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1.
Campos X Muñoz Y Selman A Yazigi R Moyano L Weinstein-Oppenheimer C Lara HE Romero C 《Gynecologic oncology》2007,104(1):168-175
OBJECTIVES: To compare the expression of nerve growth factor (NGF) and its high-affinity receptor trkA in normal ovaries and in epithelial ovarian carcinomas. Given NGF acts as an angiogenic factor through a vascular endothelial growth factor (VEGF)-mediated mechanism in several types of tissues, we examined whether NGF regulates the expression of VEGF isoforms in epithelial ovarian cancer (EOC). METHODS: The expression and localization of NGF and tyrosine kinase receptor A (trkA) in normal ovarian samples and in ovarian cancer samples were analyzed by RT-PCR and immunohistochemistry. NGF regulates the expression of three VEGF isoforms (VEGF(121), VEGF(165) and VEGF(189)); these were examined using RT-PCR in explants of EOC and ELISA in culture media. RESULTS: TrkA mRNA levels were over-expressed in ovarian cancer compared to normal ovarian samples, whereas NGF mRNA levels remained unchanged. NGF and trkA proteins were absent or found in very low levels in normal ovarian surface epithelium (OSE), whereas they were highly expressed in epithelial cells of EOC. Additionally, NGF stimulated the expression of VEGF isoforms in cancer explants. The effect was dose-dependent and inhibited by a NGF antibody and by K(252a), a trk receptor inhibitor. CONCLUSION: The abundance of NGF and trkA receptors in epithelial cells of EOC, together with the ability of NGF to increase VEGF expression strongly suggests an autocrine role of NGF in EOC. These findings suggest that blocking neurotrophin action could be a therapeutic target in treating ovarian cancer. 相似文献
2.
目的:探讨上皮性卵巢癌(epithelial ovarian cancer,EOC)腹水中M2型巨噬细胞(M2 macrophage)调控腹膜内肿瘤血管生成的机制。方法:分离卵巢癌患者腹水中M2型巨噬细胞,体外无血清刺激后,收集上清M2作为条件培养基(M2 macrophage conditional medium,M2 CM),分别采用结晶紫染色实验、Transwell小室迁移实验和小管样结构形成实验,检测共培养刺激后其对人脐静脉血管内皮细胞系EA.hy926增殖、迁移以及小管样结构形成的影响;酶联免疫吸附试验(ELISA)检测刺激后EA.hy926细胞分泌促血管蛋白因子——白细胞介素8(IL-8)以及血管内皮生长因子(VEGF)的影响。结果:①经M2 CM刺激后,EA.hy926细胞的增殖能力提高,结晶紫染色后检测OD值为0.192 6±0.002(P<0.05)。②细胞迁移能力提高,迁移细胞数为84.81±2.04(P<0.001)。③M2 CM可显著促进内皮细胞小管样结构形成,与对照组差异有统计学意义(P<0.05)。④ELISA显示经M2 CM刺激后,EA.hy926分泌IL-8为(1 570.45±118.64)ng/L,VEGF分泌量也显著升高,为(502.21±133.61)ng/L,与对照组差异有统计学意义(P<0.001)。结论:EOC腹水中M2型巨噬细胞可能通过上调内皮细胞分泌VEGF及IL-8等促血管生成因子,增加血管内皮细胞增殖、迁移能力及小管样结构形成,从而促进卵巢癌腹膜内血管生成。 相似文献
3.
Objective
nm23, a tumor metastasis suppressor gene, has been linked to protection against tumorigenesis and tumor metastasis. This study evaluated whether genetic variants in the nm23 gene were associated with susceptibility to epithelial ovarian cancer (EOC) or the clinical outcome of patients.Methods
A case-control study was performed with 302 patients with epithelial ovarian cancer and 302 control women. According to the genotypes, the outcome in 213 EOC patients was compared. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier plots and Cox models adjusted for clinical factors.Results
The case-control analysis showed that the rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter were not associated with the risk of developing EOC. In contrast, survival analysis showed that the rs2302254 C/T polymorphism was related to the prognosis of EOC patients. Compared with patients carrying the C/C genotype, patients carrying the T/T genotype had a shorter median PFS and median OS by Kaplan-Meier plots and Cox models adjusted for clinical factors. For rs16949649 T/C polymorphisms, Kaplan-Meier analysis indicated that patients carrying the homozygous C/C genotype had shorter PFS and OS than those carrying the T allele (T/T + T/C genotype). The Cox proportional hazard model analysis suggested that this relationship was only retained in OS when adjusted for clinical factors.Conclusion
Our studies suggest that rs16949649 and rs2302254 polymorphisms in the nm23 gene promoter may influence the prognosis of patients with epithelial ovarian cancer. 相似文献4.
Guerrero K Wang Z Bachvarova M Gregoire J Renaud MC Plante M Bachvarov D 《Gynecologic oncology》2012,125(3):720-726
Objective
In an attempt to analyze more profoundly aberrant DNA hypomethylation in epithelial ovarian cancer (EOC), we applied a novel genome-based approach which includes expression profiling following pharmacologic stimulation of DNA methylation with the methyl donor S-adenosyl-l-methionine (SAM).Methods
Four different EOC cell lines (OVCAR3, SKOV3, TOV21 and TOV112) were treated with SAM, and gene expression profiling was performed in SAM-treated and control EOC cells. Genes, downregulated upon SAM treatment were considered as potentially hypomethylated in EOC. DNA hypomethylation was independently validated in ovarian tumor and control tissues by bisulfite sequencing PCR (BSP).Results
Among the genes identified, one of particular interest was the type II serine protease TMPRSS3 gene variants A and D (TMPRSS3-A/D), previously recognized as overexpressed in EOC and representing potential EOC therapeutic targets. Consecutive BSP analysis demonstrated that the common putative promoter region of the TMPRSS3-A/D gene variants was significantly hypomethylated in high-grade serous EOC tumors, compared to low-malignant potential ovarian tumors and normal ovarian tissue.Conclusions
Our data imply that TMPRSS3-A/D overexpression in EOC is probably due to hypomethylation of their control region thus indicating that TMPRSS3-A/D variants could also represent novel molecular targets for epigenetic therapy of late stages of the disease. Our results also suggest that the frequently observed upregulation of different members of the type II serine proteases gene family in advanced cancer could be due to aberrant DNA hypomethylation. Furthermore, our study introduces a promising discovery approach that could be used for the identification of hypomethylated genes in different experimental cell models. 相似文献5.
Nagel CI Backes FJ Hade EM Cohn DE Eisenhauer EL O'Malley DM Fowler JM Copeland LJ Salani R 《Gynecologic oncology》2012,124(2):221-224
Introduction
Hematologic, gastrointestinal, and neurologic complications are common side effects of the platinum and taxane-based chemotherapy used in the primary treatment of epithelial ovarian cancer (EOC). These side effects and the impact of the resultant chemotherapy dose modification on disease free interval have not been extensively studied. The goal of this study was to determine the effect of chemotherapy delays and dose reductions on progression free survival (PFS) and overall survival (OS).Methods
A review of patients with primary epithelial ovarian, peritoneal, and fallopian tube carcinoma treated between 1/2000 and 12/2007 was performed. Inclusion criteria were advanced stage disease and first line chemotherapy with a platinum and taxane regimen. Cox proportional hazard models were used to determine the effect of chemotherapy reductions and delays on PFS and OS.Results
One hundred and fifty seven patients met the inclusion criteria. Patients were divided into four groups: no delays or reductions (48%), delay only (27%), reduction only (8%), and both delay and reduction (18%). The mean number of delays/reductions per patient was 1.1 (range = 0-5) and therapy was delayed a mean of 8 days. The most common reasons for delays/reductions were neutropenia (n = 51), thrombocytopenia (n = 45), and neuropathy (n = 18). There were no differences detected in PFS or OS between groups.Conclusions
There were no differences detected in survival between patients who required dose adjustments and treatment delays and those who did not. The lack of association between survival and chemotherapy alterations suggests that in specific circumstances patients with advanced ovarian cancer should have individualized treatment plans. 相似文献6.
Lee YY Kim TJ Kim MJ Kim HJ Song T Kim MK Choi CH Lee JW Bae DS Kim BG 《Gynecologic oncology》2011,122(3):541-547
Objective
To compare the survival outcome between clear cell carcinoma (CCC) and other histological subtypes in epithelial ovarian carcinoma (EOC).Methods
From January 1974 to February 2011, we identified a total of 31,800 (CCC; 2152, non-CCC; 29648) patients from 12 studies meeting the inclusion criteria.Results
Heterogeneity tests demonstrated significant between-study variation (I2 = 92.1%) with no significant difference in hazard ratio (HR) for death between CCC and non-CCC (HR; 1.16, 95% CI; 0.85-1.57, random-effects model). Comparing the HR based on stage I + II, and stage III + IV, between CCC and non-CCC, showed that CCC patients had a higher hazard rate for death than those with non-CCC of the ovary (stage I + II; HR; 1.17, 95% CI; 1.01-1.36, stage III + IV; HR; 1.65, 95% CI; 1.52-1.79). In a comparison of CCC and serous EOC, advanced stage (III and IV) CCC only showed a poorer hazard rate for death than serous EOC (HR; 1.71, 95% CI; 1.57-1.86).Conclusion
This analysis suggests that ovarian CCC patients had poorer prognosis than those with other histological subtypes of EOC, especially in advanced EOC stages. Different treatment strategies may be needed for patients with ovarian CCC. 相似文献7.
Barlin JN Yu C Hill EK Zivanovic O Kolev V Levine DA Sonoda Y Abu-Rustum NR Huh J Barakat RR Kattan MW Chi DS 《Gynecologic oncology》2012,125(1):25-30
Objective
To develop a nomogram based on established prognostic factors to predict the probability of 5-year disease-specific mortality after primary surgery for patients with all stages of epithelial ovarian cancer (EOC) and compare the predictive accuracy with the currently used International Federation of Gynecology and Obstetrics (FIGO) staging system.Methods
Using a prospectively kept database, we identified all patients with EOC who had their primary surgery at our institution between January 1996 and December 2004. Disease-specific mortality was estimated using the Kaplan-Meier method. Twenty-eight clinical and pathologic factors were analyzed. Significant factors on univariate analysis were included in the Cox proportional hazards regression model, which identified factors utilized in the nomogram. The concordance index (CI) was used as an accuracy measure, with bootstrapping to correct for optimistic bias. Calibration plots were constructed.Results
A total of 478 patients with EOC were included. The most predictive nomogram was constructed using seven variables: age, FIGO stage, residual disease status, preoperative albumin level, histology, family history suggestive of hereditary breast/ovarian cancer (HBOC) syndrome, and American Society of Anesthesiologists (ASA) status. This nomogram was internally validated using bootstrapping and shown to have excellent calibration with a bootstrap-corrected CI of 0.714. The CI for FIGO staging alone was significantly less at 0.62 (P = 0.002).Conclusion
We have developed an all-stage nomogram to predict 5-year disease-specific mortality after primary surgery for epithelial ovarian cancer. This tool is more accurate than FIGO staging and should be useful for patient counseling, clinical trial eligibility, postoperative management, and follow-up. 相似文献8.
Objective
Different histologic types of epithelial ovarian cancer may represent different diseases with unique clinical and molecular characteristics. Clear cell carcinoma (CCC) of the ovary has been reported as having a worse prognosis than high grade serous epithelial ovarian cancer (EOC). This article critically reviews the literature pertinent to the pathology, pathogenesis, diagnosis, management, and outcome of patients with ovarian CCC.Methods
MEDLINE was searched for all research articles published in English between January 01, 1977 and January 30, 2012 which reported on patients diagnosed with ovarian CCC. Given the rarity of this tumor, studies were not limited by design or number of reported patients.Results
Ovarian CCC tumors represent 5-25% of ovarian cancers. Its histologic diagnosis can be challenging, resulting often times in misclassification of these tumors. Ovarian CCC tends to present at earlier stages and has been associated with endometriosis, ARID1A and PIK3CA mutations. When compared to stage-matched controls, patients with early-stage ovarian CCCs may have a better prognosis than patients with high-grade serous tumors. For those with advanced stage disease, high-grade serous histology confers a better prognosis than ovarian CCC. Patients with Stage IC-IV have a relatively poor prognosis and efforts should center in discovery of more effective treatment strategies.Conclusions
Ovarian CCC is a biologically distinct entity, different from high-grade serous EOC. Future studies should explore the role of targeted therapies in the management of ovarian CCC. 相似文献9.
Solange Maria Diniz Bizzo Débora Dummer Meira José Marinaldo Lima José Cláudio Casali-da-Rocha 《International journal of gynaecology and obstetrics》2010,109(2):113-117
Objective
To determine whether peripheral plasma concentration, peritoneal fluid concentration, and/or peritoneal vascular endothelial growth factor (VEGF) burden can predict the possibility of optimal cytoreduction in women with epithelial ovarian carcinoma (EOC); and if so, to determine cutoff values below which optimal cytoreduction is likely to occur.Methods
We measured plasma VEGF concentration, peritoneal VEGF concentration, and VEGF burden in 46 women undergoing cytoreductive surgery. Univariate analysis, bivariate analysis, correlation tests, and stepwise regression were performed with cytoreduction as the outcome.Results
The VEGF burden best predicted the outcome. The area under the curve was 0.84 and the log-transformed cutoff value was 15.52 log pg. Overall, the chance of optimal cytoreduction was 11 times greater when the VEGF burden was less than 15.52 log pg. For women with advanced disease, the chance was 6 times greater below this value.Conclusion
The VEGF burden may quantify tumor activity, and it could be used when selecting patients likely to benefit from induction chemotherapy before undergoing cytoreductive surgery. 相似文献10.
M Cybulski B Jarosz A Nowakowski W Jeleniewicz P Seroczyński M Mazurek-Kociubowska 《Gynecologic oncology》2012,127(1):217-222
Objective
Ovarian cancer is the most lethal of all gynecologic malignancies. It is characterized by the spread of intraperitoneal tumors, accumulation of ascites, and formation of tumor blood vessels. Cyclin I has been linked with angiogenesis-related proteins, like vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR-2), in human breast cancer. We examined whether an association exists between expression of cyclin I, VEGFR-2, clinicopathologic parameters and survival of patients with epithelial ovarian cancer (EOC).Methods
Cyclin I and VEGFR-2 expressions were analyzed by immunohistochemistry in 55 human primary EOC tissue specimens.Results
Cyclin I immunoreactivity was significantly correlated with VEGFR-2 (R = 0.4587, P = 0.0004), and immunolabeling of cyclin I and VEGFR-2 significantly correlated with cancer cells' proliferative activity evaluated using cyclin A labeling index as a marker (R = 0.3107, P = 0.0209 and R = 0.4183, P = 0.0015, respectively). VEGFR-2 immunostaining was significantly higher in advanced, poorly differentiated, and suboptimally resected EOCs compared to their counterparts (P < 0.05). Finally, higher VEGFR-2 expression was significantly associated with shorter disease-free survival (P = 0.0437).Conclusions
Our results indicate that elevated expression of cyclin I and VEGFR-2 is likely to provide a proliferative advantage to the EOC cells, and that cyclin I may be linked with angiogenesis in EOC. Higher expression of VEGFR-2 is associated with more advanced disease. Further investigation of cyclin I in ovarian cancer is needed to evaluate if cyclin I may become a novel target for an anticancer therapy. 相似文献11.
Correa RJ Komar M Tong JG Sivapragasam M Rahman MM McFadden G Dimattia GE Shepherd TG 《Gynecologic oncology》2012,125(2):441-450
Objective
We propose that metastatic epithelial ovarian cancer (EOC) is a potential therapeutic target for the oncolytic agent, Myxoma virus (MYXV).Methods
Primary EOC cells were isolated from patient ascites and cultured as adherent cells or in suspension using Ultra Low-Attachment dishes. MYXV expressing green fluorescent protein was used to infect cells and spheroids. Infection was monitored by fluorescence microscopy, viral titering and immunoblotting for M-T7 and M130 virus protein expression, and cell viability by alamarBlue assay. Akti-1/2 (5 μM) and rapamycin (20 nM) were used to assay the role of PI3K-AKT signaling in mediating MYXV infection.Results
Ascites-derived EOC cells grown in adherent culture are effectively killed by MYXV infection. EOC cells grown in suspension to form three-dimensional EOC spheroids readily permit MYXV entry into cells, yet are protected from the cytopathic effects of late MYXV infection. Upon reattachment (to model secondary metastasis), EOC spheroids are re-sensitized to MYXV-mediated oncolysis. The critical determinant that facilitates efficient MYXV infection is the presence of an activated PI3K-AKT signaling pathway. Treatment with the specific AKT inhibitor Akti-1/2 reduces infection of monolayer EOC cells and spheroids. Direct infection of freshly-collected ascites demonstrated that 54.5% of patient samples were sensitive to MYXV-mediated oncolytic cell killing. We also demonstrate that factor(s) present in ascites may negatively impact MYXV infection and oncolysis of EOC cells, which may be due to a down-regulation in endogenous AKT activity.Conclusions
Differential activity of AKT serves as the mechanistic basis for regulating MYXV-mediated oncolysis of EOC spheroids during key steps of the metastatic program. In addition, we provide the first evidence that MYXV oncolytic therapy may be efficacious for a significant proportion of ovarian cancer patients with metastatic disease. 相似文献12.
Objective
Elafin has been reported to be abundantly expressed in human epithelial ovarian carcinoma (EOC), however, its functions are poorly understood. Here, we evaluated the role of elafin in modulating the sensitivity of human EOC cells to chemotherapeutic drugs.Methods
Elafin expression was determined by ELISA in 9 established human EOC cell lines. A lentivirus encoding elafin-specific shRNA was used to down-regulate elafin expression in OVCAR3 and OV433 cells, and a plasmid encoding elafin was used to ectopically express elafin in elafin-negative SKOV3 cells. Sensitivity to cisplatin and other genotoxic agents and to paclitaxel, an inhibitor of microtubule depolymerization, was examined in OVCAR3, OV433 and SKOV3 sublines. Cell viability was determined by the MTT assay, apoptosis by annexin V/7-AAD staining and caspase activation by fluorimetric assay.Results
Knockdown of the elafin gene decreases cisplatin IC50 by at least 2-folds in OVCAR3 and OVCAR433 cells (p < 0.01) but does not affect paclitaxel IC50. The sensitivity to other genotoxic agents such as carboplatin, cyclophosphamide and 5-fluorouracil was also increased by silencing the expression of elafin. Apoptosis and caspase-3 activation were significantly augmented in cisplatin-treated OVCAR3 cells with silenced elafin. Overexpression of elafin in SKOV3 cells made them more resistant to cisplatin and decreased cisplatin-induced apoptosis and caspase activation (p < 0.01).Conclusions
Expression of elafin decreases the sensitivity of human EOC cells to several genotoxic agents, which may have an important implication in predicting the response of patients with EOC to chemotherapy in the clinic. 相似文献13.
Elattar A Warburton KG Mukhopadhyay A Freer RM Shaheen F Cross P Plummer ER Robson CN Edmondson RJ 《Gynecologic oncology》2012,124(1):142-147
Objectives
In the present study we explore the effects of androgens and anti-androgens on primary cultures of EOC cells. We also investigate the effects of chemotherapy on AR expression. Epithelial ovarian cancer (EOC) arises from ovarian surface epithelial cells (OSE), which express the androgen receptor (AR). Androgen stimulation of OSE cells results in increased proliferation and protection from apoptosis. Nevertheless, in clinical trials anti-androgens have had a low objective response rate in relapsed ovarian cancer.Methods
1. Androgen receptor (AR) expression and response to androgenic stimulation were correlated in primary ovarian cancer cells derived from ascitic fluid from patients with advanced ovarian cancer,2. AR expression in primary epithelial ovarian cancer was investigated before and after chemotherapy using paired histological samples which had been incorporated into a tissue microarray.Results
Eleven primary ovarian cancer cultures were established from ascitic fluid. There was wide variation of expression of androgen receptor mRNA between cultures. Cell division increased after dihydro-testosterone (DHT) stimulation in 6 out of 11 primary cultures. The fraction of cells in S-phase increased from 4.4% in cells grown in serum-free medium to 8.3% in cells stimulated with 100 nM of DHT (P < 0.001). The increase in S-phase fraction was abrogated after treatment with the anti-androgen, bicalutamide in 4 out of 5 responsive cultures. There was a strong correlation (r2 = 0.7) between nuclear AR expression by immunohistochemistry and S-phase fraction changes in primary cultures.Paired pre- and post-chemotherapy histological samples from 29 patients were incorporated into a tissue microarray (TMA). Nuclear and cytoplasmic AR expression by immunohistochemistry (IHC) decreased significantly after chemotherapy (P < 0.01).Conclusion
AR expression correlates with increased S-phase fraction in response to androgenic stimulation. Immunohistochemical analysis of AR expression needs to be further tested in clinical trials to select AR positive EOC for anti-androgen therapy. Anti-androgen use early in the course of ovarian cancer is more likely to be effective as these data suggest that androgen receptor expression decreases with exposure to chemotherapy and this may explain the low response rates seen in clinical trials of patients heavily pre-treated with multiple courses of chemotherapy. 相似文献14.
Manal M. El Behery Abdalla E. Diab Moustafa A. Ebrahiem 《International journal of gynaecology and obstetrics》2011,112(2):119-121
Objective
To determine, by using 3-dimensional power Doppler ultrasonography, the effect of laparoscopic ovarian drilling (LOD) on the serum level of vascular endothelial growth factor (VEGF) and ovarian stromal blood flow changes in polycystic ovary syndrome (PCOS).Methods
A prospective controlled clinical study was conducted on 26 clomiphene-resistant women with PCOS who were scheduled for LOD and a control group of 22 fertile regularly menstruating women. VEGF and 3 ovarian Doppler indices—vascularization index, flow index, and vascularization flow index—were measured and compared between the 2 groups, and before and after LOD in the PCOS group.Results
Serum VEGF and the Doppler indices of ovarian stromal blood flow were significantly higher in the PCOS group than in the control group. Serum VEGF and the ovarian stromal blood flow Doppler indices were significantly reduced in the PCOS group after LOD.Conclusion
Increased vascularity in PCOS demonstrated by Doppler blood flow measurements might be explained by the high level of VEGF. LOD reduced ovarian vascularization and serum VEGF. 相似文献15.
RhoB mediates antitumor synergy of combined ixabepilone and sunitinib in human ovarian serous cancer
Vishnu P Colon-Otero G Kennedy GT Marlow LA Kennedy WP Wu KJ Santoso JT Copland JA 《Gynecologic oncology》2012,124(3):589-597
Objective
The aim was to evaluate antitumor activity of the combination of ixabepilone and sunitinib in pre-clinical models of chemotherapy naïve and refractory epithelial ovarian tumors, and to investigate the mechanism of synergy of such drug combination.Methods
HOVTAX2 cell line was derived from a metastatic serous papillary epithelial ovarian tumor (EOC) and a paclitaxel-resistant derivative was established. Dose response curves for ixabepilone and sunitinib were generated and synergy was determined using combination indexes. The molecular mechanism of antitumor synergy was examined using shRNA silencing.Results
The combination of ixabepilone and sunitinib demonstrated robust antitumor synergy in naïve and paclitaxel-resistant HOVTAX2 cell lines due to increased apoptosis. The GTPase, RhoB, was synergistically upregulated in cells treated with ixabepilone and sunitinib. Using shRNA, RhoB was demonstrated to mediate antitumor synergy. These results were validated in two other EOC cell lines.Conclusions
Ixabepilone plus sunitinib demonstrated antitumor synergy via RhoB in naïve and paclitaxel-resistant cells resulting in apoptosis. This study demonstrates a novel mechanism of action leading to antitumor synergy and provides ‘proof-of-principle’ for combining molecular targeted agents with cytotoxic chemotherapy to improve antitumor efficacy. RhoB could be envisioned as an early biomarker of response to therapy in a planned Phase II clinical trial to assess the efficacy of ixabepilone combined with a receptor tyrosine kinase inhibitor such as sunitinib. To the best of our knowledge, this is the first demonstration of antitumor synergy between these two classes of drugs in EOC and the pivotal role of RhoB in this synergy. 相似文献16.
17.
Song T Choi CH Cho YJ Sung CO Song SY Kim TJ Bae DS Lee JW Kim BG 《Gynecologic oncology》2012,125(2):427-432
Objective
67-kDa laminin receptor (67LR) has been identified as a prognostic biomarker for a variety of human cancers. We investigated the clinical significance of 67LR expression and its functional role in epithelial ovarian cancer (EOC).Methods
67LR expression was evaluated by immunohistochemistry in 62 patients with EOC. We assessed the correlation of 67LR expression with clinical characteristics. In vitro experiment was performed for 67LR with inhibition using siRNA to evaluate its role in cell survival, apoptosis, and invasion in EOC cells.Results
67LR was predominantly expressed on the cell membrane in the majority of EOC samples (45/62, 73%). 67LR expression was significantly correlated with advanced stage (P = 0.001). Patients with 67LR expression had shorter progression-free survival among all the patients (P = 0.010) and in particular among patients with advanced stages (P = 0.046). When 67LR expression was inhibited by siRNA in EOC cells (HeyA8 and A2780), there was a significant decrease of cell proliferation and invasion as well as increase of apoptosis.Conclusion
These findings suggest that 67LR expression may play an important role in tumor progression into advanced stage with poor prognosis in EOC and down-regulation of 67LR on tumor cells may be a therapeutic target in those patients. 相似文献18.
Chiang YC Qiu JT Chang CL Wang PH Ho CM Lin WC Huang YF Lin H Lu CH Chou CY 《Gynecologic oncology》2012,125(1):37-41
Objective
To evaluate the characteristics and outcome of patients with brain metastases from epithelial ovarian carcinoma.Methods
The clinical and pathologic characteristics, treatment and outcome of patients with brain metastases from epithelial ovarian carcinoma were analyzed from eight medical centers in Taiwan under the TGOG (Taiwanese Gynecologic Oncology Group).Results
A total of 64 patients were recruited in this study. The incidence of brain metastases from epithelial ovarian carcinoma seemed to be increasing in recent years. The median survival from the diagnosis of brain metastases was 8 months (range: 0-72). Prior cancer relapse before the diagnosis of brain metastases, number of brain metastases and multimodal treatment were related to the duration of survival.Conclusions
The prognosis for patients with brain metastases from epithelial ovarian carcinoma is generally poor. However, clinicians should keep alert to the neurological complaints of ovarian cancer patients and the patients might benefit from aggressive multimodal treatments. 相似文献19.
van Altena AM Karim-Kos HE de Vries E Kruitwagen RF Massuger LF Kiemeney LA 《Gynecologic oncology》2012,125(3):649-654