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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Apoptosis, Benzenesulfonates, Carcinoma, Renal Cell, Cell Line, Tumor, Cell Proliferation, Clusterin, Disease Models, Animal, Gene Knockdown Techniques, Humans, Kidney Neoplasms, Mice, Mice, Nude, Niacinamide, Oligonucleotides, Antisense, Phenylurea Compounds, Pyridines, Sorafenib, Thionucleotides, Up-Regulation, Xenograft Model Antitumor Assays.
user
Does clusterin inhibition using OGX-011 synergistically enhance antitumour activity of sorafenib in a human renal cell carcinoma model? Context: The objective of this study was to investigate whether the therapeutic activity of sorafenib could be enhanced by combining with OGX-011, an antisense oligodeoxynucleotide (ODN) targeting clusterin, in renal cell carcinoma (RCC). We investigated the effects of combined treatment with OGX-011 and sorafenib on a human RCC ACHN model both in vitro and in vivo. Although clusterin expression was increased by sorafenib, additional treatment of ACHN with OGX-011 significantly blocked the upregulation of clusterin induced by sorafenib. Despite the lack of a significant effect on the growth of ACHN, OGX-011 synergistically enhanced the sensitivity to sorafenib, reducing the IC(50) by >50%. Apoptotic changes were intensively detected in ACHN after combined treatment with OGX-011 and a sublethal dose of sorafenib, but not either agent alone. Furthermore, this combined treatment resulted in the marked downregulation of phosphorylated Akt and p44/42 mitogen-activated protein kinase in ACHN compared with treatment with either agent alone. In vivo systemic administration of OGX-011 plus sorafenib significantly decreased the ACHN tumour volume compared with control ODN plus sorafenib.
assistant
Combined use with OGX-011 may be useful in enhancing the cytotoxic effect of sorafenib on RCC by inducing apoptosis and inactivating major signal transduction pathways. Final Decision: yes