Ask about this productRelated genes to: UGT2B4 antibody
- Gene:
- UGT2B4 NIH gene
- Name:
- UDP glucuronosyltransferase family 2 member B4
- Previous symbol:
- -
- Synonyms:
- UGT2B11
- Chromosome:
- 4q13.3
- Locus Type:
- gene with protein product
- Date approved:
- 1997-07-01
- Date modifiied:
- 2016-03-01
Related products to: UGT2B4 antibody
Related articles to: UGT2B4 antibody
- Pediatric populations differ from adults in drug elimination capacity. While current scaling methods account for enzyme and transporter maturation, they overlook comorbidities, such as biliary atresia (BA), a liver disease appearing within the first 2-8 weeks of life that can progress to cirrhosis. Such conditions may impair hepatic drug clearance, requiring dose adjustments. Physiologically based pharmacokinetic (PBPK) tools aim to address such cases and have been advocated to fill gaps in clinical data instead of less formalized and evidence-based guesswork. However, the paucity of systems data in rare disease populations has hindered the development of robust PBPK models. This study used global liquid chromatography and tandem mass spectrometry (LC-MS/MS) proteomics to quantify drug-metabolizing enzymes and transporters in diseased neonatal (n = 13) and infant (n = 12) liver samples, revealing significant expression changes in biliary atresia (BA) livers vs. controls (n = 19). Based on cohort means, CYP2A6, CYP2B6, and CYP2E1 levels were 6-17-fold higher in BA livers compared to controls, while CYP4F11 and CYP20A1 were reduced. UGT1A1, UGT2B4, and UGT2B7 showed up to 16-fold higher abundance in neonates with BA. Among transporters, ABCF1 abundance increased dramatically (46-fold), whereas B3AT/SLC4A1, ADT1/SLC25A4, and S27A5/SLC27A5 were decreased. The observed alterations suggest that assuming similar liver function in BA and non-BA patients has implications, with impact varying by drug clearance pathway. While in silico models can explore this, clinical pharmacokinetic studies in BA are essential for verification. To our knowledge, such studies are absent. Our observations underscore the urgent need for dedicated pharmacokinetic studies in BA patients to improve precision dosing. - Source: PubMed
Publication date: 2026/03/04
Al-Majdoub Zubida MHoward MartynAchour BrahimBarber JillAlizai NavedRostami-Hodjegan Amin - Breast cancer in adolescents and young adults has poorer clinical outcomes, but the role of MYC in this group remains unclear. We aimed to elucidate the characteristics of MYC expression in breast cancer among adolescents and young adults. MYC expression in 42 adolescents and young adults and 110 older adults were analyzed using immunohistochemistry, fluorescence in situ hybridization, quantitative polymerase chain reaction, and RNA sequencing. Immunohistochemical c-myc expression was higher in adolescents and young adults group compared to older adults, without MYC gene amplification. In older adults, c-myc expression was associated with more aggressive features. Adolescents and young adults group showed higher c-myc expression even in tumors with less aggressive features, such as estrogen receptor positive, low Ki-67 labeling index, and early clinical stage, than older adults. RNA sequencing revealed higher expression of cholecystokinin B receptor and lower expression of uridine diphosphate glucuronosyltransferase 2 family member B4 in c-myc positive tumors of adolescents and young adults group. The preference of positive cases for both c-myc and cholecystokinin B receptor was significantly higher in adolescents and young adults group. In conclusion, c-myc overexpression makes adolescents and young adults breast cancer more aggressive through multifaceted roles including relevantly expressed cholecystokinin B receptor. Clinical trial registration: This study is not a clinical trial. - Source: PubMed
Publication date: 2025/08/26
Tanino TomoyukiNakanishi YokoNishimaki-Watanabe HarunaNozaki FumiOhni SumieTang XiaoyanHirotani YukariHashimoto SachieWatanabe ChieBando HirokoShimizu ChikakoMasuda Shinobu - Breast cancer is a very common disease affecting females on a global scale. It is responsible for approximately 10% of breast cancer-related fatalities. In 2022, approximately 2,308,897 new cases were reported globally. Recent studies focused on breast tumors have successfully recognized somatic mutations. This study aimed to identify previously unidentified somatic mutations in breast cancer patients belonging to Pakistan. - Source: PubMed
Publication date: 2025/07/31
Nawaz YasirMunir SabaTanvir FouziaRiaz Hafiza FizzahNawaz AqeelaRiaz Samreen - Although racial differences in drug response have been well documented, the mechanisms underlying these variations remain incompletely understood. The racial differences may be partially attributed to variations in the expression of drug-metabolizing enzymes (DMEs) between racial groups. We conducted a proteomics analysis of selected clinically relevant DMEs, including 12 cytochrome P450s, 10 UDP-glucuronosyltransferases (UGTs), 19 transferases, and 11 hydrolases, in liver samples from White and Black Americans and compared the protein expression levels between the 2 groups. Among the DMEs examined, CYP2C9, CYP3A5, CYP2E1, UGT1A6, UGT2B15, UGT2B4, UGT2B10, GSTA1, GSTA2, MGST1, TPMT, SULT1B1, ALB, and PON3 exhibited significantly different expression levels between the 2 populations. Genetic analysis of CYP2C9 and CYP3A5 was performed to assess the impact of genetic polymorphisms on the differential protein expression. CYP2C9 protein expression levels were significantly lower in carriers of the ∗8 and ∗11 alleles, which were found exclusively in Black Americans. Although CYP2C9 expression levels were also lower in Black subjects within the ∗1/∗1 and ∗2 or ∗3 carrier groups, the differences were not statistically significant. These results indicate that the lower CYP2C9 protein expression in Black is due to both population-specific genetic variants (ie, ∗8 and ∗11) and potentially unknown genetic or nongenetic regulators. CYP3A5 protein levels were significantly higher in Black Americans compared to White counterparts, mainly due to the greater prevalence of the functional ∗1 allele in the Black population. Our findings provide crucial insights into racial differences in hepatic DME expression and support the development of ancestry-informed personalized pharmacotherapy strategies. SIGNIFICANCE STATEMENT: This study, to our knowledge, provides the first comprehensive protein-level analysis of drug-metabolizing enzymes across racial groups, revealing differences in key enzyme expression between White and Black Americans and the associated genetic polymorphisms. These findings advance our understanding of racial differences in drug metabolism, supporting the development of an ancestry-informed personalized pharmacotherapy approach. - Source: PubMed
Publication date: 2025/07/12
Jung Sun MinShi JianWang XinwenZhu Hao-Jie - Hormone receptor-positive (HR+) breast cancer exhibits significant heterogeneity influenced by lipid metabolism and ferroptosis (LMF). While immune checkpoint inhibitors have shown promise in neoadjuvant therapy, as evidenced by the KEYNOTE-756 and CheckMate 7FL trials, identifying the optimal patient population remains challenging. This study aims to classify molecular clusters based on LMF-related genes and develop the LMF_index to predict prognosis and immunotherapy response in HR+ breast cancer. Transcriptome and clinical data of HR+ breast cancer were obtained from the Cancer Genome Atlas and Gene Expression Omnibus databases. Unsupervised clustering based on prognostic LMF-related genes identified molecular clusters, followed by tumor mutational burden (TMB) and immune microenvironment (TME) analysis. The LMF_index was constructed using least absolute shrinkage and selection operator and multivariate Cox regression analyses and validated across multiple internal and external cohorts. Its predictive value for neoadjuvant immunotherapy efficacy was assessed using GSE173839. Validation at the transcriptomic level was conducted in the Shanghai cohort, while protein-level validation was performed using multiplex immunohistochemistry (mIHC) on a tissue microarray comprising 113 breast cancer samples. Spatial analyses further examined the distribution of key panel genes within the TME. Two molecular clusters were identified in this study. Cluster 1 exhibited higher TMB, tumor purity, and Ki-67, while Cluster 2 showed greater CD8+ T cells and elevated PD-1, PD-L1, and CTLA4 expression. The LMF_index, derived from a seven-gene panel (KRT5, CD209, KLRB1, MRC1, UGT2B4, FABP7, and BIRC3), effectively stratified patients into high and low LMF_index groups, with high LMF_index patients showing significantly shorter overall survival. Patients with a low LMF_index demonstrated elevated ACSL4 expression, enhanced immune activity, higher immunophenoscores, and increased pathological complete response rates following neoadjuvant immunotherapy, indicating a greater potential benefit from immunotherapy. The prognostic value of the LMF_index was validated at the transcriptomic level in the Shanghai cohort and at the protein level using mIHC on a tissue microarray. Spatial analysis further demonstrated KLRB1 enrichment in the tumor stroma, correlating with CD8+ T cell and M1 macrophage infiltration, and an enhanced response to immunotherapy. This study identified distinct LMF-related molecular clusters in HR+ breast cancer with unique prognostic and immune characteristics. The LMF_index shows potential as a prognostic biomarker and a guide for immunotherapy strategies in HR+ breast cancer. - Source: PubMed
Publication date: 2025/06/09
Zeng ChengWang JianiZhao ShenWei YuhanQi YalongLiu ShuningWang YuanyiGe HeweiYang XiaoqiTan YujingJiang YizhouQian HailiMa Fei