• Asian Pacific Journal of Cancer Prevention
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• v.15 no.8
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• pp.3363-3368
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• 2014

Background: Curcumin, a phenolic compound extracted from the rhizomes of Curcuma longa, has shown cytotoxic effects against a variety of cancers. The aim of this study was to identify potential microRNA (miRNA) mediators of the anticancer effects of curcumin in ovarian cancer cells. Materials and Methods: SKOV3 ovarian cancer cells were treated with curcumin ($10-60{\mu}M$) and miR-9 expression, cell proliferation, and apoptosis were assessed. The effects of miR-9 depletion on curcumin-mediated growth suppression were also examined. Phosphorylation of Akt and forkhead box protein O1 (FOXO1) was measured in cells with miR-9 overexpression or curcumin treatment. Results: Curcumin caused a significant and dose-dependent increase of miR-9 expression in SKOV3 cells, while significantly impeding cell proliferation and stimulating apoptosis. Depletion of miR-9 significantly (p<0.05) attenuated the growth-suppressive effects of curcumin on SKOV3 cells, coupled with reduced percentages of apoptotic cells. In contrast, overexpression of miR-9 significantly enhanced the cleavage of caspase-3 and poly(ADP-ribose) polymerase and promoted apoptotic death in SKOV3 cells. Western blot analysis showed that both miR-9 overexpression and curcumin similarly caused a significant (p<0.05) decline in the phosphorylation of Akt and FOXO1, compared to untreated cells. Conclusions: The present study provided evidence that curcumin exerts its cytotoxic effects against SKOV3 ovarian cancer cells largely through upregulation of miR-9 and subsequent modulation of Akt/FOXO1 axis. Further studies are needed to identify direct targets of miR-9 that mediate the anticancer effects of curcumin in ovarian cancer cells.

• Journal of Yeungnam Medical Science
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• v.37 no.3
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• pp.179-185
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• 2020

Background: Approximately 100,000 women are diagnosed with cancer each year in Korea. According to a survey by the Korean central cancer registry in 2016, uterine cervical cancer, uterine corpus cancer, and ovarian cancer were the 5th, 7th, and 8th most prevalent cancers respectively among Korean women. The present study aims to review the clinico-pathologic characteristics of patients who were treated for major gynecological malignancies at Yeungnam University Medical Center. Methods: Patients with invasive gynecological cancers from January 2012 to February 2019 were retrospectively identified. We analyzed the clinical features, demographic profiles, pathologic data, treatment modality used, adjuvant treatment used, complications, recurrence, and survival outcomes. Results: A total of 287 patients (cervical cancer 115; corporal cancer 86; and ovarian, tubal, or primary peritoneal cancer 90) were included. Most cervical (82.7%) and corporal cancers (89.5%) were diagnosed in the early stages (stage I or II), while more than half (58.9%) the cases of ovarian, tubal or peritoneal cancers were diagnosed in the advanced stages (stage III or IV). Surgical complications were observed in 12.2% of cervical cancers, 16.3% of uterine corpus cancers, and 11.1% of ovarian, tubal, and peritoneal cancers, respectively. The 5-year overall survival rate was 94.1%, 91.0%, and 77.1% for cervical, corporal, and ovarian, tubal, or peritoneal cancers, respectively. Conclusion: Surgical treatment was satisfactory in terms of the incidence of complications, and survival outcomes were generally good. Clinicians should be aware of the clinical and histopathological characteristics of patients with gynecological cancers to be able to provide optimal strategies and counseling.

• 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.15 no.19
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• pp.8121-8125
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• 2014

Background: Ovarian mucinous carcinoma has a poor prognosis in advanced stages and a poor response to conventional chemotherapy. An efficient treatment is not yet available. We heere investigated HER2 expression and the potential for trastuzumab therapy in ovarian mucinous tumors. Materials and Methods: Immunohistochemistry was performed in formalin-fixed, paraffin-embedded tissue from 27 ovarian mucinous tumors including 14 carcinomas and 13 borderline tumors diagnosed in the Pathology Department, Farhet Hached Hospital, Sousse, between 1993 and 2013. The HercepTest (DAKO) was used for immunohistochemistry. Results: HER2 expression was observed in only one borderline tumor (7.7%) and in 14.3% of mucinous carcinomas of the ovary. Conclusions: Our results suggest that trastuzumab therapy would be an option for patients with mucinous carcinoma when the tumor has HER2 overexpression.

• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.96.1-96.12
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• 2018

The 3-weekly regimen of carboplatin and paclitaxel is the backbone of first line adjuvant chemotherapy for advanced ovarian cancer. The landmark Japanese Gynaecologic Oncology Group (JGOG) 3016 study demonstrated significant improvements in progression-free survival and overall survival with dose dense weekly administration of paclitaxel in combination with 3-weekly carboplatin. However, efforts to replicate these benefits have failed in subsequent phase III trials. Weekly paclitaxel is purported to have enhanced antitumor activity, with stronger anti-angiogenic effects, and yet is better tolerated. In this review, we explore the rationale for dose dense weekly paclitaxel, and compare the relevant trials as well as quality of life considerations. Possible reasons for the difference in outcomes between the JGOG 3016 and other studies are reviewed, with a focus on how the addition of bevacizumab, the variations between histological and molecular subtypes of epithelial ovarian cancers, and ethnic pharmacogenetic differences may potentially affect the efficacy of dose dense paclitaxel.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2689-2692
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• 2014

Purpose: To investigate the risk factors for appendiceal metastasis of epithelial ovarian cancer and compare findings with the previous studies. Materials and Methods: One hundred and thirty-four patients with epithelial ovarian cancer were assessed in this study. All of them had undergone a surgical procedure including appendectomy. Of these, 21 (15.7%) patients who had appendiceal metastasis were analyzed as the case group and the patients with no metastasis were the controls, compared according to stage, grade, histology of tumor, preoperative Ca125 levels, presence of ascites, peritoneal cytology, diameter and site of tumor considered as risk factors. Results: We found statistically significant differences between the groups in terms of stage, grade, right-sided tumor location, presence of ascites, diameter of tumor${\geq}10cm$ and positive peritoneal cytology (p<0.05). In the logistic regression model, stage, grade, presence of ascites, right-sided location and diameter of tumor were independent risk factors. ROC curve analysis showed that stage, grade and diameter of the tumor were discriminative factors for appendiceal metastasis. Conclusions: In epithelial ovarian cancer, stage, grade, presence of ascites, right-sided location and large tumor size have importance for estimation of risk of appendiceal metastasis. As we compare our findings with previous studies, there is no definite recommendation for the risk factors of appendiceal metastasis in epithelial ovarian cancer and more studies are needed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3635-3638
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• 2015

Several improvements in ovarian cancer treatment have been achieved in recent years, both in surgery and in combination chemotherapy with targeting. However, ovarian tumors remain the women's cancers with highest mortality rates. In this scenario, a pivotal role has been endorsed to the immunological environment and to the immunological mechanisms involved in ovarian cancer behavior. Recent evidence suggests a loss of the critical balance between immune-activating and immune-suppressing mechanisms when oncogenesis and cancer progression occur. Ovarian cancer generates a mechanism to escape the immune system by producing a highly suppressive environment. Immune-activated tumor infiltrating lymphocytes (TILs) in ovarian tumor tissue testify that the immune system is the trigger in this neoplasm. The TIL mileau has been demonstrated to be associated with better prognosis, more chemosensitivity, and more cases of optimal residual tumor achieved during primary cytoreduction. Nowadays, scientists are focusing attention on new immunologically effective tumor biomarkers in order to optimize selection of patients for recruitment in clinical trials and to identify relationships of these biomarkers with responses to immunotherapeutics. Assessing this point of view, TILs might be considered as a potent predictive immunotherapy biomarker.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3977-3982
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• 2012

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.18
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• pp.7941-7945
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• 2014

Catechol-O-methyltransferase (COMT) is involved in estrogen metabolism and is vital to estrogen-induced carcinogenesis, including that of ovarian cancer. Although many recent epidemiologic studies have investigated associations between the COMT rs4680 polymorphism and ovarian cancer risk, the results remain inconclusive. We therefore performed a meta-analysis to derive a more precise estimate of associations. Systematic searches of the PubMed, Embase, Web of Science, Cochrane Library, Wanfang, China National Knowledge Infrastructure, and Chinese Biomedicine databases were undertaken to retrieve eligible studies. Odds ratios (ORs) with their corresponding 95% confidence intervals (CIs) were pooled to assess the strength of the association. In total, 8 case-control studies involving 1,293 cases and 2,647 controls were included in the meta-analysis. Overall, the results showed no evidence of significant association between the COMT rs4680 polymorphism and ovarian cancer risk in any of the assessed genetic models. Subgroup analyses by ethnicity also did not reveal any significant association in any genetic model (p>0.05). In conclusion, our findings suggest that the COMT rs4680 polymorphism may not contribute to the risk of ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.10
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• pp.5007-5010
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• 2012

Objective: We conducted a prospective study to test the association between three amino acid substitution polymorphismic variants of DNA repair genes, XRCC1 (Arg194Trp), XRCC1(Arg280His) and XRCC1 (Arg399Gln), and clinical outcome of ovarian cancer patients undergoing adjuvant chemotherapy. Methods: 195 patients with primary advanced ovarian cancer and treated by adjuvant chemotherapy were included in our study. All were followed-up from Jan. 2007 to Jan. 2012. Genotyping of XRCC1 polymorphisms was conducted by TaqMan Gene Expression assays. Results: The XRCC1 194 Trp/Trp genotype conferred a significant risk of death from ovarian cancer when compared with Arg/Arg (HR=1.56, 95%CI=1.04-3.15). Similarly, those carrying the XRCC1 399 Gln/Gln genotype had a increased risk of death as compared to the XRCC1 399Arg/Arg genotype with an HR (95% CI) of 1.98 (1.09-3.93). Conclusion: This study is the first to provide evidence that XRCC1 gene polymorphisms would well be useful as surrogate markers of clinical outcome in ovarian cancer cases undergoing adjuvant chemotherapy.