{"doi":"10.1016/j.ctarc.2025.100864","title":"Targeting transforming growth factor-β1 by methylseleninic acid/seleno-L-methionine in clear cell renal cell carcinoma: Mechanisms and therapeutic potential","abstract":"Clear cell renal cell carcinoma (ccRCC) poses a significant global health challenge as its incidence continues to rise, resulting in a substantial annual mortality rate. Major clinical challenges to current ccRCC treatments include high drug-resistance rates as well as dose-limiting adverse events; underlining the need to identify additional 'druggable' targets. TGF-β1, VEGF, and PD-L1 are potential therapeutic targets in ccRCC. This study analyzed their expression in human ccRCC cell lines and patient tumor biopsies. Data obtained from western blotting demonstrated higher levels of TGF-β1 and PD-L1 and lower levels of VEGF in sarcomatoid ccRCC cell lines compared to non-sarcomatoid ccRCC cell lines. In patient samples, TGF-β1 was significantly upregulated in both non-sarcomatoid and sarcomatoid ccRCC tumors. It was demonstrated through two assays (cellular thermal shift assay and a size exclusion assay) that methylseleninic acid (MSA) binds specifically and directly to TGF-β1. MSA treatment significantly downregulated TGF-β1, PD-L1, and VEGF in a dose- and time-dependent manner in both non-sarcomatoid and sarcomatoid ccRCC cell lines. Seleno-L-methionine (SLM) treatment in a nude mouse xenograft model showed a significant tumor growth inhibition and TGF-β1 downregulation at non-toxic doses. These findings suggest that selenium-mediated downregulation of TGF-β1, PD-L1, and VEGF could be a viable therapeutic strategy for ccRCC.","journal":"Cancer Treatment and Research Communications","year":2024,"id":478249,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9527,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1316730,"name":"Yan Xu","orcid":"0000-0002-3625-848X","position":1,"is_corresponding":false},{"id":287600,"name":"Sean M. Geary","orcid":"0000-0003-4936-2697","position":2,"is_corresponding":false},{"id":289544,"name":"Yousef Zakharia","orcid":"0000-0001-9480-2626","position":3,"is_corresponding":false},{"id":1317096,"name":"Eman S. Kamel","orcid":null,"position":4,"is_corresponding":false},{"id":857457,"name":"Youcef M. Rustum","orcid":"0009-0002-7831-3712","position":5,"is_corresponding":false},{"id":287601,"name":"Aliasger K. Salem","orcid":"0000-0002-1923-6633","position":6,"is_corresponding":false},{"id":858269,"name":"Aseel O. Rataan","orcid":null,"position":0,"is_corresponding":true}],"reference_count":63,"raw_metadata":null,"created_at":"2026-07-19T02:06:42.155024Z","pmid":"39813754","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}