• 생명과학회지
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• 제19권7호
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• pp.871-877
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• 2009

대표적인 histone deacetylase inhibitor 저해제의 일종일 sodium butyrate에 의한 인체백혈병 U937세포의 증식 억제에 관한 기전 연구를 세포주기 조절 측면에서 조사하였다. MTT assay 및 flow cytometry 분석을 통하여 sodium butyrate의 처리 농도 증가에 따른 U937 세포의 증식억제는 세포주기 G1 arrest 및 apoptosis 유발에 의한 것임을 확인하였다. RT-PCR및 Western blotting 결과에서 sodium butrate에 의한 G1 arrest는 세포주기 G1기에서 S기로의 진입에 중요한 역할을 하는 cyclin D1, E, A, cyclin-dependent kinase (Cdk) 4 및 Cdk6발현의 저해와 p21 및 p27과 같은 Cdk inhibitor의 발현 증가와 연관성이 있었다. Sodium butyrate는 또한 retinoblastoma protein (pRB)및 p130 단백질의 인산화를 저해시켰으나, S기 진행에 중요한 전사조절인자인 E2F-1 및 E2F-4의 의 발현에는 큰 영향이 없었다. 그러나 sodium butyrate에 의한 pRB 및 p130단백질의 인산화 저해는 pRB와 E2F-1및 p130과 E2F-4와의 결합력을 증사시켰다. 본 연구의 결과는 U937세포의 증식억제에 pRB/p130 인산화 억제 및 Cdk inhibitors의 발현 증가가 중요한 역할을 하고있음을 보여주는 것으로, sodium butyrate의 항암기전 이해에 중요한 자료가 될 것이다.

• 한국가금학회지
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• 제15권4호
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• pp.269-275
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• 1988

단백질 수준이 18%인 초생추 사료와 12%인 비육우 후반기 사료를 입자도의 크기에 따라 전 사료의 80%가 1.19mm 이하인 것과 전 사료의 40%가 1.19mm 이하인 것으로 나누어서 40일간 저장후 각 처리구의 영양소 변화를 비교하였다. 영양소 변화를 비교한 후 초생추 사료만을 이용하여 입자의 크기를 다르게 하여 항곰팡이제를 처리한 사료와 처리하지 않은 사료에 대한 병아리의 성장 및 사료이용 정도 그리고 장기의 발달을 비교하였다. 항곰팡이가 처리되지 않은 사료에서는 2개의 다른 단백질 수준에서 공히 지방과 카로틴 함량은 현저히(P＜0.05) 감소를 초래하였다. 항곰팡이제가 처리된 사료에서도 입자 크기가 1.1mm 보다 작은 것이 전체 사료의 40% 이하인 구에서는 지방과 카로틴의 함량이 40일간의 저장 후 에는 감소하는 추세를 보였다. 또 입자가 큰 사료에서 항곰팡이제를 처리하지 않았을 때는 신선한 사료나 항곰팡이제를 처리한 구에 비교하여 병아리의 성장이나 사료 섭취량은 현저히 감소(P＜0.05)를 나타냈다. 사료효율 역시 항곰팡이제를 처리하지 않은 구에서 현저히 맞았다. (P＜0.05), 그러나 각 장기의 무게에는 처리간에 차이를 나타내지 못하였다.

• 대한한방부인과학회지
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• 제15권4호
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• pp.1-16
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• 2002

This work examines the effect of treatment with Gyukhachukeotang on the growth of uterine myomal cells. Comparisons of cell growth, MAP kinase activity and expression of bcl-2 (apoptosis-related gene) were made between the control and experimental samples. The results as fallows; 1. Any concentration of Gyukhachukeotang above 0.01% yielded growth inhibition. Concentrations of 5% and 10% stopped all cell growth, demonstrating the effectiveness of Gyukhachukeotang as a growth inhibitor on uterine myomal cells. 2. The MAP kinase activity in uterine myomal cells treated with Gyukhachukeotang was decreased to a high degree at the concentration of 10%, and some inhibition of activity was detected at a concentration of 5%. 3. The expression of bcl-2, a Cell Apoptosis-related gene, in uterine myoma cells treated with Gyukhachukeotang was gradually increased with increasing concentration of Gyukhachukeotang. These results indicate the ability of Gyukhachukeotang to control uterine myomal cell growth, with concurrent reduction of MAP kinase activity. Treatment with Gyukhachukeotang appears to trigger a normal apoptosis response, as indicated by increased bcl-2 expression. This observed increase in apoptosis indicates that Gyukhachukeotang is an appropriate prescription to treat uterine myomal cells.

• Biomolecules & Therapeutics
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• 제28권2호
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• pp.172-183
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• 2020

Phosphoinositide 3-kinase (PI3K) is considered as a promising therapeutic target for rheumatoid arthritis (RA) because of its involvement in inflammatory processes. However, limited studies have reported the involvement of PI3KC2γ in RA, and the underlying mechanism remains largely unknown. Therefore, we investigated the role of PI3KC2γ as a novel therapeutic target for RA and the effect of its selective inhibitor, PBT-6. In this study, we observed that PI3KC2γ was markedly increased in the synovial fluid and tissue as well as the PBMCs of patients with RA. PBT-6, a novel PI3KC2γ inhibitor, decreased the cell growth of TNF-mediated synovial fibroblasts and LPS-mediated macrophages. Furthermore, PBT-6 inhibited the PI3KC2γ expression and PI3K/AKT signaling pathway in both synovial fibroblasts and macrophages. In addition, PBT-6 suppressed macrophage migration via CCL2 and osteoclastogenesis. In CIA mice, it significantly inhibited the progression and development of RA by decreasing arthritis scores and paw swelling. Three-dimensional micro-computed tomography confirmed that PBT-6 enhanced the joint structures in CIA mice. Taken together, our findings suggest that PI3KC2γ is a therapeutic target for RA, and PBT-6 could be developed as a novel PI3KC2γ inhibitor to target inflammatory diseases including RA.

• The Plant Pathology Journal
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• 제16권3호
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• pp.125-129
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• 2000

A rapid and efficient assay to determine melanin biosynthesis inhibition of Magnaporthe grisea, a causal agent of the rice blast, by chemicals was developed. Wells in 24-well plates were loaded with spore suspension of the fungus and three known melanin biosynthesis inhibitors of KC10017, tricyclazole, and carpropamid. Subsequent color changes of mycelia and culture media in the wells were observed 7 days after incubation. The wells treated with KC10017 (an inhibitor of polyketide synthesis step and/or pentaketide cyclization step) became colorless, whereas tricyclazole (an inhibitor of 1, 3, 8-trihydroxynaphthalene reductase) or carpropamid (an inhibitor of scytalone dehydratase)-treated wells exhibited red color. They did not show any inhibitory effect on fungal growth. The inhibition of reaction steps prior to 1, 3, 6, 8-tetrahydroxynaphthalene formation was easily determined by colorless medium and mycelia. However, it was impossible to distinguish between inhibition of reduction steps and inhibition of dehydration steps by colors of the cultures. It was accomplished through HPLC analysis of the melanin biosynthesis-involving pentaketide metabolites accumulated by the inhibitors. Through screening of a number of synthetic chemicals using the in vitro assay, we could find a novel chemical group of melanin biosynthesis inhibitor.

• 대한환경공학회지
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• 제39권2호
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• pp.59-65
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• 2017

본 연구에서는 식품과 화장품 재료로 다양하게 이용되는 천연다당류의 특성인 분자구조, 분자량, 점성, 친수성, 팽윤 및 습윤/보습 등을 이용하여 $PM_{10}$에 대한 먼지 억제제를 제조하였고 Lab과 Field Test를 통하여 다양한 먼지 제어 효과를 확인하였으며 대조군인 물에 의한 단순 살수와 합성 PVA보다 우수한 결과를 도출하였다. 또한, 수분 증발 비교, 배추씨 발아와 배추 생장 비교실험(Pot Test), 물고기와 수생식물에 대한 영향 및 허브 식물 성장에 대한 영향 등의 토양 및 수질 시험 등을 통하여 토양과 수질에서의 안전성 등을 연구하여 Polysaccharides를 이용한 $PM_{10}$ 먼지 억제제의 이용 가능성을 확인할 수 있었다.

• Journal of Korean Neurosurgical Society
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• 제58권3호
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• pp.205-210
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• 2015

Objective : This study was aimed at optimizing the treatment of non-small-cell lung cancer (NSCLC) patients who are candidates for stereotactic radiosurgery (SRS) for brain metastases and harbor activating epithelial growth factor receptor (EGFR) mutations. Methods : We retrospectively reviewed the medical records from 2005 to 2010 of NSCLC patients with brain metastases harboring an activating EGFR mutation. Patients who received a combination therapy of SRS and EGFR-tyrosine kinase inhibitor (TKI) for brain metastases and those who received SRS without EGFR-TKI were compared. The primary endpoint was progression-free survival (PFS) of the brain metastases. Results : Thirty-one patients were eligible for enrolment in this study (SRS with TKI, 18; SRS without TKI, 13). Twenty-two patients (71.0%) were women and the median overall age was 56.0 years. PFS of brain lesions was not significantly prolonged in SRS with TKI treatment group than in SRS without TKI group (17.0 months vs. 9.0 months, p=0.45). Local tumor control rate was 83.3% in the combination therapy group, and 61.5% in the SRS monotherapy group (p=0.23). There were no severe adverse events related with treatment in both groups. Conclusions : Therapeutic outcome of concurrent SRS and TKI treatment was not superior to SRS monotherapy, however, there was no additive adverse events related with combined treatment.

• Maxillofacial Plastic and Reconstructive Surgery
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• 제34권4호
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• pp.239-245
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• 2012

Purpose: Vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis and lymphangiogenesis including induction of endothelial cell proliferation, migration and capillary tube formation. E7080 (S1164, Selleck chemical, Houston, TX, USA) is a muti-targeted kinase inhibitor, which targets VEGF receptor-2, 3 (VEGFR-2, 3) and inhibits survival and proliferation of tumor cell. The purpose of this study was to determine the anti-tumor effect of E7080 on oral squamous cell carcinoma. Methods: An oral squamous cell carcinoma cell line, SCC-9 was used in this study. E7080 was applied to SCC-9 cells by 3 different concentrations (1, 5, 10 ${\mu}g/mL$). Control means no application of E7080. The cellular growth was evaluated by real-time cell electronic sensing and MTT assay. The signal transduction was evaluated by Western blotting. Results: In experimental group, SCC-9 cell proliferation was decreased and the VEGFR-3 downstream pathways were inhibited compared with control. Furthermore, increasing the concentration of E7080, the ability of E7080 to disturbance of SCC-9 cell proliferation was increased. Conclusion: Proliferation of SCC-9 cells was inhibited by E7080, which was through by inhibition of VEGFR-3 downstream pathway. In vivo study with E7080 will be required to provide therapeutic benefits in oral squamous cell carcinoma.

• Tuberculosis and Respiratory Diseases
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• 제74권3호
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• pp.129-133
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• 2013

The presence of epidermal growth factor receptor (EGFR ) mutation is a prognostic and predictive marker for EGFR-tyrosine kinase inhibitor (TKI) therapy. However, inevitably, relapse occurs due to the development of acquired resistance, such as T790M mutation. We report a case of repeated responses to EGFR-TKIs in a never-smoked woman with adenocarcinoma. After six cycles of gemcitabine and cisplatin, the patient was treated by gefitinib for 4 months until progression. Following the six cycles of third-line pemetrexed, gefitinib retreatment was initiated and continued with a partial response for 6 months. After progression, she was recruited for an irreversible EGFR inhibitor trial, and the time to progression was 11 months. Although EGFR direct sequencing on the initial diagnostic specimen revealed a wild-type, we performed a rebiopsy from the progressed subcarinal node at the end of the trial. The result of peptide nucleic acid clamping showed L858R/L861Q.

• Asian Pacific Journal of Cancer Prevention
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• 제13권4호
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• pp.1395-1399
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• 2012

Background: Histone deacetylase (HDAC) inhibitors have been reported to induce cell growth arrest, apoptosis and differentiation of tumor cells. The present study aimed to examine the effects of trichostatin A (TSA), one such inhibitor, on the cell cycle, apoptosis and invasiveness of osteosarcoma cells. Methods: MG-63 cells were treated with TSA at various concentrations. Then, cell growth and apoptosis were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2H-tetrazolium bromide (MTT) and TUNEL assays, respectively; cell cycling was assessed by flow cytometry; invasion assays were performed with the transwell Boyden Chamber system. Results: MTT assays revealed that TSA significantly inhibited the growth of MG-63 cells in a concentration and time dependent manner. TSA treated cells demonstrated morphological changes indicative of apoptosis and TUNEL assays revealed increased apoptosis of MG-63 cells after TSA treatment. Flow cytometry showed that TSA arrested the cell cycle in G1/G2 phase and annexin V positive apoptotic cells increased markedly. In addition, the invasiveness of MG-63 cells was inhibited by TSA in a concentration dependent manner. Conclusion: Our findings demonstrate that TSA inhibits the proliferation, induces apoptosis and inhibits invasiveness of osteosarcoma cells in vitro. HDAC inhibitors may thus have promise to become new therapeutic agents against osteosarcoma.