• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7129-7138
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• 2015

Background: The polycystic ovary syndrome (PCOS), characterized by hyperandrogenism and chronic anovulation, is a common endocrine disorder in women. PCOS, which is associated with polycystic ovaries, hirsutism, obesity and insulin resistance, is a leading cause of female infertility. In this condition there is an imbalance in female sex hormones. All the sequelae symptoms of PCOS gradually lead to cancer in the course of time. It is heterogeneous disorder of unknown etiology so it is essential to find the exact cause. Materials and Methods: In this study both invasive and non-invasive techniques were employed to establish the etiology. Diagnosis was based on Rotterdam criteria (hyperandrogenism, ovulatory dysfunction, PCOM) and multiparameters using buccal samples and dermatoglypic analysis and cytogenetic study for 10 cases and four age and sex matched controls. Results: In clinical analysis we have observed the mean value of total testosterone level was 23.6nmol/L, total hirsutism score was from 12-24, facial acne was found in in 70% patients with 7-12 subcapsular follicular cysts, each measuring 2-8 mm in diameter. In dermatoglypic analysis we observed increases in mean value ($45.9^{\circ}$) of ATD angle when compared with control group and also found increased frequency (38%) of Ulnar loops on both fingers (UU), (18%) whorls on the right finger and Ulnar loop on left finger (WU) and (16%) arches on right and left fingers (AA) were observed in PCOS patients when compared with control subjects. Features which could be applied as markers for PCOS patients are the presence of Ulnar loops in middle and little fingers of right and left hand. The buccal micronucleus cytome assay in exfoliated buccal cells, we found decrease in frequency of micronuclei and significant increases in frequency of karyolysed nuclei in polycystic ovarian syndrome patients. Chromosome aberration analysis revealed a significant increase in frequency of chromosome aberrations (CAs) in PCOS patients when compared with controls. Conclusions: From this present work it can be concluded that non-invasive technique like dermatoglypics analysis and buccal micronucleus cytome assays with exfoliated buccal cell can also be effective biomarkers for PCOS, along with increased CAs in lymphocytes as a sign of genetic instability. There is a hypothesis that micronuclei and chromosomal aberrations could have a predictive value for cancer. From this present work it can be concluded to some extent that non-invasive technique like dermatoglypics and buccal cell analysis can also be effective for diagnosis.

• Journal of Life Science
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• v.15 no.5 s.72
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• pp.802-808
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• 2005

Human Disabled-2 (Dab2) is a candidate tumor suppressor gone that regulates cell growth by c-Fos suppression in normal cells. In many cancer cells, Dab2 expression is lost or greatly diminished in $\∼85\%$ of the breast and ovarian cancers. In this study, we have examined the methylation status of CpG island on Dab2 gene promoter using bisulfite-assisted genomic sequencing and methylation specific PCR (MSP) method in human breast cancer cell line, MDA MB-231 cells. In normal human uterus endometrial cells, Dab2 was completely unmethylated. In contrast, Dab2 was methylated on CpG dinucleotides near the TATA_ box in MDA MB-231 cells. following MDA MB-231 cells by treatment with 5-azacytidine, Dab2 gene were demethylated and reexpressed. Result of this study suggested that silencing of Dab2 gene is correlated to CpG island methylation in human breast cancer cell line, MBA MD-231 cells.

• Biomolecules & Therapeutics
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• v.22 no.2
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• pp.129-135
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• 2014

Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) via type 1 lysophosphatidic acid (LPA) receptor ($LPA_1$) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like $LPA_1/CD97-G_{i/o}$ proteins-phospholipase $C-IP_3-Ca^{2+}$ increase in these cells. In the present study, we further investigated actions of LPE not only in the $[Ca^{2+}]_i$ increasing effect but also in cell proliferation and migration in MDA-MB-231 breast cancer cells. We utilized chemically different LPEs and a specific inhibitor of $LPA_1$, AM-095 in comparison with responses in SK-OV3 ovarian cancer cells. It was found that LPE-induced $Ca^{2+}$ response in MDA-MB-231 cells was evoked in a different manner to that in SK-OV3 cells in terms of structural requirements. AM-095 inhibited LPE-induced $Ca^{2+}$ response and cell proliferation in MDA-MB-231 cells, but not in SK-OV3 cells, supporting $LPA_1$ involvement only in MDA-MB-231 cells. LPA had significant effects on cell proliferation and migration in MDA-MB-231 cells, whereas LPE had less or no significant effect. However, LPE modulations of MAPKs (ERK1/2, JNK and p38 MAPK) was not different to those by LPA in the cells. These data support the involvement of LPA1 in LPE-induced $Ca^{2+}$ response and cell proliferation in breast MDA-MB-231 cells but unknown GPCRs (not $LPA_1$) in LPE-induced responses in SK-OV3 cells. Furthermore, although LPE and LPA utilized $LPA_1$, LPA utilized more signaling cascades than LPE, resulting in stronger responses by LPA in proliferation and migration than LPE in MDA-MB-231 cells.

• Food Science and Preservation
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• v.22 no.5
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• pp.721-726
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• 2015

Phellinus baumii has been used in traditional oriental medicine for the treatment of various cancer types, such as lung cancer, ovarian cancer and malignant melanoma. It has strong anti-cancer, anti-inflammatory and antioxidant activities due to its polysaccharides including glucan, schizophyllan, heteroglycan and lentinan, as well as its polyphenolics such as protocatechuic acid, caffeic acid, coumaric acid. ${\beta}$-Glucan and polyphenolics may be the most important activ ecompounds in P. baumii. Therefore, researchers have focused on these two compounds to improve their contents in extracts. In this study, P. baumii was extracted with hot-water and ethanol at different pH conditions, and their ${\beta}$-glucan contents, antioxidant activity and antioxidant contents were determined. Extraction yield was highest for the 60% ethanol extract at pH 4. The ${\beta}$-glucan contents of the hot-water extract at pH 7 was higher than those of the ethanol extracts. The antioxidant contents and antioxidant activities of the ethanol extracts were higher than those of the hot-water extracts. Extraction with 60% ethanol at pH 7 was appropriate with respect to the antioxidant capacities.

• Journal of Life Science
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• v.16 no.1
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• pp.12-16
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• 2006

Genetic alternation of Brca1 predispose of breast and ovarian cancer. Brca1 plays critical role in cell cycle regulation following DNA damage. Previous studies revealed that Brca1 plays an important role in S phase and G2/M checkpoint regulation. However, whether Brca1 involves in spindle checkpoint is unclear. In this study, the role of Brca1 in cell cycle response following nocodazole, which is a reagent that depolymerizes microtubules and activates the spindle checkpoint, has been examined using wild type $p53^{-/-}\;and\;p53^{-/-}Brca1^{-/-}$ mouse embryonic fibroblasts (MEFs). While wild type and Brca1-proficient MEFs showed an acute mitotic arrest, Brca1-deficient MEFs failed to arrest at mitotic phase in response to nocodazole treatment. In double-thymidine block and nocodazole treatment experiment, a portion of $p53^{-/-}\;Brca1^{-/-}$ MEFs were clearly by-passed nocodazole induced mitotic arrest. Consistent with this, in morphologic analysis, $p53^{-/-}\;Brca1^{-/-}$ MEFs showed growing cell morphology after nocodazole treatment. Taken together, these results suggest that Brca1 protein is an important component for normal induction of spindlecheckpoint and impairment of Brca1 function could induce dysregulation of mitotic cell cycle that ultimately results in genomic instability.

• Journal of Life Science
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• v.29 no.1
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• pp.105-111
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• 2019

In recent years, progress has been made in the search for the development of new anti-cancer agents by employing specific inhibitors of histone deacetylase (HDAC)-6 to block signal transduction pathways in cancer cells. This study examined the effects of tubastatin A (TubA), an HDAC-6 inhibitor, on the growth and development of immature oocytes in murine ovaries using RNA sequencing analysis. The results from a gene set enrichment analysis (GSEA) indicated that the expression of most of the gene sets involved in the cell cycle and control and progression of meiosis decreased in the TubA-treated group as compared with that in germinal vesicle (GV) stage oocytes. In addition, an ingenuity pathway analysis (IPA) suggested that TubA not only caused increased expression of p53 and pRB and decreased expression of CDK4/6 and cyclin D but also caused elevated expression of genes involved in the control of the DNA check point in G2/M stage oocytes. These results suggest that TubA may induce cell cycle arrest and apoptosis through the induction of changes in the expression of genes involved in signal transduction pathways associated with DNA damage and the cell cycle of immature oocytes in the ovary.

• The Korean Journal of Nuclear Medicine Technology
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• v.25 no.2
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• pp.25-28
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• 2021

Purpose CA 72-4 is a tumor marker that uses two monoclonal antibodies, CC49 and B72.3, to measure tumor-related glycoprotein(TAG72) in the serum. CA 72-4 is used to diagnose stomach, ovarian, and pancreatic cancers, and is known to perform high specificity for stomach cancer. The purpose of this study is to re-evaluate the reference value provided by the manufacturer through revalidation of the reference value in CA 72-4. Furthermore this study was conducted to provide useful help when making a clinical diagnosis at gastric cancer center. Materials and Methods We selected 271 patients who had been to health care center in national cancer center for the month of November 2020. The gender of the subjects was 140 males and 131 females, and the age group was from 30s to 60s. The reagent used in the study was a CA 72-4 IRMA KIT (ISOTOPES, Hungary) and the results were measured using a Dream Gamma-10 gamma counter (Shinjin medics, Korea). Results Statistical analysis of the results of this study used Hoffmann's method and Bayesian's method, which are primarily used in setting reference value. As a result of measuring CA 72-4 of 271 patients, the mean value was 4.54 U/mL and the median value was 3.30 U/mL. 24 people who deviated from 3SD were excluded from the measured value, the mean calculated after that was 3.53 U/mL, median was 3.00 U/mL and SD was 1.89. The reference value calculated based on this results was set to 7.31 U/mL. Conclusion The reference value provided by the manufacturer is less than 4 U/mL. It is slightly different from the value calculated in this study, 7.31 U/mL, so it seems necessary to reset the reference value according to the laboratory environment. Currently, we are receiving inquiries about the reference value from the center for gastric cancer at National Cancer Center. If additional research is carried out along with this study, it will be possible to set more accurate reference value.

• Journal of Life Science
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• v.28 no.6
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• pp.718-725
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• 2018

Toll-like receptor 4 (TLR4) has been implicated in cell proliferation and apoptosis in several types of cancer. In this study, the impact of TLR4 activation on apoptotic cell death in gynecologic cancers induced by lipopolysaccharide (LPS) was investigated. Cervical cancer cell lines were produced from isolated surgical specimens supplied by Paik Hospital. The primary cultures of normal myometrium and gynecologic cancers, including cervical, endometrial, and ovarian cancers, were used to examine the differences in morphological characteristics between normal and cancerous cells. A reverse transcription polymerase chain reaction analysis was used to determine the relative expression levels of TLR4 gene involved in apoptosis-associated signaling in cervical cancer cells. The cancer cell colonies showed a tendency to reach high levels of confluency compared with normal cells. In addition, an enhanced growth rate and loss of contact inhibition were observed in gynecologic cancer cells compared with normal cells (doubling times of 16.6 hr vs. 26 hr, respectively). The expression level of ITGA5, an alpha-5 integrin marker, was upregulated in normal myometrial cells, but this tendency was not exhibited in cervical cancer cells. Furthermore, p53 tumor suppressor gene expression was upregulated, whereas TLR4 and caspase-3 gene expressions were downregulated in cervical cancer cells. Notably, the expression levels of TLR4 and caspase-3 were increased significantly in LPS-treated cancer cells compared with those in non-LPS-treated cells. These results suggest that the TLR4-mediated caspase-dependent apoptotic signaling pathway could be suggested as a therapeutic target for the treatment of gynecologic cancers, including cervical cancers.

• The Journal of Korean Society for Radiation Therapy
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• v.33
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• pp.145-153
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• 2021

Purpose: The purpose of this study is to evaluate the ovarian dose during radiation therapy for breast cancer in women of childbearing age through an experiment. The ovarian dose is evaluated by comparing and analyzing between the calculated dose in the treatment planning system according to the treatment technique and the measured dose using a thermoluminescence dosimeter (TLD). The clinical usefulness of lead (Pb) apron is investigated through dose analysis according to whether or not it is used. Materials and Methods: Rando humanoid phantom was used for measurement, and wedge filter radiation therapy, 3D conformal radiation therapy, and intensity modulated radiation therapy were used as treatment techniques. A treatment plan was established so that 95% of the prescribed dose could be delivered to the right breast of the Rando humanoid phantom 3D image obtained using the CT simulator. TLD was inserted into the surface and depth of the virtual ovary of the Rando hunmanoid phantom and irradiated with radiation. The measurement location was the center of treatment and the point moved 2 cm to the opposite breast from the center of the Rando hunmanoid phantom, 5cm, 10cm, 12.5cm, 15cm, 17.5cm, 20cm from the boundary of the right breast to the center of treatment and downward, and the surface and depth of the right ovary. Measurements were made at a total of 9 central points. In the dose comparison of treatment planning systems, two wedge filter treatment techniques, three-dimensional conformal radiotherapy, and intensity-modulated radiation therapy were established and compared. Treatments were compared, and dose measurements according to the use of lead apron were compared and analyzed in intensity-modulated radiation therapy. The measured value was calculated by averaging three TLD values for each point and converting using the TLD calibration value, which was calculated as the point dose mean value. In order to compare the treatment plan value with the actual measured value, the absolute dose value was measured and compared at each point (%Diff). Results: At Point A, the center of treatment, a maximum of 201.7cGy was obtained in the treatment planning system, and a maximum of 200.6cGy was obtained in the TLD. In all treatment planning systems, 0cGy was calculated from Point G, which is a point 17.5cm downward from the breast interface. As a result of TLD, a maximum of 2.6cGy was obtained at Point G, and a maximum of 0.9cGy was obtained at Point J, which is the ovarian dose, and the absolute dose was 0.3%~1.3%. The difference in dose according to the use of lead aprons was from a maximum of 2.1cGy to a minimum of 0.1cGy, and the %Diff value was 0.1%~1.1%. Conclusion: In the treatment planning system, the difference in dose according to the three treatment plans did not show a significant difference from 0.85% to 2.45%. In the ovary, the difference between the Rando humanoid phantom's treatment planning system and the actual measured dose was within 0.9%, and the actual measured dose was slightly higher. This did not accurately reflect the effect of scattered radiation in the treatment planning system, and it is thought that the dose of scattered radiation and the dose taken by CBCT with TLD inserted were reflected in the actual measurement. In dosimetry according to the with or without a lead apron, when a lead apron was used, the closer the distance from the treatment range, the more effective the shielding was. Although it is not clinically appropriate for pregnancy or artificial insemination during radiotherapy, the dose irradiated to the ovaries during treatment is not expected to significantly affect the reproductive function of women of childbearing age after radiotherapy. However, since women of childbearing age have constant anxiety, it is thought that psychological stability can be promoted by presenting the data from this study.

• Journal of Life Science
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• v.28 no.7
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• pp.874-883
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• 2018

Osteoporosis is a disease that increases the risk of fracture by decreasing the mass and strength of bone. It is caused by imbalance of osteoclast bone formation and osteoclast bone resorption. Bone formation by osteoblast is activated via bone morphogenetic proteins and runt-related transcription factor 2. $Wnt/{\beta}-catenin$ signaling and bone resorption by osteoclast are initiated by the binding of receptor activator of nuclear $factor-{\kappa}B$ ligand and receptor activator of nuclear $factor-{\kappa}B$. Menopausal women are at risk for many diseases due to hormonal imbalances, and osteoporosis is the most common metabolic disorder in 30% of postmenopausal women. When estrogen is deficient, bone resorption of osteoclasts is promoted, and the risk of osteoporosis especially increases in postmenopausal women. Hormone replacement therapy has been widely used to relieve or treat the symptoms of menopausal syndrome. However, long-term administration of hormone therapy has been associated with a high risk of side effects, such as breast cancer, ovarian cancer, and uterine cancer. Recently, phytochemicals have been actively studied as a phytoestrogen, which has an estrogen-like activity to cope with symptoms of menopausal syndrome. Therefore, in this review, we investigated the differentiation mechanism of osteoblast and osteoclast and the role of estrogen and phytoestrogen in bone metabolism in relation to previous studies.