Clinical characteristics of radiation-induced brainstem injury after radiotherapy in patients with head and neck tumors / 中华放射医学与防护杂志

Objective:To provide insight into the clinical characteristics, therapy and prognosis of patients with radiation-induced brainstem injury after radiotherapy.Methods:From August 2013 to September 2021, 13 patients with radiation-induced brainstem injury were included in this study at Sun Yat-sen Memorial Hospital, and the general information and strategy of radiotherapy were collected. A retrospective analysis was adopted to investigate the clinical and radiological characteristics, treatment and clinical outcomes.Results:There were 13 cases in total, including 4 females and 9 males. The onset age of enrolled patients ranged from 29 to 66 years with an average of (48.15±10.23) years. The median dose targeted at tumor area was 70 Gy with in 33 fractions. The median interval between radiotherapy and the diagnosis of radiation-induced brainstem injury was 24 months. The common clinical manifestations included dysphagia, bucking dysarthria, dizziness and problem with balance. The MRI radiological features were hypointense on T1WI, hyperintense on T2WI, and irregularly enhanced with contrast. The median follow-up was 45 months. Seven cases got improvements, while 3 had no obvious efficacy and 3 cases died. No significant differences in prognosis were observed between those received traditional glucocorticoid and those received bevacizumab treatment( P=0.079). Conclusions:The common symptoms of radiation-induced brainstem injury were symptoms of posterior cranial nerves injury and ataxia. Lesions mostly happened in pons and medulla, with hypointense on T1WI and hyperintense on T2WI. Half of the patients have improved after treatment. There was no significant difference in prognosis between glucocorticoid and bevacizumab treatment.

Interleukin-27 decreases ghrelin production through signal transducer and activator of transcription 3-mechanistic target of rapamycin signaling

Interleukin-27 (IL-27), a heterodimeric cytokine, plays a protective role in diabetes. Ghrelin, a gastric hormone, provides a hunger signal to the central nervous system to stimulate food intake. The relationship between IL-27 and ghrelin is still unexplored. Here we investigated that signal transducer and activator of transcription 3 (STAT3)-mechanistic target of rapamycin (mTOR) signaling mediates the suppression of ghrelin induced by IL-27. Co-localization of interleukin 27 receptor subunit alpha (WSX-1) and ghrelin was observed in mouse and human gastric mucosa. Intracerebroventricular injection of IL-27 markedly suppressed ghrelin synthesis and secretion while stimulating STAT3-mTOR signaling in both C57BL/6J mice and high-fat diet-induced-obese mice. IL-27 inhibited the production of ghrelin in mHypoE-N42 cells. Inhibition of mTOR activity induced by siRNA or rapamycin blocked the suppression of ghrelin production induced by IL-27 in mHypoE-N42 cells. siRNA also abolished the inhibitory effect of IL-27 on ghrelin. IL-27 increased the interaction between STAT3 and mTOR in mHypoE-N42 cells. In conclusion, IL-27 suppresses ghrelin production through the STAT3-mTOR dependent mechanism.