• Title/Summary/Keyword: Drug-associated

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Comparison of Glutathione S-transferase-${\pi}$ Content in Drug-resistant and -sensitive Cancer Cells

  • Hong, Soon-Duck;Lee, Sang-Han
    • Journal of Life Science
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    • v.9 no.1
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    • pp.40-44
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    • 1999
  • Glutathione S-transferase (GST) is a multifunctional protein that catalyzes the catalyzes the conjugation of glutathione with electrophilic compounds. It exists in a variety of isoenzy-matic froms with a wide range of substrate specificity and plays a pivotal role in detoxification of various drugs. In order to elucidate the GST-${\pi}$'s involvement of multidrug resistance (MDR) in drug-resistant tumor cell lines, we determined GST-${\pi}$ content by "1 step sandwich method". Consequently, adriamycin resistant cells of MCF-7 (MCF-7/ADM) have 7-fold increase of GST-${\pi}$ content than that of MCF-7 cells, while its {TEX}$IC_{50}${/TEX} was 116-fold greater than parent cell line. By northrn blotting, we compared whether MCF-7/ADM cells express GST-${\pi}$ mRNA. The GST-${\pi}$ mRNA expression in these cells was not inducible, but constitutive when treated for 24 h with a concentration of 0, 20, 200, and 2000 nM of adriamycin, respectively. Taken together, these results suggest that GST-${\pi}$ may not be directly associated with multidrug resistance in these human cancer cell lines.ell lines.

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Evidence That Temporally Alternative Expression of the Vibrio vulnificus Elastase Prevents Proteolytic Inactivation of Hemolysin

  • Rhee, Jee-Eun;Lee, Jeong-Hyun;Jeong, Hye-Sook;Park, U-Ryung;Lee, Dong-Ha;Woo, Gun-Jo;Miyoshi, Shin-Ichi;Choi, Sang-Ho
    • Journal of Microbiology and Biotechnology
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    • v.13 no.6
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    • pp.1021-1026
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    • 2003
  • Numerous secreted and cell-associated virulence factors have been proposed to account for the fulminating and destructive nature of Vibrio vulnificus infections. Among the putative virulence factors are an elastase, elastolytic protease, and a cytolytic hemolysin. Effects of the elastase on the hemolysin were assessed by evaluating changes of hemolytic activities either in the presence or absence of the protease. Although hemolytic activity in the culture supernatant was lowered by the purified elastase added in vitro, the cellular level of hemolytic activity was unaffected by the mutation of vvpE encoding the elastase. Growth kinetic studies revealed that hemolysin reached its maximum level in the exponential phase of growth, and the elastase appeared at the onset of the stationary phase. These results have provided insight into the regulation of virulence factors: temporally coordinate regulation of virulence factors is essential for the overall success of the pathogen during pathogenesis.

Evaluation of Ciclopirox as a Virulence-modifying Agent Against Multidrug Resistant Pseudomonas aeruginosa Clinical Isolates from Egypt

  • Zakaria, Azza S.;Edward, Eva A.;Mohamed, Nelly M.
    • Microbiology and Biotechnology Letters
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    • v.47 no.4
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    • pp.651-661
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    • 2019
  • Targeting the pathogen viability using drugs is associated with development of drug resistance due to selective pressure. Hence, there is an increased interest in developing agents that target bacterial virulence. In this study, the inhibitory effect of ciclopirox, an antifungal agent with iron chelation potential, on the microbial virulence factors was evaluated in 26 clinical MDR Pseudomonas aeruginosa isolates collected from Alexandria Main University Hospital, a tertiary hospital in Egypt. Treatment with 9 ㎍/ml ciclopirox inhibited the hemolytic activity in 70% isolates, reduced pyocyanin production, decreased protease secretion in 46% isolates, lowered twitching and swarming motility, and decreased biofilm formation by 1.5- to 4.5-fold. The quantitative real-time PCR analysis revealed that treatment with ciclopirox downregulated the expression levels of alkaline protease (aprA) and pyocyanin (phzA1). Ciclopirox is used to treat hematological malignancies and the systemic administration of ciclopirox is reported to have adequate oral absorption with a satisfactory drug safety profile. It is important to calculate the appropriate clinical dose and therapeutic index to reposition ciclopirox from a topical antifungal agent to a promising virulence-modifying agent agent against P. aeruginosa, a problematic Gram-negative pathogen.

Effect of Limited Oxygen Supply on Coenzyme $Q_{10}$ Production and Its Relation to Limited Electron Transfer and Oxidative Stress in Rhizobium radiobacter T6102

  • Seo, Myung-Ji;Kim, Soon-Ok
    • Journal of Microbiology and Biotechnology
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    • v.20 no.2
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    • pp.346-349
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    • 2010
  • Coenzyme $Q_{10}$ ($CoQ_{10}$) production from Rhizobium radiobacter T6102 was monitored under various oxygen supply conditions by controlling the agitation speeds, aeration rates, and dissolved oxygen levels. As the results, the $CoQ_{10}$ production was enhanced by limited oxygen supply. To investigate whether the $CoQ_{10}$ production is associated with its physiological functions of electron carrier and antioxidant, the effects of sodium azide and hydrogen peroxide on the $CoQ_{10}$ production were studied, showing that the $CoQ_{10}$ contents were slightly enhanced with increasing sodium azide (up to 0.4 mM) and hydrogen peroxide (up to $10\;{\mu}M$) concentrations. These results suggest the plausible mechanism where the limited electron transfer stimulating the environments of limited oxygen supply and oxidative stress could accumulate the $CoQ_{10}$, providing the relationship between the $CoQ_{10}$ physiological functions and its regulation system.

DNAchip as a Tool for Clinical Diagnostics (진단의학 도구로서의 DNA칩)

  • 김철민;박희경
    • Proceedings of the Korean Institute of Intelligent Systems Conference
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    • 2004.04a
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    • pp.97-100
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    • 2004
  • The identification of the DNA structure as a double-stranded helix consting of two nucleotide chain molecules was a milestone in modern molecular biology. The DNA chip technology is based on reverse hybridization that follows the principle of complementary binding of double-stranded DNA. DNA chip can be described as the deposition of defined nucleic acid sequences, probes, on a solid substrate to form a regular array of elements that are available for hybridization to complementary nucleic acids, targets. DNA chips based on cDNA clons, oligonucleotides and genomic clons have been developed for gene expression studies, genetic variation analysis and genomic changes associated with disease including cancers and genetic diseases. DNA chips for gene expression profiling can be used for functional analysis in human eel Is and animal models, disease-related gene studies, assessment of gene therapy, assessment of genetically modified food, and research for drug discovery. DNA chips for genetic variation detection can be used for the detection of mutations or chromosomal abnormalities in cnacers, drug resistances in cancer cells or pathogenic microbes, histocompatibility analysis for transplantation, individual identification for forensic medicine, and detection and discrimination of pathogenic microbes. The DNA chip will be generalized as a useful tool in clinical diagnostics in near future. Lab-on-a chip and informatics will facilitate the development of a variety of DNA chips for diagnostic purpose.

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TOXICITY TEST OF NEW SOLUBILIZER FOR PACLITAXEL IN BEAGLE DOG

  • Kim, Yeo-Woon;Min, Kyung-Nan;Syrie Pang;Song, Hye-Weon;Lee, Min-Jae;Lee, Mi-Suk;Kim, Jong-Jae;Sheen, Yhun-Yhong
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2001.11a
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    • pp.89-89
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    • 2001
  • Paclitaxel is currently administered i.v. as a slow infusion of a solution of the drug in an ethanol: cremophor EL: saline admixture. However, poor solubilization and toxicity are associated with this drug therapy. We have tried to develop a new surfactant for paclitaxel to improve efficacy and reduce toxicity of solubilizer. We performed the hemolysis test for chemicals which passed the paclitaxel-stabilizing test and 5 chemicals showing relatively low hemolytic effects were tested for a single dosing toxicity test. And then aceporol 330, which showed the most favorable result, was introduced to the repeated dosing toxicity tests in mouse and beagle dog. According to data based on body weight, mortality, dissection, homological test and biochemical test, Aceporol 330 exhibited much more reduced toxicity than cremophor EL.

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Associations of Probiotics with Vitamin D and Leptin Receptors and their Effects on Colon Cancer

  • Ranji, Peyman;Akbarzadeh, Abolfazl;Rahmati-Yamchi, Mohammad
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.9
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    • pp.3621-3627
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    • 2015
  • Colorectal cancer (CRC) is one of most common causes of cancer-related death worldwide. Recent studies have suggested that microbial and environmental factors including diet and lifestyle can impact on colon cancer development. Vitamin D deficiency and dysfunction of vitamin D receptor (VDR) also correlate with colon cancer. Moreover, leptin, a 16-kDa polypeptide, participates in the regulation of food intake and is associated with other environmental factors affecting colon cancer through the leptin receptor. Altered levels of serum leptin and patterns of expression of its receptor (LPR) may be observed in human colon tumours. Furthermore, the collected data from in vitro and in vivo studies have indicated that consuming probiotic non-pathogenic lactic acid bacteria have beneficial effects on colon cancer. Probiotics, inflammation and vitamin D/VDR have been correlated with leptin and its receptor and are also with colon cancer. Thus, in this paper, we review recent progress on the roles of probiotic, vitamin D/VDR and leptin/LPR in inflammation and colon cancer.

Pharmacokinetic Interaction between Verapamil and Tamoxifen in Rats (베라파밀과 타목시펜의 약물동태학적 상호작용)

  • Seol, Hyo-Chan;Choi, Jun-Shik
    • YAKHAK HOEJI
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    • v.49 no.5
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    • pp.380-385
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    • 2005
  • The aim of this study is to investigate the effects of verapamil on the pharmacokinetics of tamoxifen following oral administration of tamoxifen with verapamil to rats. Tamoxifen (10 mg/kg) was administered orally in the presence or absence of verapamil (1, 3 or 6 mg/kg). Compared to the control group (given tamoxifen alone), the presence of verapamil significantly (p<0.05 by 1 mg/kg, p<0.01 by 3 and 6 mg/kg) increased the areas under the plasma concentration-time curve (AUC) and the peak concentrations ($C_{max}$) of tamoxifen. Consequently, the relative bioavailability ($RB\%$) of tamoxifen with verapamil was 1.6-2.1 fold higher than that of the control. But the time to reach peak concentration ($T_{max}$) and the terminal half-life ($t_{1/2}$) of tamoxifen were not altered significantly in the presence of verapamil. The increased AUC and $C_{max}$ of tamox­ifen in the presence of verapamil might be associated with the inhibition by verapamil of the P-glycoprotein and the first­pass metabolizing enzyme CYP3A4 in small intestinal mucosa. The drug interaction should be taken into consideration when tamoxifen is used to the patient with verapamil in the clinical setting.

Metformin Synergistically Potentiates the Antitumor Effects of Imatinib in Colorectal Cancer Cells

  • Lee, Jaeryun;Park, Deokbae;Lee, Youngki
    • Development and Reproduction
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    • v.21 no.2
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    • pp.139-150
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    • 2017
  • Metformin is the most commonly prescribed anti-diabetic drug with relatively minor side effect. Substantial evidence has suggested that metformin is associated with decreased cancer risk and anticancer activity against diverse cancer cells. The tyrosine kinase inhibitor imatinib has shown powerful activity for treatment of chronic myeloid leukemia and also induces growth arrest and apoptosis in colorectal cancer cells. In this study, we tested the combination of imatinib and metformin against HCT15 colorectal cancer cells for effects on cell viability, cell cycle and autophagy. Our data show that metformin synergistically enhances the imatinib cytotoxicity in HCT15 cells as indicated by combination and drug reduction indices. We also demonstrate that the combination causes synergistic down-regulation of pERK, cell cycle arrest in S and $G_2/M$ phases via reduction of cyclin B1 level. Moreover, the combination resulted in autophagy induction as revealed by increased acidic vesicular organelles and cleaved form of LC3-II. Inhibition of autophagic process by chloroquine led to decreased cell viability, suggesting that induction of autophagy seems to play a cell protective role that may act against anticancer effects. In conclusion, our present data suggest that metformin in combination with imatinib might be a promising therapeutic option in colorectal cancer.

A Case of Pancytopenia with Hyperthyroidism

  • Kim, Tae Hoon;Yoon, Ji Sung;Park, Byung Sam;Lee, Dong Won;Cho, Jae Ho;Moon, Jun Sung;Kim, Eui Hyun;Won, Kyu Chang;Lee, Hyoung Woo
    • Journal of Yeungnam Medical Science
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    • v.30 no.1
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    • pp.47-50
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    • 2013
  • There has been an increase in the number of reports of atypical manifestations of Graves' disease (GD), such as jaundice, anemia, thrombocytopenia and leukopenia. Pancytopenia also rarely occurs in GD. In this paper, a case of pancytopenia with GD that was successfully treated with an anti-thyroid drug is reported. In this case, a 69-year-old woman showed pancytopenia with a normal peripheral blood smear, bone marrow aspiration smear and bone marrow biopsy. Her thyroid function test and thyroid scintigraphy confirmed her hyperthyroid status. Her laboratory abnormality and clinical condition improved after she was treated with an anti-thyroid drug. This is a rare case of pancytopenia associated with GD.