• 제목/요약/키워드: Overcoming resistance

검색결과 75건 처리시간 0.025초

Screening assay for tomato plants resistant to Fusarium oxysporum f. sp. lycopersici race 2 using the expression of the avr2 gene as a selection marker

  • Kim, Mi-Reu;Lee, Jeong Jin;Min, Jiyoung;Kim, Sun Ha;Kim, Dae-Gyu;Oh, Sang-Keun
    • 농업과학연구
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    • 제48권1호
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    • pp.151-161
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    • 2021
  • Fusarium wilt disease of tomato plants caused by Fusarium oxysporum f.sp. lycopersici (FOL race2) is one of the most important diseases of tomatoes worldwide. In the competition between tomato and FOL, the FOL can win by overcoming the immune system of tomato plants. Resistant interaction between the FOL race2 and tomato plants is controlled by avirulence genes (AVR2) in FOL and the corresponding resistance genes (I2) in tomato plants. In this study, 7 FOL isolates (KACC) were used to test their pathogenicity, and FOL race2 was selected because it is a broad problem in Korea. The Fol40044 isolates showed the most severe pathogenicity, and the avr2 gene was also isolated and identified. Moreover, to select resistance, 20 tomato varieties were inoculated with the Fol40044, and the degree of pathogenicity was evaluated by analyzing the expression of the avr2 gene. As a result, three resistant tomato varieties (PCNUF73, PCNUF101, PCNUF113) were selected, and the expression of the avr2 gene was much lower than that of the control Heinz cultivar. This result shows that the screening assay is very efficient when the avr2 gene is used as a marker to evaluate the expression level when selecting varieties resistant to tomato wilt disease. Based on these results, it is possible to isolate the I2 gene, which exhibits resistance and molecular biological interactions with the AVR2 gene from the three tomato-resistant varieties. The I2 gene provides breeders more opportunities for Fusarium disease resistance and may contribute to our understanding of their interactions with the FOL and host plant.

Inhibition of DNMT3B and PI3K/AKT/mTOR and ERK Pathways as a Novel Mechanism of Volasertib on Hypomethylating Agent-Resistant Cells

  • Eun-Ji Choi;Bon-Kwan Koo;Eun-Hye Hur;Ju Hyun Moon;Ji Yun Kim;Han-Seung Park;Yunsuk Choi;Kyoo-Hyung Lee;Jung-Hee Lee;Eun Kyung Choi;Je-Hwan Lee
    • Biomolecules & Therapeutics
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    • 제31권3호
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    • pp.319-329
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    • 2023
  • Resistance to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) is a concerning problem. Polo-like kinase 1 (PLK1) is a key cell cycle modulator and is known to be associated with an activation of the PI3K pathway, which is related to the stabilization of DNA methyltransferase 1 (DNMT1), a target of HMAs. We investigated the effects of volasertib on HMA-resistant cell lines (MOLM/AZA-1 and MOLM/DEC-5) derived from MOLM-13, and bone marrow (BM) samples obtained from patients with MDS (BM blasts >5%) or AML evolved from MDS (MDS/AML). Volasertib effectively inhibited the proliferation of HMA-resistant cells with suppression of DNMTs and PI3K/AKT/mTOR and ERK pathways. Volasertib also showed significant inhibitory effects against primary BM cells from patients with MDS or MDS/AML, and the effects of volasertib inversely correlated with DNMT3B expression. The DNMT3B-overexpressed AML cells showed primary resistance to volasertib treatment. Our data suggest that volasertib has a potential role in overcoming HMA resistance in patients with MDS and MDS/AML by suppressing the expression of DNMT3 enzymes and PI3K/AKT/mTOR and ERK pathways. We also found that DNMT3B overexpression might be associated with resistance to volasertib.

circRNA circSnx12 confers Cisplatin chemoresistance to ovarian cancer by inhibiting ferroptosis through a miR-194-5p/SLC7A11 axis

  • Kaiyun Qin;Fenghua Zhang;Hongxia Wang;Na Wang;Hongbing Qiu;Xinzhuan Jia;Shan Gong;Zhengmao Zhang
    • BMB Reports
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    • 제56권3호
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    • pp.184-189
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    • 2023
  • Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.

미끄럼저항성능을 고려한 바닥재 시공법의 성능평가방안 (Value Analysis of Floor Covering Methods Considering the Skid Resistance Performance)

  • 윤차웅;설재남;서종원
    • 한국건설관리학회논문집
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    • 제13권2호
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    • pp.58-69
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    • 2012
  • 현대사회는 대도시의 구조물 설계 시 협소한 공간제약을 극복하기 위해 옥상 및 지하공간을 활용하고 있으며, 이에 따라 바닥재의 시공도 증가하고 있다. 바닥재의 미끄럼저항성능은 보행자 및 운전자의 안전성 및 쾌적성 관점에서 대단히 중요한 성능임에도 불구하고, 바닥재의 미끄럼저항성능에 대한 뚜렷한 기준이 없어 개선이 되고 있지 않은 실정이다. 본 논문에서는 국토해양부의 도로안전시설 설치 및 관리지침과 서울시의 서울형 보도포장 미끄럼 저항 기준에 기초하여 미끄럼저항성능의 평가방안을 제시하였다. 세 가지의 우레탄 바닥재 시공법을 선정하여 실험적인 연구를 통해 각 바닥재의 미끄럼저항성능을 분석하고, 제시된 평가 방안에 따라 평가하였으며, VE분석을 통해 세 가지 바닥재 시공법의 성능을 종합적으로 평가함으로써 미끄럼저항성능이 우수한 바닥재가 시공될 수 있도록 독려하였다. 본 논문에서 제시된 평가방법에 따른 VE분석 결과, 미끄럼저항성능이 최대 4배 이상 향상되었던 파티클재료를 첨가한 공법이 83.86의 성능지수를 보임으로써 기타 비교안에 비해 가장 우수한 성능을 나타내었다.

Effects of resistance training on the inflammatory response

  • Celle, Mariana C.;Fernandez, Maria Luz
    • Nutrition Research and Practice
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    • 제4권4호
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    • pp.259-269
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    • 2010
  • Resistance training (RT) is associated with reduced risk of low grade inflammation related diseases, such as cardiovascular disease and type 2 diabetes. The majority of the data studying cytokines and exercise comes from endurance exercise. In contrast, evidence establishing a relationship between RT and inflammation is more limited. This review focuses on the cytokine responses both following an acute bout, and after chronic RT. In addition, the effect of RT on low grade systemic inflammation such as individuals at risk for type 2 diabetes is reviewed. Cytokines are secreted proteins that influence the survival, proliferation, and differentiation of immune cells and other organ systems. Cytokines function as intracellular signals and almost all cells in the body either secrete them or have cytokine receptors. Thus, understanding cytokine role in a specific physiological situation such as a bout of RT can be exceedingly complex. The overall effect of long term RT appears to ameliorate inflammation, but the specific effects on the inflammatory cytokine, tumor necrosis factor alpha are not clear, requiring further research. Furthermore, it is critical to differentiate between chronically and acute Interleukin-6 levels and its sources. The intensity of the RT and the characteristics of the training protocol may exert singular cytokine responses and as a result different adaptations to exercise. More research is needed in the area of RT in healthy populations, specifically sorting out gender and age RT acute responses. More importantly, studies are needed in obese individuals who are at high risk of developing low grade systemic inflammatory related diseases. Assuring adherence to the RT program is essential to get the benefits after overcoming the first acute RT responses. Hence RT could be an effective way to prevent, and delay low grade systemic inflammatory related diseases.

Histone Deacetylase-3/CAGE Axis Targets EGFR Signaling and Regulates the Response to Anti-Cancer Drugs

  • Kim, Hyuna;Kim, Youngmi;Goh, Hyeonjung;Jeoung, Dooil
    • Molecules and Cells
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    • 제39권3호
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    • pp.229-241
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    • 2016
  • We have previously reported the role of miR-326-HDAC3 loop in anti-cancer drug-resistance. CAGE, a cancer/testis antigen, regulates the response to anti-cancer drug-resistance by forming a negative feedback loop with miR-200b. Studies investigating the relationship between CAGE and HDAC3 revealed that HDAC3 negatively regulated the expression of CAGE. ChIP assays demonstrated the binding of HDAC3 to the promoter sequences of CAGE. However, CAGE did not affect the expression of HDAC3. We also found that EGFR signaling regulated the expressions of HDAC3 and CAGE. Anti-cancer drug-resistant cancer cell lines show an increased expression of $pEGFR^{Y845}$. HDAC3 was found to negatively regulate the expression of $pEGFR^{Y845}$. CAGE showed an interaction and co-localization with EGFR. It was seen that miR-326, a negative regulator of HDAC3, regulated the expression of CAGE, $pEGFR^{Y845}$, and the interaction between CAGE and EGFR. miR-326 inhibitor induced the binding of HDAC3 to the promoter sequences in anti-cancer drug-resistant $Malme3M^R$ cells, decreasing the tumorigenic potential of $Malme3M^R$ cells in a manner associated with its effect on the expression of HDAC3, CAGE and $pEGFR^{Y845}$. The down-regulation of HDAC3 enhanced the tumorigenic, angiogenic and invasion potential of the anti-cancer drug-sensitive Malme3M cells in CAGE-dependent manner. Studies revealed that $PKC{\delta}$ was responsible for the increased expression of $pEGFR^{Y845}$ and CAGE in $Malme3M^R$ cells. CAGE showed an interaction with $PKC{\delta}$ in $Malme3M^R$ cells. Our results show that HDAC3-CAGE axis can be employed as a target for overcoming resistance to EGFR inhibitors.

저항과 변화의 관리: IS 도입의 패러독스 (Managing Resistance and Change: Paradox in IS Implementation)

  • 이정우;김민석
    • 경영정보학연구
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    • 제6권2호
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    • pp.25-45
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    • 2004
  • 정보시스템은 조직의 경영효율 향상을 위해 도입되고 있으나 현실적으로는 사용자 및 이해관계자들 사이에서 많은 저항이 발생하며 이를 극복하고 성공적인 도입을 위해서는 변화관리가 필수적이다. 본 연구에서는 문헌 조사와 전문가 포커스 그룹을 통하여 정보시스템 도입시 저항의 원인들을 두려움, 의심, 부담감, 이기심의 네 가지로 분류하고 이에 따른 변화관리 방안을 역시 문헌조사와 전문가 자문을 통하여 비전, 리더쉽, 커뮤니케이션, 교육훈련, 조직문화의 다섯 가지로 분류한 뒤, 이들 각 요소들간의 관계를 실증적으로 살펴보았다. 전문 컨설턴트들의 인식을 조사한 결과 비전과 리더쉽은 변화관리의 근간으로서 다른 변화관리활동 저변에 영향을 주는 것으로 나타났고, 두려움과 부담감에는 교육훈련, 의심에는 커뮤니케이션, 이기심에는 조직문화적인 방법이 효과적이라고 인식하는 것으로 나타났다.

miR-30a Regulates the Expression of CAGE and p53 and Regulates the Response to Anti-Cancer Drugs

  • Park, Deokbum;Kim, Hyuna;Kim, Youngmi;Jeoung, Dooil
    • Molecules and Cells
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    • 제39권4호
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    • pp.299-309
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    • 2016
  • We have previously reported the role of miR-217 in anti-cancer drug-resistance. miRNA array and miRNA hybridization analysis predicted miR-30a-3p as a target of miR-217. miR-30a-3p and miR-217 formed a negative feedback loop and regulated the expression of each other. Ago1 immunoprecipitation and co-localization analysis revealed a possible interaction between miR-30a-3p and miR-217. miR-30a-3p conferred resistance to anti-cancer drugs and enhanced the invasion, migration, angiogenic, tumorigenic, and metastatic potential of cancer cells in CAGE-dependent manner. CAGE increased the expression of miR-30a-3p by binding to the promoter sequences of miR-30a-3p, suggesting a positive feedback loop between CAGE and miR-30a-3p. miR-30a-3p decreased the expression of p53, which showed the binding to the promoter sequences of miR-30a-3p and CAGE in anti-cancer drug-sensitive cancer cells. Luciferase activity assays showed that p53 serves as a target of miR-30a. Thus, the miR-30a-3p-CAGE-p53 feedback loop serves as a target for overcoming resistance to anti-cancer drugs.

Methicillin resistant staphylococcus aureus에 대한 지유산의 항균활성 (Antibacterial Activity of JiYu-san Against Methicillin-resistant Staphylococcus aureus)

  • 황해;강옥화;권동렬
    • 생약학회지
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    • 제53권2호
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    • pp.87-95
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    • 2022
  • Methicillin resistance Staphylococcus aureus (MRSA) is a gram-positive bacterium, the most commonly isolated bacterial human pathogen. JiYu-san is one of the natural products used to treat diseases in the folk recipe. In this study, we investigated the antimicrobial activity of EtOH 70% extracts of JiYu-san (JYS) against MRSA. The antibacterial activity of JYS against MRSA strain was evaluated using minimum inhibitory concentration (MIC), checkerboard dilution test, and time-kill assay. The effect of JYS on the immune mechanism of MRSA was confirmed through cell membrane permeability tests and energy metabolism tests, and the antibacterial activity mechanism was performed using qRT-PCR and western blot. As a result, in the antibacterial test of JYS, the MIC was measured to be 1.9~1000 ㎍/mL, and synergistic or showed a partial synergistic effect. In addition, JYS showed antibacterial activity in a combination test with DCCD or TX-100. In a study on the mechanism of action of antibacterial activity, it was found that JYS suppressed MRSA resistance genes and proteins. These results suggest that JYS has antibacterial activity and provides great potential as a natural antibiotic by modulating the immune mechanism against MRSA.

Regulation of glucose and glutamine metabolism to overcome cisplatin resistance in intrahepatic cholangiocarcinoma

  • So Mi Yang;Jueun Kim;Ji-Yeon Lee;Jung-Shin Lee;Ji Min Lee
    • BMB Reports
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    • 제56권11호
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    • pp.600-605
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    • 2023
  • Intrahepatic cholangiocarcinoma (ICC) is a bile duct cancer and a rare malignant tumor with a poor prognosis owing to the lack of an early diagnosis and resistance to conventional chemotherapy. A combination of gemcitabine and cisplatin is the typically attempted first-line treatment approach. However, the underlying mechanism of resistance to chemotherapy is poorly understood. We addressed this by studying dynamics in the human ICC SCK cell line. Here, we report that the regulation of glucose and glutamine metabolism was a key factor in overcoming cisplatin resistance in SCK cells. RNA sequencing analysis revealed a high enrichment cell cycle-related gene set score in cisplatin-resistant SCK (SCK-R) cells compared to parental SCK (SCK WT) cells. Cell cycle progression correlates with increased nutrient requirement and cancer proliferation or metastasis. Commonly, cancer cells are dependent upon glucose and glutamine availability for survival and proliferation. Indeed, we observed the increased expression of GLUT (glucose transporter), ASCT2 (glutamine transporter), and cancer progression markers in SCK-R cells. Thus, we inhibited enhanced metabolic reprogramming in SCK-R cells through nutrient starvation. SCK-R cells were sensitized to cisplatin, especially under glucose starvation. Glutaminase-1 (GLS1), which is a mitochondrial enzyme involved in tumorigenesis and progression in cancer cells, was upregulated in SCK-R cells. Targeting GLS1 with the GLS1 inhibitor CB-839 (telaglenastat) effectively reduced the expression of cancer progression markers. Taken together, our study results suggest that a combination of GLUT inhibition, which mimics glucose starvation, and GLS1 inhibition could be a therapeutic strategy to increase the chemosensitivity of ICC.