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You searched for +publisher:"University of New South Wales" +contributor:("Khachigian, Levon, Centre for Vascular Research, Faculty of Medicine, UNSW"). Showing records 1 – 3 of 3 total matches.

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University of New South Wales

1. Santiago, Fernando Santos. Regulatory mechanisms in vascular injury and repair.

Degree: Centre for Vascular Research, 2012, University of New South Wales

Proliferation of SMC after vascular injury accounts for clinicalconditions in transplant vasculopathy, in-stent restenosis and veinbypass graft failure. Vascular injury upregulates the expression ofmany transcription factors, two important ones are Yin yang-1 (YY-1)and early growth response-1 (Egr-1). The aims of this thesis were (1)to examine a possible mechanism by which a transcriptionalrepressor YY-1 inhibits SMC proliferation and (2) the development ofa phospho-specifc antibody to a transcription activator, Egr-1 foundto be a positive regulator of SMC proliferation. The results show thatYY-1 inhibits p21WAF1/Cip1 transcription that perturbs the formation ofp21WAF1/Cip1/cdk4/cyclin D1 complex thus blocking the downstreampRBSer249/Thr252 phosphorylation and expression of PCNA and TK-1.This inhibition was observed only in SMCs and not in ECs.Moreover, inhibition of endogenous YY-1 was performed to show thegain- and loss-of function of this transcription factor. YY-1 binds withSp1 and prevents its occupancy of a Sp1 binding element in thep21WAF1/Cip1 promoter without YY-1 itself binding to the promoter. YY-1 suppression of p21WAF1/Cip1 also involves p53 ubiquitination andproteasomal degradation. Further studies showed thatoverexpression of the first two-zinc finger region of YY-1 can inhibitsmooth muscle cell proliferation and not ECs. This cell-type specificeffect of YY-1 could be a potential tool in controlling SMCproliferation in drug eluting stent.The second part of this dissertation is the generation of phosphospecificantibody to Egr-1. Egr-1 controls a variety of genesimplicated to SMC proliferation. Phosphorylation of Egr-1 can induceor repress the expression of its target gene depending on what typeof kinase is involved. Preliminary data show that a phospho-specificantibody to Egr-1, pS26, can detect the Egr-1 phosphorylated proteinfrom cell extract. Specificity of pS26 was determined also using slotblots of synthetic peptides and recombinant proteins, peptideblocking and phosphatase treatment. Further validation is needed to6fully confirm the specificity of this new phospho-specific antibody toEgr-1. A phospho-specific antibody to Egr-1 will serve as a tool todissect mechanism by which this immediate early gene productexerts it control on fibroproliferative vasculopathies.The results generated by this thesis have added a new layer on theunderstanding of mechanism on inhibition of SMC proliferation and ageneration of potential tool to dissect the mechanism ofphosphorylation of a transcription factor implicated to SMCproliferative vasculopathy. Advisors/Committee Members: Khachigian, Levon, Centre for Vascular Research, Faculty of Medicine, UNSW.

Subjects/Keywords: YY-1; Vascular injury; Egr-1

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Santiago, F. S. (2012). Regulatory mechanisms in vascular injury and repair. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52018 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10688/SOURCE01?view=true

Chicago Manual of Style (16th Edition):

Santiago, Fernando Santos. “Regulatory mechanisms in vascular injury and repair.” 2012. Doctoral Dissertation, University of New South Wales. Accessed August 18, 2019. http://handle.unsw.edu.au/1959.4/52018 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10688/SOURCE01?view=true.

MLA Handbook (7th Edition):

Santiago, Fernando Santos. “Regulatory mechanisms in vascular injury and repair.” 2012. Web. 18 Aug 2019.

Vancouver:

Santiago FS. Regulatory mechanisms in vascular injury and repair. [Internet] [Doctoral dissertation]. University of New South Wales; 2012. [cited 2019 Aug 18]. Available from: http://handle.unsw.edu.au/1959.4/52018 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10688/SOURCE01?view=true.

Council of Science Editors:

Santiago FS. Regulatory mechanisms in vascular injury and repair. [Doctoral Dissertation]. University of New South Wales; 2012. Available from: http://handle.unsw.edu.au/1959.4/52018 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:10688/SOURCE01?view=true


University of New South Wales

2. Li, Yue. Novel strategies to inhibit smooth muscle cell hyperplasia and intimal thickening.

Degree: Centre for Vascular Research, 2013, University of New South Wales

Coronary artery disease (CAD), underpinned by atherosclerosis, remains a leading cause of morbidity and mortality, particularly in the Western World. Although the advent of percutaneous transluminal coronary angioplasty (PTCA) has provided a fundamental change in the treatment of CAD and drug-eluting stents (DES) have brought about marked improvement, there still remain significant challenges such as restenosis and late stent thrombosis. Coronary artery bypass grafting (CABG) has been acknowledged as the most effective way to treat CAD. However saphenous vein graft failures still present a problem due to stenosis. Vascular smooth muscle cell (VSMC) proliferation and migration is the primary driver of restenosis after percutaneous coronary interventions (PCI) and vein graft failure after CABG. Endothelial dysfunction also plays an important role in both restenosis and late thrombosis following PCI. Therefore, key to the prevention of restenosis and late stent thrombosis is to suppress SMC proliferation and migration, and to enhance re-endothelialisation. The broad aim of work in this thesis is to seek more effective strategies to inhibit SMC hyperplasia and intimal thickening while promoting re-endothelialisation.More specifically, the effects of three kinds of bio-molecules on prevention of restenosis are investigated in this thesis. Firstly, a novel “cocktail” consisting of a combination of VEGF-A, VEGF-D and cRGD, which has not been studied with SMC and EC in response to injury, is tested in a rat carotid balloon injury model. Secondly, the efficacy of the DNAzyme, Dz13, targeting c-Jun is tested in the rabbit autologous vein bypass graft model using the lipid-based transfection agent 1,2- dioleoyl-3-trimethylammonium propane (DOTAP) / 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE). Lastly, the anti-restenotic potential of miR-191, a natural microRNA inhibitor of the immediate early gene Egr-1, is examined in the balloon-injured rat carotid artery model.The data presented in this thesis demonstrates that localised delivery of Dz13, miR191 and a novel cocktail of VEGF-A, VEGF-D and cRGD can inhibit neointima formation in animal models. According to these studies, the cocktail, Dz13 and miR191 may be useful approaches for reducing in-stent restenosis and late thrombosis. The ability of these biomolecules to be delivered at a local level makes them ideal for inclusion in stent-based strategies. Advisors/Committee Members: Khachigian, Levon, Centre for Vascular Research, Faculty of Medicine, UNSW.

Subjects/Keywords: Vascular smooth muscle cells; Neointimal hyperplasia

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Li, Y. (2013). Novel strategies to inhibit smooth muscle cell hyperplasia and intimal thickening. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/52997 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11675/SOURCE01?view=true

Chicago Manual of Style (16th Edition):

Li, Yue. “Novel strategies to inhibit smooth muscle cell hyperplasia and intimal thickening.” 2013. Doctoral Dissertation, University of New South Wales. Accessed August 18, 2019. http://handle.unsw.edu.au/1959.4/52997 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11675/SOURCE01?view=true.

MLA Handbook (7th Edition):

Li, Yue. “Novel strategies to inhibit smooth muscle cell hyperplasia and intimal thickening.” 2013. Web. 18 Aug 2019.

Vancouver:

Li Y. Novel strategies to inhibit smooth muscle cell hyperplasia and intimal thickening. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2019 Aug 18]. Available from: http://handle.unsw.edu.au/1959.4/52997 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11675/SOURCE01?view=true.

Council of Science Editors:

Li Y. Novel strategies to inhibit smooth muscle cell hyperplasia and intimal thickening. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/52997 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11675/SOURCE01?view=true


University of New South Wales

3. Yee, Grace Pei Chien. Targeting the transcription factor c-Jun in cervical cancer cells.

Degree: Centre for Vascular Research, 2013, University of New South Wales

Despite the development of vaccines for human papillomaviruses (HPV) in cervical cancer and other efforts to improve therapy, deaths still average 275,000 annually worldwide, with most women succumbing to recurrent or metastatic disease. The c-Jun oncogene is a subunit of the activating protein-1 (AP-1) transcription factor and is strongly expressed in cervical cancer, regulating the expression of HPV16 and 18 genes. AP-1 plays a major role in cell growth, migration and apoptosis in many cell types. This work examined the role of c-Jun in modulating cervical cancer cell line (HeLa) proliferation, migration, apoptosis, invasion, susceptibility to cisplatin and the underlying mechanisms.c-Jun protein and mRNA levels were reduced by c-Jun siRNA. c-Jun silencing inhibited cell proliferation. Significantly, c-Jun suppression dramatically reduced HeLa migration and invasion and targeted down-regulation of cyclooxygenase-2 (Cox-2), intracellular adhesion molecule 1 (ICAM-1), matrix metalloproteinases (MMP)-1 and -9 genes highly expressed in cervical cancer and associated with metastatic growth. siRNA knockdown of Cox-2 also reduced HeLa migration and invasion as well as MMP-1 expression suggesting an intermediary link. In transfected cells over-expressing c-Jun, cell proliferation was not significantly increased but cell invasiveness was markedly enhanced in parallel with enhanced Cox-2 and MMP-1 expression as well as MMP-2 activity. Modulation of c-Jun expression did not synergistically combine with cisplatin to increase the susceptibility of HeLa cells to apoptosis or cell cycle disruption. In vivo, c-Jun siRNA pre-transfected HeLa-luc solid tumor growth and size were significantly retarded compared to the control groups. siRNA targeting another transcription factor, Early Growth Response-1 (Egr-1) demonstrated significant inhibition of HeLa cell migration and invasion as well as reduced MMP-1 expression and MMP-9 activity, with concomitant blockade of c-Jun and Cox-2 expression, suggesting pivotal link of these genes to HeLa cell migration and invasion.Reduced invasion potential of HeLa cells after c-Jun, Egr-1 and Cox-2 knockdown, respectively suggests the potential of these genes as targets in treatment of metastatic and recurrent cervical cancer. Data also suggest a mechanism involving c-Jun, Egr-1 and Cox-2 in the regulation of MMP-1. Advisors/Committee Members: Khachigian, Levon, Centre for Vascular Research, Faculty of Medicine, UNSW, de Souza, Paul, Clinical School - St George Hospital, Faculty of Medicine, UNSW, Chong, Beng Hock, Clinical School - St George Hospital, Faculty of Medicine, UNSW.

Subjects/Keywords: Human papillomaviruses (HPV); Cervical cancer; c-Jun oncogene; HeLa; Proliferation; Migration; Apoptosis; Invasion; Susceptibility; Early Growth Response-1 (Egr-1); Metastases

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Yee, G. P. C. (2013). Targeting the transcription factor c-Jun in cervical cancer cells. (Doctoral Dissertation). University of New South Wales. Retrieved from http://handle.unsw.edu.au/1959.4/53183 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11876/SOURCE02?view=true

Chicago Manual of Style (16th Edition):

Yee, Grace Pei Chien. “Targeting the transcription factor c-Jun in cervical cancer cells.” 2013. Doctoral Dissertation, University of New South Wales. Accessed August 18, 2019. http://handle.unsw.edu.au/1959.4/53183 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11876/SOURCE02?view=true.

MLA Handbook (7th Edition):

Yee, Grace Pei Chien. “Targeting the transcription factor c-Jun in cervical cancer cells.” 2013. Web. 18 Aug 2019.

Vancouver:

Yee GPC. Targeting the transcription factor c-Jun in cervical cancer cells. [Internet] [Doctoral dissertation]. University of New South Wales; 2013. [cited 2019 Aug 18]. Available from: http://handle.unsw.edu.au/1959.4/53183 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11876/SOURCE02?view=true.

Council of Science Editors:

Yee GPC. Targeting the transcription factor c-Jun in cervical cancer cells. [Doctoral Dissertation]. University of New South Wales; 2013. Available from: http://handle.unsw.edu.au/1959.4/53183 ; https://unsworks.unsw.edu.au/fapi/datastream/unsworks:11876/SOURCE02?view=true

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