Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and-neck cancer radiotherapy.
Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and-neck cancer radiotherapy.
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DOI：
10.1016/j.ijrobp.2011.05.055
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发表时间：
2012-05-01
影响因子：
7
通讯作者：
Gudkov, Andrei V.
中科院分区：
文献类型：
--
作者：
Burdelya, Lyudmila G.;Gleiberman, Anatoli S.;Toshkov, Ilia;Aygun-Sunar, Semra;Bapardekar, Meghana;Manderscheid-Kern, Patricia;Bellnier, David;Krivokrysenko, Vadim I.;Feinstein, Elena;Gudkov, Andrei V.
粘膜炎的发展是头颈部癌症患者放射治疗的常见副作用。我们最近报道了细菌鞭毛蛋白，一种Toll样受体5（TLR 5）的激动剂，可以保护啮齿动物和灵长类动物免受全身辐射引起的急性辐射综合征（Burdelya et al.，2008，Science 320：226-30）。在此，我们分析了TLR 5激动剂在局部、单剂量或分次放射治疗条件下的辐射防护效果。在照射前30分钟，小鼠接受头部和颈部区域的单剂量（10、15、20或25戈伊）或分次照射（累积剂量高达30戈伊），皮下注射或不皮下注射优化的鞭毛蛋白CBLB 502。CBLB 502在15或20戈伊的单次剂量后显著降低了皮炎和粘膜炎的严重程度，加速了组织恢复，并降低了辐射诱导的体重减轻的程度，但在25戈伊的辐射后则没有。CBLB 502也分别对两次（10+15戈伊）或三次（3 × 10戈伊）分次递送的25和30戈伊累积剂量具有保护作用。CBLB 502在保护正常上皮细胞的同时，不影响小鼠原位生长的同基因鳞状细胞癌SCCVII的放射敏感性。CBLB 502的使用还对表达TLR 5的肿瘤产生了辐射非依赖性生长抑制作用，这在人肺腺癌A549的小鼠异种移植模型中得到了证明。CBLB 502结合了支持性治疗（放疗辅助剂）和抗癌剂的特性，两者分别通过激活正常组织或肿瘤中的TLR 5信号传导介导。
Development of mucositis is a frequent side effect of radiotherapy of patients with head and neck cancer. We have recently reported that bacterial flagellin, an agonist of Toll-like receptor 5 (TLR5), can protect rodents and primates from acute radiation syndrome caused by total body irradiation (Burdelya et al., 2008, Science 320: 226-30). Here we analyzed the radioprotective efficacy of TLR5 agonist under conditions of local, single dose or fractionated radiation treatment. Mice received either single-dose (10, 15, 20 or 25 Gy) or fractioned irradiation (cumulative dose up to 30 Gy) of the head and neck area with or without subcutaneous injection of pharmacologically optimized flagellin, CBLB502, 30 minutes prior to irradiation. CBLB502 significantly reduced the severity of dermatitis and mucositis, accelerated tissue recovery and reduced the extent of radiation induced weight loss in mice after a single dose of 15 or 20 Gy but not from 25 Gy of radiation. CBLB502 was also protective from cumulative doses of 25 and 30 Gy delivered in two (10+15 Gy) or three (3 × 10 Gy) fractions, respectively. While providing protection to normal epithelia, CBLB502 did not affect the radiosensitivity of syngeneic squamous carcinoma SCCVII grown orthotopically in mice. Use of CBLB502 also elicited a radiation independent growth inhibitory effect upon TLR5-expressing tumors demonstrated in the mouse xenograft model of human lung adenocarcinoma A549. CBLB502 combines properties of supportive care (radiotherapy adjuvant) and anticancer agent, both mediated via activation of TLR5 signaling in the normal tissues or the tumor, respectively.
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影响因子：
45.3
作者：
Brizel, DM;Wasserman, TH;Sauer, R
通讯作者：
Sauer, R
影响因子：
29.4
作者：
Rhee, Sang Hoon;Im, Eunok;Pothoulakis, Charalabos
通讯作者：
Pothoulakis, Charalabos
氨磷汀可在正常组织和可移植肿瘤中诱导抗氧化酶活性，从而影响放射反应。
DOI：
10.1016/j.ijrobp.2008.10.061
发表时间：
2009-03-01
影响因子：
7
作者：
Grdina, David J.;Murley, Jeffrey S.;Kataoka, Yasushi;Baker, Kenneth L.;Kunnavakkam, Rangesh;Coleman, Mitchell C.;Spitz, Douglas R.
通讯作者：
Spitz, Douglas R.
影响因子：
2.2
作者：
McQuestion, Maurene
通讯作者：
McQuestion, Maurene
影响因子：
11.5
作者：
Vitolo, JM;Cotrim, AP;Baum, BJ
通讯作者：
Baum, BJ