ABSTRACT
Although the protumoral functions of polymorphonuclear neutrophils are well known, some now-forgotten studies report antitumoral roles for these cells. The present work examines the antitumoral effect of maintained neutrophilia induced via the injection of recombinant human granulocyte colony stimulating factor (rhG-CSF, 100 µg/kg/day) in a Panc-1 subcutaneous xenograft murine model of pancreatic cancer. This treatment was compared with gemcitabine administration (120 mg/kg every two days) and a saline control (n = 6-7 mice per group). Compared to the controls, both the rhG-CSF- and gemcitabine-treated mice showed significantly suppressed tumor growth by day 4 (p < 0.001 and p = 0.013 respectively). From a mean starting volume of 106.9 ± 3.1 mm3 for all treatment groups, the final mean tumor volumes reached were 282.0 ± 30.7 mm3 for the rhG-CSF-treated mice, 202.6 ± 18.1 mm3 for the gemcitabine-treated mice and 519.4 ± 62.9 mm3 for the control mice (p < 0.004 and p < 0.01, respectively, vs. control). The rhG-CSF-treated tumors showed higher percentage necrosis than those treated with gemcitabine (37.4 ± 4.6 vs. 7.5 ± 3.0; p < 0.001). This is the first report of a clear anti-tumoral effect of rhG-CSF when used in monotherapy against pancreatic cancer. Since rhG-CSF administration is known to be associated with very few adverse events, it may offer an attractive alternative in the clinical treatment of pancreatic cancer.
Subject(s)
Adenocarcinoma/drug therapy , Deoxycytidine/analogs & derivatives , Granulocyte Colony-Stimulating Factor/pharmacology , Leukocytosis/immunology , Neutrophils/immunology , Pancreatic Neoplasms/drug therapy , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Animals , Antimetabolites, Antineoplastic/pharmacology , Apoptosis , Cell Proliferation , Deoxycytidine/pharmacology , Drug Therapy, Combination , Female , Humans , Leukocytosis/chemically induced , Leukocytosis/pathology , Mice , Mice, Nude , Neutrophils/drug effects , Neutrophils/pathology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , GemcitabineABSTRACT
Tumor growth is a surface phenomenon of the molecular beam epitaxy universality class in which diffusion at the surface is the determining factor. This Letter reports experiments performed in mice showing that these dynamics can, however, be changed. By stimulating the immune response, we induced strong neutrophilia around the tumor. The neutrophils hindered cell surface diffusion so much that they induced new dynamics compatible with the slower quenched-disorder Edwards-Wilkinson universality class. Important clinical effects were also seen, including remarkably high tumor necrosis (around 80%-90% of the tumor), a general increase in survival time [the death ratio in the control group is 15.76 times higher than in the treated group (equivalent to a Cox's model hazard ratio of 0.85; 95% confidence interval 0.76-0.95, p=0.004)], and even the total elimination of some tumors.
Subject(s)
Carcinoma, Ehrlich Tumor/immunology , Carcinoma, Ehrlich Tumor/pathology , Models, Immunological , Animals , Cell Division/immunology , Mice , Mice, Inbred C57BL , Neutrophils/immunologyABSTRACT
Se expone información referida a la historia, bases técnicas, indicaciones, limitaciones, contraindicaciones de la ecografía, método diagnóstico basado en el uso de ultrasonidos. Se expone la preparación del paciente a efectos de la exploración. Se realiza el estudio pormenorizado de los órganos abdominales. Se excluyen expresamente el aparato urinario, el aparato genital y la región retroperitoneal. Se estudian sucesivamente en función de su patología: hígado, vesícula biliar, vía biliar, páncreas, sistema porta, tracto gastrointestinal. Se estudian asimismo las colecciones líquidas intraperitoneales. Se analizan nuevos campos de aplicación de los ultrasonidos: medición de flujos sanguíneos, métodos de punción combinados con radiología, la ecografia endoscópica, transrectal y peroperatoria. Se expone iconografía que ilustra el texto
