hes1-protein--human and Kidney-Neoplasms

We constructed a three-molecule score based on the expression of Notch pathway molecules: Jagged1, intracellular Notch1 (ICN1) and Hes1 (JIH score). To assess prognostic value of the JIH score in non-metastasis clear cell renal cell carcinoma (ccRCC), we identified 467 patients who underwent nephrectomy during 2008-2009 as our study population. Immunohistochemistry was used to evaluate the expression of these three molecules. Cox regression models were applied to construct the JIH score, while Kaplan-Meier methods, multivariate analyses and nomogram were used to explore prognostic value of the JIH score. Our result confirmed that JIH score was an independent prognosticator for both overall survival (OS) and recurrence-free survival (RFS). Survival analyses showed that a higher JIH score indicated worse clinical outcomes (JIH score 3: 58.3% and 58.0% for 6-year OS and RFS, respectively; JIH score 0: 96.7% and 91.6% for 6-year OS and RFS, respectively). Nomograms based on JIH score and other conventional clinicopathological features had a better capability in predicting patients with pT1 stage disease for both OS and RFS (84.6% and 83.9%, respectively). The JIH score is a novel prognosticator representing activation of Notch pathway for non-metastasis ccRCC, and raises an alternative strategy for excavating potential biomarkers for signal pathways.

Topics: Carcinoma, Renal Cell; Female; Humans; Immunohistochemistry; Jagged-1 Protein; Kaplan-Meier Estimate; Kidney Neoplasms; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Nephrectomy; Outcome Assessment, Health Care; Prognosis; Proportional Hazards Models; Receptor, Notch1; Signal Transduction; Transcription Factor HES-1

Our study is to research the effect of inhibited ADAM-17 expression through the Notch pathway in renal carcinoma.. Immunohistochemistry and western blot were used to examine the expression of ADAM-17 protein in renal cancer tissues. Proliferation and cell invasion of 786-o cells, as well as OS-RC-2 cells, after treatment with two different inhibitors of the Notch pathway, were examined by CCK-8 assay and Transwell assay, respectively. 786-o cell apoptosis was measured using the FCM test.. ADAM-17 was highly expressed in RCC tissues. Compared with blocking γ-secretase, a known mechanism of impairing Notch, blockade of ADAM-17 more effectively down-regulated the expressions of Notch1 and HES-1 proteins. Similarly, we found that the ADAM-17 inhibitor, Marimastat, could more efficiently reduce renal cell proliferation and invasive capacity in comparison with the γ-secretase inhibitor DAPT when used at the same dose. Similar results were obtained when apoptosis of 786-o was measured.. Compared with γ-secretase, inhibition of ADAM-17 expression more effectively inhibits Notch pathway-mediated renal cancer cell proliferation and invasion. ADAM-17 may be a new target for future treatment of renal carcinoma.

Topics: ADAM Proteins; ADAM17 Protein; Amyloid Precursor Protein Secretases; Apoptosis; Basic Helix-Loop-Helix Transcription Factors; Carcinoma, Renal Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Homeodomain Proteins; Humans; Hydroxamic Acids; Kidney Neoplasms; Neoplasm Staging; Receptor, Notch1; Receptors, Notch; Signal Transduction; Transcription Factor HES-1