• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.3
• /
• pp.1445-1448
• /
• 2016

Purpose: The current study aimed at assessing the association between neutrophil-lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR) for the prognosis of the surgical outcome of epithelial ovarian cancer (EOC). Materials and Methods: EOC patient medical records of surgical operations between January, 2005 and December, 2015 were reviewed and their data of clinicopathological complete blood counts (CBCs) and surgical outcomes were collected. To assess their effects on surgical outcomes, PLR and NLR optimal predictive values were determined and then compared with each other. Results: A statistically significant relation was found between surgical outcomes and NLR and PLR (p<0.001 and p<0.001), for which new cutoff points were gained (PLR: 192,3,293; NLR: 3). The sensitivity and specificity were 0.74 and 0.67, respectively for PLR and 0.74 and 0.58, for NLR. Conclusions: NLR and PLR seem to be useful methods for the prediction of surgical outcomes in patients with EOCs. Increased NLR and PLR proved to be beneficial for poor surgical outcomes. Moreover, PLR increase showed further help in the predicting outcome of EOC suboptimal debulking.

• Asian Pacific Journal of Cancer Prevention
• /
• v.16 no.6
• /
• pp.2453-2458
• /
• 2015

Background: X-linked inhibitor of apoptosis protein (XIAP) associated factor 1 (XAF1) exhibits aberrantly low or absent expression in various human malignancies, closely associated with anti-apoptosis and overgrowth of cancer cells. However, limited attention has been directed towards the contribution of XAF1 to invasion, apoptosis, and cisplatin (DDP)-resistance of epithelial ovarian cancer (EOC) cells. This study aimed to evaluate the potential effects of XAF1 on invasion, cell cycle, apoptosis, and cisplatin-resistance by overexpressing XAF1 in SKOV-3 and SKOV-3/DDP cells. Methods and Results: The pEGFP-C1-XAF1 plasmid was transfected into SKOV-3 and SKOV-3/DDP cells, and the expression of XAF1 at both mRNA and protein levels was analyzed by reverse transcription-PCR and Western blotting. Overexpression of XAF1 suppressed XIAP expression in both SKOV-3 and SKOV-3/DDP cells. Transwell invasion assays demonstrated that XAF1 exerted a strong anti-invasive effect in XAF1-overexpressing cells. Moreover, flow cytometry analysis revealed that XAF1 overexpression arrested the cell cycle at G0/G1 phase, and cell apoptosis analysis showed that overexpression of XAF1 enhanced apoptosis of SKOV-3 and SKOV-3/DDP cells apparently by activating caspase-9 and caspase-3. Furthermore, MTT assay confirmed a dose-dependent inhibitory effect of cisplatin in the tested tumor cells, and overexpression of XAF1 increased the sensitivity of SKOV-3 and SKOV-3/DDP cells to cisplatin-mediated antiproliferative effects. Conclusions: In summary, our data indicated that overexpression of XAF1 could suppress XIAP expression, inhibit invasion, arrest cell cycle, promote apoptosis, and confer cisplatin-sensitivity in SKOV-3 and SKOV-3/DDP cells. Therefore, XAF1 may be further assessed as a potential target for the treatment of both cisplatin-resistant and non-resistant EOCs.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.22
• /
• pp.9739-9745
• /
• 2014

Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.20
• /
• pp.9009-9013
• /
• 2014

Background: The aim of this study was to explore the efficacy and adverse reactions of CT-guided radioactive 125I-seed implantation treatment combined with chemotherapy for platinum-resistant recurrent ovarian carcinoma. Materials and Methods: From September 2010 to December 2012, 23 patients with platinum-resistant recurrent ovarian carcinoma were enrolled. All the patients refused, could not bear, or were not suitable for surgery. They all had no more than 3 lesions, which were detected and could also be measured by CT. All were clarified as single-lesion or multiple-lesion groups. A total of 41 lesions underwent implantation of from 8 to 106 125I seeds (median=43). Multi-plane implanting was adopted and 125I-seeds of (0.4-0.7)mCi were placed at intervals of (0.5-1.0) cm. After implantation treatment, all patients underwent 4 cycles of chemotherapy with gemcitabine $800mg/m^2$ (days 1, 8 and 15). Results: The outcome was evaluated with CT 3 weeks and every 3 months after implantation treatment. After 6 months, the volume of 32 out of 41 lesions (78.0%) was reduced at least 30%, within which 9 lesions completely disappeared(22.0%). Complete response was observed in 7 cases (30.4%), with a partial response in 4 cases (17.4%), 4 cases stable(17.4%)and 8 cases showing progression (34.8%). The total clinical remission rate was 47.8% (11/23). The clinical remission rate was 77.8% (7/9) in the single-lesion group and 28.6% (4/14) in the multiple-lesion group with a significant difference between the two(P=0.036). The common side effects observed were mild gastrointestinal reactions. Conclusions: 125I-seed implantation combined with chemotherapy applies an effective way in the treatment of platinum-resistant recurrent ovarian epithelial carcinoma with the advantages of high local control rates, good short-term effects, little trauma and less side effects.

• Molecules and Cells
• /
• v.44 no.7
• /
• pp.481-492
• /
• 2021

Tribbles homolog 2 (TRIB2) is implicated in tumorigenesis and drug resistance in various types of cancers. However, the role of TRIB2 in the regulation of tumorigenesis and drug resistance of cancer stem cells (CSCs) is still elusive. In the present study, we showed increased expression of TRIB2 in spheroid-forming and aldehyde dehydrogenase-positive CSC populations of A2780 epithelial ovarian cancer cells. Short hairpin RNA-mediated silencing of TRIB2 expression attenuates the spheroid-forming, migratory, tumorigenic, and drug-resistant properties of A2780 cells, whereas overexpression of TRIB2 increases the CSC-like characteristics. TRIB2 overexpression induced GSK3β inactivation by augmenting AKT-dependent phosphorylation of GSK3β at Ser9, followed by increasing β-catenin level via reducing the GSK3β-mediated phosphorylation of β-catenin. Treatment of TRIB2-ovexpressed A2780 cells with the phosphoinositide3-kinase inhibitor LY294002 abrogated TRIB2-stimulated proliferation, migration, drug resistance of A2780 cells. These results suggest a critical role for TRIB2 in the regulation of CSC-like properties by increasing the stability of β-catenin protein via the AKT-GSK3β-dependent pathways.

• Journal of Preventive Medicine and Public Health
• /
• v.49 no.6
• /
• pp.349-366
• /
• 2016

Objectives: We conducted a systematic review and meta-analysis to summarize current evidence regarding the association of parity and duration of breastfeeding with the risk of epithelial ovarian cancer (EOC). Methods: A systematic search of relevant studies published by December 31, 2015 was performed in PubMed and EMBASE. A random-effect model was used to obtain the summary relative risks (RRs) and 95% confidence intervals (CIs). Results: Thirty-two studies had parity categories of 1, 2, and ${\geq}3$. The summary RRs for EOC were 0.72 (95% CI, 0.65 to 0.79), 0.57 (95% CI, 0.49 to 0.65), and 0.46 (95% CI, 0.41 to 0.52), respectively. Small to moderate heterogeneity was observed for one birth (p<0.01; Q = 59.46; $I^2=47.9%$). Fifteen studies had breastfeeding categories of <6 months, 6-12 months, and >13 months. The summary RRs were 0.79 (95% CI, 0.72 to 0.87), 0.72 (95% CI, 0.64 to 0.81), and 0.67 (95% CI, 0.56 to 0.79), respectively. Only small heterogeneity was observed for <6 months of breastfeeding (p = 0.17; Q = 18.79, $I^2=25.5%$). Compared to nulliparous women with no history of breastfeeding, the joint effects of two births and <6 months of breastfeeding resulted in a 0.5-fold reduced risk for EOC. Conclusions: The first birth and breastfeeding for <6 months were associated with significant reductions in EOC risk.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.8
• /
• pp.3687-3690
• /
• 2014

MicroRNA 200c is a microRNA 200 family member that plays an important role in regulation of the epithelial-to-mesenchymal transition (EMT). The prognostic value of microRNA 200c in solid tumors remains controversial because of inconsistent data. Here, we report a meta-analysis of the association of microRNA 200c expression and survival in patients with solid tumors. Pubmed was searched up to November 2013 for studies investigating microRNA 200c expression and overall survival (OS) in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) for OS were extracted from each study. Pooled HR and CIs were calculated using the Mantel-Haenszel fixed-effects models. A total of five studies evaluating colorectal cancer, gastric cancer, ovarian cancer, pancreatic cancer and endometrial cancer were included in the analysis. Data were divided into tissue microRNA 200c expression group and serum microRNA 200c expression group. The combined HRs [95%CIs] estimated for OS were 0.62 [0.42-0.91] and 2.16 [1.32-3.52] respectively. Low expression of microRNA 200c in tumor tissue and high expression of microRNA 200c in serum are associated with worse survival in solid tumors. Further study is needed to elucidate this contradiction.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.1909-1915
• /
• 2016

Background: The purpose of this study was to determine the benefit of tertiary cytoreductive surgery (TC) for secondary recurrent epithelial ovarian cancer (EOC), focusing on whether optimal cytoreduction has an impact on disease-free survival, and whether certain patient characteristics could identify ideal candidates for TC. Materials and Methods: Retrospective analysis of secondary recurrent EOC patients undergoing TC at three Turkish tertiary institutions from May 1997 to July 2014 was performed. All patients had previously received primary cytoreduction followed by intravenous platinum-based chemotherapy and secondary cytoreduction for first recurrence. Clinical and pathological data were obtained from the patients' medical records. Survival analysis was caried out using the Kaplan Meier method. Actuarial curves were compared by the two tailed Logrank test with a statistical significance level of 0.05. Results: Median age of the patients was 49.6 years (range, 30-67) and thirty-eight (72%) had stage III-IV disease at initial diagnosis. Twenty six (49%) had optimal and 27 (51%) suboptimal cytoreduction during tertiary debulking surgery. Optimal initial cytoreduction, time to first recurrence, optimal secondary cytoreduction, time interval between secondary cytoreduction and secondary recurrence, size of recurrence, disease status at last follow-up were found to be significant risk factors to predict optimal TC. Optimal cytoreduction in initial and tertiary surgery and serum CA-125 level prior to TC were independent prognostic factors on univariate analysis. Conclusions: Our results and a literature review clearly showed that maximal surgical effort should be made in TC, since patients undergoing optimal TC have a better survival. Thus, patients with secondary recurrent EOC in whom optimal cytoreduction can be achieved should be actively selected.

• Asian Pacific Journal of Cancer Prevention
• /
• v.17 no.4
• /
• pp.2271-2275
• /
• 2016

Background: The value of 5-aminolevulinic acid (ALA) in fluorescence detection of peritoneal metastases and the underlying mechanisms were evaluated in patients with peritoneal surface malignancies. Materials and Methods: Oral 5-ALA was administered at a concentration of 20 mg/kg body weight with 50 ml of water 2 hours prior to surgery (n=115). The diagnostic value of 5-ALA based fluorescence production was evaluated following white light inspection during prior to cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Then, peptide transporter PEPT1 (ALA influx transporter) and ATP-binding cassette transporter ABCG2 (porphyrin efflux transporter) gene expression was determined with quantitative real time (qRT)-PCR and pathological diagnoses confirmed for all tissue samples. Results: The 5-ALA based photodynamic detection rate was 17% for appendiceal mucinous neoplasms, 54% for colorectal cancers, 33% for gastric cancers, 67% for diffuse malign peritoneal mesotheliomas, and 89% for epithelial ovarian cancer of peritoneal metastases. 5-ALA was detected in all cases of peritoneal metastases originating from cholangiocarcinomas whereas it was not able to detect any in granulosa cell and gastrointestinal stromal tumor cases. Furthermore, PEPT1 was overexpressed whereas ABCG2 expression was downregulated in tumors detected with fluorescence. Conclusions: 5-ALA provided 100% specificity and high sensitivity to detect peritoneal metastases in subgroups of patients with peritoneal surface mailgnancies. ALA influx transporter PEPT1 and porphyrin efflux transporter ABCG2 genes are important in tumor specific 5-ALA induced fluorescence in vivo. Further studies should clarify diagnostic utility of 5-ALA in peritoneal surface malignancies.

• Journal of Veterinary Clinics
• /
• v.32 no.6
• /
• pp.530-535
• /
• 2015

An 11-year-old intact female miniature poodle presented with a four-month history of hemorrhagic effusion. The patient was alert on physical examination, although muffled heart sounds were noted upon auscultation of the right hemithorax. The radiographic finding was pleural effusion. Ultrasonography revealed cystic changes in both ovaries and several nodules in the liver. A refractory opacity in the right lung field, as visualized with computer tomography (CT), was diagnosed as right middle lung lobe torsion with a collapsed bronchus. Five days after diagnosis, a right fifth intercostal thoracotomy was performed to remove the right middle lung lobe; the right middle lung lobe was grossly shrunken as a result of chronic lung lobe torsion. Ovariohysterectomy was also performed. Histopathologic examination revealed papillary adenocarcinoma in both ovaries and suspected metastasized ovarian adenocarcinoma cells in the lung lobe. The patient recovered favorably and had been doing well up to two months post-surgery. However, after four months, the dog presented with respiratory difficulty. The radiographic findings were pleural effusion and collapse of the right cranial and left caudal lung lobes. Malignant cells of epithelial origin were observed in the pleural effusion. The tumor cells were suspected to be metastasized cells from the previously resected lung lobe. Although cancer treatment was recommended, the suggestion was suspended and the dog was discharged from hospital. This was a case of lung lobe torsion that had occurred because of hemorrhagic effusion due to tumor. Although ovariohysterectomy and lobectomy were performed, there was a relapse of hemorrhagic effusion because of metastasized tumor from the previously resected lung lobe.