Potential therapeutic targets for growth arrest of colorectal cancer cells exposed to PTHrP

Although PTHrP is implicated in several cancers, its role in chemoresistance is not fully elucidated. We found that in CRC cells, PTHrP exerts proliferative and protective effects and induces cell migration. The aim of this work was to further study the effects of PTHrP in CRC cells. Herein we evidenced, for the first time, that PTHrP induces resistance to CPT-11 in Caco-2 and HCT116 cells; although both cell lines responded to the drug through different molecular mechanisms, the chemoresistance by PTHrP in these models is mediated through ERK, which in turn is activated by PCK, Src and Akt. Moreover, continue administration of PTHrP in nude mice xenografts increased the protein levels of this MAPK and of other markers related to tumorigenic events. The understanding of the molecular mechanisms leading to ERK 1/2 activation and the study of ERK targets may facilitate the development of new therapeutic strategies for CRC treatment.Facultad de Ciencias Veterinaria

Potential therapeutic targets for growth arrest of colorectal cancer cells exposed to PTHrP

Although PTHrP is implicated in several cancers, its role in chemoresistance is not fully elucidated. We found that in CRC cells, PTHrP exerts proliferative and protective effects and induces cell migration. The aim of this work was to further study the effects of PTHrP in CRC cells. Herein we evidenced, for the first time, that PTHrP induces resistance to CPT-11 in Caco-2 and HCT116 cells; although both cell lines responded to the drug through different molecular mechanisms, the chemoresistance by PTHrP in these models is mediated through ERK, which in turn is activated by PCK, Src and Akt. Moreover, continue administration of PTHrP in nude mice xenografts increased the protein levels of this MAPK and of other markers related to tumorigenic events. The understanding of the molecular mechanisms leading to ERK 1/2 activation and the study of ERK targets may facilitate the development of new therapeutic strategies for CRC treatment.Facultad de Ciencias Veterinaria

Potential therapeutic targets for growth arrest of colorectal cancer cells exposed to PTHrP

Although PTHrP is implicated in several cancers, its role in chemoresistance is not fully elucidated. We found that in CRC cells, PTHrP exerts proliferative and protective effects and induces cell migration. The aim of this work was to further study the effects of PTHrP in CRC cells. Herein we evidenced, for the first time, that PTHrP induces resistance to CPT-11 in Caco-2 and HCT116 cells; although both cell lines responded to the drug through different molecular mechanisms, the chemoresistance by PTHrP in these models is mediated through ERK, which in turn is activated by PCK, Src and Akt. Moreover, continue administration of PTHrP in nude mice xenografts increased the protein levels of this MAPK and of other markers related to tumorigenic events. The understanding of the molecular mechanisms leading to ERK 1/2 activation and the study of ERK targets may facilitate the development of new therapeutic strategies for CRC treatment.Fil: Martín, María Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; ArgentinaFil: Gigola, Graciela. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia; ArgentinaFil: Zwenger, Ariel. Hospital Provincial de Neuquén; ArgentinaFil: Carriquiriborde, Martin. Universidad Nacional de La Plata; ArgentinaFil: Gentil, Florencia. Universidad Nacional de La Plata; ArgentinaFil: Gentili, Claudia Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Bahía Blanca. Instituto de Ciencias Biológicas y Biomédicas del Sur. Universidad Nacional del Sur. Departamento de Biología, Bioquímica y Farmacia. Instituto de Ciencias Biológicas y Biomédicas del Sur; Argentin

Influence contamination caused by opportunist microorganisms in BALB/c.<i>Fox1<SUP>nu</SUP></i> mice transplanted with the human tumor line A549

Entre las cepas de ratones inmunodeficientes se encuentra la BALB/c.Fox1nu la cual se utiliza como modelo animal para el transplante de tumores humanos. Estos ratones se producen bajo estrictas barreras sanitarias y deben estar libres de sus patógenos específicos; entre ellos, los oportunistas más frecuentes son Pseudomonas aeruginosa, Klebsiella oxytoca, Proteus mirabilis y Citrobacter spp. El objetivo de este trabajo fue evaluar la interferencia que causan los agentes patógenos oportunistas Pseudomonas aeruginosa, K. oxytoca, P. mirabilis y Citrobacter spp. en ratones BALB/c.Fox1nu trasplantados con la línea tumoral humana A549. Cien ratones hembras BALB/c.Fox1nu de 4 a 6 semanas se dividieron en diez grupos (G) de 10 animales cada uno: G1, transplantados con la línea tumoral A549; G2 inoculados con Pseudomonas aeruginosa; G3, inoculados con K. oxytoca; G4, inoculados con P. mirabilis; G5, inoculados con Citrobacter spp, G6 transplantados con la línea tumoral e inoculados con Pseudomonas aeruginosa, G7 transplantados con la línea tumoral e inoculados con Klebsiella oxytoca, G8 transplantados con la línea tumoral e inoculados con Proteus mirabilis, G9 trasplantados con la línea tumoral e inoculados con Citrobacter spp. y G10 control. Siete de los 10 animales del G1 presentaron crecimiento tumoral, los ratones de los G2 al G 5 no mostraron signos clínicos; los de G6 al G9 no mostraron signología clínica y el desarrollo tumoral se comportó como en los 7 ratones del grupo el G1. Se concluyó que las infecciones por estos patógenos oportunistas no son fatales en ratones BALB/c.Fox1nu y no interfieren en el desarrollo del tumor.Among immunodeficient mouse strains there is the BALB/c.Fox1nu which is used as animal model for transplantation of human tumors. These mice are produced under strict sanitary barriers and should be free of their specific pathogens, among them, the most frequent opportunistic are Pseudomonas aeruginosa, Klebsiella oxytoca, Proteus mirabilis and Citrobacter spp. The aim of this study was to evaluate the interference caused by opportunistic pathogens P. aeruginosa, K. oxytoca, P. mirabilis and Citrobacter spp. BALB/c.Fox1nu hundred female mice of 4 to 6 weeks were divided into ten groups (G) of 10 animals each: G1, transplanted with tumor cell line A549, G2 inoculated with Pseudomonas aeruginosa, G3 inoculated with K. oxytoca; G4 inoculated with P. mirabilis, G5, inoculated with Citrobacter spp, G6 tumor line transplanted and inoculated with P. aeruginosa, G7 transplanted tumor line and inoculated with K. oxytoca, G8 transplanted tumor line and inoculated with P. mirabilis, G9 transplanted tumor line and inoculated with Citrobacter spp. and G10 control. Seven of the 10 animals showed tumor growth in G1, G2 and G 5mice showed no clinical signs, animals from G6 to G9 showed no clinical symptoms and behaved as tumor growth in the 7 mice of G1. It was concluded that these infections are not fatal opportunistic pathogens in mice BALB/c.Fox1nu and do not interfere with tumor development.Facultad de Ciencias Veterinaria

Influence contamination caused by opportunist microorganisms in BALB/c.<i>Fox1<SUP>nu</SUP></i> mice transplanted with the human tumor line A549

Entre las cepas de ratones inmunodeficientes se encuentra la BALB/c.Fox1nu la cual se utiliza como modelo animal para el transplante de tumores humanos. Estos ratones se producen bajo estrictas barreras sanitarias y deben estar libres de sus patógenos específicos; entre ellos, los oportunistas más frecuentes son Pseudomonas aeruginosa, Klebsiella oxytoca, Proteus mirabilis y Citrobacter spp. El objetivo de este trabajo fue evaluar la interferencia que causan los agentes patógenos oportunistas Pseudomonas aeruginosa, K. oxytoca, P. mirabilis y Citrobacter spp. en ratones BALB/c.Fox1nu trasplantados con la línea tumoral humana A549. Cien ratones hembras BALB/c.Fox1nu de 4 a 6 semanas se dividieron en diez grupos (G) de 10 animales cada uno: G1, transplantados con la línea tumoral A549; G2 inoculados con Pseudomonas aeruginosa; G3, inoculados con K. oxytoca; G4, inoculados con P. mirabilis; G5, inoculados con Citrobacter spp, G6 transplantados con la línea tumoral e inoculados con Pseudomonas aeruginosa, G7 transplantados con la línea tumoral e inoculados con Klebsiella oxytoca, G8 transplantados con la línea tumoral e inoculados con Proteus mirabilis, G9 trasplantados con la línea tumoral e inoculados con Citrobacter spp. y G10 control. Siete de los 10 animales del G1 presentaron crecimiento tumoral, los ratones de los G2 al G 5 no mostraron signos clínicos; los de G6 al G9 no mostraron signología clínica y el desarrollo tumoral se comportó como en los 7 ratones del grupo el G1. Se concluyó que las infecciones por estos patógenos oportunistas no son fatales en ratones BALB/c.Fox1nu y no interfieren en el desarrollo del tumor.Among immunodeficient mouse strains there is the BALB/c.Fox1nu which is used as animal model for transplantation of human tumors. These mice are produced under strict sanitary barriers and should be free of their specific pathogens, among them, the most frequent opportunistic are Pseudomonas aeruginosa, Klebsiella oxytoca, Proteus mirabilis and Citrobacter spp. The aim of this study was to evaluate the interference caused by opportunistic pathogens P. aeruginosa, K. oxytoca, P. mirabilis and Citrobacter spp. BALB/c.Fox1nu hundred female mice of 4 to 6 weeks were divided into ten groups (G) of 10 animals each: G1, transplanted with tumor cell line A549, G2 inoculated with Pseudomonas aeruginosa, G3 inoculated with K. oxytoca; G4 inoculated with P. mirabilis, G5, inoculated with Citrobacter spp, G6 tumor line transplanted and inoculated with P. aeruginosa, G7 transplanted tumor line and inoculated with K. oxytoca, G8 transplanted tumor line and inoculated with P. mirabilis, G9 transplanted tumor line and inoculated with Citrobacter spp. and G10 control. Seven of the 10 animals showed tumor growth in G1, G2 and G 5mice showed no clinical signs, animals from G6 to G9 showed no clinical symptoms and behaved as tumor growth in the 7 mice of G1. It was concluded that these infections are not fatal opportunistic pathogens in mice BALB/c.Fox1nu and do not interfere with tumor development.Facultad de Ciencias Veterinaria

Influence contamination caused by opportunist microorganisms in BALB/c.<i>Fox1<SUP>nu</SUP></i> mice transplanted with the human tumor line A549

Entre las cepas de ratones inmunodeficientes se encuentra la BALB/c.Fox1nu la cual se utiliza como modelo animal para el transplante de tumores humanos. Estos ratones se producen bajo estrictas barreras sanitarias y deben estar libres de sus patógenos específicos; entre ellos, los oportunistas más frecuentes son Pseudomonas aeruginosa, Klebsiella oxytoca, Proteus mirabilis y Citrobacter spp. El objetivo de este trabajo fue evaluar la interferencia que causan los agentes patógenos oportunistas Pseudomonas aeruginosa, K. oxytoca, P. mirabilis y Citrobacter spp. en ratones BALB/c.Fox1nu trasplantados con la línea tumoral humana A549. Cien ratones hembras BALB/c.Fox1nu de 4 a 6 semanas se dividieron en diez grupos (G) de 10 animales cada uno: G1, transplantados con la línea tumoral A549; G2 inoculados con Pseudomonas aeruginosa; G3, inoculados con K. oxytoca; G4, inoculados con P. mirabilis; G5, inoculados con Citrobacter spp, G6 transplantados con la línea tumoral e inoculados con Pseudomonas aeruginosa, G7 transplantados con la línea tumoral e inoculados con Klebsiella oxytoca, G8 transplantados con la línea tumoral e inoculados con Proteus mirabilis, G9 trasplantados con la línea tumoral e inoculados con Citrobacter spp. y G10 control. Siete de los 10 animales del G1 presentaron crecimiento tumoral, los ratones de los G2 al G 5 no mostraron signos clínicos; los de G6 al G9 no mostraron signología clínica y el desarrollo tumoral se comportó como en los 7 ratones del grupo el G1. Se concluyó que las infecciones por estos patógenos oportunistas no son fatales en ratones BALB/c.Fox1nu y no interfieren en el desarrollo del tumor.Among immunodeficient mouse strains there is the BALB/c.Fox1nu which is used as animal model for transplantation of human tumors. These mice are produced under strict sanitary barriers and should be free of their specific pathogens, among them, the most frequent opportunistic are Pseudomonas aeruginosa, Klebsiella oxytoca, Proteus mirabilis and Citrobacter spp. The aim of this study was to evaluate the interference caused by opportunistic pathogens P. aeruginosa, K. oxytoca, P. mirabilis and Citrobacter spp. BALB/c.Fox1nu hundred female mice of 4 to 6 weeks were divided into ten groups (G) of 10 animals each: G1, transplanted with tumor cell line A549, G2 inoculated with Pseudomonas aeruginosa, G3 inoculated with K. oxytoca; G4 inoculated with P. mirabilis, G5, inoculated with Citrobacter spp, G6 tumor line transplanted and inoculated with P. aeruginosa, G7 transplanted tumor line and inoculated with K. oxytoca, G8 transplanted tumor line and inoculated with P. mirabilis, G9 transplanted tumor line and inoculated with Citrobacter spp. and G10 control. Seven of the 10 animals showed tumor growth in G1, G2 and G 5mice showed no clinical signs, animals from G6 to G9 showed no clinical symptoms and behaved as tumor growth in the 7 mice of G1. It was concluded that these infections are not fatal opportunistic pathogens in mice BALB/c.Fox1nu and do not interfere with tumor development.Facultad de Ciencias Veterinaria