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In vitro analysis of lytic peptide to target breast and prostate cancer. / Riaz Jannoo

Swansea University Author: Riaz Jannoo

Abstract

In the United Kingdom 1 in 3 will develop some form o f cancer during their lifetime. Despite the development o f new drugs and use o f combinational therapies, mortality rates have not improved. Between 1979 and 2008, incidence rates for cancer in the United Kingdom increased by 26% The second most...

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Published: 2015
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa42824
first_indexed 2018-08-02T18:55:38Z
last_indexed 2019-10-21T16:48:31Z
id cronfa42824
recordtype RisThesis
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spelling 2018-08-29T14:55:06.5972193 v2 42824 2018-08-02 In vitro analysis of lytic peptide to target breast and prostate cancer. 40dbc4d7beae07be0cb6be7e93212603 NULL Riaz Jannoo Riaz Jannoo true true 2018-08-02 In the United Kingdom 1 in 3 will develop some form o f cancer during their lifetime. Despite the development o f new drugs and use o f combinational therapies, mortality rates have not improved. Between 1979 and 2008, incidence rates for cancer in the United Kingdom increased by 26% The second most common cause o f cancer deaths is prostate cancer in men and breast cancer in women, the first being lung cancer. Current methods for treating cancer involve radiation therapy and chemotherapy. However, resistance to these therapies is common.Targeting o f cell surface receptors specifically or over expressed in cancer cells has painted a new insight in anti-cancer therapy. The Gonadotropin-releasing hormone receptor (GnRHR), luteinizing hormone/choriogonadotropin receptor (LHCGR) and Interleukin-13 receptor alpha 2 (IL-13Ra2) are overexpressed in some human tumours, including prostate and breast cancer. IL-13, GnRH and PCG ligands bind to the cell surface receptors IL-13Ra2, GnRHR and LHCGR respectively.The gene expression o f GnRHR, LHCGR and IL-13Ra2 in a wide range o f human cancer tissues as well as in 2D cultured (monolayers) prostate and breast cancer cell lines was analysed. Their levels were shown to be overexpressed, indicating their potential use for diagnosis and targeting treatment.Unlike 2D monolayer cultures, 3D spheroid cultures achieve in vivo-like conditions in cancer. We therefore developed quick, easy and reproducible 3D tumour models o f prostate and breast cancer cell lines and used them to validate the cancers target ability for the lytic peptides.Both 2D monolayer and 3D spheroid cultures o f breast and prostate cancer cells over­expressing IL-13Ra2, GnRHR and LHCGR were targeted using Pep-1, [D-Trp6]GnRH and pCG(ala) peptides conjugated covalently to a membrane disrupting lytic peptide (Phor21). The lytic peptide drugs [D-Trp6]GnRH-Phor21, Pep-l-Phor21 and Phor21-pCG(ala) conjugates were shown to selectively kill prostate and breast cancer cells with their toxicity dependent on the expression levels o f the respective receptors at the cell surface. E-Thesis Breast cancer 31 12 2015 2015-12-31 COLLEGE NANME Swansea University Medical School COLLEGE CODE Swansea University Doctoral Ph.D 2018-08-29T14:55:06.5972193 2018-08-02T16:24:30.5701964 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Riaz Jannoo NULL 1 0042824-02082018162524.pdf 10821211.pdf 2018-08-02T16:25:24.7500000 Output 22176899 application/pdf E-Thesis true 2018-08-02T16:25:24.7500000 false
title In vitro analysis of lytic peptide to target breast and prostate cancer.
spellingShingle In vitro analysis of lytic peptide to target breast and prostate cancer.
Riaz Jannoo
title_short In vitro analysis of lytic peptide to target breast and prostate cancer.
title_full In vitro analysis of lytic peptide to target breast and prostate cancer.
title_fullStr In vitro analysis of lytic peptide to target breast and prostate cancer.
title_full_unstemmed In vitro analysis of lytic peptide to target breast and prostate cancer.
title_sort In vitro analysis of lytic peptide to target breast and prostate cancer.
author_id_str_mv 40dbc4d7beae07be0cb6be7e93212603
author_id_fullname_str_mv 40dbc4d7beae07be0cb6be7e93212603_***_Riaz Jannoo
author Riaz Jannoo
author2 Riaz Jannoo
format E-Thesis
publishDate 2015
institution Swansea University
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description In the United Kingdom 1 in 3 will develop some form o f cancer during their lifetime. Despite the development o f new drugs and use o f combinational therapies, mortality rates have not improved. Between 1979 and 2008, incidence rates for cancer in the United Kingdom increased by 26% The second most common cause o f cancer deaths is prostate cancer in men and breast cancer in women, the first being lung cancer. Current methods for treating cancer involve radiation therapy and chemotherapy. However, resistance to these therapies is common.Targeting o f cell surface receptors specifically or over expressed in cancer cells has painted a new insight in anti-cancer therapy. The Gonadotropin-releasing hormone receptor (GnRHR), luteinizing hormone/choriogonadotropin receptor (LHCGR) and Interleukin-13 receptor alpha 2 (IL-13Ra2) are overexpressed in some human tumours, including prostate and breast cancer. IL-13, GnRH and PCG ligands bind to the cell surface receptors IL-13Ra2, GnRHR and LHCGR respectively.The gene expression o f GnRHR, LHCGR and IL-13Ra2 in a wide range o f human cancer tissues as well as in 2D cultured (monolayers) prostate and breast cancer cell lines was analysed. Their levels were shown to be overexpressed, indicating their potential use for diagnosis and targeting treatment.Unlike 2D monolayer cultures, 3D spheroid cultures achieve in vivo-like conditions in cancer. We therefore developed quick, easy and reproducible 3D tumour models o f prostate and breast cancer cell lines and used them to validate the cancers target ability for the lytic peptides.Both 2D monolayer and 3D spheroid cultures o f breast and prostate cancer cells over­expressing IL-13Ra2, GnRHR and LHCGR were targeted using Pep-1, [D-Trp6]GnRH and pCG(ala) peptides conjugated covalently to a membrane disrupting lytic peptide (Phor21). The lytic peptide drugs [D-Trp6]GnRH-Phor21, Pep-l-Phor21 and Phor21-pCG(ala) conjugates were shown to selectively kill prostate and breast cancer cells with their toxicity dependent on the expression levels o f the respective receptors at the cell surface.
published_date 2015-12-31T07:31:31Z
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score 11.048149

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