title: The relationship between the antitumor effect of the IL-12 gene therapy and the expression of Th1 cytokines in an HPV16-positive murine tumor model.
abstract: OBJECTIVE
  The goal of the present study was to investigate the effect of IL-12 expressed in plasmid on the Th1 cytokine profile in an experimental HPV16-positive murine tumor model and the association with the IL-12's antitumor effect.
  
  
  METHODS
  Mice were injected with BMK-16/myc cells to establish HPV16-positive tumor and then pNGVL3-mIL-12 plasmid; pcDNA3 plasmid or PBS was injected directly into tumor site. The antitumor effect of the treatment was evaluated and the cytokines expression profile in each tumor tissue was analyzed.
  
  
  RESULTS
  Treatment with pNGVL3-mIL-12 plasmid had a significant antitumor effect, and a Th2-Th3-type cytokines prolife was detected in the murine tumor model with expression of the cytokines IL-10, IL-4, and TGF-β1. However, after the tumor was treated with three intratumoral injections of plasmid containing IL-12 cDNA, it showed a cytokine profile associated with Th1 with expression of IL-2, IL-12, and IFN-γ cytokines and reduced expression of IL-10, IL-4, and TGF-β1.
  
  
  CONCLUSIONS
  The treatment with the IL-12 gene in the experimental HPV16-positive tumor model promoted the activation of the cellular immune response via expression of a Th1-type cytokine profile and was associated with the inhibition of tumor growth. Thus, IL-12 treatment represents a novel approach for gene therapy against cervical cancer.
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Flor
authors.initials: F
authors.lastname: García Paz
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Vicente
authors.initials: V
authors.lastname: Madrid Marina
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Ausencio
authors.initials: A
authors.lastname: Morales Ortega
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Abimelec
authors.initials: A
authors.lastname: Santander González
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Oscar
authors.initials: O
authors.lastname: Peralta Zaragoza
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Ana
authors.initials: A
authors.lastname: Burguete García
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Kirvis
authors.initials: K
authors.lastname: Torres Poveda
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Moreno
authors.affiliation: Institute of Immunology and Virology, School of Biological Sciences, Autonomous University of Nuevo Leon, Avenida Pedro de Alba y Manuel Barragán, 66450 Monterrey, NL, Mexico.
authors.forename: Juan
authors.initials: J
authors.lastname: Alcocer González
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Eva
authors.initials: E
authors.lastname: Hernandez Marquez
authors.affiliation: Division Chronic Infection and Cancer, Research Center in Infections Diseases, National Institute of Public Health, Avenida Universidad 655, Col. Santa María Ahuacatitlán, 62100 Cuernavaca, MOR, Mexico.
authors.forename: Victor
authors.initials: V
authors.lastname: Bermúdez Morales
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy; D052162:Human papillomavirus 16 / Q000472:pathogenicity*; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018417:Th1 Cells / Q000378:metabolism*
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma