• Title/Summary/Keyword: MDR

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A Comparison Study on SVM MDR and D-MDR for Detecting Gene-Gene Interaction in Continuous Data (연속형자료의 유전자 상호작용 규명을 위한 SVM MDR과 D-MDR의 방법 비교)

  • Lee, Jong-Hyeong;Lee, Jea-Young
    • Communications for Statistical Applications and Methods
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    • v.18 no.4
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    • pp.413-422
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    • 2011
  • We have used a multifactor dimensionality reduction(MDR) method to study the major gene interaction effect in general; however, without application of the MDR method in continuous data. In light of this, many methods have been suggested such as Expanded MDR, Dummy MDR and SVM MDR. In this paper, we compare the two methods of SVM MDR and D-MDR. In addition, we identify the gene-gene interaction effect of single nucleotide polymorphisms(SNPs) associated with economic traits in Hanwoo(Korean cattle). Lastly, we discuss a new method in consideration of the advantages that the other methods present.

A Study on the Comparison between E-MDR and D-MDR in Continuous Data (연속형 데이터에서 E-MDR과 D-MDR방법 비교)

  • Lee, Jea-Young;Lee, Ho-Guen
    • Communications for Statistical Applications and Methods
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    • v.16 no.4
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    • pp.579-586
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    • 2009
  • We have used multifactor dimensionality reduction(MDR) method to study interaction effect of statistical model in general. But MDR method cannot be applied in all cases. It can be applied to the only case-control data. So, two methods are suggested E-MDR and D-MDR method using regression tree algorithm and dummy variables. We applied the methods on the identify interaction effects of single nucleotide polymorphisms(SNPs) responsible for longissimus mulcle dorsi area(LMA), carcass cold weight(CWT) and average daily gain(ADG) in a Hanwoo beef cattle population. Finally, we compare the results using permutation test.

Increases in Doxorubicin Sensitivity and Radioiodide Uptake by Transfecting shMDR and Sodium/Iodide Symporter Gene in Cancer Cells Expressing Multidrug Resistance (다약제내성 암세포에서 shMDR과 Sodium/Iodide Symporter 유전자의 이입에 의한 Doxorubicin 감수성과 방사성옥소 섭취의 증가)

  • Ahn, Sohn-Joo;Lee, Yong-Jin;Lee, You-La;Choi, Chang-Ik;Lee, Sang-Woo;Yoo, Jeong-Soo;Ahn, Byeong-Cheol;Lee, In-Kyu;Lee, Jae-Tae
    • Nuclear Medicine and Molecular Imaging
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    • v.41 no.3
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    • pp.209-217
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    • 2007
  • Purpose: Multidrug resistance (MDR) of the cancer cells related to mdr1 gene expression can be effectively treated by selective short hairpin RNA for mdr1 gene (shMDR). Sodium/iodide symporter (NIS) gene is well known to have both reporter and therapeutic gene characteristics. We have co-transfected both shMDR and NIS gene into colon cancer cells (HCT15 cell) expressing MDR and Tc-99m sestamibi and I-125 uptake were measured. In addition, cytotoxic effects of doxorubicin and I-131 therapy were also assessed after transfection. Material and Methods: At first, shMDR was transfected with liposome reagent into human embryonic kidney cells (HEK293) and HCT cells. shMDR transfection was confirmed by RT-PCR and western blot analysis. Adenovirus expressing NIS (Ad-NIS) gene and shMDR (Ad-shMDR) were co-transfected with Ad-NIS into HCT15 cells. Forty-eight hours after infection, inhibition of P-gycoprotein (Pgp) function by shMDR was analyzed by a change of Tc-99m sestamibi uptake and doxorubicin cytotoxicity, and functional activity of induced NIS gene expression was assessed with I-125 uptake assay. Results: In HEK293 cells transfected with shMDR, mdr1 mRNA and Pgp protein expressions were down regulated. HCT15 cells infected with 20 MOI of Ad-NIS was higher NIS protein expression than control cells. After transfection of 300 MOI of Ad-shMDR either with or without 10 MOI of Ad-NIS, uptake of Tc-99m sestamibi increased up to 1.5-fold than control cells. HCT15 cells infected with 10 MOI of Ad-NIS showed approximately 25-fold higher I-125 uptake than control cells. Cotransfection of Ad-shMDR and Ad-NIS resulted in enhanced cytotoxic by doxorubicin in HCT15 cells. I-131 treatment on HCT15 cells infected with 20 MOI of Ad-NIS revealed increased cytotoxic effect. Conclusion: Suppression of mdr1 gene expression, retention of Tc-99m sestamibi, enhanced doxorubicin cytotoxicity and increases in I-125 uptake were achieved in MDR expressing cancer cell by co-transfection of shMDR and NIS gene. Dual therapy with doxorubicin and radioiodine after cotransfection shMDR and NIS gene can be used to overcome MDR.

Isolation and characterization of BrMDR1 a novel MDR-type ATP-binding cassette (ABC) transporter in Brassica rapa L.

  • Lee, Sun-Yong;Jung, Yu-Jin;Kang, Kwon-Kyoo
    • Korean Journal of Plant Resources
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    • v.22 no.3
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    • pp.273-280
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    • 2009
  • A cDNA clone encoding a MDR-like ABC transporter protein was isolated from Brassica rapa seedlings, through rapid amplification of cDNA ends (RACE). This gene (named as Brmdr 1; GenBank accession no.: DQ296184 ) had a total length of 4222 bp with an open reading frame of 3900 bp, and encoded a predicted polypeptide of 1300 amino acids with a molecular weight of 143.1 kDa. The BrMDR1 protein shared 71.0, 62.5, 60.0 and 58.2% identity with other MDR proteins isolated from Arabidopsis thaliana (AAN28720), Coptis japonica (CjMDR), Gossypium hirsutum (GhMDR) and Triticum aestivum (TaMDR) at amino acid level, respectively. Southern blot analysis showed that Brmdr1 was a low-copy gene. Expression pattern analysis revealed that Brmdr1 constitutively expressed in the root, stem petals and stamens, but with lower expression in leaves and open flowers. The domains analysis showed that BrMDR1 protein possessed two transmembrane domains (TMDs) and two nucleotide binding domains (NBDs) arranging in "TMD1-NBD1-TMD2-NBD2" direction, which is consistent with other MDR transporters. Within NBDs three characteristic motifs common to all ABC transporters, "Walker A", "Walker B" and C motif, were found. These results indicate that BrMDR1 is a MDR-like ABC transporter protein that may be involved in the transport and accumulation of secondary metabolites.

Statistical Interaction for Major Gene Combinations (우수 유전자 조합 선별을 위한 통계적 상호작용 방법비교)

  • Lee, Jea-Young;Lee, Yong-Won;Choi, Young-Jin
    • The Korean Journal of Applied Statistics
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    • v.23 no.4
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    • pp.693-703
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    • 2010
  • Diseases of human or economical traits of cattles are occured by interaction of genes. We introduce expanded multifactor dimensionality reduction(E-MDR), dummy multifactor dimensionality reduction(D-MDR) and SNPHarvester which are developed to find interaction of genes. We will select interaction of outstanding gene combinations and select final best genotype groups.

Designing a Meatadata Registry Using SemanticWeb Technology (시맨틱웹 기반 메타데이터 레지스트리 설계에 관한 연구)

  • Oh, Sam-Gyun
    • Journal of Korean Library and Information Science Society
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    • v.36 no.3
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    • pp.109-136
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    • 2005
  • This paper describes the major components of ISO/IEC 11179 metadata registry (MDR) standard designed to promote data interoperability between systems, explains and discusses semantic web technology and Web ontology languages initiated by W3C that can be employed to further enhance data interoperability, and finally proposes a framework for a new RDF/OWL-based MDR to convert from the current human-readable MDR to machine-readable MDR. If the new MDR is successful, we might be able to offer a better customized information service to users. The future research will be concerned with evaluating objectively the effectiveness of machine-readable MDR in meeting the needs of real users.

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Knockdown of MDR1 Increases the Sensitivity to Adriamycin in Drug Resistant Gastric Cancer Cells

  • Zhu, Chun-Yu;Lv, Yan-Ping;Yan, Deng-Feng;Gao, Fu-Lian
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.11
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    • pp.6757-6760
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    • 2013
  • Gastric cancer is one of the most frequently occurring malignancies in the world. Development of multiple drug resistance (MDR) to chemotherapy is known as the major cause of treatment failure for gastric cancer. Multiple drug resistance 1/P-glycoprotein (MDR1/p-gp) contributes to drug resistance via ATP-dependent drug efflux pumps and is overexpressed in many solid tumors including gastric cancer. To investigate the role of MDR1 knockdown on drug resistance reversal, we knocked down MDR1 expression using shRNA in drug resistant gastric cancer cells and examined the consequences with regard to adriamycin (ADR) accumulation and drug-sensitivity. Two shRNAs efficiently inhibited mRNA and protein expression of MDR1 in SGC7901-MDR1 cells. MDR1 knockdown obviously decreased the ADR accumulation in cells and increased the sensitivity to ADR treatment. Together, our results revealed a crucial role of MDR1 in drug resistance and confirmed that MDR1 knockdown could reverse this phenotype in gastric cancer cells.

New Medical Device Regulations (MDR) in Europe (유럽의 새로운 의료기기 규제제도 MDR)

  • Jeong, Hyun-Woo;Yeom, Hojun;Park, Sangsoo
    • The Journal of the Convergence on Culture Technology
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    • v.8 no.5
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    • pp.29-37
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    • 2022
  • MDR, a new European medical device regulation newly enacted in 2017, requires that medical device products that have received CE conformity certification through MDD be re-certified by May 2024 in line with the new CE MDR regulation. The new MDR requires more stringent medical device clinical evaluation and clinical investigation than the previous MDD required, and also require the submission of documented post-marketing surveillance data. Korean medical device makers also need to meet the new MDR requirements and obtain conformity certification, but the industry is still confused because they do not understand the new regulations thoroughly. In this study, medical device regulations in Korea, the United States, and Europe are compared, and the European MDR is further compared with the previous European Medical Device Directive MDD to help understand the requirements of the new European Medical Device Act.

Metadata Registry Access Control Model based on RBAC (RBAC기반의 메타데이타 레지스트리 접근제어 모델)

  • Hwang, Sun-Hong;Kim, Jin-Hyung;Jeong, Dong-Won;Kim, Heui-Seog;Baik, Doo-Kwon
    • Proceedings of the Korean Information Science Society Conference
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    • 2008.06c
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    • pp.165-170
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    • 2008
  • 다양한 분야에서 ISO/IEC 11179를 기반으로 MDR(Metadata Registry)시스템들이 개발되었다. 그러나 현재 구축된 메타데이타 관리 시스템들은 표준을 따라서 생성되지 않아 메타데이타 간 불일치가 발생하는 문제가 있다. 그리고 메타데이타를 공유하고 교환할 수 있는 표준화된 접근방법을 제공하지 않아 MDR 시스템마다 상이한 방법을 이용하여 개발되는 문제점을 야기한다. 이러한 문제점들을 해결하기 위해 SQL/MDR이 제안되었다. SQL/MDR은 MDR에 대한 사용하기 쉬운 표준 인터페이스를 제공함으로써 반복적인 메타데이터 레지스트리 접근연산 개발 시 메타데이터 레지스트리 간 데이터 불일치를 개선할 수 있게 한다. 그러나 SQL/MDR은 검색을 위한 연산만을 지원할 뿐, MDR 구축 시 접근제어를 위한 연산은 제공하지 않아 정확하고 표준화된 MDR 구축 및 안전한 접근제어를 보장하지 못한다. 이 논문에서는 앞서 언급한 SQL/MDR문제점 중에서 안전한 접근제어를 보장할 수 있는 방법으로 MCL(Metadata Control Language)을 제안한다. MCL은 ISO/IEC 11179 Part 6에서 제안하는 사용자 그룹의 역할과 권한을 미리 정의하여 사용자를 사용자 그룹으로 할당하는 간단한 연산자를 사용함으로써 사용상의 편이성과 보안성을 증대시킨다. 또한 시스템 관리자가 쉽고 정확하게 MDR에 대한 접근제어 규칙을 쉽게 정의할 수 있게 하여 시스템 관리 시간 및 비용을 감소시킨다.

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Differential Sensitivities of Human Multidrug-resistant Cancer Cells to BIIB021 and Modulation of Hsp90 Inhibitors by NSAIDs and Niclosamide (항암제 다제내성(MDR) 암세포의 Hsp90 저해제 BIIB021에 대한 감수성의 차이 및 NSAIDs 및 Niclosamide에 의한 Hsp90 저해제의 활성 변화)

  • Moon, Hyun-Jung;Lee, Su-Hoon;Kim, Sun-Hee;Kang, Chi-Dug
    • Journal of Life Science
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    • v.28 no.10
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    • pp.1212-1219
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    • 2018
  • The critical role of heat shock protein 90 (Hsp90) in tumorigenesis led to the development of several first- and second-generation Hsp90 inhibitors, which have demonstrated promising responses in cancers. In this study, we found second-generation Hsp90 inhibitor BIIB021-resistant multidrug-resistant (MDR) human cancer cells, although BIIB021 was shown to be active in first-generation Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin (17-AAG)-resistant MDR cells. MCF7-MDR and HeyA8- MDR cells were more resistant to BIIB021 than their parental counterparts, indicating that BIIB021 cannot be applicable to all cancer cells expressing MDR proteins. We revealed that dimethyl-celecoxib (DMC), one of the non-steroidal anti-inflammatory drugs (NSAIDs), potentiated cytotoxicity of BIIB021 against both BIIB021-resistant and BIIB021-sensitive MDR cells. The effectiveness of NSAIDs involving celecoxib and DMC in combination with BIIB021 led to the autophagic degradation/down-regulation of mutant p53 (mutp53) that overexpressed MDR cells and the suppression of Hsp70 induction. This resulted in sensitization of MDR cells to BIIB021. Moreover, autophagy induction by sulindac sulfide, another type of NSAID, and niclosamide, an FDA-approved anthelmintic drug, potentiated 17-AAG-mediated autophagic degradation/down-regulation of mutp53 and c-Myc, client proteins of Hsp90. Therefore, our results suggest that NSAIDs and niclosamide positively enhance the anticancer activity of Hsp90 inhibitors through an autophagic pathway. They may also be new candidates for sensitizing MDR cells to Hsp90 inhibitors.