Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three m...Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.展开更多
Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha （TNF-c0 and its receptors TNF receptor subtyp...Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha （TNF-c0 and its receptors TNF receptor subtype-I （TNFR1） and TNFR2 in acute and chronic itch in mice. Compared to wild-type （WT） mice, TNFRl-knockout （TNFR1-KO） and TNFR1/R2 double-KO （DKO）, but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine （CQ）. Application of the TNF-synthesis inhibitor thalidomide and the TNF-at antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia （DRG） and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etaner- cept and in TNFR1/R2 DKO mice. Dry skin induced TNF- expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-c^-fNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be benefi- cial for chronic itch treatment.展开更多
基金supported by the National Natural Science Foundation of China,No.81060182the Natural Science Foundation of Xinjiang Uygur Autonomous Region,No.2012211B34the Key Technology Research and Development and Major Program of Xinjiang Uygur Autonomous Region,No.200833116
文摘Tumor models were simulated in purebred Beagles at the T9-10 levels of the spinal cord and treated with spinal image-guided radiation therapy or conventional radiation therapy with 50 or 70 Gy total radiation. Three months after radiation, neuronal injury at the T9-10 levels was observed, including reversible injury induced by spinal image-guided radiation therapy and apoptosis induced by conventional radiation therapy. The number of apoptotic cells and expression of the proapoptotic protein Fas were significantly reduced, but expression of the anti-apoptotic protein heat shock protein 70 was significantly increased after image-guided radiation therapy compared with the conventional method of the same radiation dose. Moreover, the spinal cord cell apoptotic index positively correlated with the ratio of Fas/heat shock protein 70. These findings indicate that 3 months of radiation therapy can induce a late response in the spinal cord to radiation therapy; image-guided radiation therapy is safer and results in less neuronal injury compared with conventional radiation therapy.
基金supported by grants from the National Natural Science Foundation of China(31371179 and 81300968)the Natural Science Foundation of Jiangsu Province,China(BK20140372)+2 种基金the Scientific Funding from Jiangsu Province,China(2015-JY-029)the Second Affiliated Hospital of Soochow University Preponderant Clinic Discipline Group Project Funding(XKQ2015007)a Project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions,Jiangsu Province,China
文摘Increasing evidence suggests that cytokines and chemokines play crucial roles in chronic itch. In the present study, we evaluated the roles of tumor necrosis factor-alpha （TNF-c0 and its receptors TNF receptor subtype-I （TNFR1） and TNFR2 in acute and chronic itch in mice. Compared to wild-type （WT） mice, TNFRl-knockout （TNFR1-KO） and TNFR1/R2 double-KO （DKO）, but not TNFR2-KO mice, exhibited reduced acute itch induced by compound 48/80 and chloroquine （CQ）. Application of the TNF-synthesis inhibitor thalidomide and the TNF-at antagonist etanercept dose-dependently suppressed acute itch. Intradermal injection of TNF-α was not sufficient to evoke scratching, but potentiated itch induced by compound 48/80, but not CQ. In addition, compound 48/80 induced TNF-α mRNA expression in the skin, while CQ induced its expression in the dorsal root ganglia （DRG） and spinal cord. Furthermore, chronic itch induced by dry skin was reduced by administration of thalidomide and etaner- cept and in TNFR1/R2 DKO mice. Dry skin induced TNF- expression in the skin, DRG, and spinal cord and TNFR1 expression only in the spinal cord. Thus, our findings suggest that TNF-c^-fNFR1 signaling is required for the full expression of acute and chronic itch via peripheral and central mechanisms, and targeting TNFR1 may be benefi- cial for chronic itch treatment.
