• Proceedings of the Korean Society of Veterinary Clinics Conference
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• 2006.05a
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• pp.166-166
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• 2006

• Proceedings of the PSK Conference
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• 2000.04a
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• pp.207.2-208
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• 2000

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.160.2-161
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• 2001

• Proceedings of the PSK Conference
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• 2000.10a
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• pp.274.2-275
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• 2000

• Proceedings of the PSK Conference
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• 2003.10a
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• pp.44-46
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• 2003

Although Cyclosporin A (CsA) is a powerful immunosuppresant with little adverse effect on the bone marrow, CsA administered orally in the general formulation cannot obtain high bioavailability due to its poor aqueous solubility. To improve the solubility and enhance the bioavailability of poorly water-soluble CsA, many different approaches have been made in our laboratory. (omitted)

• Biomolecules & Therapeutics
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• v.9 no.1
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• pp.40-45
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• 2001

The activity of taurine transporter is affected by various extracellular stimuli such as ion, hormone and stress. To assess effects of steroid hormones antral cyclosporin A (CsA) on the taurine transporter activity, murine monocytic RAW264.7 cell line was stimulated with dexamethasone (DM), triamcinolone (TA), cortisone (CS), hydrocortisone (HCS), prednisone (PSN), prednisolone (PSL) and methylprednisolone (MPSL) in the presence of 12-0-tetradecanoylphorbol-13-acetate(TPA). Treatment of TPA on the cell line led to significant reduction of taurine transporter activity. However, in case of stimulation of the cells with steroid hormones in the presence of TPA, all of them recovered TPA-induced reduction of the taurine transporter activity. Treatment of the cells with CsA led to significant reduction of the taurine transporter activity. Ionomycin (IM) recovered the reduced taurine transporter activity by CsA, but failed in the presence of EDTA, a calcium chelating agent. These results showed that glucocorticoid hormone recovered TPA-induced reduction of taurine transporter activity and that IM recovered CsA-induced reduction of the transporter activity by increasing intracellular free $Ca^{++}$ concentration.n.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1997.04a
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• pp.117-117
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• 1997

Sandimmune Neoral$\^$(R)/ and Neoplanta$\^$(R)/ capsules were administered to twenty four healthy Korean male subjects at a cyclosporin A (CsA) dose of 175 mg in a 2 ${\times}$ 2 crossover investigation with a two-week wash-out phase. Concentrations of CsA in blood were measured by RIA method for over a period of 48 h. Result : The two formulations were found bioequivalent, but analysis of variance (ANOVA) indicated that there is a significant (p<0.01) period effect in AUC$\_$0-LAST/ (area under the blood concentration above assay limit of quantification-time curve) and C$\_$MAX/ (maximum blood concentration) between the administrations. Paired t-test revealed 6 and 9% decreases in AUC$\_$0-LAST/ and C$\_$MAX/, respectively at the second administration. This period effect on the pharmacokinetics of CsA may be relevant for the patients who need consecutive administration of the drug. A number of mechanisms, such as induction of the enzymes responsible for metabolism of the drug in the gut wall and/or liver and modulation of P-glycoprotein upon the consecutive dosing, appear consistent with the change, and needs experimental proof.

• Journal of Microbiology and Biotechnology
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• v.16 no.2
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• pp.295-298
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• 2006

Actinomycetes are ubiquitous Gram-positive soil bacteria and a group of the most important industrial microorganisms for the biosynthesis of many valuable secondary metabolites as well as the source of various bioconversion enzymes. Cytochrome P450 hydroxylase (CYP), a hemebinding protein, is known to be involved in the modification of various natural compounds, including polyketides, fatty acids, steroids, and some aromatic compounds. Previously, six different novel CYP genes were isolated from a rare actinomycetes called Sebekia benihana, and they were completely sequenced, revealing significant amino acid similarities to previously known CYP genes involved in Streptomyces secondary metabolism. In the present study, these six CYP genes were functionally expressed in Streptomyces lividans, using an $ermE^{*}$ promoter-containing Streptomyces expression vector. Among six CYP genes, two S. benihana CYP genes (CYP503 and CYP504) showed strong hydroxylation activities toward 7-ethoxycoumarin. Furthermore, the recombinant S. lividans containing both the S. benihana CYP506-ferredoxin genes as well as the S. coelicolor feredoxin reductase gene also demonstrated cyclosporin A hydroxylation activity, suggesting potential application of actinomycetes CYPs for the biocatalysts of natural product bioconversion.

• Tuberculosis and Respiratory Diseases
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• v.46 no.2
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• pp.229-240
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• 1999

Background: The impact of the immune response on cancer gene therapy using viral vectors to deliver a "suicide gene" is currently unclear. A vigrous immune response targeted at viral proteins or transgene may enhance the efficacy of tumor destruction and even augment responses to tumor antigens. These responses may involve the release of cytokines and stimulation of tumor specific cytotoxic T-lymphocytes that enhance therapeutic efficacy. On the other hand, a vigorous rapid cellular immune response may destroy cells expressing the therapeutic gene and attenuate the response to therapy. Furthermore, development of neutralizing antibody responses may prevent readministration of virus, a potentially significant limitation. Evaluating the significance of these limitations in animal models and developing solutions are therefore of obvious importance. Methods: After retroviral transduction of mouse mesothelioma cell line(AB12) with Herpes Simplex Virus thymidine kinase (HSVtk) gene in vitro, subcutaneous flank tumors were established. To study the effect of intact immune system on efficacy of tumor erradication, the ability of the HSVtk/ganciclovir system to inhibit tumor growth was compared among normal Balb/c mice, immunodeficient Balb/c-nude and SCID mice, and Balb/c mice immunosuppressed with cyclosporin. Results: Ganciclovir treatment resulted in greater inhibition of tumor growth in Balb/c mice compared with immunodeficient Balb/c-nude mice and SCID mice(in immunodeficient mice, there were no growth inhibition by ganciclovir treatment). Ganciclovir treatment resulted in greater inhibition of tumor growth in noncyclosporin (CSA) treated Balb/c mice compared with CSA treated Balb/c mice. On day 8, mean ganciclovir-treated tumor volume were 65% of control tumor volume in Balb/c mice versus 77% control tumor volume in CSA-treated Balb/c mice. This effect was still evident during therapy (day 11 and 13). On day 13, non-CSA treated tumor volume was 35% of control tumor volume versus 60% of control tumor volume in CSA treated Balb/c mice. Duration of expression of HSVtk was not affected by the immunosuppression with CSA. Conclusion: These results indicate that the immune responses against retrovirally transduced cells enhance the efficacy of the HSVtk/ganciclovir system. These findings have important implications for clinical trials using currently available retrovirus vectors as well as for future vector design.

• The Korean Journal of Nuclear Medicine
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• v.37 no.3
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• pp.178-189
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• 2003

Purpose: Cellular uptakes of $^{99m}Tc-sestamibi(MIBI)\;and\;\;^{99m}Tc-tetrofosmin$ into cancer cell lines expressing multidrug resistance(MDR) were investigated and compared. The effects of verapamil and cyclosporin A, well-known multidrug resistant reversing agents, on cellular uptakes of both tracers were also compared. Materials and Methods: Doxorubicin-resistant HCT15/CL02 human colorectal cell and doxorubicin-resistant K562(Adr) and vincristine-resistant K562(Vcr) human leukemic cells were studied. RT-PCR analysis was used for the detection of mdr1 mRNA expression. MDR-reversal effects with verapamil and cyclosporine A were evaluated at different drug concentrations after incubation with MIBI and tetrofosmin for 1, 15, 30, 45 and 60 min, using single-cell suspensions at $1{\times}10^6cells/ml$ incubated at $37^{\circ}C$. Radioactivity in supernatants and pellets were measured with gamma well counter. Results: The cellular uptakes of MIBI and tetrofosmin in K562(Adr) and K562(Vcr) were lower than those of parental K562 cell. In HCT15/CL02 cells and K562(Adr) cells, there were no significant difference in cellular uptakes of both tracers, but cellular uptake of MIBI was higher than that of tetrofosmin in K562(Vcr) cells. Coincubation with verapamil resulted in a increase In cellular uptakes of MIBI and tetrofosmin. Verapamil increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 11.9- and 6.8-fold, by K562(Adr) cell by 14.3- and 8-fold and by K562(Vcr) cell by 7- and 5.7-fold in maximum, respectively. Cyciosporin A increased cellular uptakes of MIBI and tetrofosmin by HCT15/CL02 cell by 10- and 2.4-fold, by K562(Adr) cell by 44- and 13-fold and by K562(Vcr) cell by 18.8- and 11.8-fold in maximum, respectively Conclusion: Taking together, MIBI and tetrofosmin are considered as suitable radiopharmaceuticals for defecting multidrug resistance. However, MIBI seems to be a better tracer than tetrofosmin for evaluating MDR reversal effect of the modulators. Since cellular uptakes of both tracers might differ in different cell types, further experiments regarding differences in cellular uptakes between cell types should be explored.