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http://purl.uniprot.org/citations/33921102http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/33921102http://www.w3.org/2000/01/rdf-schema#comment"RRM1-an important DNA replication/repair enzyme-is the primary molecular gemcitabine (GEM) target. High RRM1-expression associates with gemcitabine-resistance in various cancers and RRM1 inhibition may provide novel cancer treatment approaches. Our study elucidates how RRM1 inhibition affects cancer cell proliferation and influences gemcitabine-resistant bladder cancer cells. Of nine bladder cancer cell lines investigated, two RRM1 highly expressed cells, 253J and RT112, were selected for further experimentation. An RRM1-targeting shRNA was cloned into adenoviral vector, Ad-shRRM1. Gene and protein expression were investigated using real-time PCR and western blotting. Cell proliferation rate and chemotherapeutic sensitivity to GEM were assessed by MTT assay. A human tumor xenograft model was prepared by implanting RRM1 highly expressed tumors, derived from RT112 cells, in nude mice. Infection with Ad-shRRM1 effectively downregulated RRM1 expression, significantly inhibiting cell growth in both RRM1 highly expressed tumor cells. In vivo, Ad-shRRM1 treatment had pronounced antitumor effects against RRM1 highly expressed tumor xenografts (p < 0.05). Moreover, combination of Ad-shRRM1 and GEM inhibited cell proliferation in both cell lines significantly more than either treatment individually. Cancer gene therapy using anti-RRM1 shRNA has pronounced antitumor effects against RRM1 highly expressed tumors, and RRM1 inhibition specifically increases bladder cancer cell GEM-sensitivity. Ad-shRRM1/GEM combination therapy may offer new treatment options for patients with GEM-resistant bladder tumors."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.org/dc/terms/identifier"doi:10.3390/ijms22084102"xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/author"Liu D."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/author"Zhang X."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/author"Sugimoto M."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/author"Matsuoka Y."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/author"Kakehi Y."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/author"Taoka R."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/author"Tohi Y."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/date"2021"xsd:gYear
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/name"Int J Mol Sci"xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/pages"4102"xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/title"Knockdown of RRM1 with Adenoviral shRNA Vectors to Inhibit Tumor Cell Viability and Increase Chemotherapeutic Sensitivity to Gemcitabine in Bladder Cancer Cells."xsd:string
http://purl.uniprot.org/citations/33921102http://purl.uniprot.org/core/volume"22"xsd:string
http://purl.uniprot.org/citations/33921102http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/33921102
http://purl.uniprot.org/citations/33921102http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/33921102
http://purl.uniprot.org/uniprot/#_E9PL69-mappedCitation-33921102http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33921102
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http://purl.uniprot.org/uniprot/#_B4DXB0-mappedCitation-33921102http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33921102
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http://purl.uniprot.org/uniprot/#_B4DS95-mappedCitation-33921102http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33921102
http://purl.uniprot.org/uniprot/#_B4E0I8-mappedCitation-33921102http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33921102
http://purl.uniprot.org/uniprot/#_P23921-mappedCitation-33921102http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33921102
http://purl.uniprot.org/uniprot/#_Q53GZ5-mappedCitation-33921102http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/33921102