• 대한세포병리학회지
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• 제3권2호
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• pp.104-110
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• 1992

Although there have been a few reports of cases in which cancer cells of extrauterine origin were observed in vaginal smears, such findings are relatively uncommon. We recently experienced a case of ovarian serous cystadenocarcinoma diagnosed by cervicovaginal smear in a 56-year-old woman in routine work-up of carcinoma peritonei. The cellular features were several scattered cellular clusters of adenocarcinoma cells in clear background without tumor diathesis. Psammoma body was not present. Exploratory laparotomy confirmed the diagnosis of bilateral ovarian serous cystadenocarcinoma with multiple metastases.

• Molecules and Cells
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• 제44권7호
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• pp.481-492
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• 2021

Tribbles homolog 2 (TRIB2) is implicated in tumorigenesis and drug resistance in various types of cancers. However, the role of TRIB2 in the regulation of tumorigenesis and drug resistance of cancer stem cells (CSCs) is still elusive. In the present study, we showed increased expression of TRIB2 in spheroid-forming and aldehyde dehydrogenase-positive CSC populations of A2780 epithelial ovarian cancer cells. Short hairpin RNA-mediated silencing of TRIB2 expression attenuates the spheroid-forming, migratory, tumorigenic, and drug-resistant properties of A2780 cells, whereas overexpression of TRIB2 increases the CSC-like characteristics. TRIB2 overexpression induced GSK3β inactivation by augmenting AKT-dependent phosphorylation of GSK3β at Ser9, followed by increasing β-catenin level via reducing the GSK3β-mediated phosphorylation of β-catenin. Treatment of TRIB2-ovexpressed A2780 cells with the phosphoinositide3-kinase inhibitor LY294002 abrogated TRIB2-stimulated proliferation, migration, drug resistance of A2780 cells. These results suggest a critical role for TRIB2 in the regulation of CSC-like properties by increasing the stability of β-catenin protein via the AKT-GSK3β-dependent pathways.

• Molecules and Cells
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• 제43권2호
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• pp.121-125
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• 2020

The identification of adult stem cells is challenging because of the heterogeneity and plasticity of stem cells in different organs. Within the same tissue, stem cells may be highly proliferative, or maintained in a quiescent state and only to be activated after tissue damage. Although various stem cell markers have been successfully identified, there is no universal stem cell marker, which is exclusively expressed in all stem cells. Here, we discuss the roles of master developmental regulator RUNX1 in stem cells and the development of a 270 base pair fragment of the Runx1 enhancer (eR1) for use as stem cell marker. Using eR1 to identify stem cells offers a distinct advantage over gene promoters, which might not be expressed exclusively in stem cells. Moreover, RUNX1 has been strongly implicated in various cancer types, such as leukemia, breast, esophageal, prostate, oral, skin, and ovarian cancers-it has been suggested that RUNX1 dysfunction promotes stem cell dysfunction and proliferation. As tissue stem cells are potential candidates for cancer cells-of-origin and cancer stem cells, we will also discuss the use of eR1 to target oncogenic gene manipulations in stem cells and to track subsequent neoplastic changes.

• Biomolecules & Therapeutics
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• 제30권4호
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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.

• 생명과학회지
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• 제22권12호
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• pp.1621-1627
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• 2012

세포의 이동은 성장, 면역 작용, 그리고 혈관 신생 등 많은 생리현상에 중요한 역할을 한다. 또한 염증 및 종양 세포 침윤 등의 다양한 병리적 현상과도 밀접한 연관이 있다. 본 연구에서는 lysophosphatidic acid (LPA)는 활성산소의 생성을 통해 SKOV-3 난소암세포의 이동을 조절한다는 것을 관찰하였다. 먼저, 난소 암세포인 SKOV-3에서 LPA에 의한 세포의 이동이 강하게 일어남을 확인하였다. LPA에 의한 SKOV-3 세포의 이동은 phosphatidylinositol 3-kinase (PI3K)/Akt 신호전달체계를 저해시키는 약물에 의해서 완벽히 억제됨을 확인하였으나 ERK 신호전달체계를 저해시키는 약물에 의해서는 전혀 영향을 받지 않았다. 그리고 SKOV-3 세포에서 LPA에 의한 활성산소 형성이 시간에 따라 강하게 일어남을 확인하였다. 더욱이 LPA에 의한 활성산소 형성도 PI3K 또는 Akt의 저해제에 의해서 완벽히 억제됨을 확인하였으나 ERK 신호전달을 억제하였을 때는 거의 영향을 받지 않았다. SKOV-3 세포에서 LPA에 의해 생성된 활성산소는 diphenylene idonium (DPI, $10{\mu}M$), apocyanin (Apo, $10{\mu}M$)과 같은 NADPH oxidase 억제제를 전 처리하였을 때 활성산소가 형성되지 못함을 관찰하였다. 그러나 xanthine oxidase (allopurinol, Allo, $10{\mu}M$), cyclooxygenase (indomethacin, Indo, $10{\mu}M$), 또는 mitochondrial respiratory chain complex I (rotenone, Rot, $10{\mu}M$)를 억제하였을 때는 LPA에 의한 활성산소 형성에 영향을 주지 못함을 확인하였다. 마지막으로 활성산소 억제제인 N-acetylcysteine (NAC, $10{\mu}M$)에 의해서 LPA에 의한 암세포의 이동이 억제됨을 관찰하였다. 이와 더불어 LPA에 의한 SKOV-3 세포의 이동도 NADPH oxidase 억제에 의해 저해가 됨을 확인하였다. 이러한 연구결과로 보아 LPA에 의한 활성산소의 형성에는 PI3K/Akt/NADPH oxidase 신호전달체계가 중추적인 역할을 하며 이를 통해 암세포의 이동을 조절한다는 것을 알 수 있었다.

• BMB Reports
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• 제51권11호
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• pp.557-562
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• 2018

Reactive oxygen species (ROS) are major sources of cellular oxidative stress. Specifically, cancer cells harbor genetic alterations that promote a continuous and elevated production of ROS. While such oxidative stress conditions could be harmful to normal cells, they facilitate cancer cell growth in multiple ways by causing DNA damage and genomic instability, and ultimately by reprogramming cancer cell metabolism. This review provides up to date findings regarding the roles of ROS generation induced by diverse biological molecules and chemicals in representative women's cancer. Specifically, we describe the cellular signaling pathways that regulate direct or indirect interactions between ROS homeostasis and metabolism within female genital cancer cells.

• Biomolecules & Therapeutics
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• 제13권3호
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• pp.143-149
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• 2005

We have demonstrated previously on a replication incompetent recombinant adenoviral vector, AdLPCD, in which the expression of cytosine deaminase (CD) gene is driven by the tumor-specific L-plastin promoter. The object of this study was to evaluate the efficacy of AdLPCD together with 5-fluorocytosine (5-FC) in suppression of the growth of established human tumor cells of ovary, Consistent with the knowledge that infection of OVCAR-3 cells with AdLPCD resulted in expression of a functional intracellular CD enzyme capable of converting 5-FC to 5-fluorouracil (5-FU) (Chung and Deisseroth, 2004), statistically significant differences in cytotoxicity were observed when AdLPCD infected cells were also exposed to 5-FC for 6 days (p=0.05), 9 days (p<0.0005) and 12 days (p<0.005), compared to 5-FC exposure alone, These results indicate that the CD gene delivered by adenoviral vector could efficiently sensitize OVCAR-3, otherwise non-toxic 5-FC. On the other hand, SKOV-3 cells, an ovarian carcinoma cell line, were more resistant to the CD/5-FC strategy compared with OVCAR-3 cells under the same condition. The results of present study suggest that the replacement of 5-FU with CD/5-FC in combination chemotherapy would be less toxic and much greater cytotoxicity than the conventional combination chemotherapy in some patients.

• Food Science and Biotechnology
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• 제17권1호
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• pp.216-218
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• 2008

The present study was designed to determine how the phytochemical genistein activates caspase-3 to cause cell cycle arrest and apoptosis. When human ovarian cancer SK-OV-3 cells were treated with $200\;{\mu}M$ genistein for 24 hr, cell growth decreased significantly (p<0.05). Conversely, genistein treatment significantly increased cytotoxicity (measured as lactate dehydrogenase release) under the same conditions (p<0.05). To elucidate the mechanism behind the induction of apoptosis by genistein, we studied the cell cycle and caspase-3 activation. When cells were treated with genistein, the population of cells in sub-G1 phase increased by 44.2% compared to untreated cells. Genistein caused decrease in precursor caspase-3, increase in cleaved caspase-3 and a significant increase in caspase-3 activity (p<0.05). Therefore, genistein may induce apoptosis via caspase-3 activation. However, high-dose genistein treatment must be viewed with caution because of its potential cytotoxicity.

• 한국발생생물학회지:발생과생식
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• 제14권2호
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• pp.83-89
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• 2010

세포 사멸(apoptosis)은 세포의 항상성을 적절하게 유지하기 위한 중요한 메커니즘이다. BCL-2 family 단백질들은 세포의 생존과 세포 사멸을 조절하는 중요한 단백질이다. MCL-1 단백질은 세포의 생존을 촉진시키는 기능을 하는 pro-survival BCL-2 family member이며, 난소암, 혈액암, 자궁 경부암과 같은 다양한 암 조직에서 높게 발현하고 있다. 이전 연구에서, 본 연구진에 의해서 IEX-1 단백질은 MCL-1의 결합 단백질로 밝혀졌다. 본 연구에서는, 난소암 세포에서 IEX-1의 과다 발현에 의한 세포 사멸이 유도되는 것을 밝혔다. 더욱이, IEX-1 단백질은 MCL-1 단백질의 세포 생존을 위한 기능을 감소시켰으며, IEX-1에 의한 세포 사멸 효과는 MCL-1의 발현 정도의 변화에 의해서 그 기능이 영향을 받고 있었다. 그러므로 이러한 결과들은 IEX-1과 MCL-1은 세포 사멸과 생존을 조절하는 서로의 기능에 영향을 미치고, MCL-1의 기능에 대한 IEX-1의 세포 생존율 억제 효과는 항암치료 방법의 개발에 응용될 수 있는 가능성을 제시해 준다.

• 대한약학회:학술대회논문집
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• 대한약학회 2001년도 Proceedings of International Convention of the Pharmaceutical Society of Korea
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• pp.246.3-247
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• 2001