ABSTRACT
Epithelial ovarian carcinoma is the most common cause of death from gynecologic cancers largely due to advanced, relapsed and chemotherapy-resistant peritoneal metastasis, which is refractory to the currently used treatment approaches. Mechanisms supporting advanced and relapsed peritoneal metastasis are largely unknown, precluding development of more effective targeted therapies. In this study, we investigated the function of a potentially targetable fractalkine axis in the formation and the development of advanced and relapsed peritoneal metastasis and its impact on patients' outcomes. Our mouse model studies support a role for the fractalkine receptor (CX3CR1) in the initiation of peritoneal adhesion important for recolonization of relapsed peritoneal metastasis. We show that downregulation of CX3CR1 results in reduction of metastatic burden at several peritoneal sites commonly colonized by advanced and relapsed metastatic ovarian carcinoma. We show that the chemokine fractalkine (CX3CL1), an activating ligand of CX3CR1, regulates organ-specific peritoneal colonization. High expression of CX3CR1 correlates with significantly shorter survival, specifically in post-menopausal patients with advanced and terminal stages of the disease. Taken together, our studies support a key regulatory role for the fractalkine axis in advanced and relapsed peritoneal metastasis in epithelial ovarian carcinoma.
Subject(s)
Chemokine CX3CL1/physiology , Neoplasms, Glandular and Epithelial/pathology , Ovarian Neoplasms/pathology , Peritoneal Neoplasms/secondary , Receptors, Chemokine/physiology , Animals , CX3C Chemokine Receptor 1 , Carcinoma, Ovarian Epithelial , Cell Line, Tumor , Chemokine CX3CL1/genetics , Female , Humans , Mice , Mice, Inbred C57BL , Neoplasm Invasiveness , Neoplasm Metastasis , Neoplasms, Glandular and Epithelial/genetics , Neoplasms, Glandular and Epithelial/mortality , Ovarian Neoplasms/genetics , Ovarian Neoplasms/mortality , Peritoneal Neoplasms/genetics , Peritoneal Neoplasms/mortality , Peritoneal Neoplasms/pathology , Receptors, Chemokine/genetics , Signal Transduction/genetics , Survival AnalysisABSTRACT
Hyaline cartilage plays an essential role in the maintenance of normal synovial joint function by reducing friction and distributing loads. Histologic analysis of hyaline cartilage reveals zonal variation in cellular morphology, proteoglycan concentration, and collagen fiber size and orientation. High-resolution magnetic resonance (MR) imaging reveals an analogous laminar anatomy that is often visible on clinical images obtained with proper attention to technique. In vitro and in vivo pulse sequences show three distinct laminae: a hypointense superficial lamina, a hyperintense intermediate lamina, and a heterogeneous deep lamina that consists of alternating hyperintense and hypointense bands perpendicular to the subchondral bone. Imaging pitfalls include magic angle effects, truncation artifact, partial volume effect, regional anatomic variation, chemical shift, and magnetic susceptibility effects. Pathologic conditions that affect articular cartilage include chondromalacia patellae, osteoarthritis, and localized traumatic lesions. Although detection of early cartilage disease remains elusive, MR imaging can demonstrate intermediate and advanced lesions.
Subject(s)
Cartilage, Articular/pathology , Hyalin/ultrastructure , Magnetic Resonance Imaging , Adult , Artifacts , Collagen/ultrastructure , Female , Humans , Image Enhancement , Image Processing, Computer-Assisted , Knee Joint/pathology , Male , Middle Aged , Osteochondritis/pathology , Reference ValuesABSTRACT
Sera from five animal species were studied as complement source in the preparation of zymosan-C3 complexes used to detect human B lymphocytes. There was no significant difference in the determination of the percentage of ZC rosette forming cells due to differences in complement source. Human B lymphocytes could not discriminate C3 from different species studied. Every one of these sources of complement may be used interchangeably without altering the percentage of B cells detected by this method.