Zebularine suppressed gemcitabine-induced senescence and improved the cellular and plasma pharmacokinetics of gemcitabine, augmented by liposomal co-delivery

Tang, Mingtan; Hernandez, Lina Lozano; Reginald-Opara, Joy N.; Svirskis, Darren; Leung, Euphemia; Wang, Hongbo; Wu, Zimei

doi:10.1016/j.ijpharm.2021.120659

Cited by 11 publications

(2 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Zebularine also inhibits cytidine deaminase, which confers resistance to nucleoside analogs ( Tang et al, 2021 ). Zebularine can be incorporated into DNA and form covalent complexes with DNMT to competitively inhibit DNMT activity, demethylate tumor suppressor genes, such as SFRP2, Dkk3, and p16, and inhibit tumor cell proliferation, differentiation, and metastasis.…”

Section: Dna Methylation Inhibitorsmentioning

confidence: 99%

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

et al. 2023

View full text Add to dashboard Cite

Liver fibrosis is a repair response to injury caused by various chronic stimuli that continually act on the liver. Among them, the activation of hepatic stellate cells (HSCs) and their transformation into a myofibroblast phenotype is a key event leading to liver fibrosis, however the mechanism has not yet been elucidated. The molecular basis of HSC activation involves changes in the regulation of gene expression without changes in the genome sequence, namely, via epigenetic regulation. DNA methylation is a key focus of epigenetic research, as it affects the expression of fibrosis-related, metabolism-related, and tumor suppressor genes. Increasing studies have shown that DNA methylation is closely related to several physiological and pathological processes including HSC activation and liver fibrosis. This review aimed to discuss the mechanism of DNA methylation in the pathogenesis of liver fibrosis, explore DNA methylation inhibitors as potential therapies for liver fibrosis, and provide new insights on the prevention and clinical treatment of liver fibrosis.

show abstract

Section: Dna Methylation Inhibitorsmentioning

confidence: 99%

Role and mechanism of DNA methylation and its inhibitors in hepatic fibrosis

et al. 2023

View full text Add to dashboard Cite

show abstract

“…After screening by the univariate Cox regression analysis, log-rank test, and LASSO Cox method, 5 genes were ultimately regarded to construct the stable and effective prognostic SRG_score and validate its predictive ability, including TRPS1, KCNH3, CDA, ATP1A3, and FLRT3, which was proved to be efficient by survival and ROC analysis. These genes had been reported to be related with other cancers and might be potential novel prognostic factors of PC [ 30 , 31 ]. In this study, the SRG score could link senescence and prognosis and showed good performance in predicting the survival of patients.…”

Section: Discussionmentioning

confidence: 99%

The Senescence-Related Signature Predicts Prognosis and Characterization of Tumor Microenvironment Infiltration in Pancreatic Cancer

Hua

Zheng

Fan

et al. 2022

BioMed Research International

View full text Add to dashboard Cite

Background. Senescence is thought to be an imperative effect on the development of cancer. However, few studies pay an attention to the senescence-associated genes in pancreatic cancer (PC). The prognostic value of senescence-related genes (SRGs) and their involvement in tumor microenvironment (TME) in the PC remain obscure. The aim of this research was to investigate the prognostic role of senescence-associated genes and their affection in TME in PC. Methods. The transcriptome and clinical information of PC patients were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. Two SRG-mediated molecular clusters were comprehensively identified. In total, data from the 285 PC patients were randomly used to develop a senescence-associated gene signature in the training set and verified in the validation set. Immune microenvironment analysis pertained to senescence-related genes was performed. Results. A SRG_score including five senescence-associated genes was established to separate PC patients into two risk groups. High-risk patients had worse overall survival than low-risk patients. The result of the multivariate Cox regression analysis identified the risk score and stage as independent prognostic factors for PC patients. Receiver operating characteristic curve (ROC) analysis confirmed the credible predictive ability of the nomogram. The area under time-dependent ROC curve (AUC) reached 0.746 at 1 year, 0.781 at 3 years, and 0.868 at 5 years in the training set and 0.653 at 1 year, 0.755 at 3 years, and 0.785 at 5 years in the validation set. Moreover, the SRG_score was associated with TME, tumor mutation burden (TMB), and chemotherapeutic drug sensitivity. Conclusions. This study found that the novel SRG_score could be an independent prognostic target for PC patients. Senescence-associated genes had a vital impact on the immune microenvironment and the treatment of PC patients.

show abstract