• Title/Summary/Keyword: Multi-Drug Resistance (MDR)

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Effects of Non-Saponin Red Ginseng Components on Multi-drug Resistance

  • Kim, Eun-Hye;Park, Jong-Dae;Pyo, Suhk-Neung;Rhee, Dong-Kwon
    • Journal of Ginseng Research
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    • v.31 no.2
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    • pp.74-78
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    • 2007
  • Multi-drug resistance (MDR) is a major problem in cancer chemotherapy and has often ended up with termination of the therapy. The aim of this study was to identify any fractions of Korean red ginseng that would be effective in modulating for MDR. Although ginsenosides have been reviewed as possible MDR modulators, the MDR modulation activity of the other component is unknown. Therefore, a red ginseng was extracted with methanol, ether, ethylacetate, and n-butanol, followed by several fractionations by silica gel chromatography. And the activity of MDR modulating for these fractions was examined via sulforrhodamine B assay. We have found that several ether fractions, as nonsaponin components are effective on MDR modulation. We have expect that these results helpful to improvement of cancer chemotherapy.

Polyamines in Multi-drug Resistant Cancer Cells (다제 내성 암세포에서의 Polyamine 특성)

  • 권혁영;이종호;이동권
    • Biomolecules & Therapeutics
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    • v.5 no.3
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    • pp.265-271
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    • 1997
  • Since the advent of chemotherapy, certain types of cancer have been particularly resistant to chemotherapeutic treatment. One of the most well-studied types of resistance is resistance to multiple struc-turally dissimialr hydrophobic chemotherapeutic agents, or multidrug resistance (MDR). We found that MDR cells (KBV20C, KB7D) being highly resistant to colchicine, etoposide, and vincristine were found to have very low level of putrescine and low level of spermidine than the drug sensitive parental cells (KB) but they had almost same level of spermine as the drug sensitive cells. Although both MDR and drug sensitive cells had almost same rate of polyamine uptake, MDR cells were much more sensitive to an inhibitor of polyamine synthesis, methylglyoxal-bis guanylhydrazone (MGBG), suggesting that MDR cells might be defective in polyamine synthesis. These results also suggest that HGBG can be used for treatment of MDR in vivo.

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Role of Integrin-Linked Kinase in Multi-drug Resistance of Human Gastric Carcinoma SGC7901/DDP Cells

  • Song, Wei;Jiang, Rui;Zhao, Chun-Ming
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5619-5625
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    • 2012
  • Gastric carcinoma is a leading cause of cancer death in the world and multi-drug resistance (MDR) is an essential aspect of gastric carcinoma chemotherapy failure. Recent studies have shown that integrin-linked kinase (ILK) is involved in metastasis of human tumors, expression silencing of ILK inhibiting the metastasis of several types of cultured human cancer cells. However, the role and potential mechanism of ILK to reverse the multi-drug resistance in human gastric carcinoma is not fully clear. In this report, we focused on roles of expression silencing of ILK in multi-drug resistance reversal of human gastric carcinoma SGC7901/DDP cells, including increased drug sensitivity to cisplatin, cell apoptosis rates, and intracellular accumulation of Rhodamine-123, and decreased mRNA and protein expression of multi-drug resistance gene (MDR1), multi-drug resistance-associated protein (MRP1), excision repair cross-complementing gene 1 (ERCC1), glutathione S-transferase -${\pi}$ (GST-${\pi}$) and RhoE, and transcriptional activation of AP-1 and NF-${\kappa}B$ in ILK silenced SGC7901/DDP cells. We also found that there was a decreased level of p-Akt and p-ERK. The results indicated that ILK might be used as a potential therapeutic strategy to combat multi-drug resistance through blocking PI3K-Akt and MAPK-ERK pathways in human gastric carcinoma.

Effects of Vinorelbine on Cisplatin Resistance Reversal in Human Lung Cancer A549/DDP Cells

  • Zhou, Yu-Ting;Li, Kun;Tian, Hui
    • Asian Pacific Journal of Cancer Prevention
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    • v.14 no.8
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    • pp.4635-4639
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    • 2013
  • Multi-drug resistance (MDR) is an essential aspect of human lung cancer chemotherapy failure. Recent studies have shown that vinorelbine is involved in underlying processes in human tumors, reversing the MDR inseveral types of cancer cells. However, the roles and potential mechanism are not fully clear. In this study, we explored effects of vinorelbine in multi-drug resistance reversal of human lung cancer A549/DDP cells. We found that vinorelbine increased drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123, while decreasing expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase ${\pi}$ (GST-${\pi}$) in A549/DDP cells. At the same time, we also established downregulation of p-Akt and decreased transcriptional activation of NF-${\kappa}B$ and twist after vinorelbine treatment. The results indicated that vinorelbine might be used as a potential therapeutic strategy in human lung cancer.

Comparative Study on Antioxidant Activity and Multi-drug Resistance Reversing Activity in Korean Colored Soybean Cultivars

  • Boo, Hee-Ock;Lee, Jong-Ill;Koshio, Kaihei;Song, Won-Seob;Chon, Sang-Uk
    • Korean Journal of Plant Resources
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    • v.24 no.3
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    • pp.319-323
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    • 2011
  • The purpose of this study is to analyze antioxidant activity and multidrug resistance reversing activity in several Korean colored soybean (Glycine max Merr.) cultivars. Antioxidant activity of methanol extracts from colored soybean cultivars was evaluated by TBARS (thiobarbituric acid reactive substances), DPPH (1, 1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) methods. By means of TBARS, cultivar "Jeonnam #1" showed the highest activity until 7 days, and followed by "Black #1", "Jinyul" and "Black #3", showing lower activity than that of BHT (butylated hydroxytoluene). Methanol extracts of all cultivars proved that DPPH radical scavenging activity is dose-dependent. Methanol extract from cultivar "Jeonnam #1" showed highest DPPH radical scavenging activity, and followed by cultivars "Black #1". MDR (multi-drug resistance reversing) activity, however, showed the highest effect in "Black #3" and the lowest "Black #1" cultivar. These results suggest that seed colors of soybean may play an important role in antioxidant activity and MDR activity.

The resistance rate of anti-tuberculosis drug isolated from initial tuberculosis patients at a general hospital in Daejeon area (대전지역 일개 종합병원 초진결핵 환자들로부터 분리(分離)된 결핵균(結核菌)의 약제(藥劑) 내성률(耐性率))

  • Lee, Dong-Hoon;Kim, Sang-Ha;Kim, Young-Kwon
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.12 no.11
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    • pp.5012-5018
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    • 2011
  • According to the nationwide survey of tuberculosis from 1965 to 1995, the incidence and drug resistance rate of tuberculosis have been decreased in Korea, but the prevalence of multidrug resistance of Mycobacterium tuberculosis is still a serious problem. The purpose of this study is to investigate the drug resistance rate and pattern of tuberculosis in Daejeon from 2001 to 2008. Of the total 581cases where the drug susceptibility test was performed, resistance to at least one anti-TB drug was found in 104 cases(17.9%) of these, 68(11.7%) were resistant to at least INH and 41(7.1%) were resistant to at least RFP. Single-drug resistance was found for isolates from 37(6.4%) ; 18(3.1%) of these were resistant to INH and 5(0.9%) to RFP. Multidrug resistance, where TB was resistant to at least isoniazid and refampin, was found in 35 cases(6.0%). and Factors associated with MDR-TB included age under 40-60.The drug-resistance rate of pulmonary TB, especially MDR-TB, is higher in the initial treated patients at a private referral hospital than in those in the pubulic sector. Initial drug resistance is common and the drug susceptibility test is informative for pulmonary TB patients who have not received previous TB treatment. The need for an improved control program, coupled with early diagnosis of MDR-TB, to reduce the spread and development of resistance. Multidrug resistance rate is still problem in korea. Efforts to decrease multidrug resistance rate either independently or in cooperation with the pubulic sector will be needed.

Combination of Curcumin and Paclitaxel-loaded Solid Lipid Nanoparticles to Overcome Multidrug Resistance

  • Li, Rihua;Xu, Wenting;Eun, Jae-Soon;Lee, Mi-Kyung
    • Journal of Pharmaceutical Investigation
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    • v.41 no.6
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    • pp.381-386
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    • 2011
  • Multi-drug resistance (MDR) has been known as a major hurdle in cancer chemotherapy. One of the most clinically significant causes of MDR was the efflux of anticancer agents mediated by p-glycoprotein (p-gp) over-expressed in MDR cancer cells. To overcome MDR, there have been several strategies such as co-administration with p-gp inhibitors and encapsulation of anticancer drugs into drug delivery systems. In the present study, curcumin was evaluated for its potential as p-gp inhibitor and MDR reversal activity when combined with paclitaxel incorporated into lipid nanoparticles (PTX/LN). Western blot assay showed curcumin did not modulate the level of p-gp expression in MCF-7/ADR which is a MDR variant of human breast cancer cell line, MCF-7, and over-expresses p-gp. However, curcumin inhibited p-gp-mediated efflux of calcein in a dose-dependent manner even though it showed lower activity compared to verapamil, a well-known p-gp inhibitor. Incorporation of paclitaxel into lipid nanoparticles partially recovered the anticancer activity of paclitaxel in MCF-7/ADR. The combined use of curcumin and PTX/LN exhibited further full reversal of MDR, suggesting susceptibility of PTX/LN to the efflux system. In conclusion, combined approach of using p-gp inhibitors and incorporation of the anticancer agents into nano-delivery systems would be an efficient strategy to overcome MDR.

Effect of Ultrasound-Induced Hyperthermia on Cellular Uptake of P-gp Substrate and Non-P-gp Substrate in MDR Cells

  • Cho, Cheong-Weon;Kim, Dong-Chool;Shin, Sang-Chul
    • Journal of Pharmaceutical Investigation
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    • v.37 no.3
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    • pp.131-135
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    • 2007
  • A previous report recently demonstrated that ultrasound-induced hyperthermia (USHT:0.4 watts (W)/$cm^2$ at $41^{\circ}C$) could increase cellular uptake of P-glycoprotein (P-gp) substrates in P-gp expressing cancer cell lines. Since P-gp plays a major role in limiting drug permeability in the multi-drug resistant (MDR) cells, studies were conducted to elucidate the mechanism of USHT on cellular accumulation of P-gp and non-P-gp substrate in MDR cells. To accomplish this aim, we studied the effects of USHT on the accumulation of P-gp substrate, R123 and non-P-gp substrate, antipyrine in MDR cells. We demonstrated that USHT increased permeability of hydrophobic molecules (R123 and $[^{14}C]$-antipyrine). The enhanced permeability is reversible and size-dependent as USHT produces a much larger effect on cellular accumulation of $[^{14}C]$-antipyrine (MW 188) than that of R123 (MW 380.8). These results suggest that USHT could affect MDR cells more sensitive than BBMECs. Also, the present results point to the potential use of USHT to increase cellular uptake of P-gp recognized substrates, mainly anti-cancer agents into cancer cells.

Antimicrobial Resistance and Multi-Drug Resistance Patterns of Pathogenic Bacteria Isolated from Food Poisoning Patients in Incheon (인천지역 식중독 환자에서 분리한 병원성 세균의 항생제 내성 및 다제 내성 양상)

  • Huh, Myung-Je;Oh, Sung-Suck;Jang, Jae-Seon
    • The Korean Journal of Food And Nutrition
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    • v.26 no.1
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    • pp.132-136
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    • 2013
  • Antimicrobial resistance and multi-drug resistance patterns have been carried out on total of 210 isolated of Salmonella spp. and pathogenic E. coli isolated from food poisoning patients on January through December 2012 in Incheon, Korea. The highest percentage of antibiotics resistance was found to the following antimicrobial agents: tetracycline 43.8%, ampicillin 34.8%, nalidixic acid 23.8%, sulfamethoxazole/trimethoprim and chloramphenicol 12.4%, and ampicillin/sulbactam 11.4%. The highest percentage of resistance was 37.5% to ampicillin for Salmonella spp. and 59.0% to tetracycline for pathogenic E. coli. Overall the multidrug resistance rates of 1 drug was 26.2%, 2 drugs 9.0%, 3 drugs 9.5%, 4 drugs 7.1%, and 5 or more drugs 12.46%. The multi-drug (MDR) strains to four or more antimicrobial agents among the resistant organisms were quite high: 15.9% and 22.1% for Salmonella spp. and pathogenic E. coli, respectively. The study implies that limitation of unnecessary medication use is pertinent in order to maintaining the efficacy of drugs.

Comparison of Clinical Characteristics between Pulmonary Tuberculosis Patients with Extensively Drug-resistance and Multi-drug Resistance at National Medical Center in Korea (국립의료원에 내원한 광역내성 폐결핵 환자와 다제내성 폐결핵 환자의 임상적 특성 비교)

  • Kim, Chong Kyung;Song, Ha Do;Cho, Dong Il;Yoo, Nam Soo
    • Tuberculosis and Respiratory Diseases
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    • v.64 no.6
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    • pp.414-421
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    • 2008
  • Background: Recently, in addition to multi-drug resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB) has become rapidly growing public health threat. This study examined the clinical differences between pulmonary TB patients with extensively drug resistance (XDR) and multi-drug resistance (MDR) at the National Medical Center in Korea in order to determine the clinical characteristics associated more with XDR-TB than MDR-TB. Methods: Patients who received a diagnosis of culture-confirmed pulmonary TB and a drug sensitivity test (DST) for anti-TB drugs at the National Medical Center between January 2000 and August 2007 were enrolled in this study. The patients were identified into the XDR-TB or MDR-TB group according to the DST results. The clinical characteristics were reviewed retrospectively from the medical records. Statistical analysis for the comparisons was performed using a ${\chi}^2$-test, independent samples t-test or binary logistic regression where appropriate. Results: A total 314 patients with culture-confirmed pulmonary TB were included. Among them, 18 patients (5.7%) had XDR-TB and 69 patients (22%) had MDR-TB excluding XDR-TB. A comparison of the clinical characteristics, revealed the XDR-TB group to have a higher frequency of a prior pulmonary resection for the treatment of TB (odds ratio [OR], 3.974; 95% confidence interval [CI], 1.052~15.011; P value 0.032) and longer average previous treatment duration with anti-TB drugs, including a treatment interruption period prior to the diagnosis of XDR, than the MDR-TB group (XDR-TB group, 72.67 months; MDR-TB group, 13.09 months; average treatment duration difference between two groups, 59.582 months; 95% CI, 31.743~87.420; P value, 0.000). In addition, a longer previous treatment duration with anti-TB drugs was significantly associated with XDR-TB (OR, 1.076; 95% CI, 1.038~1.117; P value, 0.000). A comparison of the other clinical characteristics revealed the XDR-TB group to have a higher frequency of male gender, diabetes mellitus (DM), age under 45, treatment interruption history, cavitations on simple chest radiograph and positive result of sputum AFB staining at the time of diagnosis of XDR. However, the association was not statistically significant. Conclusion: Pulmonary TB patients with XDR have a higher frequency of a prior pulmonary resection and longer previous treatment duration with anti-TB drugs than those with MDR. In addition, a longer previous treatment duration with anti-TB drugs is significantly associated with XDR-TB.