RESUMO
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.
Assuntos
Quimiocina CX3CL1/fisiologia , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/secundário , Receptores de Quimiocinas/fisiologia , Animais , Receptor 1 de Quimiocina CX3C , Carcinoma Epitelial do Ovário , Linhagem Celular Tumoral , Quimiocina CX3CL1/genética , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Invasividade Neoplásica , Metástase Neoplásica , Neoplasias Epiteliais e Glandulares/genética , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Neoplasias Peritoneais/genética , Neoplasias Peritoneais/mortalidade , Neoplasias Peritoneais/patologia , Receptores de Quimiocinas/genética , Transdução de Sinais/genética , Análise de SobrevidaRESUMO
The study reviews causes of urolithiasis and its manifestations in North-West (NW) Libya. Libyan childhood urolithiasis accounted for 3.6% of nephrology out-patient work load. There were 59 children with urolithiasis, including 34 boys and 25 girls with a mean age of 2.8 ± 2.42 years. Urolithiasis was more common among younger age groups (P = 0.001) and in boys with primary oxaluria and infective etiology. The causes of urolithiasis included metabolic stones in 64%, infective in 26%, and it was idiopathic in 10%. Overall, family history of renal stone disease was elicited in 59%; it was 92% in patients with primary oxaluria. The main presenting features were abdominal pain (27%), gross hematuria (22%), associated urinary tract infection (UTI; 24%), and stone release in 19%. Stone location was bilateral in 64%, multiple in 68%, and in the upper tract in 93% (P = 0.05). Important complications encountered included chronic renal failure (13%), hydronephrosis (34%), systemic hypertension (8%), and rickets in 17%. Calcium oxalate was the most prominent constituent, seen in 41% of the calculi, followed by struvite (21%), uric acid (10%), carbapatite (7%), and cystine (3.5%). Diagnostically helpful findings were family history, age at presentation, UTI by urease producing organisms, rickets, imaging and chemical analysis of calculi. Early detection and prompt treatment helps in preventing long-term sequelae in patients with urolithiasis.
