siRNA抑制survivin的表达诱导人卵巢癌SKOV-3细胞凋亡的研究

目的筛选能有效抑制survivin基因表达的小干扰RNA(siRNA),探讨survivin基因抑制对人卵巢癌SKOV-3细胞凋亡的影响。方法设计3段survivin siRNA靶位点,用PCR扩增siRNA表达框,与survivin-绿色荧光蛋白融合基因表达质粒共转染293T细胞,再构建有效siRNA的表达载体,转染卵巢癌SKOV-3细胞,分析sur-vivin基因的表达及细胞凋亡情况。结果筛选出了1段能高效抑制survivin表达的siRNA,能显著下调SKOV-3细胞内的survivin表达,并导致SKOV-3细胞凋亡。结论利用RNA干扰能有效抑制survivin基因表达并诱导人卵巢癌SKOV-3细胞凋亡,为进一步的靶向survivin分子的体内抗肿瘤研究奠定了基础。

血清HE4、CA-125和ROMA指数在盆腔恶性肿瘤中的诊断价值

目的探讨血清中人附睾分泌蛋白4(HE4)、糖类抗原125(CA-125)水平和卵巢癌风险预测模型(ROMA)在盆腔恶性肿瘤中的诊断价值。方法采用电化学发光免疫测定卵巢癌组、子宫内膜癌组、宫颈癌组、卵巢良性肿瘤组、子宫良性疾病组以及对照组的血清HE4和CA-125水平,并结合绝经状态计算ROMA值。结果 (1)卵巢癌组和子宫内膜癌组血清HE4的表达水平明显高于其它各组(P<0.01);卵巢癌组血清CA-125的表达水平明显高于除子宫内膜癌组的其它各组(P<0.01);卵巢良性肿瘤组及子宫良性疾病组血清CA-125的表达水平明显高于对照组(P<0.05)。(2)以卵巢良性肿瘤组为对照组,绝经前HE4对卵巢癌的特异性和阳性预测值高达100%,准确性93.9%,均明显高于CA-125和ROMA值(P<0.01);CA-125对卵巢癌的敏感性最高88.9%,与HE4比较差别有统计学意义(P<0.05)。绝经后三指标在对卵巢癌的特异性、敏感性和准确性上差别无统计学意义(P>0.05)。不考虑绝经与否,HE4的特异性、阳性预测值和准确性最高(98.1%、91.7%和91.4%);ROMA指数的敏感性和阴性预测值最高(81.3%和93.6%)。(3)以卵巢良性肿瘤+健康人为参照人群,HE4、CA-125和ROMA指数单项检测诊断卵巢癌的ROC曲线下面积分别为0.919、0.814和0.921。以子宫良性疾病组为对照组,单独检测HE4在诊断子宫内膜癌的特异性、阳性预期值和准确性方面均明显高于CA-125(P<0.05);HE4与CA-125联合检测子宫内膜癌的敏感性高于单独检测。以子宫良性疾病组+健康人为参照人群,HE4、CA-125单项检测诊断子宫内膜癌的ROC曲线下面积分别为0.916、0.731。结论血清HE4对卵巢癌和子宫内膜癌具重要诊断价值,其鉴别诊断效能优于CA-125,且与CA-125联合检测有助于提高子宫内膜癌的诊断率;ROMA指数的应用有助于提高对卵巢癌的诊断效能。

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.

The Relationship between Methylation and Expression Defect of Tumor Suppressor Gene p16INK4A in Epithelial Ovarian Cancer

Objective： To evaluate the expression of p16INK4A gene in ovarian cancer and analyze the relation between this alteration and the promoter methylation of p16INK4A DNA. Methods： Seven ovarian cancer cell lines and eighteen ovarian cancer specimens were selected for the study. Genomic DNA and RNA were extracted from fresh tissues and cell lines, DNA was treated with sodium bisulfite and then analyzed with methylation-specific PCR （MSP） to detect p16INK4A methylation. The expression of p16INK4A mRNA was detected by reverse transcription-polymerase chain reaction （RT-PCR）. In addition, the proliferation of methylated cell lines before and after treatment of demethylating agent 5-Aza-2＇-deoxycytidine （5-ADC） was examined with 3-（4, 5-dimethylthiazol-2-yl）-2, 5-diphenyltetrazolium bromide （MTT） assay in vivo. Results： Compared with the control, the expression of p16INK4A mRNA decreased significantly or absolutely defaulted in 10 of 18 （55.56%） ovarian cancer specimens and 71.4% （5/7） ovarian cancer cell lines （P〈0.05）, and the expression of p16INK4A protein also decreased （P〈0.05）. The decrease of p16INK4A was due, in part, to p16INK4A methylation, which was found in the first exon of three cell lines and six ovarian cancer specimens and the rate was 42.86% and 33.33% in ovarian cancer cell lines and specimens respectively. All the methylated cells and tissues showed expression defect of p16INK4A, but the treatment of 5-ADC reactivated the expression of p16INK4A in methylated cells and decreased the proliferation of tumor cells in vitro and in vivo. Conclusion： The expression defect of p16INK4A gene possibly has an important role in the development of ovarian cancer, and this alteration is due, in part, to the methylation of the first exon in p16INK4A.

EFFECTS OF MUTATION AND EXPRESSION OF PTEN GENEmRNA ON TUMORIGENESIS AND PROGRESSION OFEPITHELIAL OVARIAN CANCER

Objective To investigate the mutation and expression of tumor suppressor gene-PTEN mRNA and explore their roles in tumorigenesis and progression of ovarian cancer. Methods Mutated exon 5 of PTEN gene was examined in normal ovary(n = 5), ovarian cyst (n =5), ovarian borderline tumor (n = 9), epithelial ovarian cancer(n = 60), and ovarian cancer cell line (n = 1)by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP). mRNA expression of PTEN gene was evaluated in corresponding tissues and cell line by reverse transcription polymerase chain reaction(RT-PCR). The mutation and mRNA expression of PTEN gene were compared with clini-copathological features of ovarian cancer. Results Mutated exon 5 of PTEN gene was detected only in 5(7.1%)cases of epithelial ovarian cancer. mRNA expression level of PTEN gene in ovarian borderline tumor or ovarian cancer was lower than that in normal ovary or ovarian cyst(P < 0.05). The level of PTEN gene mRNA expression was negatively correlated with clinicopathological staging of ovarian cancer, whereas positively correlated with histological differentiation (P < 0.05). mRNA expression level of PTEN gene in ovarian endometrioid cancer was significantly lower than that in ovarian serous or mucinous cancer (P < 0.05=. Conclusions Mutation of PTEN gene occurs in ovarian cancer. Down-regulated expression of PTEN is probably an important molecular event in tumorigenesis of ovarian cancer. Abnormal expression of PTEN gene is involved in progression of ovarian cancer. Reduced expression of PTEN gene is closely associated with tumorigenesis and pathobiological behaviors of ovarian endometrioid cancer.

ROLE OF ERK1/2 KINASE IN CISPLATIN-INDUCED APOPTOSIS IN HUMAN OVARIAN CARCINOMA CELLS

Objective To investigate the role of extracellular regulated kinase (ERK1/2) pathway in cisplatin-induced apoptosis in human ovarian carcinoma cells. Methods Cisplatin-induced apoptosis were stained with DAPI and was assessed microscopically in human epithelial adenocarcinoma ovarian cell line SKOV3 cells. ERK activation was determined by Western blotting using an anti-phospho-ERK antibody to detect ERK activity. The effect of PD98059 on ERK activity induced by cisplatin was detected by MTT assay. Results Marked apoptosis of SKOV3 cells resulted from 48 hours treatment with 20 μg/mL cisplatin. Strong activation of ERK was led to by 15 μg/mL cisplatin. Dose response and time course of cisplatin induced apoptosis in SKOV3 cells. Cisplatin-induced ERK activation occurred at 12 hours and increased to highest induction at 24 hours by Western blotting. The effect of PD 98059 on ERK activity induced by cisplatin at the concentration of 100 μmol/L PD 98059. Statistically significant decreased in cell survival were observed with 100 μmol/L PD 98059 at 15 and 20 μg/mL cisplatin (P< 0.05). Conclusions Cisplatin activates the ERK signaling pathway in ovarian cancer cell line SKOV3. Inhibition of ERK acti-vity enhances sensitivity to cisplatin cytotoxity in ovarian cancer cell line SKOV3. Evaluation of ERK activity could be useful in predicting which ovarian cancer will response most favorably to cisplatin therapy.

The Effect of the MDM2-p53 Loop on the Sensitivity of Ovarian Cancer Cells to Cisplatin

OBJECTIVE To explore whether MDM2 transfection can alter the MDM2-p53 autoregulatory feedback loop so as to change the sensitivity of ovarian cancer cell lines to cisplatin. METHODS The ovarian cancer cell line A2780 expressing wild-type P53 and the ovarian cancer cell line SKOV-3 with the p53 null type were stably transfected with pCMV-MDM2 or pCMV as a control. The blocked expression of P53 was determined by Western blots. Cytotoxicity was assessed using the MTT assay and the trypan blue exclusion assay. Flow cytometry was used to detect changes in the cell cycle and removal of platinum -DNA adducts was measured by atomic absorption spec-troscopy. RESULTS (1) Parental A2780 and A2780-V cells (IC50= 15.14±1.39 μmol) have similar cisplatin sensitivities, whereas sensitivity to cisplatin in A2780-M cells (IC50=7.98±1.32 μmol) was 2 to 3 fold greater (P=0.001). The trypan blue exclusion assay demonstrated that cisplatin killed a higher percentage of A2780-M cells compared to A2780-V cells. There was no significant change following MDM2 transfection in SKOV-3 cells. (2) After cisplatin treatment, A2780-M cells showed a pronounced S-phase arrest, however, A2780 cells with the intact wild-type P53, arrested primarily at the G2/M transition. (3) Platinum uptake was similar for all of the A2780 cell lines after ciaplatin treatment, but the removal of plat-inum-DNA adducts was reduced in the A2780-M cells compared with A2780-V cells. CONCLUSION MDM2 increases cisplatin cytotoxicity in ovarian cancer cells by blocking the expression of p53 through the MDM2-p53 autoregulatory feedback loop.

Comprehensive management of epithelial ovarian cancer with peritoneal metastases

Ovarian cancer has as its predominant pattern of dissemination metastases to the peritoneal surfaces and disease spread within the abdomen and pelvis that most commonly causes the patients demise. To combat peritoneal metastases, cytoreductive surgery with peritoneal and visceral resections is combined with intraperitoneal and systemic chemotherapy. Chemotherapy given in the operating room after the complete visible removal of ovarian cancer is hyperthermic intraperitoneal chemotherapy. The results of the combined treatment are determined by the extent of prior surgery, the extent of disease as established by the peritoneal cancer index, and the quality of the cytoreduction as measured by the completeness of cytoreduction score. Recent clinical information on patients with recurrent ovarian cancer suggest a median overall survival of up to 60 mo. These data are greatly improved over the one year survival observed in the past.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in epithelial ovarian cancer: State of the art

Advanced stage epithelial ovarian cancer(EOC) is diffi cult to treat with low overall cure rates. A new strategy combining maximal cytoreductive surgery(CRS) with intraoperative hyperthermic intraperitoneal chemotherapy(HIPEC) has been proposed to treat advanced stage EOC in the primary setting. Numerous small, heterogeneous studies have been conducted exploring outcomes in patients with predominantly advanced, recurrent or refractory disease treated with CRS + HIPEC. Although morbidity rates approaching 35% have been reported, oncologic outcomes are promising. Incorporation of HIPEC for the treatment of primary EOC has continued to gain interest. Several prospective phase 2 clinical trials were recently completed evaluating the impact of CRS + HIPEC in the primary setting. This article will briefl y discuss the benefi ts of optimal surgical cytoreduction and the theoretical basis of intraperitoneal chemotherapy in patients with advanced stage EOC, and will then review existing literature describing oncologic outcomes in EOC patients treated with HIPEC in the primary setting.

The Effect of 17 β-Estradiol on Invasion by the Ovarian Clear Cell Adenocarcinoma Cell Line ES-2 and the Molecular Mechanism Involved

OBJECTIVE To assess the effect of 17 β-estradiol（E2） on cell proliferation, cell invasiveness and its regulation of MTA3, Snail and matrix metalloproteinase 2 （MMP-2） expression in the ovarian clear cell adenocarcinoma cell line ES-2, and to further investigate the mechanism involved. METHODS We first investigated expression of ERα, ERβ, PR and E-cadherin of ES-2 cells by RT-PCR and Western blots. Before all experiments, the ES-2 cells were grown in medium depleted of steroid for more than 7 days. Following treatment with 10^-7,10^-8 and 10^-9 M E2, cell viability of the ES-2 cells was determined by the MTT method, and the cell cycle distribution and apoptosis were examined by flow cytometry （FCM）. Invasion and mobility assays were performed using modified Boyden chambers. MTA3, Snail and MMP-2 mRNA expression was measured by RT-PCR, and Snail, MMP-2 protein levels were determined by IHC. MMP-2 activity was assayed by zymography. RESULTS RT-PCR and Western Blots showed that theexpression of ERα and E-cadherin mRNA and protein in the ES-2 cells was negative, while ERβ and PR expression was positive. E2 at 10^-7,10^-8 or 10^-9M stimulated cell proliferation. A level of 10^-8M E2 reduced the proportion of G0-G1 phase cells and increased the proportion of cells in the S phase, but it had no effect on apoptosis. Invasiveness and mobility of the ES-2 cells was significantly increased by 10^-8M E2. Treatment with 10^-8M E2 led to reduced MTA3 mRNA expression, and elevated Snail and MMP-2 mRNA and protein levels. CONCLUSION E2 enhanced invasion by the ES-2 cells. The effects observed maybe mediated by down-regulation of MTA3 and up-reguation of Snail and MMP-2.

Cytoreductive surgery in primary advanced epithelial ovarian cancer

Epithelial ovarian cancer is one of the most common malignancy and one of the principal causes of death among gynaecological neoplasm. The majority of patients(about 70%) present with an advanced International Federation of Gynaecology and Obstetrics stage disease. The current standard treatment for these patients consists of complete cytoreduction and combined systemic chemotherapy(CT). An increasing proportion of patients undergoing complete cytoreduction to no gross residual disease(RD) is associated with progressively longer overall survival. As a counterpart, some authors hypothesized the improving in survival could be due more to a less diffused initial disease than to an increase in surgical cytoreduction rate. Moreover the biology of the tumor plays an important role in survival benefi t of surgery. It's still undefi ned how the intrinsic features of the tumor make intra-abdominal implants easier to remove.Adjuvant and hyperthermic intraperitoneal CT could play a decisive role in the coming years as the completeness of macroscopic disease removal increases with advances in surgical techniques and technology. The introduction of neo-adjuvant CT moreover will play a decisive role in the next years Anyway cytoreduction with no macroscopic residual of disease should always be attempted. However the defi nition of RD is not universal. A unique and defi nitive defi nition is needed.

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.

Pharmacology of cancer chemotherapy drugs for hyperthermic intraperitoneal peroperative chemotherapy in epithelial ovarian cancer

The peritoneal parietal and visceral surfaces of the abdomen and pelvis are an important anatomic site for the dissemination of epithelial ovarian cancer(EOC). The transcoelomic spread of cancer cells gives rise to peritoneal carcinomatosis(PC) which, without special treatments, is a fatal manifestation of EOC. In order to control PC cytoreductive surgery to remove macroscopic disease is combined with perioperative intraperitoneal(IP) and perioperative intravenous chemotherapy to eradicate microscopic residual disease. Chemotherapy agents are selected to be administered by the IP or intravenous route based on their pharmacologic properties. A peritoneal-plasma barrier which retards the clearance of high molecular weight chemotherapy from the peritoneal cavity results in a large exposure of small cancer nodules on abdominal and pelvic surfaces. Tissue penetration is facilitated by moderate hyperthermia(41-42 ℃) of the IP chemotherapy solution. Timing of the chemotherapy as a planned part of the surgical procedure to maximize expo-sure of all peritoneal surfaces is crucial to success.

Clinical experience of Pseudo-Meigs' Syndrome due to colon cancer

We report a rare case of Pseudo-Meigs' Syndrome caused by ovarian metastasis from sigmoid colon cancer, which was accompanied by peritoneal dissemination. A 58-year-old female patient presented with massive right pleural effusion, ascites and a huge pelvic mass. Under the diagnosis of an advanced ovarian tumor, bilateral oophorectomy was performed and sigmoidectomy was also carried out after intraoperative diagnosis of peritoneal dissemination involving the sigmoid colon. How- ever, immunohistochemical staining revealed that the ovarian lesions were metastasis from the primary advanced colon cancer. Postoperatively, ascites and pleural effusion subsided, and the diagnosis of Pseudo-Meigs' Syndrome due to a metastatic ovarian tumor from colon cancer was determined. The patient is now undergoing a regimen of chemotherapy for colon cancer without recurrence of ascites or hydrothorax 10 mo after the surgery. Pseudo-Meigs' Syndrome due to a metastaticovarian tumor from colon cancer is rare but clinically important because long-term alleviation of symptoms can be achieved by surgical resection. This case report suggests that selected patients, even with peritoneal dissemination, may obtain palliation from surgical resection of metastatic ovarian tumors.

Effects of HLEC on the secreted proteins of epithelial ovarian cancer cells prone to metastasize to lymph nodes

Objective： To study explores the effect of HLEC on the secreted proteins of epithelial ovarian cancer （EOC） cells （SKOV3-PM4） with directional highly lymphatic metastasis. Methods： Supernatants of four groups of cultured cells, namely, SKOV3 （A）, SKOV3＋HLEC （B）, SKOV3-PM4 （C）, SKOV3-PM4＋HLEC （D）, were collected, and their proteins were detected by antibody arrays and iTRAOcZD-LC-MALDI- TOF/TOF/MS. Significantly differential proteins were further analyzed via bioinformatics and validated in human serums and cell media via ELISA. Results： Results of antibody arrays and mass spectrometry demonstrated that GRN and VEGFA were upregulated in group C （compared with group A）, whereas IGFBP7 and SPARC were downregulated in group D （compared with group C）. Comprehensive bioinformatics analysis results showed that IGFBP7 and VEGFA were closely linked to each other. Further validation with serums showed statistical significance in VEGFA and IGFBP7 levels among groups of patients with ovarian cancers, benign tumors, and control groups. Two proteins were upegulated in the first group. VEGFA in the control group was downregulated. For IGFBP, upregulation in the control group and down-regulation in the first group were also observed. Conclusion： The HLEC microenvironment is closely associated with directional metastasis to lymph nodes and with differential proteins including cell stromal proteins and adhesion factors. The upregulation of VEGFA and GRN and the downregulation of SPARC and IGFBP7 are closely associated with directional metastasis to lymph nodes in EOC cells.

Advanced ovarian cancer: Neoadjuvant chemotherapy plus surgery and HIPEC as up-front treatment

Epithelial ovarian cancer （EOC） is one of the most com-mon malignancies and one of the principal causes of death in gynecological neoplasms. The majority of EOC patients present with an advanced International Fed-eration of Gynecology and Obstetrics stage disease. The current standard treatment for these patients con-sists of complete cytoreduction and combined systemic chemotherapy of a platinum agent and paclitaxel. Even if the majority of patients with EOC respond to frst-line platinum based chemotherapy, almost 20% of them are resistant or refractory. According to these data, the main risk is for a certain number of patients to have undergone cytoreductive surgery （CRS） and subsequent hyperthermic intraoperative peritoneal chemotherapy （HIPEC） in a useful way. Radical surgery, especially in advanced cases, is associated with a high incidence of postoperative morbidity and mortality, which could be increased by the HIPEC. Every effort should be made for previously selected patients to improve outcome and optimize resources. Over the last decade, new options have been introduced to prolong survival. Im-proved long-term results can be achieved using CRS in combination with intraoperative HIPEC. This combina-tion has also been used in an up-front setting. Contro-versial outcomes have been reported for neoadjuvant platinum-based chemotherapy. Different papers have been published reporting discordant results. Further studies are needed.

Peritoneal carcinomatosis from advanced ovarian cancer: To treat or not to treat ethical issues suggested by a case study

This article provides a brief description of an epithelial ovarian cancer （EOC） case （stage Ⅳ） treated with the association of complete CytoReductive Surgery and hy-pertermic intraPEritoneal chemotherapy （HIPEC）. The use of HIPEC in EOC makes theoretic sense in view of the high rates of recurrence following standard treat-ment, but there are no randomized clinical trial to date and HIPEC for these patients still represents a radical treatment where the choice of no treatment may be acceptable since defnitive cure is unlikely. We reviewed the entire decision making process considering the risk/beneft of the procedure in term of mortality/morbidity, the quality of life and the psychological profile of the patient 1 year after surgery. The platform World Health Organization-International Classification of Function-ing, Disability and Health that permits evaluation of the person in relation to the psycho-social context is pre-sented. A person-centred approach and assessment of health-related quality-of-life and disability in EOC survi-vors are of central importance for decision making.

Correlation between epithelial ovarian cancer and thrombocytosis

Objective： To evaluate the clinical significance of platelet （PLT） count in epithelial ovarian cancer, and to investigate the correlation between thrombocytosis and the incidence of epithelial ovarian cancer. Methods： We evaluated 220 epithelial ovarian tumor patients divided into early stage epithelial ovarian cancer group （n = 80）, advanced stage epithelial ovarian cancer group （n = 50） and benign ovarian tumor group （n = 90） as controls, who underwent primary surgical treatment. Three groups were evaluated with the relationship between platelet counts and preoperative and postoperative CA125, histopathology, abdominal edema, residual tumor, and lymph node metastasis. Epithelial ovarian cancer patients were evaluated whether platelet count was decreased after surgery. Results： The mean platelet counts were （234.55 ± 71.51）× 10^9/L in the early stage epithelial ovarian cancer group, （308.12±111.95）× 10^9/L in the advanced stage epithelial ovarian cancer group, and （206.28± 52.62） × 10^9/L in the benign ovarian tumor group, with a significant difference among the 3 groups （P 〈 0.05）. In the early stage epithelial ovarian cancer group, the platelet count was correlated with histopathology. In the advanced stage epithelial ovarian cancer group, there was a correlation between thrombocytosis and the incidence of that residual tumor diameter was greater than 2 cm. But there was no relationship between platelet count and histopathology, CA125, abdominal edema, or lymph node metastasis. In general the platelet count was decreased after surgery. Conclusion： An increased platelet count is commonly seen in patients with epithelial ovarian cancer, but it usually decreases after surgery. Patients with thrombocytosis have poor prognosis. Platelet count can be used as a marker for the development and prognosis of epithelial ovarian cancer.

Establishment of orthotopic impact/metastasis model of human ovary cancer in nude mice

Objective: To establish a patient-like human ovary carcinoma /spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue. Methods: An highly metastatic ovarian tumor line (HO-8910PM: Human serum carcinoma of the ovary )previously grown substaneously was transplanted into the ovicapsule using microsurgery technique .Histologically intact human ovary tumor pieces gained from implantation site were passaged between ovicapsules for four generations. Results: All mice developed ovary tumors and the metastatic rates were about 75%. The tumors only metastasized to liver but no other organs. The earliest appearance of metastasis was 14 d and the average survival period was 20.7±4.89 d.The microscopic appearance of the metastases was similar to the tumor observed in the substaneous xenografts and orthotopically transplanted. Chromosomes analysis exhibited the feature of human carcinoma and retained genetic stability during the processes of passage. Conclusion: Orthotopic implanation provides a suitable micro-enviroment in which ovarian cancer can express its intrinsic clinically-relevant properties. This approach is relevant to the spontaneous development of ovarian cancer and is thought to be a useful model for studies of metastatic mechanism and therapy for ovary cancer.

Natural history of epithelial ovarian cancer and its relation to surgical and medical treatment

Epithelial ovarian cancer(EOC) represents approximately 90% of primary malignant ovarian tumors, the sixth most common cancer in women and the second most common gynecologic cancer. Approximately 80%-85% of all ovarian carcinomas in Western society are serous and up to 95% of patients are in advanced stages(FIGO stage Ⅲ-Ⅳ) at diagnosis. Treatment of ovarian cancer is mainly based on three key approaches: surgical removal of neoplasia; chemotherapy to kill cancer cells; direct chemotherapy on peritoneal surfaces. The application of hyperthermic chemotherapy to the peritoneal cavity(HIPEC) after radical surgery may also be an attractive option. We analyzed the natural history of EOC in the literature and identified various time-points where sensitivity to chemotherapy, freedom from disease and overall survival are different. We propose eight time-points in EOC history with homogeneous oncological fi ndings. The effectiveness of HIPEC in EOC treatment should be evaluated based on these eight time-points and we believe that retrospective and prospective studies of HIPEC should be evaluated according to these time-points.