title: Differential effect of soy isoflavones in enhancing high intensity radiotherapy and protecting lung tissue in a pre-clinical model of lung carcinoma.
abstract: BACKGROUND
  Radiotherapy of locally-advanced non-small cell lung cancer is limited by radiation-induced pneumonitis and fibrosis. We have further investigated the role of soy isoflavones to improve the effect of a high intensity radiation and reduce lung damage in a pre-clinical lung tumor model.
  
  
  METHODS
  Human A549 NSCLC cells were injected i.v. in nude mice to generate a large tumor burden in the lungs. Mice were treated with lung irradiation at 10 Gy and with oral soy. The therapy effect on the tumor cells and surrounding lung tissue was analyzed on lung sections stained with H&E, Ki-67 and Masson's Trichrome. Pneumonitis and vascular damage were evaluated by measurements of alveolar septa and immunofluorescent staining of vessel walls.
  
  
  RESULTS
  Combined soy and radiation caused a significantly stronger inhibition of tumor progression compared to each modality alone in contrast to large invasive tumor nodules seen in control mice. At the same time, soy reduced radiation injury in lung tissue by decreasing pneumonitis, fibrosis and protecting alveolar septa, bronchioles and vessels.
  
  
  CONCLUSIONS
  These studies demonstrate a differential effect of soy isoflavones on augmenting tumor destruction induced by radiation while radioprotecting the normal lung tissue and support using soy to alleviate radiotoxicity in lung cancer.
authors.affiliation: Department of Radiation Oncology, Wayne State University School of Medicine, Detroit, USA. Electronic address: hillmang@karmanos.org.
authors.forename: Gilda G
authors.initials: GG
authors.lastname: Hillman
authors.forename: Vinita
authors.initials: V
authors.lastname: Singh-Gupta
authors.forename: David J
authors.initials: DJ
authors.lastname: Hoogstra
authors.forename: Lisa
authors.initials: L
authors.lastname: Abernathy
authors.forename: Joseph
authors.initials: J
authors.lastname: Rakowski
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Yunker
authors.forename: Shoshana E
authors.initials: SE
authors.lastname: Rothstein
authors.forename: Fazlul H
authors.initials: FH
authors.lastname: Sarkar
authors.forename: Shirish
authors.initials: S
authors.lastname: Gadgeel
authors.forename: Andre A
authors.initials: AA
authors.lastname: Konski
authors.forename: Fulvio
authors.initials: F
authors.lastname: Lonardo
authors.forename: Michael C
authors.initials: MC
authors.lastname: Joiner
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008168:Lung / Q000528:radiation effects; D008175:Lung Neoplasms / Q000532:radiotherapy*; D051379:Mice; D017564:Radiation Pneumonitis / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D013025:Glycine max / Q000737:chemistry*
chemical_list: D016207:Cytokines; D007529:Isoflavones; D011837:Radiation-Protective Agents; D011838:Radiation-Sensitizing Agents
keywords: Lung cancer; Radiation; Soy isoflavones
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