• The Plant Pathology Journal
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• v.28 no.2
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• pp.207-211
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• 2012

It has been known that streptomycin resistance in bacteria can occur as a results of chromosomal mutation or through gene acquisition or both. Chromosomal mutations for resistances are point mutations in the rpsL gene, which alter ribosomal protein S12. Acquired resistance has occurred when an $Sm^R$ plasmid carrying transposon Tn5393 with tandem strA-strB gene is transferred by conjugation. A total of 686 isolates of Xanthomonas smithii subsp. citri causal agent of citrus canker disease were collected from 26 citrus orchards in Jeju Island in 2003 and 2004 seasons. Forty-nine of 111 isolates from streptomycin non-sprayed orchards in 2003 season were resistant to streptomycin. Of 107 isolates from orchards sprayed one time with streptomycin, 58 isolates were resistant, and 166 of 221 isolates from orchards sprayed two times with streptomycin were resistant. In 12 orchards sprayed three or more times with streptomycin, 219 of 247 isolates were resistant to streptomycin. Twenty-five isolates of X. smithii subsp. citri were surveyed to identify the mechanisms of streptomycin resistance in this study. Twenty-one of these 25 isolates were resistant to streptomycin, and it was proven by PCR assay that 18 of the 21 streptomycin resistant isolates have the strB gene. In sixteen of the 21 streptomycin resistant isolates, it was occurred a point mutation altered codon lysine (AAG)-41 of rpsL gene to arginine (AGG). The streptomycin-sensitive isolates easily acquired the resistance by mixed culture with resistant isolates. The strB gene was amplified from the isolates that acquired the resistance by mixed culture, and one isolate of them was also point-mutated in codon 41 of rpsL gene to be resistant. In this study, most of the streptomycin-resistant isolates of X. smithii sub sp. citri in Jeju island expressed the resistance by both chromosomal point mutation and gene acquisition, and the resistance was easily acquired through conjugation by culture mixed with streptomycin resistant and sensitive strains.

• Biomolecules & Therapeutics
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• v.12 no.2
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• pp.85-91
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• 2004

In all attempt to elucidate the role of apoptosis in drug resistance, cisplatin-resistant human chronic myelogenous leukemia (CML) K562 cells (K562/CDDP) were established and compared with drug sensitive parent cells (K562) in the induction of apoptosis. K562/CDDP cells were 5-fold more resistant to cisplatin compared to K562 cells. In addition, K562/CDDP cells were significantly more resistant to apoptois as judged by DNA fragmentation and DAPI staining. K562/CDDP cells exhibited decreased proleolytic activity of caspase-3 and this was further demonstrated by decreased cleavage of its substrate poly (ADP-ribose) polymerase (PARR- Western blot analysis showed that K562/CDDP cells had longer sustained levels of BCL-$X_L$ whereas no difference was noted in the level of Bcl-2. the translocation of Bax to mitochondria was significantly delayed in K562/CDDP cells. These results suggest that the reduced translocation of Bax and the sustained expression of BCL-$X_L$ may cause resistance to apoptosis through prevention of mitochondria release of cytochrome c, which subsequently induces reduction of caspase-3 activity and that this response is partly responsible for the acquired resistance to cisplatin ill K562 cells.

• The Plant Pathology Journal
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• v.16 no.5
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• pp.264-268
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• 2000

A fluorescent material was accumulated in inoculated leaves showing necrotic local lesions of tobacco plants with N gene, Nicotiana tabacum cvs. Xanthi-nc NN, Samsun NN, Burley 21 and KF 114, and N. glutinosa, and Datura stramonium at the early growth stages by the inoculation of Tobacco mosaic virus (TMV). It was identified as a coumarin phytoalexin, scopoletin. Although the material was most prominently produced in TMV-inoculated tobacco leaves with local necrotic lesions, its accumulation was also noted in uninoculated leaves of TMV-inoculated plants. Its accumulation was somewhat greater in high resistance-induced leaves than low resistance-induced and intact leaves. Scopoletin treatment induced the expression of a pathogenesis-related protein, PR-1, prominently at the concentration of 500 or 1000 ${\mu}$g/ml. This suggests that scopoletin is a phytoalexin abundantly accumulating in N gene-containing resistant plants in response to TMV infection, and may be related to hypersensitive responses (HR) and systemic acquired resistance (SAR) in the resistant tobacco plants.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.167.2-168
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• 2003

Anticancer drug resistance occasionally occurs in malignant hematologic diseases such as acute myelocytic leukemia (AML) treated with chemotherapy and is a major problem to complete remission. Malignant cells primarily induce intrinsic resistance to treatment of anticancer drug, but gradually obtain acquired resistance to cytotoxic activities of chemotherapy. In this study, we monitored the expression profiles of doxorubicin resistance-related genes in AML-2/DX100, a doxorubicin-resistant human acute myelocytic leukemia cell line. (omitted)

• Biomolecules & Therapeutics
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• v.21 no.2
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• pp.114-120
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• 2013

Most patients with mutant B-Raf melanomas respond to inhibitors of oncogenic B-Raf but resistance eventually emerges. To better understand the mechanisms that determine the long-term responses of mutant B-Raf melanoma cells to B-Raf inhibitor, we used chronic selection to establish B-Raf (V600E) melanoma clones with acquired resistance to the new oncogenic B-Raf inhibitor UI-152. Whereas the parental A375P cells were highly sensitive to UI-152 ($IC_{50}$ < $0.5{\mu}M$), the resistant sub-line (A375P/Mdr) displayed strong resistance to UI-152 ($IC_{50}$ < $20{\mu}M$). Immunofluorescence analysis indicated the absence of an increase in the levels of P-glycoprotein multidrug resistance (MDR) transporter in A375P/Mdr cells, suggesting that resistance was not attributable to P-glycoprotein overexpression. In UI-152-sensitive A375P cells, the anti-proliferative activity of UI-152 appeared to be due to cell-cycle arrest at $G_0/G_1$ with the induction of apoptosis. However, we found that A375P/Mdr cells were resistant to the apoptosis induced by UI-152. Interestingly, UI-152 preferentially induced autophagy in A375P/Mdr cells but not in A375P cells, as determined by GFP-LC3 puncta/cell counts. Further, autophagy inhibition with 3-methyladenine (3-MA) partially augmented growth inhibition of A375P/Mdr cells by UI-152, which implies that a high level of autophagy may protect UI-152-treated cells from undergoing growth inhibition. Together, our data implicate high rates of autophagy as a key mechanism of acquired resistance to the oncogenic B-Raf inhibitor, in support of clinical studies in which combination therapy with autophagy targeted drugs is being designed to overcome resistance.

• The Plant Pathology Journal
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• v.27 no.2
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• pp.170-182
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• 2011

Plants possess multiple resistance mechanisms that protect themselves against pathogen attack. To identify unknown components of the defense machinery in Arabidopsis, gene-expression changes were monitored in Arabidopsis thaliana under 18 different biotic or abiotic conditions using a DNA microarray representing approximately 25% of all Arabidopsis thaliana genes (www.genevestigator.com). Seventeen genes which are early responsive to salicylic acid (SA) treatment as well as pathogen infection were selected and their T-DNA insertion mutants were obtained from SALK institute. To elucidate the role of each gene in defense response, bacterial pathogen Pseudomonas syringae pv. tomato (Pst) DC3000 was inoculated onto individual T-DNA insertion mutants. Four mutants exhibited decreased resistance and five mutants displayed significantly enhanced resistance against Pst DC3000-infection as measured by change in symptom development as compared to wild-type plants. Among them, member of uridin diphosphate (UDP)-glycosyltransferase (UGT) was of particular interest, since a UGT mutant (At1g05680) showed enhanced resistance to Pst-infection in Arabidopsis. In systemic acquired resistance (SAR) assay, this mutant showed enhanced activation of SAR. Also, the enhanced SAR correlated with increased expression of defense-related gene, AtPR1. These results emphasize that the glycosylation of UGT74E2 is a part of the SA-mediated disease-resistance mechanism.

• Korean Journal of Environmental Agriculture
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• v.16 no.3
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• pp.212-215
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• 1997

Parent isolates and $first-generation(F_1)$ progenies from single-sporangium of Phytophthora infestans were investigated for the acqusition of metalaxyl and streptomycin sulfate(SM) resistance. The parent isolates, KM10, U6, CDB6 showed resistance to metalaxyl, and F817, DNC303, DN107 to SM. Especially, the average mycelial growth of $F_1$ progenies of F817, CDB6, JD1 was more than 51% than parent isolates on 25ppm metalaxyl added V-8 juice agar, whereas those of KM10, U6, JD1 were extended more than 51% similar on 200ppm SM treatment. They acquired resistance on the basis of the standard in this experiment. There were positive correlations between parent isolates and $F_1$colonies in resistance. The $F_1$ colonies obtained from parent isolates showing above interinediate resistance on metalaxyl amended agar acquired much resistance.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10847-10853
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• 2015

Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance has become a very serious clinical problem that hampers the use of this agent. In this study, we aimed to screen small molecule drugs that might reverse lapatinib-resistance of breast cancer by exploring differentially expressed genes (DEGs) via a bioinformatics method. Materials and Methods: We downloaded the gene expression profile of BT474-J4 (acquired lapatinib-resistant) and BT474 (lapatinib-sensitive) cell lines from the Gene Expression Omnibus (GEO) database and selected differentially expressed genes (DEGs) using dChip software. Then, gene ontology and pathway enrichment analyses were performed with the DAVID database. Finally, a connectivity map was utilized for predicting potential chemicals that reverse lapatinib-resistance. Results: A total of 1, 657 DEGs were obtained. These DEGs were enriched in 10 pathways, including cell cycling, regulation of actin cytoskeleton and focal adhesion associate examples. In addition, several small molecules were screened as the potential therapeutic agents capable of overcoming lapatinib-resistance. Conclusions: The results of our analysis provided a novel strategy for investigating the mechanism of lapatinib-resistance and identifying potential small molecule drugs for breast cancer treatment.

• Proceedings of the Korean Society of Plant Pathology Conference
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• 2003.10a
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• pp.64.1-64
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• 2003

Inoculation of primary pepper leaves with an avirulent strain of Xanthomonas campestris pv. vesicatoria induced systemic acquired resistance (SAR) in secondary leaves. This SAR response was accompanied by the systemic expression of defense-related genes, a systemic microoxidative burst generating H2O2, and the systemic induction of ion-leakage and callose deposition in the non-inoculated, secondary leaves. Some defense-related genes encoding PR-1, chitinase, peroxidase, PR10, thionin, defensin and zinc-finger protein were distiilctly induced in the systemic leaves. The systemically striking accumulation of H$_2$O$_2$and strong increase in peroxidase activity in pepper was suggested to contribute to the triggering of cell death In the systemic micro-HRs, leading to the induction of SAR. Treatment of non-inoculated, secondary leaves with diphenylene iodinium (DPI), an inhibitor of the oxidative burst, substantially reduced the induction of some defense-related genes and subsequently SAR.

• Journal of Microbiology
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• v.45 no.1
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• pp.64-68
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• 2007

In this study we examined the multi-drug resistance profiles of the tetracycline (TC) resistant genus Vibrio to determine its susceptibility to two ${\beta}-lactams$, ampicillin (ABPC), and mecillinam (MPC), as well as to macrolide, erythromycin (EM). The results showed various patterns of resistance among strains that were isolated from very close geographical areas during the same year, suggesting diverse patterns of drug resistance in environmental bacteria from this area. In addition, the cross-resistance patterns suggested that the resistance determinants among Vibrio spp. are acquired differently within the sediment and seawater environments.