Journal article 1118 views
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells
E. McAdam,
H.N. Haboubi,
A.P. Griffiths,
J.N. Baxter,
S. Spencer-Harty,
C. Davies,
G.J. Jenkins,
Gareth Jenkins 
International Journal of Cancer, Volume: 136, Pages: 527 - 535
Swansea University Author:
Gareth Jenkins
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DOI (Published version): 10.1002/ijc.29029
Abstract
Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. Howeve...
| Published in: | International Journal of Cancer |
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| Published: |
2015
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa18151 |
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<?xml version="1.0"?><rfc1807><datestamp>2019-06-21T15:01:03.3362332</datestamp><bib-version>v2</bib-version><id>18151</id><entry>2014-07-21</entry><title>Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells</title><swanseaauthors><author><sid>a44095d26187304e903da7ca778697b6</sid><ORCID>0000-0002-5437-8389</ORCID><firstname>Gareth</firstname><surname>Jenkins</surname><name>Gareth Jenkins</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2014-07-21</date><deptcode>BMS</deptcode><abstract>Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. However, this often does little to control carcinogenic bile acid reflux. The transcription factor nuclear factor kappa B (NF-κB) plays a key role in the pathogenesis of OA and its activity is associated with a poor response to chemotherapy, making it an attractive therapeutic target. We sought to decipher the role of different bile acids in NF-κB activation in oesophageal cell lines using short, physiologically relevant exposure times. The effect of an acidic or neutral extracellular pH was investigated concurrently, to mimic in vivo conditions associated with or without acid suppression. We found that some bile acids activated NF-κB to a greater extent when combined with acid, whereas others did so in its absence, at neutral pH. The precise composition of an individual's reflux, coupled with whether they are taking acid suppressants may therefore dictate the extent of NF-κB activation in the oesophagus, and hence the likelihood of histological progression and chemotherapy success. Regardless of pH, the kinase inhibitor of κB kinase was pivotal in mediating reflux induced NF-κB activation. Its importance was confirmed further as its increased activation was associated with histological progression in patient samples. We identified further kinases important in acid or bile induced NF-κB signalling in oesophageal cells, which may provide suitable targets for therapeutic intervention.</abstract><type>Journal Article</type><journal>International Journal of Cancer</journal><volume>136</volume><paginationStart>527</paginationStart><paginationEnd>535</paginationEnd><publisher/><keywords/><publishedDay>1</publishedDay><publishedMonth>2</publishedMonth><publishedYear>2015</publishedYear><publishedDate>2015-02-01</publishedDate><doi>10.1002/ijc.29029</doi><url/><notes></notes><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm/><lastEdited>2019-06-21T15:01:03.3362332</lastEdited><Created>2014-07-21T11:05:55.2809761</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>E.</firstname><surname>McAdam</surname><order>1</order></author><author><firstname>H.N.</firstname><surname>Haboubi</surname><order>2</order></author><author><firstname>A.P.</firstname><surname>Griffiths</surname><order>3</order></author><author><firstname>J.N.</firstname><surname>Baxter</surname><order>4</order></author><author><firstname>S.</firstname><surname>Spencer-Harty</surname><order>5</order></author><author><firstname>C.</firstname><surname>Davies</surname><order>6</order></author><author><firstname>G.J.</firstname><surname>Jenkins</surname><order>7</order></author><author><firstname>Gareth</firstname><surname>Jenkins</surname><orcid>0000-0002-5437-8389</orcid><order>8</order></author></authors><documents/><OutputDurs/></rfc1807> |
| spelling |
2019-06-21T15:01:03.3362332 v2 18151 2014-07-21 Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells a44095d26187304e903da7ca778697b6 0000-0002-5437-8389 Gareth Jenkins Gareth Jenkins true false 2014-07-21 BMS Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. However, this often does little to control carcinogenic bile acid reflux. The transcription factor nuclear factor kappa B (NF-κB) plays a key role in the pathogenesis of OA and its activity is associated with a poor response to chemotherapy, making it an attractive therapeutic target. We sought to decipher the role of different bile acids in NF-κB activation in oesophageal cell lines using short, physiologically relevant exposure times. The effect of an acidic or neutral extracellular pH was investigated concurrently, to mimic in vivo conditions associated with or without acid suppression. We found that some bile acids activated NF-κB to a greater extent when combined with acid, whereas others did so in its absence, at neutral pH. The precise composition of an individual's reflux, coupled with whether they are taking acid suppressants may therefore dictate the extent of NF-κB activation in the oesophagus, and hence the likelihood of histological progression and chemotherapy success. Regardless of pH, the kinase inhibitor of κB kinase was pivotal in mediating reflux induced NF-κB activation. Its importance was confirmed further as its increased activation was associated with histological progression in patient samples. We identified further kinases important in acid or bile induced NF-κB signalling in oesophageal cells, which may provide suitable targets for therapeutic intervention. Journal Article International Journal of Cancer 136 527 535 1 2 2015 2015-02-01 10.1002/ijc.29029 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2019-06-21T15:01:03.3362332 2014-07-21T11:05:55.2809761 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine E. McAdam 1 H.N. Haboubi 2 A.P. Griffiths 3 J.N. Baxter 4 S. Spencer-Harty 5 C. Davies 6 G.J. Jenkins 7 Gareth Jenkins 0000-0002-5437-8389 8 |
| title |
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells |
| spellingShingle |
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells Gareth Jenkins |
| title_short |
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells |
| title_full |
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells |
| title_fullStr |
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells |
| title_full_unstemmed |
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells |
| title_sort |
Reflux composition influences the level of NF-κB activation and upstream kinase preference in oesophageal adenocarcinoma cells |
| author_id_str_mv |
a44095d26187304e903da7ca778697b6 |
| author_id_fullname_str_mv |
a44095d26187304e903da7ca778697b6_***_Gareth Jenkins |
| author |
Gareth Jenkins |
| author2 |
E. McAdam H.N. Haboubi A.P. Griffiths J.N. Baxter S. Spencer-Harty C. Davies G.J. Jenkins Gareth Jenkins |
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Journal article |
| container_title |
International Journal of Cancer |
| container_volume |
136 |
| container_start_page |
527 |
| publishDate |
2015 |
| institution |
Swansea University |
| doi_str_mv |
10.1002/ijc.29029 |
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Faculty of Medicine, Health and Life Sciences |
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facultyofmedicinehealthandlifesciences |
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Faculty of Medicine, Health and Life Sciences |
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facultyofmedicinehealthandlifesciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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| description |
Oesophageal adenocarcinoma (OA) incidence is rising and prognosis is poor. Understanding the molecular basis of this malignancy is key to finding new prevention and treatment strategies. Gastroesophageal reflux disease is the primary cause of OA, usually managed with acid suppression therapy. However, this often does little to control carcinogenic bile acid reflux. The transcription factor nuclear factor kappa B (NF-κB) plays a key role in the pathogenesis of OA and its activity is associated with a poor response to chemotherapy, making it an attractive therapeutic target. We sought to decipher the role of different bile acids in NF-κB activation in oesophageal cell lines using short, physiologically relevant exposure times. The effect of an acidic or neutral extracellular pH was investigated concurrently, to mimic in vivo conditions associated with or without acid suppression. We found that some bile acids activated NF-κB to a greater extent when combined with acid, whereas others did so in its absence, at neutral pH. The precise composition of an individual's reflux, coupled with whether they are taking acid suppressants may therefore dictate the extent of NF-κB activation in the oesophagus, and hence the likelihood of histological progression and chemotherapy success. Regardless of pH, the kinase inhibitor of κB kinase was pivotal in mediating reflux induced NF-κB activation. Its importance was confirmed further as its increased activation was associated with histological progression in patient samples. We identified further kinases important in acid or bile induced NF-κB signalling in oesophageal cells, which may provide suitable targets for therapeutic intervention. |
| published_date |
2015-02-01T03:21:12Z |
| _version_ |
1763750625512783872 |
| score |
11.013171 |