Cristin-resultat-ID: 1646417
Sist endret: 16. januar 2019, 15:23
NVI-rapporteringsår: 2018
Resultat
Vitenskapelig artikkel
2018

DCE-MRI of Sunitinib-Induced Changes in Tumor Microvasculature and Hypoxia: A Study of Pancreatic Ductal Adenocarcinoma Xenografts

Bidragsytere:
  • Catherine E Sem Wegner
  • Anette Hauge
  • Trude Golimo Simonsen
  • Jon-Vidar Gaustad
  • Lise Mari Klepp Andersen og
  • Einar K Rofstad

Tidsskrift

Neoplasia
ISSN 1522-8002
e-ISSN 1476-5586
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2018
Volum: 20
Hefte: 7
Sider: 734 - 744
Open Access

Importkilder

Scopus-ID: 2-s2.0-85048526257

Beskrivelse Beskrivelse

Tittel

DCE-MRI of Sunitinib-Induced Changes in Tumor Microvasculature and Hypoxia: A Study of Pancreatic Ductal Adenocarcinoma Xenografts

Sammendrag

The purpose of this study was dual: to investigate (a) whether sunitinib may induce changes in tumor microvasculature and hypoxia in pancreatic ductal adenocarcinoma (PDAC) and (b) whether any changes can be detected by DCE-MRI. Sunitinib-treated and untreated control tumors of two PDAC xenograft models (BxPC-3 and Panc-1) were subjected to DCE-MRI before the imaged tumors were prepared for quantitative analysis of immunohistochemical preparations. Pimonidazole was used as a hypoxia marker, and fraction of hypoxic tissue (HFPim), density of CD31-positive microvessels (MVDCD31), and density of αSMA-positive microvessels (MVDαSMA) were measured. Parametric images of Ktrans and ve were derived from the DCE-MRI data by using the Tofts pharmacokinetic model. BxPC-3 tumors showed increased HFPim, decreased MVDCD31, unchanged MVDαSMA, and increased vessel maturation index (VMI = MVDαSMA/MVDCD31) after sunitinib treatment. The increase in VMI was seen because sunitinib induced selective pruning rather than maturation of αSMA-negative microvessels. Even though the microvessels in sunitinib-treated tumors were less abnormal than those in untreated tumors, this microvessel normalization did not improve the function of the microvascular network or normalize the tumor microenvironment. In Panc-1 tumors, HFPim, MVDCD31, MVDαSMA, and VMI were unchanged after sunitinib treatment. Median Ktrans increased with increasing MVDCD31 and decreased with increasing HFPim, and the correlations were similar for treated and untreated BXPC-3 and Panc-1 tumors. These observations suggest that sunitinib may induce significant changes in the microenvironment of PDACs, and furthermore, that Ktrans may be an adequate measure of tumor vascular density and hypoxia in untreated as well as sunitinib-treated PDACs.

Bidragsytere

Catherine E Sem Wegner

  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF

Anette Hauge

  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF

Trude Golimo Simonsen

  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF

Jon-Vidar Gaustad

  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF

Lise Mari Klepp Hansem

Bidragsyterens navn vises på dette resultatet som Lise Mari Klepp Andersen
  • Tilknyttet:
    Forfatter
    ved Seksjon for strålingbiologi ved Oslo universitetssykehus HF
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