• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8599-8604
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• 2016

Ovarian cancer is the main cause of mortality in gynecological malignancy and extensive studies have been conducted to study the underlying molecular mechanisms. The BRCA2 gene is known to be an important tumor suppressor in ovarian cancer, thereby BRCA2 alterations may lead to cancer progression. However, the BRCA2 gene is rarely mutated, and loss of function is suspected to be mediated by epigenetic regulation. In this study we investigated the methylation status and gene expression of BRCA2 in ovarian cancer patients. Ovarian cancer pateints (n=69) were recruited and monitored for 54 months in this prospective cohort study. Clinical specimens were used to study the in situ expression of aberrant BRCA2 proteins and the methylation status of BRCA2. These parameters were then compared with clinical parameters and overall survival rate. We found that BRCA2 methylation was found in the majority of cases (98.7%). However, the methylation status was not associated with protein level expression of BRCA2 (49.3%). Therefore in addition to DNA methylation, other epigenetic mechanisms may regulate BRCA2 expresison. Our findings may become evidence of BRCA2 inactivation mechanism through DNA methylation in the Indonesian population. More importantly, from multivariate analysis, BRCA2 expression was correlated with better overall survival (HR 0.32; p=0.05). High percentage of BRCA2 methylation and correlation of BRCA2 expression with overall survival in epithelial ovarian cancer cases may lead to development of treatment modalities specifically to target methylation of BRCA genes.

• Journal of Embryo Transfer
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• v.27 no.2
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• pp.87-92
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• 2012

A study on estrus synchronized dairy cows using progesterone intravaginal device was done to classify each cow's reproductive status from calving to synchronization and to evaluate the reproductive performance according to ovarian and uterine status, and calving season. From calving to estrus synchronization, silent heat or error of estrus detection among ovarian status and endometritis among uterine disorders were exposed in the most distribution (75.4% and 48.3%, respectively). The pregnancy rate of cows with inactive ovaries was lower than those in the follicular and luteal phase. And according to the uterine status before estrus synchronization, the pregnancy rate was similar in three groups; normal, endometritis, and pyometra (70.9, 69.1 and 100%, respectively). The interval from calving to conception was shorter (p<0.05) in cows calved during autumn than in cows calved during spring and winter.

• Journal of Veterinary Clinics
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• v.40 no.3
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• pp.238-241
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• 2023

This study determined the effect of ovarian status at the beginning of the modified Double-Ovsynch program on reproductive performance in dairy cows. In the study, 1,302 cows were treated with a modified Double-Ovsynch program at 56 days after calving. This program comprises administering gonadotropin-releasing hormones (GnRH), prostaglandin F_2α (PGF_2α) 10 days later, GnRH 3 days later, GnRH 7 days later, and GnRH 56 h later, followed by timed artificial insemination (TAI) 16 h later. At the beginning of the program, cows were categorized according to the size of the largest follicle and the presence of a corpus luteum (CL) in the ovaries as follows: 1) small follicle (<5 mm, SF group, n = 100), 2) medium follicle (8-20 mm, MF group, n = 538), and 3) large follicle (≥25 mm, LF group, n = 354) without a CL, or 4) the presence of a CL (CL group, n = 310). The pregnancies per AI after the first TAI were analyzed by logistic regression using the LOGISTIC procedure, and the logistic model included the fixed effects of the herd size, parity, body condition score (BCS) at the first TAI, TAI period, and ovarian status. A larger herd size, higher BCS at the first TAI, and TAI period with no heat stress increased (p < 0.05) the probability of pregnancy per AI after the first TAI. However, ovarian status at the beginning of the program did not affect (p > 0.05) the pregnancies per AI (ranges of 37.9% to 42.9%). These results show that the modified Double-Ovsynch program can be used effectively while maintaining good fertility regardless of the ovarian status in dairy herds.

• Korean Journal of Veterinary Service
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• v.27 no.1
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• pp.41-52
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• 2004

To establish the differential diagnosis and functional status in ovarian cystic cows, progesterone(P$_4$) and estrogen(E$_2$) level of cystic follicular fluid, ultrasonography for measuring the cystic diameter and thickness of cystic wall, and histological findings were investigated in cystic ovaries from slaughtered Korean native cows. Ovarian follicles were classified as systic if the diameter was greater than 25 mm by ultrasonography. Ovarian cysts < 3 mm of cystic wall thickness, < 10 ng/ml P$_4$ concentration and >10 ng/ml E$_2$ concentration were classified follicular cyst, ovarian cysts 3 mm of cystic wall thickness, 10 ng/ml P$_4$ concentration and <10 ng/ml E$_2$ concentration were classified luteal cyst, and ovarian cysts 3 mm of cystic wall thickness, < 10 ng/ml P$_4$ concentration and <10 ng/ml E$_2$ concentration were classified non-functional ovarian cyst, respectively. Also ovarian cysts were classified 8 types by anatomical and hisctological findings. Ovarian cysts with corpus luteum were 3 of 73 cows and ovarian cysts without corpus luteum were 70 cows. The incidence rates of 8 various types of ovarian cysts were as follows; 2Aa 56.2%, 2Ba 20.5% and 2Ab 15.1%, respectively. The incidence rates of ovarian cysts without corpus luteum were follicular cyst 76.7% and luteal cyst 19.2%. The thickness of cystic wall were lAb 3.9 mm, 2Ab 3.3 mm and 2Bb 3.2 mm, and the cystic fluid P$_4$ concentrations were above 10.0 ng/ml in lAb, 2Ab and 2Bb, respectively. There was significantly correlations between the thickness of cystic wall and cystic fluid P$_4$ concentration in ovarian cysts(p<0.05). The ovarian cyst was classified follicular cysts, luteal cyst and non-functional ovarian cyst by hormone analysis. The luteal cyst was accuratly dignosed by cystic wall thickness. But follicular cysts was misdiagnosed 13 cows of 56 cystic cows. The 13 cystic cows was determined as had non-fuctional ovarian cysts. The cystic fluid P$_4$ concentration was 3.3 ng/ml in follicular ovarian cysts and 30.1 ng/ml luteinized ovarian cysts. There was significantly positive correlations between thickness of cystic wall and serum P$_4$ concentration in follicular(r$^2$ =0.59, p<0.001) and luteal cysts(r$^2$=0.65, p<0.001). These results indicated that ovarian cysts had various stages of degeneration and luteal cyst was accuratly diagnosed measurement of cystic wall thickness by ultrasonography, but follicular cysts was not diagnosed only cystic diameter and cystic wall thickness. In conclusion, it is suggest that ovarian cysts was diagnosed by combination of clinical sign and anatomical cystic features.

• BMB Reports
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• v.56 no.6
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• pp.347-352
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• 2023

The protein family of poly (ADP-ribose) polymerases (PARPs) is comprised of multifunctional nuclear enzymes. Several PARP inhibitors have been developed as new anticancer drugs to combat resistance to chemotherapy. Herein, we characterized PARP4 mRNA expression profiles in cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines. PARP4 mRNA expression was significantly upregulated in cisplatin-resistant ovarian cancer cell lines, and this upregulation was associated with the hypomethylation of specific cytosine-phosphate-guanine (CpG) sites (cg18582260 and cg17117459) on its promoter. Reduced PARP4 expression was restored by treating cisplatin-sensitive cell lines with a demethylation agent, implicating the epigenetic regulation of PARP4 expression by promoter methylation. Depletion of PARP4 expression in cisplatin-resistant cell lines reduced cisplatin chemoresistance and promoted cisplatin-induced DNA fragmentation. The differential mRNA expression and DNA methylation status at specific PARP4 promoter CpG sites (cg18582260 and cg17117459) according to cisplatin responses, was further validated in primary ovarian tumor tissues. The results showed significantly increased PARP4 mRNA expressions and decreased DNA methylation levels at specific PARP4 promoter CpG sites (cg18582260 and cg17117459) in cisplatin-resistant patients. Additionally, the DNA methylation status at cg18582260 CpG sites in ovarian tumor tissues showed fairly clear discrimination between cisplatin-resistant patients and cisplatin-sensitive patients, with high accuracy (area under the curve = 0.86, P = 0.003845). Our findings suggest that the DNA methylation status of PARP4 at the specific promoter site (cg18582260) may be a useful diagnostic biomarker for predicting the response to cisplatin in ovarian cancer patients.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9479-9485
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• 2014

Background: Cancer initiation and progression are controlled by genetic and epigenetic events. One epigenetic process which is widely known is DNA methylation, a cause of gene silencing. If a gene is silenced the protein which it encodes will not expressed. Objectives: 1. Identify the methylation status of BRCA1 in patients with epithelial ovarian cancer (EOC)and assess BRCA1 protein expression in tumor tissue. 2. Examine whether BRCA1 gene methylation and BRCA1 protein are associated with survival of epithelial ovarian cancer patients. Methods: The study design was a prospective-cohort study, conducted at Sardjito hospital, Yogyakarta, Indonesia. Results: A total of 69 cases were analyzed in this study. The data showed that the methylation status of BRCA1 in EOC was positive in 89.9%, with clear protein expression of BRCA1 in 31.9%. Methylation status and expression of BRCA1 were not prognosticators of EOC patients. Menarche, CA125 level, clinical stage and residual tumor were independent factors for prognosis.

• The Journal of Korean Obstetrics and Gynecology
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• v.32 no.4
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• pp.170-180
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• 2019

Objectives: The purpose of this study is to report the case of Korean medicine treatment on primary ovarian insufficiency. Methods: The patient in this case was 29-year-old female who was diagnosed with primary ovarian insufficiency. She had irregular menstruation and hypomenorrhea more than 6 months. She also suffered from hot flash and vaginal dryness. She was treated over 1 year with Korean medicine treatment, such as herbal medicine, acupuncture, and pharmacopuncture. We assessed the clinical symptoms, menstrual status and serum hormone level during the treatment. Results: After treatment, symptoms of primary ovarian insufficiency were relieved, level of serum FSH decreased and level of serum E2 increased. We maintained the treatment over 1 year and kept follow-up measurements of serum hormone level. Conclusions: This study shows that Korean medicine treatment can be effective in treating primary ovarian insufficiency. The report suggests the long treatment procedure for primary ovarian insufficiency.

• 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.16 no.16
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• pp.7267-7270
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• 2015

Introduction: Kelantan is one of the states in Malaysia which has a high prevalence of type 2 diabetes (DM2). Other than with endometrial carcinoma, the association of DM2 with particular female cancers is not known. Objective: To determine the proportion of breast, cervical, ovarian and endometrial cancers among females with DM2 diagnosed in Hospital Universiti Sains Malaysia (HUSM) over an 11 year period. Materials and Methods: All histologically confirmed cases of breast, endometrial, cervical and ovarian carcinomas admitted to the Hospital were included in the study. The patient diabetic status was traced from the hospital medical records. Results: There was a total of 860 cases of breast, cervical, ovarian and endometrial carcinomas over this period. Breast carcinoma was the commonest, accounting for 437/860 (50.8%) followed by cervix, 159/860 (18.5%), ovarian, 143/860 (16.6%) and endometrial carcinomas, 121/860 (14.1%). Out of these, 228/860 (26.5%) were confirmed diabetics. Endometrial carcinoma patients showed the highest proportion being diabetics, 42.1% (51/121), followed by ovarian cancer, 25.9% (37/143), breast carcinoma, 23.6% (103/437) and cervical cancer 23.3% (37/159). Conclusions: There is a significant proportion of DM2 among women with these four cancers, endometrial carcinoma being the highest followed by ovarian, breast and cervical carcinoma. The rising trend of these four cancers is in tandem with an increasing trend of DM2 in the community. In populations where diabetes is prevalent, screening for epithelial cancers should be rigourous. Diabetic clinics should include screening for these cancers among their female patients and gynecology clinics should screen the women they treat for their diabetes status.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.3
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• pp.1171-1176
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• 2014

Objective: The tumor suppressor gene, Ras-association domain family (RASSF)2A, is inactivated by promoter hypermethylation in many cancers. The current study was performed to evaluate the methylation status of RASSF2A in epithelial ovarian cancer (EOC) tissues and plasma, and correlations with gene expression and clinicopathologic characteristics. Method: We detected methylation of the RASSF2A gene in tissues and corresponding plasma samples from 47 EOC patients and 14 patients with benign ovarian tumors and 10 with normal ovarian tissues. The methylation status was determined by methylation-specific PCR while gene expression of mRNA was examined by RT-PCR. The EOC cell line, SKOV3, was treated with 5-aza-2'-deoxycytidine (5-azadC). Results: RASSF2A mRNA expression was significantly low in EOC tissues. The frequency of aberrant methylation of RASSF2A was 51.1% in EOC tissues and 36.2% in corresponding plasma samples, whereas such hypermethylation was not detected in the benign ovarial tumors and normal ovarian samples. The expression of RASSF2A mRNA was significantly down-regulated or lost in the methylated group compared to the unmethylated group (p<0.05). After treatment with 5-aza-dC, RASSF2A mRNA expression was significantly restored in the Skov3 cell line. Conclusion: Epigenetic inactivation of RASSF2A through aberrant promoter methylation may play an important role in the pathogenesis of EOC. Methylation of the RASSF2A gene in plasma may be a valuable molecular marker for the early detection of EOC.