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Objective:To evaluate the safety of ensartinib in the treatment of anaplastic lymphoma kinase (ALK) -positive non-small cell lung cancer (NSCLC) in the real-world clinical setting.Methods:Clinical data of 2 221 patients with ALK-positive locally advanced or metastatic NSCLC who received ensartinib treatment (225 mg/d) from December 16, 2020 to December 16, 2021 were collected and analyzed to assess drug adverse reactions in all population including elderly patients (≥ 65 years old) .Results:Among the total 2 221 patients, 511 patients (23.01%) experienced adverse events, including 8 patients (0.36%) who experienced serious adverse events. Adverse events led to dose modification in 67 patients (3.02%) and discontinuation in 18 patients (0.81%). The common adverse events were rash (407/2 221, 18.33%), pruritus (41/2 221, 1.85%), constipation (41/2 221, 1.85%), and facial edema (31/2 221, 1.40%). Thirty-six patients (1.62%) experienced ≥grade 3 adverse events. After symptomatic treatment of 511 patients with adverse reactions, 50 patients (9.78%) were healed, 271 patients (53.03%) were improved, 120 patients (23.48%) were persisted, and 70 patients (13.71%) were unknown due to loss of follow-up or other reasons. Forty-three patients (1.94%) reported 57 unintended adverse reactions. Among the 599 elderly patients, 116 patients (19.37%) experienced adverse events, including 1 patient (0.17%) who experienced serious adverse events. Adverse events led to dose modification in 25 patients (4.17%) and discontinuation in 5 patients (0.83%). The common adverse events of elderly patients were rash (88/599, 14.69%), constipation (14/599, 2.34%), facial edema (12/599, 2.00%), and pruritus (10/599, 1.67%). Twelve patients (2.00%) experienced ≥grade 3 adverse events. Among the 116 elderly patients with adverse reactions following the symptomatic treatment, 11 patients (9.48%) were healed, 58 patients (50.00%) were improved, 28 patients (24.13%) were persisted, and 19 patients (16.39%) were unknown due to loss of follow-up or other reasons. During the treatment, 1 patient (0.05%) experienced grade 2 interstitial lung disease, and no patient died due to adverse events.Conclusion:Ensartinib has a favorable safety profile in the real-world populations, with the most frequent adverse events being rash, mostly mild, and low incidence of ≥grade 3 adverse events. Overall, adverse reactions were tolerable and manageable.
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Objective To establish an efficient method for isolating migrasomes from RAW264.7 macrophages and identifying these isolated migrasomes. Methods Scanning electron microscopy was used to observe the morphological characteristics of migrasomes produced by RAW264.7 cells. A 0.45 μm filter was employed for reverse filtration and elution to isolate the migrasomes. The morphological characteristics of the migrasomes were then observed using transmission electron microscopy. Western blot analysis was performed to determine the expression of characteristic markers of the migrasomes. The RNA carried by the migrasomes was analysed by using LabChip bioanalyzer. Results Scanning electron microscopy revealed that the migrasomes, with membranous structures, were attached to the tip or bifurcation of the retraction fiber formed in the tail of RAW264.7 cells. Transmission electron microscopy showed that the isolated migrasomes had a typical oval vesicle-like structure with wrinkled membrane surfaces. Western blot analysis confirmed the expression of the characteristic markers phosphatidylinositol glycan anchor biosynthesis class K (PIGK), epidermal growth factor domain-specific O-linked N-acetylglucosamine transferase (EOGT) and tetraspanin 4 (TSPAN4) in the migrasomes, while the EV (extracellular vesicle) markers tumor susceptibility gene 101 (TSG101) and Arabidopsis homolog of apoptosis-linked gene 2-interacting protein X (ALIX) were not detected. Furthermore, the isolated migrasomes were found to be rich in small RNA, which were approximately 25-200 nt in length. Conclusion A method for the extraction of well-structured and high quality migrasomes from macrophages is established.
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Vesículas Extracelulares , Microscopia Eletrônica de Transmissão , RNA , MacrófagosRESUMO
Obesity and type 2 diabetes (T2DM) are all the metabolic diseases with high incidence rate. There is a clear correlation between the them. Weight-loss surgery is the important treatment of surgical method for obesity and T2DM.However, the mechanism of T2DM for weight loss surgery is not yet clear.The secretion level of glucagon like peptide-1 (GLP-1) was affected after weight loss surgery. The secretion of GLP-1 can delay gastric emptying, increase satiety, improve insulin resistance (IR) and promote β insulin release, inhibition of glucagon synthesis and secretion, and improvement of pancreatic function β cell function. All of these changes were conducive to glycemic control. Therefore, this paper aims to summarize and describe the relationship between the effect of laparoscopic sleeve gastrectomy (LSG) on blood glucose and GLP-1/dipeptidyl peptidase-4 (DPP-4) pathway in obese T2DM patients.
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Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.
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Objective:To study the effect of culture supernatant of rat bone marrow mesenchymal stem cells (BMSCs) on biological characteristics of RSC96 Schwann cells.Methods: BMSCs of Sprague Dawley rat were cultured and purified in vitro.The BMSCs culture supernatant medium (BMSC-CM) was collected from the third generation of BMSCs.Using MTT method to detect proliferation influence of BMSC-CM on RSC96 cells,and using plate cloning assay to analysis a single cell proliferation effect.The migration analysis of BMSC-CM on RSC96 cells were detected by scratch and TranswellTM chamber assay,Western blot tested Bax and Bcl-2 proteins changes in RSC96 cells.Results: The third generation of BMSCs was long spindle-shaped and vortex-like;the result of Osteogenesis staining was positive;lipid droplets appeared after adipogenesis induction.BMSC-CM inhibited the proliferation and migration of RSC96 cells.Meanwhile,Bcl-2 protein decreased and Bax protein increased in RSC96 cells after BMSC-CM treatment.Conclusion: BMSC-CM can promote apoptosis and inhibit the proliferation and migration of RSC96 cells.
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Phospholipid membrane vesicles from cells play key roles in cell communication, antigen presentation, and transmission of infectious agents.Extracellular vesicles(EVs) carry various proteins, mRNA, and microRNA(miRNA), like a truck to bring different molecular cargoes to remote cells.Furthermore, the encapsulated molecules by EVs can be prevented from being degraded by enzymes in body fluids, making EVs as a natural, novel drug delivery system.In this paper, we review the progress of EVs for biological application and drug delivery vehicles from the classification and composition, which provides a theoretical basis for seeking new drug delivery systems for the treatment of diseases.
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BACKGROUND:It is important to produce and save a large amount of high-activity feeder cel s for the culture of human embryonic stem cel s. OBJECTIVE:To establish the optimal method for isolation and culture of Kunming mouse embryonic fibroblasts, and to evaluate the feasibility of preparing feeder layers for culture of human embryonic stem cel s. METHODS:Embryonic fibroblasts were isolated and cultured by different concentrations of trypsin from Kunming mouse fetuses in vitro. The biological characteristics and growth rule of mouse embryonic fibroblasts were investigated, and then the feeder layers for human embryonic stem cel s culture were produced. The growth of human embryonic stem cel s on the prepared feeder layer was tested. RESULTS AND CONCLUSION:The optimal fetal age for preparing Kunming mouse embryonic fibroblast feeder layer was 13.5 days. Kunming mouse embryonic fibroblasts at different concentrations grew wel with high purity and active proliferation by trypsin digestion method. There was no significant difference in the survival rate of cel s after cryopreservation for 2 weeks, 1 month, 3 months and 6 months. The cel s were proliferative from the second to fourth passage and declined sharply after the fifth passage. Human embryonic stem cel s which grew on Kunming mouse embryonic fibroblasts feeder layers were stil to remain the typical undifferentiated morphology and were strongly positive for alkaline phosphatase and periodic acid-Schiff after long-term subculture. The mouse embryonic fibroblasts can be used as the stable and high-quality feeder cel s for human embryonic stem cel s.