title: Antitumor effect of inhalatory lipopolysaccharide and synergetic effect in combination with cyclophosphamide.
abstract: BACKGROUND
  Macrophage cells differentiate into killer macrophages, named M1 macrophages, that effectively eliminate cancer cells by generating cytokines. We examined the feasibility of a lung cancer therapy using lipopolysaccharide (LPS), which triggers this differentiation. It is expected that the delivery via inhalation of LPS directly into the lungs, where alveolar macrophages reside abundantly, would be effective at minimizing the possible toxic effect of LPS.
  
  
  METHODS
  We determined the effects of intratracheal insufflation of LPS on (i) the exudation of lactate dehydrogenase, (ii) generation of tumor necrosis factor-α and interleukin-12, and (iii) tumor metastases in Lewis lung carcinoma-bearing C57BL/6 mice.
  
  
  RESULTS
  Pulmonary insufflation of LPS resulted in a consistent accumulation of tumor necrosis factor-α, and transient increase in interleukin-12 without significant release of lactate dehydrogenase from the lung cells. In addition, a significant antitumor effect of LPS was observed; and this antitumor effect was potentiated by combination of LPS with the antitumor agent cyclophosphamide.
  
  
  CONCLUSIONS
  Pulmonary inhalation of LPS combined with a chemotherapeutic agent is a promising approach to lung cancer therapy.
authors.affiliation: Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki Noda, Chiba 278-8510, Japan.
authors.forename: Keiji
authors.initials: K
authors.lastname: Hirota
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Oishi
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Keiichi
authors.initials: K
authors.lastname: Sawachi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Inagawa
authors.forename: Chie
authors.initials: C
authors.lastname: Kohchi
authors.forename: Gen-Ichiro
authors.initials: G
authors.lastname: Soma
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Terada
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D018827:Carcinoma, Lewis Lung / Q000473:pathology*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000494:pharmacology; D004357:Drug Synergism; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D000970:Antineoplastic Agents; D008070:Lipopolysaccharides; D003520:Cyclophosphamide