ABSTRACT
Most testicular neoplasms are germ cell tumors, the vast majority of which represent seminomas. Most seminomas present localized to the testis, whereas nonseminomatous germ cell tumors more often present with lymph node metastases. Psoas abscesses generally arise from a contiguous intra-abdominal or pelvic infectious process, an adjacent focus of osteomyelitis or septic emboli from distant infectious foci. In this study, the case of a 24-year-old man who presented with a right psoas mass presumptively diagnosed as an abscess secondary to fever and leukocytosis is presented. The patient had a history of right testicular seminoma, and normal serum levels of alpha-fetoprotein and human chorionic gonadotropin. Surgical exploration and biopsy demonstrated seminoma metastasis. This case represents an extremely unusual clinical presentation of metastatic germ cell tumor presenting as a psoas abscess. This unique case represents an unusual presentation of a recurrent germ cell tumor mimicking a psoas abscess. Awareness of possible metastatic testicular germ cell neoplasm as a psoas abscess could prevent diagnosis delay before retroperitoneal tumor debulking.
Subject(s)
Neoplasms, Germ Cell and Embryonal/diagnosis , Psoas Abscess/diagnosis , Retroperitoneal Neoplasms/secondary , Adult , Diagnosis, Differential , Humans , Male , Neoplasms, Germ Cell and Embryonal/diagnostic imaging , Neoplasms, Germ Cell and Embryonal/pathology , Psoas Abscess/diagnostic imaging , Retroperitoneal Neoplasms/diagnosis , Retroperitoneal Neoplasms/diagnostic imaging , Tomography, X-Ray ComputedABSTRACT
AIMS: Interleukin-7 (IL-7) is a master regulator of T-cell development and homoeostasis. Increased IL-7 levels are associated with inflammatory diseases. The aims of this study were to determine whether IL-7 is a biomarker for inflammatory conditions or an active participant in atherogenesis. METHODS AND RESULTS: Advanced atherosclerotic lesions in Apoe(-/-) mice were regressed by long-term cholesterol lowering through treatment with a helper-dependent adenovirus expressing apolipoprotein E (n= 6-10). Using this model, gene expression patterns in the aorta were analysed at an early phase of regression by microarray. After stringent statistical analysis, we found that IL-7 expression is significantly reduced in response to lowering of cholesterol (n= 6). To understand the importance of IL-7 down-regulation for atherosclerotic regression, we studied the effects and mechanisms of action of IL-7 on endothelial cells (ECs) in vitro as well as in vivo. Our major findings are: (i) IL-7 up-regulates cell adhesion molecules and monocyte chemoattractant protein-1 in ECs and promotes monocyte adhesion to ECs; (ii) this regulation is mediated by phosphatidylinositol 3-kinase (PI3K)/AKT-dependent and -independent activation of NF-κB; (iii) elevation of plasma IL-7 induces recruitment of monocytes/macrophages to endothelium without affecting plasma cholesterol (n= 5, 6); and (4) lack of IL-7 in bone marrow-derived cells reduces migration of monocytes/macrophages to the lesions (n= 5, 6). CONCLUSION: These results suggest that IL-7 inflames endothelium via PI3K/AKT-dependent and -independent activation of NF-κB and recruits monocytes/macrophages to the endothelium, thus playing an active role in atherogenesis.
Subject(s)
Atherosclerosis/etiology , Endothelium, Vascular/drug effects , Interleukin-7/pharmacology , Macrophages/drug effects , Monocytes/drug effects , Adenoviridae , Animals , Aorta, Thoracic , Apolipoprotein E3/genetics , Atherosclerosis/metabolism , Atherosclerosis/pathology , Cell Adhesion Molecules/drug effects , Cell Adhesion Molecules/metabolism , Cell Movement/drug effects , Cells, Cultured , Chemokine CCL2/drug effects , Chemokine CCL2/metabolism , Down-Regulation , Female , Gene Expression Profiling , Genetic Vectors , Interleukin-7/physiology , Mice , Mice, Inbred C57BL , NF-kappa B/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Up-RegulationABSTRACT
A reduction in low density lipoprotein (LDL) cholesterol or an increase in high density lipoprotein (HDL) cholesterol can reduce the risk of development of atherosclerosis through overlapping or independent mechanisms. However, the clinical outcome of combined therapy remains in debate. In this study, we first characterized effects of various constructs of helper-dependent adenoviral vector (HDAd) expressing apolipoprotein E3 or LDL receptor (LDLR) in vivo on plasma cholesterol levels. Using this information, we designed experiments and compared the effects of long-term (28 weeks) LDL cholesterol lowering or raising HDL cholesterol, or a combination of both on advanced atherosclerosis in Ldlr(-/-) mice, a mouse model of familial hypercholesterolemia. Our major findings are: (i) various factors influence in vivo functional activity, which appear to be context dependent; (ii) apolipoprotein AI (APOAI) gene transfer, which raises HDL cholesterol, retards progression of atherosclerosis but does not induce regression; (iii) LDLR or LDLR and APOAI combination gene therapy induces lesion regression; however, LDLR gene transfer accounts for the majority of the effects of combined gene therapy; (iv) LDLR gene therapy reduces interleukin-7, which is a master regulator of T-cell homeostasis, but APOAI gene therapy does not. These results indicate that LDL cholesterol lowering is effective and sufficient in protection against atherosclerosis and induction of regression of pre-existing atherosclerosis.
