Logan Richard M, Stringer Andrea M, Bowen Joanne M, Gibson Rachel J, Sonis Stephen T, Keefe Dorothy M K
Oral Pathology, School of Dentistry, Faculty of Health Sciences, The University of Adelaide, South Australia, Australia.
Cancer Biol Ther. 2008 Jul;7(7):1139-45. doi: 10.4161/cbt.7.7.6207. Epub 2008 Apr 29.
Alimentary tract (AT) mucositis is a serious complication of cancer treatment. Determining changes that occur in the AT can be difficult as invasive procedures are usually contraindicated in these patients. Changes in tissue levels of the transcription factor NFkappaB and pro-inflammatory cytokines have been demonstrated. The aims of this study were to determine whether changes in serum levels of NFkappaB, TNF, IL-1beta and IL-6 following administration of different drugs predicted histological evidence of tissue damage.
Changes in serum levels of NFkappaB, TNF, IL-1beta and IL-6 were observed following administration of each drug. These changes differed according to the drug administered. In most instances, peaks in serum levels occurred following initial histological changes, Although following MTX administration, serum IL-1beta peaked before histological changes and following 5-FU administration, serum NFkappaB, TNF, IL-1beta and IL-6 all peaked before histological evidence of tissue damage.
Female DA rats (n = 243) were given a single dose of irinotecan (200 mg/kg intraperitoneally), methotrexate (1.5 mg/kg intramuscularly) or 5-fluorouracil (150 mg/kg intraperitoneally) and killed 30, 60, 90 minutes, 2, 6, 12, 24, 48 or 72 hours later. Control rats received no treatment. Blood samples were taken via cardiac puncture and centrifuged at 5000 rpm to collect serum. Serum levels of NFkappaB, and pro-inflammatory cytokines were measured by ELISA.
Although changes in serum levels of NFkappaB, TNF, IL-1beta and IL-6 preceded histological changes in tissues, it was concluded that measurement of these factors was not useful in predicting mucosal damage because of the critical time constraints between detectable serun changes and the histological damage. This study highlighted the systemic effects of the drugs. Further studies are required to determine the possible relationships between different toxicities and determine how, once these links are known, patient management can be improved.
消化道（AT）黏膜炎是癌症治疗的一种严重并发症。由于通常对这些患者禁忌进行侵入性操作，因此确定AT中发生的变化可能很困难。已证实转录因子NFκB和促炎细胞因子的组织水平发生了变化。本研究的目的是确定给予不同药物后血清中NFκB、TNF、IL-1β和IL-6水平的变化是否能预测组织损伤的组织学证据。
给予每种药物后均观察到血清中NFκB、TNF、IL-1β和IL-6水平的变化。这些变化因所给药的不同而有所差异。在大多数情况下，血清水平峰值出现在最初的组织学变化之后，尽管在给予甲氨蝶呤（MTX）后，血清IL-1β在组织学变化之前达到峰值，而在给予5-氟尿嘧啶（5-FU）后，血清NFκB、TNF、IL-1β和IL-6均在组织损伤的组织学证据出现之前达到峰值。
给243只雌性DA大鼠腹腔注射单次剂量的伊立替康（200mg/kg）、肌肉注射甲氨蝶呤（1.5mg/kg）或腹腔注射5-氟尿嘧啶（150mg/kg），并在30、60、90分钟、2、6、12、24、48或72小时后处死。对照大鼠不接受治疗。通过心脏穿刺采集血样并以5000转/分钟离心以收集血清。通过酶联免疫吸附测定（ELISA）测量血清中NFκB和促炎细胞因子的水平。
尽管血清中NFκB、TNF、IL-1β和IL-6水平的变化先于组织的组织学变化，但得出的结论是，由于可检测到的血清变化与组织学损伤之间存在关键的时间限制，测量这些因子对预测黏膜损伤并无用处。本研究突出了这些药物的全身作用。需要进一步研究以确定不同毒性之间可能的关系，并确定一旦了解这些联系后如何改善患者管理。
