• 제목/요약/키워드: tumor response

검색결과 1,398건 처리시간 0.024초

Clinical Observations on Associations Between the UGT1A1 Genotype and Severe Toxicity of Irinotecan

  • Lu, Yan-Yan;Huang, Xin-En;Wu, Xue-Yan;Cao, Jie;Liu, Jin;Wang, Lin;Xiang, Jin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권7호
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    • pp.3335-3341
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    • 2014
  • Background: Severe toxicity is commonly observed in cancer patients receiving irinotecan (CPT-11) UDPglucuronosyltransferase1A1 (UGT1A1) catalyzes the glucuronidation of the active metabolite SN-38 but the relationship between UGT1A1 and severe toxicity remains unclear. Our study aimed to assess this point to guide clinical use of CPT-11. Materials and Methods: 89 cancer patients with advanced disease received CPT-11-based chemotherapy for at least two cycles. Toxicity, including GI and hematologic toxicity was recorded in detail and UGT1A1 variants were genotyped. Regression analysis was used to analyse relationships between these variables and tumor response. Results: The prevalence of grade III-IV diarrhea was 10.1%, this being more common in patients with the TA 6/7 genotype (5 of 22 patients, 22.7%) (p<0.05). The prevalence of grade III-IV neutropenia was 13.4%and also highest in patients with the TA 6/7 genotype (4 of 22 patients; 18.2%) but without significance (p>0.05). The retreatment total bilirubin levels were significantly higher in TA6/7 patients (mean, $12.75{\mu}mol/L$) with compared to TA6/6 (mean, $9.92{\mu}mol/L$) with p<0.05. Conclusions: Our study support the conclusion that patients with a $UGT1A1^*28$ allele (s) will suffer an increased risk of severe irinotecan-induced diarrhea, whether with mid-or low-dosage. However, the $UGT1A1^*28$ allele (s) did not increase severe neutropenia. Higher serum total bilirubin is an indication that patients UGT1A1 genotype is not wild-type, with significance for clinic usage of CPT-11.

Tumorigenic Effects of Endocrine-Disrupting Chemicals are Alleviated by Licorice (Glycyrrhiza glabra) Root Extract through Suppression of AhR Expression in Mammalian Cells

  • Chu, Xiao Ting;Cruz, Joseph Dela;Hwang, Seong Gu;Hong, Heeok
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권13호
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    • pp.5117-5121
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    • 2014
  • Endocrine-disrupting chemicals (EDCs) have been reported to interfere with estrogen signaling. Exposure to these chemicals decreases the immune response and causes a wide range of diseases in animals and humans. Recently, many studies showed that licorice (Glycyrrhiza glabra) root extract (LRE) commonly called "gamcho" in Korea exhibits antioxidative, chemoprotective, and detoxifying properties. This study aimed to investigate the mechanism of action of LRE and to determine if and how LRE can alleviate the toxicity of EDCs. LRE was prepared by vacuum evaporation and freeze-drying after homogenization of licorice root powder that was soaked in 80% ethanol for 72 h. We used 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) as an EDC, which is known to induce tumors or cancers; MCF-7 breast cancer cells were used as a tumorigenic model. These were treated with TCDD and various concentrations of LRE (0, 50, 100, 200, $400{\mu}g/mL$) for 24, 48, and 72 h. As a result, TCDD stimulated MCF-7 cell proliferation, but LRE significantly inhibited TCDD-induced MCF-7 cell proliferation in a dose- and time-dependent manner. Expression of TCDD toxicity-related genes, i.e., aryl hydrocarbon receptor (AhR), AhR nuclear translocator, and cytochrome P450 1A1, were subsequently down-regulated by LRE in a dose-dependent manner. Analysis of cell cycle distribution after treatment of MCF-7 cells with TCDD and various concentrations of LRE showed that LRE inhibited the proliferation of MCF-7 cells via G2/M phase arrest. Reverse transcription-polymerase chain reaction and Western blot analyses also revealed that LRE dose-dependently increased the expression of the tumor suppressor genes p53 and p27 and down-regulated the expression of cell cycle-related genes. These data suggest that LRE can mitigate the tumorigenic effects of TCDD in breast cancer cells by suppression of AhR expression and cell cycle arrest. Thus, LRE can be used as a potential toxicity-alleviating agent against EDC-mediated disease.

Butyrate and taurine exert a mitigating effect on the inflamed distal intestine of European sea bass fed with a high percentage of soybean meal

  • Rimoldi, Simona;Finzi, Giovanna;Ceccotti, Chiara;Girardello, Rossana;Grimaldi, Annalisa;Ascione, Chiara;Terova, Genciana
    • Fisheries and Aquatic Sciences
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    • 제19권10호
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    • pp.40.1-40.14
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    • 2016
  • Background: Due to the paucity of oceanic resources utilized in the preparation of diets for cultured fish, commercial feed producers have been trying to replace fishmeal (FM) using alternative protein sources such as vegetable protein meals (VMs). One of the main drawbacks of using VMs in fish feed is related to the presence of a variety of anti-nutritional factors, which could trigger an inflammation process in the distal intestine. This reduces the capacity of the enterocytes to absorb nutrients leading to reduced fish growth performances. Methods: We evaluated the mitigating effects of butyrate and taurine used as feed additives on the morphological abnormalities caused by a soybean meal (SBM)-based diet in the distal intestine of sea bass (Dicentrarchus labrax). We used three experimental diets, containing the same low percentage of FM and high percentage of SBM; two diets were supplemented with either 0.2% sodium butyrate or taurine. Histological changes in the intestine of fish were determined by light and transmission electron microscopy. Infiltration of $CD45^+$ leucocytes in the lamina propria and in the submucosa was assessed by immunohistochemistry. We also quantified by One-Step Taqman$^{(R)}$ real-time RT-PCR the messenger RNA (mRNA) abundance of a panel of genes involved in the intestinal mucosa inflammatory response such as $TNF{\alpha}$ (tumor necrosis factor alpha) and interleukins: IL-8, IL-$1{\beta}$, IL-10, and IL-6. Results: Fish that received for 2 months the diet with 30% soy protein (16.7% SBM and 12.8% full-fat soy) developed an inflammation in the distal intestine, as confirmed by histological and immunohistochemistry data. The expression of target genes in the intestine was deeply influenced by the type of fish diet. Fish fed with taurine-supplemented diet displayed the lowest number of mRNA copies of IL-$1{\beta}$, IL-8, and IL-10 genes in comparison to fish fed with control or butyrate-supplemented diets. Dietary butyrate caused an upregulation of the $TNF{\alpha}$ gene transcription. Among the quantified interleukins, IL-6 was the only one to be not influenced by the diet. Conclusions: Histological and gene expression data suggest that butyrate and taurine could have a role in normalizing the intestinal abnormalities caused by the SBM, but the underling mechanisms of action seem different.

Biological Activity of Bamboo Salt

  • Shin, Hye-Young;Na, Ho-Jeong;Moon, Phil-Dong;Seo, Sang-Wan;Shin, Tae-Yong;Hong, Seoung-Heon;Lee, Ki-Nam;Park, Rae-Kil;Kim, Hyung-Min
    • 식품산업과 영양
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    • 제9권1호
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    • pp.36-45
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    • 2004
  • Bamboo salt has been used for the purpose of prevention and treatment of various diseases in Korea. Present study was carried out to ascertain the effects of purple bamboo salt upon anti-allergic effect, anti-inflammatory activity and immune-enhance effect as well. Purple bamboo salt significantly inhibited the ear swelling response and histamine release induced by compound 48/80 in mice and rat peritoneal mast cells. Purple bamboo salt (0.01 ∼ lg/kg) also dose-dependently inhibited the passive cutaneous anaphylaxis by oral administration. Purple bamboo salt (1 mg/mL) in hibited phorbol 12-myristate 13-acetate plus calcium ionophore A23187-stimulated tumor necrosis factor (TNF)-${\alpha}$, interleukin (IL)-1${\beta}$ and IL-6 secretion, by 67.04${\pm}$0.08%, 68.01${\pm}$1.85%, 69.48${\pm}$0.54%, respectively. In addition, purple bamboo salt inhibited the expression of TNF-${\alpha}$ mRNA in HMC-1 cells. Finally, we investigated the effect of purple bamboo salt in the forced swimming test (FST) and the change of purple bamboo salt-mediated cytokine production from MOLT-4 cells. At the 7th, immobility time was significantly decreased in the purple bamboo salt-administration group (35.4 ${\pm}$5.9 s for 1 g/kg) in comparison with the control group (93.2 ${\pm}$ 15.45). After FST, the content of glucose in the blood serum was increased and the levels of blood urea nitrogen, lactic dehydrogenase was decreased in purple bamboo salt-administration group. However, it had no effect on the elevation of CK and TP level. Purple bamboo salt (1 mg/mL) significantly increased the interferon (IFN)-${\gamma}$ and IL-2 level compared with media control (about 3.7-fold for IFN-${\gamma}$, about 3.5-fold for IL-2, p〈0.05) but did not affect the IL-4.

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자가 탈회골의 조직반응에 관한 실험적 연구 (EXPERIMENTAL STUDY ON HEALING PROCESS OF AUTOGENIC DEMINERALIZED BONE)

  • 이재은;이동근;엄인웅;김영조;김장언
    • Maxillofacial Plastic and Reconstructive Surgery
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    • 제15권3호
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    • pp.199-210
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    • 1993
  • Many surgeons are on the point of bone excision and reconstruction of the bone defects by autograft. xenograft, and allograft in the treatment of begin and malignant tumors of bone. Of all type of bone grafts, we received the autograft as the best ideal bone graft. Of autogenic bone graft, replantation of excised autogenic bone for reconstructiong the bone defects has been the ideal method until now, but early bone healing reponses and tumor cell devitalization after replantation of excised autogenic bone have not been identified for clinical applications. So, to evaluate bone healing response after replantation in rabbit's calvarial bone, we divided the experimental group into three groups. Group 1 is a fresh autogenous bone group. Group 2 is a deep frozen group. Group 3 is freeze-dried demineralized group. Obtained result were as followed: 1. Inflammatory cell infiltration appeared at I week and disappeared at 4 weeks in all experimental group, Especially, severe inflammatory cell infiltration showed in fresh autogenous bone group at 2 weeks. Group 3 is the least showing group on the point of inflammatory cell infiltration. 2. Osteoblastic activity evenly increased upto 4 weeks and maintained to 6 weeks and decreased after this period, especially osteoblastic activity in group 2 is less than group 1 and group 3. We can't discriminate between osteoblastic activity of group 1 and that of group 3. 3. In new bone formation, group 3 was more active than any other groups at early stage, but there were little differences among three experimental groups at later state. 4. Bone resorption around the grafted bone slightly appeared at 1 week and disappeared at 4 weeks in all experimental groups. We can find the more bone resorption in group 2 at 2 weeks than any other groups. We could suggest, as appears from our results, that freeze-dried deminiralized bone graft is the useful bone graft in the clinical applications of excised autogenic bone.

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Production of pro-inflammatory cytokines by Porphyromonas gingivalis in THP-1 macrophagic cells

  • Choi, Eun-Kyoung;Kang, In-Chol
    • International Journal of Oral Biology
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    • 제34권2호
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    • pp.87-95
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    • 2009
  • Porphyromonas gingivalis is a major etiologic agent of chronic periodontitis and cytokines produced by macrophages play important roles in the pathogenesis of periodontal diseases. In this study we investigated the cytokine response of phorbol myristate acetatedifferentiated THP-1 cells exposed to P. gingivalis. Compared with the prominent cell wall components of P. gingivalis (lipopolysaccharide and the major fimbrial protein FimA), live P. gingivalis stimulated much higher levels of cytokine production. In addition, whereas low multiplicity of infection challenges (MOI=10) of P. gingivalis 381 stimulated high levels of monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), interleukin-6 (IL-6), and IL-1${\beta}$, high dose challenges with this bacterium (MOI = 100) resulted in a substantially diminished production of MCP-1 and IL-6. Moreover, high MOI P. gingivalis challenges achieved only low levels of induction of MCP-1 and IL-6 mRNA. The decreased production of MCP-1 and IL-6 appeared to be mediated by P. gingivalis proteases, because high MOI challenges with congenic protease mutant strains of this microorganism (MT10 and MT10W) did not result in a diminished production of MCP-1 and IL-6. Similar to its protease mutant strains, leupeptin (a protease inhibitor)- treated P. gingivalis at high doses induced high levels of MCP-1 production. To examine the mechanisms underlying the diminished production of MCP-1 by P. gingivalis proteases, the activation of mitogen-activated protein (MAP) kinases and NF-${\kappa}$B was compared between the 381 and MT10W strains. Whilst high doses of both 381 and MT10W similarly activated the three members of the MAP kinase family, the DNA binding activity of NF-${\kappa}$B, as revealed by gel shift assays, was greatly increased only by MT10W. Taken together, our data indicate that P. gingivalis stimulates the production of high levels of TNF-${\alpha}$, IL-1${\beta}$, IL-6, and MCP-1 but that high dose challenges with this bacterium result in a diminished production of MCP-1 and IL-6 via the protease-mediated suppression of NF-${\kappa}$B activation in THP-1 macrophagic cells.

TLR-4 로 유도한 동물 복강 대식세포에서 창이자 추출물의 NO 합성과 $IkB-{\alpha}$ 분해 억제에 의한 염증 반응 억제 효과 (Extrat of Xanthii Fructus down-regulate TLR-4 mediated murine peritoneal macrophage inflammatory response by limiting NO synthase and $IkB-{\alpha}$ degradation)

  • 정원석;서상완;조준기;손지우;박민철;최창민;염승룡;황상욱;김영우;송달수;채영석;최원석;노정은;윤한룡;김영목;박성주;신민교;송호준
    • 대한본초학회지
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    • 제21권3호
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    • pp.103-109
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    • 2006
  • Objectives : The purpose of this study was to investigate the TLR-4 mediated anti-inflammatory effects of extract from Xanthii Fructus(XF) on the peritoneal macrophage. Methods : To evaluate of TLR-4 mediated inflammatory of XF, we examined NO and cytokine production in TRL-4 ligand(LPS-lipopolysacchride) induced macrophages. Furthermore, we checked molecular mechanism using western blot. Results : l.Extract from XF reduced LPS-induced Nitric oxide (NO), tumor necrosis factor-a (TNF-a), interleukin (IL)-6 and IL-12 production in peritoneal macrophages 2.Extract from XF itself does not have any cytotoxic effect.XS inhibited degradation of IkBa in the TLR-4 mediated peritoneal macrophages Conclusion : XF down-regulated TLR4 ligand(LPS)-induced NO and cytokine productions.

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삼차신경통 진단 및 치료의 중요 고려사항 (Clinical Considerations of Trigeminal Neuralgia)

  • 전영미;태일호;최종훈;안형준;심우현;권정승
    • Journal of Oral Medicine and Pain
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    • 제32권4호
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    • pp.449-453
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    • 2007
  • 삼차신경통은 삼차신경의 하나 이상 분지에서 나타나는 안면 편측 통증 질환으로 짧은 찌르는 듯한 통증이다. 삼차 신경통의 가장 흔한 원인은 인접 삼차신경이나 삼차신경근 부위를 압박하는 혈관에 의하거나 특발성으로 나타나는 특발성 삼차신경통과 구조적 병소에 의해 나타나는 증후성 삼차신경통으로 분류된다. 증후성 삼차신경통은 수막종, 청신경종, 표피양암종 등이 주된 원인이며, 감각 결함, 운동 결함, 운동실조, 안구진탕 등과 같은 신경계 증상이 동반된다. 삼차 신경통의 치료는 크게 약물 치료와 외과적 치료가 있다. 이 중 가장 효과적으로 사용되는 약물은 Carbamazepine이며, 졸음, 현기증, 불안, 오심, 식욕부진 등의 다양한 부작용을 나타낼 수 있다. 특히 간독성, 골수 기능 억제 등의 위험한 부작용이 나타날 수 있으므로 주기적으로 혈액검사, 간 및 신장 기능 검사가 필요하다. 이에 삼차신경통의 임상 증례를 통해 증후성 삼차신경통과 특발성 삼차신경통의 예를 들어 진단과 치료를 시행함에 있어 여러 고려 사항들 중 특히 우리가 소홀히 하거나 간과하기 쉬운 중요 고려사항을 되짚어 보고자 한다.

상황버섯의 기술개발 동향과 시장분석 (Phellinus linteus; Market and Technology Trends Analysis)

  • 손은화;노현숙;박영서;손은수;강세찬;강남성;표석능
    • KSBB Journal
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    • 제23권2호
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    • pp.109-117
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    • 2008
  • 담자균류의 버섯은 대부분 영양생장단계의 균사체와 포자를 형성하는 생식생장단계인 자실체로 나누어진다. 그러나 자연산 상황버섯은 자연계에서의 분포수가 극히 적어 그 자실체를 얻기 어려우며, 이러한 희귀성으로 인해 매우 고가로 거래되고 있다. 1990년대 중반 상황버섯은 균사체 배양기술과 인공재배법이 확립된 후 농가에서 대량생산되기 시작하였으며, 이에 따라 상황버섯의 유효성분을 이용한 기능성 식품 및 의약품의 개발이 활발하였다. 그러나 인공재배법에 의한 상황버섯 추출물은 자연산 추출물의 항암 및 효능면에서 차이를 나타내고 있어, 자연산 자실체와 같은 수준에서의 약효를 나타내기 위한 인공배양기술과 고농도 유효성분을 획득하기 위한 추출법이 핵심기술로 대두되었고, 인공배양된 상황버섯과 자연산의 다각도적인 약효 비교에 관한 연구가 아직까지 진행되고 있다. 따라서 상황버섯의 유효성분이 높게 함유된 저렴한 추출물이 생산될 수 있는 기반 기술들이 기능성 음료용수, 식품 및 의약품으로 개발에 중요한 핵심기술로 떠오르고 있다. 국내 상황버섯 기능성 식품의 시장은 상황버섯의 효능에 대한 인지 증대, 웰빙열풍을 의한 건강 음료에 대한 선호도 증대 등으로 인해 향후에도 10% 이상의 높은 성장률을 보일 것으로 예상된다. 현재는 중소기업들이 주로 활동하고 있어 마케팅 및 유통의 한계로 인해 시장이 크게 확대되고 있지 않으나, 사업매력도가 긍정적으로 평가되고 있어 대기업에서도 상황버섯을 이용한 기능성 식품 시장에의 진출을 모색하고 있다.

RAW 264.7 대식세포에서 NO, TNF-α, IL-6 생산에 관한 Squalene, Alkoxy Glycerol, Batyl, Chimyl의 효과 (Production of NO, TNF-α and IL-6 by Squalene, Alkoxy Glycerol, Batyl and Chimyl Solutions in RAW 264.7 Macrophage Cells)

  • 김영호;윤현중;문명이;이준행;박행순;김종세
    • 한국식품영양과학회지
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    • 제34권10호
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    • pp.1503-1508
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    • 2005
  • 본 연구에서는 대식세포인 RAW 264.7 세포주에 SQ ($0.1{\%}$), AG($0.1{\%}$), Batyl(1 mg/mL), Chimyl(1 mg/mL) 용액 등을 단독 혹은 C. albicans와 함께 첨가하여 배양한 후LDH, NO, TNF-$\alpha$, IL-6 발현에 어떤 영향을 주는 지를 관찰하였다. 모든 실험군에서 실험에 사용한 농도는 LDH, NO생산에 영향을 주지 못하였다. 실험에 사용한 용액을 단독 처리한 실험의 경우 TNF-$\alpha$와 IL-6발현의 경우 6시간째에는 큰 차이를 나타내지는 못하였으나, 24시간째에는 발현에 영향을 주었다(p < 0.05). C. albicans을 함께 처리한 실험의 경우에는 C. albicans단독 처리군에 비해 실험 용액을 함께 처리한 군에서 C. albicans유도 TNF-$\alpha$와 IL-6발현을 감소시키는 효과를 관찰하였다(p < 0.05, p < 0.01). 본 연구를 통해 SQ, AG, Batyl, Chimyl 용액이 C. albicans 유도에 의해 감소된 면역반응을 증가시킬 수 있을 것으로 생각되어진다.