• Title/Summary/Keyword: immune toxicity

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The Role of Modern Radiotherapy Technology in the Treatment of Esophageal Cancer

  • Moon, Sung Ho;Suh, Yang-Gun
    • Journal of Chest Surgery
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    • v.53 no.4
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    • pp.184-190
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    • 2020
  • Radiation therapy (RT) has improved patient outcomes, but treatment-related complication rates remain high. In the conventional 2-dimensional and 3-dimensional conformal RT (3D-CRT) era, there was little room for toxicity reduction because of the need to balance the estimated toxicity to organs at risk (OARs), derived from dose-volume histogram data for organs including the lung, heart, spinal cord, and liver, with the planning target volume (PTV) dose. Intensity-modulated RT (IMRT) is an advanced form of conformal RT that utilizes computer-controlled linear accelerators to deliver precise radiation doses to the PTV. The dosimetric advantages of IMRT enable better sparing of normal tissues and OARs than is possible with 3D-CRT. A major breakthrough in the treatment of esophageal cancer (EC), whether early or locally advanced, is the use of proton beam therapy (PBT). Protons deposit their highest dose of radiation at the tumor, while leaving none behind; the resulting effective dose reduction to healthy tissues and OARs considerably reduces acute and delayed RT-related toxicity. In recent studies, PBT has been found to alleviate severe lymphopenia resulting from combined chemo-radiation, opening up the possibility of reducing immune suppression, which might be associated with a poor prognosis in cases of locally advanced EC.

Effects of Lobophytum crassum extract(MC-1) on Various Immunological Factors Related to Pathogenesis of Atopic Dermatitis in Dermatophagoides Pteronyssinus Treated NC/Nga mice (연산호 추출물(MC-1)이 아토피피부염 유발 NC/Nga 생쥐의 혈액내 면역 관련 인자에 미치는 영향)

  • Choi, Hak-Joo;Sim, Boo-Yong;Miyamoto, Tomofumi
    • The Korea Journal of Herbology
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    • v.30 no.1
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    • pp.95-101
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    • 2015
  • Objectives : The aim of this study was to confirm whether or not coral has a preventive effect on development of atopic dermatitis induced by house mite(dermatophagoides pteronyssinus) in NC/Nga mice. Methods : This study was undertaken by using a reliable Atopic dermatitis mouse model demonstrating similar immune response. Lobophytum crassum was administered orally to NC/Nga mouse for 3 weeks. In order to verify the effectiveness of Lobophytum crassum in atopic dermatitis treatment, its role in immune factors were observed in NC/Nga mice. Results : ALT, AST, BUN and creatine levels were all within in the normal ranges in MC-1 200 and 400 (mg/kg) treated groups, indicating no induced toxicity. MC-1 200 and 400 (mg/kg) groups decreased of atopic dermatitis skin manifestation in NC/Nga mouse of MC-1 200 and 400 (mg/kg) groups compared to that of the control group and decreased the ratio of WBC and lymphocyte in blood. Also, MC-1 200 and 400 (mg/kg) groups significant decreased the ratio of CD4+, CD8+, CD11b+/Gr1+, B220/CD23 and CD4/CD25 immune cell ratio in ALN. Finally MC-1 200 and 400 (mg/kg) groups significantly increased the ratio of CD4+, CD8+, B220/CD23 and CD4/CD25 immune cells in DLN. Conclusions : Theses results suggested that Lobophytum crassum has suppressive effects on aberrant and overactive immunological activities in dermatophagoides pteronyssinus-induced dermatitis mice of NC/Nga.

The effects of estradiol and its metabolites on the regulation of CYP 1A1 expression.

  • Joung, Ki-Eun;Sheen, Yhun-Yhong
    • Proceedings of the PSK Conference
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    • 2002.10a
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    • pp.294.1-294.1
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    • 2002
  • The effects of estradiol and its metabolites on the regulation of CYP1A1 expression. K.E. Joung and Y.Y. Sheen College of Pharmacy, Ewha womans University, Seoul. 120-750, Korea 2, 3.7.8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity. immune suppression. and reproductive and developmental toxicity. (omitted)

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Suppression of colon cancer by administration of Canavalia gladiata D.C. and Arctium lappa L., Redix extracts in tumor-bearing mice model (종양이식 생쥐모델에서 도두(刀豆), 우방근(牛蒡根) 추출물의 대장암 억제 효과)

  • Jang, Ji-Hye;Ji, Kon-Young;Choi, Hyung-Seok;Yang, Won-Kyung;Kim, Han-Young;Kim, Kun-hoae;Kang, Hyung-Sik;Lee, Young-Cheol;Kim, Seung-Hyung
    • The Korea Journal of Herbology
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    • v.32 no.5
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    • pp.27-38
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    • 2017
  • Objective : In the present study, we examined whether Canavalia gladiata D.C. (CG) and Arctium lappa L., Redix (AL) mixture (CGAL), their components, lupeol and chicoric acid, regulate immune system and suppress the tumor in vitro and in vivo. Methods : LPS-induced reactive oxygen species (ROS) and nitric oxide (NO) were measured after treatment with CG extract (CGE), CGAL, lupeol, chicoric acid and lupeol and chicoric acid mixture (lupeol+CA) in Raw264.7 cell. To determine the effect of CGE on immune responses, immune cell population and IgG production were assessed in mice. To investigate the effect of CGAL and their component on anti-tumor activity, tumor volume and weight were measured, cell cycles and immune cell population were analyzed in MC38 injected tumor bearing mice. Also, NK cell activity was determined in splenocyte isolated from tumor bearing mice. Results : CGE, CGAL, lupeol, chicoric acid and lupeol+CA decreased the LPS-induced ROS and NO production without cell toxicity in RAW264.7 cells. CGE increased the immune cell populations of $CD4^+T$, $CD8^+T$ and macrophages in various immune organ of mice. In tumor bearing mice, CGAL, lupeol, chicoric acid and lupeol+CA suppressed tumor volume and weight. In cell cycle analysis, they decreased the percentages of S phase. In addition, CGAL, lupeol, chicoric acid and lupeol+CA immune cell populations of $CD4^+T$, $CD8^+Tcell$, NK cell and macrophage in tumor as well as NK cell activity. Conclusion : CGAL and its compounds may enhance immune responses and suppress tumor growth, and may be capable of developing health functional foods.

Research of Efficacy of Curculiginis Rhizoma aquaous extract on collagen induced arthritis (선모(仙茅) 열수(熱水) 추출물의 Collagen 유발 관절염에 대한 약리 효능 연구)

  • Seo, Bu Il;Roh, Seong Soo;Park, Ji Ha;Park, Chan Ik;Koo, Jin Suk
    • The Korea Journal of Herbology
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    • v.31 no.4
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    • pp.1-10
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    • 2016
  • Objectives: In Korean medicine, Curculiginis Rhizoma was treated for arthritis in remedy. But efficacy of Curculiginis Rhizoma on collagen induced arthritis was not revealed.Methods: Anti inflammatory effect of Curculiginis Rhizoma was researched in vitro with RAW264.7 cell and cell toxicity, levels of proinflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-12) and PGE2 were analyzed by ELISA assay. Inflammatory protein were analyzed by western blotting assay (JNK, ERK, COX-2, TNF-α and IL-1β). In vivo, collagen induced arthritis mice model was used to evaluate anti-inflammation effect through arthritis index, immune cell number and cytokine levels (TNF-α, IL-6 and IL-1β) in serum.Results: ECR(Extract of Curculiginis Rhizoma) has not shown cell toxicity in 200 ㎍/㎖ on RAW264.7 cell. ECR suppressed releases of NO, TNF-α, IL-1β, IL-6, IL-12 and PGE2 on RAW264.7 cell treated with lipopolysacharide (1 ㎍/㎖). And ECR inhibited regulation of TNF-α, IL-1β and IL-6 mRNA, reduced protein release of JNK, ERK, iNOS, COX-2, IL-1β and TNF-α. AI of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly decreased compared to vihicle arthritis mice, the number of immune cell in foot joint was increased on control mice but those of group treated with ECR 200 ㎎/㎏ and 100 ㎎/㎏ were significantly reduced. This results correspond with contens of cytokines (TNF-α, IL-1β and IL-6) in serum.Conclusions: Curculiginis Rhizoma has anti-inflammation effect on RAW264.7 cell in vitro and collagen induced arthritis in vivo. So it is necessary to research more mechanism for cascade imfact.

Genotoxicity and Identification of Differentially Expressed Genes of Formaldehyde in human Jurkat Cells

  • Kim, Youn-Jung;Kim, Mi-Soon;Ryu, Jae-Chun
    • Molecular & Cellular Toxicology
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    • v.1 no.4
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    • pp.230-236
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    • 2005
  • Formaldehyde is a common environmental contaminant found in tobacco smoke, paint, garments, diesel and exhaust, and medical and industrial products. Formaldehyde has been considered to be potentially carcinogenic, making it a subject of major environmental concern. However, only a little information on the mechanism of immunological sensitization and asthma by this compound has been known. So, we performed with Jurkat cell line, a human T lymphocyte, to assess the induction of DNA damage and to identify the DEGs related to immune response or toxicity by formaldehyde. In this study, we investigated the induction of DNA single strand breaks by formaldehyde using single cell gel electrophoresis assay (comet assay). And we compared gene expression between control and formaldehyde treatment to identify genes that are specifically or predominantly expressed by employing annealing control primer (ACP)-based $GeneFishing^{TM}$ method. The cytotoxicity ($IC_{30}$) of formaldehyde was determined above the 0.65 mM in Jurkat cell in 48 h treatment. Based on the $IC_{30}$ value from cytotoxicity test, we performed the comet assay in this concentration. From these results, 0.65 mM of formaldehyde was not revealed significant DNA damages in the absence of S-9 metabolic activation system. And the one differentially expressed gene (DEG) of formaldehyde was identified to zinc finger protein 292 using $GeneFishing^{TM}$ method. Through further investigation, we will identify more meaningful and useful DEGs on formaldehyde, and then can get the information on the associated mechanism and pathway with immune response or other toxicity by formaldehyde exposure.

Experimental Research of Baecksunpijibujabokhap-banng(BJBB) on Atopic Dermatitis Treatment (백선피지부자복합방(白鮮皮地膚子複合方)의 항아토피피부염 효능에 관한 실험적 연구)

  • Sim, Boo-Yong;Ji, Joong-Gu;Lee, Won-Yung;Kim, Su-Jung;Kim, Hyo-Young;Lee, Ji-Young;Kim, Dong-Hee
    • Journal of Haehwa Medicine
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    • v.22 no.2
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    • pp.67-79
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    • 2014
  • In order to investigate the efficacy of BJBB on atopic dermatitis, various immune related factors were studied. The results and conclusions are as follows. Atopic dermatitis symptoms were improved in BJBB treated group and significant decrease in dermatitis index were observed in 13 weeks. ALT, AST and BUN, Cr levels were all with in the normal ranges in BJBB treated group, indicating no induced toxicity. BJBB treated group showed significant decrease in CD4+, CD11b+/Gr-1+ immune cell ratio in dorsal skin by 33% and 62% respectively. BJBB treated group showed significant decrease in the expression of IL-4, IL-5, IL-13 and histamine by 83%, 62%, 53% and 61% respectively. Also the group showed decrease in the transcription of IL-4, IL-5 and IL-13 mRNA in spleen by 41%, 52% and 50% respectively. BJBB treated group showed decrease in the expression of IgE by 57% respectively. The results above indicated that treatment of BJBB improved atopic dermatitis symptoms by immune modulation activity a clinical evidence. thus, BJBB has a potential use as a composition of medicinal plants for treatment against inflammation related disease.

Updates to Clinical Information on Anticancer Immunotherapy (항암 면역 치료제에 관한 최근 임상 정보)

  • Choi, Eunjoo;Yang, Jae Wook
    • Korean Journal of Clinical Pharmacy
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    • v.28 no.1
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    • pp.65-75
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    • 2018
  • Objective: Over the last several years, immunotherapy has become one of the most promising therapeutic options for cancer. This study aims to summarize the updates on cancer immunotherapy focusing on immune checkpoint inhibitors, such as programmed cell death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitors, which have received attention as new anticancer therapeutic agents. Methods: A literature survey was carried out on PubMed to identify high-impact papers on cancer immunotherapy from 2010. The most recent data on clinical efficacy and safety have been included highlighting the response characteristics to recently approved immunotherapeutic agents. Results: In various cancers, immune checkpoints are a means for cancer cells to evade the immune system. Furthermore, CTLA-4 and PD-L1 can be overexpressed, allowing malignant cells to evade T-cells. Numerous clinical trials have been performed to seek appropriate indication of these products in various cancer types. Among them, the most conspicuous types are melanoma, non-small-cell lung cancer, and head and neck cancer. The approval of ipilimumab by Food and Drug Administration (FDA) commenced a new era of cancer immunotherapy. This was followed by the approval of nivolumab and pembrolizumab. Currently, combination therapies are being investigated for various cancer types. Conclusion: In this study, we reviewed recently reported scientific and clinical evidence for currently approved immune checkpoint inhibitors. Although these novel checkpoint inhibitors are ever evolving for cancer therapies, there exist limitations that need to be overcome, indicating the necessity for further studies aiming to improve their efficacy, toxicity, and cost.

Study for Possibility of N,N,N-Trimethylphytosphingosine (TMP) for Management of Chronic Skin Diseases (N,N,N-Trimethylphytosphingosine (TMP)의 염증성 피부질환 치료제 가능성에 관한 연구)

  • Seo, Won-Sang;Oh, Han-Na;Park, Woo-Jung;Um, Sang-Young;Kang, Sang-Mo
    • KSBB Journal
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    • v.29 no.1
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    • pp.36-41
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    • 2014
  • Skin disease is one of the most common diseases and its incidence is increasing dramatically in modern society. Specially, many attempts have been made to treat chronic skin inflammation diseases, such as psoriasis and atopic dermatitis, but effective therapies for the immune cell-mediated skin diseases, including psoriasis and atopic dermatitis have not been developed. Until recently, several drug candidates which were claimed to be effective for skin diseases have been reported, but most of them are not used to treat chronic skin disease. Especially, Psoriasis is characterized by excessive growth and aberrant differentiation of keratinocytes, but is fully reversible with appropriate therapy. The trigger of the keratinocyte response is thought to be activation of the cellular immune system, with T cells and various immune-related cytokines. Formation of new blood vessels starts with early psoriatic changes and disappears with disease clearance. Several angiogenic mediators are up-regulated in psoriasis development. Contact- and mediator-dependent factors derived from keratinocytes, mast cells and immune cells may contribute to the strong blood vessel formation of psoriasis. New technologies and experimental models provide new insights into the role of angiogenesis in psoriasis pathogenesis. TMP and its derivatives themselves effectively inhibited in vitro cell migration, tube formation, and the expression of angiogenic factors. However, TMP and its derivatives induced side effects including hemolysis and local side effects. Therefore, in an attempt to reduce the toxicity and the undesirable side effects of TMP and derivatives, a liposomal formulation was prepared and tested for its effectiveness. TMP and derivatives liposomes retained the effectiveness of TMP in vitro while side effects were reduced. These results support the conclusion that TMP effectively inhibits in vitro angiogenesis, with the possibility that use as a psoriasis relief agent.