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| 041 |
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|a eng
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| 100 |
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|9 539058
|a Amawi, Haneen
|e Author
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| 245 |
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|a Optimization of Synthetic Flavonolignans to Target Embryonic Signaling in Metastatic Ovarian and Colon Cancer
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| 260 |
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|a توليدو
|c 2017
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| 300 |
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|a 1 - 354
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| 336 |
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|a رسائل جامعية
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| 502 |
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|b رسالة دكتوراه
|c University of Toledo
|f The Graduate Faculty
|g الولايات المتحدة الأمريكية
|o 0001
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| 520 |
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|a This thesis work reports the synthesis and anticancer activity evaluation of twelve novel silybin analogues designed using a novel ring disjunctive based natural product lead (RDNPL) optimization approach. The twelve synthetic novel derivatives (HM015a- HM015k) were screened for their cytotoxicities against several cancerous cell lines and normal epithelial cells. HM015k or 15k, was selected as a leading compound where it induced potent and selective cytotoxicity against both ovarian (OV2008, A2780) and colon (HCT116, S, and LOVO) cancer cell lines. The cytotoxicity of 15k was further confirmed and 15k treatment induced significant inhibition in the cancer cells proliferation with time and their colony formation rates. Mechanistic studies indicated that the antiproliferative efficacy of 15k was mediated through significant induction of cell cycle arrest, oxidative stress, and apoptosis. Furthermore, 15k inhibited cellular microtubules dynamic and assembly by binding to tubulin and inhibiting its levels and function in both colon and ovarian cancer cells. The compound 15k reversed cancer cells migration and invasion potentials. Further, the 15k treatment induced significant reversal in EMT morphology and markers with significant downregulation in Wnt/ B-catenin signaling in both cancers. Finally, 15k was safe in zebrafish in vivo model at concentrations up to 10 μM and induced no cardiac or morphological toxicities.
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| 653 |
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|a العلوم الطبية
|a مركبات الفلافونوليجان
|a الأمراض السرطانية
|a سرطان المبيض
|a سرطان القولون
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| 700 |
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|9 539060
|a Tiwari, Amit K.
|e Advisor
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| 856 |
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|u 9824-194-006-0001-T.pdf
|y صفحة العنوان
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| 856 |
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|u 9824-194-006-0001-A.pdf
|y المستخلص
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| 856 |
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|u 9824-194-006-0001-C.pdf
|y قائمة المحتويات
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| 856 |
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|u 9824-194-006-0001-F.pdf
|y 24 صفحة الأولى
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| 856 |
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|u 9824-194-006-0001-0.pdf
|y الفصل التمهيدي
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| 856 |
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|u 9824-194-006-0001-1.pdf
|y 1 الفصل
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| 856 |
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|u 9824-194-006-0001-2.pdf
|y 2 الفصل
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| 856 |
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|u 9824-194-006-0001-3.pdf
|y 3 الفصل
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| 856 |
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|u 9824-194-006-0001-4.pdf
|y 4 الفصل
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| 856 |
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|u 9824-194-006-0001-5.pdf
|y 5 الفصل
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| 856 |
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|u 9824-194-006-0001-O.pdf
|y الخاتمة
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| 856 |
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|u 9824-194-006-0001-R.pdf
|y المصادر والمراجع
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| 856 |
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|u 9824-194-006-0001-S.pdf
|y الملاحق
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| 930 |
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|d n
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| 995 |
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|a +Dissertations
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| 999 |
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|c 999428
|d 999428
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