conducted 48 hours after transfection: the interfering efficiency of hPTTG1 mRNA was measured by real-time polymerase chain reaction, the expression of survivin gene and survivin protein was examined by semiquantitative reverse transcriptase-polymerase chain reaction and Western blot, cell apoptosis was detected by DNA fragmentation gel electrophoresis and propidium iodide staining kit, and the activity of caspase-3 was assayed by caspases colorimetric assay kit. Results The expression of hPTTG1 mRNA was expressly inhibited after hPTTG1 siRNA transfection. DNA ladder was observed in the hPTTG1 siRNA group. The apoptotic rate of hPTTG1 siRNA transfection in the hPTTG1 siRNA group was (17.53±2.17)%, higher than those in the normal group and the negative control group [(8.97±1.56)% and (9.64±1.31)%, respectively], with statistically significant differences between them (P<0.05). The expression levels of survivin mRNA and survivin protein were down-regulated. The activity of caspase-3 was raised. Conclusions siRNA targeting hPTTG1 could induce apoptosis of A2780 by inhibition of survivin expression and activation of caspase-3. It may be a potential target for gene therapy of ovarian cancer.
Ovarian cancer is one of the common malignant tumors of female genital organs. In gynecological tumors, the incidence rate of ovarian cancer ranks the third after cervical cancer and uterine body cancer, but the death rate of ovarian cancer ranks the first, posing a serious threat to women’s life and health. In recent years, the National Comprehensive Cancer Network (NCCN) clinical practice guidelines for ovarian cancer has become an important basis for diagnosis and treatment of ovarian cancer. In this paper, we interpret the latest version (version 4. 2017) of NCCN clinical practice guidelines for ovarian cancer for its better clinical application.
Objective To make an individualized therapeutic regimen for a patient with stage III relapsed ovarian cancer guided by evidence-based medicine.Methods According to the clinical problems this patient showed and the PICO (patient, intervention, comparison and outcome) principle, the best clinical evidence associated with relapsed ovarian cancer was retrieved and evaluated. Results The current evidence showed that the relapsed ovarian cancer with platinum resistance tended to be treated by pharmacotherapy. Consequently, on the basis of combining the recommended guidelines, randomized controlled trials (RCTs), systematic reviews or meta-analyses on RCTs, clinical experience from doctors and willingness of patient, the regimen of Irinotecan plus Pegylated Liposomal Doxorubicin for interventional chemotherapy was recommended for this patient. After three courses of the treatment, the disease got some relieved; the medical team would like to keep conducting the same regimen for another six to eight courses, and the follow-up visit was undergoing. Conclusion For patients with relapsed ovarian cancer with platinum resistance, an individualized therapeutic regimen under the guidance of evidence-based methods can not only improve the therapeutic efficacy but also guide both doctors and patients to take the indeterminate risk of medicine.
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.
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.
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.
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.