卵巢癌诊断技术的研究进展

卵巢癌是女性3大恶性肿瘤之一,其发病率呈逐年上升的趋势[1],严重影响女性的生存质量。因早期缺乏典型症状,辅助检查不易发现其早期病变,故多数病例发现时已属晚期。晚期卵巢癌的5年生存率为15%～20%[2],而早期卵巢癌的5年生存率可高达70%～90%[3],因此寻找可靠的早期诊断和病情监测的指标显得尤为重要。

卵巢癌的早期诊断

卵巢组织复杂,是全身各脏器肿瘤类型最多的部位,也是＂癌细胞＂滋生的地方。卵巢恶性肿瘤是女性生殖器三大恶性肿瘤之一,仅次于子宫颈癌、子宫体癌而占第三位。

CA125和CA199检测对卵巢上皮癌诊断和预后的价值

目的探讨CA125和CA199检测对卵巢上皮癌诊断和预后的临床价值。方法用微粒子化学发光法测定CA125和CA199水平,并对卵巢上皮癌患者术后3个月内连续测定,观察不同疗效者治疗前后CA125、CA199的变化。结果卵巢上皮癌患者血清CA125、CA199水平明显高于卵巢上皮类良性肿瘤患者,CA125、CA199检测的敏感度分别为71.9%、42.8%,二者联合检测的敏感度为85.7%。结论血清CA125和CA199是卵巢上皮癌诊断和判断预后的敏感性指标,二者联合检测可提高卵巢上皮癌诊断的敏感性。

血清CA125检测对早期卵巢癌的诊治效果评价

目的探讨血清CA125浓度检测对卵巢癌早期诊断与治疗的临床意义。方法运用化学发光免疫法对卵巢肿瘤患者血清CA125浓度进行检测,其中包括良性肿瘤32例,恶性肿瘤46例,同时检测自愿参加体检的健康妇女30例作为对照组。结果卵巢癌患者组血清CA125浓度均高于卵巢良性肿瘤患者组和正常对照组,差异均有统计学意义(P<0.05)。结论检测血清CA125对卵巢癌的早期诊断以及卵巢癌治疗效果的动态监测具有重要价值。

卵巢癌CT检查58例护理

目的探讨卵巢癌患者CT检查时护理配合的价值。方法做好扫描前准备工作和心理护理,检查中帮患者保持正确体位。常规放置阴道栓。分次口服2%泛影蒲胺300～400ml/次,总量1000～1200ml;使肠管显影。上CT床前口服清水300～500ml使胃充盈。对疑似直肠病变、乙状结肠病变者可自肛门注气200ml。检查后加强患者病情观察。结果 CT图像清晰,患者情绪均基本稳定,无体位性低血压,无低血糖,无意外损伤。结论有针对性、完善的全程护理对CT检查获得清晰图像起着重要的保障作用。

Apoptosis Rate and Objective Diagnosis of Drug Resistance of Ovarian Cancer Cell Lines

Objective： To investigate whether the change of drug resistance degree could be evaluated by apoptotic rate in ovarian cancer cell lines. Methods： Human epithelia ovarian cancer cell line A2780 and its platinum （DDP） resistance cell line AD4 were used. They were divided into 4 groups respectively （A2780-DDP group, A2780-DDP＋VRM group, AD4-DDP group and AD4-DDP＋VRM group）. 3-（4, 5- dimethylthiazol-2-yl）-2, 5-diphenyl-2H-tetrazolium bromide （MTT） was used to measure the multiple of drug resistance. The expression of drug-resistance genes （mdrl, TopoⅡα and GSTπ） was detected by using reverse transcription polymerase chain reaction （RT-PCR）. Semi-quantity assay was proceed by rate the of multidrug resistance genes to G3 PDH gene. Apoptosis was measured by DNA gel electrophoresis and flow cytometry respectively. The advantages and disadvantage of evaluating drug-resistance with these three methods were analyzed. Results： The 50% inhibition concentration （IC50） of A2780 and AD4 was 19.2 μg/mL and 66 μg/mL respectively, and the resistance fold of the AD4 was 3.4. Some drug-resistance genes could be detected by RT-PCR in A2780 and AD4 cell lines. The expression of mdrl was only （0.09±0.03）×10^-2 ： 1 and （0.10±0.02） × 10^-2：1 respectively （rate to G3 PDH gene） with the difference being not significant between them. The expression of TopoⅡα in the A2780 cells was （2.60±0.12）×10^-2：1 and （0.11±0.03）× 10^-2：1 in the AD4 cells respectively with the difference between them being significant. On the contrary, the expression of GSTπ in A2780 cells was lower than in AD4 cells, and the ratio was （0.11±0.03）×10^-2：1 and （3.13±0.14）×10^-2：1 respectively with tile difference being significant between them. There was no significant difference among the genes expression after the drugs were given for 6 h, 12 h and 24 h. couldn＇t reflect the change of drug-resistance timely. DNA gel electrophoresis used to detect apoptosis was only a qualitative analysis. Different drug resistance degrees may be detected by flow cytometry as early as few hours after drugs were given, which realized the earlier and quantities detection of drug resistance. Conclusion： Detection of apoptosis with flow cytometry may not be affected by the variety of drug-resistance genes, suggested this was a general, quantitative and objective method to reflect drug resistance.

An integrated approach utilizing proteomics and bioinformatics to detect ovarian cancer

Objective: To find new potential biomarkers and establish the patterns for the detection of ovarian cancer. Methods: Sixty one serum samples including 32 ovarian cancer patients and 29 healthy people were detected by surface-enhanced laser desorption/ionization mass spectrometry (SELDI-MS). The protein fingerprint data were analyzed by bioinformatics tools. Ten folds cross-validation support vector machine (SVM) was used to establish the diagnostic pattern. Results: Five potential bio- markers were found (2085 Da, 5881 Da, 7564 Da, 9422 Da, 6044 Da), combined with which the diagnostic pattern separated the ovarian cancer from the healthy samples with a sensitivity of 96.7%, a specificity of 96.7% and a positive predictive value of 96.7%. Conclusions: The combination of SELDI with bioinformatics tools could find new biomarkers and establish patterns with high sensitivity and specificity for the detection of ovarian cancer.

Advances in circulating microRNAs as diagnostic and prognostic markers for ovarian cancer

Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70% of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30% because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA （miR） is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injur）n Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer.

MicroRNA: a new and promising potential biomarker for diagnosis and prognosis of ovarian cancer

Epithelial ovarian cancer(EOC) is the leading cause of death among all gynecological malignancies. Despite the technological and medical advances over the past four decades, such as the development of several biological markers(mRNA and proteins biomarkers), the mortality rate of ovarian cancer remains a challenge because of its late diagnosis, which is specifically attributed to low specificities and sensitivities. Under this compulsive scenario, recent advances in expression biology have shifted in identifying and developing specific and sensitive biomarkers, such as micro RNAs(miRNAs) for cancer diagnosis and prognosis. MiRNAs are a novel class of small non-coding RNAs that deregulate gene expression at the posttranscriptional level, either by translational repression or by mRNA degradation. These mechanisms may be involved in a complex cascade of cellular events associated with the pathophysiology of many types of cancer. MiRNAs are easily detectable in tissue and blood samples of cancer patients. Therefore, miRNAs hold good promise as potential biomarkers in ovarian cancer. In this review, we attempted to provide a comprehensive profile of key miRNAs involved in ovarian carcinoma to establish mi RNAs as more reliable non-invasive clinical biomarkers for early detection of ovarian cancer compared with protein and DNA biomarkers.

Feasibility Evaluation for Selection of Neoadjuvant Chemotherapy before Cytoreduction of Advanced Ovarian Carcinoma

Ovarian carcinoma is one of three gynecological neoplasms. It typically develops as an insidious disease, with few warning signs or symptoms, because the ovary is situated at a deep part of the pelvic cavity. Advanced ovarian carcinoma （AOC） is highly malignant, so the prognosis of the patients is poor. Initial debulking surgery, followed by chemotherapy, is currently the main therapeutic choice for AOC. During operations, efforts should be made to excise the tumor and minimize the residual lesion, so as to achieve the optimal cytoreduction and improve the prognosis. As a feasible therapeutic regimen for the patients with primary unresectable AOC, neoadjuvant chemotherapy can improve the surgical condition and can increase the optimality of cytoreduction. It is important therefore to evaluate the feasibility of surgical treatment and make a proper selection of the primary treatment plan and neoadjuvant chemotherapy, so as to enhance the optimality of surgery and to avoid unnecessary exploratory laparotomy. At present, methods of feasibility evaluation for optimal cytoreduction of AOC are as follows： 1） radiography, i.e., CT, PET and MRI scanning; 2） CA-125 value; 3） laparoscopic exploration; 4） other tumor markers such as p53. However, any method lacks the ability to cover all the predicting factors influencing the outcome of cytoreduction, and to evaluatethe surgery across the board. Searching for new methods and combining two or more procedures to evaluate the feasibility of cytoreduction may increase the optimality, reduce the residual focus, prolong survival time and improve the prognosis. In this study, recent advances in evaluation of the feasibility for optimal cytoreduction and the selection of neoadjuvant chemotherapeutic regimens were reviewed.

OVEREXPRESSION OF p53, EGFR,C-ERBB2 AND C-ERBB3 IN ENDOMETRIOIDCARCINOMA OF THE OVARY

Objectives. To determine overexpression of p53, EGFR, c-erbB-2 and c-erbB-3 in endometrioid carcinoma of the ovary and to evaluate the prognostic significance of these results, especially, coexisting overexpression of p53 and one of the member of type I growth factor receptor family.Methods. Overexpressions of the p53, EGFR, c-erbB-2 and c-erbB-3 protein were studied by im-munohistochemistry in paraffin-embedded tumor tissue from 28 patients with endometrioid carcinoma of the ovary.Results. 11 (39.3%), 13 (46. 4%), and 14 (50. 0%) were stained positively with p53, c-erbB-2 and c-erbB-3 monoclonal antibodies. 13 (46- 4%) was stained positively with EGFR polyclonal antibody. There were no relationship between p53, EGFR, C-erbB-2, c-erbB-3 and histologic grade, lymph node metastasis. The percentage of tumors with over expression of p53, EGFR, C-erbB-2 and c-erbB-3 was higher in those with stage Ⅱ-Ⅲ tumors compared with those with stage Ⅰ , in patients with residual tumor after initial surgery compared with those without. A high survival rate was observed in patients without p53, EGFR, c-erbB-2 and c-erbB-3 overexpression respectively than those with. A highest survival rate was observed in patients with both p53 and one of EGFR, c-erbB-2 and c-erbB-3 negative compared with those both positive or either of both positive.Conclusion. Overexpression of p53, EGFR, c-erbB-2 and C-erbB-3 resulted in a poorer prognosis respectively. Overexpression of both p53 and one of the EGFR, c-erbB-2 and c-erbB-3 is a worse prognostic indicator in patients with endometrioid carcinoma of the ovary.

Purple-bluish tongue is associated with platelet counts, and the recurrence of epithelial ovarian cancer

OBJECTIVE： To evaluate the relationship between purple-bluish tongue and platelet counts, and further to examine their associations with the recurrence of epithelial ovarian cancer.METHODS： A total of 82 epithelial ovarian cancer patients were enrolled in this study. Cluster analysis was used for grouping patients＇ P_（RGB）（Red-R;Green-G; Blue-B; Average percentage of RGB, P_（RGB））values. Receiver operating characteristic（ROC）curve was performed for detecting the diagnostic standard of purple-bluish tongue. χ~2 test was used to assess the relationship between purple-bluishtongue and platelet counts, and the recurrence of epithelial ovarian cancer. The perioperative（preoperative） platelet level was examinedwith tongue image and disease recurrence.RESULTS： Tongue images were classified into two groups basing on P_（RGB） values of images by cluster analysis. The numbers of cases in cluster ＂1＂（normal color tongue） was 16 and cluster ＂2＂（purple-bluish tongue） was 66. Two groups of P_（RGB） values, classified by cluster analysis, were significantly correlated with vision-based tongue color recognition（Kappa = 0.852, P 0.001）. ROC curve showed that the ratio of P_B to PRhad the highest diagnostic value. The sensitivity and the specificity of the ratio of P_B to P_R were 95.3% and 88.9% respectively and the optimal cut-off point was 0.71. Purple-bluish tongue was significantly correlated with increased platelet counts（P 0.001）. Both the increased platelet counts（P = 0.01） and purple-bluish tongue were associated with recurrence of epithelial ovarian cancer（P 0.001）.CONCLUSION： The ratio of P_B to P_R greater than 0.71 could serve as an indicator for purple-bluish tongue diagnosing used in symptom pattern identification in Traditional Chinese Medicine. Purple-bluish tongue, associated with increased platelet counts, was also closely correlated with the recurrence of epithelial ovarian cancer.

Reprogramming of ovarian granulosa cells by YAP1 leads to development of high-grade cancer with mesenchymal lineage and serous features

Understanding the cell-of-origin of ovarian high grade serous cancer(HGSC)is the prerequisite for efficient prevention and early diagnosis of this most lethal gynecological cancer.Recently,a mesenchymal type of ovarian HGSC with the poorest prognosis among ovarian cancers was identified by both TCGA and AOCS studies.The cell-of-origin of this subtype of ovarian cancer is unknown.While pursuing studies to understand the role of the Hippo pathway in ovarian granulosa cell physiology and pathology,we unexpectedly found that the Yes-associated protein 1(YAP1),the major effector of the Hippo signaling pathway,induced dedifferentiation and reprogramming of the ovarian granulosa cells,a unique type of ovarian follicular cells with mesenchymal lineage and high plasticity,leading to the development of high grade ovarian cancer with serous features.Our research results unveil a potential cell-of-origin for a subtype of HGSC with mesenchymal features.