{"id":{"repo_id":"soton","oai_identifier":"oai:eprints.soton.ac.uk:67628"},"canonical_url":"https://search.dev.ndltd.org/etd/soton/oai:eprints.soton.ac.uk:67628","repository":{"repo_id":"soton","name":"University of Southampton","base_url":"https://eprints.soton.ac.uk/cgi/oai2"},"display":{"title":"Mechanisms of multidrug resistance in bladder cancer: the role of the nuclear membrane","abstract":"Multidrug resistance (MDR) describes the phenomenon whereby cancer cells
exposed to a single cytotoxic drug develop cross resistance to numerous other
structurally unrelated chemotherapeutics. The development of MDR is a major
cause of cancer chemotherapy treatment failure in all types of cancer.
Numerous mechanisms of MDR have been elucidated which include ATPbinding
cassette (ABC) transporter proteins, cytoplasmic vaults, alterations in
topoisomerase II and increased expression of glutathione-S-transferases, all of
which result in reduced chemotherapeutic efficacy.
Superficial bladder cancer is commonly treated with adjuvant intravesical
chemotherapy using mitomycin C or epirubicin (an anthracycline), following
surgical resection. However, despite this treatment, the recurrence rates of
these tumours can approach 60%. This high recurrence rate represents the
development of MDR in many cases.
Previous work using anthracycline fluorescence has shown that MDR cells
have reduced levels of anthracycline uptake and also demonstrate a
characteristic nuclear sparing of drug uptake. This nuclear sparing
phenomenon in MDR cells transcends tissue type and suggests that the
nuclear membrane may also play a role in MDR.
The work described herein discusses the current role of chemotherapy in the
treatment of superficial bladder cancer, mechanisms of MDR and the role of the
nuclear membrane in MDR. Following this our investigation of the role of the
nuclear membrane is described, using a number of novel techniques including
cell fusion and microinjection. In addition, we investigated MDR modulation by
verapamil, with analysis of changes in cellular, cytoplasmic and nuclear drug
uptake mediated by this known MDR reversing agent.","abstract_html":"Multidrug resistance (MDR) describes the phenomenon whereby cancer cells<br/>exposed to a single cytotoxic drug develop cross resistance to numerous other<br/>structurally unrelated chemotherapeutics. The development of MDR is a major<br/>cause of cancer chemotherapy treatment failure in all types of cancer.<br/><br/>Numerous mechanisms of MDR have been elucidated which include ATPbinding<br/>cassette (ABC) transporter proteins, cytoplasmic vaults, alterations in<br/>topoisomerase II and increased expression of glutathione-S-transferases, all of<br/>which result in reduced chemotherapeutic efficacy.<br/><br/>Superficial bladder cancer is commonly treated with adjuvant intravesical<br/>chemotherapy using mitomycin C or epirubicin (an anthracycline), following<br/>surgical resection. However, despite this treatment, the recurrence rates of<br/>these tumours can approach 60%. This high recurrence rate represents the<br/>development of MDR in many cases.<br/><br/>Previous work using anthracycline fluorescence has shown that MDR cells<br/>have reduced levels of anthracycline uptake and also demonstrate a<br/>characteristic nuclear sparing of drug uptake. This nuclear sparing<br/>phenomenon in MDR cells transcends tissue type and suggests that the<br/>nuclear membrane may also play a role in MDR.<br/><br/>The work described herein discusses the current role of chemotherapy in the<br/>treatment of superficial bladder cancer, mechanisms of MDR and the role of the<br/>nuclear membrane in MDR. Following this our investigation of the role of the<br/>nuclear membrane is described, using a number of novel techniques including<br/>cell fusion and microinjection. In addition, we investigated MDR modulation by<br/>verapamil, with analysis of changes in cellular, cytoplasmic and nuclear drug<br/>uptake mediated by this known MDR reversing agent.","abstract_has_math":false,"creators":["Featherstone, Jonathan Mark"],"institution":"University of Southampton","degree_name":"Ph.D.","degree_level":"doctoral","degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Primrose, J.","Cooper, A."],"committee_chairs":[],"committee_members":[],"year":2007,"date_issued":"2007-12","date_published":"2007-12","updated_at":"2026-07-24T04:36:02Z","subjects":[],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":null,"outbound_label":null,"outbound_source":null},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Primrose, J.","Cooper, A."]},{"key":"dc:creator","label":"Author","values":["Featherstone, Jonathan Mark"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2007-12"]},{"key":"dc:date.issued","label":"Date","values":["2007-12"]},{"key":"dc:publisher.department","label":"Dc Publisher Department","values":["Cancer Sciences (pre 2011 reorg)","School of Medicine"]},{"key":"dc:publisher.institution","label":"Dc Publisher Institution","values":["University of Southampton"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://eprints.soton.ac.uk/67628/"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"dc:type.qualificationlevel","label":"Dc Type Qualificationlevel","values":["doctoral"]},{"key":"dc:type.qualificationname","label":"Dc Type Qualificationname","values":["Ph.D."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["https://eprints.soton.ac.uk/67628/1/Featherstone_DM_Thesis_2009_PDF.pdf"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Multidrug resistance (MDR) describes the phenomenon whereby cancer cells
exposed to a single cytotoxic drug develop cross resistance to numerous other
structurally unrelated chemotherapeutics. The development of MDR is a major
cause of cancer chemotherapy treatment failure in all types of cancer.
Numerous mechanisms of MDR have been elucidated which include ATPbinding
cassette (ABC) transporter proteins, cytoplasmic vaults, alterations in
topoisomerase II and increased expression of glutathione-S-transferases, all of
which result in reduced chemotherapeutic efficacy.
Superficial bladder cancer is commonly treated with adjuvant intravesical
chemotherapy using mitomycin C or epirubicin (an anthracycline), following
surgical resection. However, despite this treatment, the recurrence rates of
these tumours can approach 60%. This high recurrence rate represents the
development of MDR in many cases.
Previous work using anthracycline fluorescence has shown that MDR cells
have reduced levels of anthracycline uptake and also demonstrate a
characteristic nuclear sparing of drug uptake. This nuclear sparing
phenomenon in MDR cells transcends tissue type and suggests that the
nuclear membrane may also play a role in MDR.
The work described herein discusses the current role of chemotherapy in the
treatment of superficial bladder cancer, mechanisms of MDR and the role of the
nuclear membrane in MDR. Following this our investigation of the role of the
nuclear membrane is described, using a number of novel techniques including
cell fusion and microinjection. In addition, we investigated MDR modulation by
verapamil, with analysis of changes in cellular, cytoplasmic and nuclear drug
uptake mediated by this known MDR reversing agent."]},{"key":"dc:format","label":"Dc Format","values":["text"]},{"key":"dc:title","label":"Title","values":["Mechanisms of multidrug resistance in bladder cancer: the role of the nuclear membrane"]}]}],"canonical_facts":{"dc:contributor.advisor":["Primrose, J.","Cooper, A."],"dc:creator":["Featherstone, Jonathan Mark"],"dc:date":["2007-12"],"dc:date.issued":["2007-12"],"dc:description.abstract":["Multidrug resistance (MDR) describes the phenomenon whereby cancer cells
exposed to a single cytotoxic drug develop cross resistance to numerous other
structurally unrelated chemotherapeutics. The development of MDR is a major
cause of cancer chemotherapy treatment failure in all types of cancer.
Numerous mechanisms of MDR have been elucidated which include ATPbinding
cassette (ABC) transporter proteins, cytoplasmic vaults, alterations in
topoisomerase II and increased expression of glutathione-S-transferases, all of
which result in reduced chemotherapeutic efficacy.
Superficial bladder cancer is commonly treated with adjuvant intravesical
chemotherapy using mitomycin C or epirubicin (an anthracycline), following
surgical resection. However, despite this treatment, the recurrence rates of
these tumours can approach 60%. This high recurrence rate represents the
development of MDR in many cases.
Previous work using anthracycline fluorescence has shown that MDR cells
have reduced levels of anthracycline uptake and also demonstrate a
characteristic nuclear sparing of drug uptake. This nuclear sparing
phenomenon in MDR cells transcends tissue type and suggests that the
nuclear membrane may also play a role in MDR.
The work described herein discusses the current role of chemotherapy in the
treatment of superficial bladder cancer, mechanisms of MDR and the role of the
nuclear membrane in MDR. Following this our investigation of the role of the
nuclear membrane is described, using a number of novel techniques including
cell fusion and microinjection. In addition, we investigated MDR modulation by
verapamil, with analysis of changes in cellular, cytoplasmic and nuclear drug
uptake mediated by this known MDR reversing agent."],"dc:format":["text"],"dc:identifier.uri":["https://eprints.soton.ac.uk/67628/1/Featherstone_DM_Thesis_2009_PDF.pdf"],"dc:publisher.department":["Cancer Sciences (pre 2011 reorg)","School of Medicine"],"dc:publisher.institution":["University of Southampton"],"dc:relation.isreferencedby":["https://eprints.soton.ac.uk/67628/"],"dc:title":["Mechanisms of multidrug resistance in bladder cancer: the role of the nuclear membrane"],"dc:type":["Thesis"],"dc:type.qualificationlevel":["doctoral"],"dc:type.qualificationname":["Ph.D."]},"updated_at":"2026-07-24T04:36:02Z"}