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1.
ACS Omega ; 9(25): 27002-27016, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38947843

RESUMO

Liriodendron chinense has been widely utilized in traditional Chinese medicine to treat dispelling wind and dampness and used for alleviating cough and diminishing inflammation. However, the antioxidant, antimicrobial, and anti-inflammatory effects of L. chinense leaves and the key active constituents remained elusive. So, we conducted some experiments to support the application of L. chinense in traditional Chinese medicine by investigating the antioxidant, antibacterial, and anti-inflammatory abilities, and to identify the potential key constituents responsible for the activities. The ethanol extract of L. chinense leaves (LCLE) was isolated and extracted, and assays measuring ferric reducing antioxidant power, total reducing power, DPPH•, ABTS•+, and •OH were used to assess its in vitro antioxidant capacities. Antimicrobial activities of LCLE were investigated by minimal inhibitory levels, minimum antibacterial concentrations, disc diffusion test, and scanning electron microscope examination. Further, in vivo experiments including macro indicators examination, histopathological examination, and biochemical parameters measurement were conducted to investigate the effects of LCLE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LCLE was further isolated and purified through column chromatography, and LPS-induced RAW264.7 cells were constructed to assess the diminished inflammation potential of the identified chemical composites. ABTS•+ and •OH radicals were extensively neutralized by the LCLE treatment. LCLE administration also presented broad-spectrum antimicrobial properties, especially against Staphylococcus epidermidis by disrupting cell walls. LPS-induced ALI in mice was significantly ameliorated by LCLE intervention, as evidenced by the histological changes in the lung and liver tissues as well as the reductions of nitric oxide (NO), TNF-α, and IL-6 production. Furthermore, three novel compounds including fragransin B2, liriodendritol, and rhamnocitrin were isolated, purified, and identified from LCLE. These three compounds exhibited differential regulation on NO accumulation and IL-10, IL-1ß, IL-6, TNF-α, COX-2, and iNOS mRNA expression in RAW264.7 cells induced by LPS. Fragransin B2 was more effective in inhibiting TNF-α mRNA expression, while rhamnocitrin was more powerful in inhibiting IL-6 mRNA expression. LCLE had significant antioxidant, antimicrobial, and anti-inflammatory effects. Fragransin B2, liriodendritol, and rhamnocitrin were probably key active constituents of LCLE, which might act synergistically to treat inflammatory-related disorders. This study provided a valuable view of the healing potential of L. chinense leaves in curing inflammatory diseases.

2.
Front Genet ; 15: 1391936, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38826802

RESUMO

Niemann Pick disease B (NPB) often presents with hepatosplenomegaly and lung pathological changes, but it usually does not present with central nervous system symptoms. This report presents the unique case of a 21-year-old woman with a 10-year history of hard skin and hepatosplenomegaly. Genetic sequencing revealed NPB and also suggested Segawa syndrome. Although symptomatic supportive treatments were administered in an attempt to improve muscle tone and treat the skin sclerosis, their efficacy was not satisfactory, and the patient refused further treatment. This case provides several noteworthy findings. First, although NPB and Segawa syndrome are rare, both are autosomal recessive inherited diseases that share common clinical symptoms and imaging manifestations. Second, when NPB and Segawa syndrome are highly suspected, screening for tyrosine hydroxylase (TH) and sphingomyelin phosphodiesterase-1 (SMPD1) gene mutations is critical to determine an accurate diagnosis. Finally, early diagnosis and comprehensive therapies are crucial for improving the prognosis of patients with NPB and Segawa syndrome.

3.
Carbohydr Polym ; 339: 122253, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38823920

RESUMO

In vitro tumor models are essential for understanding tumor behavior and evaluating tumor biological properties. Hydrogels that can mimic the tumor extracellular matrix have become popular for creating 3D in vitro tumor models. However, designing biocompatible hydrogels with appropriate chemical and physical properties for constructing tumor models is still a challenge. In this study, we synthesized a series of ß-cyclodextrin (ß-CD)-crosslinked polyacrylamide hydrogels with different ß-CD densities and mechanical properties and evaluated their potential for use in 3D in vitro tumor model construction, including cell capture and spheroid formation. By utilizing a combination of ß-CD-methacrylate (CD-MA) and a small amount of N,N'-methylene bisacrylamide (BIS) as hydrogel crosslinkers and optimizing the CD-MA/BIS ratio, the hydrogels performed excellently for tumor cell 3D culture and spheroid formation. Notably, when we co-cultured L929 fibroblasts with HeLa tumor cells on the hydrogel surface, co-cultured spheroids were formed, showing that the hydrogel can mimic the complexity of the tumor extracellular matrix. This comprehensive investigation of the relationship between hydrogel mechanical properties and biocompatibility provides important insights for hydrogel-based in vitro tumor modeling and advances our understanding of the mechanisms underlying tumor growth and progression.


Assuntos
Resinas Acrílicas , Hidrogéis , Esferoides Celulares , beta-Ciclodextrinas , Esferoides Celulares/efeitos dos fármacos , Humanos , Resinas Acrílicas/química , Resinas Acrílicas/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Hidrogéis/síntese química , beta-Ciclodextrinas/química , beta-Ciclodextrinas/farmacologia , Células HeLa , Animais , Camundongos , Reagentes de Ligações Cruzadas/química , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Técnicas de Cultura de Células em Três Dimensões/métodos , Metacrilatos/química , Técnicas de Cocultura , Neoplasias/patologia
4.
J Colloid Interface Sci ; 667: 259-268, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38636227

RESUMO

Indocyanine green (ICG) is an FDA-approved medical diagnostic agent that is widely used as a near-infrared (NIR) fluorescent imaging molecular probe. However, ICG tends to aggregate to form dimers or H-aggregates in water and lacks physical and optical stability, which greatly decreases its absorbance and fluorescence intensity in various applications. Additionally, ICG has no tissue- or tumor-targeting properties, and its structure is not easy to modify, which has further limited its application in cancer diagnosis. In this study, we addressed these challenges by developing a supramolecular colloidal carrier system that targets tumor cells. To this end, we synthesized a water-soluble ß-cyclodextrin (ß-CD) polymer conjugated with folate (FA), denoted PCD-FA, which is capable of forming inclusion complexes with ICG in water through host-guest interactions between the ß-CD moieties and ICG molecules. The inclusion complexes formed by PCD-FA and ICG, called ICG@PCD-FA, dispersed stably in solution as colloidal nanoparticles, greatly improving the physical and optical properties of ICG by preventing ICG dimer formation, where ICG appeared as monomers and even J-aggregates. This resulted in stronger and more stable absorption at a longer wavelength of 900 nm, which may allow for deeper tissue penetration and imaging with reduced interference from biological tissues' autofluorescence. Moreover, ICG@PCD-FA showed a targeting effect on folate receptor-positive (FR+) tumor cells, which specifically highlighted FR+ cells via NIR endoscopic imaging. Notably, ICG@PCD-FA further improved permeation and accumulation in FR+ 3D tumor spheroids. Therefore, this ICG@PCD-FA supramolecular colloidal system may have a great potential for use in tumor NIR imaging and diagnostic applications.


Assuntos
Coloides , Ácido Fólico , Verde de Indocianina , Esferoides Celulares , beta-Ciclodextrinas , Verde de Indocianina/química , beta-Ciclodextrinas/química , Ácido Fólico/química , Humanos , Coloides/química , Imagem Óptica , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Tamanho da Partícula , Células Tumorais Cultivadas , Polímeros/química , Nanopartículas/química
5.
Plant Biotechnol J ; 22(8): 2348-2363, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38578842

RESUMO

Potassium (K+) plays a crucial role as a macronutrient in the growth and development of plants. Studies have definitely determined the vital roles of K+ in response to pathogen invasion. Our previous investigations revealed that rice plants infected with rice grassy stunt virus (RGSV) displayed a reduction in K+ content, but the mechanism by which RGSV infection subverts K+ uptake remains unknown. In this study, we found that overexpression of RGSV P1, a specific viral protein encoded by viral RNA1, results in enhanced sensitivity to low K+ stress and exhibits a significantly lower rate of K+ influx compared to wild-type rice plants. Further investigation revealed that RGSV P1 interacts with OsCIPK23, an upstream regulator of Shaker K+ channel OsAKT1. Moreover, we found that the P1 protein recruits the OsCIPK23 to the Cajal bodies (CBs). In vivo assays demonstrated that the P1 protein competitively binds to OsCIPK23 with both OsCBL1 and OsAKT1. In the nucleus, the P1 protein enhances the binding of OsCIPK23 to OsCoilin, a homologue of the signature protein of CBs in Arabidopsis, and facilitates their trafficking through these CB structures. Genetic analysis indicates that mutant in oscipk23 suppresses RGSV systemic infection. Conversely, osakt1 mutants exhibited increased sensitivity to RGSV infection. These findings suggest that RGSV P1 hinders the absorption of K+ in rice plants by recruiting the OsCIPK23 to the CB structures. This process potentially promotes virus systemic infection but comes at the expense of inhibiting OsAKT1 activity.


Assuntos
Oryza , Doenças das Plantas , Proteínas de Plantas , Potássio , Proteínas Virais , Oryza/metabolismo , Oryza/genética , Oryza/virologia , Potássio/metabolismo , Doenças das Plantas/virologia , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética
6.
Biomacromolecules ; 25(5): 2980-2989, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38587905

RESUMO

We developed a supramolecular system for codelivery of doxorubicin (Dox) and p53 gene based on a ß-CD-containing star-shaped cationic polymer. First, a star-shaped cationic polymer consisting of a ß-CD core and 3 arms of oligoethylenimine (OEI), named CD-OEI, was used to form a supramolecular inclusion complex with hydrophobic Dox. The CD-OEI/Dox complex was subsequently used to condense plasmid DNA via electrostatic interactions to form CD-OEI/Dox/DNA polyplex nanoparticles with positive surface charges that enhanced the cellular uptake of both Dox and DNA. This supramolecular drug and gene codelivery system showed high gene transfection efficiency and effective protein expression in cancer cells. The codelivery of Dox and DNA encoding the p53 gene resulted in reduced cell viability and enhanced antitumor effects at low Dox concentrations. With its enhanced cellular uptake and anticancer efficacy, the system holds promise as a delivery carrier for potential combination cancer therapies.


Assuntos
Doxorrubicina , Nanopartículas , Eletricidade Estática , Proteína Supressora de Tumor p53 , Humanos , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/química , Antibióticos Antineoplásicos/administração & dosagem , beta-Ciclodextrinas/química , Sobrevivência Celular/efeitos dos fármacos , DNA/química , Doxorrubicina/farmacologia , Doxorrubicina/química , Doxorrubicina/administração & dosagem , Portadores de Fármacos/química , Técnicas de Transferência de Genes , Nanopartículas/química , Proteína Supressora de Tumor p53/genética
7.
Medicine (Baltimore) ; 103(13): e37449, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38552088

RESUMO

RATIONALE: Clear cell carcinoma (CCC) is a highly invasive malignant tumor. CCCs of the female reproductive system occur mostly in the endometrium and ovaries and rarely in the cervix. So, it is difficult to diagnose cervical clear cell carcinoma (CCAC) on imaging. This report helps to further deepen our understanding of CCAC. PATIENT CONCERNS: A 39-year-old female patient presented with vaginal discharge with no obvious cause, elevated levels of carcinoembryonic antigen (CEA), CA125, CA153, and squamous cell carcinoma antigen (SCC), and underwent ultrasonography (US) CT and MRI examination in our hospital, which showed a mass in the cervix of the uterus, considered of cervical squamous carcinoma. DIAGNOSES: The cervix biopsy guided by vaginoscope biopsy and immunohistochemistry confirmed CCAC, combined Magnetic Resonance Imaging examination, CCAC with pelvic lymph node metastasis was considered. INTERVENTIONS AND OUTCOMES: The patient refused further treatment and was discharged from hospital. LESSONS: CCAC exhibited no specific symptoms, and is slightly different from cervical squamous carcinoma in image features, mainly relying on immunohistochemistry for diagnosis. The reported case raised awareness of CCAC.


Assuntos
Adenocarcinoma de Células Claras , Carcinoma de Células Escamosas , Neoplasias do Colo do Útero , Neoplasias Vaginais , Humanos , Feminino , Adulto , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/patologia , Colo do Útero/patologia , Carcinoma de Células Escamosas/diagnóstico por imagem , Carcinoma de Células Escamosas/patologia , Linfonodos/patologia , Adenocarcinoma de Células Claras/diagnóstico por imagem , Adenocarcinoma de Células Claras/patologia , Neoplasias Vaginais/patologia
8.
New Phytol ; 242(3): 1043-1054, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38184789

RESUMO

The timing of vegetative phase change (VPC) in plants is regulated by a temporal decline in the expression of miR156. Both exogenous cues and endogenous factors, such as temperature, light, sugar, nutrients, and epigenetic regulators, have been shown to affect VPC by altering miR156 expression. However, the genetic basis of natural variation in VPC remains largely unexplored. Here, we conducted a genome-wide association study on the variation of the timing of VPC in Arabidopsis. We identified CYCLIC NUCLEOTIDE-GATED ION CHANNEL 4 (CNGC4) as a significant locus associated with the diversity of VPC. Mutations in CNGC4 delayed VPC, accompanied by an increased expression level of miR156 and a corresponding decrease in SQUAMOSA PROMOTER BINDING-LIKE (SPL) gene expression. Furthermore, mutations in CNGC2 and CATION EXCHANGER 1/3 (CAX1/3) also led to a delay in VPC. Polymorphisms in the CNGC4 promoter contribute to the natural variation in CNGC4 expression and the diversity of VPC. Specifically, the early CNGC4 variant promotes VPC and enhances plant adaptation to local environments. In summary, our findings offer genetic insights into the natural variation in VPC in Arabidopsis, and reveal a previously unidentified role of calcium signaling in the regulation of VPC.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , MicroRNAs , Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Sinalização do Cálcio , Canais de Cátion Regulados por Nucleotídeos Cíclicos/genética , Canais de Cátion Regulados por Nucleotídeos Cíclicos/metabolismo , Regulação da Expressão Gênica de Plantas , Estudo de Associação Genômica Ampla , MicroRNAs/genética , MicroRNAs/metabolismo , Nucleotídeos Cíclicos/metabolismo
9.
J Ethnopharmacol ; 324: 117749, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38219880

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity has become a public burden worldwide due to its booming incidence and various complications, and browning of white adipose tissue (WAT) is recognized as a hopeful strategy to combat it. Blossom of Citrus aurantium L. var. amara Engl. (CAVA) is a popular folk medicine and dietary supplement used for relieving dyspepsia, which is recorded in the Chinese Materia Medica. Our previous study showed that blossom of CAVA had anti-obesity potential, while its role in browning of WAT was still unclear. AIM OF THE STUDY: This study aimed to characterize the constituents in flavonoids from blossom of CAVA (CAVAF) and to clarify the anti-obesity capacities especially the effects on browning of WAT. MATERIALS AND METHODS: Gradient ethanol eluents from blossom of CAVA were obtained by AB-8 macroporous resin. 3T3-L1 cells and pancreatic lipase inhibition assay were employed to investigate the potential anti-obesity effects in vitro. HPLC and UPLC/MS assays were performed to characterize the chemical profiles of different eluents. Network pharmacology and molecular docking assays were used to reveal potential anti-obesity targets. Furthermore, high-fat diet (HFD)-induced mice were constructed to explore the anti-obesity actions and mechanisms in vivo. RESULTS: 30% ethanol eluents with high flavonoid content and great inhibition on proliferation of 3T3-L1 preadipocytes and pancreatic lipase activity were regarded as CAVAF. 19 compounds were identified in CAVAF. Network pharmacology analysis demonstrated that AMPK and PPARα were potential targets for CAVAF in alleviating obesity. Animal studies demonstrated that CAVAF intervention significantly decreased the body weight, WAT weight, serum TG, TC and LDL-C levels in HFD-fed obese mice. HFD-induced insulin resistance and morphological changes in WAT and brown adipose tissue were also markedly attenuated by CAVAF treatment. CAVAF supplementation potently inhibited iWAT inflammation by regulating IL-6, IL-1ß, TNF-α and IL-10 mRNA expression in iWAT of mice. Furthermore, the gene expression levels of thermogenic markers including Cyto C, ATP synthesis, Cidea, Cox8b and especially UCP1 in iWAT of mice were significantly up-regulated by CAVAF administration. CAVAF intervention also markedly increased the expression levels of PRDM16, PGC-1α, SIRT1, AMPK-α1, PPARα and PPARγ mRNA in iWAT of mice. CONCLUSION: CAVAF treatment significantly promoted browning of WAT in HFD-fed mice. These results suggested that flavonoid extracts from blossom of CAVA were probably promising candidates for the treatment of obesity.


Assuntos
Citrus , Flavonoides , Camundongos , Animais , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Proteínas Quinases Ativadas por AMP/metabolismo , Simulação de Acoplamento Molecular , PPAR alfa , Tecido Adiposo Branco , Obesidade/metabolismo , Etanol/farmacologia , Citrus/química , RNA Mensageiro , Lipase , Camundongos Endogâmicos C57BL
10.
J Agric Food Chem ; 72(2): 1096-1113, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38169317

RESUMO

This study was sought to investigate the chemical composition and antibacterial and antiulcerative colitis (UC) effects of essential oil from Pruni Semen (PSEO). A GC-MS assay showed that the major compounds in PSEO were products of amygdalin hydrolysis, which possessed great antibacterial and anti-inflammatory potential. In vitro antibacterial experiments demonstrated that PSEO treatment inhibited activity of four kinds of intestinal pathogens probably by disrupting the cell wall. Further in vivo studies showed that PSEO administration significantly improved physiological indexes, attenuated histopathological characteristics, and inhibited proinflammatory cytokine production in dextran sulfate sodium (DSS)-induced UC mice. Network pharmacology and molecular docking results predicted that PSEO might prevent UC via regulating the PI3K/AKT pathway. Western blotting and immunofluorescence assays were further conducted for verification, and the results evidenced that PSEO intervention significantly regulated the PI3K/AKT pathway and the expression of its downstream proteins in DSS-induced mice. PSEO might provide a new dietary strategy for UC treatment.


Assuntos
Colite Ulcerativa , Colite , Óleos Voláteis , Camundongos , Animais , Óleos Voláteis/química , Proteínas Proto-Oncogênicas c-akt/genética , Sêmen/metabolismo , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Simulação de Acoplamento Molecular , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/metabolismo , Antibacterianos/farmacologia , Colite Ulcerativa/induzido quimicamente , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Colo/metabolismo
11.
World J Clin Oncol ; 15(1): 115-129, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38292661

RESUMO

BACKGROUND: Multiple myeloma (MM) is a terminal differentiated B-cell tumor disease characterized by clonal proliferation of malignant plasma cells and excessive levels of monoclonal immunoglobulins in the bone marrow. The translocation, (t)(4;14), results in high-risk MM with limited treatment alternatives. Thus, there is an urgent need for identification and validation of potential treatments for this MM subtype. Microarray data and sequencing information from public databases could offer opportunities for the discovery of new diagnostic or therapeutic targets. AIM: To elucidate the molecular basis and search for potential effective drugs of t(4;14) MM subtype by employing a comprehensive approach. METHODS: The transcriptional signature of t(4;14) MM was sourced from the Gene Expression Omnibus. Two datasets, GSE16558 and GSE116294, which included 17 and 15 t(4;14) MM bone marrow samples, and five and four normal bone marrow samples, respectively. After the differentially expressed genes were identified, the Cytohubba tool was used to screen for hub genes. Then, the hub genes were analyzed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Using the STRING database and Cytoscape, protein-protein interaction networks and core targets were identified. Potential small-molecule drugs were identified and validated using the Connectivity Map database and molecular docking analysis, respectively. RESULTS: In this study, a total of 258 differentially expressed genes with enriched functions in cancer pathways, namely cytokine receptor interactions, nuclear factor (NF)-κB signaling pathway, lipid metabolism, atherosclerosis, and Hippo signaling pathway, were identified. Ten hub genes (cd45, vcam1, ccl3, cd56, app, cd48, btk, ccr2, cybb, and cxcl12) were identified. Nine drugs, including ivermectin, deforolimus, and isoliquiritigenin, were predicted by the Connectivity Map database to have potential therapeutic effects on t (4;14) MM. In molecular docking, ivermectin showed strong binding affinity to all 10 identified targets, especially cd45 and cybb. Ivermectin inhibited t(4;14) MM cell growth via the NF-κB pathway and induced MM cell apoptosis in vitro. Furthermore, ivermectin increased reactive oxygen species accumulation and altered the mitochondrial membrane potential in t(4;14) MM cells. CONCLUSION: Collectively, the findings offer valuable molecular insights for biomarker validation and potential drug development in t(4;14) MM diagnosis and treatment, with ivermectin emerging as a potential therapeutic alternative.

12.
Lancet Respir Med ; 12(3): 217-224, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38101437

RESUMO

BACKGROUND: Sunvozertinib is an oral, irreversible, and selective tyrosine kinase inhibitor that has a favourable safety profile and encouraging antitumour activity, as shown in phase 1 studies of patients with heavily pretreated non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation (exon20ins). We aimed to assess the antitumour efficacy of sunvozertinib in patients with platinum-pretreated locally advanced or metastatic NSCLC with EGFR exon20ins. METHODS: WU-KONG6 is a single-group, open-label, multicentre phase 2 trial of sunvozertinib monotherapy, conducted across 37 medical centres in China. We enrolled adult patients with pathologically or cytologically confirmed locally advanced or metastatic NSCLC whose tumour tissue carried an EGFR exon20ins mutation. All patients had received at least one line of previous systemic therapy, with at least one line containing platinum-based chemotherapy. The primary endpoint was objective response rate (ORR), as assessed by the independent review committee. The ORR was defined as the percentage of patients who achieved complete or partial response, confirmed by two separate assessments with at least 4-week time interval, until disease progression or initiation of any new anti-cancer therapy. Enrolled patients received sunvozertinib 300 mg once daily until meeting discontinuation criteria per the protocol. Patients who received at least one dose of treatment and were evaluable for efficacy analysis were included in the primary analysis, and all patients who received at least one dose of treatment were included in the safety analysis. This study is registered with ChinaDrugTrials.org, CTR20211009, and ClinicalTrials.gov, NCT05712902, and efficacy and safety follow-up are ongoing. FINDINGS: Between July 19, 2021, and May 6, 2022, 104 patients were enrolled. At data cutoff (Oct 17, 2022), the last enrolled patient had been followed up for about 6 months. Among 97 patients evaluable for efficacy analysis, 59 (61%) patients achieved tumour response, with a confirmed ORR of 61% (95% CI 50-71). All tumour responses were partial responses. Tumour responses were observed irrespective of age, sex, smoking history, EGFR exon20ins subtypes, brain metastasis at baseline, previous lines of therapy, and history of onco-immunotherapy. In total, 19 death events occurred over a median follow-up period of 7·6 months (IQR 6·1-9·4). Sunvozertinib was well tolerated at 300 mg once daily. The most common grade 3 or worse treatment-related adverse events were blood creatine phosphokinase increased (18 [17%] of 104), diarrhoea (eight [8%]), and anaemia (six [6%]). The most common serious treatment-related adverse events were interstitial lung disease (five [5%] of 104), anaemia (three [3%]), vomiting (two [2%]), nausea (two [2%]) and pneumonia (two [2%]). INTERPRETATION: In this phase 2 study, sunvozertinib demonstrated antitumour efficacy in patients with platinum-based chemotherapy pretreated NSCLC with EGFR exon20ins, with a manageable safety profile. A multinational randomised, phase 3 study of sunvozertinib versus platinum-doublet chemotherapy in EGFR exon20ins NSCLC is ongoing (NCT05668988). FUNDING: Dizal Pharmaceutical.


Assuntos
Anemia , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Adulto , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Mutagênese Insercional , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , China , Receptores ErbB/genética , Éxons/genética
13.
Front Pharmacol ; 14: 1269158, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38259282

RESUMO

Objectives: This study aimed to investigate the prevalence and influencing factors of medication adherence in children with central precocious puberty (CPP), and provide references for clinical practice. Methods: Children under 12 years of age with CPP and their caregivers at a women's and children's hospital were selected for a cross-sectional study from February to May 2023, and a questionnaire was used to collect basic characteristics of pediatric patients and their caregivers, information of medication, cognition of medication, and medication adherence. The 8-item Morisky Medication Adherence Scale (MMAS-8) was adopted to assess medication adherence, and the potential influencing factors were explored by univariate and multivariate analyses. Results: A total of 125 valid questionnaires were collected. The medication adherence rate of children with CPP reported by caregivers was 76.0%. The univariate analysis showed that the percentage of parental caregivers (p = 0.027), the age of caregivers (p = 0.029), the education level of caregivers (p = 0.001), the financial burden (p < 0.000), the incidence of adverse effects (p = 0.008), and the cognition of medication including the importance of medication (p = 0.002), the dosage of medication (p = 0.002), the adverse effects of medication (p = 0.007), the harm of non-compliance with medication (p < 0.000), and the evaluation of the price of medication (p = 0.003) in the poor adherence group were significantly inferior to those in the better adherence group. The multivariate analysis showed that the higher incidence of adverse effects (p = 0.20), not understanding the harm of non-compliance with medication (p = 0.004), and evaluation of the price of medication as expensive (p = 0.043) were independent risk factors for poor medication adherence. Conclusion: Medication adherence in children with CPP is relatively better, and the factors leading to poor medication adherence are mainly on the caregivers of pediatric patients. It is recommended to increase the health education among caregivers of children with CPP to enhance the cognition of the condition and medication, and further improve the therapeutic efficacy for CPP.

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