• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7929-7934
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• 2014

Background: The primary objective of this study was to assess the proportion of malignancies in ovarian masses during $1^{st}$ January 2002, to $31^{st}$ December 2011 at the Department of Obstetrics and Gynecology, King Chulalongkorn Memorial Hospital. A secondary objective was to evaluate associations with patients' clinical characteristics and ovarian malignancy proportion and subtypes. Materials and Methods: Retrospective descriptive study analyzed data of ovarian masses larger than 3 centimeters in maximal diameter, from the division of Gynecologic Cyto-Pathology at KCMH. SPSS software version 17 (SPSS, Inc, Chicago, IL, USA) was used. Results: A total number of 6,115 patients were included. Among the total ovarian masses studied, 13.7% were malignant. After the age of sixty, the proportion reached almost 40%. It was also above 20% in women younger than 20 years old. During premenarche period, proportion of ovarian malignancies was 50%. Only 1% of ovarian masses were found to be malignant during the pregnancy and post-partum periods. Parity decreased the probability of ovarian malignancy during postmenopausal years. Period of menopause did not have any impact on this probability. During the first two decades of life, germ cell malignancy dominated. As the age increased, the percentage of surface epithelial-stromal malignancy increased with a peak at the fifth decade. In contrast, malignant sex cord-stromal cell tumors occurred at a constant rate in each age group after the thirties. Conclusions: Proportion of ovarian cancers in each age group, menstrual and pregnancy status are similar. However there are differences in the distribution of ovarian subtypes especially for the surface epithelial-stromal category.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.4
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• pp.1333-1340
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• 2012

Epithelial ovarian cancer represents the most lethal gynecological cancer, and the high mortality rate makes this malignancy a major health concern. Poor prognosis results from an inability to detect ovarian cancers at an early, curable stage, as well as from the lack of an effective therapy. Thus, effective and novel strategies for prevention and treatment with non-toxic agents merit serious consideration. Resveratrol, obtained from grapes, berries, peanuts and red wine, has been shown to have a potent growth-inhibitory effect against various human cancer cells as well as in in vivo preclinical cancer models. The objective here was to evaluate potential antitumor effects of resveratrol in both in vitro and in vivo NuTu-19 ovarian cancer models. In vitro an invasion assay was performed. After 48 h, the numbers of viable cells that invaded the extracellular matrix layer were reduced by 94% with resveratrol in comparison to control. For the in vivo anti-tumor assessment, 10 rats were injected with NuTu-19 cells into the ovarian bursa. Thereafter, half were provided with a diet mixed with a dose of 100 mg resveratrol/kg body weight/day for 28 days. Following sacrifice, anticancer effects were assessed by histological evaluation of ovarian as well as surrounding tissues, and immunohistochemical detection of cell proliferation and apoptosis, but there were no observable differences between the control and resveratrol-treated groups for any of the biological endpoints. While resveratrol is effective in suppressing the in vitro cellular invasion of NuTu-19 ovarian cancer cells, these effects do not appear to impact on in vivo NuTu-19 ovarian cancers in rats.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.380-388
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• 2022

Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.

• BMB Reports
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• v.47 no.1
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• pp.33-38
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• 2014

The chemokine receptor 4 (CXCR4) plays an important role in the growth, angiogenesis and metastasis of various cancers, including epithelial ovarian cancer (EOC). However, the correlation between CXCR4 and the clinical response of EOC patients to chemotherapy remains unknown. 124 EOC patients were recruited to assess the relationship between CXCR4 and the response to cisplatin-based chemotherapy. The results showed that patients with a higher CXCR4 expression had a significantly lower chemosensitivity, a poorer progression-free survival and a lower overall survival than those with lower CXCR4 expression. In addition, knockdown of CXCR4 by small interfering RNA suppressed cell proliferation and resulted in G1/S arrest, increased apoptosis and chemosensitivity in both cisplatin-sensitive A2780 cells and cisplatin-resistant cell A2780/cis in vitro. Our data suggest that CXCR4 is one of the key molecules in cisplatin-based chemotherapy for EOC patients and that CXCR4 inhibition is a potential strategy to address the chemoresistance of EOC.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.80-80
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• 1997

The object of this study was to develop a gene therapy strategy for ovarian cancer. We have previously shown that AV with a L-plastin (LP) promoter infects breast and ovarian cancer cells and expressed ${\beta}$-galactosidase cDNA in preference to normal fibroblast cells and hematopoietic cells. We now report on the cytotoxicity of Ad.LP.CD, an AV carrying a CD cDNA which converts the pro-drug, 5-Fluorocytosine (5-FC) into the toxic drug 5-Fluorouracil (5-FU). Infection of Ad.LP.CD into either 293 cells or ovarian cancer cells generated the functional CD as measured by HPLC analysis. Using a ratio of AV to OVCAR3 cell of 100 and a 5-FC concentration of 100 ${\mu}$M, we achieve an over 95 % of cell growth inhibition. We are using flow cytometry analysis for ${\beta}$ -galactosidase and ovarian cancer associated folate receptor to screen primary ascites samples for infectivity after infection with an adenoviral vector, i.e., Ad.LP.LacZ. This vector system may be of value in the treatment of microscopic disease of ovarian cancer in the peritoneal cavity.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.3003-3007
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• 2015

Objective: To explore the application of multiplex nested methylated specific polymerase chain reaction (PCR) in the early diagnosis of epithelial ovarian carcinoma (EOC). Materials and Methods: Serum and fresh tissue samples were collected from 114 EOC patients. RUNX3, TFPI2 and OPCML served as target genes. Methylation levels of tissues were assessed by multiplex nested methylated specific PCR, the results being compared with those for carcinoma antigen 125 (CA125). Results: The serum free deoxyribose nucleic acid (DNA) methylation spectrum of EOC patients was completely contained in the DNA spectrum of cancer tissues, providing an accurate reflection of tumor DNA methylation conditions. Serum levels of CA125 and free DNA methylation in the EOC group were evidently higher than those in benign lesion and control groups (p<0.05). Patients with early EOC had markedly lower serum CA125 than those with advanced EOC (p<0.05), but there was no significant difference in free DNA methylation (p>0.05). The sensitivity, specificity and positive predicative value (PPV) of multiplex nested methylated specific PCR were significantly higher for detection of all patients and those with early EOC than those for CA125 (p<0.05). In the detection of patients with advanced EOC, the PPV of CA125 detection was obviously lower than that of multiplex nested methylated specific PCR (p>0.05), but there was no significant difference in sensitivity (p>0.05). Conclusions: Serum free DNA methylation can be used as a biological marker for EOC and multiplex nested methylated specific PCR should be considered for early diagnosis since it can accurately determine tumor methylation conditions.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1881-1886
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• 2016

Background: CA125 is very helpful in treatment monitoring and detection of epithelial ovarian cancer (EOC) recurrence. However there is controversy as to its accuracy and optimal usage. What is the impact of the CA125 levels before primary surgery treatment to the survival of patients? This study aimed to detect any association of preoperative serum levels with prognosis and survival in EOC patients. Materials and Methods: Our cohort comprised EOC patients in Dr. Sardjito Hospital, Yogyakarta, Indonesia, who complied with follow up. To explore the effect of preoperative CA125 levels and other variables on survival Cox's regression models were applied. Results: A total of 90 cases of EOC who had surgery were available for follow up. The level of CA125 proved to be a prognostic factor for overall survival of EOC patients, with an adjusted HR of 4.10 (p = 0.03). Adjuvant chemotherapy was another prognostic factor, 1 - 2 cycles having an adjusted HR of 0.17 (p = 0.04) and 3 - 8 cycles HR 0.39 (p = 0.06). Other factors such as age of patients adjusted HR 1.54 (p = 0.32), moderate differentiation (adjusted HR 1.61, p = 0.51) poor differentiation (adjusted HR 3.41, p = 0.15), and stage of disease (adjusted HR 1.98,p=0.27) were statistically not significant. However, this might have been because the power of the study was low. Conclusions: Preoperative level of CA125 is a prognostic factor for overall survival in EOC patients. The best cut-off for prognostic classification of CA125 serum level is 70 U/ml.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.99.1-99.11
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• 2018

Objective: The present study is to evaluate the biological functions of long non-coding RNA (lncRNA), X-inactive specific transcript, X-inactive specific transcript (XIST) in human epithelial ovarian cancer (EOC). Methods: XIST was upregulated in EOC cell lines, CAOV3 and OVCAR3 cells by lentiviral transduction. The effects of XIST overexpression on cancer cell proliferation, invasion, chemosensitivity and in vivo tumor growth were investigated, respectively. Possible sponging interaction between XIST and human microRNA hsa-miR-214-3p was further evaluated. Furthermore, hsa-miR-214-3p was overexpressed in XIST-upregulated CAOV3 and OVCAR3 cells to evaluate its effect on XIST-mediated EOC regulation. Results: Lentivirus-mediated XIST upregulation had significant anticancer effects in CAOV3 and OVCAR3 cells by suppressing cancer cell proliferation, invasion, increasing cisplatin chemosensitivity and inhibiting in vivo tumor growth. Hsa-miR-214-3p was confirmed to directly bind XIST, and inversely downregulated in XIST-upregulated EOC cells. In EOC cells with XIST upregulation, secondary lentiviral transduction successfully upregulated hsa-miR-214-3p expression. Subsequently, hsa-miR-214-3p upregulation functionally reversed the anticancer effects of XIST-upregulation in EOC. Conclusion: Upregulation of lncRNA XIST may suppress EOC development, possibly through sponging effect to induce hsa-miR-214-3p downregulation

• BMB Reports
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• v.52 no.3
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• pp.226-226
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• 2019

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2929-2932
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• 2014

Purpose: To evaluate the diagnostic performances of risk of malignancy index (RMI), CA-125 and ultrasound score in differentiating between benign and borderline or malignant ovarian tumors and find the best diagnostic test for referral of suspected malignant ovarian cases to gynaecologic oncologists. Materials and Methods: This prospective study covered 467 women with pelvic tumors scheduled for surgery at our hospital between July 2011 and July 2013. The RMI was obtained from ultrasound score, CA125 and menopausal status. The diagnostic values of each parameter and the RMI were determined and compared using Statistical Packages for Social Sciences Version 14.0.1. Results: In our study, 61% of ovarian tumors were malignant in the post-menopausal age group. RMI with a cut-off 150 had sensitivity of 84% and specificity of 97% in detecting ovarian cancer. CA-125>30 had a sensitivity of 84% and a specificity of 83%. An ultrasound score more than 2 had a sensitivity of 96% and specificity of 81%. RMI had the least false malignant cases thus avoiding unnecessary laparotomies. Ultrasound when used individually had the best sensitivity but poor specificity. Conclusions: Our study has demonstrated the RMI to be an easy, simple and applicable method in the primary evaluation of patients with pelvic masses. It can be used to refer suspected malignant patients to be operated by a gynaecologic oncologist. Other models of preoperative evaluation should be developed to improve the detection of early stage invasive, borderline and non-epithelial ovarian cancers.