Related Experiment Video
Updated: Jun 19, 2026
Gene Regulation and Targeted Therapy in Gastric Cancer Peritoneal Metastasis: Radiological Findings from Dual Energy CT and PET/CT
Published on: January 22, 2018
Increase in tumour permeability following TGF-beta type I receptor-inhibitor treatment observed by dynamic
T Minowa1, K Kawano, H Kuribayashi
1Institute of Medicinal Chemistry, Hoshi University, Ebara 2-4-41, Shinagawa, Tokyo 142-8501, Japan.
Background:
To enhance the success rate of nanocarrier-mediated chemotherapy combined with an anti-angiogenic agent, it is crucial to identify parameters for tumour vasculature that can predict a response to the treatment of the anti-angiogenic agent.
Methods:
To apply transforming growth factor (TGF)-beta type I receptor (TbetaR-I) inhibitor, A-83-01, to combined therapy, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was carried out in mice bearing colon 26 cells using gadolinium (Gd)-DTPA and for its liposomal formulation to evaluate changes in tumour microvasculature following A-83-01. Tumour vascular parameters from DCE-MRI were compared with histological assessment and apparent diffusion coefficient of water in tumour generated by diffusion-weighted MRI.
Results:
Contrary to evaluations reported for anti-angiogenic agents, A-83-01 treatment increased the initial area under the Gd concentration-time curve (IAUGC60), volume transfer constant (K(trans)) and fractional plasma volume (v(p)) significantly within 24 h, that was positively related to alpha-smooth muscle actin-positive pericyte coverage and tumour cell proliferation, and was correlated inversely with the apparent diffusion coefficient. The vascular function of the tumour improved by A-83-01 treatment was well assessed on post-liposomal Gd-DTPA-enhanced MR images, which predicted delivery of a liposomal drug to the tumour.
Conclusion:
These findings suggest that DCE-MRI and, in particular, K(trans) and v(p) quantitation, provide important additional information about tumour vasculature by A-83-01 treatment.
Insights
Dynamic contrast-enhanced MRI (DCE-MRI) can predict tumor response to anti-angiogenic therapy. Key parameters like K(trans) and v(p) reveal changes in tumor vasculature, guiding combined nanocarrier chemotherapy.
Area of Science:
- Oncology
- Radiology
- Nanomedicine
Background:
- Optimizing nanocarrier chemotherapy combined with anti-angiogenic agents requires identifying predictive tumor vasculature parameters.
- Understanding treatment response is crucial for enhancing therapeutic success rates.
Purpose of the Study:
- To evaluate the efficacy of transforming growth factor (TGF)-beta type I receptor (TbetaR-I) inhibitor A-83-01 in combined therapy.
- To assess changes in tumor microvasculature using dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) after A-83-01 treatment.
Main Methods:
- DCE-MRI with gadolinium (Gd)-DTPA was performed on mice bearing colon 26 cells.
- Tumor vascular parameters from DCE-MRI were correlated with histological assessments and apparent diffusion coefficient (ADC) from diffusion-weighted MRI.
- Liposomal Gd-DTPA was used to assess vascular function and drug delivery.
Main Results:
- A-83-01 treatment significantly increased IAUGC60, K(trans), and v(p) within 24 hours.
- These increases positively correlated with pericyte coverage and tumor cell proliferation, and inversely with ADC.
- Improved tumor vascular function post-treatment was accurately assessed by DCE-MRI, predicting liposomal drug delivery.
Conclusions:
- DCE-MRI, specifically K(trans) and v(p) quantitation, provides valuable insights into tumor vasculature changes induced by A-83-01.
- These findings support the use of DCE-MRI for predicting treatment response in combined anti-angiogenic and nanocarrier chemotherapy.
