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1.
Nat Med ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740994

RESUMO

Emotional distress (ED), commonly characterized by symptoms of depression and/or anxiety, is prevalent in patients with cancer. Preclinical studies suggest that ED can impair antitumor immune responses, but few clinical studies have explored its relationship with response to immune checkpoint inhibitors (ICIs). Here we report results from cohort 1 of the prospective observational STRESS-LUNG study, which investigated the association between ED and clinical efficacy of first-line treatment of ICIs in patients with advanced non-small-cell lung cancer. ED was assessed by Patient Health Questionnaire-9 and Generalized Anxiety Disorder 7-item scale. The study included 227 patients with 111 (48.9%) exhibiting ED who presented depression (Patient Health Questionnaire-9 score ≥5) and/or anxiety (Generalized Anxiety Disorder 7-item score ≥5) symptoms at baseline. On the primary endpoint analysis, patients with baseline ED exhibited a significantly shorter median progression-free survival compared with those without ED (7.9 months versus 15.5 months, hazard ratio 1.73, 95% confidence interval 1.23 to 2.43, P = 0.002). On the secondary endpoint analysis, ED was associated with lower objective response rate (46.8% versus 62.1%, odds ratio 0.54, P = 0.022), reduced 2-year overall survival rate of 46.5% versus 64.9% (hazard ratio for death 1.82, 95% confidence interval 1.12 to 2.97, P = 0.016) and detriments in quality of life. The exploratory analysis indicated that the ED group showed elevated blood cortisol levels, which was associated with adverse survival outcomes. This study suggests that there is an association between ED and worse clinical outcomes in patients with advanced non-small-cell lung cancer treated with ICIs, highlighting the potential significance of addressing ED in cancer management. ClinicalTrials.gov registration: NCT05477979 .

2.
Org Lett ; 26(11): 2212-2217, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38452132

RESUMO

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.


Assuntos
Azidas , Benzeno , Ciclização , Aminas , DNA
3.
Fitoterapia ; 130: 180-183, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30145336

RESUMO

A novel pyrone derivative (1) bearing two fused five-member rings, together with two new naphthalenone derivatives (2, 3), as well as two known compounds (4, 5) were obtained from the endophytic fungus Fusarium sp. HP-2, which was isolated from "Qi-Nan" agarwood. The structures of the new compounds were elucidated by analysis of 1D and 2D NMR, and by HRESIMS spectra, as well as by comparison with the literature. Bioactivity results indicated that compound 3 showed weak acetylcholinesterase inhibitory activity.


Assuntos
Fusarium/química , Pironas/isolamento & purificação , Thymelaeaceae/microbiologia , Madeira/microbiologia , Linhagem Celular Tumoral , Inibidores da Colinesterase/isolamento & purificação , Endófitos/química , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Naftalenos/isolamento & purificação , Metabolismo Secundário
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