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1.
Pathology ; 56(5): 653-661, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38811262

RESUMO

Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (E20ins) are the third most frequent mutations observed in non-small cell lung cancer, accounting for approximately 1-10% of all EGFR mutations. In the era of precision medicine and targeted therapies, consistent naming of genetic alterations is crucial to avoid confusion and errors. However, the annotation of EGFR E20ins mutations has been inconsistent, leading to confusion in the scientific literature and product documentation. In this study, our primary objective was to investigate the usage of different annotation related to EGFR E20ins in independent studies. Additionally, we assessed the distribution of EGFR E20ins mutations and estimated the detection coverage expected from each available EGFR E20ins detection assay. A total of 1,418 EGFR E20ins mutations were collected from six studies (FoundationInsights, Geneseeq Technology Inc, mobocertinib phase I/II trial, poziotinib phase II trial, sunvozertinib phase I trial, and Samsung Medical Center) and reorganised according to Human Genome Variation Society (HGVS) nomenclature. Our analysis revealed that the majority of EGFR E20ins mutations requiring correction were 'insertion' or 'deletion-insertion', which should be appropriately designated as 'duplication'. Additionally, duplicated variants were reported using different annotations in each study, and furthermore, even identical variant sequences were annotated differently within the same study. In all six studies, p.A767_V769dup and p.S768_D770dup were the most frequently observed EGFR E20ins. The Oncomine Dx Target Test showed the highest patient coverage at 77.2%, followed by the Droplex EGFR Mutation Test v2 with a patient coverage of 70.5% for EGFR E20ins patients. To ensure comprehensive coverage in real-world settings, it is essential to standardise the annotations for each variant, for example using the HGVS nomenclature. The accurate classification and analysis of drug responsiveness in EGFR E20ins necessitate consideration of the nomenclature, particularly with respect to the locations where the actual mutations occur.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Éxons , Neoplasias Pulmonares , Medicina de Precisão , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Éxons/genética , Mutação , Mutagênese Insercional/genética , Terminologia como Assunto
2.
Transplant Proc ; 56(3): 701-704, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38548510

RESUMO

BACKGROUND: Liver fibrosis is a chronic inflammatory disease that progresses and has a high mortality rate. This study was performed to investigate the protective effect of rapamycin on experimentally induced chronic liver injury in mice models using both biochemical parameters of liver function enzymes. METHODS: Twenty-four mice were divided randomly into 4 equal groups: [1] the normal group, n = 6; [2] the liver fibrosis (LF) group, n = 6; [3] the LF with the treatment of rapamycin group, n = 6; [4] the LF with the treatment of silimaryn, n = 6. RESULTS: In the group receiving oral administration of rapamycin, aspartate aminotransferase, alanine aminotransferase, urea, and creatinine were found to significantly decrease compared to the liver fibrosis group. Rapamycin, in the orally administered group, demonstrated a statistically significant decrease in the expression of interleukin (IL) 10, IL-1B, inducible nitric oxide synthase, and tumor necrosis factor alpha compared to the liver fibrosis group. CONCLUSIONS: In this study, we explored the potential therapeutic effects of rapamycin on liver fibrosis in an animal model.


Assuntos
Modelos Animais de Doenças , Cirrose Hepática , Camundongos Endogâmicos C57BL , Sirolimo , Animais , Sirolimo/farmacologia , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/patologia , Camundongos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Aspartato Aminotransferases/sangue , Alanina Transaminase/sangue , Óxido Nítrico Sintase Tipo II/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Creatinina/sangue
3.
Vaccine ; 42(4): 871-878, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38225184

RESUMO

BACKGROUND: Despite the demonstrated immunogenicity and safety of the 20-valent pneumococcal conjugate vaccine (PCV20) in older adults, the cost-effectiveness of the PCV20 was not examined compared to the 23-valent pneumococcal polysaccharide vaccine (PPSV23) in South Korea. Therefore, this study aimed to evaluate the cost-effectiveness of PCV20 compared with PPSV23 in adults aged 65 years and older in South Korea. METHODS: We constructed a Markov model that included susceptible states, invasive pneumococcal disease (IPD), non-bacteremic pneumonia (NBP), and death. The population was categorized by disease risk status (low risk, moderate risk, and high risk) and age group (65-74/75-84/85-99 years) at model entry. The annual incidence and mortality of IPD and NBP associated with PCV20 and PPSV23 were estimated based on serotype coverage, vaccine coverage, and vaccine effectiveness. The disease costs and utilities were obtained from previous studies. The incremental cost-effectiveness ratio (ICER) was used to evaluate cost-effectiveness within the threshold of 16,824 USD per quality-adjusted life-year (QALY). RESULTS: Among the total population (n = 8,843,072), PCV20 prevented 1941 and 50,575 cases of IPDs and NBPs, respectively, and 898 and 8593 deaths due to IPDs and NBPs compared to PPSV23. The total medical cost per person was 12.11 USD higher in PCV20, with a gain of 0.0053 LYs and 0.0045 QALYs per person. The ICER for PCV20 and PPSV23 was 2270 USD/LY and 2677 USD/QALY. CONCLUSIONS: In South Korea, PCV20 is a cost-effective option compared with PPSV23 for adults aged 65 years and older. These cost-effectiveness results provide evidence for decision-making regarding the approval and National Immunization Program implementation of PCV20.


Assuntos
Infecções Pneumocócicas , Vacinas Pneumocócicas , Humanos , Idoso , Análise Custo-Benefício , Vacinas Conjugadas/uso terapêutico , Vacinas Pneumocócicas/uso terapêutico , Infecções Pneumocócicas/epidemiologia , Infecções Pneumocócicas/prevenção & controle , Vacinação/métodos , República da Coreia/epidemiologia
4.
Expert Opin Pharmacother ; 23(11): 1247-1257, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35759783

RESUMO

INTRODUCTION: Although tyrosine kinase inhibitors (TKIs) have improved the efficacy of treatment for non-small cell lung cancer (NSCLC), the accessibility of TKIs is limited due to high costs. Despite the critical role of the cost-effectiveness of TKIs on decision-making, no systematic reviews have compared the cost-effectiveness of comparable TKIs. Therefore, we systemically reviewed the economic evaluation studies on various TKIs for NSCLC. AREAS COVERED: We searched PubMed and the Cochran Library to identify the published economic evaluation studies of TKIs in NSCLC patients that were published by January 2022. All of the included studies (n = 38) evaluated the cost-effectiveness of epidermal growth factor receptor (EGFR)-TKIs (n = 29) or anaplastic lymphocyte kinase (ALK)-TKIs (n = 9). The cost-effectiveness results were reported as the incremental cost-effectiveness ratio per quality-adjusted life-year, except for three studies. EXPERT OPINION: We found that the economic evaluation studies of the first and second generation of EGFR-TKIs and ALK-TKIs varied by the country and study settings, such as comparator and input parameters. In 12 studies, osimertinib (EGFR-TKI) was not cost-effective compared to other first/second EGFR-TKIs, regardless of the study settings. More evidence can be provided about cost-effectiveness of the third-generation TKIs in future research.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Inibidores de Proteínas Quinases , Quinase do Linfoma Anaplásico/antagonistas & inibidores , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/economia , Análise Custo-Benefício , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/economia , Mutação , Inibidores de Proteínas Quinases/economia , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores
5.
Chem Commun (Camb) ; 57(79): 10222-10225, 2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34523638

RESUMO

We developed a one-minute, one-step SARS-CoV-2 antigen assay based on protein-induced fluorescence enhancement of a DNA aptamer. The system showed significant selectivity and sensitivity towards both nucleocapsid protein and SARS-CoV-2 virus lysate, but with marked improvements in speed and manufacturability. We hence propose this platform as a mix-and-read testing strategy for SARS-CoV-2 that can be applied to POC diagnostics in clinical settings, especially in low- and middle-income countries.


Assuntos
Antígenos Virais/química , Aptâmeros de Nucleotídeos/química , Teste para COVID-19/métodos , COVID-19/diagnóstico , Proteínas do Nucleocapsídeo de Coronavírus/química , SARS-CoV-2 , Bioensaio , Carbocianinas/química , Fluorescência , Corantes Fluorescentes/química , Fosfoproteínas/química
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