Intra-Arterial Infusion of Magnetic Nanoparticle-Based Theragnostic Agent to Treat Colorectal Cancer Liver Implants in Rats

2020 ◽  
pp. 1-7
Author(s):  
Borja Herrero de la Parte ◽  
Mireia Irazola Duñabeitia ◽  
Jose Antonio Carrero ◽  
Nestor Etxebarria Loizate ◽  
Ignacio García-Alonso ◽  
...  

<b><i>Introduction:</i></b> Nowadays, surgical excision remains the gold standard to treat liver metastases of colorectal cancer (CRCLM). However, as more than 50% of patients are not eligible for surgery, other alternatives such as percutaneous or intravascular interventional therapies (thermal ablation, chemoembolization, or radioembolization), are quite relevant. Recently, the use of magnetic nanoparticles (MNPs) has been suggested as an adjuvant for these therapies, as they could increase their necrotising effect on the tumour while reducing doses and exposure times of thermal therapies. To investigate the potential curative effect of these compounds, animal models are needed, both for the development of experimental interventional procedures and for MNPs toxicity and distribution assessment. Herein, we describe both an experimental infusion procedure in CRCLM-bearing rats and analytical and histological methods to evaluate MNPs deposits in the tissue. <b><i>Methods:</i></b> Eighteen male WAG/RijHsd rats were subjected to intrahepatic injection of 250,000 colorectal cancer cells. Twenty-eight days later, half of the tumour-positive animals (<i>n</i> = 6) were administered with MNPs while the other half (<i>n</i> = 6) did not receive any injection and were used as control. Under microscope magnification, the splenic artery was carefully and completely dissected, and a catheter was inserted through the splenic artery to the common hepatic artery where 1 mL MNPs suspension was administered in 5 min; then STIR, DP*, and T2 MRI sequences were obtained (and signal intensity measured) and both tumour and liver tissue samples were collected for elemental and histological analyses. <b><i>Conclusion:</i></b> Our method for selective administration of MNPs is reproducible and well-tolerated and it fairly mimics the approach used in clinical practice when intravascular interventional therapies are applied.

2021 ◽  
Vol 22 (15) ◽  
pp. 8337
Author(s):  
Bohan Chen ◽  
Yiping Ma ◽  
Jinfang Bi ◽  
Wenbin Wang ◽  
Anshun He ◽  
...  

Enhancers regulate multiple genes via higher-order chromatin structures, and they further affect cancer progression. Epigenetic changes in cancer cells activate several cancer-specific enhancers that are silenced in normal cells. These cancer-specific enhancers are potential therapeutic targets of cancer. However, the functions and regulation networks of colorectal-cancer-specific enhancers are still unknown. In this study, we profile colorectal-cancer-specific enhancers and reveal their regulation network through the analysis of HiChIP data that were derived from a colorectal cancer cell line and Hi-C and RNA-seq data that were derived from tissue samples by in silico analysis and in vitro experiments. Enhancer–promoter loops in colorectal cancer cells containing colorectal-cancer-specific enhancers are involved in more than 50% of the topological associated domains (TADs) changed in colorectal cancer cells compared to normal colon cells. In addition, colorectal-cancer-specific enhancers interact with 152 genes that are significantly and highly expressed in colorectal cancer cells. These colorectal-cancer-specific enhancer target genes include ITGB4, RECQL4, MSLN, and GDF15. We propose that the regulation network of colorectal-cancer-specific enhancers plays an important role in the progression of colorectal cancer.


2019 ◽  
Author(s):  
Qi Zhang ◽  
Qi Qi ◽  
Xuemeng Qian ◽  
Jiajing Cai ◽  
Xing Shen ◽  
...  

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