title: Hematological Effects, Serum, and Pulmonary Cytokine Profiles in a Melanoma Mouse Model Treated with GK1.
abstract: OBJECTIVE
  In a previous study, we demonstrated the therapeutic efficacy of a subcutaneous injection of GK1 peptide in a melanoma mouse model, effectively increasing the mean survival time by 42.58%, delaying tumor growth, and increasing intratumoral necrosis compared with the control. As a first approach to investigate the anti-melanoma effect of GK1, this study was carried out to determine the hematological effects along with both serum and lung cytokine profiles in a melanoma lung metastatic model.
  
  
  METHODS
  Thirteen C57BL6 female mice were transfected in the lateral tail vein with 2×10(5) B16-F0 melanoma cells. After 7 days, mice were separated in two different groups and treatments were initiated (day 0): The GK1-treated group (seven mice) were injected every 5 days intravenously with GK1 (10 μg) in the lateral tail vein, and the control group (six mice) were injected every 5 days with intravenous saline solution. Blood samples were collected every 5 days from day 0; tumor samples were obtained for cytokine measurements on the day of sacrifice.
  
  
  RESULTS
  In the peripheral blood, mice treated with GK1 presented a statistically significant decrease in IFN-γ (p<0.05), and lymphocytes tended to be lower compared with the control mice (p=0.06). Lung metastatic analysis demonstrated a significant increase in IFN-γ and IL-12p70 (p<0.05); a significant decrease in IL-17, IL-4, IL-22, IL-23, and IL-12p40 (p<0.05); and a marginal decrease in IL-1β (p=0.07) compared with the control.
  
  
  CONCLUSIONS
  Our results suggest that an intratumoral increase of cytokines with antitumor activity along with an intratumoral decrease of cytokines with protumor activity could explain, in part, the anti-melanoma effects of GK1 in a lung metastatic melanoma mouse model. Further studies must be performed to elucidate the precise mechanisms of action for GK1 peptide against melanoma, and their eventual application in humans.
authors.affiliation: 1 Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México , México City, México .
authors.forename: Armando
authors.initials: A
authors.lastname: Pérez-Torres
authors.affiliation: 2 Department of Internal Medicine, TTUHSC-Permian Basin , Odessa, Texas.
authors.forename: Jesus
authors.initials: J
authors.lastname: Vera-Aguilera
authors.affiliation: 3 Corporación para Investigaciones Biológicas (CIB) , Unidad de Micología Médica y Experimental, Medellín, Colombia.
authors.forename: Jorge H
authors.initials: JH
authors.lastname: Sahaza
authors.affiliation: 1 Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México , México City, México .
authors.forename: Carlos
authors.initials: C
authors.lastname: Vera-Aguilera
authors.affiliation: 4 Servicio de Gastrocirugía, Hospital de Especialidades , Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, México DF, México .
authors.forename: Eduardo
authors.initials: E
authors.lastname: Moreno-Aguilera
authors.affiliation: 1 Departamento de Biología Celular y Tisular, Facultad de Medicina, Universidad Nacional Autónoma de México , México City, México .
authors.forename: Evelyn
authors.initials: E
authors.lastname: Pulido-Camarillo
authors.affiliation: 5 Departamento de Patología Clínica/Oncología, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México , México City, México .
authors.forename: Luis
authors.initials: L
authors.lastname: Nuñez-Ochoa
authors.affiliation: 6 Department of Mathematics and Statistics, Texas Tech University , Lubbock, Texas.
authors.forename: Pratheepa
authors.initials: P
authors.lastname: Jeganathan
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008175:Lung Neoplasms / Q000235:genetics*; D008546:Melanoma, Experimental / Q000235:genetics* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D016207:Cytokines
keywords: animal model; drug development; immunotherapy; interleukins; melanoma