000 03017cam a2200325 a 4500
003 EG-GiCUC
008 160730s2016 ua dh f m 000 0 eng d
040 _aEG-GiCUC
_beng
_cEG-GiCUC
041 0 _aeng
049 _aDeposite
097 _aPh.D
099 _aCai01.08.01.Ph.D.2016.He.C
100 0 _aHebatullah Samy Mohamed Helmy
245 1 0 _aComparative study of the effect of certain antitumor drugs on neoplastic transformations of rats liver /
_cHebatullah Samy Mohamed Helmy ; Supervised Tarek Mohamed Kamal Motawi , Noha Ahmed Elboghdady , Abeer Moustafa Elsayed
246 1 5 _aدراسة مقارنة لتأثير بعض الأدوية المضادة للسرطان علي التحول السرطاني في كبد الجرذان
260 _aCairo :
_bHebatullah Samy Mohamed Helmy ,
_c2016
300 _a122 P. :
_bcharts , facsimiles ;
_c25cm
502 _aThesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Biochemistry
520 _aCancer stem cells (CSCs) in hepatocellular carcinoma (HCC) possess tumor initiating, metastatic and drug resistance properties. This study was conducted to evaluate the effect of pegylated interferon-Ü2a (PEG-IFN-Ü2a) and 5-fluorouracil (5-FU) on the expression of CSCs markers and on specific pathways that contribute to the propagation of CSCs in HCC. HCC was initiated in rats using a single intraperitoneal dose of diethylnitrosamine (DENA) (200 mg/kg) and promoted by weekly subcutaneous injections of carbon tetrachloride (CCl4) for six weeks. After the appearance of dysplastic nodules, the animals received either PEG-IFN-Ü2a or 5-FU for eight weeks. CSCs markers (OV6, CD90) and molecules related to transforming growth factor-Ý (TGF-Ý) and other signaling pathways were assessed in hepatic tissues. PEG-IFN-Ü2a treatment effectively suppressed the hepatic expression of OV6 and CD90, ameliorated the diminished hepatic expression of TGF-Ý receptor II (TGF-ÝRII) and Ý2 spectrin (Ý2SP) and significantly reduced the elevated hepatic expression of TGF-Ý1, interleukin6 (IL6), signal transducer and activator of transcription3 (STAT3) and vascular endothelial growth factor (VEGF). In contrast, 5-FU treatment failed to reduce the over-expression of CSCs markers and barely affected the disrupted TGF-Ý signaling. Furthermore, it had no effect on angiogenesis or nitrosative stress. In conclusion, PEG-IFN-Ü2a, but not 5-FU, could reduce the propagation of CSCs during the progression of HCC by upregulating the disrupted TGF-Ý signaling, suppressing the IL6/STAT3 pathway and reducing angiogenesis
530 _aIssued also as CD
653 4 _a5-fluorouracil
653 4 _aHepatocellular carcinoma
653 4 _aPegylated interferon-Ü2a
700 0 _aAbeer Moustafa Elsayed ,
_eSupervisor
700 0 _aNoha Ahmed Elboghdady ,
_eSupervisor
700 0 _aTarek Mohamed Kamal Motawi ,
_eSupervisor
905 _aEnas
_eCataloger
905 _aNazla
_eRevisor
942 _2ddc
_cTH
999 _c57265
_d57265