Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Older patients who are diagnosed with colon cancer face unique challenges, specifically regarding to cancer treatment. The aim of this study was to identify prognostic signatures to predicting prognosis in colon cancer patients through a detailed transcriptomic analysis. RNA-seq expression profile, miRNA expression profile, and clinical phenotype information of all the samples of TCGA colon adenocarcinoma were downloaded and differentially expressed mRNAs (DEMs), differentially expressed lncRNAs (DELs) and differentially expressed miRNAs (DEMis) were identified. A competing endogenous RNA (ceRNA) network was constructed further and DEMs related with prognosis in the ceRNA network was screened using Cox regression analysis. Risk score models for predicting the prognosis of colon cancer patients were built using these DEMs. A total of 1476 DEMs, 9 DELs, and 243 DEMis between the tumor and normal samples were identified and functional enrichment analyses showed that the DEMs were significantly enriched in the nervous system development, ribosome biogenesis pathways in eukaryotes, and drug metabolism cytochrome P450. Twelve DEMs related with prognosis were screened from the ceRNA network. Thereafter, the risk score models of prognostic DEMs were obtained, involving seven DEMs (SGCG, CLDN23, SLC4A4, CCDC78, SLC17A7, OTOP3, and SMPDL3A). Additionally, cancer stage was identified as a prognostic clinical factor. This prognostic signature was further validated in two independent datasets. Our study developed a seven-mRNA and one-clinical factor signature that are associated with prognosis in colon cancer patients, which may serve as possible biomarkers and therapeutic targets in the future.
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PMID:Association of a novel seven-gene expression signature with the disease prognosis in colon cancer patients. 3161 69

ATP-binding cassette (ABC) transporters, such as breast cancer resistance protein (BCRP), are key players in resistance to multiple anti-cancer drugs, leading to cancer treatment failure and cancer-related death. Currently, there are no clinically approved drugs for reversal of cancer drug resistance caused by ABC transporters. This study investigated if a novel drug candidate, SCO-201, could inhibit BCRP and reverse BCRP-mediated drug resistance. We applied in vitro cell viability assays in SN-38 (7-Ethyl-10-hydroxycamptothecin)-resistant colon cancer cells and in non-cancer cells with ectopic expression of BCRP. SCO-201 reversed resistance to SN-38 (active metabolite of irinotecan) in both model systems. Dye efflux assays, bidirectional transport assays, and ATPase assays demonstrated that SCO-201 inhibits BCRP. In silico interaction analyses supported the ATPase assay data and suggest that SCO-201 competes with SN-38 for the BCRP drug-binding site. To analyze for inhibition of other transporters or cytochrome P450 (CYP) enzymes, we performed enzyme and transporter assays by in vitro drug metabolism and pharmacokinetics studies, which demonstrated that SCO-201 selectively inhibited BCRP and neither inhibited nor induced CYPs. We conclude that SCO-201 is a specific, potent, and potentially non-toxic drug candidate for the reversal of BCRP-mediated resistance in cancer cells.
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PMID:The Pyrazolo[3,4-d]pyrimidine Derivative, SCO-201, Reverses Multidrug Resistance Mediated by ABCG2/BCRP. 3214 47


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