Effect of vascular marker Hoechst 33342 on tumour perfusion and cardiovascular function in the mouse

Trotter, M.J.; Olive, Peggy L.; Dj, Chaplin

doi:10.1038/bjc.1990.406

Cited by 38 publications

(21 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This approach is original, objective, and feasible when HPLC technology is available. H33342 is vasoactive at doses above 10 mg kg À1 (Trotter et al, 1990). However, the validity of the data is not affected, as such an effect would only be expected to influence absolute, but not relative, uptake.…”

Section: Determination Of Vascular Function Using the Perfusion Markementioning

confidence: 93%

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Wildiers¹,

Guetens²,

Boeck³

et al. 2003

Br J Cancer

303

150

View full text Add to dashboard Cite

Promising preclinical activity with agents blocking the function of vascular endothelial growth factor (VEGF) has been observed in various cancer types, especially with combination therapy. However, these drugs decrease microvessel density, and it is not known whether this reduced vessel density (VD) results in decreased delivery of concomitantly administered classical anticancer drugs. We designed an in vivo study to investigate the relation between VEGF-blocking therapy, tumoral blood vessels, and intratumoral uptake of anticancer drugs. Nude NMRI mice bearing colon adenocarcinoma (HT29) were treated with the anti-VEGFmAb A4.6.1 or placebo. After 1 week, CPT-11 was administered 1 h prior to killing the animals. In A4.6.1 treated tumours, there was a significant decrease in VD, more pronounced with potentially functional large vessels than endothelial cords. Interestingly, a trend to increased intratumoral CPT-11 concentration was observed (P ¼ 0.09). In parallel, we measured an increase in tumour perfusion, as estimated by high-performance liquid chromatography determination of intratumoural Hoechst 33342 concentration. In the growth delay study, CPT-11 was at least equally effective with or without pretreatment with A4.6.1. These data suggest that tumour vascular function and tumour uptake of anticancer drugs improve with VEGF-blocking therapy, and indicate the relevance for further investigations.

show abstract

Section: Determination Of Vascular Function Using the Perfusion Markementioning

confidence: 93%

Effect of antivascular endothelial growth factor treatment on the intratumoral uptake of CPT-11

Wildiers¹,

Guetens²,

Boeck³

et al. 2003

Br J Cancer

303

150

View full text Add to dashboard Cite

show abstract

“…Hoechst 33342 is known to be vasoactive at high concentrations (Trotter et al, 1990), so intratumour injection of this drug could lead to a localized decrease in blood flow and might explain the hypoxia associated with the injection site. Alternatively, injection of a significant volume of fluid into a tumour could increase interstitial fluid pressure, leading to vascular collapse and a subsequent increase in hypoxia.…”

Section: Resultsmentioning

confidence: 99%

Local hypoxia is produced at sites of intratumour injection

2002

Br J Cancer

View full text Add to dashboard Cite

Intratumour injection, commonly used for gene or drug delivery but also associated with needle biopsy or insertion of invasive measuring devices, may damage tumour microvessels. To examine this possibility, SCCVII tumours grown subcutaneously in C3H mice were injected with a 26 gauge needle containing 0.1 ml of the fluorescent dye Hoechst 33342 to label cells lining the track of the needle. Hoechst-labelled cells sorted from these tumours were more sensitive to killing by hypoxic cell cytotoxins (tirapazamine, RSU-1069) and less sensitive to damage by ionizing radiation. Hoechst-labelled cells also bound the hypoxia marker pimonidazole when given by i.p. injection. Intratumour injection transiently increased hypoxia from 18 to 70% in the tumour cells adjacent to the track of the needle. The half-time for return to pre-treatment oxygenation was about 30 min; oxygenation of tumour cells along the track had recovered by 20 h after intratumour injection. This effect could have significant implications for intratumour injection of drugs, cytokines or vectors that are affected by the oxygenation status of the tumour cells as well as potential effects on biodistribution via local microvasculature.

show abstract

“…(3) require documentation of the validity of the method to be reliable (Trotter et al, 1990). The validity of the method depends on an adequate choice of dye concentrations since both dyes show dose-dependent vasoactive effects (Trotter et al, 1989b(Trotter et al, , 1990. Usable combinations of dye concentrations were found for the four tumour lines studied here by varying the concentrations of Hoechst 33342 and DiOC7(3) systematically.…”

Section: Resultsmentioning

confidence: 89%

“…The level of perfusion mismatch in these regions ranged from 1% to 7% following simultaneous administration (Figure 3a) and from 1% to 4% following sequential administration ( Figure 3b). (3) require documentation of the validity of the method to be reliable (Trotter et al, 1990). The validity of the method depends on an adequate choice of dye concentrations since both dyes show dose-dependent vasoactive effects (Trotter et al, 1989b(Trotter et al, , 1990.…”

Section: Resultsmentioning

confidence: 99%

“…Hoechst 33342 and DiOC7(3) have short distribution half-lives in blood and provide selective staining of tumour cells adjacent to functional vessels (Trotter et al, 1989b(Trotter et al, , 1990. The excitation and emission spectra differ between the dyes, allowing separate detection by fluorescence microscopy (Trotter et al, 1989a).…”

Section: Double-fluorescent Staining Techniquementioning

confidence: 99%

See 1 more Smart Citation