ABSTRACT
Objective:To evaluate the pancreatic subclinical dysfunction after intensity-modulated radiation therapy (IMRT) for gastric cancer by analyzing biochemical indexes and pancreatic volume changes, and to reduce the dose of pancreas by dosimetric prediction and dose limitation.Methods:30 patients with gastric cancer who received 45 Gy postoperative adjuvant radiotherapy were retrospectively selected. The pancreas was delineated and its dose and anatomical relationship with planning target volume (PTV) were evaluated. Fasting blood glucose, serum lipase and amylase, and pancreatic volume changes before and after radiotherapy were analyzed. The correlation between the changes of biochemical indexes and volume and pancreatic dose was evaluated by Pearson analysis. The threshold of the dosimetric prediction was obtained by receiver operating characteristic (ROC) curve. Finally, the feasibility of dosimetric limitation in IMRT was assessed.Results:The pancreatic volume of 30 patients was 37.6 cm 3, and 89.0% of them were involved in PTV. D mean of the pancreas was 45.92 Gy, and 46.45 Gy, 46.46 Gy and 45.80 Gy for the pancreatic head, body and tail, respectively. The fasting blood glucose level did not significantly change. The serum lipase levels were significantly decreased by 66% and 77%(both P<0.001), and the serum amylase levels were significantly declined by 24% and 38%(both P<0.001) at 6 and 12 months after radiotherapy. Pancreatic volumes of 22 patients was decreased by 47% within 18 months after radiotherapy. ROC curve analysis showed that pancreatic V 45Gy had the optimal predictive value for the decrease by 1/3 of serum lipase and amylase levels at 6 months and serum amylase level at 12 months after radiotherapy, and the cut-off value was V 45Gy<85%. Pancreatic D mean yielded the optimal predictive value for the decrease by 2/3 of serum lipase level at 12 months after radiotherapy, and the cut-off value was D mean<45.01 Gy. After" whole pancreas" and" outside PTV pancreas" dose limit, V 45Gy of the pancreas was decreased by 11% and 7%, D mean of the pancreas was declined by 2% and 2%, and D mean of the pancreatic tail was decreased by 3%, respectively. Conclusions:Serum lipase and amylase levels significantly decline at 6 and 12 months after adjuvant radiotherapy for gastric cancer, and pancreatic volume is decreased significantly within 18 months after radiotherapy. Pancreatic V 45Gy<85% and D mean<45.01 Gy are the dose prediction values for the decrease of serum lipase and amylase levels. The dose can be reduced to certain extent by dosimetric restriction.
ABSTRACT
Objective:To verify the protective effect of terazosin on cognitive function of rats after whole-brain irradiation (WBI) and to investigate its mechanism.Methods:A total of 64 1-month-old male SD rats were randomly divided into the untreated control group, terazosin group, irradiation group and irradiation plus terazosin group (combination group). WBI was administered at a single dose of 20 Gy in the irradiation and combination groups. The open field test and the Morris water maze (MWM) test were used to evaluate the effect of terazosin on cognitive function after WBI.Starting from the three aspects of juvenile neuron apoptosis, neurogenesis disorderand microglia activation, the possible cellular mechanism wasassayed by double-label immunofluorescence staining for BrdU (bromodeoxyuridine) / NeuN, DCX(Doublecortin) / Caspase-3 and single-label immunofluorescence staining for Iba-1 (ionized calcium binding adaptor molecule-1).Results:Terazosin intervention improved the short-term memory retention of irradiated rats ( P=0.032). After terazosin treatment, the number of DCX + cells in the combination groupwas increased by approximately 35% compared with that in the irradiation group ( P=0.038). The number of BrdU +/NeuN + cells in the combination group was increased by approximately 15% than that in the irradiation group ( P>0.05). The number of Iba-1 + cells in the irradiation plus terazosin group was decreased by 49% compared with that in the irradiation group ( P=0.036). Conclusion:Terazosin may reduce the hippocampal juvenile neuron loss and inhibit neuroinflammation via microglia activation, which can alleviate WBI-induced cognitive dysfunction to a certain extent.
ABSTRACT
Objective:To investigate whether irradiated U251 glioma cells can induce bystander effects in unexposed neural stem cells (NSCs) thus affecting its proliferation, stemness and differentiation.Methods:The cells were divided into NSCs group, NSCs+ U251 group (co-cultured with U251) and NSCs+ IR U251 group (co-cultured with 10 Gy irradiated U251). Glioma cells and NSCs were co-cultured in a transwell insert set. Cell counting and neurosphere diameter measuring were carried out to evaluate the proliferation and neurosphere formation ability of NSCs. Immunofluorescence assay was performed to detect the expression of Nestin protein to evaluate the stemness maintenance of NSCs, and to measure the expression levels of Tuj1 and GFAP proteins, the number of neuronal dendrites, synaptic length, the number of glial protrusions, as well as the length of glial protrusions.Results:The number of NSCs cultured with irradiated U251 cells was obviously smaller than that of NSCs cultured with sham-irradiated U251 cells ( t=2.52, P<0.05). The neurosphere formation ability of NSCs and the percentage of Nestin positive NSCs after co-culture with irradiated U251 cells significantly reduced in comparison with those after co-culture with sham-irradiated U251 cells ( t=-3.50, P<0.05). The percentages and the extent of NSCs differentiating into neuronal cells and glial cells( t=6.09, P<0.05)decreased obviously after co-culture with irradiated U251 cells in comparison with those after co-culture with sham-irradiated U251 cells. Conclusions:Irradiated glioma cells can significantly inhibit the proliferation, stemness and differentiation of unexposed NSCs due to bystander effect.