Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 45
Filtrar
1.
Biotechnol Biofuels Bioprod ; 17(1): 62, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38715100

RESUMO

BACKGROUND: The use of ionic liquids (ILs) to fractionate lignocelluloses for various bio-based chemicals productions is in the ascendant. On this basis, the protic ILs consisting of triethylammonium hydrogen sulfate ([TEA][HSO4]) possessed great promise due to the low price, low pollution, and high efficiency. In this study, the microwave-assistant [TEA][HSO4] fractionation process was established for corn stover fractionation, so as to facilitate the monomeric sugars production and supported the downstream acetone-butanol-ethanol (ABE) fermentation. RESULTS: The assistance of microwave irradiation could obviously shorten the fractionation period of corn stover. Under the optimized condition (190 W for 3 min), high xylan removal (93.17 ± 0.63%) and delignification rate (72.90 ± 0.81%) were realized. The mechanisms for the promotion effect of the microwave to the protic ILs fractionation process were ascribed to the synergistic effect of the IL and microwaves to the depolymerization of lignocellulose through the ionic conduction, which can be clarified by the characterization of the pulps and the isolated lignin specimens. Downstream valorization of the fractionated pulps into ABE productions was also investigated. The [TEA][HSO4] free corn stover hydrolysate was capable of producing 12.58 g L-1 of ABE from overall 38.20 g L-1 of monomeric sugars without detoxification and additional nutrients supplementation. CONCLUSIONS: The assistance of microwave irradiation could significantly promote the corn stover fractionation by [TEA][HSO4]. Mass balance indicated that 8.1 g of ABE and 16.61 g of technical lignin can be generated from 100 g of raw corn stover based on the novel fractionation strategy.

3.
Sci Rep ; 14(1): 2677, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302642

RESUMO

Cellular automata (CA) are computational systems that exhibit complex global behavior arising from simple local rules, making them a fascinating candidate for various research areas. However, challenges such as limited flexibility and efficiency on conventional hardware platforms still exist. In this study, we propose a memristor-based circuit for implementing elementary cellular automata (ECA) by extending the stateful three-memristor logic operations derived from material implication (IMP) logic gates. By leveraging the inherent physical properties of memristors, this approach offers simplicity, minimal operational steps, and high flexibility in implementing ECA rules by adjusting the circuit parameters. The mathematical principles governing circuit parameters are analyzed, and the evolution of multiple ECA rules is successfully demonstrated, showcasing the robustness in handling the stochastic nature of memristors. This approach provides a hardware solution for ECA implementation and opens up new research opportunities in the hardware implementation of CA.

4.
Phys Rev Lett ; 132(3): 033401, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38307087

RESUMO

Motivated by recent surprising experimental findings, we develop a strong-coupling theory for Bose-Fermi mixtures capable of treating resonant interspecies interactions while satisfying the compressibility sum rule. We show that the mixture can be stable at large interaction strengths close to resonance, in agreement with the experiment, but at odds with the widely used perturbation theory. We also calculate the sound velocity of the Bose gas in the ^{133}Cs-^{6}Li mixture, again finding good agreement with the experimental observations both at weak and strong interactions. A central ingredient of our theory is the generalization of a fermion mediated interaction to strong Bose-Fermi scatterings and to finite frequencies. This further leads to a predicted hybridization of the sound modes of the Bose and Fermi gases, which can be directly observed using Bragg spectroscopy.

5.
ACS Nano ; 18(1): 581-591, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38126349

RESUMO

Neural networks based on low-power artificial synapses can significantly reduce energy consumption, which is of great importance in today's era of artificial intelligence. Two-dimensional (2D) material-based floating-gate transistors (FGTs) have emerged as compelling candidates for simulating artificial synapses owing to their multilevel and nonvolatile data storage capabilities. However, the low erasing/programming speed of FGTs renders them unsuitable for low-energy-consumption artificial synapses, thereby limiting their potential in high-energy-efficient neuromorphic computing. Here, we introduce a FGT-inspired MoS2/Trap/PZT heterostructure-based polarized tunneling transistor (PTT) with a simple fabrication process and significantly enhanced erasing/programming speed. Distinct from the FGT, the PTT lacks a tunnel layer, leading to a marked improvement in its erasing/programming speed. The PTT's highest erasing/programming (operation) speed can reach ∼20 ns, which outperforms the performance of most FGTs based on 2D heterostructures. Furthermore, the PTT has been utilized as an artificial synapse, and its weight-update energy consumption can be as low as 0.0002 femtojoule (fJ), which benefits from the PTT's ultrahigh operation speed. Additionally, PTT-based artificial synapses have been employed in constructing artificial neural network simulations, achieving facial-recognition accuracy (95%). This groundbreaking work makes it possible for fabricating future high-energy-efficient neuromorphic transistors utilizing 2D materials.

6.
Nano Lett ; 23(22): 10196-10204, 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37926956

RESUMO

Low-power electronic devices play a pivotal role in the burgeoning artificial intelligence era. The study of such devices encompasses low-subthreshold swing (SS) transistors and neuromorphic devices. However, conventional field-effect transistors (FETs) face the inherent limitation of the "Boltzmann tyranny", which restricts SS to 60 mV decade-1 at room temperature. Additionally, FET-based neuromorphic devices lack sufficient conductance states for highly accurate neuromorphic computing due to a narrow memory window. In this study, we propose a pioneering PZT-enabled MoS2 floating gate transistor (PFGT) configuration, demonstrating a low SS of 46 mV decade-1 and a wide memory window of 7.2 V in the dual-sweeping gate voltage range from -7 to 7 V. The wide memory window provides 112 distinct conductance states for PFGT. Moreover, the PFGT-based artificial neural network achieves an outstanding facial-recognition accuracy of 97.3%. This study lays the groundwork for the development of low-SS transistors and highly energy efficient artificial synapses utilizing two-dimensional materials.

7.
Blood Adv ; 7(22): 6801-6811, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-37682792

RESUMO

The primary analysis of MAGNOLIA, an open-label, single-arm, multicenter, phase 2 study, demonstrated that the next-generation Bruton tyrosine kinase (BTK) inhibitor zanubrutinib provided a high overall response rate (ORR) in patients with relapsed/refractory marginal zone lymphoma (R/R MZL), with a favorable safety/tolerability profile. Presented here, is the final analysis of MAGNOLIA, performed to characterize the durability of response and longer-term safety and tolerability. Zanubrutinib (160 mg twice daily) was evaluated in 68 patients with R/R MZL who had received at least 1 anti-CD20-directed regimen. The primary end point was independent review committee (IRC)-assessed ORR. Secondary end points included investigator-assessed ORR, duration of response (DOR), progression-free survival (PFS), overall survival (OS), health-related quality of life, safety, and tolerability. With a median follow-up of 27.4 months, the IRC-assessed ORR was 68.2% (95% confidence interval [CI], 55.6-79.1), with a 24-month DOR event-free rate of 72.9% (95% CI, 54.4-84.9). PFS and OS at 24 months were 70.9% (95% CI, 57.2-81.0) and 85.9% (95% CI, 74.7-92.4), respectively. The zanubrutinib safety profile was consistent with the primary analysis, with no new safety signals observed. Atrial fibrillation/flutter (n = 2 [2.9%]) and hypertension (n = 3 [4.4%]) were uncommon. Neutropenia (n = 8 [11.8%]) was the most common grade ≥3 adverse event. In this final analysis of MAGNOLIA, zanubrutinib demonstrated sustained clinical responses beyond 2 years, with 73% of responders alive and progression free. Zanubrutinib continued to demonstrate a favorable safety/tolerability profile with the additional time on treatment. This trial was registered at www.clinicaltrials.gov as #NCT03846427.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Magnolia , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Qualidade de Vida , Resultado do Tratamento
8.
ACS Nano ; 17(16): 16204-16220, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37531596

RESUMO

Bone marrow mesenchymal stem cells (BMSCs) are suggested as candidates for neurodegeneration therapy by autologous stem cells to overcome the lack of neural stem cells in adults. However, the differentiation of BMSCs into functional neurons is a major challenge for neurotherapy. Herein, a methodology has been proposed to induce functional neuronal differentiation of BMSCs on a conductive three-dimensional graphene framework (GFs) combined with a rotating magnetic field. A wireless electrical signal of about 10 µA can be generated on the surface of GFs by cutting the magnetic field lines based on the well-known electromagnetic induction effect, which has been proven to be suitable for inducing neuronal differentiation of BMSCs. The enhanced expressions of the specific genes/proteins and apparent Ca2+ intracellular flow indicate that BMSCs cultured on GFs with 15 min/day rotating magnetic field stimulation for 15 days can differentiate functional neurons without any neural inducing factor. The animal experiments confirm the neural differentiation of BMSCs on GFs after transplantation in vivo, accompanied by stimulation of an external rotating magnetic field. This study overcomes the lack of autologous neural stem cells for adult neurodegeneration patients and provides a facile and safe strategy to induce the neural differentiation of BMSCs, which has potential for clinical applications of neural tissue engineering.


Assuntos
Grafite , Células-Tronco Mesenquimais , Células-Tronco Neurais , Animais , Grafite/metabolismo , Células Cultivadas , Neurônios/metabolismo , Diferenciação Celular , Células da Medula Óssea/metabolismo
9.
ACS Omega ; 8(26): 23545-23553, 2023 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-37426208

RESUMO

Shallow geothermal energy reserves are abundant and widely distributed in Shandong Province. Vigorously developing and utilizing shallow geothermal energy will play a significant role in improving energy pressure in Shandong Province. The energy efficiency of ground source heat pumps is closely related to geological and other conditions. However, few studies on geothermal exploitation and utilization have been affected by economic policies. This article will investigate the operation of shallow geothermal engineering in Shandong Province, summarize the current number of operating projects, calculate the engineering annual comprehensive performance coefficient (ACOP), analyze the size characteristics of different cities, and analyze their correlation with economy and policy. Through research, it is found that the number of shallow geothermal energy development and utilization is significantly positively correlated with socioeconomic level and policy orientation, and has a relatively small relationship with ACOP. The research results provide a basis and suggestions for improving and optimizing the energy efficiency coefficient of geothermal heat pumps and promoting the development and utilization of shallow geothermal.

10.
Front Neurosci ; 17: 1192993, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37351423

RESUMO

Working memory refers to the brain's ability to store and manipulate information for a short period. It is disputably considered to rely on two mechanisms: sustained neuronal firing, and "activity-silent" working memory. To develop a highly biologically plausible neuromorphic computing system, it is anticipated to physically realize working memory that corresponds to both of these mechanisms. In this study, we propose a memristor-based neural network to realize the sustained neural firing and activity-silent working memory, which are reflected as dual functional states within memory. Memristor-based synapses and two types of artificial neurons are designed for the Winner-Takes-All learning rule. During the cognitive task, state transformation between the "focused" state and the "unfocused" state of working memory is demonstrated. This work paves the way for further emulating the complex working memory functions with distinct neural activities in our brains.

11.
Materials (Basel) ; 16(6)2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-36984135

RESUMO

Experimental characterization of the in-plane stress tensor is a basic requirement for the development of GaN strain engineering. In this work, a theoretical model of stress characterization for GaN using polarized micro-Raman spectroscopy was developed based on elasticity theory and lattice dynamics. Compared with other works, the presented model can give the quantitative relationship between all components of the in-plane stress tensor and the measured Raman shift. The model was verified by a calibration experiment under step-by-step uniaxial compression. By combining the stress characterization model with the expanding cavity model, the in-plane residual stress component field around Berkovich indentation on the (0001) plane GaN was achieved. The experimental results show that the distributions of the stress components, which significantly differed from the distribution of the Raman shift, were closely related to the GaN crystal structure and exhibited a gradient along each crystal direction.

12.
Front Oncol ; 13: 1101738, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814813

RESUMO

Introduction: Flumatinib is a novel, oral breakpoint cluster region-abelson (BCR-ABL) tyrosine kinase inhibitor that has demonstrated manageable safety and promising efficacy in patients with newly diagnosed chronic phase (CP) chronic myeloid leukemia (CML). Methods: This study evaluated the pharmacokinetic (PK) profiles of flumatinib mesylate tablets at a dose of 400 mg and 600 mg in patients with CML-CP. The study was registered at chictr.org Identifier (ChiCTR2100044700). In this open-label, pharmacokinetic study, eligible patients were administered a single-dose of flumatinib 400 mg or 600 mg on day 1, followed by 2-day washout and 8 consecutive days of once-daily administration. Serial plasma samples were assayed for flumatinib and its metabolites (N-demethylate metabolite M1 and amide-bond hydrolytic metabolite M3). Results: Twenty-nine patients were assigned to flumatinib 400 mg (n=14) or 600 mg (n=15). Serum concentrations of flumatinib reached maximum measured plasma concentration (Cmax) at a median time of 2 hours after each single dose, and then eliminated slowly with a mean apparent terminal disposition half-life (t1/2) from 16.0 to 16.9 hours. Following single- and multiple-dose administration, flumatinib exposure (Cmax, area under the concentration-time curve from 0 to t hours (AUC0-t), area under the concentration-time curve from 0 hours to infinity (AUC0-∞)) increased in an approximately dose-proportional manner. There was approximately 4.1- and 3.4- fold drug accumulation at steady-state after multiple-dose administration at 400 mg and 600 mg, respectively. The drug-related AEs associated with both treatments were primarily low-grade and tolerable events. Conclusion: Analysis of PK parameters indicated that flumatinib exposure increased in an approximately dose-proportional manner. Further research needs to be conducted in a large sample-size study.

13.
Soft Matter ; 19(7): 1293-1299, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36524440

RESUMO

Precise manipulation of liquid metal (LM) droplets possesses the potential to enable a wide range of applications in reconfigurable electronics, robotics, and microelectromechanical systems. Although a variety of methods have been explored to actuate LM droplets on a 2D plane, versatile 3D manipulation remains a challenge due to the difficulty in overcoming their heavy weight. Here, foam-core liquid metal (FCLM) droplets that can maintain the surface properties of LM while significantly reducing the density are developed, enabling 3D manipulation in an electrolyte. The FCLM droplet is fabricated by coating LM on the surface of a copper-grafted foam sphere. The actuation of the FCLM droplet is realized by electrically inducing Marangoni flow on the LM surface. Two motion modes of the FCLM droplet are observed and studied and the actuation performance is characterized. Multiple FCLM droplets can be readily controlled to form 3D structures, demonstrating their potential to be further developed to form collaborative robots for enabling wider applications.

14.
Micromachines (Basel) ; 13(10)2022 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-36296112

RESUMO

Harmful algal blooms (HABs) are common disastrous ecological anomalies in coastal waters. An effective algae monitoring approach is important for natural disaster warning and environmental governance. However, conducting rapid and sensitive detection of multiple algae is still challenging. Here, we designed an ultrasensitive, rapid and portable double-layer microfluidic biochip for the simultaneous quantitative detection of six species of algae. Specific DNA probes based on the 18S ribosomal DNA (18S rDNA) gene fragments of HABs were designed and labeled with the fluorescent molecule cyanine-3 (Cy3). The biochip had multiple graphene oxide (GO) nanosheets-based reaction units, in which GO nanosheets were applied to transfer target DNA to the fluorescence signal through a photoluminescence detection system. The entire detection process of multiple algae was completed within 45 min with the linear range of fluorescence recovery of 0.1 fM-100 nM, and the detection limit reached 108 aM. The proposed approach has a simple detection process and high detection performance and is feasible to conduct accurate detection with matched portable detection equipment. It will have promising applications in marine natural disaster monitoring and environmental care.

15.
Anal Chem ; 94(42): 14785-14793, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36223308

RESUMO

Antibiotics are powerful tools to treat bacterial infections, but antibiotic pollution is becoming a severe threat to the effective treatment of human bacterial infections. The detection of antibiotics in water has been a crucial research area for bioassays in recent years. There is still an urgent need for a simple ultrasensitive detection approach to achieve accurate antibiotic detection at low concentrations. Herein, a field-effect transistor (FET)-based biosensor was developed using ultraclean graphene and an aptamer for ultrasensitive tetracycline detection. Using a newly designed camphor-rosin clean transfer (CRCT) scheme to prepare ultraclean graphene, the carrier mobility of the FET is found to be improved by more than 10 times compared with the FET prepared by the conventional PMMA transfer (CPT) method. Based on the FET, aptamer-functionalized transistor antibiotic biosensors were constructed and characterized. A dynamic detection range of 5 orders of magnitude, a sensitivity of 21.7 mV/decade, and a low detection limit of 100 fM are achieved for the CRCT-FET biosensors with good stability, which are much improved compared with the biosensor prepared by the CPT method. The antibiotic sensing and sensing performance enhancement mechanisms for the CRCT-FET biosensor were studied and analyzed based on experimental results and a biosensing model. Finally, the CRCT-FET biosensor was verified by detecting antibiotics in actual samples obtained from the entrances of Bohai Bay.


Assuntos
Técnicas Biossensoriais , Grafite , Humanos , Transistores Eletrônicos , Antibacterianos , Polimetil Metacrilato , Cânfora , Técnicas Biossensoriais/métodos , Oligonucleotídeos , Água , Tetraciclinas
16.
RSC Adv ; 12(37): 23912-23921, 2022 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-36093240

RESUMO

In this paper, a core-shell structure nickel disulfide and ZIF-67 composite electrode material (NiS2/ZIF-67) was synthesized by a two-step method. Firstly, spherical NiS2 was synthesized by a hydrothermal method, dispersed in methanol, then reacted and coated by adding cobalt ions and 2-methylimidazole to obtain the NiS2/ZIF-67 core-shell composite. The NiS2/ZIF-67 composite shows a high specific capacitance (1297.9 F g-1 at 1 A g-1) and excellent cycling durability (retaining 110.0% after 4000 cycles at 5 A g-1). Furthermore, the corresponding hybrid supercapacitor (NiS2/ZIF-67//AC HSC) has an energy density of 9.5 W h kg-1 at 411.1 W kg-1 (6 M KOH) and remarkable cycling stability (maintaining 133.3% after 5000 cycles). Its excellent electrochemical performance may be due to the core-shell structure and the synergistic effect between the transition metal sulfide and metal-organic framework. These results indicate that the NiS2/ZIF-67 composite as an electrode material with a core-shell structure has potential application in high-efficiency supercapacitors.

17.
Adv Ther ; 39(9): 4250-4265, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35900694

RESUMO

INTRODUCTION: Zanubrutinib is a highly selective irreversible inhibitor of Bruton tyrosine kinase which has shown significant activity in lymphoid malignancies in early phase studies. We report here the long-term follow-up outcomes of zanubrutinib in various lines of therapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). METHODS: This post hoc analysis pooled patients with treatment-naïve (TN) or relapsed/refractory (R/R) CLL/SLL receiving zanubrutinib monotherapy from three phase 1/2 studies (BGB-3111-1002, BGB-3111-AU-003, BGB-3111-205). RESULTS: A total of 211 patients with CLL/SLL (TN 19, R/R 192) were included. After weighting (TN 19, R/R 24), the overall response rate (ORR) was 95.4% and significantly higher in the TN group than in the R/R group (100 vs. 91.0%, p < 0.0001). ORR was also significantly higher in the TN group than in the one prior line of therapy group (100 vs. 98.9%, p < 0.0001). Among those with R/R disease, the ORR was 97.8% in patients with one prior line of therapy (n = 79) and 90.7% in those with > 1 prior lines of therapy (n = 85; p = 0.080). The median follow-up times were 50.1, 35.7, and 45.9 months for TN, R/R and all cohorts, respectively. Progression-free survival and overall survival were significantly longer in the TN group and only one prior line of therapy group compared with the > 1 prior lines of therapy group (all p < 0.05) and were similar in the TN group compared with the one prior line therapy group. Efficacy was similar regardless of the presence of genomic aberrations. Most frequent grade ≥ 3 adverse events were infections (41.7%), neutropenia (34.1%), and thrombocytopenia (9.4%). Atrial fibrillation occurred in only 1.9% of patients. CONCLUSIONS: With extended follow-up, zanubrutinib yielded long-term benefits and demonstrated a favorable safety profile for patients with TN or RR CLL/SLL. Earlier utilization of zanubrutinib was associated with better outcomes. TRIAL REGISTRATION: Clinical Trials.gov identifiers, NCT03189524, NCT02343120 (retrospectively registered), and NCT03206918 (retrospectively registered).


Assuntos
Leucemia Linfocítica Crônica de Células B , Linfoma de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Piperidinas/efeitos adversos , Pirazóis/efeitos adversos , Pirimidinas/efeitos adversos
18.
Materials (Basel) ; 15(13)2022 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-35806739

RESUMO

Micro Raman spectroscopy is an effective method to quantitatively analyse the internal stress of semiconductor materials and structures. However, the decoupling analysis of the stress components for {100} monocrystalline silicon (c-Si) remains difficult. In the work outlined, physical and simulation experiments were combined to study the influence of the objective lens numerical aperture (NA) on the Raman stress characterization. The physical experiments and simulation experiments show that the spectral results obtained by using lenses with different NAs can accurately obtain the principal stress sum but cannot decouple the components of the in-plane stress. Even if the spectral resolution of the simulated experiment is ideal (The random errors of the polarization directions of less than ±1° and the systematic random errors of less than ±0.02 cm-1). The analysis based on the theoretical model demonstrates that the proportion of the principal stress sum in the Raman shift obtained in an actual experiment exceeded 98.7%, while the proportion of the principal stress difference part was almost negligible. This result made it difficult to identify the variable effects of different stress states from the experimental results. Further simulation experiments in this work verify that when the principal stress sum was identical, the differences in the Raman shifts caused by different stress states were much smaller than the resolution of the existing Raman microscope system, which was hardly possible to identify in the experimental results. It was proven that decoupling analysis of stress components using the large-NA objective lens lacked actual practicability.

19.
Br J Haematol ; 198(1): 62-72, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35383885

RESUMO

This single-arm, multicentre, phase I study is the first study of zanubrutinib, a potent, specific, irreversible Bruton tyrosine kinase (BTK) inhibitor, in Chinese patients with relapsed/refractory B-cell malignancies. The objectives were to evaluate safety and preliminary anti-tumour activity. Forty-four patients received zanubrutinib 320 mg once daily (QD) (n = 10) or 160 mg twice daily (BID) (n = 34) until disease progression or unacceptable toxicity. 29.5% of patients received zanubrutinib for at least two years. The most common adverse event (AE) and the most common grade 3 or higher AE was neutrophil count decreased (54.5% and 25.0% respectively). Two patients (4.5%) discontinued treatment due to AEs and one treatment-emergent AE led to death. All haemorrhagic events were grade 1-2 (except for one non-serious grade 3 purpura). No second primary malignancies, tumour lysis syndrome, or atrial fibrillation/flutter occurred. The overall response rate was 52.3% (complete response rate, 18.2%). Patients with all cancer subtypes benefited from treatment. BTK C481S/R or L528W mutations were found in zanubrutinib-progressive patients. The safety/efficacy profiles of patients treated with 320 mg QD and 160 mg BID were comparable and similar daily area under the curve (AUC) was achieved. Overall, zanubrutinib was well tolerated and either of these two regimens is clinically practical. Registered at ClinicalTrials.gov (NCT03189524, on 16 June 2017, https://clinicaltrials.gov/ct2/show/NCT03189524).


Assuntos
Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases , Tirosina Quinase da Agamaglobulinemia , China , Doença Crônica , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Piperidinas , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis , Pirimidinas
20.
Clin Cancer Res ; 27(23): 6323-6332, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34526366

RESUMO

PURPOSE: Marginal zone lymphoma (MZL) is an uncommon non-Hodgkin lymphoma with malignant cells that exhibit a consistent dependency on B-cell receptor signaling. We evaluated the efficacy and safety of zanubrutinib, a next-generation selective Bruton tyrosine kinase inhibitor, in patients with relapsed/refractory (R/R) MZL. PATIENTS AND METHODS: Patients with R/R MZL were enrolled in the phase II MAGNOLIA (BGB-3111-214) study. The primary endpoint was overall response rate (ORR) as determined by an independent review committee (IRC) based on the Lugano 2014 classification. RESULTS: Sixty-eight patients were enrolled. After a median follow-up of 15.7 months (range, 1.6 to 21.9 months), the IRC-assessed ORR was 68.2% and complete response (CR) was 25.8%. The ORR by investigator assessment was 74.2%, and the CR rate was 25.8%. The median duration of response (DOR) and median progression-free survival (PFS) by independent review was not reached. The IRC-assessed DOR rate at 12 months was 93.0%, and IRC-assessed PFS rate was 82.5% at both 12 and 15 months. Treatment was well tolerated with the majority of adverse events (AE) being grade 1 or 2. The most common AEs were diarrhea (22.1%), contusion (20.6%), and constipation (14.7%). Atrial fibrillation/flutter was reported in 2 patients; 1 patient had grade 3 hypertension. No patient experienced major hemorrhage. In total, 4 patients discontinued treatment due to AEs, none of which were considered treatment-related by the investigators. CONCLUSIONS: Zanubrutinib demonstrated high ORR and CR rate with durable disease control and a favorable safety profile in patients with R/R MZL.


Assuntos
Linfoma de Zona Marginal Tipo Células B , Magnolia , Humanos , Piperidinas , Inibidores de Proteínas Quinases/efeitos adversos , Pirazóis , Pirimidinas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA