http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
Protective effects of Fc-fused PD-L1 on two different animal models of colitis
Song, Mi-Young,Hong, Chun-Pyo,Park, Seong Jeong,Kim, Jung-Hwan,Yang, Bo-Gie,Park, Yunji,Kim, Sae Won,Kim, Kwang Soon,Lee, Ji Yeung,Lee, Seung-Woo,Jang, Myoung Ho,Sung, Young-Chul BMJ Publishing Group Ltd 2015 Gut Vol.64 No.2
<P><B>Objective</B></P><P>Programmed death-ligand 1 (PD-L1) has been shown to negatively regulate immune responses via its interaction with PD-1 receptor. In this study, we investigated the effects of PD-L1-Fc treatment on intestinal inflammation using two murine models of inflammatory colitis induced by dextran sulfate sodium (DSS) and T-cell transfer.</P><P><B>Design</B></P><P>The anti-colitis effect of adenovirus expressing Fc-conjugated PD-L1 (Ad/PD-L1-Fc) and recombinant PD-L1-Fc protein was evaluated in DSS-treated wild-type and Rag-1 knockout (KO) mice. We examined differentiation of T-helper cells, frequency of innate immune cells, and cytokine production by dendritic cells (DCs) in the colon from DSS-treated mice after PD-L1-Fc administration. In Rag-1 KO mice reconstituted with CD4 CD45RB<SUP>high</SUP> T cells, we assessed the treatment effect of PD-L1-Fc protein on the development of colitis.</P><P><B>Results</B></P><P>Administration of Ad/PD-L1-Fc significantly ameliorated DSS-induced colitis, which was accompanied by diminished frequency of interleukin (IL)-17A-producing CD4 T cells and increased interferon-γ-producing CD4 T cells in the colon of DSS-fed mice. The anti-colitic effect of PD-L1-Fc treatment was also observed in DSS-treated Rag-1 KO mice, indicating lymphoid cell independency. PD-L1-Fc modulated cytokine production by colonic DCs and the effect was dependent on PD-1 expression. Furthermore, PD-L1-Fc protein could significantly reduce the severity of colitis in CD4 CD45RB<SUP>high</SUP> T-cell-transferred Rag-1 KO mice.</P><P><B>Conclusions</B></P><P>Based on the protective effect of PD-L1-Fc against DSS-induced and T-cell-induced colitis, our results suggest that PD-1-mediated inhibitory signals have a crucial role in limiting the development of colonic inflammation. This implicates that PD-L1-Fc may provide a novel therapeutic approach to treat inflammatory bowel disease.</P>
Philippine産 Eucheuma cottonii의 carrageenan 含量과 그 性狀에 대하여
김순선(Soon-Seon Kim),김선봉(Seun-Bong Kim),김인수(In-Su Kim),정미희(Mi-Hee Jeung),박영호(Yeung-Ho Park) 한국식품영양과학회 1979 한국식품영양과학회지 Vol.8 No.1
Philippine産 原藻인 Eucheuma cottonii의 carrageenan 含量과 이로부터 抽出한 carrageenan의 SO₃ 및 3, 6-anhydro-D-galactose 含量, KCl溶液에 대한 溶解度, KCl 濃度別에 따라 分劃한 劃分의 含量에 대하여 調査하였으며 原料學的인 比較目的으로 우리나라産 진두발(Chondrus ocellatus)의 carageenan含量과 그 化學的 性狀을 比較 檢討하였다.<br/> 1. Carrageenan含量은 Eucheuma cottonii가 진두발보다 높은 값을 나타내어 乾物當 약 59%의 含量을 보였다.<br/> 2. Carrageenan의 SO₃ 및 3, 6-anhydro-D-galactose의 含量을 보면 Eucheuma cottonii가 진두발보다 SO₃含量은 적고 3, 6-anhydro-D-galactose의 含量이 많은 傾向을 나타내었다.<br/> 3. Carrageenan의 KCl溶液에 대한 溶解度는 0.125M KCl濃度에서 沈澱하는 比率 및 0.125M과 2.0M KCl濃度사이에서 沈澱하는 比率은 Eucheuma cottonii가 진두발보다 높았으나 2.0M KCl濃度에서 溶存하는 比率은 진두발이 Eucheuma cottonii보다 높은 값을 나타내었다.<br/> 4. Carrageenan을 KCl溶液에 대한 溶解度의 差異로부터 3劃分으로 分劃하였을 때 劃分 Ⅰ, Ⅱ의 收率은 Eucheuma cottonii와 진두발이 큰 차이가 없었으나 劃分Ⅲ의 收率은 Eucheuma cottonii가 월등히 많아 약 8倍의 값을 나타내었다.<br/> 5. 各劃分의 SO₃ 및 3, 6-anhydro-D-galactose의 含量은 서로 逆相關關係를 나타내었고, KCl溶液에 대한 溶解度가 큰 劃分일수록 SO₃含量이 높고 3, 6-anhydro-D-galactose의 含量이 낮은 값을 나타내었다. One species of Rhodophyceae namely Eucheuma cottonii from the coast of Philippine was analyzed with respect to the content of carrageenan and such chemical characteristics as the content of sulphate and 3, 6-anhydro-D-galactose and its solubility in potassium chloride solution.<br/> In addition, the same chemical properties were tested in the fractions separated by the different concentrations of potassium chloride.<br/> In comparison of the results of carrageenan in Eucheuma cottonii samples from Philippine and Chondrus ocellatus samples from Korea, carrageenan content in Eucheuma cottonii was higher than that of Chondrus ocellatus. Both samples showed more than forty-five percent carrageenan content. The Eucheuma cottonii carrageenan showed a higher 3, 6-anhydro-D-galactose than the Chondrus ocellatus carrageenan. The sulphate content was higher in Chondrus ocellatus than Eucheuma cottonii.<br/> In fractionation of carrageenan by the solubility methods using potassium chloride solution, the yield of Eucheuma cottonii was highest in fraction Ⅰ, fraction Ⅲ was next and fraction Ⅱ was the lowest.
부인암 세포주에서 항암제 투여에 따른 신생혈관 형성 관련 유전자 전령 리보핵산 및 단백질 표현 양상에 관한 연구
김영재 ( Young Jae Kim ),공미숙 ( Mi Sook Kong ),이영미 ( Young Me Lee ),장성렬 ( Sung Yeoul Chang ),김승룡 ( Seung Ryong Kim ),김경태 ( Kyung Tai Kim ),황윤영 ( Youn Yeung Hwang ),조삼현 ( Sam Hyun Cho ) 대한산부인과학회 2007 Obstetrics & Gynecology Science Vol.50 No.3
연구목적: 본 연구자는 확립된 세포주에서 세포독성제 및 면역 조정제에 의한 항신혈관 형성효과를 확인하고자 하였다. 유방암 세포주 MCF-7, 자궁 경부 편평 상피암 세포주 SiHa, 난소암 세포주 A2780, 그리고 cisplatin 내성 난소암 세포주 A2780-CDDP에서 cisplatin, paclitaxe l(taxol), 및 thalidomide로 처리한 후에 vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), 그리고 thrombospondin-1,2 (TSP-1,2)의 전령 리보 핵산 및 단백질의 표현 양상의 변화를 규명하고자하였다. 연구대상 및 방법: 유방암 세포주 MCF-7, 자궁 경부 편평 상피암 세포주 SiHa, 난소암 세포주 A2780, 그리고 cisplatin 내성 난소암 세포주 A2780-CDDP에서 cisplatin, paclitaxel (taxol), 및 thalidomide로 각각 처리한 후에 vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), 그리고 thrombospondin-1,2 (TSP-1,2)의 전령 리보 핵산 및 단백질의 표현 양상의 변화를 규명하고자 RT-PCR, 단백 추출 및 Western blot assay를 사용하였다. 결과: 난소암 세포주 A2780과 동일 세포주에서 분리한 cisplatin 내성 주 A2780-CDDP, 유방암 세포주 MCF-7 및 자궁경부 편평 상피암 세포주인 SiHa에서 VEGF gene은 212 bp, bFGF는 238 bp, 그리고 TSP-1은 492 bp로 합성되었으나 TSP-2 는 합성되지 않았으며 VEGF 및 bFGF 단백질은 각각 21 KDa와 17 KDa로 합성되었으나 TSP-1 단백질은 합성되지 않았다. 각 세포주의 VEGF gene의 발현 정도는 cisplatin, taxol 및 thalidomide에 별 큰 영향을 받지 않았다. bFGF gene의 발현 정도는 taxol처리 후 유방암 세포주에서 만 감소하였으며 TSP-1 gene의 발현도는 taxol 처리 후 유방암 세포주에서 자궁경부암 세포주 보다 큰 폭의 감소가 있었고 난소암 세포주에서 thalidomide처리 후 뚜렷한 감소를 보였다. Cisplatin, taxol, 그리고 thalidomide에 VEGF 및 bFGF 단백질 발현도는 아무런 영향을 받지 않았다. 결론: 난소암 세포주 A2780, cisplatin 내성 난소암 세포주 A2780-CDDP, 유방암 세포주 MCF-7, 그리고 자궁경부 편평 상피암 세포주 SiHa에서 VEGF, bFGF 그리고 TSP-1 gene들 및 단백질의 발현 양상은 cisplatin 처리에 의해 변화되지는 않는 것으로 확인되어 난소암, 유방암 그리고 자궁경부암에서 cisplatin의 신혈관 형성 억제 효과 판정에는 VEGF, bFGF 및 TSP-1 등의 직접적인 단백 발현 양상만을 표적으로 삼기 보다는 기저층 파괴를 담당하는 신호 전달체등의 발현 변화를 동시에 분석하여야 할 것으로 사료되며, 통계적으로 유의하지는 않았지만 taxol 처리에 따른 신혈관 형성 단백 유전자들의 발현 양상에 있어 bFGF가 유방암 세포주에서 약간 감소되었고, TSP-1은 유방암 세포주에서 자궁경부암 세포주보다 약간 더 많은 감소를 보여 bFGF와 TSP-1은 유방암 및 자궁경부암에서 taxol의 신혈관 형성 저해 연구의 평가 기준으로 재연구될 필요가 있을 것으로 생각된다. 역시 통계적으로 유의한 정도는 아니었으나 Thalidomide 처리에 따른 전기 단백질들의 표현 양상에는 난소암 세포주 A2780에서 TSP-1 단백 발현의 감소가 다른 세포주보다 많은 것으로 나타나, 실험 방법에 따라 같은 세포 독성제라도 신혈관 형성 저해 효과 판정이 다르다는 것을 확인시켜 줌과 동시에 향후 thalidomide를 난소암의 보조적 치료제로 이용하는 연구의 필요성을 제시하였다. Objective: Angiogenesis is central role to both the proliferation and metastasis of malignant tumor. The intense interest in angiogenesis has also lead to a re-examination of the activity of established cytotoxic agents which are known to be an antiangiogenic effect anecdotally. In this study, anti-angiogenic effect of cisplatin, paclitaxel and thalidomide was evaluated in human ovarian cancer cell lines and cervical cancer cell line. Methods: Human ovarian cancer cell line A2780, cisplatin resistant human ovarian cancer cell line A2780-CDDP, human breast cancer cell line MCF-7, and squamous cell uterine cervical carcinoma cell line SiHa were used to evaluate the level of mRNA and protein expression of VEGF, bFGF and TSP-1, 2 before and after the treatment with cisplatin, paclitaxel, and thalidomide using RT-PCR, protein extraction, and Western blot. The results were analyzed with Wilcoxon signed rank test in the SAS ver 8.1. Results: Targeted mRNAs were synthesized as 212 bp VEGF, 238 bp bFGF, and 492 bp band sized except mRNA of TSP-2 via RT-PCR. The protein of VEGF and bFGF were appeared as 21KDa and 17 KDa size, however, the protein of TSP-1 was not appeared through western blot. No effect of cisplatin on protein expression was measured in these cell lines, but paclitaxel influenced the expression of bFGF in MCF-7 cell line and the expression of TSP-1 in MCF-7 and SiHa cell lines. TSP-1 expression was influenced by thalidomide in A2780 cell line. The protein expression of VEGF and bFGF were not influenced following treatment with cisplatin, paclitaxel, and thalidomide. Conclusion: These results were suggested that bFGF and TSP-1 will be used as a target gene for the assay of antiangiogenic effect of paclitaxel in breast and uterine cervical cancer tissue and TSP-1 will be used as that of thalidomide in ovarian cancer. Furthermore, thalidomide will be tried as an adjunctive agent for the improvement of the survival in the case of the patient with ovarian cancer.
Human breast cancer cells display different sensitivities to ABT-263 based on the level of survivin
Lee, Eun Young,Gong, Eun-Yeung,Shin, Jae-Sik,Moon, Jai-Hee,Shim, Hyun Jae,Kim, Seung-Mi,Lee, Seul,Jeong, Joonyee,Gong, Ji Hee,Kim, Mi Jin,Lee, Dae Hee,Park, Yoon Sun,Shin, Jimin,Hong, Seung-Woo,Kim, Y Elsevier 2018 Toxicology in vitro Vol.46 No.-
<P><B>Abstract</B></P> <P>ABT-263 (navitoclax), a Bcl-2 family protein inhibitor, was clinically tested as an anti-cancer agent. However, the clinical trials were limited given the occurrence of resistance to monotherapy in breast cancer cells. Our study investigates the mechanisms for overcoming navitoclax resistance by combining it with an mTOR inhibitor to indirectly target survivin. The apoptotic effects of navitoclax occurred in MDA-MB-231 breast cancer cells in a time- and dose-dependent fashion, but MCF-7 cells were resistant to navitoclax treatment. The expression of Bcl-2 family genes was not altered by navitoclax, but the expression of survivin, a member of the inhibitors of apoptosis proteins (IAP) family, was downregulated, which increased death signaling in MDA-MB-231 cells. In MCF-7 cells, a navitoclax-resistant cell line, combined treatment with navitoclax and everolimus synergistically reduced survivin expression and induced cell death. These data indicate that navitoclax induces cell death in MDA-MB-231 cells but not in MCF-7 cells. Decreased survivin expression in MDA-MB-231 cells may be a primary pathway for death signaling. Combined navitoclax and everolimus treatment induces cell death by reducing the stability of survivin in MCF-7 cells. Given that survivin-targeted therapy overcomes resistance to navitoclax, this strategy could be used to treat breast cancer patients.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MDA-MB-231 and MCF-7 cell lines exhibit differential sensitivity to navitoclax induced apoptosis. </LI> <LI> Navitoclax-induced apoptotic cell death occurs through the regulation of survivin. </LI> <LI> Reduced expression levels of survivin restore navitoclax sensitivity in MCF-7 cell lines. </LI> <LI> Combined treatments with navitoclax and everolimus induces cell death in MCF-7 cells. </LI> </UL> </P>