• Journal of Gynecologic Oncology
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• v.29 no.6
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• pp.90.1-90.12
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• 2018

Objective: We performed small-scale mutation and large genomic rearrangement (LGR) analysis of BRCA1/2 in ovarian cancer patients to determine the prevalence and the characteristics of the mutations. Methods: All ovarian cancer patients who visited a single institution between September 2015 and April 2017 were included. Sanger sequencing, multiplex ligation-dependent probe amplification (MLPA), and long-range polymerase chain reaction (PCR) were performed to comprehensively study BRCA1/2. The genetic risk models BRCAPRO, Myriad, and BOADICEA were used to evaluate the mutation analysis. Results: In total, 131 patients were enrolled. Of the 131 patients, Sanger sequencing identified 16 different BRCA1/2 small-scale mutations in 20 patients (15.3%). Two novel nonsense mutations were detected in 2 patients with a serous borderline tumor and a large-cell neuroendocrine carcinoma. MLPA analysis of BRCA1/2 in Sanger-negative patients revealed 2 LGRs. The LGRs accounted for 14.3% of all identified BRCA1 mutations, and the prevalence of LGRs identified in this study was 1.8% in 111 Sanger-negative patients. The genetic risk models showed statistically significant differences between mutation carriers and non-carriers. The 2 patients with LGRs had at least one blood relative with breast or ovarian cancer. Conclusion: Twenty-two (16.8%) of the unselected ovarian cancer patients had BRCA1/2 mutations that were detected through comprehensive BRCA1/2 genetic testing. Ovarian cancer patients with Sanger-negative results should be considered for LGR detection if they have one blood relative with breast or ovarian cancer. The detection of more BRCA1/2 mutations in patients is important for efforts to provide targeted therapy to ovarian cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.941-946
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• 2013

Objective: The nucleotide excision repair (NER) and base excision repair (BER) pathways, two DNA repair pathways, are related to platinum resistance in cancer treatment. In this paper, we studied the association between single nucleotide polymorphisms (SNPs) of involved genes and response to platinum-based chemotherapy in epithelial ovarian cancer. Method: Eight SNPs in XRCC1 (BER), XPC and XPD (NER) were assessed in 213 patients with epithelial ovarian cancer using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) techniques. Results: The median progression-free survival (PFS) of patients carrying the Lys/Lys and Lys/Gln+Gln/Gln genotype of the XPC Lys/Gln polymorphism were 25 and 12 months, respectively (P=0.039); and the mean overall survival (OS) of patients was 31.1 and 27.8 months, respectively (P=0.048). Cox's multivariate analysis suggested that patients with epithelial ovarian cancer with the Gln allele had an increased risk of death (HR=1.75; 95% CI=1.06-2.91) compared to those with the Lys/Lys genotype. There are no associations between the XPC PAT+/-, XRCC1 Arg194Trp, Arg280His, Arg399Gln, and XPD Asp312Asn, Lys751Gln polymorphisms and the survival of patients with epithelial ovarian cancer when treated with platinum-based chemotherapy. Conclusion: Our results indicated that the XPC Lys939Gln polymorphism may correlate with clinical outcome of patients with epithelial ovarian cancer when treated with platinum-based chemotherapy in Northern China.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1251-1254
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• 2015

Background: To compare prevalence of anxiety in ovarian cancer patients following primary treatment to that of normal women and to examine predicting factor. Materials and Methods: In this cross-sectional study, 56 ovarian cancer patients who had primary surgical treatment within the past five years (cancer group) and 56 age-matched women who attended an outpatient clinic for check-ups (non-cancer group) were recruited from June 2013 to January 2014. The hospital anxiety and depression scale (HADS), was used to determine anxiety level of the participants with the score of ${\geq}11$ suggestive of anxiety. The prevalence of anxiety symptoms and mean HADS scores for anxiety were compared between the study groups. For those with ovarian cancer, associations of demographic and clinical factors with anxiety was examined. A p-value of <0.05 was considered significant. Results: Participants in the non-cancer group had higher rate of medical comorbidity, higher salary, and more frequent university education. The prevalence of anxiety was not different between the groups, at 7.1% each. The mean HADS scores for anxiety subscale were not significantly different between the groups, 5.0 in the cancer group vs 6.1 in the non-cancer group (p=0.09). On multivariable analysis, no demographic or clinical factors significantly associated with anxiety were identified. For the cancer group, no association between any particular factors and anxiety was demonstrated. Conclusions: The prevalence of anxiety in women with ovarian cancer following primary treatment was comparable to that of normal women seeking routine check-up.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8409-8411
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• 2014

Purpose: To assess the value of multi-tumor marker protein chips in the diagnosis and treatment of ovarian cancer. Materials and Methods: Twelve tumor markers (CA19-9, NSE, CEA, CA242, CK19, ${\beta}$-HCG, AFP, SCC, c-PSA, CA125, CA724 and CA15-3) were detected by protein biochip in 220 patients with ovarian carcinomas, 205 with benign ovarian tumors and 200 healthy subjects. Results: The positivity rate was obviously higher in ovarian cancer (77.7%), than that in the benign cases (26.3%, p<0.01) and healthy subjects (4.5%, p<0.01). Serum levels of tumor markers were furthermore significantly higher in cases with lymph node metastasis (86.8%) than those without metastasis (44.7%), p<0.01. Conclusions: Multi-tumor marker protein chips provide important assistance in the diagnosis and treatment evaluation in ovarian cancers.

• Animal cells and systems
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• v.1 no.2
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• pp.389-394
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• 1997

We examined the effect of modulation of PKA isozymes on the growth of human ovarian cancer cells. Three ovarian cancer cell lines, 2774, SK-OV-3, and OVCAR-3, were examined in this study. The treatment of 5 uM 8-CI-cAMP, which has been known to down-regulate RI (or type 1 PKA) and up-regulate RII (or type II PKA), markedly inhibited the growth of all cell lines (50-80% at day 6). To test whether alteration in PKA regulatory subunits level can change the growth characteristics of ovarian cancer cells, we introduced RIIB- expression construct and Rla antisense-expression construct into 2774 cells. The overexpression of RIIB down-regulated Rla protein, and the antisense-expression of Rla up-regulated RIIB protein, showing that the intracellular levels of RI and RII are reciprocally regulated. In both cases, cell growth was reduced by 30% at day 2. These results indicate that the growth of ovarian cancer cells is controlled by the signals from PKA isozymes, and the modulation of PKA isozymes can be employed for the human ovarian cancer therapy.

• The Journal of Korean Obstetrics and Gynecology
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• v.31 no.2
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• pp.18-30
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• 2018

Objective: This study was designed to investigate the anti-cancer effects of AAH on ovarian cancer in vitro and by using allograft model in vivo. Methods: In this experiment, the effects of AAH on proliferation rates, cell morphology, cell death type, cell cycle, caspase activities and p38 mitogen-activated protein kinase (MAPK) pathway were investigated in A2780, human ovarian cell line. Results: AAH inhibited proliferation of A2780 cells in a dose dependent manner. In addition, AAH induced apoptosis but did not affect cell cycle of A2780 cells. AAH also effectively inhibited caspase 3 and caspase 9 activities respectively. In allograft tumor model, AAH reduced tumor volume and expanded life span in a dose dependent manner. Conclusion: It can be inferred that AAH can induce apoptosis in ovarian cancer cells and has possibility as an anticancer agent for ovarian cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2719-2725
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• 2014

Background: Secreted frizzled-related protein (SFRP) genes, new tumor suppressor genes, are negative regulators of the Wnt pathway whose alteration is associated with various tumors. In ovarian cancer, SFRPs genes promoter methylation can lead to gene inactivation. This study investigated mechanisms of SFRP and adenomatous polyposis coli (APC) genes silencing in ovarian cancer infected with high risk human papillomavirus. Materials and Methods: DNA was extracted from 200 formalin-fixed paraffin-embedded ovarian cancer and their normal adjacent tissues (NAT) and DNA methylation was detected by methylation specific PCR (MSP). High risk human papillomavirus (HPV) was detected by nested PCR with consensus primers to amplify a broad spectrum of HPV genotypes. Results: The percentages of SFRP and APC genes with methylation were significantly higher in ovarian cancer tissues infected with high risk HPV compared to NAT. The methylated studied genes were associated with suppression in their gene expression. Conclusion: This finding highlights the possible role of the high risk HPV virus in ovarian carcinogenesis or in facilitating cancer progression by suppression of SFRP and APC genes via DNA methylation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.12
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• pp.7669-7674
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• 2013

Background: The hypothesis that patients who primarily progress on two consecutive chemotherapy regimens without evidence of clinical benefit may opt for supportive care was investigated. The purpose was to determine the quality of life in recurrent ovarian cancer patients choosing to receive salvage chemotherapy in addition to supportive care or palliative care alone. A secondary objective was to evaluate factors that affect quality of life in ovarian cancer patients. Materials and Methods: A descriptive study was conducted in patients who had histological confirmed epithelial ovarian cancer and failed to respond to at least one regimen of chemotherapy, coming for treatment at the King Chulalongkorn Memorial Hospital in Bangkok, Thailand over a six-month period from August 2012-March 2013. Each patient was asked to complete the FACT-G and a general personal questionnaire. The median quality of life score was analyzed. The Mann Whitney U Test was used to compare the difference between salvage chemotherapy and palliative care groups, and the Kruskal Wallis was used to evaluate other variables. Results: Thirty-eight ovarian cancer patients were identified who failed to respond to chemotherapy. Of the 38, 30 chose salvage chemotherapy and eight palliative care for further treatment. By histology the carcimnomas were predominantly endometrioid subtype and poorly differentiated. The majority of patients in this study had FIGO stage III, and ECOG status 0-1. The median quality of life score was 76.3 (35.8-94.0), with no significant differences between the groups. Factors associated with the quality of life were the ECOG score and number of chemotherapeutic courses. Conclusions: In the setting of refractory or recurrent epithelial ovarian cancer, patients who receive salvage chemotherapy have comparable quality of life scores with patients treated with palliative care alone, providing a contrast with previous studies.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.1799-1802
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• 2012

Objective: We aimed to analyze the association between excision repair cross-complementing rodent repair deficiency complementation group 1 (XRCC1) and ovarian cancer risk. Methods: We performed a hospital-based case-control study with 155 cases and 313 controls in China. All Chinese cases with newly diagnosed primary ovarian cancer between May 2005 to May 2010 in our hospital were invited to participate within 2 months of diagnosis. Controls were randomly selected from people who requested general health examinations in the same hospital during the same period. SNPs in EXCC1, ERCC1 C8092A and ERCC1 T19007C, were analyzed by PCR-RFLP method. Results: We observed a non-significantly increased risk of ovarian cancer among individuals with ERCC1 8092TT compared with those with the 8092CC genotype (adjusted OR=1.55, 95% CI%=0.74-2.97). Moreover, 19007TT genotype carriers also showed a non-significant increased risk of ovarian cancer over those with the 19007CC genotype (adjusted OR=1.78, 95% CI%=0.91-3.64). Conclusion: Our firstly investigation of links between polymorphisms in the ERCC1 gene and the risk of ovarian cancer in Chinese population demonstrated no significant association. Further large sample studies in Chinese populations are needed.

• BMB Reports
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• v.53 no.12
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• pp.622-627
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• 2020

Cancer stem cells (CSCs) or tumor-initiating cells are thought to play critical roles in tumorigenesis, metastasis, drug resistance, and tumor recurrence. For the diagnosis and targeted therapy of CSCs, the molecular identity of biomarkers or therapeutic targets for CSCs needs to be clarified. In this study, we identified CD166 as a novel marker expressed in the sphere-forming CSC population of A2780 epithelial ovarian cancer cells and primary ovarian cancer cells. The CD166+ cells isolated from A2780 cells and primary ovarian cancer cells highly expressed CSC markers, including ALDH1a1, OCT4, and SOX2, and ABC transporters, which are implicated in the drug resistance of CSCs. The CD166+ cells exhibited enhanced CSC-like properties, such as increased sphere-forming ability, cell migration and adhesion abilities, resistance to conventional anticancer drugs, and high tumorigenic potential in a xenograft mouse model. Knockdown of CD166 expression in the sphere-forming ovarian CSCs abrogated their CSC-like properties. Moreover, silencing of CD166 expression in the sphere-forming CSCs suppressed the phosphorylation of focal adhesion kinase, paxillin, and SRC. These results suggest that CD166 plays a key role in the regulation of CSC-like properties and focal adhesion kinase signaling in ovarian cancer.