Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts.

2.50
Hdl Handle:
http://hdl.handle.net/10541/82315
Title:
Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts.
Authors:
Cummings, Jeffrey; Ritchie, Alison; Butler, John; Ward, Timothy H; Langdon, Simon
Abstract:
BACKGROUND: RH1 and MeDZQ represent novel aziridinylbenzoquinones that can be activated by DT-diaphorase to form unique DNA lesions. RH1 is due to enter a phase 1 clinical trial in the United Kingdom in the summer of 2003, where pharmacodynamic monitoring of DT-diaphorase will be performed. MATERIALS AND METHODS: The antitumour efficacy of RH1 and MeDZQ has been studied in 4 human xenografts (3 non-small cell lung cancer and 1 colon cancer), and compared to the level of constitutive DT-Diaphorase activity measured by the DCPIP assay. RESULTS: The 4 xenografts exhibited a wide range of DT-diaphorase activity (4.8-303 nmol/min/mg). Greater antitumour activity was recorded in the xenografts expressing high levels of DT-diaphorase (e.g. NX002, DT-diaphorase activity, 303 +/- 52 nmol/min/mg, T/C to MeDZQ, 33.3% and to RH1, 43.4%). CONCLUSION: These data add in vivo support to a role for DT-Diaphorase in the antitumour activity of RH1.
Affiliation:
Cancer Research UK, Edinburgh Medical Oncology Unit, Western General Hospital, Edinburgh, EH4 2XR, U.K. jcummings@picr.man.ac.uk
Citation:
Activity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts., 23 (5A):3979-83 Anticancer Res.
Journal:
Anticancer Research
Issue Date:
23-Sep-2009
URI:
http://hdl.handle.net/10541/82315
PubMed ID:
14666706
Type:
Article
Language:
en
ISSN:
0250-7005
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorCummings, Jeffrey-
dc.contributor.authorRitchie, Alison-
dc.contributor.authorButler, John-
dc.contributor.authorWard, Timothy H-
dc.contributor.authorLangdon, Simon-
dc.date.accessioned2009-09-23T11:45:22Z-
dc.date.available2009-09-23T11:45:22Z-
dc.date.issued2009-09-23T11:45:22Z-
dc.identifier.citationActivity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts., 23 (5A):3979-83 Anticancer Res.en
dc.identifier.issn0250-7005-
dc.identifier.pmid14666706-
dc.identifier.urihttp://hdl.handle.net/10541/82315-
dc.description.abstractBACKGROUND: RH1 and MeDZQ represent novel aziridinylbenzoquinones that can be activated by DT-diaphorase to form unique DNA lesions. RH1 is due to enter a phase 1 clinical trial in the United Kingdom in the summer of 2003, where pharmacodynamic monitoring of DT-diaphorase will be performed. MATERIALS AND METHODS: The antitumour efficacy of RH1 and MeDZQ has been studied in 4 human xenografts (3 non-small cell lung cancer and 1 colon cancer), and compared to the level of constitutive DT-Diaphorase activity measured by the DCPIP assay. RESULTS: The 4 xenografts exhibited a wide range of DT-diaphorase activity (4.8-303 nmol/min/mg). Greater antitumour activity was recorded in the xenografts expressing high levels of DT-diaphorase (e.g. NX002, DT-diaphorase activity, 303 +/- 52 nmol/min/mg, T/C to MeDZQ, 33.3% and to RH1, 43.4%). CONCLUSION: These data add in vivo support to a role for DT-Diaphorase in the antitumour activity of RH1.en
dc.language.isoenen
dc.subjectLung Canceren
dc.subjectXenograft Model Antitumour Assaysen
dc.subjectColonic Canceren
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshAziridines-
dc.subject.meshBenzoquinones-
dc.subject.meshCarcinoma, Non-Small-Cell Lung-
dc.subject.meshColonic Neoplasms-
dc.subject.meshDose-Response Relationship, Drug-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshLung Neoplasms-
dc.subject.meshMice-
dc.subject.meshMice, Nude-
dc.subject.meshNAD(P)H Dehydrogenase (Quinone)-
dc.subject.meshTransplantation, Heterologous-
dc.subject.meshXenograft Model Antitumor Assays-
dc.titleActivity profile of the novel aziridinylbenzoquinones MeDZQ and RH1 in human tumour xenografts.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK, Edinburgh Medical Oncology Unit, Western General Hospital, Edinburgh, EH4 2XR, U.K. jcummings@picr.man.ac.uken
dc.identifier.journalAnticancer Researchen
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