• 제목/요약/키워드: Tumor necrosis

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Molecules of the Tumor Necrosis Factor (TNF) Receptor and Ligand Superfamilies: Endless Stories

  • Kwon, Byung-Suk;Kwon, Byoung-Se
    • BMB Reports
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    • 제32권5호
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    • pp.419-428
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    • 1999
  • Tumor necrosis factor (TNF) receptor members have unique structures composed of 2-4 cysteine - rich pseudorepeats in the extracellular domain. On ligation by trimeric ligand molecules, oligomerization of three receptor molecules occurs, which in turn activates the receptor and recruits intracellular signaling molecules to the cytoplasmic tail to initiate biological events. Recently, the numbers of tumor necrosis factor receptor and ligand family members have been rapidly expanding. Functional characterization of the new members has indicated redundant roles with other known members as well as provided insights into novel functions. In particular, identification of soluble decoy receptors which have the ability to bind multiple ligands highlights a complex control mechanism of immune responses by these molecules. Studies of the new members have also revealed that the TNF receptor and ligand family members play an important role in other than the immune system.

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Anti-Tumor Necrosis Factor Therapy in Intestinal Behçet's Disease

  • Park, Jihye;Cheon, Jae Hee
    • Gut and Liver
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    • 제12권6호
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    • pp.623-632
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    • 2018
  • Intestinal Behçet's disease is a rare, immune-mediated chronic intestinal inflammatory disease; therefore, clinical trials to optimize the management and treatment of patients are scarce. Moreover, intestinal Behçet's disease is difficult to treat and often requires surgery because of the failure of conventional medical treatment. Administration of anti-tumor necrosis factor-${\alpha}$, a potential therapeutic strategy, is currently under active clinical investigation, and evidence of its effectiveness for both intestinal Behçet's disease and inflammatory bowel diseases has been accumulating. Here, we review updated data on current experiences and outcomes after the administration of anti-tumor necrosis factor-${\alpha}$ for the treatment of intestinal Behçet's disease. In addition to infliximab and adalimumab, which are the most commonly used agents, we describe agents such as golimumab, etanercept, and certolizumab pegol, which have recently been shown to be effective in refractory intestinal Behçet's disease. This review also discusses safety issues associated with anti-tumor necrosis factor-${\alpha}$, including vulnerability to infections and malignancy.

In Vivo Experimental Study on the Effects of Fluid in Increasing the Efficiency of Radiofrequency Ablation

  • Sun, Yi-Xin;Cheng, Wen;Han, Xue;Liu, Zhao;Wang, Qiu-Cheng;Shao, Hua
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권14호
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    • pp.5799-5804
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    • 2014
  • Background: Radiofrequency ablation (RFA) is the most widely used and studied method internationally for the local treatment of liver tumors. However, the extension of coagulation necrosis in one RFA procedure is limited and incomplete coverage of the damaged area can lead to a high local recurrence rate. Objective: In this study, we compared the effects of different solutions in enhancing hepatic radiofrequency by establishing a rabbit VX2 liver cancer model. We also determined the optimal solution to maximise effects on the extent of RFA-induced coagulation necrosis. Methods: Thirty VX2 tumor rabbits were randomly assigned to five groups: group A, RFA alone; group B, RFA with anhydrous ethanol injection; group C, RFA with 5% hypertonic saline injection; group D, RFA with lidocaine injection; and group E, RFA with a mixed solution. Routine ultrasound examinations and contrast-enhanced ultrasound (CEUS) of the ablation areas were performed after RFA. Then, we measured the major axis and transverse diameter and compared the areas of coagulation necrosis induced by RFA. Results: The mean ablation area range increased in groups B, C and especially E, and the scopes were greater compared with group A. Preoperative application of anhydrous ethanol, hypertonic saline, lidocaine and the mixed solution (groups B, C, D and E, respectively) resulted in larger coagulation necrosis areas than in group A (p<0.05). Among the groups, the coagulation necrosis areas in group E was largest, and the difference was statistically significant compared with other groups (p<0.05). Pathological findings were consistent with imaging results. Conclusions: A mixture of dehydrated alcohol, hypertonic saline and lidocaine injected with RFA increases the extent of coagulation necrosis in the liver with a single application, and the mixed solution is more effective than any other injection alone.

광역학적 치료법을 이용한 쥐의 악성종양 괴사 (Mouse Tumor Necrosis Using Photodynamic Therapy)

  • 임현수;변상현
    • 대한의용생체공학회:의공학회지
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    • 제25권1호
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    • pp.49-55
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    • 2004
  • 본 논문은 쥐의 악성종양에 대한 광역학적 치료효과를 조사한 연구이다. 실험방법으로서는 쥐를 대조군과 대상군의 두 그룹으로 나누어 HepG2 and Hela cell line을 주입하여 암조직을 배양하였다. 쥐의 악성종양에 포토포린을 30시간 전에 주입하고 630nm와 650nm의 레이저를 적용하였다. 광역학적 치료후에 쥐의 두 그룹에 대한 악성종양크기, 괴사율, 악성종양 성장률, 악성종양조직의 병리학적 변화를 분석하였다. 실험결과 조직에서 악성종야세포의 괴사를 보였으며, 광조사 시간과 광량에 따라 악성종양 크기가 줄어들고 악성종양의 괴사변화를 나타냈다. 그러나 630nm와 650nm의 파장차이에 대한 악성종양의 변화의 차이는 발견할 수 없었으며 다른 정상조직에서의 손상도 발견되지 않았다.

Size Heterogeneity of Murine Tumor Necrosis Factors Induced from Mouse Peritoneal Macrophages

  • Baik, Na-Gyoung;Jeong, Jee-Yeong;Kim, Soung-Soo
    • BMB Reports
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    • 제28권1호
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    • pp.46-50
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    • 1995
  • Three kinds of mouse tumor necrosis factor (TNF), which have molecular weights of 35 kDa, 45 kDa, and 18 kDa on SDS-PAGE, were partially purified from serum-free culture supernatants of mouse peritoneal macrophages induced with lipopolysaccharide. Analysis of the native molecular weights by gel filtration indicated that the 18 kDa and 45 kDa TNFs aggregate into 50 kDa and 100 kDa molecules, respectively, while the 35 kDa TNF is contained in high molecular weight aggregates of approximately 200 kDa. The three kinds of cytotoxic factors all elicited tumor reducing responses.

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Expression of Tumor Necrosis Factor (TNF)-z${\alpha}$ from Cells Undergoing Death by FADD

  • Kim, Koanhoi
    • Journal of Life Science
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    • 제12권2호
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    • pp.57-60
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    • 2002
  • Apoptosis of vascular smooth muscle cell is observed in the vascular diseases such as atherosclerosis and restenosis. The death of vascular smooth muscle cells can be induced by cytokines and activation of Fas-pathways. It is widely accepted that apoptosis occurs without inflammation. There are, however, reports that apoptosis is not silent. Vascular smooth muscle cells dying by Fas-pathway secreted inflammatory cytokines including monocyte chemoattractant protein-1. This study have investigated whether apoptosis is associated with potent inflammatory cytokine tumor tumor necrosis factor (TNF)-${\alpha}$. The cells which undergo apoptosis by expressing FADD in the absence of tetracycline expressed and secreted TNF-${\alpha}$. When the level of TNF-${\alpha}$ transcript was investigated, dying smooth muscle cells exhibited transcriptional activation of TNF-${\alpha}$. The data indicate that dying vascular smooth muscle cells contribute to inflammation by expressing inflammatory cytokines. The present study suggests that apoptosis could not be silent in certain pathological situations.

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Development of human tumor necrosis factor-α muteins with improved therapeutic potential

  • Jang, Seung-Hwan;Kim, Hyo-Jin;Cho, Kwang-Hwi;Shin, Hang-Cheol
    • BMB Reports
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    • 제42권5호
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    • pp.260-264
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    • 2009
  • Tumor necrosis factor-$\alpha$ (TNF-$\alpha$) exhibits cytotoxicity towards various tumor cells in vitro and induces apoptotic necrosis in transplanted tumors in vivo. It also shows severe toxicity when used systemically for the treatment of cancer patients, hampering the development of TNF-$\alpha$ as a potential anticancer drug. In order to understand the structure-function relation of TNF-$\alpha$ with respect to receptor binding, we selected four regions on the bottom of the TNF-$\alpha$ trimer that are in close contact with the receptor and carried out mutagenesis studies and computational modeling. From the study, various TNF-$\alpha$ muteins with a high therapeutic index were identified. These results will provide a structural basis for the design of highly potent TNF-$\alpha$ for therapeutic purposes. By conjugating TNF-$\alpha$ muteins with a high therapeutic index to a fusion partner, which targets a marker of angiogenesis, it could be possible to develop TNF-$\alpha$ based anticancer drugs.

Tumor Necrosis Factor-Alpha가 정자운동성에 미치는 직접 영향의 부족 (The Lack of a Direct Effect of Tumor Necrosis Factor-Alpha on Sperm Motility)

  • 송은섭;임영구;송윤섭
    • Clinical and Experimental Reproductive Medicine
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    • 제26권1호
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    • pp.97-101
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    • 1999
  • Male genital tract inflammatory conditions may be associated with unexplained infertility. The presence of cytokine such as tumor necrosis factor-alpha (TNF-${\alpha}$) was reported in the semen of infertile men. However, the effect of these cytokines on human sperm function is still unclear. The purpose of this study was to investigate the in-vitro effects of TNF-alpha on human sperm motility with computer assisted sperm analysis. Washed sperm from 16 normal men were incubated without and with TNF-${\alpha}$ (0.1, 10, 1000 ng/ml). The changes of parameters of sperm motility were recorded at different time intervals (0, 5, 24 hour). There was no significant change of parameters of sperm motility in the incubation with TNF-${\alpha}$. It is suggested that TNF-${\alpha}$ alone does not interfere with the sperm motility and more studies are needed.

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