Hypoxic cell turnover in different solid tumor lines

Ljungkvist, Anna S. E.; Bussink, Johan; Kaanders, Johannes H.A.M.; Rijken, Paulus F.J.W.; Begg, Adrian C.; Raleigh, James A.; Kogel, Albert J. van der

doi:10.1016/j.ijrobp.2005.03.049

Cited by 77 publications

(64 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These bioreductive compounds differ only in the immunologically detectable side chain. Double staining of consecutively injected markers in nontreated tumors results in a good spatial match, although pimonidazole generally covers a slightly larger area than CCI-103F (36,37). Pimonidazole was dissolved in saline and injected intraperitoneally (i.p.)…”

Section: Tumor Model and Markers Of Hypoxia Perfusion And Proliferationmentioning

confidence: 99%

“…Pimonidazole, which is very stable once it is reduced and bound in hypoxic cells (37,43), was given 1 h before irradiation followed by the mixture of CCI-103F and BrdUrd at 4, 8 and 28 h after irradiation ( Fig. 1).…”

Section: Irradiation and Experimental Setupmentioning

confidence: 99%

“…At 200ϫ magnification, composite images with pimonidazole and either proliferation or apoptosis were obtained. The grayscale images were thresholded into binary images (37,47), which were used for quantitative analysis of spatial relationships between proliferation, hypoxia and apoptosis. A consecutive H&E-stained tumor section was used to define the tumor area excluding non-tumor tissue, necrosis and staining artifacts.…”

Section: Image Acquisition Processing and Analysismentioning

confidence: 99%

“…Bioreductive hypoxia markers can be reduced and bound only in viable cells (intact and metabolically active). Therefore, elimination of pimonidazole-positive cells reflects clearance of cells that have died in the interval between pimonidazole injection and tumor harvest, reflecting the turnover of initially hypoxic cells (37). This was illustrated as a reduction of the tumor areas showing co-localization of pimonidazole and CCI-103F (yellow).…”

Section: Dynamics Of Hypoxia In Unirradiated Compared To Irradiated Tmentioning

confidence: 99%

“…Several exogenous markers of hypoxia such as pimonidazole, EF5 and CCI-103F are available (7,8,32,35). With consecutive injection of two hypoxic cell markers, pimonidazole and CCI-103F, treatment-induced changes in hypoxia can be measured, allowing each tumor to serve as its own control (36)(37)(38). For detection of proliferation, the exogenous markers bromodeoxyuridine (BrdUrd) and iododeoxyuridine (IdUrd) can be used (4,39,40).…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Dynamics of Hypoxia, Proliferation and Apoptosis after Irradiation in a Murine Tumor Model

et al. 2006

Self Cite

View full text Add to dashboard Cite

Section: Tumor Model and Markers Of Hypoxia Perfusion And Proliferationmentioning

confidence: 99%

Section: Irradiation and Experimental Setupmentioning

confidence: 99%

Section: Image Acquisition Processing and Analysismentioning

confidence: 99%

Section: Dynamics Of Hypoxia In Unirradiated Compared To Irradiated Tmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Dynamics of Hypoxia, Proliferation and Apoptosis after Irradiation in a Murine Tumor Model

et al. 2006

Self Cite

View full text Add to dashboard Cite

Comparison between pimonidazole binding, oxygen electrode measurements, and expression of endogenous hypoxia markers in cancer of the uterine cervix

Janković¹,

Aquino‐Parsons²,

Raleigh³

et al. 2006

Cytometry Part B Clinical

View full text Add to dashboard Cite

Background: Although tumor hypoxia has been associated with a more aggressive phenotype and lower cure rate, there is no consensus as to the method best suited for routine measurement. Binding of the chemical hypoxia marker, pimonidazole, and expression of the endogenous hypoxia markers HIF-1a and CAIX were compared for their ability to detect hypoxia in tumor biopsies from 67 patients with advanced carcinoma of the cervix.Methods: Two biopsies were taken one day after administration of pimonidazole and were analyzed for pimonidazole binding using flow cytometry or immunohistochemistry. CAIX and HIF-1a expression and degree of colocalization were measured in sequential antibody-stained sections. Patient subsets were examined for tumor oxygen tension using an Eppendorf electrode, S phase DNA content, or change in HIF1a expression over the course of treatment.Results: Approximately 6% of the tumor area stained positive for pimonidazole, HIF-1a, or CAIX. The CAIX positive fraction correlated with the pimonidazole positive fraction (r = 0.60). Weaker but significant correlations were observed between pimonidazole and HIF-1a (r = 0.31) and CAIX and HIF-1a (r = 0.41). Taking the extent of marker colocalization into consideration increased the confidence that all markers were identifying hypoxic regions. Over 65% of stained areas showed a high degree of colocalization with the other markers. Oxygen microelectrode measurements and S phase fraction were not correlated with the hypoxic fraction measured using the three hypoxia markers. HIF-1a levels tended to decrease with time after the start of therapy.Conclusions: Endogenous hypoxia marker binding shows reasonable agreement, in extent and location, with binding of pimonidazole. CAIX staining pattern is a better match to the pimonidazole staining pattern than is HIF-1a, and high CAIX expression in the absence (or low levels) of HIF-1a may indicate a different biology. q

show abstract

Tumor microenvironment in head and neck squamous cell carcinomas: Predictive value and clinical relevance of hypoxic markers. A review

et al. 2007

Self Cite

View full text Add to dashboard Cite

show abstract

Hypoxic cell turnover in different solid tumor lines

Cited by 77 publications

References 41 publications

Dynamics of Hypoxia, Proliferation and Apoptosis after Irradiation in a Murine Tumor Model

Dynamics of Hypoxia, Proliferation and Apoptosis after Irradiation in a Murine Tumor Model

Comparison between pimonidazole binding, oxygen electrode measurements, and expression of endogenous hypoxia markers in cancer of the uterine cervix

Tumor microenvironment in head and neck squamous cell carcinomas: Predictive value and clinical relevance of hypoxic markers. A review

Contact Info

Product

Resources

About