title: Inhibition and eradication of human glioma with tumor-targeting Salmonella typhimurium in an orthotopic nude-mouse model.
abstract: Malignant glioma tumors are the most common primary central nervous system tumors. Despite the multidisciplinary approach to treatment, prognosis remains poor. In this study, we demonstrated that the Salmonella typhimurium A1-R tumor-targeting strain can inhibit and eradicate human glioma in an orthotopic nude-mouse model. S. typhimurium A1-R was administered by injection through a craniotomy open-window or intravenously in nude mice. To establish the model, 2x10(5) U87-RFP human glioma cells were injected stereotactically into the mouse brain through the craniotomy open window. Two weeks after glioma-cell implantation, mice were treated with S. typhimurium A1-R [2x10(7) CFU/200 μl intravenous injection (i.v.) or 1x10(6) CFU/1 μl intracranial injection (i.c.)] once a week for 3 weeks. Brain tumors were observed by fluorescence imaging through the craniotomy open window over time. S. typhimurium A1-R, administered i.c., inhibited brain tumor growth 7.6-fold compared with untreated mice (p=0.009) and improved survival 73% (p=0.001). Two of ten mice appeared to have their tumors eradicated. Intravenous administration of S. typhimurium A1-R was not effective. The craniotomy open window enabled observation of tumor growth in the brain in real time in both treated and untreated mice. The results of the present study demonstrate that bacterial therapy of brain cancer is a novel, effective and safe treatment strategy in a highly treatment-resistance cancer.
authors.affiliation: AntiCancer, Inc., San Diego, CA, USA.
authors.forename: Masashi
authors.initials: M
authors.lastname: Momiyama
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kimura
authors.forename: Benjamin
authors.initials: B
authors.lastname: Tran
authors.forename: Takashi
authors.initials: T
authors.lastname: Chishima
authors.forename: Michael
authors.initials: M
authors.lastname: Bouvet
authors.forename: Itaru
authors.initials: I
authors.lastname: Endo
authors.forename: Robert M
authors.initials: RM
authors.lastname: Hoffman
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor; D003399:Craniotomy; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007275:Injections, Intravenous; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D012486:Salmonella typhimurium / Q000472:pathogenicity*; D015996:Survival Rate; D014183:Transplantation, Heterologous; D000070584:Tripartite Motif Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins