• Journal of Ginseng Research
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• 제31권2호
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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.

• Biomolecules & Therapeutics
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• 제5권3호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제13권11호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제14권8호
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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.

• 한국자원식물학회지
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• 제24권3호
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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.

• 한국산학기술학회논문지
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• 제12권11호
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• pp.5012-5018
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• 2011

1965년부터 1995까지 결핵의 전국적인 조사에 의하면, 한국에서 결핵의 발생과 약제 내성율은 감소하였지만 다재약제내성율의 유행은 여전히 심각한 문제이다. 본 연구의 목적은 2001 년부터 2008까지 대전에 약제 내성율과 성향을 조사하였다. 총 581건의 약제감수성 검사가 수행 되었으며 이중 하나이상의 항결핵제의 약물에 내성이 있는 경우가 104건(17.9%)이였고 적어도 INH에 내성이 있는 경우가 68건 (11.7 %), RFP내성이 41건(7.1 %)이였다. 단일 약제 내성율은 37건 (6.4 %) 분리되었으며 이들 중 INH에서 18건 (3.1 %) RFP에서 5건(0.9 %)이 분리 되었다. 적어도 isoniazid와 refampin에 내성인 다제내성결핵은 35건(6.0 %)에서 발견되었다. 그리고 MDR - TB와 관련된 나이요인에 40-60 세 포함되었다. 폐결핵의 약제내성율, 특히 MDR - TB의 약제내성율은 공공의료분야보다 민간 병원의 초치료 환자에서 높게 나왔다. 초기 약제내성은 일반적이며 약제감수성 검사는 이전 결핵 치료를 받지 않은 폐결핵 환자에 대해 유용성이 있다. 내성의 확산과 증가를 줄이기 위해 MDR - TB의 조기 진단과 함께 향상된 제어프로그램이 필요하다. 다제내성율은 여전히 한국에서 문제이다. 독립적으로 혹은 공공의료분야와 공동으로 다제내성율을 감소하기 위한 노력이 필요하다.

• Journal of Pharmaceutical Investigation
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• 제41권6호
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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.

• Journal of Pharmaceutical Investigation
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• 제37권3호
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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.

• 한국식품영양학회지
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• 제26권1호
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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.

• Tuberculosis and Respiratory Diseases
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• 제64권6호
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• pp.414-421
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• 2008

연구배경: 최근 광역내성 결핵은 공공보건에 중대한 문제가 되고 있다. 본 연구의 목적은 국립의료원에 내원한 폐결핵 환자들 중 광역내성 폐결핵 환자와 다제내성 폐결핵 환자의 임상적 특성을 비교 연구 하여 광역내성 및 다제내성 폐결핵에 대한 관심을 높이고 폐결핵 퇴치에 이바지하고자 하였다. 방 법: 2000년 1월부터 2007년 8월까지 객담 결핵균배 양양성 및 항결핵 약제에 대한 감수성검사가 행해진 환자를 대상으로 하였다. 감수성결과에 따라 광역내성군과 다제내성군으로 나눈 뒤, 의무기록을 토대로하여 임상적 특성을 후향적으로 비교분석 하였다. 결 과: 총 314명의 환자들 중 18명(5.7%)이 광역내성, 69명(22%)이 다제내성이었고 광역내성을 다제내성에 포함시켰을 때 광역내성이 다제내성에서 차지하는 비율은 20.69%였다. 연구된 임상적 특성들 중, 광역내성 또는 다제내성이 진단될 당시 결핵치료를 위한 폐절제술의 과거력이 광역내성군에서 더 많았으며(OR, 3.974; 95% CI, 1.052~15.011; p value, 0.032), 광역내성이나 다제내성으로 진단되기 전 복용중단기간을 포함한 이전 항결핵약제 복용기간의 평균도 광역내성군에서 더 길었다(광역내성군: 72.67개월, 다제내성군: 13.09개월, 평균복용기간의차이, 59.582개월; 95% CI, 31.743~87.420; p value, 0.000). 또한 복용기간이 길수록 광역내성 발생과 유의한 관계가 있었다(OR, 1.076; 95% CI, 1.038~1.117; p value, 0.000). 그 외 남성의 비율, 당뇨병의 빈도, 45세 미만의 연령, 2개월 이상 항결핵약제 복용을 중단한 경력, 다제내 성이나 광역내성으로 진단될 당시 흉부방사선사진에서 공동의 존재 빈도와 내성 진단 당시 객담 항산성균 도말 양성 검사 비율은 전체적으로 광역내성군에서 더 높았으나 통계적으로 유의하지는 않았다. 결 론: 광역내성 폐결핵 환자들에서 광역내성으로 진단될 당시 결핵치료를 위한 폐절제술의 과거력의 비율이 더 높았으며, 내성 진단 전 더 긴 항결핵약제 복용기간을 보여주었다. 또한 긴 복용기간은 유의하게 광역내성의 발생과 관련되어 있었다.