Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea
碩士 === 高雄醫學大學 === 生物醫學暨環境生物學研究所 === 100 === Development specific inhibitors for bacterial beta-glucuronidase will be able to prevent drug to reply toxicity in the intestine, and thus harm the intestinal cells. For this purpose, we cooperator with Professor Steve Luo (Academia Sinica, Taipei), who cr...
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ndltd-TW-100KMC051140012015-10-13T21:55:42Z http://ndltd.ncl.edu.tw/handle/38405597985363876791 Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea 發展細菌葡萄醣醛酸酶專一性抑制劑對減緩化療誘發腹瀉之功效 Yei-Chung Huang 黃彥鈞 碩士 高雄醫學大學 生物醫學暨環境生物學研究所 100 Development specific inhibitors for bacterial beta-glucuronidase will be able to prevent drug to reply toxicity in the intestine, and thus harm the intestinal cells. For this purpose, we cooperator with Professor Steve Luo (Academia Sinica, Taipei), who crystal the structure of E.coli βG (eβG). And also cooperator with the Professor Chien-Shu Chen (China Medical University, Taichung) who use computer simulation technology for active site structure differences between human and E.coli βG (hβG and eβG) finding 59 candidate maybe with specificity inhibition of eβG. Through the inhibition of hβG and eβG functional screening, we successfully get 11 eβG specific inhibitors. Through the cytotoxicity test and inhibition of E.coli endogenous βG test, we get the most effective eβG specific inhibitor #57,and it will not affect bacterial growth. According to inhibit ability of eβG specific inhibitors in vivo by image assay, we give mouse merge inhibitors # 57 and βG precursor image probe (FDGlcU). We found that the inhibitor # 57 can inhibit FDGlcU be activated in the intestine, to prove inhibitors #57 can inhibit intestinal eβG activity. Finally through the experiment of CPT-11 induced diarrhea, we found that inhibitor # 57 can slow down weight loss induced by Chemotherapy-induced diarrhea (CID) in mice. we successful development of eβG specific inhibitors will overcome the CID. eβG specific inhibitors may also prevent reactivation of glucuronidated carcinogens in the gut, and reduce the incidence of colon cancer. Tian-Lu Cheng 鄭添祿 2012 學位論文 ; thesis 39 zh-TW |
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碩士 === 高雄醫學大學 === 生物醫學暨環境生物學研究所 === 100 === Development specific inhibitors for bacterial beta-glucuronidase will be able to prevent drug to reply toxicity in the intestine, and thus harm the intestinal cells. For this purpose, we cooperator with Professor Steve Luo (Academia Sinica, Taipei), who crystal the structure of E.coli βG (eβG). And also cooperator with the Professor Chien-Shu Chen (China Medical University, Taichung) who use computer simulation technology for active site structure differences between human and E.coli βG (hβG and eβG) finding 59 candidate maybe with specificity inhibition of eβG. Through the inhibition of hβG and eβG functional screening, we successfully get 11 eβG specific inhibitors. Through the cytotoxicity test and inhibition of E.coli endogenous βG test, we get the most effective eβG specific inhibitor #57,and it will not affect bacterial growth. According to inhibit ability of eβG specific inhibitors in vivo by image assay, we give mouse merge inhibitors # 57 and βG precursor image probe (FDGlcU). We found that the inhibitor # 57 can inhibit FDGlcU be activated in the intestine, to prove inhibitors #57 can inhibit intestinal eβG activity. Finally through the experiment of CPT-11 induced diarrhea, we found that inhibitor # 57 can slow down weight loss induced by Chemotherapy-induced diarrhea (CID) in mice. we successful development of eβG specific inhibitors will overcome the CID. eβG specific inhibitors may also prevent reactivation of glucuronidated carcinogens in the gut, and reduce the incidence of colon cancer.
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author2 |
Tian-Lu Cheng |
author_facet |
Tian-Lu Cheng Yei-Chung Huang 黃彥鈞 |
author |
Yei-Chung Huang 黃彥鈞 |
spellingShingle |
Yei-Chung Huang 黃彥鈞 Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea |
author_sort |
Yei-Chung Huang |
title |
Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea |
title_short |
Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea |
title_full |
Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea |
title_fullStr |
Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea |
title_full_unstemmed |
Development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea |
title_sort |
development of bacteria-specific beta-glucuronidase inhibitor for the prevention of chemotherapy-induced diarrhea |
publishDate |
2012 |
url |
http://ndltd.ncl.edu.tw/handle/38405597985363876791 |
work_keys_str_mv |
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