• Biomolecules & Therapeutics
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• 제13권2호
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• pp.65-77
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• 2005

Present article reviews about clinical pharmacology of mycophenolic acid (MPA), the active form of mycophenolate mofetil (MMF), as widely used component of immunosuppressive regimens in the organ transplantation field. MMF, used alone or concomitantly with cyclosporine or tacrolimus, has approved in reducing the incidence of acute rejection and has gained widespread use in solid organ such as kidney, heart and liver transplantation. The application of MPA and development of MMF has shown a considerable impact on immunosuppressive therapy for organ transplantation as a new immunosuppressive agent with different mechanism of action from other drugs after early 1990s. In particular aspect, use of MMF, a morpholinoethyl ester of MPA, represented a significant advance in the prevention of organ allograft rejection as well as allograft and patient survival. In considering MMF clinical data, it is important to note that there is a strong correlation between high MPA area under curve(AUC) values and a low probability of acute allograft rejection. Individual trials have shown that MMF is generally well tolerated and revealed that MMF decreased the relative risk of developing chronic allograft rejection compared with azathioprine. Recent clinical investigations suggested that improved effectiveness and tolerability will results from the incorporation of MPA therapeutic drug monitoring into routine clinical practice, providing effective MMF dose individualization in renal and heart transplant patients. Therefore, MMF has a selective immunosuppressive effect with minimal toxicity and has shown to be more effective that other agents as next step of immunosuppressive agents and regimens that deliver effective graft protection and immunosuppression along with a more favorable side effect.

• 동의생리병리학회지
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• 제28권5호
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• pp.499-505
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• 2014

Immunosuppressors cyclosporine A(CsA) and tacrolimus(FK506), the primary cellular target of which is calcineurin/nuclear factor of activated T cells(NFAT) signalling pathways, decrease beta-cell insulin content and mRNA expression. The posttransplantation diabetes mellitus(PTDM) is a frequent complication in immunosuppressive therapy. The present study was to examine the effect of a crude water extracts of medicinal herbs such as Sanguisorba officinalis(SOE) on the immunosuppressive activity with lymphocyte and insulin secretion in insulinoma cell lines with RIN-5mF. It was found that SOE treatment had effect of immunosuppressor on lymphocytes and also significantly increased insulin secretion in RIN-5mF compared to other agents. we might suggest a mechanism on insulin secretion by HNF4a. Taken together, the present study suggested that SOE might serve as immunosuppressive drug in PTDM.

• The Korean Journal of Physiology and Pharmacology
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• 제16권2호
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• pp.145-151
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• 2012

In the present work, we studied the structure-activity relationship (SAR) of tautomycetin (TMC) and its derivatives. Further, we demonstrated the correlation between the immunosuppressive fuction, anticancer activity and protein phosphatase type 1 (PP1) inhibition of TMC and its derivatives. We have prepared some TMC derivatives via combinatorial biosynthesis, isolation from fermentation broth or chemical degradation of TMC. We found that the immunosuppressive activity was correlated with anticancer activity for TMC and its analog compounds, indicating that TMC may home at the same targets for its immunosuppressive and anticancer activities. Interestingly, TMC-F1, TMC-D1 and TMC-D2 all retained significant, albeit reduced PP1 inhibitory activity compared to TMC. However, only TMC-D2 showed immunosuppressive and anticancer activities in studies carried out in cell lines. Moreover, TMC-Chain did not show any significant inhibitory activity towards PP1 but showed strong growth inhibitory effect. This observation implicates that the maleic anhydride moiety of TMC is critical for its phosphatase inhibitory activity whereas the C1-C18 moiety of TMC is essential for the inhibition of tumor cell proliferation. Furthermore, we measured $in$ $vivo$ phosphatase activities of PP1 in MCF-7 cell extracts treated with TMC and its related compounds, and the results indicate that the cytotoxicity of TMC doesn't correlate with its $in$ $vivo$ PP1 inhibition activity. Taken together, our study suggests that the immunosuppressive and anticancer activities of TMC are not due to the inhibition of PP1. Our results provide a novel insight for the elucidation of the underlying molecular mechanisms of TMC's important biological functions.

• BMB Reports
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• 제53권10호
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• pp.512-520
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• 2020

T-cell-based cancer immunotherapies, such as immune checkpoint blockers (ICBs) and chimeric antigen receptor (CAR)-T-cells, have significant anti-tumor effects against certain types of cancer, providing a new paradigm for cancer treatment. However, the activity of tumor infiltrating T-cells (TILs) can be effectively neutralized in the tumor microenvironment (TME) of most solid tumors, rich in various immunosuppressive factors and cells. Therefore, to improve the clinical outcomes of established T-cell-based immunotherapy, adjuvants that can comprehensively relieve multiple immunosuppressive mechanisms of TME are needed. In this regard, recent studies have revealed that metformin has several beneficial effects on anti-tumor immunity. In this mini-review, we understand the immunosuppressive properties of TME and how metformin comprehensively enhances anti-tumor immunity. Finally, we will discuss this old friend's potential as an adjuvant for cancer immunotherapy.

• 한방안이비인후피부과학회지
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• 제16권2호
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• pp.119-137
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• 2003

Younggaechulgam-tang has been used for treating skin diseases. In this study, I investigated the immunosuppressive effect of Younggaechul-tang in the human T cell line MOLT-4 cells. MOLT-4 cells were stimulated with the phytohemagglutinin (PHA) and phorbol 12-myristate 13-acetate (PMA) + A23187. The secretion appeared to be greater when cells were stimulated with PHA than with PMA + A23187. Younggaechulgam-tang had no affect proliferation stimulated by PHA. I showed that IL-2 secretion and expression by PHA stimulated MOLT-4 cells were inhibited by Younggaechugam-tang treatment. Maximal inhibition rate of IL-2, TNF-${\alpha}$ secretion was 80$\%$ and 30$\%$, respectively. Younggaechulgam-tang also inhibited nuclear translocation of p65 subunit of nuclear factor-kB and nuclear factor of activated T cells (NFAT). In conclusion, these results suggest that Younggaechulgam-tang may contribute to the immunosuppressive oriental drug clinically.

• Advances in Traditional Medicine
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• 제10권3호
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• pp.150-154
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• 2010

The immunosuppressive activity of the Methanol extract of bark of Madhuca longifolia (Koenig) consisting of a mixture of saponins, flavonoids, tannins, steroids, phenol and glycosides was studied on the immune responses in mice. Methanol extract of Madhuca longifolia (MLL) was administered orally at doses of 50, 100 and 150 mg/kg/day to healthy mice divided into four groups consisting of six animals each. The assessment of immunomodulatory activity was carried out by testing the humoral (antibody titre) and cellular (foot pad swelling) immune responses to the antigenic challenge by sheep RBCs. Furthermore, the effect on hematological parameters as well as relative organ weight was determined. On oral administration MML showed a significant decrease delayed type hypersensitivity (DTH) response whereas the humoral response to sheep RBCs was unaffected. Thus MLL significantly suppressed the cellular immunity by decreasing the footpad thickness response to sheep RBCs in sensitized mice. With a dose of 100 and 150 mg/kg/day the DTH response was $7.66{\pm}2.75$ and $6.41{\pm}1.21$ respectively in comparison to corresponding value of $14.50{\pm}2.38$ for untreated control group. These differences in DTH response were statistically significant (P < 0.05). The study demonstrates that MLL shows preferential suppression of the components of cell-mediated immunity and shows no effect on the humoral immunity.

• Journal of Radiation Protection and Research
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• 제20권3호
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• pp.169-179
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• 1995

• 한국광과학회:학술대회논문집
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• 한국광과학회 2000년도 학술대회지
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• pp.37-37
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• 2000

• Parasites, Hosts and Diseases
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• 제36권2호
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• pp.121-126
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• 1998

닭와포자충 감염이 다른 병원체에 대한 닭의 체액성 면역에 미치는 영향을 규명하기 위한 연구의 일환으로 2일령 SPF 병아리에 $5{\;}{\times}10^5$의 닭와포자충 오오시스트를 한 번에 경구투여한 다음 4일과 21일 두 번에 걸척 뉴캣슬병 불활화 (사독) 백신을 접종하였다. 오오시스트 접종 후 2주부터 1주 간격으로 13주까지 채혈하여 혈구응집억제반응으로 ND HI $log_2$ 역가를 경시적으로 측정하여 대조군과 비교, 검토하였다. 일반적으로 뉴캣슬병 바이러스에 대한 Hl가는 전 실험기간을 통하여 대조군에 비하여 실험군이 상당히 낮았으며 (p<0.01), 보다 빨리 음전하는 경향이었다. 백신의 보강주사 후 역가는 점점 높아져서 2주 ($5.00(\;}{\pm}{\;}0$; 비감염 대조군)와 4주 ($3.88{\;}{\pm}{\;}0.6658$; 감염 실험군)에 최고치에 이른 다음 점점 낮아졌다. 한편, 분변 내의 오오시스트 배설 양상은 통상적인 감염례와 같았다. 이로 미루어 보아 병아리가 닭와포자충에 감염되면 건강한 병아리에 비하여 뉴캣슬병 바이러스에 대한 면역억제 현상이 일어나 감수성이 증가할 수 있을 것으로 생각된다.

• Parasites, Hosts and Diseases
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• 제36권3호
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• pp.203-206
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• 1998

닭에 있어서 닭와포자충 감염이 다른 중요 가금 질병에 대한 체액성 면역억제 현상을 규명하기 위해 2일령의 보통 병아리에 $2{\;}{\times}{\;}10^6$의 닭와포자충 난포낭을 한번에 경구 투여한 다음 4일과 14 일 두 번에 걸쳐 닭전염성기관지염 생독백신을 접종하여 1주 간격으로 혈구응집억제반응으로 항체 가를 측정하였다 감염 및 비감염군 모두 평균 항체가는 점점 낮아져 2차 예방접종 후 2주에 최저 에 이른 다음 점점 높아져 일정한 수준을 유지하였다. 일반적으로 평균 항체가는 비감염군에 비하 여 감염군이 의의있게 낮았다 (p<0.05). 한편, 이 두 병원체를 접종하지 않은 진정 대조군의 1일 령의 모체이행항체가 $log_2{\;}5.16{\;}{\pm}{\;}1.39$는 시간이 경과함에 따라 점점 낮아져 6주령에 이르러 완 전히 음전하였다. 이는 직선적인 변화를 하였으며, 주를 함수 (X)로 한 Y = -0.90X + 4.67의 일차방정식에 잘 부합하였으며, 실측치와 추정치와의 상관계수는 R = 0.9454이었다. 닭와포자충 감염 병아리는 건강한 것에 비하여 닭전염성기관지염 바이러스에 대한 면역억제현상이 일어나 아마도 감수성이 증가할 것으로 생각된다.