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You searched for +publisher:"NSYSU" +contributor:("Shiuan, David"). One record found.

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NSYSU

1. Chen, Heng-Chi. Studies on the Inhibitory Mechanism of Angiogenesis Inhibitor, Endostatin.

Degree: Master, Biological Sciences, 2000, NSYSU

Antiangiogenic tomor therapies have attracted intense interest for their broad-spectrum action, low toxicity, and in the case of direct endothelial targeting, an absence of drug resistance. Among the growing list of antiangiogenic agents, endostatin has attracted most attention and been under the spotlight of numerous debates. Like other angiogenesis inhibitors, endostatin is also a proteolytic fragment (~20 kDa) from an extracellular protein, collagen XVIII. It potently inhibits endothelial cell proliferation and angiogenesis, but has no cytotoxic effects on cancer cells. Above all, therapy of experimental cancer with endostatin in rodents leads to tumor dormancy and does not induce resistance. However, the exact mechanism on how endostatin inhibited endothelial cells proliferation remains largely unknown. We have cloned mouse endostatin cDNA from mice liver by RT-PCR. After verification by DNA sequencing, endostatin cDNA was subcloned in to E.coli expression vector to express and generate large quantities of recombinant GST-fused endostatin (GST-endostatin). Unlike His-tagged endostatin, GST-endostatin is soluble and capable of inhibiting various endothelial cell lines including HUVEC, EA.hy926 and BAEC with IC50 ~ 20 nM. Flow cytometry analysis indicated GST-endostatin induced apoptosis in EA.hy926 cells. GST-endostatin also inhibited the cell migration of EA.hy926 cells toward chemoattractant bFGF with IC50 ~ 0.5 nM. Further more, GST-endostatin inhibited in vivo angiogenesis in chicken chorioallantoic membrane and suppressed tumor growth in mice bearing Lewis lung carcinoma cells. After functional characterization of GST-endostatin, we decided to use GST-endostatin and EA.hy926 cells as a model system to study the inhibitory mechanism of endostatin in endothelial cells. By using fura-2 fluorescence probe, GST-endostatin was shown to elevate the cytosolic calcium in dose-dependent manner from extracellular source. Chelation of extracellular Ca2+ by EGTA or inhibition of calcium channel by nifedipine abolished the cytotoxic effect endostatin, suggesting the calcium rise by endostatin play an important role in its inhibitory mechanism. Besides, endostatin also stimulated activity of a large- conductance calcium-activated potassium (Bkca) channel, further supporting endostatin initiated serial changes in ion channels activities in endothelial cells. Respiratory enzyme activities and endogenous ATP synthesis in endothelial cells were significantly inhibited by GST-endostatin treatment, indicating GST-endostatin depleted the energy source for endothelial cells. In summary, present study demonstrated GST-endostatin caused dramatic changes in electrophysiologic properties and decreased endogenous ATP synthesis in endothelial cells, which may participate in its inhibitory mechanism. Advisors/Committee Members: Shiuan, David (chair), Cheng, Jiin-Tsuey (committee member), Hong Yi-Ren (chair), Ming-Hong Tai (committee member).

Subjects/Keywords: angiogenesis; endostatin

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

APA (6th Edition):

Chen, H. (2000). Studies on the Inhibitory Mechanism of Angiogenesis Inhibitor, Endostatin. (Thesis). NSYSU. Retrieved from http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0704100-014039

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Chen, Heng-Chi. “Studies on the Inhibitory Mechanism of Angiogenesis Inhibitor, Endostatin.” 2000. Thesis, NSYSU. Accessed April 11, 2021. http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0704100-014039.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Chen, Heng-Chi. “Studies on the Inhibitory Mechanism of Angiogenesis Inhibitor, Endostatin.” 2000. Web. 11 Apr 2021.

Vancouver:

Chen H. Studies on the Inhibitory Mechanism of Angiogenesis Inhibitor, Endostatin. [Internet] [Thesis]. NSYSU; 2000. [cited 2021 Apr 11]. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0704100-014039.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Chen H. Studies on the Inhibitory Mechanism of Angiogenesis Inhibitor, Endostatin. [Thesis]. NSYSU; 2000. Available from: http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0704100-014039

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

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