Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer
Objective To examine mitomycin‐C (MMC)‐induced apoptosis in an ex vivo model of superficial TCC, and relate it to the in vivo response to chemotherapy. Materials and methods Dose‐ and time‐response curves were constructed to determine the optimal conditions for the induction of apoptosis by MMC in a...
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| Veröffentlicht in: | BJU international 2000-05, Vol.85 (7), p.911-917 |
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| creator | Kelly, J.D. Williamson, K.E. Weir, H.P. McManus, D.T. Hamilton, P.W. Keane, P.F. Johnston, S.R. |
| description | Objective To examine mitomycin‐C (MMC)‐induced apoptosis in an ex vivo model of superficial TCC, and relate it to the in vivo response to chemotherapy.
Materials and methods Dose‐ and time‐response curves were constructed to determine the optimal conditions for the induction of apoptosis by MMC in an ex vivo model of superficial bladder cancer. Subsequently, 41 individual tumours were exposed to MMC in the model and the effects assessed by measuring of apoptosis before and after chemotherapy. The relationships between tumour grade and stage and the intrinsic and induced apoptotic counts were determined. In tandem, in a clinical study, the relationship between in vivo response of a marker tumour to MMC and the ex vivo induction of apoptosis was determined.
Results In the ex vivo model, apoptosis was induced at a MMC concentration of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic apoptotic index (AI) was higher with increased grade and stage of tumour (P = 0.048). There was no correlation between the intrinsic AI and the AI after treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did not increase above a predetermined response threshold and these tumours were considered resistant to MMC. Resistance to MMC was related to tumour grade (P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy. There was a significant association between ex vivo sensitivity and in vivo marker tumour response (P = 0.02).
Conclusions Apoptosis is differentially induced in an ex vivo incubation model of superficial TCC by MMC and evidence suggests that this response matches that seen in vivo. The measurement of apoptosis before therapy does not predict the apoptotic response of a tumour to chemotherapy. The ability to undergo apoptosis correlates with clinical outcome. |
| doi_str_mv | 10.1046/j.1464-410x.2000.00667.x |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_71083242</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>71083242</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3937-d8115e500a3c076069775054b53df5aa18a4c598300db8b3407c24af5f07a2173</originalsourceid><addsrcrecordid>eNqNkEtOwzAQhi0EolC4AvICsWsYx69EYgMVj6IiNlRiZzmOI7lK4hK3pd1xBM7ISUhoK1iy8sjz_TOjDyFMICLAxOU0IkywASOwimIAiACEkNFqDx3tGq_7uxpS0UPHIUwB2g_BD1GPgExjIsURehrV-cLMna-xL7Ce-dncBxdwtsaVm_tqbVz99fE5xK7GusZ2hZdu6XHlc1t2iazUeW4bbHRtbHOCDgpdBnu6fftocnf7MnwYjJ_vR8Pr8cDQlMpBnhDCLQfQ1IAUIFIpOXCWcZoXXGuSaGZ4mlCAPEsyykCamOmCFyB1ezfto4vN3Fnj3xY2zFXlgrFlqWvrF0FJAgmNWdyCyQY0jQ-hsYWaNa7SzVoRUJ1KNVWdJdWpVJ1K9aNSrdro2XbHIqts_ie4cdcC51tAB6PLomkVuPDLUclS4C12tcHeXWnX_96vbh4nbUG_AXRWjpc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>71083242</pqid></control><display><type>article</type><title>Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer</title><source>MEDLINE</source><source>Wiley Online Library Journals Frontfile Complete</source><creator>Kelly, J.D. ; Williamson, K.E. ; Weir, H.P. ; McManus, D.T. ; Hamilton, P.W. ; Keane, P.F. ; Johnston, S.R.</creator><creatorcontrib>Kelly, J.D. ; Williamson, K.E. ; Weir, H.P. ; McManus, D.T. ; Hamilton, P.W. ; Keane, P.F. ; Johnston, S.R.</creatorcontrib><description>Objective To examine mitomycin‐C (MMC)‐induced apoptosis in an ex vivo model of superficial TCC, and relate it to the in vivo response to chemotherapy.
Materials and methods Dose‐ and time‐response curves were constructed to determine the optimal conditions for the induction of apoptosis by MMC in an ex vivo model of superficial bladder cancer. Subsequently, 41 individual tumours were exposed to MMC in the model and the effects assessed by measuring of apoptosis before and after chemotherapy. The relationships between tumour grade and stage and the intrinsic and induced apoptotic counts were determined. In tandem, in a clinical study, the relationship between in vivo response of a marker tumour to MMC and the ex vivo induction of apoptosis was determined.
Results In the ex vivo model, apoptosis was induced at a MMC concentration of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic apoptotic index (AI) was higher with increased grade and stage of tumour (P = 0.048). There was no correlation between the intrinsic AI and the AI after treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did not increase above a predetermined response threshold and these tumours were considered resistant to MMC. Resistance to MMC was related to tumour grade (P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy. There was a significant association between ex vivo sensitivity and in vivo marker tumour response (P = 0.02).
Conclusions Apoptosis is differentially induced in an ex vivo incubation model of superficial TCC by MMC and evidence suggests that this response matches that seen in vivo. The measurement of apoptosis before therapy does not predict the apoptotic response of a tumour to chemotherapy. The ability to undergo apoptosis correlates with clinical outcome.</description><identifier>ISSN: 1464-4096</identifier><identifier>EISSN: 1464-410X</identifier><identifier>DOI: 10.1046/j.1464-410x.2000.00667.x</identifier><identifier>PMID: 10792176</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Science Ltd</publisher><subject>Antibiotics, Antineoplastic - therapeutic use ; Antineoplastic agents ; Apoptosis ; Biological and medical sciences ; bladder ; Carcinoma, Transitional Cell - drug therapy ; Carcinoma, Transitional Cell - pathology ; Carcinoma, Transitional Cell - physiopathology ; Chemotherapy ; Dose-Response Relationship, Drug ; Humans ; Medical sciences ; Mitomycin - therapeutic use ; Pharmacology. Drug treatments ; TCC ; Time Factors ; tissue culture ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms - drug therapy ; Urinary Bladder Neoplasms - pathology ; Urinary Bladder Neoplasms - physiopathology</subject><ispartof>BJU international, 2000-05, Vol.85 (7), p.911-917</ispartof><rights>2000 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3937-d8115e500a3c076069775054b53df5aa18a4c598300db8b3407c24af5f07a2173</citedby><cites>FETCH-LOGICAL-c3937-d8115e500a3c076069775054b53df5aa18a4c598300db8b3407c24af5f07a2173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1046%2Fj.1464-410x.2000.00667.x$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1046%2Fj.1464-410x.2000.00667.x$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1374905$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10792176$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kelly, J.D.</creatorcontrib><creatorcontrib>Williamson, K.E.</creatorcontrib><creatorcontrib>Weir, H.P.</creatorcontrib><creatorcontrib>McManus, D.T.</creatorcontrib><creatorcontrib>Hamilton, P.W.</creatorcontrib><creatorcontrib>Keane, P.F.</creatorcontrib><creatorcontrib>Johnston, S.R.</creatorcontrib><title>Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer</title><title>BJU international</title><addtitle>BJU Int</addtitle><description>Objective To examine mitomycin‐C (MMC)‐induced apoptosis in an ex vivo model of superficial TCC, and relate it to the in vivo response to chemotherapy.
Materials and methods Dose‐ and time‐response curves were constructed to determine the optimal conditions for the induction of apoptosis by MMC in an ex vivo model of superficial bladder cancer. Subsequently, 41 individual tumours were exposed to MMC in the model and the effects assessed by measuring of apoptosis before and after chemotherapy. The relationships between tumour grade and stage and the intrinsic and induced apoptotic counts were determined. In tandem, in a clinical study, the relationship between in vivo response of a marker tumour to MMC and the ex vivo induction of apoptosis was determined.
Results In the ex vivo model, apoptosis was induced at a MMC concentration of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic apoptotic index (AI) was higher with increased grade and stage of tumour (P = 0.048). There was no correlation between the intrinsic AI and the AI after treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did not increase above a predetermined response threshold and these tumours were considered resistant to MMC. Resistance to MMC was related to tumour grade (P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy. There was a significant association between ex vivo sensitivity and in vivo marker tumour response (P = 0.02).
Conclusions Apoptosis is differentially induced in an ex vivo incubation model of superficial TCC by MMC and evidence suggests that this response matches that seen in vivo. The measurement of apoptosis before therapy does not predict the apoptotic response of a tumour to chemotherapy. The ability to undergo apoptosis correlates with clinical outcome.</description><subject>Antibiotics, Antineoplastic - therapeutic use</subject><subject>Antineoplastic agents</subject><subject>Apoptosis</subject><subject>Biological and medical sciences</subject><subject>bladder</subject><subject>Carcinoma, Transitional Cell - drug therapy</subject><subject>Carcinoma, Transitional Cell - pathology</subject><subject>Carcinoma, Transitional Cell - physiopathology</subject><subject>Chemotherapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Mitomycin - therapeutic use</subject><subject>Pharmacology. Drug treatments</subject><subject>TCC</subject><subject>Time Factors</subject><subject>tissue culture</subject><subject>Tumor Cells, Cultured</subject><subject>Urinary Bladder Neoplasms - drug therapy</subject><subject>Urinary Bladder Neoplasms - pathology</subject><subject>Urinary Bladder Neoplasms - physiopathology</subject><issn>1464-4096</issn><issn>1464-410X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkEtOwzAQhi0EolC4AvICsWsYx69EYgMVj6IiNlRiZzmOI7lK4hK3pd1xBM7ISUhoK1iy8sjz_TOjDyFMICLAxOU0IkywASOwimIAiACEkNFqDx3tGq_7uxpS0UPHIUwB2g_BD1GPgExjIsURehrV-cLMna-xL7Ce-dncBxdwtsaVm_tqbVz99fE5xK7GusZ2hZdu6XHlc1t2iazUeW4bbHRtbHOCDgpdBnu6fftocnf7MnwYjJ_vR8Pr8cDQlMpBnhDCLQfQ1IAUIFIpOXCWcZoXXGuSaGZ4mlCAPEsyykCamOmCFyB1ezfto4vN3Fnj3xY2zFXlgrFlqWvrF0FJAgmNWdyCyQY0jQ-hsYWaNa7SzVoRUJ1KNVWdJdWpVJ1K9aNSrdro2XbHIqts_ie4cdcC51tAB6PLomkVuPDLUclS4C12tcHeXWnX_96vbh4nbUG_AXRWjpc</recordid><startdate>200005</startdate><enddate>200005</enddate><creator>Kelly, J.D.</creator><creator>Williamson, K.E.</creator><creator>Weir, H.P.</creator><creator>McManus, D.T.</creator><creator>Hamilton, P.W.</creator><creator>Keane, P.F.</creator><creator>Johnston, S.R.</creator><general>Blackwell Science Ltd</general><general>Blackwell</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200005</creationdate><title>Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer</title><author>Kelly, J.D. ; Williamson, K.E. ; Weir, H.P. ; McManus, D.T. ; Hamilton, P.W. ; Keane, P.F. ; Johnston, S.R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3937-d8115e500a3c076069775054b53df5aa18a4c598300db8b3407c24af5f07a2173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Antibiotics, Antineoplastic - therapeutic use</topic><topic>Antineoplastic agents</topic><topic>Apoptosis</topic><topic>Biological and medical sciences</topic><topic>bladder</topic><topic>Carcinoma, Transitional Cell - drug therapy</topic><topic>Carcinoma, Transitional Cell - pathology</topic><topic>Carcinoma, Transitional Cell - physiopathology</topic><topic>Chemotherapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Mitomycin - therapeutic use</topic><topic>Pharmacology. Drug treatments</topic><topic>TCC</topic><topic>Time Factors</topic><topic>tissue culture</topic><topic>Tumor Cells, Cultured</topic><topic>Urinary Bladder Neoplasms - drug therapy</topic><topic>Urinary Bladder Neoplasms - pathology</topic><topic>Urinary Bladder Neoplasms - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kelly, J.D.</creatorcontrib><creatorcontrib>Williamson, K.E.</creatorcontrib><creatorcontrib>Weir, H.P.</creatorcontrib><creatorcontrib>McManus, D.T.</creatorcontrib><creatorcontrib>Hamilton, P.W.</creatorcontrib><creatorcontrib>Keane, P.F.</creatorcontrib><creatorcontrib>Johnston, S.R.</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>BJU international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kelly, J.D.</au><au>Williamson, K.E.</au><au>Weir, H.P.</au><au>McManus, D.T.</au><au>Hamilton, P.W.</au><au>Keane, P.F.</au><au>Johnston, S.R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer</atitle><jtitle>BJU international</jtitle><addtitle>BJU Int</addtitle><date>2000-05</date><risdate>2000</risdate><volume>85</volume><issue>7</issue><spage>911</spage><epage>917</epage><pages>911-917</pages><issn>1464-4096</issn><eissn>1464-410X</eissn><abstract>Objective To examine mitomycin‐C (MMC)‐induced apoptosis in an ex vivo model of superficial TCC, and relate it to the in vivo response to chemotherapy.
Materials and methods Dose‐ and time‐response curves were constructed to determine the optimal conditions for the induction of apoptosis by MMC in an ex vivo model of superficial bladder cancer. Subsequently, 41 individual tumours were exposed to MMC in the model and the effects assessed by measuring of apoptosis before and after chemotherapy. The relationships between tumour grade and stage and the intrinsic and induced apoptotic counts were determined. In tandem, in a clinical study, the relationship between in vivo response of a marker tumour to MMC and the ex vivo induction of apoptosis was determined.
Results In the ex vivo model, apoptosis was induced at a MMC concentration of 0.5 mg/mL after an incubation time of 8 h. In 41 tumours the intrinsic apoptotic index (AI) was higher with increased grade and stage of tumour (P = 0.048). There was no correlation between the intrinsic AI and the AI after treatment with MMC (induced AI). In 21 tumours (51%) the induced AI did not increase above a predetermined response threshold and these tumours were considered resistant to MMC. Resistance to MMC was related to tumour grade (P = 0.037) with a trend for G3 pT1 tumours to be resistant to the therapy. There was a significant association between ex vivo sensitivity and in vivo marker tumour response (P = 0.02).
Conclusions Apoptosis is differentially induced in an ex vivo incubation model of superficial TCC by MMC and evidence suggests that this response matches that seen in vivo. The measurement of apoptosis before therapy does not predict the apoptotic response of a tumour to chemotherapy. The ability to undergo apoptosis correlates with clinical outcome.</abstract><cop>Oxford, UK</cop><pub>Blackwell Science Ltd</pub><pmid>10792176</pmid><doi>10.1046/j.1464-410x.2000.00667.x</doi><tpages>7</tpages></addata></record> |
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| subjects | Antibiotics, Antineoplastic - therapeutic use Antineoplastic agents Apoptosis Biological and medical sciences bladder Carcinoma, Transitional Cell - drug therapy Carcinoma, Transitional Cell - pathology Carcinoma, Transitional Cell - physiopathology Chemotherapy Dose-Response Relationship, Drug Humans Medical sciences Mitomycin - therapeutic use Pharmacology. Drug treatments TCC Time Factors tissue culture Tumor Cells, Cultured Urinary Bladder Neoplasms - drug therapy Urinary Bladder Neoplasms - pathology Urinary Bladder Neoplasms - physiopathology |
| title | Induction of apoptosis by mitomycin‐C in an ex vivo model of bladder cancer |
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