التفاصيل البيبلوغرافية
| العنوان: |
Non-Invasive Monitoring of Stromal Biophysics with Targeted Depletion of Hyaluronan in Pancreatic Ductal Adenocarcinoma. |
| المؤلفون: |
Maloney, Ezekiel, DuFort, Christopher C., Provenzano, Paolo P., Farr, Navid, Carlson, Markus A., Vohra, Ravneet, Park, Joshua, Hingorani, Sunil R., Lee, Donghoon |
| المصدر: |
Cancers; Jun2019, Vol. 11 Issue 6, p772, 1p |
| مصطلحات موضوعية: |
ADENOCARCINOMA, BIOPHYSICS, COLLAGEN, DIFFUSION, FIBROBLASTS, GLYCOSAMINOGLYCANS, HYALURONIC acid, MAGNETIC resonance imaging, PANCREATIC tumors, PERFUSION, IMAGING phantoms, DUCTAL carcinoma |
| مستخلص: |
Pancreatic ductal adenocarcinoma (PDA) is characterized by a pronounced fibroinflammatory stromal reaction consisting of inordinate levels of hyaluronan (HA), collagen, immune cells, and activated fibroblasts that work in concert to generate a robust physical barrier to the perfusion and diffusion of small molecule therapeutics. The targeted depletion of hyaluronan with a PEGylated recombinant human hyaluronidase (PEGPH20) lowers interstitial gel–fluid pressures and re-expands collapsed intratumoral vasculature, improving the delivery of concurrently administered agents. Here we report a non-invasive means of assessing biophysical responses to stromal intervention with quantitative multiparametric magnetic resonance imaging (MRI) at 14 Tesla (T). We found that spin-spin relaxation time T2 values and glycosaminoglycan chemical exchange saturation transfer (GagCEST) values decreased at 24 h, reflecting depletion of intratumoral HA content, and that these parameters recovered at 7 days concurrent with replenishment of intratumoral HA. This was also reflected in an increase in low-b apparent diffusion coefficient (ADC) at 24 h, consistent with improved tumor perfusion that again normalized at 7 days after treatment. Phantom imaging suggests that the GagCEST signal is driven by changes in HA versus other glycosaminoglycans. Thus, multiparametric magnetic resonance imaging (MRI) can be used as a non-invasive tool to assess therapeutic responses to targeted stromal therapy in PDA and likely other stroma-rich solid tumors that have high levels of hyaluronan and collagen. [ABSTRACT FROM AUTHOR] |
|
Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) |
| قاعدة البيانات: |
Complementary Index |
Full Text Finder