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研究生:許棠閔
研究生(外文):Tang-Min Hsu
論文名稱:真菌幾丁聚醣降低癌症化療藥物副作用之效果評估及其機制之探討
論文名稱(外文):Study on the Prevention Effects of Chitosan in Cancer Chemotherapy – Induced Adverse Effects and Related Mechanisms
指導教授:王應然王應然引用關係
指導教授(外文):Ying-Jan Wang
學位類別:碩士
校院名稱:國立成功大學
系所名稱:環境醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:77
中文關鍵詞:副作用5-氟尿嘧啶幾丁聚醣癌症化學治療
外文關鍵詞:5-Fluorouracilside effectsChitosanCancer Chemotherapy
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  癌症化學治療通常被用來對付無法用手術去除的癌細胞,不過在接受癌症化學治療的過程中,會對病人產生不良的副作用,影響病人健康。真菌幾丁聚醣(Chitosan)為真菌類細胞壁中的主要成分。研究發現幾丁聚醣具有許多生物活性作用,如增進免疫功能、保護腸胃道及抑制腫瘤細胞生長等。本研究的目的在探討真菌幾丁聚醣對於癌症化學治療所產生的副作用是否有改善的效果,且不影響癌症化療藥物的抗癌效果,並探討其相關的機制。首先利用動物實驗模式,以骨髓毒性、胃腸毒性、免疫功能作為副作用指標,來評估真菌幾丁聚醣對於癌症化學治療藥物(5-氟尿嘧啶,5-FU) 所引發的副作用是否有改善的效果。小鼠實驗中單獨以5-FU給藥及5-FU合併真菌幾丁聚醣方式給藥,藉由測定腫瘤體積與重量、骨髓中CD 19細胞百分比、血液中白血球與淋巴球數量、小腸蔗糖酶活性、腹瀉發生率、微核試驗及彗星分析來評估抗癌效果、副作用發生情形和相關機轉的探討。研究結果顯示,5-FU合併真菌幾丁聚醣給藥並不影響5-FU抑制癌細胞生長的效果。真菌幾丁聚醣減輕了由5-FU所造成骨髓中CD 19百分比及血液中白血球與淋巴球細胞數量的下降情形。5-FU合併真菌幾丁聚醣可以降低小腸黏膜受到損害及延緩小鼠腹瀉的發生率。在微核測驗與彗星分析結果中顯示出5-FU合併真菌幾丁聚醣減少了5-FU對於正常細胞染色體與DNA的傷害。由實驗結果推論,真菌幾丁聚醣可能經由降低5-FU對於正常細胞之DNA傷害,而改善了5-FU所誘發骨髓毒性、免疫毒性與腸胃毒性之副作用。
 Cancer chemotherapy is used to treat tumor cells that can not be removed by surgery. In the process of treatment, however, cancer chemotherapy often induces side effects and reduces health of cancer patients. Chitosan is the main component of the fungi’s cell wall. Chitosan has several biological activities such as immuno-enhancing ability, protection mucosa damage in gastrointestinal track and anti-tumor activity. The purpose of this study was to investigate whether Chitosan could improve the side effects induced by chemotherapeutic agent without loss its anti-tumor ability and their related mechanisms. The study examined the anti-tumor activity and side effects (meylotoxicity, immunotoxicity and gastrointestinal toxicity) of combined treatment of chemotherapeutic drug 5-Fluorouracil (5-FU) and Chitosan in vivo. We measured the weight and volume of tumor, percentage of CD19 in bone marrow, leukocyte number, lymphocyte number, sucrase activity, incidence of diarrhea, micronucleated polychromatic erythrocytes (MNPCE) frequency and Comet assay in mice treated with 5-FU plus Chitosan or 5-FU alone to evaluate the effects of Chitosan on the 5-FU-induced anti-tumor activity and side effects. The results showed that 5-FU plus Chitosan inhibited the tumor growth as well as 5-FU alone. Chitosan improved the reduction of leukocyte number, lymphocyte number and CD19 percentage of bone marrow induced by 5-FU. 5-FU combined with Chitosan reduced the injury of the small intestinal mucosa and delayed the onset of diarrhea in mice. 5-FU combined with Chitosan also decreased MNPCE frequency and DNA damage caused by 5-FU in bone marrow cells. The results demonstrate that Chitosan may improve adverse effects induced by 5-FU through reduction DNA damage of normal cell.
中文摘要 1
Abstract 2
第一章、緒論 7
第二章、文獻回顧 8
第一節、癌症化學治療 8
第二節、5-氟尿嘧啶簡介 9
第三節、幾丁質與幾丁聚醣簡介 10
第四節、CD3-T淋巴球與CD19-B淋巴球 11
第五節、微核試驗 12
第六節、彗星分析(Comet assay) 13
第七節、癌症化學治療與腹瀉 13
第三章、研究目的 15
第四章、研究架構 16
第一節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之抑癌能力 16
第二節、Pilot study -小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情況 17
第三節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情況 18
第四節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之腹瀉發生率 19
第五節、小鼠實驗模式評估真菌幾丁聚醣降低5-FU藥物副作用機制之探討 20
第五章、研究材料與方法 21
第一節、研究材料 21
第二節、研究方法 23
第三節、統計分析 36
第六章、實驗結果 37
第一節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之抑癌能力 37
第二節、Pilot study -小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情形 37
第三節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之副作用情形 39
第四節、腫瘤小鼠實驗模式評估真菌幾丁聚醣合併5-FU藥物之腹瀉發生率 41
第五節、小鼠實驗模式評估真菌幾丁聚醣降低5-FU藥物副作用機制之探討 41
第七章、討論 43
第八章、結論 47
第九章、參考文獻 48
附 錄 57
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