Suppression of radiation-induced salivary gland dysfunction by IGF-1.
Suppression of radiation-induced salivary gland dysfunction by IGF-1.
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DOI：
10.1371/journal.pone.0004663
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Anderson, Steven M.
中科院分区：
文献类型：
--
作者：
Limesand, Kirsten H.;Said, Sherif;Anderson, Steven M.
放射治疗是头颈癌的主要或次要治疗手段。颈部放射治疗的一个常见副作用是唾液腺功能障碍引起的口干症。在美国，每年大约有40,000例新的口干症病例是由放射治疗引起的。随之而来的唾液腺功能低下会导致严重的发病率，并降低抗癌治疗的有效性和这些患者的生活质量。以前在大鼠模型中的研究表明，唾液腺细胞凋亡的诱导与γ辐射治疗后唾液功能的即刻或慢性下降之间没有相关性。经γ照射后，FVB小鼠的唾液腺中可检测到明显的细胞凋亡，而在表达AKT激活突变体(myr-Akt1)的转基因小鼠中，这种凋亡被抑制。重要的是，这种对MYR-Akt1小鼠细胞凋亡的抑制保留了唾液功能，这是通过γ放射治疗后3天和30天的唾液产量来衡量的。为了将这些研究转化为前倾模型，我们发现静脉注射IGF1在体内刺激唾液腺内源性Akt的激活。在暴露于γ辐射前单次注射IGF1可减少涎腺腺泡细胞的凋亡，并在照射后3天和30天完全保留唾液腺功能。这些研究表明，唾液腺泡细胞的凋亡是继发于头颈部放射治疗的唾液腺功能减退的原因。向接受头颈部照射的患者的唾液腺定向注射IGF1可能有助于减少或消除口干症，恢复这些患者的生活质量。
Radiation is a primary or secondary therapeutic modality for treatment of head and neck cancer. A common side effect of irradiation to the neck and neck region is xerostomia caused by salivary gland dysfunction. Approximately 40,000 new cases of xerostomia result from radiation treatment in the United States each year. The ensuing salivary gland hypofunction results in significant morbidity and diminishes the effectiveness of anti-cancer therapies as well as the quality of life for these patients. Previous studies in a rat model have shown no correlation between induction of apoptosis in the salivary gland and either the immediate or chronic decrease in salivary function following γ-radiation treatment. A significant level of apoptosis can be detected in the salivary glands of FVB mice following γ-radiation treatment of the head and neck and this apoptosis is suppressed in transgenic mice expressing an activated mutant of Akt (myr-Akt1). Importantly, this suppression of apoptosis in myr-Akt1 mice preserves salivary function, as measured by saliva output, three and thirty days after γ-radiation treatment. In order to translate these studies into a preclinal model we found that intravenous injection of IGF1 stimulated activation of endogenous Akt in the salivary glands in vivo. A single injection of IGF1 prior to exposure to γ-radiation diminishes salivary acinar cell apoptosis and completely preserves salivary gland function three and thirty days following irradiation. These studies suggest that apoptosis of salivary acinar cells underlies salivary gland hypofunction occurring secondary to radiation of the head and neck region. Targeted delivery of IGF1 to the salivary gland of patients receiving head and neck irradiation may be useful in reducing or eliminating xerostomia and restoring quality of life to these patients.
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DOI：
10.1111/j.1754-4505.1985.tb00593.x
发表时间：
1985-11-01
期刊：
Special care in dentistry : official publication of the American Association of Hospital Dentists, the Academy of Dentistry for the Handicapped, and the American Society for Geriatric Dentistry
影响因子：
--
作者：
Baum, B J;Bodner, L;Wright, W E
通讯作者：
Wright, W E
影响因子：
3.8
作者：
Nagler, RM
通讯作者：
Nagler, RM
影响因子：
3
作者：
HIRAMATSU, Y;NAGLER, RM;BAUM, BJ
通讯作者：
BAUM, BJ
影响因子：
3.3
作者：
KOHN, WG;GROSSMAN, E;BAUM, BJ
通讯作者：
BAUM, BJ
影响因子：
12.4
作者：
Limesand, KH;Barzen, KA;Anderson, SM
通讯作者：
Anderson, SM