GLORIA

GEOMAR Library Ocean Research Information Access

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 110, No. 47 ( 2013-11-19), p. 19059-19064
    Abstract: Antiangiogenic therapy has shown clear activity and improved survival benefit for certain tumor types. However, an incomplete understanding of the mechanisms of action of antiangiogenic agents has hindered optimization and broader application of this new therapeutic modality. In particular, the impact of antiangiogenic therapy on tumor blood flow and oxygenation status (i.e., the role of vessel pruning versus normalization) remains controversial. This controversy has become critical as multiple phase III trials of anti-VEGF agents combined with cytotoxics failed to show overall survival benefit in newly diagnosed glioblastoma (nGBM) patients and several other cancers. Here, we shed light on mechanisms of nGBM response to cediranib, a pan-VEGF receptor tyrosine kinase inhibitor, using MRI techniques and blood biomarkers in prospective phase II clinical trials of cediranib with chemoradiation vs. chemoradiation alone in nGBM patients. We demonstrate that improved perfusion occurs only in a subset of patients in cediranib-containing regimens, and is associated with improved overall survival in these nGBM patients. Moreover, an increase in perfusion is associated with improved tumor oxygenation status as well as with pharmacodynamic biomarkers, such as changes in plasma placenta growth factor and sVEGFR2. Finally, treatment resistance was associated with elevated plasma IL-8 and sVEGFR1 posttherapy. In conclusion, tumor perfusion changes after antiangiogenic therapy may distinguish responders vs. nonresponders early in the course of this expensive and potentially toxic form of therapy, and these results may provide new insight into the selection of glioblastoma patients most likely to benefit from anti-VEGF treatments.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2013
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 2
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 6 ( 2023-02-07)
    Abstract: Immune checkpoint blockers (ICBs) have failed in all phase III glioblastoma trials. Here, we found that ICBs induce cerebral edema in some patients and mice with glioblastoma. Through single-cell RNA sequencing, intravital imaging, and CD8 + T cell blocking studies in mice, we demonstrated that this edema results from an inflammatory response following antiprogrammed death 1 (PD1) antibody treatment that disrupts the blood–tumor barrier. Used in lieu of immunosuppressive corticosteroids, the angiotensin receptor blocker losartan prevented this ICB-induced edema and reprogrammed the tumor microenvironment, curing 20% of mice which increased to 40% in combination with standard of care treatment. Using a bihemispheric tumor model, we identified a “hot” tumor immune signature prior to losartan+anti-PD1 therapy that predicted long-term survival. Our findings provide the rationale and associated biomarkers to test losartan with ICBs in glioblastoma patients.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    RVK:
    RVK:
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
  • 3
    In: Physics in Medicine & Biology, IOP Publishing, Vol. 65, No. 22 ( 2020-11-21), p. 225020-
    Abstract: Dynamic susceptibility contrast (DSC) imaging is a widely used technique for assessment of cerebral blood volume (CBV). With combined gradient-echo and spin-echo DSC techniques, measures of the underlying vessel size and vessel architecture can be obtained from the vessel size index (VSI) and vortex area, respectively. However, how noise, and specifically the contrast-to-noise ratio (CNR), affect the estimations of these parameters has largely been overlooked. In order to address this issue, we have performed simulations to generate DSC signals with varying levels of CNR, defined by the peak of relaxation rate curve divided by the standard deviation of the baseline. Moreover, DSC data from 59 brain cancer patients were acquired at two different 3 T-scanners (N = 29 and N = 30, respectively), where CNR and relative parameter maps were obtained. Our simulations showed that the measured parameters were affected by CNR in different ways, where low CNR led to overestimations of CBV and underestimations of VSI and vortex area. In addition, a higher noise-sensitivity was found in vortex area than in CBV and VSI. Results from clinical data were consistent with simulations, and indicated that CNR 〈 4 gives highly unreliable measurements. Moreover, we have shown that the distribution of values in the tumour regions could change considerably when voxels with CNR below a given cut off are excluded when generating the relative parameter maps. The widespread use of CBV and attractive potential of VSI and vortex area, makes the noise-sensitivity of these parameters found in our study relevant for further use and development of the DSC imaging technique. Our results suggest that the CNR has considerable impact on the measured parameters, with the potential to affect the clinical interpretation of DSC-MRI, and should therefore be taken into account in the clinical decision-making process.
    Type of Medium: Online Resource
    ISSN: 0031-9155 , 1361-6560
    RVK:
    Language: Unknown
    Publisher: IOP Publishing
    Publication Date: 2020
    detail.hit.zdb_id: 1473501-5
    SSG: 12
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...