title: Toll-like receptor 5 agonist protects mice from dermatitis and oral mucositis caused by local radiation: implications for head-and-neck cancer radiotherapy.
abstract: OBJECTIVE
  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. Here we analyzed the radioprotective efficacy of TLR5 agonist under conditions of local, single dose or fractionated radiation treatment.
  
  
  METHODS
  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 min before irradiation.
  
  
  RESULTS
  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 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.
  
  
  CONCLUSIONS
  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.
authors: Department of Cell Stress Biology, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Lyudmila G
authors: LG
authors: Burdelya
authors: Anatoli S
authors: AS
authors: Gleiberman
authors: Ilia
authors: I
authors: Toshkov
authors: Semra
authors: S
authors: Aygun-Sunar
authors: Meghana
authors: M
authors: Bapardekar
authors: Patricia
authors: P
authors: Manderscheid-Kern
authors: David
authors: D
authors: Bellnier
authors: Vadim I
authors: VI
authors: Krivokrysenko
authors: Elena
authors: E
authors: Feinstein
authors: Andrei V
authors: AV
authors: Gudkov
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy; D045744:Cell Line, Tumor; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism; D051379:Mice; D009061:Mouth Mucosa / Q000528:radiation effects; D010455:Peptides / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011836:Radiation Tolerance / Q000187:drug effects; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011855:Radiodermatitis / Q000517:prevention & control*; D013280:Stomatitis / Q000209:etiology / Q000517:prevention & control*; D051198:Toll-Like Receptor 5 / Q000819:agonists* / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: C528306:CBLB502; D010455:Peptides; D011837:Radiation-Protective Agents; D051198:Toll-Like Receptor 5