• 한국정보통신학회논문지
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• 제14권10호
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• pp.2365-2370
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• 2010

마이크로어레이를 기반으로 하는 암 분류 방법은 암 종류에 따라 다르게 발현되는 유전자 양상을 통계적으로 발견함으로써 정확한 암 분류에 기여할 수 있다. 따라서 현재의 마이크로어레이 기술을 이용해서 효과적으로 암을 분류하기 위해서는 특정 암과 밀접하게 관련이 있는 정보력 있는 유전자를 선택하는 과정이 필수적이다. 본 논문에서는 난소 암 마이크로어레이 데이터를 이용하여 암에 영향을 미치는 가장 다르게 발현할 가능성이 있는 표지 유전자를 추출할 수 있는 시스템을 고안하고, 다층퍼셉트론 분류기를 이용하여 기존의 마이크로어레이 시스템과 분류 성능을 비교분석하였다. 그 결과 ANOVA를 이용하여 선택된 표지 유전자를 포함하는 마이크로어레이 데이터 셋에서 98.61%의 향상된 분류 성능을 보였다.

• BMB Reports
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• 제46권2호
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• pp.92-96
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• 2013

The breast cancer susceptibility gene BRCA1 encodes a nuclear protein, which functions as a tumor suppressor and is involved in gene transcription and DNA repair processes. Many families with inherited breast and ovarian cancers have mutations in the BRCA1 gene. However, only a few studies have reported on the mechanism underlying the regulation of BRCA1 expression in humans. In this study, we investigated the transcriptional regulation of BRCA1 in HeLa cells treated with etoposide. We found that three Egr-1-binding sequences (EBSs) were located at -1031, -1005, and -385 within the enhancer region of the BRCA1 gene. Forced expression of Egr-1 stimulated the BRCA1 promoter activity. EMSA data showed that Egr-1 bound directly to the EBS within the BRCA1 gene. Knockdown of Egr-1 through the expression of a small hairpin RNA (shRNA) attenuated etoposide-induced BRCA1 promoter activity. We conclude that Egr-1 targets the BRCA1 gene in HeLa cells exposed to etoposide.

• Asian Pacific Journal of Cancer Prevention
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• 제16권4호
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• pp.1501-1506
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• 2015

Gemcitabine is an anti-cancer drug with clinically uses in the treatment of various neoplasms, including breast, ovarian, non-small cell lung, pancreaticand cervical cancers, T-cell malignancies, germ cell tumours, and hepatocellular carcinomas. However, it has also been reported to have many adverse effects. Naturally occurring anti-mutagenic effects, especially those of plant origin, have recently become a subject of intensive research. The present study was therefore designed to investigate the anti-mutagenic effects of Salvia merjamie (Family: Lamiaceae) plant extracts against the mutagenic effects of gemcitabine. The anti-mutagenic properties of Salvia merjamie were tested in Inbred SWR/J male and female mice bone marrow cells. The mice were treated in four groups; a control group treated with 30 mg/kg body weight gemcitabine and three treatment groups, each with 30 mg/kg body weight gemcitabine together with, respectively, 50, 100 and 150 mg/kg body weight Salvia merjamie extract. Chromosomal aberration and mitotic index assays were performed with the results demonstrating that Salvia merjamie extract protects bone marrow cells in mice against gemcitabine induced mutagenicity. This information can be used for the development of a potential therapeutic anti-mutagenic agents.

• Molecules and Cells
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• 제25권4호
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• pp.457-461
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• 2008

DNA damage checkpoint is an important self-defense mechanism for the maintenance of genome stability. Defects in DNA damage signaling and repair lead to various disorders and increase tumor incidence in humans. In the past 10 years, we have identified many components involved in the DNA damage-signaling pathway, including the product of breast cancer susceptibility gene 1 (BRCA1). Mutations in BRCA1 are associated with increased risk of breast and ovarian cancers, highlighting the importance of this DNA damage-signaling pathway in tumor suppression. While it becomes clear that BRCA1 plays a crucial role in the DNA damage responsive pathway, exactly how BRCA1 receives DNA damage signals and exerts its checkpoint function has not been fully addressed. A series of recent studies reported the discovery of many novel components involved in DNA damage-signaling pathway. These newly identified checkpoint proteins, including RNF8, RAP80 and CCDC98, work in concern in recruiting BRCA1 to DNA damage sites and thus regulate BRCA1 function in G2/M checkpoint control. This review will summarize these recent findings and provide an updated view of the regulation of BRCA1 in response to DNA damage.

• Journal of Pharmaceutical Investigation
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• 제34권2호
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• pp.125-130
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• 2004

Paclitaxel is an effective antineoplastic drug for various cancers especially ovarian and breast cancer. This study is to find the optimum condition for the preparation of nanoemulsions and to improve the stability and loading amount of paclitaxel in nanoemulsions. Nanoemulsions were prepared by modified spontaneous emulsification solvent diffusion method. It was composed of phosphatidylcholine:cholesterol:1,2-Distearoyl-sn-Glycero-3-Phosphoethanolamine-N-[Metoxy (Polyethylene glycol)-2000]:paclitaxel at a weight ratio of 5:3:1:1 and the Tween 80 as a surfactant. The particle size and the shape of nanoemulsions were measured by particle analyzer and SEM, respectively. The loading amount of paclitaxel in nanoemulsion was measured by UV-visible spectroscopy at 227 nm. The particle sizes were $80{\sim}120\;nm$ and the loading efficiency of paclitaxel was $8{\sim}39%$. The optimum conditions for the preparation of nanoemulsions were 8% w/w phospholipid, 16% w/v Tween 80 and 2% w/w paclitaxel, respectively.

• 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.

• BMB Reports
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• 제57권2호
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• pp.104-109
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• 2024

Gefitinib exerts anticancer effects on various types of cancer, such as lung, ovarian, breast, and colon cancers. However, the therapeutic effects of gefitinib on cervical cancer and the underlying mechanisms remain unclear. Thus, this study aimed to explore whether gefitinib can be used to treat cervical cancer and elucidate the underlying mechanisms. Results showed that gefitinib induced a caspase-dependent apoptosis of HeLa cells, which consequently became round and detached from the surface of the culture plate. Gefitinib induced the reorganization of actin cytoskeleton and downregulated the expression of p-FAK, integrin β1 and E-cadherin, which are important in cell-extracellular matrix adhesion and cell-cell interaction, respectively. Moreover, gefitinib hindered cell reattachment and spreading and suppressed interactions between detached cells in suspension, leading to poly (ADP-ribose) polymerase cleavage, a hallmark of apoptosis. It also induced detachment-induced apoptosis (anoikis) in C33A cells, another cervical cancer cell line. Taken together, these results suggest that gefitinib triggers anoikis in cervical cancer cells. Our findings may serve as a basis for broadening the range of anticancer drugs used to treat cervical cancer.

• Journal of Preventive Medicine and Public Health
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• 제31권4호
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• pp.801-813
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• 1998

우리 나라의 주요사망원인에 해당하는 암질환을 대상으로 YLD를 측정하여 주요암질환간 질병부담의 우선 순위 측정하고 이의 활용범위를 알아보고자 수행한 본 연구에서 다음과 같은 결과를 얻었다. 우리 나라 남성의 암으로 인한 질병부담의 우선 순위 위암(4081.4년), 간암(3104.2년), 대장 및 직장암(3086.2년), 식도암(1511.9년), 폐암(1166.7년), 췌장암(1093.8년), 방광암(665.6년), 전립선암(421.7년), 백혈병(397.2년), 임파선암(259.7년)으로 계산되었다. 여성의 경우 암으로 인한 질병부담의 우선 순위 위암(2707.1년), 식도암(1536.7년), 간암(1468.5년), 자궁암(1311.8년), 난소암(974.3년), 췌장암(763.5년), 유방암(724.5년), 폐암(689.9년), 백혈병(351.3년), 임파선암(241.1년)로 계산되었다. 이러한 결과는 본 연구에 사용한 연구재료 및 연구 방법의 불완전성에도 불구하고 향후 보건의료정책의 우선순위결정, 즉 한정된 자원을 보다 더 효율적으로 활용하는데 보다 구체적인 정보를 계량적으로 제공해 줄 수 있다는 점에서 중요한 의의를 갖는다고 하겠다.

• 생명과학회지
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• 제28권6호
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• pp.718-725
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• 2018

Toll 유사수용체의 TLR4는 세포자연사(apoptosis)와 관련하여 세포의 생존과 증식에 영향을 미치는 것으로 알려져 있다. 본 연구에서는 TLR4의 활성이 부인과 질환 특이적 종양세포의 세포사멸기작에 어떠한 영향을 미치는지 살펴보았다. TLR4의 활성에 의한 세포자연사를 확인하기 위하여 부인암 조직(자궁경부암, 자궁내막암, 난소암)에서 종양세포를 분리하여 초대배양시스템을 구축하였고, lipopolysaccharide (LPS)에 의한 TLR4의 활성유도 과정에서 종양세포의 형태학적 변화를 살펴보았다. 또한, TLR4 매개성 세포사멸 기작을 확인하기 위하여 역전사 중합효소 연쇄반응(RT-PCR)을 통해 유전자 분석을 진행하였다. 연구 결과, 부인암의 초대배양세포에서 세포접촉저지(contact inhibition)현상이 감소되었고, 세포의 배가시간(doubling time)이 단축되어, 종양세포의 성장률 변화를 확인하였다(p<0.05). 자궁근육층(정상조직)의 초대배양세포에서는 민무늬근육 확인 인자인 ITGA5 (an alpha5 integrin marker)의 유전자 발현이 나타났으나, 자궁경부조직의 초대배양세포에서는 발현변화를 확인할 수 없었다. 종양세포의 유전자분석 결과에서 p53과 같은 종양억제인자의 발현이 유의적으로 증가한 반면(p<0.05), 세포사멸 신호기작과 관련하여 TLR4와 Caspase-3의 발현은 감소하였다(Caspase-3, p<0.05). LPS를 처리한 종양세포에서는 LPS 비처리군과 비교 시, TLR4의 발현증가와 함께 Caspase-3의 발현변화가 동반되었다. 이러한 결과들은 TLR4 매개성 apoptosis 유도가 종양세포의 증식억제에 중요한 영향을 미치는 것을 의미하며, TLR4 신호기작을 이용한 종양세포의 새로운 치료적 접근법을 제시할 것으로 기대한다.

• BMB Reports
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• 제34권3호
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• pp.237-243
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• 2001

Taxol, a natural product extracted from the Taxus brevifolia, is known to have significant anti-tumor activities against many common cancers, including ovarian and breast cancers. Despite the pronounced anti-tumor activity of this compound, its poor solubility in aqueous solutions hampers its clinical applications. We studied the anticancer mechanisms of the water-soluble taxol diethylenetriamine pentaacetate (DTPA) used for radiolabeling, and compared it to that of taxol. In vitro cytotoxicities of taxol and taxol-DTPA conjugate were tested in HT29 human colorectal cancer cells by the MTT method. As the result, the $IC_{50}$ value of the taxol-DTPA conjugate was about three fold higher than that of taxol. When analyzed by an agarose gel electrophoresis, the DNA ladders became evident after the incubation of cells with the taxol-DTPA conjugate for 24 h. We also found morphological changes of the cells undergoing apoptosis with electron microscopy Next, we examined the signal pathway of taxol-DTPA conjugate-induced apoptosis in HT29 cells. The activation of extracellular signal-regulated protein kinase (ERK1/2) occurred at 10, 30, 60 and 120 min after 200 nM taxol-DTPA conjugate treatment. The pretreatment of the MEK inhibitor (PD98059) completely blocked the taxol-DTPA conjugate-induced ERK1/2 activation. The activated ERK1/2 translocated into the nucleus at the same time and phosphorylated its transcriptional factor, c-Jun. These results suggest that the taxol-DTPA conjugate has an apoptotic activity in HT29 cells, and that its proapoptic activity might be related with the signal transduction via ERK1/2 and c-Jun similar to that of taxol.