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The role of LL-37 in prostate cancer...

Hensel, Jonathan Adam.

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The role of LL-37 in prostate cancer and its potential as a therapeutic target.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	The role of LL-37 in prostate cancer and its potential as a therapeutic target./
作者:	Hensel, Jonathan Adam.
面頁冊數:	120 p.
附註:	Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
Contained By:	Dissertation Abstracts International72-08B.
標題:	Health Sciences, Pathology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3457153
ISBN:	9781124672113

The role of LL-37 in prostate cancer and its potential as a therapeutic target.
Hensel, Jonathan Adam.

The role of LL-37 in prostate cancer and its potential as a therapeutic target. - 120 p.

Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .

Thesis (Ph.D.)--The University of Alabama at Birmingham, 2011.

LL-37 is the only cathelicidin-derived anti-microbial peptide in humans and has been shown to stimulate proliferation, angiogenesis, cellular migration and inhibit apoptosis, in addition to serving as a chemoattractant for leukocytes. It is produced primarily by epithelial cells and leukocytes, and has recently been discovered to be over-expressed in breast, ovarian and lung cancers.

ISBN: 9781124672113Subjects--Topical Terms:

1017854
Health Sciences, Pathology.

The role of LL-37 in prostate cancer and its potential as a therapeutic target.
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245 1 4 $a The role of LL-37 in prostate cancer and its potential as a therapeutic target.
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500 $a Source: Dissertation Abstracts International, Volume: 72-08, Section: B, page: .
500 $a Adviser: Selvarangan Ponnazhagan.
502 $a Thesis (Ph.D.)--The University of Alabama at Birmingham, 2011.
520 $a LL-37 is the only cathelicidin-derived anti-microbial peptide in humans and has been shown to stimulate proliferation, angiogenesis, cellular migration and inhibit apoptosis, in addition to serving as a chemoattractant for leukocytes. It is produced primarily by epithelial cells and leukocytes, and has recently been discovered to be over-expressed in breast, ovarian and lung cancers.
520 $a Based on these findings, we compared levels of LL-37 expression in benign and cancerous human prostate tissues. Results of this investigation demonstrated that LL-37 is increasingly over-expressed in primary prostate tumors in a grade dependent manner and in metastatic lesions. Since the physiological mechanisms of LL-37 are also key factors that become exaggerated in prostate cancer (PCa) and based on our preliminary findings regarding the over-expression of LL-37 in PCa in a grade dependent manner, we hypothesized that LL-37 may have a significant role in the neoplastic progression of PCa and serve as a potential therapeutic target.
520 $a We analogously examined the role of LL-37 in the neoplastic progression of PCa within an immunocompetent mouse PCa model, utilizing the murine orthologue of LL-37, Cathelicidin Related Anti-Microbial Peptide (CRAMP). Similar to the grade dependent over-expression of LL-37 in human PCa, we found CRAMP is increasingly over-expressed with advancing severity of primary prostate tumors and in metastatic lesions of the Transgenic Adenocarcinoma Mouse Prostate (TRAMP) model.
520 $a Modulation of CRAMP within TRAMP PCa cell lines significantly altered in vitro and in vivo pro-tumorigenic mechanisms. Our study demonstrated that CRAMP modulates the proliferation, invasiveness and matrix metalloproteinase (MMP) levels of these cells in a positive manner through the Erk1/2 and Akt pathways. In addition to replicating these findings, CRAMP knockdown in TRAMP-C1 cells also led to a significant in vivo reduction in tumor burdens, angiogenesis and the number of myeloidderived suppressor cells (MDSC) infiltrating into the tumor microenvironment.
520 $a The effects of CRAMP modulation on cellular proliferation, angiogenesis, invasion, MMP levels and the chemoattraction of MDSC in a mouse PCa model, support our hypothesis that LL-37 has a significant role in the neoplastic progression of PCa and may serve as an efficacious therapeutic target for PCa, and other cancers over-expressing the peptide.
520 $a Keywords: LL-37, CRAMP, prostate cancer, angiogenesis, MDSC,
590 $a School code: 0005.
650 4 $a Health Sciences, Pathology. $3 1017854
650 4 $a Health Sciences, Oncology. $3 1018566
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710 2 $a The University of Alabama at Birmingham. $b Pathology. $3 1684960
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790 1 0 $a Ponnazhagan, Selvarangan, $e advisor
790 1 0 $a Hel, Zdenek $e committee member
790 1 0 $a Lopez, Richard D. $e committee member
790 1 0 $a Mountz, John D. $e committee member
790 1 0 $a Siegal, Gene P. $e committee member
790 1 0 $a Strong, Theresa V. $e committee member
790 $a 0005
791 $a Ph.D.
792 $a 2011
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