東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

A functional metabolomics approach t...

Ippolito, Joseph Edward.

FindBook

Google Book

Amazon

博客來

A functional metabolomics approach to prostate and neuroendocrine carcinogenesis.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	A functional metabolomics approach to prostate and neuroendocrine carcinogenesis./
作者:	Ippolito, Joseph Edward.
面頁冊數:	350 p.
附註:	Source: Dissertation Abstracts International, Volume: 68-06, Section: B, page: .
Contained By:	Dissertation Abstracts International68-06B.
標題:	Chemistry, Biochemistry. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3268042
ISBN:	9780549070160

A functional metabolomics approach to prostate and neuroendocrine carcinogenesis.
Ippolito, Joseph Edward.

A functional metabolomics approach to prostate and neuroendocrine carcinogenesis. - 350 p.

Source: Dissertation Abstracts International, Volume: 68-06, Section: B, page: .

Thesis (Ph.D.)--Washington University in St. Louis, 2007.

Human neuroendocrine (NE) cancers range from relatively indolent to highly aggressive. This thesis introduces novel methods to identify metabolomic features of NE cancers associated with a poor outcome. One method represents a "forward metabolomics approach": it consists of transcriptome-directed metabolomics and uses the high throughput of DNA microarrays to acquire a profile of transcripts whose levels are enriched in metastatic prostate NE tumors in transgenic mice plus derived prostate NE cancer (PNEC) cell lines compared to normal prostate. This transcript 'signature' was then used for (i) in silico metabolic reconstructions of NE cell metabolism, (ii) directed liquid chromatography-tandem MS analysis of metabolites in mouse prostatic NE tumors and PNEC cells, and (iii) analysis of microarray datasets obtained from human NE tumors with good or poor prognoses. The results indicated that a distinguishing feature of poor-prognosis NE tumors is a glutamic acid decarboxylase-independent pathway for production of gamma-aminobutyric acid (GABA), and a pathway for production of imidazole-4-acetate involving dopa decarboxylase and a membrane-associated amine oxidase, amiloride-binding protein 1 (ABP1). Electrophysiological studies disclosed that PNEC cells express functional glutamate, glycine and GABA A receptors, and that GABA and imidazole-4-acetate can bind and activate GABAA receptors, thus providing a previously uncharacterized paradigm for NE tumor cell signaling. I demonstrated that GABA also plays a role in intracellular energy production, as PNEC cells have the ability to convert GABA to succinate through a pathway known as the GABA shunt of the TCA cycle. A parallel "reverse metabolomics approach" was also taken using magic angle spinning (MAS) NMR to profile metabolites in prostate NE tumors and correlate the results with in silico metabolic reconstructions from microarray studies. MAS-NMR disclosed that prostate NE cancer cells accumulate large amounts of propylene glycol, a precursor to pyruvate. In silico metabolic reconstructions indicated that ABP1 was part of a propylene glycol biosynthetic pathway from glycine. Together, these findings disclose a potential link between cellular signaling and energy utilization in poor prognosis cancers. Furthermore, I have discovered that transcriptional and metabolic features of transformed mouse NE cells are evident in hematopoietic and neural stem cell populations, as well as in cancers with a non-NE origin.

ISBN: 9780549070160Subjects--Topical Terms:

1017722
Chemistry, Biochemistry.

A functional metabolomics approach to prostate and neuroendocrine carcinogenesis.
LDR:03430nmm 2200289 4500 001 1835720
005 20071226140439.5
008 130610s2007 eng d
020 $a 9780549070160
035 $a (UMI)AAI3268042
035 $a AAI3268042
040 $a UMI $c UMI
100 1 $a Ippolito, Joseph Edward. $3 1924343
245 1 2 $a A functional metabolomics approach to prostate and neuroendocrine carcinogenesis.
300 $a 350 p.
500 $a Source: Dissertation Abstracts International, Volume: 68-06, Section: B, page: .
500 $a Adviser: Jeffrey I. Gordon.
502 $a Thesis (Ph.D.)--Washington University in St. Louis, 2007.
520 $a Human neuroendocrine (NE) cancers range from relatively indolent to highly aggressive. This thesis introduces novel methods to identify metabolomic features of NE cancers associated with a poor outcome. One method represents a "forward metabolomics approach": it consists of transcriptome-directed metabolomics and uses the high throughput of DNA microarrays to acquire a profile of transcripts whose levels are enriched in metastatic prostate NE tumors in transgenic mice plus derived prostate NE cancer (PNEC) cell lines compared to normal prostate. This transcript 'signature' was then used for (i) in silico metabolic reconstructions of NE cell metabolism, (ii) directed liquid chromatography-tandem MS analysis of metabolites in mouse prostatic NE tumors and PNEC cells, and (iii) analysis of microarray datasets obtained from human NE tumors with good or poor prognoses. The results indicated that a distinguishing feature of poor-prognosis NE tumors is a glutamic acid decarboxylase-independent pathway for production of gamma-aminobutyric acid (GABA), and a pathway for production of imidazole-4-acetate involving dopa decarboxylase and a membrane-associated amine oxidase, amiloride-binding protein 1 (ABP1). Electrophysiological studies disclosed that PNEC cells express functional glutamate, glycine and GABA A receptors, and that GABA and imidazole-4-acetate can bind and activate GABAA receptors, thus providing a previously uncharacterized paradigm for NE tumor cell signaling. I demonstrated that GABA also plays a role in intracellular energy production, as PNEC cells have the ability to convert GABA to succinate through a pathway known as the GABA shunt of the TCA cycle. A parallel "reverse metabolomics approach" was also taken using magic angle spinning (MAS) NMR to profile metabolites in prostate NE tumors and correlate the results with in silico metabolic reconstructions from microarray studies. MAS-NMR disclosed that prostate NE cancer cells accumulate large amounts of propylene glycol, a precursor to pyruvate. In silico metabolic reconstructions indicated that ABP1 was part of a propylene glycol biosynthetic pathway from glycine. Together, these findings disclose a potential link between cellular signaling and energy utilization in poor prognosis cancers. Furthermore, I have discovered that transcriptional and metabolic features of transformed mouse NE cells are evident in hematopoietic and neural stem cell populations, as well as in cancers with a non-NE origin.
590 $a School code: 0252.
650 4 $a Chemistry, Biochemistry. $3 1017722
650 4 $a Biophysics, Medical. $3 1017681
650 4 $a Health Sciences, Oncology. $3 1018566
690 $a 0487
690 $a 0760
690 $a 0992
710 2 0 $a Washington University in St. Louis. $3 1017519
773 0 $t Dissertation Abstracts International $g 68-06B.
790 1 0 $a Gordon, Jeffrey I., $e advisor
790 $a 0252
791 $a Ph.D.
792 $a 2007
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3268042