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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 陳俊任(Chun-Jen Chen) | |
| dc.contributor.author | Hsin-Tien Hsieh | en |
| dc.contributor.author | 謝信典 | zh_TW |
| dc.date.accessioned | 2021-07-11T14:47:05Z | - |
| dc.date.available | 2025-08-18 | |
| dc.date.copyright | 2020-09-10 | |
| dc.date.issued | 2020 | |
| dc.date.submitted | 2020-08-14 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78233 | - |
| dc.description.abstract | 臺灣紫芝 (Ganoderma formosanum) 是於臺灣發現的靈芝屬特有種。在本實驗室前人的研究中，臺灣紫芝藉由深層發酵培養所產生的胞外多醣體、再經膠體過濾分劃所得之PS-F2於小鼠體內實驗中具抗腫瘤的效果。在本研究之中，我們探討了PS-F2的抗腫瘤效果是否為透過調節具免疫抑制性的腫瘤相關巨噬細胞 (tumor associated macrophages, TAMs) 來達成。將分離自小鼠C26腫瘤組織的TAM (tumor TAMs, tTAMs) 與naïve小鼠之脾臟巨噬細胞做比較，可得知iNOS、IL-6、IL-1β、TNF-α、arginase-1、IL-10、VEGF-A、CCL-3、CXCL-4、MMP-9、MMP-12、osteopontin (OPN) 等基因於tTAMs之中表現上升。在PS-F2的刺激下，可發現其M1相關基因如iNOS與IL-6等有進一步的表現上升，而arginase-1則下降。tTAMs能抑制CD4+ T cell之增生，此抑制效果能被PS-F2所逆轉。另一方面，本研究亦透過將發炎性單核球 (inflammatory monocytes, IM) 與腫瘤細胞共培養，於體外產生腫瘤相關巨噬細胞 (cultured TAM, cTAMs)。結果顯示，在共培養3天以後與單獨培養組相比，可發現IM已分化為cTAMs，且CD80、CD206等表面分子於cTAMs之表現上升；此外，iNOS、arginase-1、VEGF-A、CXCL-4、OPN等基因表現也較單獨培養組提升。另方面，cTAMs對於抑制T 細胞增生的能力也大於tTAMs。總的來說，PS-F2能促使tTAMs極化為M1，並能減緩tTAMs抑制CD4+ T細胞增生的作用；此外也初步建立了cTAMs之體外分化系統，能作為體外研究TAMs之平台。 | zh_TW |
| dc.description.abstract | Ganoderma formosanum is a native species of Ganoderma first discovered in Taiwan. Our previous studies showed that PS-F2, a polysaccharide fraction purified from the submerged fermentation broth of G. formosanum, exhibits antitumor activities in mice. In this study, we investigated whether PS-F2 may exert the antitumor function by modulating the immunosuppressive phenotypes of tumor-associated macrophages (TAMs). Compared with splenic macrophages, TAMs purified from C26 colon carcinoma (tumor TAMs, tTAMs) expressed elevated levels of iNOS, IL-6, IL-1β, TNF-α, arginase-1, IL-10, VEGF-A, CCL-3, CXCL-4, MMP-9, MMP-12, and osteopontin (OPN). Upon PS-F2 stimulation, the expression of iNOS and IL-6 were further upregulated, and the expression of arginase-1 was downregulated. tTAMs inhibited the proliferation of CD4+ T cells, which could be reversed by PS-F2 treatment. In this study, we also generated TAMs in vitro (cultured TAMs, cTAMs) by coculturing inflammatory monocytes with tumor cells. After coculturing with tumor cells for 3 days, inflammatory monocytes differentiated into macrophages with elevated surface expression of CD80 and CD206 compared with monocultured macrophages. In addition, cTAMs also expressed higher levels of iNOS, arginase-1, VEGF-A, CXCL-4 and OPN than monocultured macrophages. Moreover, compared with TAMs purified from C26 tumors, cTAMs showed stronger suppression on T cell proliferation. In conclusion, our results showed that PS-F2 stimulation promotes M1 polarization of TAMs and alleviates the immunosuppression exerted by TAMs, and the cTAMs differentiation system may serve as a platform for identifying modulatory agents targeting TAMs. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T14:47:05Z (GMT). No. of bitstreams: 1 U0001-1308202014393700.pdf: 4912631 bytes, checksum: 858d69e9fd743d72999e04ba88a03870 (MD5) Previous issue date: 2020 | en |
| dc.description.tableofcontents | 中文摘要 I Abstract II 圖表目錄 V 縮寫表 VI 緒論 １ 1 靈芝 １ 2 單核球與巨噬細胞 ３ 3 癌症腫瘤 ５ 研究動機 ７ 材料與方法 ８ 1 臺灣紫芝培養 ８ 2 臺灣紫芝多醣體之純化與處理 ９ 3 細胞培養與處理 １１ 4 腫瘤相關巨噬細胞之製備與純化 １２ 5 T細胞免疫抑制試驗 (T cell suppression assay) １３ 6 單核球/巨噬細胞-腫瘤細胞共培養 １４ 7 免疫螢光染色 １６ 8 即時定量反轉錄聚合酶連鎖反應 (qRT-PCR) １６ 9 動物使用 １８ 10 統計軟體與分析 １８ 實驗結果 １９ 1 PS-F2對腫瘤相關巨噬細胞的影響 １９ 1.1 C26腫瘤分離出之F4/80+ TAMs皆不表現Gr-1 １９ 1.2 tTAMs之M1/M2/TAM相關基因表現大多高於naïve脾臟巨噬細胞或發炎性單核球 １９ 1.3 PS-F2使tTAMs基因表現趨向於M1並影響TAM相關基因表達 ２０ 1.4 PS-F2使tTAMs對CD4+ T cells 增生的抑制效果下降 ２０ 2 cTAM共培養系統之建立 ２１ 2.1 3T3壞死細胞能於BALB/c誘導出發炎性單核球 ２１ 2.2 發炎性單核球與C26腫瘤細胞共培養後表面分子的改變 ２２ 2.3 cTAMs為M2-like並表現部分TAM相關基因 ２２ 2.4 cTAMs具有抑制T細胞增生的能力 ２３ 2.5 Thioglycolate誘導之發炎性單核球與C26腫瘤細胞共培養後表面分子的改變 ２３ 2.6 發炎性單核球與B16 melanoma共培養後表面分子的改變 ２４ 討論 ２５ 圖表 ３１ 參考文獻 ５５ | |
| dc.language.iso | zh-TW | |
| dc.subject | 基因表現 | zh_TW |
| dc.subject | 臺灣紫芝 | zh_TW |
| dc.subject | 多醣體 | zh_TW |
| dc.subject | 免疫 | zh_TW |
| dc.subject | 抗腫瘤 | zh_TW |
| dc.subject | 腫瘤相關巨噬細胞 | zh_TW |
| dc.subject | T細胞增生 | zh_TW |
| dc.subject | T cell proliferation | en |
| dc.subject | Ganoderma formosanum | en |
| dc.subject | polysaccharides | en |
| dc.subject | immune | en |
| dc.subject | anti-tumor | en |
| dc.subject | tumor associated macrophage | en |
| dc.subject | gene expression | en |
| dc.title | 臺灣紫芝多醣體對腫瘤相關巨噬細胞的影響 | zh_TW |
| dc.title | The effects of Ganoderma formosanum polysaccharides on tumor associated macrophages | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 108-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 徐立中(Li-Chung Hsu),陳念榮(Nien-Jung Chen) | |
| dc.subject.keyword | 臺灣紫芝,多醣體,免疫,抗腫瘤,腫瘤相關巨噬細胞,T細胞增生,基因表現, | zh_TW |
| dc.subject.keyword | Ganoderma formosanum,polysaccharides,immune,anti-tumor,tumor associated macrophage,T cell proliferation,gene expression, | en |
| dc.relation.page | 60 | |
| dc.identifier.doi | 10.6342/NTU202003252 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2020-08-16 | |
| dc.contributor.author-college | 生命科學院 | zh_TW |
| dc.contributor.author-dept | 生化科技學系 | zh_TW |
| dc.date.embargo-lift | 2025-08-18 | - |
| 顯示於系所單位： | 生化科技學系 | |
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