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Cancer Lett ; 348(1-2): 119-25, 2014 Jun 28.
Article in English | MEDLINE | ID: mdl-24657658

ABSTRACT

The anti-tumour mechanisms following Bacillus Calmette-Guérin (BCG) treatment of bladder-cancer remain largely unknown. Previous studies have shown involvement of nitric-oxide (NO) formation in the BCG-mediated effect. We analyzed the effects of macrophage secreted factors (MSFs) from BCG-stimulated RAW264.7 cells on the bladder-cancer cell line MBT2. Direct treatment with BCG did not induce NO in MBT2-cells whereas supernatant from BCG-stimulated macrophages increased NOS2 mRNA and protein expression, NO concentrations and cell-death. Blocking NO-synthesis with the NOS-inhibitor L-NAME did not affect levels of cell-death suggesting cytotoxic pathways involving other signalling molecules than NO. Several such candidate genes were identified in a microarray.


Subject(s)
Antineoplastic Agents/therapeutic use , BCG Vaccine/therapeutic use , Macrophages/drug effects , Nitric Oxide/metabolism , Paracrine Communication/drug effects , Urinary Bladder Neoplasms/drug therapy , Animals , Cell Death/drug effects , Cell Line, Tumor , Culture Media, Conditioned/metabolism , Dose-Response Relationship, Drug , Enzyme Inhibitors/pharmacology , Gene Expression Profiling/methods , Humans , Macrophages/immunology , Macrophages/metabolism , Mice , Nitric Oxide Synthase Type II/antagonists & inhibitors , Nitric Oxide Synthase Type II/genetics , Nitric Oxide Synthase Type II/metabolism , Oligonucleotide Array Sequence Analysis , RNA, Messenger/metabolism , Signal Transduction/drug effects , Treatment Outcome , Up-Regulation , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/immunology , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
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