• Title/Summary/Keyword: 세포독성 치료

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Water Extract of Rhei Rhizoma Prevent Production of Reactive Oxygen Species and Loss of Mitochondrial Membrane Potential in a Hypoxia Model of Cultured Neurons (배양 신경세포의 저산소증모델에서 대황 물추출액의 항산화 및 사립체막전위 소실 억제 효능)

  • Lee, Hyun-Sook;Moon, Il-Soo
    • Journal of Life Science
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    • v.18 no.12
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    • pp.1631-1636
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    • 2008
  • Rhei Rhizoma (RR; 大黃) consists of the underground parts (rhizome and root) of Rheum officinale Baill. and Rheum palmatum L. (Polygonaceae), and is widely used in Southeast Asian folk medicine to alleviate liver and kidney damages. In this study, we investigated into the efficacy and mechanism of RR water extract in supporting neuronal survival in a hypoxia model of cultured rat hippocampal neurons. RR exhibited no cytotoxicity up to 10 ${\mu}g$/ml and exhibited neurosupportive effects at 2.5 ${\mu}g$/ml in normoxia. When RR was added to the culture media on 10 days in vitro (DIV10) and given a hypoxic shock (2% $O_2$/5% $CO_2$, 3 hr, $37^{\circ}C$) on DIV13, RR exhibited neuroprotective effects on 5 days post-shock. $H_2DCF$ stainings indicated that RR effectively prevents ROS production in both normoxia and hypoxia. JC-1 stainings showed that RR prevents dissipation of MMP in hypoxia. These results indicate that RR protects neurons by suppressing ROS production and MMP loss.

In vitro Anti-oxidative and Anti-inflammatory Activities of Horse-bone Extract via Up-regulation of Heme-oxygenase 1 (말뼈추출물의 Hemeoxygenase-1의 발현 조절을 통한 시험관내 항염증 효과)

  • Im, Eun Ju;Lee, Ki-Ja;Cho, Gil-Jae;Kim, Hyun-Kyoung;Kim, Suk;Rhee, Man Hee
    • Journal of agriculture & life science
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    • v.50 no.2
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    • pp.139-150
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    • 2016
  • Few studies have been reported that horse-bone extract(HBE) can prevent and treatment of bone diseases. However, HBE' therapeutic activities are still not fully understood. This study determined whether HBE up-regulates hemeoxygenase 1(HO-1) and this mediates its anti-inflammatory effect in murine macrophages.Nitric oxide(NO) assay, MTT assay and DPPH assay were performed. In addition, Western blotting and real time PCR were used to determine protein expression, and gene expression, respectively. HBE significantly inhibited NO production without observable cytotoxicity. In addition, HBE attenuated inducible nitric oxide synthase (iNOS), cyclooxygenase-2(COX-2) and phospho (p)-ERK protein expressions in LPS(0.1㎍/ml) stimulated RAW264.7 cells. On the other hand, HBE alone up-regulated HO-1 and Nrf-2 expressions, which mediated HBE's anti-inflammatory effect in RAW264.7 cells. Finally, HBE up-regulated HO-1 and impaired ERK1/2 signaling pathways, and thus it may provide protection against cellular oxidation and inflammation.

Improving effect of psoriasis dermatitis by yakuchinone A in the TNF-α stimulated HaCaT cells (TNF-α 자극에 활성화된 HaCaT 세포주에서 Yakuchinone-A에 의한 건선 피부염 개선 효과)

  • Kim, Min Young;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.63 no.1
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    • pp.95-101
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    • 2020
  • Psoriasis is an autoimmune skin disease that is accompanied by hyper proliferation of the epidermis, erythema of various sizes, and ulceration. However, the mechanism of the development of psoriasis dermatitis is unclear. Recently, it is known that the inflammatory cytokines and Th17 cells as well as chemokine (CC motif) ligand 20 (CCL20) are involved in the process of keratinocytes hyper-differentiation, which is common in psoriasis dermatitis. Therefore, we studied the effects of yakuchinone-A, an active ingredient of Alpinia oxyphylla Miquel known for its anti-inflammatory activity, to improve psoriasis dermatitis. First, cytotoxicity of yakuchinone-A was observed in cell counting kit-8 assay and not observed in 10 ㎍/mL concentration on the human keratinocyte HaCaT cells. Yakuchinone-A in the presence of tumor necrosis factor-alpha (TNF-α) on HaCaT cells inhibited mRNA expression of IL-6, IL-8, and TNF-α by up to 61.4±7.5, 23.6±1.5, 46.0±4.8%. CCL20, a chemokine that attracts immune cells such Th17 cells to the inflammation location, was also significantly suppressed by yakuchinone-A. In addition, IκB and STAT3 phosphorylation involved in the CCL20 expression was inhibited by yakuchinone-A in a concentration-dependent manner up to the level of 79.1±5.0, 80.8±2.3%. Furthermore, yakuchinone-A downregulated CCL20 mRNA expression level on IL-17A-activated HaCaT cells as a concentration-dependent manner. Based on these results, yakuchinone-A is expected to be developed as a new material for improving psoriasis dermatitis in the future.

Pulmonary Toxicity Following High-Dose Chemotherapy With Peripheral Blood Stem Cell Transplantation (고용량 항암화학요법 후에 발생한 폐손상)

  • Lee, Sun-Min;Park, Kwang-Joo;Oh, Yoon-Jung;Cheong, Seong-Cheoll;Hwang, Sung-Chul;Lee, Yi-Hyung;Kim, Hyun-Soo;Lim, Ho-Yeong;Kim, Hugh-Chul;Yim, Hyun-Ee;Hahn, Myung-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.1
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    • pp.77-89
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    • 1999
  • Background: High-dose chemotherapy is increasingly employed in many refractory malignant diseases. This therapy has been reported to increase response rate and survival benefits but it is also associated with higher treatment-related morbidity and mortality. We evaluated clinical characteristics and course of the pulmonary toxicity following high-dose chemotherapy with peripheral blood stem cell transplantation. Methods: Ninety-seven patients who had received high-dose chemotherapy with peripheral blood stem cell transplantation were evaluated. Five patients who developed lung lesions which were not related to infection nor primary malignant disease underwent transbronchial lung biopsy. The patients' clinical characteristics, treatments, and prognosis were reviewed retrospectively. Results: Five patients(5.1%) developed idiopathic pneumonia syndrome. The high dose chemotherapy regimens employed were cyclophosphamide, BCNU, and cisplatin in 3 cases, one case of BCNU, etoposide, Ara-C, and cyclophosphamide combination, and a regimen consisting of BCNU, etoposide, Ara-C, and melphalan. The total dose of BCNU used was 300-400 mg/$m^2$ and that of cyclophosphsmide was 6,000 mg/$m^2$. All of 5 patients received radiation therapy before this treatment. After an average duration of 14 weeks (4-26 weeks) of high-dose chemotherapy, patients developed cough, dyspnea and fever. The chest X-rays showed bilateral diffuse infiltration in 3 cases and the focal infiltration in the other 2 cases. All the patients received corticosteroid therapy as a treatment for the lung lesions. Two of them progressed to acute respiratory distress syndrome and died. Three patients recovered without residual lung lesion but one of them died of dilated cardiomyopathy. Conclusion: High-dose chemotherapy with peripheral blood stem cell transplantation especially which containing BCNU regimen may develop idiopathic pneumonia syndrome related to pulmonary toxicity and corticosteroid therapy may be bel1eficial in some cases.

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Antioxidative, Antimicrobial and Cytotoxic activities of Fagopyrum esculentum $M{\ddot{o}}ench$ Extract in Germinated Seeds (발아 메밀 추출물의 항산화.항균활성 및 세포독성)

  • Hwang, Eun-Ju;Lee, Sook-Young;Kwon, Su-Jung;Park, Min-Hee;Boo, Hee-Ock
    • Korean Journal of Medicinal Crop Science
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    • v.14 no.1
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    • pp.1-7
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    • 2006
  • This research was conducted to investigate the possibilities of usage of germinated-buckwheat (Fagopyrum esculentum $M{\ddot{o}}ench$) by examining antioxidative, antimicrobial and cytotoxic effects of extracts from different germinated root length of buckwheat. Antioxidant activity $(RC_{50})$ was shown higher in extracts of non-germinated seed $(50.41\;{\mu}g/mL)$ and root length 10 mm $(80.57\;{\mu}g/mL)$, 2 mm $(93.77\;{\mu}g/mL)$, 5 mm $(107.09\;{\mu}g/mL)$ than BHT $(163.96\;{\mu}g/mL)$ as a synthetic antioxidant. In antimicrobial activity, non-germinated and germinated seeds were formed inhibitory zone against S. aureus $(4{\sim}10\;mm)$, P. aeruginosa $(2{\sim}9\;mm)$ at the concentrations of $10{\sim}40\;mg/mL$ but B. subtilis, E. coli and S. typhimurium were not apparent antimicrobial activity. Extracts of germinated seed also decreased their antimicrobial activity compared to non-germinated seed extract. In addition, the growth of Calu-6 was inhibited of both 5 mm root length germinated and non-germinated seeds $(800\;{\mu}g/mL)$ as 95.12% and 87.15%, respectively, but these did not show any influence on cytotoxic effect against MCF-7 and Caco-2 cell lines. Extracts of 2 mm and 5 mm germinated seeds were also inhibited against Calu-6 and SNU-601 cell lines.

Concurrent Chemoradiotherapy with Biweekly Gemcitabine and Cisplatin in Patients with Locally Advanced Non-small Cell Lung Cancer (진행성 비소세포폐암 환자에서 Gemcitabine/Cisplatin을 이용한 동시 화학 방사선 요법)

  • Oak, Chul-Ho;Kim, Ja-Kyung;Jang, Lee-La;Moon, Dae-Sung;Jang, Tae-Won;Jung, Maan-Hong;Cho, Sung-Whan;Jeung, Tae-Sig
    • Radiation Oncology Journal
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    • v.26 no.3
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    • pp.160-165
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    • 2008
  • Purpose: In cases of locally advanced non-small cell lung cancer (NSCLC), concurrent chemoradiotherapy(CCRT) is the leading therapeutic modality. However, much controversy exists about the chemotherapeutic regimens and radiation methods. Materials and Methods: During concurrent chemoradiotherapy, three or four cycles of gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were administered every two weeks while 50.4 Gy of irradiation was administered in 28 fractions (once/day, 5 treatment days/week) to the tumor site, mediastinum, and the involved lymph node region. In addition, a booster irradiation dose of 18 Gy in 10 fractions was administered to the primary tumor site unless the disease progressed. Two or three cycles of consolidation chemotherapy were performed with gemcitabine ($1,200\;mg/m^2$, $1^{st}$ and 8th day) and cisplatin ($60\;mg/m^2$) every three weeks. Results: A total of 29 patients were evaluable for modality response. Response and treatment toxicities were assessed after concurrent chemoradiotherapy and consolidation chemotherapy, respectively. One patient (4%) achieved a complete response; whereas 20 patients (69%) achieved a partial response after concurrent chemoradiotherapy. Following the consolidation chemotherapy, three patients (10.3%) achieved complete responses and 21 patients (72.4%) achieved partial responses. The median follow-up period was 20 months (range $3{\sim}39$ months) and the median survival time was 16 months (95% CI; $2.4{\sim}39.2$ months). The survival rates in one, two, and three years after the completion of treatment were 62.7%, 43.9%, and 20%, respectively. Complications associated to this treatment modality included grade 3 or 4 esophagitis, which occurred in 15 patients (51.7%). In addition, an incidence of 24% for grade 3 and 14% for grade 4 neutropenia. Lastly, grade 2 radiation pneumonitis occurred in 6 patients (22%). Conclusion: The response rate and survival time of concurrent chemoradiotherapy with biweekly gemcitabine ($500\;mg/m^2$) and cisplatin ($30\;mg/m^2$) were encouraging in patients with locally advanced NSCLC. However, treatment related toxicities were significant, indicating that further modification of therapy seems to be warranted.

항균제 임상시험 Guideline

  • 우준희
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1994.11a
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    • pp.27-30
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    • 1994
  • 잠재적으로 항감염 약제로 사용될 가능성이 있는 약제들의 초기 연구과정에서 주된 관심사는 이들이 미생물(세균, 바이러스, 기타 기생충)에 대한 작용들이 있는가 하는 점이다. 이러한 작용들이 실험적으로 충분히 연구가 된 후에야 실험동물에서 그 효과를 연구한다. 항 바이러스 제제의 경우에는 세포배양을 통한 연구가 그 약제의 독성과 효용성을 나타내는데 필수적인 것이 된다. 여러 종류의 동물을 이용한 생체실험에서 약제의 일반적인 흡수와 배설, 분포 등에 관한 정보와 약제 자체와 동물 내에서의 대사적 변화에 대한 정보가 제공된다. 여러 가지 미생물로 감염을 시킨 적합한 동물과 여러 가지 용량으로 치료하는 실험을 통하여 약제의 항 감염 능력이 알려지게 된다. 동물에서의 생체실험과 실험관내에서 실험을 하고 나서야 사람에서의 연구가 이루어지게 된다. 소위 전임상시험에서 대표적 병원성 미생물에 대한 생물학적효과, 약리학적 효과와 독성 그리고 동물실험모델에서의 가능한 효과가 결정된 후에 임상시험에 들어가기 마련이다. 항균제의 임상시험에는 각각의 감염질환에 대한 진단 및 치료기준을 반영하는 것이 기본이다. 새로운 항균제의 임상시험에서는 안전성과 효과가 반드시 밝혀져야 한다. 1상에서는 인체에서의 약리효과, 안전성이 주목적이며, 2상과 3상은 겹쳐지는 점도 있으나 하나 또는 그 이상의 적응증에 대한 항균제의 효과와 단기간의 부작용은 2상에서 관찰하여야하며, 다수의 환자에서 제안된 적응질환의 무작위임상시험과 다수에서의 안전성도 3상에서 관찰하여야 한다. 4상에서는 이상에서의 자료로 시판된 후에도 계속해서 감시하는 것으로 지속적으로 안전성을 관찰하는 것이다. 이러한 기본사항외에도 소아, 임산부, 고령자등에서의 임상시험도 넓은 의미에서 포함되어야 할 것이며 또한 질적인 면에서 조절하는 Quality Assurance도 중요하다.양상은 세 용량군 간 차이가 없었으나, 시험기에서 발열의 발현율이 낮았으며, 발열일 수와 항생제 사용일 수가 짧았다. 결론: 골수억제 조절 효과는 용량에 따른 혈액소견에 미치는 영향, 부작용, 감염의 빈도, 감염발생에 따른 항생제 사용기간 등을 고려하여 그 임상 유효성 평가시, 제 3상 시험에 사용할 권장량 (recommended dose) 은 250 ug/$m^2$/d $\times$ 10d 으로 관찰되었다.5주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 모든 처리군들이 대조군에 비하여 높게 발현되는. 것이 관찰되었으나 시험개시후 26주에 부검한 랫드의 간에서 c-myc 종양단백의 발현은 대조군에 비하여 차이가 거의 없었다. 따라서 랫드에서 화학적으로 유도한 간암발생 과정에서 NK 세포활성이 현저하게 억제되는 것으로 생각되며, c-myc 종양단백의 발현은 시험개시후 15주에 그 발현이 확실한 것으로 사료되어 진다.에 영향을 주는 성분이 있음을 제시하였다.1과 항우울약들의 항혈소판작용은 PKC-기질인 41-43 kD와 20 kD의 인산화를 억제함에 기인되는 것으로 사료된다.다. 것으로 사료된다.다.바와 같이 MCl에서 작은 Dv 값을 갖는데, 이것은 CdCl$_{4}$$^{2-}$ 착이온을 형성하거나 ZnCl$_{4}$$^{2-}$ , ZnCl$_{3}$$^{-}$같은 이온과 MgCl$^{+}$, MgCl$_{2}$같은 이온종을 형성하기 때문인것 같다. 한편 어떠한 용리액에서던지 NH$_{4}$$^{+}$의 경우 Dv값이 제일 작았다. 바. 본 연구의 목적중의 하나인 인체유

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A Case of Subcutaneous Panniculitis-like T Cell Lymphoma in Childhood (소아에서 발생한 Subcutaneous Panniculitis-like T Cell Lymphoma 1례)

  • Choi, Yoon Seok;Shin, Kyung Mi;Won, Sung Chul;Lyu, Chuhl Joo;Yang, Chang Hyun;Kim, Byung Soo;Kim, Moon Kyu
    • Clinical and Experimental Pediatrics
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    • v.45 no.8
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    • pp.1028-1032
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    • 2002
  • Subcutaneous pannicultis-like T cell lymphoma is a rare cutaneous T cell lymphoma. It presents with multiple subcutaneous nodules or plaques involving the extremities or trunk, and with constitutional symptoms that include fever, malaise, fatigue, myalgia, chills and weight loss. Histologically, the lesions of this disease are reminiscent of panniculitis and are composed of a mixture of small and large atypical lymphoid cells infiltrating between adipocytes. The optimal treatment for this disease is undefined and prognosis of this disease is poor, even when treated with multiagent chemotherapy regimens considered optimal for agressive lymphoma of other types. Poor prognosis factors include clinical features such as anemia, leukocytopenia, hepatosplenomegaly, lymphadenopathy and coagulopathy, which are suggestive of hemophagocytosis. Much of the mortality of this disease is due not to disseminated lymphoma with organ failure, but rather to complications of the cytopenias associated with the hemophagocytic syndrome. We report a case of subcutaneous panniculitis-like T cell lymphoma in a 12 year-old boy who presented with initial complaints of fever and multiple subcutaneous nodules, and briefly review the related literature.

Inhibitory Effects of Locusta migratoria Ethanol Extracts on RANKL-induced Osteoclast Differentiation (RANKL 유도된 파골세포 분화에 대한 풀무치 에탄올 추출물의 분화 억제 효과)

  • Baek, Minhee;Seo, Minchul;Lee, Joon Ha;Lee, Hwa Jeong;Kim, In-Woo;Kim, Sun Young;Kim, Mi-Ae;Kim, Sunghyun;Hwang, Jae-Sam
    • Journal of Life Science
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    • v.29 no.10
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    • pp.1104-1110
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    • 2019
  • Recently, there has been an increase in the elderly population of the world. Consequently, bone metabolic diseases such as osteoporosis are emerging as a social problem. Osteoclasts play a role in bone resorption, and osteoporosis is induced when bone resorption occurs excessively. Because currently used bone resorption inhibitors may cause side effects when used for a long period of time, it is necessary to develop a new material that effectively inhibits osteoclast differentiation. This study aimed to confirm the inhibitory effect of ethanol extract of Locusta migratoria on RANKL-induced osteoclast differentiation and its mechanism. The toxicity and proliferation effects of LME on RAW264.7 osteoclasts were measured by an MTS assay. There was no cytotoxicity or proliferation when the osteoclasts were treated with up to $2,000{\mu}g/ml$ of LME. In order to confirm the effect of LME on the differentiation of osteoclasts, osteoclasts were treated with RANKL alone or with LME for 3 days. As a result of a TRAP (tartrate-resistant acid phosphatase) assay, the increasing osteoclast differentiation by RANKL decreased in a concentration-dependent manner with the treatment of LME. In addition, LME suppressed the expression of differentiation-related marker genes (TRAP, RANK, NFATc1, and CK) and proteins (NFATc1 and c-Src) that had been increased by RANKL. Also, LME influenced the $NF-{\kappa}B$, ERK and JNK signaling pathways, resulting in the inhibition of osteoclast differentiation. These results suggest that LME may be used as a novel functional material for the prevention and treatment of osteoporosis by playing a role in inhibiting bone absorption.

Effects of complex extracts having Drynariae Rhizoma on suppression of collagenolysis and bone resorption in mouse calvarial osteoblasts (골쇄보(骨碎補) 복합제제가 생쥐의 calvarial osteoblast에서 collagen 용해와 골재흡수에 미치는 영향)

  • Hong, Shi-Nae;Jeong, Ji-Cheon
    • The Journal of Dong Guk Oriental Medicine
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    • v.9
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    • pp.179-191
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    • 2000
  • Anti-bone resorption properties of the Korean herbal medicine, CEDR, which is comprised 5 herbs of [Drynariae Rhizoma, Loranthi Ramus, Cibotii Rhizoma, Amydae carapax, Psoraleae semen], were investigated. Mouse calvarial osteoblast cells were isolated and cultured. Mouse osteoblasts, which were stimulated by PTH, $1,25(OH)_2D_3$, $TNF-\alpha$ and IL-1 as bone resorption agents, showed increased collagenolysis by producing the active gelatinase. IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. The results of in vitro cytotoxicities showed that CEDR extracts have no any cytotoxicities in concentrations of $1-60{\mu}g/ml$ and furthermore there is no any cytotoxicity even in concentration of $120{\mu}g/ml$ on mouse calvarial bone cells. CEDR extracts had protective activity against PTH (5 units/ml, or $IL-1{\alpha}$ (1 ng/ml) or $TNF-\alpha$ or $1,25(OH)_2D_3$ (20 ng/ml), $IL-1{\alpha}$ and $IL-1{\beta}-induced$ collagenolysis in the mouse calvarial cells. Pretreatment of the CEDR extracts for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore, the medicinal extracts were shown to have the protective effects against collagenolysis induced by $IL-1{\alpha}$ and $IL-1{\beta}$. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the CEDR extracts were shown to have the inhibiting effects against gelatinase enzyme and processing activity induced by the bone resorption agents of PTH, $1,25(OH)_2D_3$, $TNF-\alpha$, $IL-1{\beta}$ and $IL-1{\alpha}$ with strong protective effect in pretreatment with the extracts. CEDR extracts were shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. These results indicated that the CEDR extracts are highly stable and applicable to clinical uses in osteoporosis.

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