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

Evaluation of the Effects of Oncolyt...

Kostalas, Marcos.

FindBook

Google Book

Amazon

博客來

Evaluation of the Effects of Oncolytic Vaccinia Virus on Colorectal Liver Metastases in Cell Lines and in Organotypic Cultures.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Evaluation of the Effects of Oncolytic Vaccinia Virus on Colorectal Liver Metastases in Cell Lines and in Organotypic Cultures./
作者:	Kostalas, Marcos.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2019,
面頁冊數:	221 p.
附註:	Source: Dissertations Abstracts International, Volume: 80-11, Section: C.
Contained By:	Dissertations Abstracts International80-11C.
標題:	Pharmacology. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13894313
ISBN:	9781083523723

Evaluation of the Effects of Oncolytic Vaccinia Virus on Colorectal Liver Metastases in Cell Lines and in Organotypic Cultures.
Kostalas, Marcos.

Evaluation of the Effects of Oncolytic Vaccinia Virus on Colorectal Liver Metastases in Cell Lines and in Organotypic Cultures. - Ann Arbor : ProQuest Dissertations & Theses, 2019 - 221 p.

Source: Dissertations Abstracts International, Volume: 80-11, Section: C.

Thesis (M.D.)--University of Surrey (United Kingdom), 2019.

This item must not be sold to any third party vendors.

Vaccinia virus is one of several live viruses currently being evaluated in clinical trials as cancer therapies. One oncolytic virus, T-VEC, is already in clinical use and is NICE approved for the treatment of melanoma. We have investigated a genetically modified, Copenhagen strain vaccinia virus encoding the fusion suicide gene (FCU1) that is able to convert non-toxic fluorocytosine into the active compound fluorouracil. The mode of cell death attributed to vaccinia virus is variable and multiple modes have been implicated based on tumour type. Through our work with colorectal cancer cell lines we have established that this form of oncolytic vaccinia virus induces cell death through a predominant picture of apoptosis. Furthermore, assessment of its immunogenicity has found there to be an increase in markers of immunogenic cell death following infection with the virus. We have developed an organotypic culture system in our laboratory which enables us to assess oncolytic viruses on ex vivo tissue. Treatment of organotypic cultures from colorectal liver metastases have shown that vaccinia virus successfully infects and replicates in the tumour tissue. A dose-response relationship was observed with the highest doses of virus exerting the most effect on tumour tissue. Assessment of the pro-drug activation system through the conversion of 5-fluorocytosine to 5-fluorouracil in supernatant showed a high percentage conversion, whilst immunohistochemical staining did show evidence of an improved effect with the pro-drug system compared with virus alone. We have evaluated the combination of cavitational ultrasound and sulphur hexafluoride microbubbles to enhance infection with oncolytic virus. Our results have shown that this method enhances infection of organotypic cultures treated with oncolytic vaccinia virus. This has enabled the use of a lower dose of virus whilst maintaining the same effects in tissue as that of virus at higher doses. This finding has translational implications that may enhance the efficacy of systemically administered oncolytic vaccinia virus.

ISBN: 9781083523723Subjects--Topical Terms:

634543
Pharmacology.

Evaluation of the Effects of Oncolytic Vaccinia Virus on Colorectal Liver Metastases in Cell Lines and in Organotypic Cultures.
LDR:03280nmm a2200349 4500 001 2207306
005 20190916101817.5
008 201008s2019 ||||||||||||||||| ||eng d
020 $a 9781083523723
035 $a (MiAaPQ)AAI13894313
035 $a (MiAaPQ)Surrey850720
035 $a AAI13894313
040 $a MiAaPQ $c MiAaPQ
100 1 $a Kostalas, Marcos. $3 3434287
245 1 0 $a Evaluation of the Effects of Oncolytic Vaccinia Virus on Colorectal Liver Metastases in Cell Lines and in Organotypic Cultures.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2019
300 $a 221 p.
500 $a Source: Dissertations Abstracts International, Volume: 80-11, Section: C.
500 $a Publisher info.: Dissertation/Thesis.
500 $a Advisor: Pandha, Hardev;Annels, Nicola.
502 $a Thesis (M.D.)--University of Surrey (United Kingdom), 2019.
506 $a This item must not be sold to any third party vendors.
520 $a Vaccinia virus is one of several live viruses currently being evaluated in clinical trials as cancer therapies. One oncolytic virus, T-VEC, is already in clinical use and is NICE approved for the treatment of melanoma. We have investigated a genetically modified, Copenhagen strain vaccinia virus encoding the fusion suicide gene (FCU1) that is able to convert non-toxic fluorocytosine into the active compound fluorouracil. The mode of cell death attributed to vaccinia virus is variable and multiple modes have been implicated based on tumour type. Through our work with colorectal cancer cell lines we have established that this form of oncolytic vaccinia virus induces cell death through a predominant picture of apoptosis. Furthermore, assessment of its immunogenicity has found there to be an increase in markers of immunogenic cell death following infection with the virus. We have developed an organotypic culture system in our laboratory which enables us to assess oncolytic viruses on ex vivo tissue. Treatment of organotypic cultures from colorectal liver metastases have shown that vaccinia virus successfully infects and replicates in the tumour tissue. A dose-response relationship was observed with the highest doses of virus exerting the most effect on tumour tissue. Assessment of the pro-drug activation system through the conversion of 5-fluorocytosine to 5-fluorouracil in supernatant showed a high percentage conversion, whilst immunohistochemical staining did show evidence of an improved effect with the pro-drug system compared with virus alone. We have evaluated the combination of cavitational ultrasound and sulphur hexafluoride microbubbles to enhance infection with oncolytic virus. Our results have shown that this method enhances infection of organotypic cultures treated with oncolytic vaccinia virus. This has enabled the use of a lower dose of virus whilst maintaining the same effects in tissue as that of virus at higher doses. This finding has translational implications that may enhance the efficacy of systemically administered oncolytic vaccinia virus.
590 $a School code: 0597.
650 4 $a Pharmacology. $3 634543
650 4 $a Medicine. $3 641104
650 4 $a Virology. $3 642304
650 4 $a Oncology. $3 751006
690 $a 0419
690 $a 0564
690 $a 0720
690 $a 0992
710 2 $a University of Surrey (United Kingdom). $3 3286108
773 0 $t Dissertations Abstracts International $g 80-11C.
790 $a 0597
791 $a M.D.
792 $a 2019
793 $a English
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=13894313