Document Detail

Tumour cell proliferation under hypoxic conditions in human head and neck squamous cell carcinomas.
MedLine Citation:
PMID:  17689286     Owner:  NLM     Status:  MEDLINE    
Two mechanisms of radiotherapy resistance of major importance in head and neck cancer are tumour cell repopulation and hypoxia. Hypoxic tumour cells that retain their clonogenic potential can survive radiation treatment and lead to local recurrences. The aim of this study was to quantify this cellular population in a cohort of human head and neck carcinomas and to investigate the prognostic significance. The proliferation marker iododeoxyuridine (IdUrd) and the hypoxia marker pimonidazole were administered intravenously prior to biopsy taking in patients with stage II-IV squamous cell carcinoma of the head and neck. Triple immunohistochemical staining of blood vessels, IdUrd and pimonidazole was performed and co-localization of IdUrd and pimonidazole was quantitatively assessed by computerized image analysis. The results were related with treatment outcome. Thirty-nine biopsies were analyzed. Tumours exhibited different patterns of proliferation and hypoxia but generally the IdUrd signal was found in proximity to blood vessels whereas pimonidazole binding was predominantly at a distance from vessels. Overall, no correlations were found between proliferative activity and oxygenation status. The fraction of IdUrd-labelled cells positive for pimonidazole ranged from 0% to 16.7% with a mean of 2.4% indicating that proliferative activity was low in hypoxic areas and occurring mainly in the well-oxygenated tumour compartments. IdUrd positive cells in hypoxic areas made up only 0.09% of the total viable tumour cell mass. There were no associations between the magnitude of this cell population and local tumour control or survival. Co-localization between proliferating cells and hypoxia in head and neck carcinomas was quantified using an immunohistochemical triple staining technique combined with a computerized simultaneous analysis of multiple parameters. The proportion of cells proliferating under hypoxic conditions was small and no correlation with treatment outcome could be found.
Karien I E M Wijffels; Henri A M Marres; Johannes P W Peters; Paulus F J W Rijken; Albert J van der Kogel; Johannes H A M Kaanders
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-08-06
Journal Detail:
Title:  Oral oncology     Volume:  44     ISSN:  1368-8375     ISO Abbreviation:  Oral Oncol.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-17     Completed Date:  2008-09-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  335-44     Citation Subset:  IM    
Department of Otorhinolaryngology, Head and Neck Surgery, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
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MeSH Terms
Aged, 80 and over
Carcinoma, Squamous Cell / blood supply,  pathology*,  radiotherapy
Cell Hypoxia*
Cell Proliferation
Head and Neck Neoplasms / blood supply,  pathology*,  radiotherapy
Idoxuridine / diagnostic use
Image Processing, Computer-Assisted / methods
Middle Aged
Neoplasm Staging
Neovascularization, Pathologic / metabolism
Nitroimidazoles / diagnostic use
Nucleic Acid Synthesis Inhibitors / diagnostic use
Radiation-Sensitizing Agents / diagnostic use
Treatment Outcome
Reg. No./Substance:
0/Nitroimidazoles; 0/Nucleic Acid Synthesis Inhibitors; 0/Radiation-Sensitizing Agents; 54-42-2/Idoxuridine; 70132-51-3/pimonidazole

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