ABSTRACT
BACKGROUND: A large number of studies have shown that leptin plays an important role in the regulation of fertility via the hypothalamus-pituitary-gonad axis. However, its peripheral function in epididymis was still elusive. OBJECTIVE: The purpose of this study was to determine the pro-secretion effect of leptin on the rat epididymal epithelium. MATERIALS AND METHODS: In the present study, real-time quantitative polymerase chain reaction, western blot, and immunohistochemical analysis were employed to detect the expression pattern of leptin receptors in rat epididymis. The pro-secretion effect of leptin on epididymal epithelial cells was measured by short-circuit current, and the prostaglandin E2 and cyclic adenosine monophosphate level was evaluated by enzyme-linked immunosorbent assay. RESULTS: We verified that the leptin receptor was located on the epididymal epithelium, with a relatively high expression level in corpus and cauda epididymis. Ussing chamber experiments showed that leptin stimulated a significant rise of the short-circuit current in rat epididymal epithelial cells, which could be abolished by the specific leptin receptor antagonist peptide Allo-aca, or by removing the ambient Cl- and HCO3 -. Furthermore, the leptin-stimulated short-circuit current response could be abrogated by blocking the apical cystic fibrosis transmembrane regulator or the basolateral Na+-K+-2Cl- cotransporter. Our pharmacological experiments manifested that interfering with the prostaglandin H synthase-2-prostaglandin E2-EP2/EP4-adenylate cyclase pathways could significantly blunt the cystic fibrosis transmembrane regulator-mediated anion secretion induced by leptin. The enzyme-linked immunosorbent assay demonstrated that leptin could induce a substantial increase in prostaglandin E2 release and cyclic adenosine monophosphate synthesis of primary cultured rat cauda epididymal epithelial cells. Our data also suggested that JAK2, ERK, and PI3K-dependent phosphorylation may be involved in the activation of prostaglandin H synthase-2 and the subsequent prostaglandin E2 production. CONCLUSIONS: The present study demonstrated the pro-secretion function of leptin in rat epididymal epithelium via the activation of cystic fibrosis transmembrane regulator and Na+-K+-2Cl- cotransporter, which was dependent on the paracrine/autocrine prostaglandin E2 stimulated EP2/EP4-adenylate cyclase pathways, and thus contributed to the formation of an appropriate microenvironment essential for sperm maturation.
ABSTRACT
Aims: The levels of coagulation system tests have been studied in various cancers. In this study, our aim is to evaluate the prognostic value of pretreatment plasma coagulation tests in hepatocellular carcinoma (HCC) patients. Patient and methods: A retrospective study was performed in 539 patients with HCC, and follow-up period was at least 60 months until recurrence or death. The prognostic significance of coagulation system tests (prothrombin time, activated partial thromboplastin time, thrombin time, fibrinogen) were determined by univariate and multivariate Cox hazard models. Then, according to the results of the multivariate analyses, we proposed the coagulation-Based Stage, which combined the independent risk factors (prothrombin time and fibrinogen). Results: Coagulation system tests including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen (Fbg) were analyzed. Patients with prolonged PT (≥12.1 sec) levels had significantly poor overall survival (OS) and disease-free survival (DFS), not only in the entire cohort (HR: 1.661, 95%CI: 1.125-2.451, p=0.011 vs. HR: 1.660, 95%CI: 1.125-2.451, p=0.011), but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). Additionally, high Fbg (≥2.83 g/L) levels experienced significantly decreased OS and DFS (HR: 2.158, 95%CI: 1.427-3.263, p<0.001 vs. HR: 2.161, 95%CI: 1.429-3.267, p<0.001), not only in the entire cohort but also in the subgroups stratified by pathological stage (stage I-II and stage III-IV). All the patients were then stratified (based on combined PT and Fbg) into three groups, The OS for HCC patients were (41.37±17.76), (31.83±19.84) and (18.68±18.41) months, and the DFS for HCC patients were (41.15±17.88), (31.65±19.81) and (18.66±18.39) months. Conclusions: Our findings suggest that the combination of plasma PT and Fbg levels should be evaluated as the valuable predictor of survival in patients with HCC.
ABSTRACT
BACKGROUND: With a trend that renal tumors are being detected at an earlier stage, classical radical nephrectomy is being reconsidered. More conservative techniques are being proposed. To clarify the indication for synchronous adrenalectomy in radical nephrectomy for renal cell carcinoma which has been questioned since the 1980s, this study evaluates the role of adrenalectomy and recommends a new indication for adrenalectomy in renal cell carcinoma. METHODS: A systemic search was performed, using PubMed and Google Scholar, of all English language studies published up to March 2012 that compared adrenalectomy with adrenal-sparing surgery, in surgery for renal cell carcinoma. We assessed preoperative imaging for adrenal involvement and the relationship of tumor location with adrenal metastases. Twenty-one studies (20 retrospective and 1 prospective) involving 11 736 patients were included. RESULTS: The mean incidence of ipsilateral adrenal involvement from renal cell carcinoma was 4.5%. Synchronous adrenalectomy did not alter survival (hazard ratio (HR) = 0.89, 95% confidence interval (CI) 0.67 - 1.19, P = 0.43; odds ratio (OR) = 1.10, 95%CI 0.84 - 1.44, P = 0.49). Upper pole tumors were not associated with a higher incidence of ipsilateral adrenal metastases. Pooled preoperative imaging: sensitivity, specificity, positive predictive value and negative predictive value were 92% (95%CI 0.84 - 0.97), 95% (95%CI 0.93 - 0.96), 71.6% and 98.5% respectively. CONCLUSIONS: Adrenal involvement from renal cell carcinoma is rare, even in advanced tumours. Synchronous adrenalectomy does not offer any benefit, even for "high risk" patients. We suggest that only patients with a positive preoperative adrenal finding on preoperative imaging for a solitary adrenal metastasis should undergo adrenalectomy as part of the radical nephrectomy.
