Pharmacogenomics Journal最新文献_第2页

Implementation of pharmacogenetic testing in pediatric oncology: barriers and facilitators assessment at eight Canadian academic health centres 在儿科肿瘤学中实施药物基因检测：加拿大八家学术健康中心的障碍和促进因素评估。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-11-19 DOI: 10.1038/s41397-024-00356-9

Jeanette Cooper, Joshua Pratt, Jamie Park, Christine Fahim, Jessica M. Lovnicki, Gabriella S. S. Groeneweg, Bruce Carleton, Sharon Straus

引用次数: 0

Correction to: A pharmacogenomic study on the pharmacokinetics of tacrolimus in healthy subjects using the DMETTM Plus platform 更正：使用 DMETTM Plus 平台对健康受试者他克莫司药代动力学进行药物基因组学研究。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-11-18 DOI: 10.1038/s41397-024-00354-x

Y Choi, F Jiang, H An, H J Park, J H Choi, H Lee

引用次数: 0

TMEM158, as plasma cfRNA marker, promotes proliferation and doxorubicin resistance in ovarian cancer 作为血浆 cfRNA 标记的 TMEM158 可促进卵巢癌的增殖和多柔比星耐药性。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-11-15 DOI: 10.1038/s41397-024-00357-8

Xiaolin Zhu, Tongchao Liu, Xuexue Yin

{"title":"TMEM158, as plasma cfRNA marker, promotes proliferation and doxorubicin resistance in ovarian cancer","authors":"Xiaolin Zhu, Tongchao Liu, Xuexue Yin","doi":"10.1038/s41397-024-00357-8","DOIUrl":"10.1038/s41397-024-00357-8","url":null,"abstract":"The current study aimed to identify the potential biomarker for the diagnosis of ovarian cancer within plasma cell-free RNA (cfRNA) species and to characterize their oncogenic properties. cfRNAs were isolated from the peripheral blood of ovarian cancer patients and sequenced using an NGS platform. Principal component analysis (PCA) was performed using Salmon software. Gene ontology (GO) analysis was conducted with clusterProfiler. The relative abundance of TMEM158 transcripts was determined by real-time PCR. Cell viability and proliferation was monitored using the MTT and cell counting assays, respectively. The protein levels of TMEM158 and ABCG2 were quantified by immunoblotting. We observed a clear separation of cfRNAs between ovarian cancer patients and healthy individuals. Additionally, we identified TMEM158 as the most significantly differential gene in both peripheral blood and tumor tissues. Overexpression of TMEM158 stimulated cell viability and promoted cell proliferation in ovarian cancer cells. Notably, the aberrant upregulation of TMEM158 was closely associated with doxorubicin resistance in ovarian cancer. Mechanistically, we demonstrated that TMEM158 positively regulates ABCG2 expression, which consequently contributes to drug resistance. In summary, we identified cfRNA TMEM158 as a potential diagnostic biomarker for ovarian cancer and elucidated the critical involvement of TMEM158-ABCG2 signaling axis in the development of doxorubicin resistance.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The ZNF263/CPT1B axis regulates fatty acid β-oxidation to affect cisplatin resistance in lung adenocarcinoma ZNF263/CPT1B轴调节脂肪酸β-氧化，从而影响肺腺癌的顺铂耐药性。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-11-05 DOI: 10.1038/s41397-024-00355-w

Renhe Yan, Caibin Zheng, Suting Qian, Kezhi Li, Xiangsheng Kong, Shunhang Liao

{"title":"The ZNF263/CPT1B axis regulates fatty acid β-oxidation to affect cisplatin resistance in lung adenocarcinoma","authors":"Renhe Yan, Caibin Zheng, Suting Qian, Kezhi Li, Xiangsheng Kong, Shunhang Liao","doi":"10.1038/s41397-024-00355-w","DOIUrl":"10.1038/s41397-024-00355-w","url":null,"abstract":"Cisplatin is widely used as a conventional chemotherapy drug for lung adenocarcinoma (LUAD) patients. However, the chemical resistance greatly limits its therapeutic potential. The study aimed to uncover the specific role and new mechanisms of CPT1B in the cisplatin resistance of LUAD. Bioinformatics analysis was utilized to analyze the expression level and enriched pathway of CPT1B in LUAD. The expression of CPT1B in LUAD cells was determined by utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot (WB). The cisplatin resistance in LUAD was measured with IC50 values obtained from the CCK-8 assay. We used the corresponding reagent kit and WB analysis to determine the levels of triglycerides, cholesterol, phospholipids, fatty acid β-oxidation (FAO) rate, and expression of lipid metabolism-related proteins. Finally, the regulation relationship between CPT1B and ZNF263 was confirmed through bioinformatics analysis, dual-luciferase, and chromatin immunoprecipitation assays. The present investigation revealed that CPT1B was upregulated in LUAD, participating in fatty acid metabolism pathways. In vitro studies have shown that upregulation of CPT1B promoted cisplatin resistance in LUAD cells. This promotion effect induced by the high expression of CPT1B on cisplatin resistance in LUAD was weakened after the addition of the FAO inhibitor Etomoxir. Mechanistically, ZNF263 was capable of binding to the promoter of CPT1B to activate its transcription, thereby enhancing FAO and promoting cisplatin resistance in LUAD cells. In summary, ZNF263 enhances cisplatin resistance in LUAD cells by upregulating CPT1B expression. This study enriches the molecular mechanisms of LUAD chemotherapy resistance and provides new directions for exploring therapeutic targets for LUAD.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142583442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cost analysis of CYP2C19 genetic testing in percutaneous coronary intervention patients 经皮冠状动脉介入治疗患者的 CYP2C19 基因检测成本分析。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-10-08 DOI: 10.1038/s41397-024-00353-y

Samuel Huxley, James Moriarty, Mark A. Hlatky, Ryan Lennon, Kent Bailey, Malcolm Bell, Nancy Geller, Amir Lerman, Verghese Mathew, Yves Rosenberg, Michael Farkouh, Charanjit Rihal, Bijan Borah, Naveen L. Pereira

{"title":"Cost analysis of CYP2C19 genetic testing in percutaneous coronary intervention patients","authors":"Samuel Huxley, James Moriarty, Mark A. Hlatky, Ryan Lennon, Kent Bailey, Malcolm Bell, Nancy Geller, Amir Lerman, Verghese Mathew, Yves Rosenberg, Michael Farkouh, Charanjit Rihal, Bijan Borah, Naveen L. Pereira","doi":"10.1038/s41397-024-00353-y","DOIUrl":"10.1038/s41397-024-00353-y","url":null,"abstract":"CYP2C19 loss of function (LOF) carriers undergoing percutaneous coronary intervention (PCI) have an increased risk of ischemic events when treated with clopidogrel. PCI patients in TAILOR-PCI were randomized to clopidogrel or genotype-guided (GG) therapy in which LOF carriers received ticagrelor and non-carriers clopidogrel. Direct medical costs associated with a GG approach have not been described before. TAILOR-PCI participants for whom direct medical costs were available for the duration from the date of PCI to one-year post PCI were included. Primary cost estimates were obtained from the Mayo Clinic Cost Data Warehouse. There were no differences in direct medical costs between the GG and clopidogrel groups (mean $20,682 versus $19,747, p = 0.11) however total costs were greater in the GG group (mean $21,245 versus $19,891, p = 0.02) which was primarily driven by ticagrelor costs. In conclusion the increased expense of a GG strategy post PCI as compared to clopidogrel for all is primarily driven by the cost of ticagrelor.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"1-7"},"PeriodicalIF":2.9,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395293","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effects and interaction of single nucleotide polymorphisms at the pharmacokinetic/pharmacodynamic site: insights from the Rotterdam study into metformin clinical response and dose titration 单核苷酸多态性在药代动力学/药效学部位的影响和相互作用：鹿特丹研究对二甲双胍临床反应和剂量滴定的启示。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-10-07 DOI: 10.1038/s41397-024-00352-z

Soroush Mohammadi Jouabadi, Payam Peymani, Mitra Nekouei Shahraki, Jeroen G. J. van Rooij, Linda Broer, Anton J. M. Roks, Bruno H. Stricker, Fariba Ahmadizar

{"title":"Effects and interaction of single nucleotide polymorphisms at the pharmacokinetic/pharmacodynamic site: insights from the Rotterdam study into metformin clinical response and dose titration","authors":"Soroush Mohammadi Jouabadi, Payam Peymani, Mitra Nekouei Shahraki, Jeroen G. J. van Rooij, Linda Broer, Anton J. M. Roks, Bruno H. Stricker, Fariba Ahmadizar","doi":"10.1038/s41397-024-00352-z","DOIUrl":"10.1038/s41397-024-00352-z","url":null,"abstract":"Our study investigated the impact of genetic variations on metformin glycemic response in a cohort from the Rotterdam Study, comprising 14,926 individuals followed for up to 27 years. Among 1285 metformin users of European ancestry, using linear mixed models, we analyzed the association of single nucleotide polymorphisms (SNPs) and a Polygenic Risk Score (PRS) with glycemic response, measured by changes in metformin dosage or HbA1c levels. While individual genetic variants showed no significant association, rs622342 on SLC2A1 correlated with increased glycemic response only in metformin monotherapy patients (β = −2.09, P-value < 0.001). The collective effect of variants, as represented by PRS, weakly correlated with changes in metformin dosage (β = 0.023, P-value = 0.027). Synergistic interaction was observed between rs7124355 and rs8192675. Our findings suggest that while higher PRS correlates with increased metformin dosage, its modest effect size limits clinical utility, emphasizing the need for future research in diverse populations to refine genetic risk models.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 6","pages":"1-8"},"PeriodicalIF":2.9,"publicationDate":"2024-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41397-024-00352-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142395294","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical and economic outcomes of a pharmacogenomics-enriched comprehensive medication management program in a self-insured employee population 在自保员工群体中开展药物基因组学强化综合用药管理项目的临床和经济效果。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-10-02 DOI: 10.1038/s41397-024-00350-1

Maren S. Fragala, Murray Keogh, Steven E. Goldberg, Raymond A. Lorenz, Jeffrey A. Shaman

{"title":"Clinical and economic outcomes of a pharmacogenomics-enriched comprehensive medication management program in a self-insured employee population","authors":"Maren S. Fragala, Murray Keogh, Steven E. Goldberg, Raymond A. Lorenz, Jeffrey A. Shaman","doi":"10.1038/s41397-024-00350-1","DOIUrl":"10.1038/s41397-024-00350-1","url":null,"abstract":"Clinical and economic outcomes from a pharmacogenomics-enriched comprehensive medication management program were evaluated over 26 months in a self-insured U.S. employee population (n = 452 participants; n = 1500 controls) using propensity matched pre-post design with adjusted negative binomial and linear regression models. After adjusting for baseline covariates, program participation was associated with 39% fewer inpatient (p = 0.05) and 39% fewer emergency department (p = 0.002) visits, and with 21% more outpatient visits (p < 0.001) in the follow-up period compared to the control group. Results show pharmacogenomics-enriched comprehensive medication management can favorably impact healthcare utilization in a self-insured employer population by reducing emergency department and inpatient visits and can offer the potential for cost savings. Self-insured employers may consider implementing pharmacogenomics-enriched comprehensive medication management to improve the healthcare of their employees.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-6"},"PeriodicalIF":2.9,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11446811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142367382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extreme phenotype sampling and next generation sequencing to identify genetic variants associated with tacrolimus in African American kidney transplant recipients 通过极端表型取样和新一代测序技术，确定非裔美国肾移植受者中与他克莫司相关的基因变异。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-23 DOI: 10.1038/s41397-024-00349-8

Moataz E. Mohamed, Bin Guo, Baolin Wu, David P. Schladt, Amutha Muthusamy, Weihua Guan, Juan E. Abrahante, Guillaume Onyeaghala, Abdelrahman Saqr, Nathan Pankratz, Gaurav Agarwal, Roslyn B. Mannon, Arthur J. Matas, William S. Oetting, Rory P. Remmel, Ajay K. Israni, Pamala A. Jacobson, DeKAF Genomics and GEN03 Investigators, Casey R. Dorr

{"title":"Extreme phenotype sampling and next generation sequencing to identify genetic variants associated with tacrolimus in African American kidney transplant recipients","authors":"Moataz E. Mohamed, Bin Guo, Baolin Wu, David P. Schladt, Amutha Muthusamy, Weihua Guan, Juan E. Abrahante, Guillaume Onyeaghala, Abdelrahman Saqr, Nathan Pankratz, Gaurav Agarwal, Roslyn B. Mannon, Arthur J. Matas, William S. Oetting, Rory P. Remmel, Ajay K. Israni, Pamala A. Jacobson, DeKAF Genomics and GEN03 Investigators, Casey R. Dorr","doi":"10.1038/s41397-024-00349-8","DOIUrl":"10.1038/s41397-024-00349-8","url":null,"abstract":"African American (AA) kidney transplant recipients (KTRs) have poor outcomes, which may in-part be due to tacrolimus (TAC) sub-optimal immunosuppression. We previously determined the common genetic regulators of TAC pharmacokinetics in AAs which were CYP3A5 *3, *6, and *7. To identify low-frequency variants that impact TAC pharmacokinetics, we used extreme phenotype sampling and compared individuals with extreme high (n = 58) and low (n = 60) TAC troughs (N = 515 AA KTRs). Targeted next generation sequencing was conducted in these two groups. Median TAC troughs in the high group were 7.7 ng/ml compared with 6.3 ng/ml in the low group, despite lower daily doses of 5 versus 12 mg, respectively. Of 34,542 identified variants across 99 genes, 1406 variants were suggestively associated with TAC troughs in univariate models (p-value < 0.05), however none were significant after multiple testing correction. We suggest future studies investigate additional sources of TAC pharmacokinetic variability such as drug-drug-gene interactions and pharmacomicrobiome.","PeriodicalId":54624,"journal":{"name":"Pharmacogenomics Journal","volume":"24 5","pages":"1-9"},"PeriodicalIF":2.9,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047493","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

STRIPE partners in precision medicine series: provider perspective STRIPE 合作伙伴精准医疗系列：医疗服务提供者视角。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-23 DOI: 10.1038/s41397-024-00348-9

Christine M. Formea, Paldeep Atwal, Kathryn Meintsma, Martin Dawes, Gary Marchant, Ben L. Kong, J. Shawn Jones, Sara L. Rogers

引用次数: 0

A collaborative force for precision medicine progress: the STRIPE pharmacogenomics conference series 精准医学进步的合作力量：STRIPE 药物基因组学系列会议。

IF 2.9 3区医学

Pharmacogenomics Journal Pub Date : 2024-08-15 DOI: 10.1038/s41397-024-00345-y

Sara L. Rogers, J. Shawn Jones, Ben L. Kong, Christine M. Formea, Jacob Awkal, Benjamin G. Brown

引用次数: 0