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        Melatonin acts synergistically with pazopanib against renal cell carcinoma cells through p38 mitogen-activated protein kinase-mediated mitochondrial and autophagic apoptosis

        ( Chien-pin Lai ),( Yong-syuan Chen ),( Tsung-ho Ying ),( Cheng-yen Kao ),( Hui-ling Chiou ),( Shao-hsuan Kao ),( Yi-hsien Hsieh ) 대한신장학회 2023 Kidney Research and Clinical Practice Vol.42 No.4

        Background: Mounting evidence indicates that melatonin has possible activity against different tumors. Pazopanib is an anticancer drug used to treat renal cell carcinoma (RCC). This study tested the anticancer activity of melatonin combined with pazopanib on RCC cells and explored the underlying mechanistic pathways of its action. Methods: The 786-O and A-498 human RCC cell lines were used as cell models. Cell viability and tumorigenesis were detected with the MTT and colony formation assays, respectively. Apoptosis and autophagy were assessed using TUNEL, annexin V/propidium iodide, and acridine orange staining with flow cytometry. The expression of cellular signaling proteins was investigated with western blotting. The in vivo growth of tumors derived from RCC cells was evaluated using a xenograft mouse model. Results: Together, melatonin and pazopanib reduced cell viability and colony formation and promoted the apoptosis of RCC cells. Furthermore, the combination of melatonin and pazopanib triggered more mitochondrial, caspase-mediated, and LC3-II-mediated autophagic apoptosis than melatonin or pazopanib alone. The combination also induced higher activation of the p38 mitogen-activated protein kinase (p38MAPK) in the promotion of autophagy and apoptosis by RCC cells than melatonin or pazopanib alone. Finally, tumor xenograft experiments confirmed that melatonin and pazopanib cooperatively inhibited RCC growth in vivo and predicted a possible interaction between melatonin/pazopanib and LC3-II. Conclusion: The combination of melatonin and pazopanib inhibits the growth of RCC cells by inducing p38MAPK-mediated mitochondrial and autophagic apoptosis. Therefore, melatonin might be a potential adjuvant that could act synergistically with pazopanib for RCC treatment.

      • KCI등재후보

        Metallic Stent Placement in Hemodialysis Graft Patients after Insufficient Balloon Dilation

        Huei-Lung Liang,Huay-Ben Pan,Yih-Huie Lin,Chiung-Yu Chen,Hsiao-Min Chung,Tung-Ho Wu,Kang-Ju Chou,Pin-Hong Lai,Chien-Fang Yang 대한영상의학회 2006 Korean Journal of Radiology Vol.7 No.2

        Objective: We wanted to report our experience of metallic stent placement after insufficient balloon dilation in graft hemodialysis patients. Materials and Methods: Twenty-three patients (13 loop grafts in the forearm and 10 straight grafts in the upper arm) underwent metallic stent placement due to insufficient flow after urokinase thrombolysis and balloon dilation. The indications for metallic stent deployment included 1) recoil and/or kinked venous stenosis in 21 patients (venous anastomosis: 17 patients, peripheral outflow vein: four patients); and 2) major vascular rupture in two patients. Metallic stents 8 10mm in diameter and 40 80 mm in length were used. Of them, eight stents were deployed across the elbow crease. Access patency was determined by clinical follow-up and the overall rates were calculated by Kaplan-Meier survival analysis. Results: No procedure-related complications (stent fracture or central migration) were encountered except for a delayed Wallstent shortening/migration at the venous anastomosis, which resulted in early access failure. The overall primary and secondary patency rates ( standard error) of all the vascular accesses in our 23 patients at 3, 6, 12 and 24 months were 69% 9 and 88% 6, 41% 10 and 88% 6, 30% 10 and 77% 10, and 12% 8 and 61% 13, respectively. For the forearm and upper-arm grafts, the primary and secondary patency rates were 51% 16 and 86% 13 vs 45% 15 and 73% 13 at 6 months, and 25% 15 and 71% 17 vs 23% 17 and 73% 13 at 12 months (p = .346 and .224), respectively. Conclusion: Metallic stent placement is a safe and effective means for treating peripheral venous lesions in dialysis graft patients after insufficient balloon dilation. No statistically difference in the patency rates between the forearm and upper-arm patient groups was seen.

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