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Gene delivery for treating liver fib...

Cheng, Kun.

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Gene delivery for treating liver fibrosis and improving human islet transplantation.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	Gene delivery for treating liver fibrosis and improving human islet transplantation./
Author:	Cheng, Kun.
Description:	206 p.
Notes:	Adviser: Ram I. Mahato.
Contained By:	Dissertation Abstracts International68-03B.
Subject:	Health Sciences, Pharmacology. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3256243

Gene delivery for treating liver fibrosis and improving human islet transplantation.
Cheng, Kun.

Gene delivery for treating liver fibrosis and improving human islet transplantation. - 206 p.

Adviser: Ram I. Mahato.

Thesis (Ph.D.)--The University of Tennessee Health Science Center, 2007.

In conclusion, we have demonstrated that target delivery of therapeutic genes, ODNs or siRNAs can significantly enhance gene expression and silencing for treating liver fibrosis and diabetes.Subjects--Topical Terms:

1017717
Health Sciences, Pharmacology.

Gene delivery for treating liver fibrosis and improving human islet transplantation.
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035 $a (UMI)AAI3256243
035 $a AAI3256243
040 $a UMI $c UMI
100 1 $a Cheng, Kun. $3 1262885
245 1 0 $a Gene delivery for treating liver fibrosis and improving human islet transplantation.
300 $a 206 p.
500 $a Adviser: Ram I. Mahato.
500 $a Source: Dissertation Abstracts International, Volume: 68-03, Section: B, page: 1575.
502 $a Thesis (Ph.D.)--The University of Tennessee Health Science Center, 2007.
520 $a In conclusion, we have demonstrated that target delivery of therapeutic genes, ODNs or siRNAs can significantly enhance gene expression and silencing for treating liver fibrosis and diabetes.
520 $a This dissertation deals with developing gene delivery systems for two disease models, liver fibrosis and type I diabetes.
520 $a We firstly highlighted the liver fibrogenesis and critically discussed the therapeutic strategies of liver fibrosis using gene therapy strategies. For TFO project, we determined the biodistribution of TFO in normal and liver fibrotic rats at whole body, organ (liver), cellular (different liver cells) and subcellular (cytoplasm, nuclei and plasma membrane) levels. Cholesterol was successfully conjugated to TFO via disulfide bond with high efficiency. Conjugation of cholesterol increased the uptake of the TFO by hepatic stellate cells in cell culture and after systemic administration into rats. Inhibition of type I collagen gene expression was also increased after conjugation.
520 $a We designed nine TGF-beta1 siRNAs and found two siRNAs have potent silencing effect when transfected into HSC-T6 cells. Inhibition of TIMP-1, alpha-SMA and type I collagen mRNA were also observed after transfection with a siRNA. In vivo silencing effect of siRNA was tested in DMN induced liver fibrotic mouse model. No silencing effect was observed after systemic administration at normal pressure, but hydrodynamic injection showed some silencing effect as well as improvement in liver/body weight ratio. Future studies will be performed using hydrodynamic injection at higher dose and hydrodynamic injection of saline will be used as control.
520 $a For adenovirus project, we successfully generated adenovirus using 293 cell lines and titration of amplified adenovirus was determined using TCID 50 method. Transfection condition was optimized and dose dependent hVEGF expression was observed at mRNA and protein levels. DNA fragmentation test showed that transfection of adenovirus had more effect on early apoptosis than necrosis. Immunohistochemical staining confirmed the higher hVEGF expression in transfected human islets and the expression was localized in peripheral region. These findings suggest that adenoviral vectors efficiently transducer genes into human islets. However, care must be taken since adenovirus vectors induced apoptosis when used at high MOI.
590 $a School code: 0783.
650 4 $a Health Sciences, Pharmacology. $3 1017717
690 $a 0419
710 2 0 $a The University of Tennessee Health Science Center. $3 1262886
773 0 $t Dissertation Abstracts International $g 68-03B.
790 $a 0783
790 1 0 $a Mahato, Ram I., $e advisor
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3256243