• Title/Summary/Keyword: Drug tolerance

Search Result 105, Processing Time 0.023 seconds

Mechanism of Fatty Acid Synthase in Drug Tolerance Related to Epithelial-mesenchymal Transition of Breast Cancer

  • Li, Jun-Qin;Xue, Hui;Zhou, Lan;Dong, Li-Hua;Wei, Da-Peng;Li, Hua
    • Asian Pacific Journal of Cancer Prevention
    • /
    • v.15 no.18
    • /
    • pp.7617-7623
    • /
    • 2014
  • Objective: The mechanism of action of fatty acid synthase (FASN) in drug tolerance of breast cancer cells with epithelial-mesenchymal transition (EMT) features was investigated. Methods: The breast cancer cell line MCF-7-MEK5 with stably occurring EMT and tumour necrosis factor-${\alpha}$ (TNF-${\alpha}$) tolerance was used as the experimental model, whereas MCF-7 acted as the control. Tumour cells were implanted into nude mice for in vivo analysis, and cerulenin was used as a FASN inhibitor. RT-PCR, real-time quantitative PCR and Western blot were employed to detect the expression of FASN, TNFR-1, TNFR-2, Wnt-1, ${\beta}$-catenin and cytC at the RNA and protein levels. Results: Compared with MCF-7, TNFR-1 expression in MCF-7-MEK5 was slightly changed, TNFR-2 was decreased, and FASN, Wnt-1, ${\beta}$-catenin and cytC were increased. The expression of Wnt-1 and ${\beta}$-catenin in MCF-7-MEK5 decreased after cerulenin treatment, whereas cytC expression increased. Conclusions: The important function of FASN in the drug tolerance of breast cancer may be due to the following mechanisms: FASN downregulated TNFR-2 expression through lipid rafts to make the cells less sensitive to TNF-${\alpha}$, and simultaneously activated the Wnt-$1/{\beta}$-catenin signalling pathway. Thus, cytC expression increased, which provided cells with anti-apoptotic capacity and induced drug tolerance.

Inhibitory Action of the Ginseng Total Saponin on the Nalbuphine-Induced Tolerance and Withdrawal Syndrome

  • Kim, Dong-Hyun;Yoo, Hwan-Soo;Jang, Choon-Gon;Kang, Jong-Seok;Kim, Dong-Sup;Choi, Ki-Hwan;Jang, So-Yong;Oh, Sei-Kwan
    • Journal of Ginseng Research
    • /
    • v.29 no.2
    • /
    • pp.86-93
    • /
    • 2005
  • This study was undertaken to determine the antagonism of the ginseng total saponin (GTS) on the development of nalbuphine-induced tolerance and physical dependence. GTS is blown to have antinarcotic action with a dose of 100mg/kg (i.p.) in rats. STS significantly inhibits the development of nalbuphine-induced physical dependence as well as the tolerance. The level of pCREB was elevated in the striatum by the chronic treatment with nalbuphine or GTS, how-ever, the elevation of pCREB was inhibited by the GTS co-treatment. It has been suggested that NMDA receptor and/or NO is involved in the penomena of opioid dependence and withdrawal. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or GTS on the cortex, hippocampus and striatum in the rat brain. These results suggest that the GTS could be used to ameliorate the nalbuphine tolerance and withdrawal symptoms.

Technique of Drug Tolerance Test for Selection of Antibacterial Agents and It′s Clinical Value (항균제내성의 검사요령과 임상적응용)

  • Kim Kyo-Joon
    • Journal of Veterinary Clinics
    • /
    • v.1 no.1
    • /
    • pp.41-47
    • /
    • 1984
  • The author carried out bovine mastitis test by California Mastitis test(CMT) for the milk from dairy cows in the surburbs of Taejeon. In order to select prefer commercial therapeutic antibacterial agents for mastitis treatment, Staphylococcus aureus were isolated from the CMT positive milk and the strains were tested for the tolerance test to the agents. The results obtained were summarized as follows : 1. The tolerance test appeared graduate tolerance in cases with continuously repeat of therapeutic agents. 2. The antibacterial agents revealed strong tolerance were D-and E-ointments. 3. The antibacterial agents revealed suspect tolerance were A-and F-ointments and ampicillin, penicillin, kanamycin and streptomycin. 4. The antibacterial agents revealed non or rare tolerance were B-and G-ointments and chloramphenicol, erythromycin and oxytetracycline. 5, It is concluded that the use of 3-day-interval in turn with antibacterial agents selected by tolerance test may be beneficial.

  • PDF

Gene Expression Profiling in C57BL/6 Mice Treated with the Anorectic Drugs Sibutramine and Phendimetrazine and Their Mechanistic Implications

  • Ko, Moon-Jeong;Choi, Hyo-Sung;Ahn, Joon-Ik;Kim, So-Young;Jeong, Ho-Sang;Chung, Hye-Joo
    • Genomics & Informatics
    • /
    • v.6 no.3
    • /
    • pp.117-125
    • /
    • 2008
  • Recently, obesity has become a worldwide public health concern and the use of anorectic drugs has drastically increased. In this study, sibutramine and phendimetrazine, representative marketed anorectics, were repeatedly administered per os on a daily basis into C57BL/6 mice and the effects of these drugs on food intakes, body weight changes and gene expression profiles were monitored for up to following 7 days. Methamphetamine, which has a potent anorectic effect, was used as a positive control. Anorectic effects were sustained only for two days by phendimetrazine or methamphetamine, but for six days by sibutramine. The modulations of gene expressions in the hypothalamus and the striatum were investigated using microarrays on day 2 and day 7 post-administration, which corresponded to the anorectic period and a return of appetite respectively, for all three drugs tested. Differences in overall gene expression profiles in the stratum on day 2 for sibutramine and phendimetrazine seems to reflect difference between the two in terms of the onsets of drug tolerance. According to microarray findings, the Ankrd26 gene appears to have an important anorectic role, whereas the up-regulation of the olfaction system appeared to be involved in the drug tolerance of anorectics. The microarray data presented in this study demonstrates the usefulness of gene expression analysis for gathering information on the efficacy and safety of anorectic drugs.

Procedures in Establishing Residue Limits of Pesticides on Food Crops in Codex Alimentarius Commission and Foreign Countries (국제기구 및 외국에서 농산물중 농약잔류 허용기준의 설정절차)

  • Lee, Mi-Gyung;Hong, Moo-Gi;Park, Kun-Sang;Choi, Dong-Mi;Lim, Moo-Hyuk;Lee, Su-Rae
    • Korean Journal of Environmental Agriculture
    • /
    • v.24 no.1
    • /
    • pp.45-55
    • /
    • 2005
  • This study was undertaken to find out necessary measures to improve the tolerance setting system of pesticide residues on food crops in Korea which is scientifically reasonable and harmonizable with international standards. Information on tolerance setting systems of pesticide residues by Codex Alimentarius Commission, Joint FAO/WHO Meeting of Experts on Pesticide Residues, USA, EU, Japan and Taiwan was collected and analyzed. On the basis of information in the above countries, necessary actions to be taken by the Korean regulatory authorities were recommended with respect to priority setting, maximum residue limits (MRLs) setting based on field residue data, group MRLs, minor crop problems, quantitation limit and dietary intake assessment.

Psychological Factors of High School Girl Students on Drug Use (여고생의 약품사용과 심리적 특성)

  • Jeon, Suk-Za;Park, Young-Soo
    • The Journal of Korean Society for School & Community Health Education
    • /
    • v.1 no.1
    • /
    • pp.45-59
    • /
    • 2000
  • This study was designed to figure out current situation of use of non prescription drugs and psychological factors of high school girl students on drug use, and conducted from Nov. 1 through Nov. 20. 1998. 536 girl students were randomly selected for this study. Symptom Check list-90-Revision questionnaires used for interview. The data obtained were analyzed by SAS program. The results are as follows: 1. 94.8% of students had experiences of using more than one kind of drug; lenitive(57.8%), digestant(74.1%), remedy for colds(84.9%), antibiotic(9.3%), stimulant(3.2%) remedy for constipation(22.4%). 2. Students had experiences of using non prescription drug, lenitive(88.1%), digestant(91.7%), remedy for colds(57.4%), antibiotic(58.0%), stimulant(88.2%) remedy for constipation(88.3%) 3. 19.4% of students had experiences using drugs more than one time a week and 23.5% of students experienced tolerance, prescription group(11.1%) and non prescription group(88.9%) and 21.4% of students were keeping some medicine who experienced tolerance. 4. The scores of Symptom Check list-90-Revision of students' were higher than Kim's standard group and the psychological states were worse than Kim's standard group. 5. There were significant differences among groups(no use of drug, use of less than three kinds of drugs, use of more than three kinds of drugs) in Symptom Dimension without Paranoid Ideation and Phobic Anxiety and between using group and non using group of drug in Psychological factors on Drug use by lenitive, antibiotic, and stimulant.

  • PDF

Experimental Studies on Oxygen Tolerance and Poisoning under Hyperbaric Oxygen Environment (고압산소환경(高壓酸素環境)에서의 산소중독(酸素中毒) 및 내성(耐性)에 관(關)한 실험적(實驗的) 연구(硏究))

  • Lee, Won-Chang
    • Korean Journal of Veterinary Research
    • /
    • v.9 no.1
    • /
    • pp.11-22
    • /
    • 1969
  • Experimental studies were performed to observe the difference in tolerance of small animals to oxygen poisoning, and also to examine the effects of certain drug for it. The three experimental groups consisted of mature rat group, immature rat group and mouse group. The animals were exposed to 5 atm. of 100% oxygen using hyperbaric chamber, and they were observed for oxygen poisoning by pulmonary and central nervous system manifestation. The tolerance to oxygen poisoning was represented by half fatality time in each experimental group. The drug applied was ammonium chloride $NH_4Cl$ and it was administered intraperitoneally in various dosages for particular attribution of its prophylactic effect. The following conclusions were made; 1. The immature rat group showed the higher degree of tolerance to oxygen poisoning, as evidenced by a more prolonged half fatality time in the group. No significant difference in the half fatality time between the mature rat and the mouse group was observed. 2. The fact that the immature group showed the higher degree of tolerance as compared with the mature rat group represented by delayed onset of convulsion. 3. There was a remarkable difference in the Lung Weight/Body Weight ratio between the experimental and control group. 4. The animals with a shorter half fatality time uniformally displayed an earlier onset of convulsive seizure as the sign of oxygen poisoning and a significant elevated Lung Weight/Body Weight ratio. 5. Ammonium chloride at the dosage of 450mg per kg body weight had the most pronounced prophylactic effect on oxygen poisoning.

  • PDF

Benzodiazepine계 약물과 그 문제점

  • O Gang-Seop
    • 대한불안의학회:학술대회논문집
    • /
    • 2005.05a
    • /
    • pp.88-103
    • /
    • 2005
  • o Rational Use of BZ - relative safe, widely useful o Hidden side effects/disastrous effects in vulnerable patients o Review tolerance, dependency, withdrawal symptoms o Consider Drug interaction o Periodic Evaluation of Risk/Benefit of BZ o Advice to patients planning a pregnancy

  • PDF