Drug Metabolism and Disposition, Год журнала: 2023, Номер 51(3), С. 348 - 349
Опубликована: Фев. 27, 2023
The special section in the March 2023 issue of Drug Metabolism and Disposition features articles on "Drug Precision Medicine" contributed by Dr. Namandje N. Bumpus, recipient 2015 Richard Okita Early Career Award (the Award, [Fig
Язык: Английский
Journal of Pharmaceutical Analysis, Год журнала: 2023, Номер 13(10), С. 1102 - 1116
Опубликована: Авг. 23, 2023
Cellular heterogeneity is crucial for understanding tissue biology and disease pathophysiology. Pharmacological research being advanced by single-cell metabolic analysis, which offers a technique to identify variations in RNA, proteins, metabolites, drug molecules cells. In this review, the recent advancement of analysis techniques their applications metabolism response are summarized. High-precision controlled isolation manipulation provided microfluidics-based methods, such as droplet microfluidics, microchamber, open microfluidic probe, digital microfluidics. They used tandem with variety detection techniques, including optical imaging, Raman spectroscopy, electrochemical detection, RNA sequencing, mass spectrometry, evaluate changes administration. The advantages disadvantages different discussed along challenges future directions analysis. These employed pharmaceutical studying resistance pathway, therapeutic targets discovery, vitro model evaluation.
Язык: Английский
Процитировано
11
International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1628 - 1628
Опубликована: Янв. 28, 2024
Known as a diverse collection of neoplastic diseases, breast cancer (BC) can be hyperbolically characterized dynamic pseudo-organ, living organism able to build complex, open, hierarchically organized, self-sustainable, and self-renewable tumor system, population, species, local community, biocenosis, or an evolving dynamical ecosystem (i.e., immune metabolic ecosystem) that emphasizes both developmental continuity spatio-temporal change. Moreover, cell also known oncobiota, has been described non-sexually reproducing well migratory invasive species expresses intelligent behavior, endangered parasite fights survive, optimize its features inside the host’s ecosystem, is exploit disrupt host circadian cycle for improving own proliferation spreading. BC tumorigenesis compared with early embryo placenta development may suggest new strategies research therapy. Furthermore, environmental disease ecological disorder. Many mechanisms progression have explained by principles ecology, biology, evolutionary paradigms. authors discussed ecological, developmental, more successful anti-cancer therapies, understanding bases exploitable vulnerabilities. Herein, we used integrated framework three theories: Bronfenbrenner’s theory human development, Vannote’s River Continuum Concept (RCC), Ecological Evolutionary Developmental Biology (Eco-Evo-Devo) theory, explain understand several eco-evo-devo-based govern progression. Multi-omics fields, taken together onco-breastomics, offer better opportunities integrate, analyze, interpret large amounts complex heterogeneous data, such various big-omics data obtained multiple investigative modalities, drive treatment. These integrative eco-evo-devo theories help clinicians diagnose treat BC, example, using non-invasive biomarkers in liquid-biopsies emerged from omics-based accurately reflect biomolecular landscape primary order avoid mutilating preventive surgery, like bilateral mastectomy. From perspective preventive, personalized, participatory medicine, these hypotheses patients think about this process governed natural rules, possible causes disease, gain control on their health.
Язык: Английский
Процитировано
4
Food and Chemical Toxicology, Год журнала: 2024, Номер 185, С. 114499 - 114499
Опубликована: Фев. 2, 2024
Язык: Английский
Процитировано
4
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
0
Pharmacogenetics and Genomics, Год журнала: 2024, Номер unknown
Опубликована: Май 17, 2024
Objective Varied expression of drug-metabolizing enzymes (DME) genes dictates the intensity and duration drug response in cancer treatment. This study aimed to investigate transcriptional profile DMEs tumor microenvironment (TME) at single-cell level their impact on individual responses anticancer therapy. Methods Over 1.3 million cells from 481 normal/tumor samples across 9 solid types were integrated changes DME genes. A ridge regression model based PRISM database was constructed predict influence gene sensitivity. Results Distinct patterns revealed resolution different types. Several highly enriched epithelial (e.g. GPX2, TST CYP3A5 ) or TME components CYP4F3 monocytes). Particularly, GPX2 differentially expressed compared those normal samples. Utilizing database, we found that elevated reduced linked enhanced sensitivity particular chemo-drugs gemcitabine, daunorubicin, dasatinib, vincristine, paclitaxel oxaliplatin). Conclusion Our findings underscore varied pattern components, highlighting potential as biomarkers for selecting appropriate chemotherapy agents.
Язык: Английский
Процитировано
3
Chemical Research in Toxicology, Год журнала: 2024, Номер 37(6), С. 850 - 872
Опубликована: Июнь 4, 2024
Humans are exposed to numerous electrophilic chemicals either as medicines, in the workplace, nature, or through use of many common cosmetic and household products. Covalent modification human proteins by such chemicals, protein haptenation, is a occurrence cells may result generation antigenic species, leading development hypersensitivity reactions. Ranging severity symptoms from local cutaneous reactions rhinitis potentially life-threatening anaphylaxis severe Stephen-Johnson syndrome (SJS) toxic epidermal necrolysis (TEN), all these have same Molecular Initiating Event (MIE), i.e. haptenation. However, not individuals who develop hypersensitivity. In present review, we examine chemistry behind haptenation formation neoantigens. We explore simple involving single molecule additions nucleophilic side chain complex multiple centers on more than one well reactive molecules interaction with cellular detoxification mechanisms. Besides species enabling activation immune system, additional events which directly presence cells, including key defense mechanisms immediate consequences those reactions, their potential effects. discuss factors that work concert act prevent it developing. also review harnessing specificity design potent covalent therapeutic inhibitors.
Язык: Английский
Процитировано
3
Springer eBooks, Год журнала: 2024, Номер unknown, С. 1 - 15
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0
Carcinogenesis, Год журнала: 2024, Номер unknown
Опубликована: Окт. 5, 2024
Abstract Using LC–MS/MS analysis we previously showed for the first time (Carcinogenesis 43:746–753, 2022) that levels of DNA damage induced by benzo[a]pyrene (B[a]P), an oral carcinogen and tobacco smoke (TS) constituent, were significantly higher in buccal cells smokers than those nonsmokers; these results suggest potential contribution B[a]P development squamous cell carcinoma (OSCC) humans. Treating cancers, including OSCC, at late stages, even with improved targeted therapies, continues to be a major challenge. Thus interception/prevention remains preferable approach OSCC management control. In previous preclinical studies, others demonstrated protective effects black raspberry (BRB) against carcinogen-induced OSCC. Thus, translate findings, tested hypothesis Phase 0 clinical study BRB administration reduces smokers. After enrolling 27 smokers, baseline collected before lozenges (5/day 8 weeks, 1 gm powder/lozenge) baseline, middle end administration. The last samples 4 weeks after cessation (washout period). B[a]P-induced (BPDE-N2-dG) was evaluated LC–MS/MS. resulted significant reduction damage: 26.3% midpoint (P = .01506) compared 36.1% .00355), 16.6% .007586). Our benefits as chemopreventive agent TS-initiated
Язык: Английский
Процитировано
0
Drug Metabolism and Disposition, Год журнала: 2024, Номер 52(11), С. 1208 - 1216
Опубликована: Май 31, 2024
Over the past 20 years, quantitative proteomics has contributed a wealth of protein expression data, which are currently used for variety systems pharmacology applications, as complement or surrogate activity corresponding proteins. A symposium at 25th North American ISSX meeting, in Boston, September 2023, was held to explore current and emerging applications translational strategies improved integration into model-informed drug development based on practical experience each presenters. summary talks discussions is presented this perspective alongside future outlooks that were outlined meetings. Significance Statement This explores precision medicine, outlines development.
Язык: Английский
Процитировано
0
Springer eBooks, Год журнала: 2024, Номер unknown, С. 1 - 15
Опубликована: Янв. 1, 2024
Язык: Английский
Процитировано
0