ABSTRACT
La poliangeítis con granulomatosis (GPA) es una enfermedad inflamatoria sistémica; los hallazgos histopatológicos incluyen necrosis tisular, formación de granulomas y vasculitis predominantemente devasos de pequeño y mediano calibre. Se caracteriza por la presencia en plasma de anticuerpos anti-citoplasma de neutrófilo dirigidos contra la proteinasa 3 (PR3-ANCA). La GPA comúnmente afecta la vía aérea superior, los pulmones y los riñones. El compromiso oftalmológico es una importante causa de morbilidad, ocurriendo aproximadamente en la mitad de los pacientes. La escleritis necrotizante (EN) es una manifestación infrecuente y grave de la GPA. Las complicaciones de la EN son la perforación ocular y pérdida de la visión. El tratamiento de inducción consiste en esteroides e inmunosupresores (ciclofosfamida o rituximab). El objetivo de este trabajo es describir 3 casos de GPA con EN como manifestación clínica rara y dominante.
Granulomatosis with polyangiitis (GPA) is a systemic inflammatory disease; histopathologic features often include necrosis, granulomaformation, and vasculitis of small-to-medium size vessels. Its characterizedby the presence of anti-neutrophil cytoplasm directedagainst proteinase 3 (PR3-ANCA). The GPA commonly affects the upperairways, lungs and kidneys. Ophthalmological involvement is animportant cause of morbidity in GPA, occurring in approximately inone-half of patients. Necrotizing scleritis is a rare and severe formof ocular manifestation in GPA. Complications are ocular perforationand loss of vision. Induction therapy involves steroids and immunosuppressants (cyclophosphamide or rituximab). The aim of this studyis to describe 3 cases of GPA with necrotizing scleritis as a rare anddominant clinical manifestation.
Subject(s)
Humans , Granulomatosis with Polyangiitis , ScleritisABSTRACT
Murine melanoma B16F0 cells were transfected with SA:DPPC:DOPE (2:1:1 molar ratio) liposomes associated with a plasmid encoding murine IL-12. Stearylamine, a cationic lipid, showed a greater transfection efficiency compared to DOTAP-containing liposomes. The lipid:DNA ratio was 2:1 (w/w). Control groups were mock transfected or transfected with an empty plasmid (pNeo). pNeo or IL-12 transfected cells and controls were inoculated intradermically into the dorsal region of the foot or the lateral flank of C57BL6 mice. Results showed that IL-12 expression had a marked effect on in vivo growth of B16 melanoma tumors developed in both anatomic sites, significantly retarding their growth and prolonging host survival.
Subject(s)
Interleukin-12/genetics , Melanoma, Experimental/therapy , Transfection/methods , Amines , Analysis of Variance , Animals , Cell Line, Tumor , Cell Survival , Disease Progression , Fatty Acids, Monounsaturated , Genes, Reporter , Interleukin-12/metabolism , Liposomes , Melanoma, Experimental/metabolism , Melanoma, Experimental/mortality , Melanoma, Experimental/pathology , Mice , Mice, Inbred C57BL , Neoplasm Transplantation , Quaternary Ammonium Compounds , Tumor BurdenABSTRACT
MC-C fibrosarcoma and B16F0 melanoma tumors were implanted intradermally in the dorsal region of the foot of mice. Tumor progression was compared to standard implantation in the flank. Although foot tumors only reached 13% (MC-C) and 25% (B16F0) of the mean volume of flank tumors, a more malignant phenotype in terms of histology and survival rate was observed in this type of tumors. Moreover, lung metastases were only detected in hosts bearing foot tumors, in contrast to MC-C and B16F0 populations with tumors growing in the flank. In addition, cellular influx and local immune reaction were higher in the dorsal region of the foot. According to our results, the dermis of the flank allows excessive tumor growth due to its low reactivity. Thus, differences in innate and adaptive immune effectors between the evaluated tumor microenvironments would account for the differences in tumor malignancy. Due to its striking differences with the standard flank inoculation, the tumor implantation model herein introduced could be a valuable tool to study the metastatic potential of different cell lines and the microenvironment components affecting tumor growth.
Subject(s)
Disease Models, Animal , Fibrosarcoma/pathology , Melanoma, Experimental/pathology , Neoplasm Invasiveness , Neoplasm Metastasis , Animals , Back/pathology , Cell Line, Tumor , Disease Progression , Fibrosarcoma/immunology , Fibrosarcoma/mortality , Foot/pathology , Immunity, Cellular , Immunity, Innate , Melanoma, Experimental/immunology , Melanoma, Experimental/mortality , Mice , Neoplasm Transplantation/methods , Sheep , Survival RateABSTRACT
A small primary or secondary tumor load can occasionally induce more deleterious effects than a histologically identical larger one. In the four murine models studied herein this enhanced tumor aggressiveness could not be attributed to NRAS mutations or other hereditary changes, differential vascularization of live tumor tissues, or necrosis content. Instead, the main tumor feature associated with a more aggressive behavior was the presence of a high number of vessels, sometimes filled with inflammatory cells, inside a tumor area, which we have identified and designated as the transition zone between the live and the necrotic zones. Our experiments suggest that during tumor growth, different cachectic factors are produced within the transition and necrotic zones by dying tumor cells and by tumor infiltrating macrophages only reaching the general circulation through the vessels present in the transition zone. Therefore, a small tumor displaying high vascularization of its transition area could be harmful to its host, while, in contrast, a large tumor could behave as a relatively benign one if its transition zone exhibited little or no vascularization, and in consequence its cachectic factors remained "trapped." Similar histological images to those observed in mice were seen in a significant percentage of human cancer biopsies, raising the possibility that such images might have a prognostic value.
