Changes in cell cycle, apoptosis and necrosis following the establishment of a 125I brachytherapy model in the spinal cord in Banna mini-pigs

Abstract

Abstract. Brachytherapy is regarded as the most effective method in the treatment of metastatic spinal tumors since little damage is caused to surrounding healthy tissue. However, this method may cause radiation myelopathy if an overdose occurs. In the present study, we established a Banna mini-pig 125 I spinal cord implantation model to provide a tool for the study of how to reduce these types of side effects. Cell cycle alteration, apoptosis and necrosis of spinal cord neurons in the presence of various doses and durations of 125 I brachytherapy were also investigated. The pigs were randomly divided into four groups, A, B, C and D. In group A, four 125 I seeds (total radioactivity, 4.0 mCi) were implanted into the dura mater of the spinal canal at the level of T13. In groups B and C, eight 125 I sources (total radioactivity, 8.0 mCi) were inserted at the same location. Groups A and C were raised for up to 8 months and group B for only 2 months. Neurons from the swine spinal cord at the T13 level were collected and cell cycle analysis was performed. Apoptosis and necrosis were tested by a terminal deoxynucleotidyl transferase dUTP nick endlabeling (TUNEL) assay. The Banna mini-pig brachytherapy model was successfully established. Radiation myelopathy was closely associated with radiation dose and duration, more neurons were blocked in the G2 and S phases as dose and time increased, and an increase in apoptosis and necrosis was detected. Ratios of apoptosis and necrosis were reduced as lower doses and shorter durations of radiation were applied. Our results demonstrate that the Banna mini-pig is an ideal animal to study 125 I brachytherapy. Low-dose and short-term brachytherapy may effectively decrease apoptosis and necrosis in spinal cord cells in Banna mini-pigs.

Regulation of Autophagy Via PERK-eIF2α Effectively Relieve the Radiation Myelitis Induced by Iodine-125

“…In the study, we also successfully reduced PERK expression by intrathecal administration of the lentivirus vector in radiation myelitis banna pigs [10], [11] caused by 125 I brachytherapy, the apoptosis rates were significantly higher than that in control group and deteriorated radiation myelitis of banna pigs, which was consistent with that in neural cells. In conclusion, autophagy caused by 125 I radiation was mainly as an attempt of cell survival at an early stage, and it would be a self-destructive process and promoted the process of apoptosis and necrosis radiated by 125 I for more than 72 hours.…”

“…In both groups, eight brachytherapy seeds were implanted into the spinal dura mater at the T13 level. Radiation dosimetry was based on previous studies [10], [11]. The average radiation dose for each group was 16.76±0.32Gy and 17.02±0.58Gy.…”

“…In previous study, we had successfully established 125 I brachytherapy induced radiation myelitis animal model [10], [11]. Shrinkage of cell membrane, increased mounts of lysosome, swelled mitochondria and autophagic vacuoles with double-membrane structure accumulated in spinal cord lesions were observed by electron microscopy.…”

Effect of brachytherapy on NF-κB and VEGF in gastric carcinoma xenografts

“…Several recent studies suggest that apoptosis and cell cycle arrest may have important roles in the therapeutic effects of continuous low-energy 125 I irradiation (14,15,18). In addition, the VEGF and NF-κB signaling pathway may be involved in the gastric cancer oncogenic signaling pathway (19).…”

Advances in the clinical research of the minimally invasive treatment for the posterior edge of vertebral-body defects by spinal metastases

“…Particles are planted beyond the target range and the radiation dose decreased rapidly, which makes a high dose and long half-life of particles in the target area, and allows the spinal cord tissue to achieve a sufficient amount for the prescription (39). Yang et al (40)(41)(42) conducted a comparative study of the treatment method for spinal metastases: Simple PVP and PVP combined with 125 I seed implantation. The analgesic effect and vertebral-body changes were observed 1 day, and 1, 3 and 6 months after surgery, respectively.…”