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1.
BMC Cancer ; 21(1): 515, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962574

RESUMO

BACKGROUND: The treatment landscape for advanced non-small cell lung cancer (aNSCLC) has evolved rapidly since immuno-oncology (IO) therapies were introduced. This study used recent data to assess real-world treatment patterns and clinical outcomes in aNSCLC in the United Kingdom. METHODS: Electronic prescribing records of treatment-naive patients starting first-line (1 L) treatment for aNSCLC between June 2016 and March 2018 (follow-up until December 2018) in the United Kingdom were assessed retrospectively. Patient characteristics and treatment patterns were analyzed descriptively. Outcomes assessed included overall survival (OS), time to treatment discontinuation, time to next treatment, and real-world tumor response. RESULTS: In all, 1003 patients were evaluated (median age, 68 years [range, 28-93 years]; 53.9% male). Use of 1 L IO monotherapy (0-25.9%) and targeted therapy (11.8-15.9%) increased during the study period, but chemotherapy remained the most common 1 L treatment at all time points (88.2-58.2%). Median OS was 9.5 months (95% CI, 8.8-10.7 months) for all patients, 8.1 months (95% CI, 7.4-8.9 months) with chemotherapy, 14.0 months (95% CI, 10.7-20.6 months) with IO monotherapy, and 20.2 months (95% CI, 16.0-30.5 months) with targeted therapy. In the 28.6% of patients who received second-line treatment, IO monotherapy was the most common drug class (used in 51.6%). CONCLUSIONS: Although use of 1 L IO monotherapy for aNSCLC increased in the United Kingdom during the study period, most patients received 1 L chemotherapy. An OS benefit for first-line IO monotherapy vs chemotherapy was observed but was numerically smaller than that reported in clinical trials. Targeted therapy was associated with the longest OS, highlighting the need for improved treatment options for tumors lacking targetable mutations.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/análise , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
2.
Methods Mol Biol ; 2118: 199-211, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32152981

RESUMO

Conjugation of gold nanoparticles (AuNPs) with biologically relevant molecules underpins many applications in medicine and biochemistry. Immobilization of functional proteins on AuNPs often affects protein structure and function. Such effects are protein dependent and require thorough investigation using suitable quantitative tests. Good experimental design and the use of a comprehensive set of control samples are essential when characterizing the consequences of protein immobilization and its effect on protein structure and function. However, traditional approaches to making control samples, that is, immobilized protein versus protein in solution in absence of any nanoparticles, do not provide sufficiently identical reaction conditions and complicate interpretation of the results. Accurate quantification of protein conjugation to AuNPs and ensuring complete removal of unconjugated protein remain the two key challenges in such functional assays. This report describes a simple and straightforward procedure allowing for quantitative analysis of protein conjugation to AuNPs. The principles are illustrated using fluorescence and circular dichroism measurements, and can be applied to other analytical techniques or be adapted with minor modifications for use with other proteins.


Assuntos
Ouro/química , Proteínas/química , Dicroísmo Circular , Difusão Dinâmica da Luz , Nanopartículas Metálicas , Tamanho da Partícula , Soluções
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