Аннотация:The purpose of this study is to clarify the optimal strain-type for xenograft of human lung cancer, ovarian cancer or uterine carcinosarcoma among the two immune-deficient mice, NOG (NOD.Cg-Prkdc scid ll2rg tm1Sug /Jic) and NSG (NOD.Cg-Prkdc scid ll2rg tm1Wji /Szj).Five 8-week-old male mice of each type were used in this experiment.Human tumor tissues, confirmed as cancer by pathologists, were collected from patients treated in the Fukushima Medical University Hospital.The tumor tissues were cut into square-shaped pieces, 1 sub-millimeter in thickness, and dipped in HBSS medium.Small slits were made on the right and left dorsal skin of each mouse, and 100 μL of the medium containing tissue were injected subcutaneously.The xenograft tumors were pathologically observed after the euthanasia.Tissues of lung cancer, ovarian cancer or uterine carcinosarcoma showed successful xenografting in the immune-deficient mice, the success ratio of xenografting between each type of mice were not different.Lung cancer was successfully xenografted in three out of five NOG mice and NSG mice, while ovarian cancer or uterine carcinosarcoma showed successful xenografting in all the immune-deficient mice.Pathological difference between xenografted tumors in each immune-deficient mice was not observed in all cancers.In this study, NOG mice and NSG mice showed no difference in patient-derived xenograft model mice.The Ali18 and Ali14 mutatant strains induced by ENU (N-ethyl-N-nitrosourea) show spontaneous inflammation on peripheral paws in mice.The Ali18 and Ali14 are gain-of-function mutations in cell signaling effector enzyme genes, and trigger autoinflammation through the innate immune cells by unknown mechanisms.We assumed mast cells as candidate initiator of autoinflammation, because double mutants with Ali18 homozygous and W/W v (Ali18/ Ali18;W/W v ), which lack mast cell population, did not show autoinflammation.Thus, the gene expression profiles of mast cells from Ali18 and Ali14 mice may represent predominant pathways leading to autoinflammation.Our micro-array analysis using cultured mast cells from each mutant bone marrow with and without antigen stimulation identified 1124 and 750 up-regulated (> twohold) genes specifically in Ali18 and Ali14 mast cells, respectively.Further, 127 genes were up-regulated in both mutant mast cells.Cell signaling pathways involving these up-regulated genes might provide insight into extensive repression against autoinflammation.
