• Title/Summary/Keyword: 면역 억제 치료

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A Study of the Bystander Effect and Its Enhancement in HSV-TK Gene Therapy Using a Murine Neuroblastoma Model (마우스 신경모세포종 모델을 이용한 HSV-TK 유전자 치료에서 Bystander 효과 및 증폭에 관한 연구)

  • Cho, Hyun Sang;Kim, Moon Kyu;Park, Chong Young
    • Clinical and Experimental Pediatrics
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    • v.45 no.3
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    • pp.354-361
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    • 2002
  • Purpose : Selective introduction of genes conferring chemosensitivity into proliferating tumor cells may be used to treat cancer. We first investigated the bystander effect of retrovirus-mediated gene transfer of herpes simplex virus thymidine kinase(HSV-TK) gene to murine neuroblstoma cell line(neuro-2a) in vitro and in vivo. Second, we examined the mechanism and its enhancement of the bystander effect in murine neuroblastoma. Methods : To investigate the bystander effect, we studied tumor growth and survival time after HSV-TK/ganciclovir(GCV) treatment in a syngenic A/J mouse neuroblastoma model by mixing various ratios of HSV-TK-expressing neuro-2a cells with wild type neuro-2a cells followed by GCV treatment. To investigate the mechanism of the bystander effect in murine neuroblastoma, immunohistochemistry using connexin 43, CD4 and CD8-specific monoclonal antibodies was analyzed. We studied whether IL-2-secreting neuro-2a cells(neuro-2a/IL-2) would potentiate the bystander effect. Results : A strong bystander effect was observed in vitro and in vivo. The bystander effect in murine neuroblastoma was dependent on the immune response rather than connexin-mediated gap junction. Neuro-2a/IL-2 treatment enhanced the bystander effect in the HSV-TK/GCV system in murine neuroblastoma model. Conclusion : We conclude that the bystander effect in murine neuroblastoma depends on immune response and is enhanced by neuro-2a/IL-2.

Immunostimulatory Activity of Agarwood through Activation of MAPK Signaling Pathway in RAW 264.7 Murine Macrophages (RAW 264.7 대식세포에서 MAPKs 신호 전달 경로의 활성화를 통한 침향의 면역 자극 활성)

  • Ji, Seon Yeong;Hwangbo, Hyun;Lee, Hyesook;Koo, Young Tae;Kim, Jin Soo;Lee, Ki Won;Noh, Dong Jin;Choi, Yung Hyun
    • Journal of Life Science
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    • v.31 no.8
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    • pp.745-754
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    • 2021
  • Deterioration of the immune function weakens the body's resistance to various infections, leading to a series of diseases. Immunomodulatory biomaterials have been used to reduce the side effects of immunosuppressants or to enhance immunity. Agarwood is the aromatic resinous portion of Aquilaria trees that has been traditionally used as a medicinal herb for the treatment of various diseases. Although previous studies have shown that agarwood can improve the body's immunity, evidence for this claim is still lacking. In this study, the immune-enhancing effects of the agarwood methanol extracts of Aquilaria malaccensis Lamk were evaluated in a RAW 264.7 macrophage model. Based on the results, the agarwood extracts markedly enhanced phagocytosis in the absence of cytotoxicity. The agarwood extract-treated RAW 264.7 cells exhibited the typical morphology of activated macrophages, which are spindle-shaped with elongated filopodia. Agarwood extract also significantly increased the production of nitric oxide (NO), which is associated with the increased expression of inducible NO synthase. Moreover, the secretion and expression levels of cytokines, such as tumor necrosis factor-α and interleukin (IL)-1β and IL-6, were increased by agarwood treatment. Notably, these are also associated with a mitogen-activated protein kinase signaling pathway. Taken together, our findings provide scientific evidence that agarwood has potential immune-enhancing effects in vitro.

Effects of Immunostimulatory CpG-Oligodeoxynucleotides on Bronchial Asthma in Rat (백서 천식에서 면역 증강성 CpG 올리고 뉴클레오티드 투여의 효과)

  • Lee, Sin-Hyung;Kim, Je-Hyeong;Jeong, Hye-Cheol;Kim, Kyung-Kyu;Jung, Ki-Hwan;Kim, Byung-Gyu;Lee, Seung-Heon;Park, Sang-Myun;Sin, Cheol;Cho, Jae-Youn;Shim, Jae-Jeong;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.50 no.1
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    • pp.12-28
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    • 2001
  • Background and Object : Immunostimulatory CpG-oligodeoxynucleotides (ISS CpG-ODN) up-regulate the $T_{H1}$-type immune response and down-regulate the $T_{H2}$-type response. This study was performed to investigate the immune response changes resulting from ISS CpG-ODN on bronchial hyperresponsiveness, eosinophilic inflammation and mucus hypersecretion in rat asthma. Materials and Methods : 10 normal controls(NC) and 26 asthmatic rats, which were generated by ovalbumin(OVA) sensitization and challenge, were studied. The asthmatic rats were randomized into 11 asthma controls(AC) and 15 in the asthma-CpG treatment group(CpG). The CpG group was administered ISS CpG-ODN intramuscularly and the AC group was administered a placebo(0.9% NaCl) on day 15 and 20. After CpG-ODN or placebo administration, we measured the IFN-${\gamma}$($T_{H1}$-type cytokine) and IL-4($T_{H2}$-type cytokine) levels in the bronchoalveolar lavage fluid(BALF), the specific airway resistance(sRaw), eosinophilic fraction in BALF, eosinophilic infiltration, goblet cell dysplasia and MUC5AC gene expression in the lung tissue. Results : In the BALF of the CpG group, the IFN-${\gamma}$ concentration was significantly high and the IL-4 concentration was significantly low when compared with the AC group. Both the sRaw and eosinophilic fraction, and infiltration into the BALF and lung tissue significantly lower in the CpG group when compared with the AC group. However, little difference in goblet cell dysplasia and MUC5AC gene expression was observed between the CpG group and the AC group. Conclusion : ISS CpG-ODN decreases bronchial hyperresponsiveness and eosinophilic inflammation in the rat asthma model through the up-regulation of the $T_{H1}$-type immune response with the down-regulation of the $T_{H2}$-type response. However, the effect of these immune response changes on mucus hypersecretion was is not remarkable in this study.

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The Effects of Cyclooxygenase-2(COX-2) Inhibitor on COX-2 and Prostaglandin E2 Expression in Ovalbumin Induced Early Phase Bronchoconstriction of Rats (Ovalbumin으로 유발된 백서의 즉시형 기관지 수축 반응에서 Cyclooxygenase-2(COX-2) 발현 양상 및 혈중 프로스타글란딘 E2 농도와 COX-2 억제제의 효과)

  • Lee, Sung-Yong;Lee, Sin-Hyung;Jung, Ki-Hwan;Kim, Byung-Gyu;Jung, Hae-Chul;Kim, Kyung-Kyu;Kwon, Young-Hwan;Kim, Ja-Hyeong;Lee, Ju-Han;Lee, Sang-Youb;Cho, Jae-Yoen;Shim, Jae-Joeng;In, Kwang-Ho;Yoo, Se-Hwa;Kang, Kyung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.191-202
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    • 2000
  • Background: Bronchial asthma is characterized by airway hyperresponsiveness(BHR) and inflammation. The cyclooxygenase(COX) is believed to be one of the important enzymes in these inflammatory reactions. Recently, the COX was divided into two isoforms, COX1 and COX2. COX2 is induced by lipopolysaccharide and some cytokines at the inflammation site. Prostaglandin E2(PGE2), produced from COX2, may affect airway inflammation. The purpose of this study is to evaluate the effect of COX2 inhibitor on COX2 expression, plasma PGE2, airway resistance and histologic finding in an animal asthma model. Methods : Sprague-Dawley rats were divided into 3 groups. The normal control group did not receive any treatment, but the asthma control group was sensitized by ovalbumin but not treated with the COX2 inhibitor(nimesulide, Mesulid$^{(R)}$). The treatment group was sensitized and treated with nimesulide. Specific airway resistance(sRaw) before and after nimesulide ingestion was investigated. The PGE2 level in the plasma was examined and COX2 immunogold-silver stain on lung tissue was performed. Results: sRaw and eosionophilic infiltration on airway, which increased in the asthma control group, was compared to normal control(p=0.014). However, there was no difference in eosinophilic infiltration between asthma control and treatment groups(p=0.408) and no difference in COX2 expression on bronchiolar epithelium among the three groups. Plasma PGE2 levels were not statically different among the three groups. Conclusion: The role of COX2 in the allergen-induced BHR was not significant The effect of nimesulide was not observed on BHR, COX2 expression, and plasma PGE2 level. Therefore, COX2 may not be a major substance of allergic asthma.

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A Case of Aggravation of Thyroid Goiter after Treatment with PD-1 Inhibitor for Breast Cancer in Patients with Underlying Hashimoto's Thyroiditis (기저 하시모토 갑상선염이 있던 유방암 환자에서 PD-1 억제제 투약 후 악화된 갑상선 종대의 증례)

  • Kim, Hana;Kim, Min Joo;Song, Young Shin;Cho, Sun Wook
    • International journal of thyroidology
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    • v.11 no.2
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    • pp.172-175
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    • 2018
  • Anti-programmed cell death-1 (PD-1) humanized monoclonal antibody inhibits PD-1 activity by binding to the PD-1 receptor on T-cells and blocking PD-1 ligands and induces immune tolerance of cancer cells. It has been widely used for various kinds of cancer treatment. However, many immune-related adverse events (irAEs) have been reported because it modulates our immune system. In this case study, we reported a case of 42-year-old woman with Hashimoto's thyroiditis who showed rapid aggravation of thyroid goiter and acute hyperventilation syndrome after treatment with PD-1 inhibitor as a neoadjuvant chemotherapy for breast cancer.

Effect of Sophora flavescens Extract on Reinforcing Skin Barrier and Alleviating Inflammation (고삼 추출물의 피부장벽 강화와 염증완화 효과)

  • Roh, Kyung-Baeg;Shin, Seoungwoo;Yoon, Sohyun;Weon, Jin Bae;Oh, Se-young;Kim, Junoh;Park, Deokhoon;Jung, Eunsun
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.46 no.4
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    • pp.361-369
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    • 2020
  • Atopic dermatitis (AD) is a common and multifactorial inflammatory skin disease that is characterized by skin barrier dysfunction, inflammation, and chronic pruritus. AD has a complex etiology that includes genetic, immunological, and environmental factors that cause skin barrier abnormalities and immune dysfunctions. Sophora flavescens (SF) has been used in traditional Chinese medicine, but little research has been conducted on its anti-AD efficacy. In this study, we evaluated the effect of SF extract (SFE) on improving skin barrier function and immune abnormalities, which are the main symptoms of AD. SFE has the capacity to enhance the formation of cornified envelope (CE) that plays an important role in the skin barrier function. In addition, it was confirmed that SFE increased the expression of hyaluronic acid related to skin moisture. The effect of SFE against Staphylococcus aureus (S. aureus), which increases specifically in AD lesions, confirmed that SFE inhibited the production of pro-inflammatory cytokines induced by S. aureus. Furthermore, SFE was shown to inhibit the expression of pro-inflammatory cytokines induced by substance P (SP), the cause of skin neurogenic inflammation. These results demonstrate that SFE could be one of potential candidate agent for the treatment of AD by improving the skin barrier function and immune responses.

Candida Infection in a Patient with Gastric Carcinoma; 1 Case Report (위선암에서 발견된 칸디다증 1예)

  • Chyung, Ju-Won;Yoo, Chang-Young;Cheung, Dae-Young;Hur, Hoon;Jeon, Hae-Myung
    • Journal of Gastric Cancer
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    • v.9 no.1
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    • pp.31-35
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    • 2009
  • Most gastric candida infections have been reported in immune-insufficient patients with peptic ulcer, but there have been few reports on gastric candidiasis with malignant ulcer in the stomach. We experienced a case of candida infection with gastric carcinoma in a 72-year-old female with diabetic mellitus. The endoscopic view showed multiple whitish necrotic plaques with a huge ulcer in the body of the stomach. The pathologic findings showed that budding yeast and pseudohyphae had infiltrated through the ulcerated stomach wall and the stomach wall contained tubular adenocarcinoma. After treatment with Fluconazole medication for 14 days, the patient underwent total gastrectomy along with D2 lymph node dissection. For the final pathologic results, there was no evidence of any remnant candidiasis, and the patient was discharged without specific complications. Through our experience and with reviewing articles about gastric candidiasis, we recommend that the gastric candidiasis that is accompanied with gastric malignancy should be treated before administering definite treatments for the gastric cancer.

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The Effect of Nebulized Frankincense Essential Oil in an OVA-Induced Allergic Asthma Mouse Model (프랑킨센스 에센셜 오일 흡입이 OVA로 유도된 알러지성 천식 모델 생쥐에 미치는 영향)

  • Lee, Hye-Youn;Kim, Kum-Ran;Kang, Sang-Mo
    • Microbiology and Biotechnology Letters
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    • v.38 no.1
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    • pp.93-104
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    • 2010
  • In this study, we investigated the effects of frankincense essential oil (BSEO) on the immune cell change in the lung, BALF and PBMC using a mouse model of asthma. BALB/c mice after intraperitoneal OVA sensitization (day 1) were challenged intratracheally with OVA on day 14. Then, the asthma was induced by repeated OVA inhalation challenged. The asthma induced mice group inhaled 0.3% BSEO for 30 minutes per trial, three times a week, for 8 weeks using the nebulizer. After 12 weeks from the experiment, the mice was killed and the lung, bronchoalveolar lavage fluid (BALF) and peripheral blood mononuclear cell (PBMC) were obtained. Next, the change of immune cells inside the separated tissues was observed to identity the effects of BSEO on the allergic asthma mice. In conclusion, the hypersensitive reaction of airway to the bronchoconstrictor in the allergic asthma induced mice was effectively suppressed in Frankincense group, in Bermagot, Eucalyptus, Chamomile, Marjoram and Frankincense groups, the natural aromatic essential oil groups. Furthermore, it was also confirmed that the weight of lung, total number of alveolus cells and the number of BALF, MNL and DLN increased after inducing allergic asthma were reduced. BSEO suppressed the percentage of $CD3e^+/CD19^-$, $B220^+/CD23^+$ and $CD11b^+/Gr-1^+$ cells in the lung tissue of allergic asthma mice. Moreover, BSEO also reduced the percentage of $CD4^+/CD8^-$, $B220^+/CD23^+$ and $CD3^+/CCR3^+$ cells in BALF. In addition, the percentage of $CD3e^+/CD19^-$, $CD3^+/CD69^+$ and $B220^+/CD23^+$ cells in PBMC was reduced. The results of this study indicate that BSEO would be effective to treat allergic asthma by the immune control suppressing the activity of immune cells in each tissue.

Comparison of Clinical Characteristics of Pneumocystis Carinii Pneumonia Between HIV Infected and Non-infected Persons (인간 면역결핍 바이러스 감염자와 비감염자에서 발생한 주폐포자충 폐렴의 임상 양상 비교)

  • Choi, Jun Yong;Lee, Kkot Sil;Park, Yoon Soo;Cho, Cheong Ho;Han, Sang Hoon;Choi, Suk Hoon;Chin, Bum Sik;Park, Yoon Seon;Chang, Kyung Hee;Song, Young Goo;Kim, June Myung
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.4
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    • pp.370-377
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    • 2003
  • Background : Pneumocystis carinii pneumonia (PCP) is one of the most common cause of infection in patients with HIV infection. Recently, the incidence of PCP have been increasing in immunocompromised hosts without HIV infection. We compared the clinical characteristics of PCP between HIV infected and non-infected persons. Patients and Methods : We retrospectively reviewed the charts of 25 patients diagnosed as PCP from 1996 to 2002. Age, sex, underlying conditions, use of immunosuppressants, clinical courses, laboratory findings, treatment and prognosis were compared between HIV infected and non-infected persons. Results : Twenty-five patients with PCP were identified. 16 were HIV infected, and 9 were HIV non-infected. The mean age of overall patients was $43.4{\pm}13.2$ years. Underlying conditions in HIV non-infected persons were hematologic malignancy (7 cases), solid organ transplant (1 case), and autoimmune disease (1 case). Seven cases (77.8%) of HIV non-infected persons had a history of steroid use. Mean duration of symptoms was longer in HIV infected persons than in HIV non-infected persons, but it was not statistically significant. PaO2 was lower in HIV infected persons ($61.2{\pm}16.9$ mmHg vs. $65.4{\pm}15.4$), but it was not statistically significant. Chest X ray showed typical ground glass opacity in 12 cases (75%) of HIV infected persons and in 4 cases (44.4%) of HIV non-infected persons. Twelve cases (75%) of HIV infected persons were treated with steroid, as were 6 cases (66.7%) of HIV non-infected persons. Ventilator care was needed in 6 cases (37.5%) of HIV infected persons and in 2 cases (22.2%) of HIV non-infected persons. Mortality of HIV infected persons was 50%, and that of HIV non-infected persons was 11.1%. Conclusions : PCP showed some different clinical characteristics between HIV infected and non-infected persons. Prospective studies regarding the risk factors of PCP, prophylaxis, treatment and prognosis in HIV infected and non-infected persons are warranted.

Antiestrogen등 약물이 cytochrome P450와 AEBS에 미치는 효과의 관계

  • 신윤용;정세영
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.100-100
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    • 1993
  • Antiestrogen은 에스트로젠 의존성 유방암 치료에 사용되는 약물로써 표적 세포 내에서 에스트로젠 수용체와 작용하여 세포 증식 억제 작용을 나타내고 동시에 에스트로젠 수용체와는 구분되는 소포체 분획의 antiestrogen specific binding site (AEBS) 와도 결합을 하는 것으로 알려져 있다. 그러나, 아직 이 AEBS의 생리적 또는 약리적 기능은 밝혀져 있지 않다. 따라서 본 실험에서는 AEBS의 기능을 조사하기 위하여 cytochrome P45O III 효소군과 AEBS와의 관계를 자옹 백서를 이용하여 면역 화학 반응 실험 및 경쟁적 결합 반응 실험을 하였고, 그 결과는 다음과 같다. 1) AEBS에 대해서 SKF-525A와 metyrapone은 결합 능력을 나타내었다. 2) 자성쥐에서는 주령이 증가함에 따라 cytochrome P450양이 감소하였다. 3) 자옹성쥐 모두에서 phenobarbital 처치에 의해 cytochrome P450 III 효소양이 증가하였고, AEBS도 증가하였다. 4) 웅성쥐에서는 testosterone에 의하여 AEBS가 증가하였다. 5) 자웅성쥐 모두에 tamoxifen 관류시 cytochrome P450 III 효소양이 증가하였고 estradiol과 병용 관류시에는 tamonifen 단독 관류시보다 감소하였다. 이상의 결과에서 tamoxifen이 cytochrome P450 III을 유도할 수 있는 것으로 사료되며 cytochrome P450 III 효소군과 안티에스트로젠 결합부위와 밀접한 관련이 있는 것으로 생각된다.

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