Retroductal颌下腺灌输和本地化分割照射在涎腺功能减退症大鼠模型
Summary
Salivary gland hypofunction, a major adverse effect of head and neck radiotherapy diminishes a patient’s quality of life. The demonstration of efficacy of new therapies in animal models is a prerequisite before clinical transition. This protocol describes retroductal administration and local irradiation of rat submandibular glands.
Abstract
Normal tissues that lie within the portals of radiation are inadvertently damaged. Salivary glands are often injured during head and neck radiotherapy. Irreparable cell damage results in a chronic loss of salivary function that impairs basic oral activities, and increases the risk of oral infections and dental caries. Salivary hypofunction and its complications gravely impact a patient’s comfort. Current symptomatic management of the condition is ineffective, and newer therapies to assuage the condition are needed.
Salivary glands are exocrine glands, which expel their secretions into the mouth via excretory ducts. Cannulation of these ducts provides direct access to the glands. Retroductal delivery of a contrast agent to major salivary glands is a routine out-patient procedure for diagnostic imaging. Using a similar procedure, localized treatment of the glands is feasible. However, performing this technique in preclinical studies with small animals poses unique challenges. In this study we describe the technique of retroductal administration in rat submandibular glands, a procedure that was refined in Dr. Bruce Baum’s laboratory (NIH)1, and lay out a procedure for local gland irradiation.
Introduction
健康组织的侧支破坏占了许多癌症治疗的有害副作用。与该辐射场位于大唾液腺的一部分或全部都不可避免地破坏。因此，经历骨髓移植前头部和颈部癌，子宫颈癌淋巴瘤，或全身辐射放疗大多数患者遭受的辐射，唾液腺机能减退2-6的最常见和最 持久的不利效果之一。
唾液腺的流体产生腺泡细胞对辐射十分敏感。损坏唾液腺导致唾液流，称为唾液腺机能减退的条件的急剧减少。在唾液流量慢性减少损害的关键口腔活动，如咀嚼，吞咽，语言和口味，但剧烈的疼痛，黏膜撕裂，吞咽困难，机会性感染病态的后遗症，和龋齿恶化一个病人的福祉和功能2,3。
由于放疗相关的唾液腺细胞的损失是不可逆的，有口干没有矫正治疗。专注于人工唾液替代品和药品prosecretory平息目前的症状治疗无效的长期救援6。虽然改进的辐射递送技术已经帮助减少的病症的严重程度，正常组织的毒性及其并发症留在癌症治疗中6,7-一个限制因素。先发制人的措施，以防止放射治疗相关的并发症，因此，成为常态。正在探索的清除自由基的氧，促进细胞再增殖，或增强DNA修复放射保护剂，以避免唾液功能减退8-11。
外分泌腺唾液腺分泌物流入通过主排泄管道口。个的口腔内插管E对于造影剂注射排泄管道作为门诊手术常规做。利用类似的方法，唾液腺可以直接针对局部治疗12。除了降低的全身性副作用的风险，retroductal腺滴注增加的好处。围绕导管树唾液腺细胞的单层布置允许指定所有唾液腺上皮细胞，以及腺充当屏障纤维封装，以减少不必要的治疗性传播。从本质上讲，唾液腺是最适宜于腺体的苦难，如放射性唾液腺功能减退的有针对性的治疗。
（ – 2.5格雷/分/天，每周五天1.8），为期两周的用于癌症治疗常规辐射中的小剂量输送。因此，无线电防护治疗，显示在实验模型对旷日持久的辐射方案的疗效有较大的临床影响。康博分次辐射后mised唾液腺功能已被记录在小动物，但辐射源，剂量分数，和使用的协议是多种多样9,10,13。
该报告建立了retroductal交付使用病人相关的辐射源和剂量率大鼠颌下腺局部放射方法。
Protocol
Representative Results
Discussion
唾液腺经常接受的辐射剂量超出经历了头颈部肿瘤，颈淋巴结选修消融或地区血液系统恶性肿瘤放疗的病人组织恢复的门槛。尽管腺的流体分泌腺泡细胞终末分化，它们是矛盾的对辐射敏感。分泌功能辐射和不可逆转的破坏腺体结果的第一周内滴在慢性低口水输出。为了打击穷人腺体功能和随之而来的口腔干燥，保存或分泌功能的恢复是至关重要的。新的治疗方法，以防止或修复辐射的伤害正在?…
Divulgaciones
The authors have nothing to disclose.
Acknowledgements
We thank Dr. John Chang (Radiation Oncology, LSU Health Science Center) for assistance with radiation dose measurements. The study was supported by the American Cancer Society (Grant number: 116945-RSG-09-038-01-CCE), National Institute of Health (Grant number: R21CA173162) and the Feist-Weiller Cancer Center.
Materials
| Intramedic Polyethylene tubing (PE10) | Becton Dickson | 427401 | |
| 1/2 cc Insulin Syringe U-100 | Becton Dickson | 309306 | |
| Artificial Tears | Miller Vet Supply | 5098-9840-64 | |
| Hot Bead Sterilizer | Fine Science Tools | 18000-45 | |
| Perma-Hand silk suture | Ethicon | K833H | |
| Graefe forcep | Fine Science Tools | 11051-10 | |
| Olympus SZX16 Stereo Microscope | Hunt Optics and Imaging | ||
| 6MV Linear Accelerator | Elekta | ||
| Bolus – Skinless | Civco | MTCB410 | |
| Heat Lamp | Braintree Scientific | HL-1 110V |
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