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Drug-induced alterations in tumour perfusion yield increases in tumour cell radiosensitivity.
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MedLine Citation:
PMID:  11720448     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The perfusion of human tumour xenografts was manipulated by administration of diltiazem and pentoxifylline, and the extent that observed changes in tumour perfusion altered tumour radiosensitivity was determined. 2 tumour systems having intrinsically different types of hypoxia were studied. The responses of SiHa tumours, which have essentially no transient hypoxia, were compared to the responses of WiDr tumours, which contain chronically and transiently hypoxic cells. We found that relatively modest increases in net tumour perfusion increased tumour cell radiosensitivity in WiDr tumours to a greater extent than in SiHa tumours. Moreover, redistribution of blood flow within WiDr tumours was observed on a micro-regional level that was largely independent of changes in net tumour perfusion. Through fluorescence-activated cell sorting coupled with an in vivo-in vitro cloning assay, increases in the radiosensitivity of WiDr tumour cells at intermediate levels of oxygenation were observed, consistent with the expectation that a redistribution of tumour blood flow had increased oxygen delivery to transiently hypoxic tumour cells. Our data therefore suggest that drug-induced changes in tumour micro-perfusion can alter the radiosensitivity of transiently hypoxic tumour cells, and that increasing the radiosensitivity of tumour cells at intermediate levels of oxygenation is therapeutically relevant.
Authors:
K L Bennewith; R E Durand
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  British journal of cancer     Volume:  85     ISSN:  0007-0920     ISO Abbreviation:  Br. J. Cancer     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-11-26     Completed Date:  2002-02-14     Revised Date:  2010-09-14    
Medline Journal Info:
Nlm Unique ID:  0370635     Medline TA:  Br J Cancer     Country:  Scotland    
Other Details:
Languages:  eng     Pagination:  1577-84     Citation Subset:  IM    
Affiliation:
Medical Biophysics Department, British Columbia Cancer Research Centre, 601 West 10th Avenue, Vancouver, B.C., Canada V5Z 1L3.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium Channel Blockers / pharmacology*
Diltiazem / pharmacology*
Dose-Response Relationship, Drug
Flow Cytometry
Hematologic Agents / pharmacology*
Humans
Kinetics
Mice
Neoplasms / blood,  radiotherapy*
Pentoxifylline / pharmacology*
Perfusion
Radiation Tolerance*
Regional Blood Flow
Rubidium Radioisotopes / administration & dosage
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Chemical
Reg. No./Substance:
0/Calcium Channel Blockers; 0/Hematologic Agents; 0/Rubidium Radioisotopes; 42399-41-7/Diltiazem; 6493-05-6/Pentoxifylline
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Br J Cancer
ISSN: 0007-0920
ISSN: 1532-1827
Publisher: Nature Publishing Group
Article Information
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Copyright 2001, Cancer Research Campaign
Received Day: 11 Month: 12 Year: 2000
Revision Received Day: 17 Month: 07 Year: 2001
Accepted Day: 19 Month: 07 Year: 2001
Print publication date: Month: 11 Year: 2001
Volume: 85 Issue: 10
First Page: 1577 Last Page: 1584
ID: 2363939
Publisher Item Identifier: 6692123
DOI: 10.1054/bjoc.2001.2123
PubMed Id: 11720448

Drug-induced alterations in tumour perfusion yield increases in tumour cell radiosensitivity
K L Bennewith1
R E Durand1
1Medical Biophysics Department, British Columbia Cancer Research Centre, 601 West 10th Avenue, Vancouver, V5Z 1L3, Canada


Article Categories:
  • Regular Article

Keywords: hypoxia, tumour perfusion, radiosensitivity, pentoxifylline, diltiazem.

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