Restoration of radiation therapy-induced salivary gland dysfunction in mice by post therapy IGF-1 administration.
Restoration of radiation therapy-induced salivary gland dysfunction in mice by post therapy IGF-1 administration.
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DOI：
10.1186/1471-2407-10-417
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发表时间：
2010-08-10
期刊：
影响因子：
3.8
通讯作者：
Limesand KH
中科院分区：
文献类型：
--
作者：
Grundmann O;Fillinger JL;Victory KR;Burd R;Limesand KH
头颈部癌症的放射治疗在大多数个体中导致严重和慢性唾液腺功能障碍。这会导致严重的副作用，包括口干、吞咽困难和营养不良，这些副作用与患者生活质量的显著降低有关。目前，很少有口干症的治疗方法，提供长期的结果，没有显着的副作用。为了解决这个问题，我们研究了治疗后IGF-1逆转辐射诱导的唾液腺功能障碍的潜力。用靶向头颈部放射治疗FVB小鼠，并且在治疗后3天确认唾液功能的显著降低。在辐射后第4-8天，一组小鼠静脉内注射IGF-1，而第二组作为载体对照。在第30、60和90天评价刺激的唾液流速，并在第9、30、60和90天进行组织学分析。接受溶媒注射的辐照动物在整个时间过程中刺激唾液流速降低40-50%。接受IGF-1注射的小鼠在治疗后30天改善了刺激的唾液流速。到第60-90天，注射IGF-1的小鼠已将唾液流速恢复到未照射的对照小鼠水平。对腮腺组织切片进行淀粉酶染色，作为功能腺泡细胞的指标，在所有天数中，与未照射组相比，在照射动物中检测到总淀粉酶面积显著减少。治疗后注射IGF-1导致淀粉酶阳性腺泡细胞面积增加和淀粉酶分泌改善。接受IGF-1的辐照小鼠显示出与未处理小鼠相似的增殖指数，表明恢复到组织稳态。治疗后IGF-1治疗可能通过细胞增殖的正常化和淀粉酶表达的改善来恢复唾液腺功能。这些发现有助于合理设计治疗方案或药物，用于治疗已完成抗癌治疗的患者中放射诱导的唾液腺功能障碍。
Radiotherapy for head and neck cancer results in severe and chronic salivary gland dysfunction in most individuals. This results in significant side effects including xerostomia, dysphagia, and malnutrition which are linked to significant reductions in patients' quality of life. Currently there are few xerostomia treatment approaches that provide long-term results without significant side effects. To address this problem we investigated the potential for post-therapeutic IGF-1 to reverse radiation-induced salivary gland dysfunction. FVB mice were treated with targeted head and neck radiation and significant reductions in salivary function were confirmed 3 days after treatment. On days 4-8 after radiation, one group of mice was injected intravenously with IGF-1 while a second group served as a vehicle control. Stimulated salivary flow rates were evaluated on days 30, 60, and 90 and histological analysis was performed on days 9, 30, 60, and 90. Irradiated animals receiving vehicle injections have 40-50% reductions in stimulated salivary flow rates throughout the entire time course. Mice receiving injections of IGF-1 have improved stimulated salivary flow rates 30 days after treatment. By days 60-90, IGF-1 injected mice have restored salivary flow rates to unirradiated control mice levels. Parotid tissue sections were stained for amylase as an indicator of functioning acinar cells and significant reductions in total amylase area are detected in irradiated animals compared to unirradiated groups on all days. Post-therapeutic injections of IGF-1 results in increased amylase-positive acinar cell area and improved amylase secretion. Irradiated mice receiving IGF-1 show similar proliferation indices as untreated mice suggesting a return to tissue homeostasis. Post-therapeutic IGF-1 treatment restores salivary gland function potentially through normalization of cell proliferation and improved expression of amylase. These findings could aid in the rational design of therapy protocols or drugs for the treatment of radiation-induced salivary gland dysfunction in patients who have completed their anti-cancer therapies.
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干细胞移植在辐照腺体中的干细胞移植后拯救唾液腺功能。
影响因子：
3.7
作者：
Lombaert, Isabelle M. A.;Brunsting, Jeanette F.;Wierenga, Pieter K.;Faber, Hette;Stokman, Monique A.;Kok, Tineke;Visser, Willy H.;Kampinga, Harm H.;de Haan, Gerald;Coppes, Robert P.
通讯作者：
Coppes, Robert P.
影响因子：
5.3
作者：
Limesand, Kirsten H.;Schwertfeger, Kathryn L.;Anderson, Steven M.
通讯作者：
Anderson, Steven M.
影响因子：
4.8
作者：
Henson, BS;Eisbruch, A;Ship, JA
通讯作者：
Ship, JA
影响因子：
2.1
作者：
Muhvic-Urek, M;Bralic, M;Tomac, J
通讯作者：
Tomac, J
DOI：
10.1016/j.ijrobp.2008.09.036
发表时间：
2009-02-01
影响因子：
7
作者：
Avila, Jennifer L.;Grundmann, Oliver;Burd, Randy;Limesand, Kirsten H.
通讯作者：
Limesand, Kirsten H.