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1.
J Sci Food Agric ; 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33426672

RESUMO

BACKGROUND: Ultrasonic pretreatment is a novel physical method which can be used in the extraction process of okra pectin. Real-time online monitoring technologies were introduced in time and frequency domains when okra was pretreated. Preparation time of dried okra and yield of okra pectin were studied; and physicochemical properties of okra pectin were analyzed at the optimum ultrasonic parameter. RESULTS: Results showed that ultrasonic intensity of sweeping frequency ultrasonic (SFU) pretreatment was stronger than that of fixed frequency ultrasonic (FFU). SFU pretreatment (60±1 kHz) at 30 min had the strong ultrasonic voltage peak of 0.05387 V and signal power peak of -6.62 dBm. The preparation time of dried okra was 160±14.14 min in pretreated group, 44.83% lower than control without SFU pretreatment. The intercellular space got 56.03% higher than control. Water diffusion coefficient increased from 1.41×10-9 to 2.14 ×10-9 m2 ·s-1 . Mono basic quadratic equations were developed for the monitored ultrasonic intensity and pectin yield. Compared to control, extraction yield (16.70%), pectin content (0.564 mg·mg-1 ), solubility (0.8187 g·g-1 ) and gel strength (30.91 g) were improved in the pretreated group. The viscosity decreased, values of G' and G" crossed at 63 rad·s-1 revealed the viscoelastic behavior and the beginning of the viscous behavior with a sol state. CONCLUSION: Decrement of dried preparation time and increment of yield were achieved by ultrasonic pretreatment during the extraction process of okra pectin, and relationship of ultrasonic intensity monitored by real-time online technologies and the yield was given. This article is protected by copyright. All rights reserved.

2.
J Orthop Surg Res ; 16(1): 12, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407705

RESUMO

BACKGROUND: The principles of choosing an appropriate implant height remain controversial in total cervical disc replacement (TDR). By performing an in vitro biomechanical study and exploring the biomechanical impact of implant height on facet joint and motion function, the study aimed to offer valid proposals regarding implant height selection during TDR. METHODS: A total of 6 fresh-frozen male cadaveric cervical spines (C2-C7) with 5 mm intervertebral disc height at C5/6 level were enrolled in the study. Specimens with the intact condition and with different height artificial discs were tested. Facet joint pressures and range of motion under each condition were recorded using a specialized machine. RESULTS: The artificial disc heights that were involved in this study were 5 mm, 6 mm, and 7 mm. The range of motion decreased along with the increment of implant height, while facet joint pressure showed an opposite trend. Specimens with a 5 mm implant height could provide a similar range of motion (11.8° vs. 12.2° in flexion-extension, 8.7° vs. 9.0° in rotation, 7.9° vs. 8.2° in lateral bending) and facet joint pressure (27.8 psi vs. 25.2 psi in flexion, 59.7 psi vs. 58.9 psi in extension, 24.0 psi vs. 22.7 psi in rotation, 32.0 psi vs. 28.8 psi in lateral bending) compared with intact specimens. Facet joint pressure of specimens with 6 mm implant height (≥ 1 mm in height) increased during flexion at the C5-6 segment (30.4 psi vs. 25.2 psi, P = 0.076). However, specimens with 7 mm implant height (≥ 2 mm in height) showed a significant reduction in motion (9.5° vs. 12.2° in flexion-extension, P < 0.001) and increment of facet joint pressure at C5-6 segment (44.6 psi vs. 25.2 psi in flexion, 90.3 psi vs. 58.9 psi in extension, P < 0.0001) and adjacent segments. CONCLUSIONS: This study suggested that an appropriate artificial disc height can achieve near-normal biomechanical properties and is recommended. We should be very cautious when using artificial discs ≥ 1 mm in height compared to normal. However, implants ≥ 2 mm in height compared to normal significantly increased the facet joint pressure and decreased the range of motion; therefore, it should not be used in clinical practice.

3.
PLoS Biol ; 19(1): e3001061, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33444322

RESUMO

Mosaic animals have provided the platform for many fundamental discoveries in developmental biology, cell biology, and other fields. Techniques to produce mosaic animals by mitotic recombination have been extensively developed in Drosophila melanogaster but are less common for other laboratory organisms. Here, we report mosaic analysis by gRNA-induced crossing-over (MAGIC), a new technique for generating mosaic animals based on DNA double-strand breaks produced by CRISPR/Cas9. MAGIC efficiently produces mosaic clones in both somatic tissues and the germline of Drosophila. Further, by developing a MAGIC toolkit for 1 chromosome arm, we demonstrate the method's application in characterizing gene function in neural development and in generating fluorescently marked clones in wild-derived Drosophila strains. Eliminating the need to introduce recombinase-recognition sites in the genome, this simple and versatile system simplifies mosaic analysis in Drosophila and can in principle be applied in any organism that is compatible with CRISPR/Cas9.

4.
J Orthop Surg Res ; 16(1): 58, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446228

RESUMO

BACKGROUND: Fractures of the base of the coracoid process are relatively rare, but an increasing number of studies have reported using screws to fix coracoid process base fractures. This study was performed to simulate the surgical procedure and obtain the ideal diameter, length, insertion point and angle of the screw from a 3-D axial perspective in Chinese patients. METHODS: We randomly collected right scapula computed tomography (CT) scans from 100 adults. DICOM-formatted CT scan images were imported into Mimics software. A 3D digital model of the right scapula was established. Two virtual cylinders representing two screws were placed from the top of the coracoid process to the neck of the scapula and across the base of the coracoid process to fix the base of the coracoid process. The largest secure diameters and lengths of the virtual screws were measured. The positions of the insertion points and the directions of the screws were also examined. RESULTS: The screw insertion safe zone can exhibit an irregular fusiform shape according to the reconstructed scapula model. The mean maximum diameters of the medial and lateral screws were 7.08 ± 1.19 mm and 7.34 ± 1.11 mm, respectively. The mean maximum lengths of the medial and lateral screws were 43.11 ± 6.31 mm and 48.16 ± 6.94 mm, respectively. A screw insertion corridor with a diameter of at least 4.5 mm was found in all patients. We found sex-dependent differences in the mean maximum diameters and maximum lengths of the two screws. The positions of the two insertion points were statistically different across sexes. CONCLUSIONS: The study provides a valuable guideline for determining the largest secure corridor for two screws in fixing a fracture at the base of the coracoid process. For ideal screw placement, we suggest individualised preoperative 3D reconstruction simulations. Further biomechanical studies are needed to verify the function of the screws.

5.
Anal Chem ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33410662

RESUMO

Selective and sensitive determination of trace kanamycin in complex food samples is of great importance for food safety because of its high toxicity. Here, we report a sensitive and autofluorescence-free persistent luminescence (PL) aptasensor for selective, sensitive, and autofluorescence-free determination of kanamycin in food samples. The aptamer for kanamycin was first conjugated onto the surface of magnetic nanoparticles Fe3O4 to serve as the recognition unit as well as the separation element, while the PL nanoparticles ZnGa2O4:Cr (PLNPs) were functionalized with the aptamer complementary DNA (cDNA) as the PL signal. The PL aptasensor consisted of the aptamer-conjugated MNPs (MNPs-apt) and cDNA-functionalized PLNPs (PLNPs-cDNA) and combined the merits of the long-lasting luminescence of PLNPs, the magnetic separation ability of MNPs as well as the selectivity of the aptamer, offering a promising approach for autofluorescence-free determination of kanamycin in food samples. The proposed aptasensor showed excellent linearity in the range from 1 pg mL-1 to 5 ng mL-1 with a limit of detection of 0.32 pg mL-1. The precision for 11 replicate determinations of 100 pg mL-1 kanamycin was 3.1% (relative standard deviation). The developed aptasensor was applied for the determination of kanamycin in milk and honey samples with the recoveries of 95.4-106.3%. The proposed aptasensor is easily extendable to other analytes by simply replacing the aptamer, showing great potential as a universal aptasensor platform for selective, sensitive, and autofluorescence-free detection of hazardous analytes in food samples.

6.
AIDS Res Hum Retroviruses ; 37(1): 62-69, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32972239

RESUMO

Investigation of disease and intervention in populations of men having sex with men (MSM) has garnered attention globally, a primary reason being the rapid increase in the prevalence of human immunodeficiency virus (HIV)-1 among MSM. The purpose of this study was to understand the current HIV-1 molecular characteristics and characterize HIV-1 transmission networks in the MSM population. Nine hundred and fourteen newly diagnosed HIV-positive MSM were included in this study. The HIV-1 pol gene region was amplified and sequenced. A maximum likelihood phylogenetic tree was constructed, and transmission clusters were identified using 1.5% distance and 0.9 bootstrap values. In total, 767 sequences were successfully obtained, with CRF01_AE being the major genotype (43.3%, 332/767), followed by CRF07_BC (31.3%, 240/767), CRF67_01B (7.2%, 55/767), and URF (6.4%, 49/767). The transmitted HIV drug resistance rate was 4.0% (31/767), and the most common mutations were E138G (n = 4) and G190A (n = 4). A total of 182 (23.7%) sequences were included in the HIV-1 transmission networks, forming 79 clusters. Four clusters were identified as fast-growing, and the proportion of young MSM was higher than that of non-MSM (51.6% vs. 31.8%). The genetic diversity of HIV-1 in Jiangsu was complex, and cross-region transmission might exist for CRF67_01B. Transmission among young MSM within networks was greater than the other age groups; thus, they could be essential in the control of the HIV epidemic in Jiangsu. This study was approved by the ethical review board of the National Center for AIDS/STD Control and Prevention (Project No. X140617334).

7.
Eur J Med Chem ; 210: 113068, 2021 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-33310292

RESUMO

Glioblastoma multiform (GBM) is the highly aggressive brain tumor with poor prognosis. Glioma stem cells (GSCs), small population of cancer cells that exist in GBM tissues, resistant to chemotherapy and radiotherapy and usually driving GBM recurrence, have been developed as effective therapeutic target. Steroidal saponins are one of important resources for anti-tumor agent and may be benefited to selectively clear GSCs. In this report, total of 97 natural steroidal saponins were investigated the relationship among structures/cytotoxicity/selectivity against GSCs, glioma cell lines and human untransformed cells, and revealed that tribulosaponin A was the most potent compound. Further investigation suggested that tribulosaponin A up-regulated the expression of NCF1 and NOX1 to accumulate ROS for triggering apoptosis in GSCs, but not in untransformed cells, and it was further supported by the assay that N-acetyl-l-cysteine (NAC) clearing ROS delayed GSCs apoptosis. Besides, tribulosaponin A damaged GSCs recapturing tumor spheres formation.

10.
Cell Death Dis ; 11(11): 1024, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-33262329

RESUMO

Fulminant hepatic failure (FHF) is a clinical syndrome characterized by a sudden and severe impairment in liver function. However, the precise mechanism of immune dysregulation that is significant to FHF pathogenesis remains unclear. Enhancer of zeste homolog 2 (EZH2) has been implicated in inflammation as a regulator of immune cell function. In this study, we investigated the role of EZH2 in an animal model of human FHF induced by Propionibacterium acnes (P. acnes) and lipopolysaccharide (LPS). We demonstrated that EZH2 depletion in dendritic cells (DCs) and pharmacological inhibition of EZH2 using GSK126 both significantly ameliorated liver injury and improved the survival rates of mice with P. acnes plus LPS-induced FHF, which could be attributed to the decreased infiltration and activation of CD4+ T cells in the liver, inhibition of T helper 1 cells and induction of regulatory T cells. The expression of EZH2 in DCs was increased after P. acnes administration, and EZH2 deficiency in DCs suppressed DC maturation and prevented DCs from efficiently stimulating CD4+ T-cell proliferation. Further mechanistic analyses indicated that EZH2 deficiency directly increased the expression of the transcription factor RUNX1 and thereby suppressed the immune functions of DCs. The functional dependence of EZH2 on RUNX1 was further illustrated in DC-specific Ezh2-deficient mice. Taken together, our findings establish that EZH2 exhibits anti-inflammatory effects through inhibition of RUNX1 to regulate DC functions and that inhibition of EZH2 alleviates P. acnes plus LPS-induced FHF, probably by inhibiting DC-induced adaptive immune responses. These results highlight the effect of EZH2 on DCs, serving as a guide for the development of a promising immunotherapeutic strategy for FHF.

11.
Am J Perinatol ; 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33285607

RESUMO

OBJECTIVE: Despite known benefits, the timing of and method used for umbilical cord clamping (UCC) in neonates remain controversial in China, as well as internationally. The objective of this study was to assess knowledge, attitudes, and practice of UCC amongst health care providers in China, as recommended by medical professional organizations. STUDY DESIGN: A web-based questionnaire on cord clamping practices was administered to midwives, obstetricians, and neonatologists in 126 hospitals from 16 provinces. The provinces were selected from seven different regions of China. RESULTS: A total of 5,005 (60.5% of eligible respondents) health care providers returned completed questionnaires. The awareness rates for immediate cord clamping (ICC) and delayed cord clamping (DCC) were over 85%, but the implementation rate for DCC was relatively low (ICC 58.3% vs. DCC 41.6%). Most neonates were placed below the introitus (92.8%) during cord clamping and this correlated with the route of delivery. The choice of UCC was impelled by different factors. Benefits for neonates influenced the choice of ICC (50%) and promoting a larger blood volume to stabilize systemic circulation influenced the choice of DCC (92.3%). Majority (91.5%) of respondents acquiesced that it was necessary to develop national clinical guidelines for UCC. CONCLUSION: The majority of obstetricians, neonatologists, and midwives who participated in this study had a positive perception of DCC. However, this did not translate to daily practice. The practice of UCC is variable and there are no standard guidelines. KEY POINTS: · The first large-scale epidemiological investigation of umbilical cord ligation is in China.. · The survey included three commonly used umbilical cord clamping methods.. · The respondents included neonatologists..

12.
J Hazard Mater ; 405: 124613, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33301973

RESUMO

This paper presents a detailed chemical and toxicological characterization of the diesel particulate matter (PM) emitted from diesel vehicles running on a chassis dynamometer under different driving conditions. Chemical analyses were performed to characterize the contents of organic carbon (OC), elemental carbon (EC), and 31 polycyclic aromatic hydrocarbons (PAHs) in the collected PM samples. The OC-EC analysis results revealed that PM emissions from diesel vehicles in this study were dominated by OC and that the emission of vehicles equipped with diesel particulate filters had high OC/EC ratios. The PAH analysis results revealed that 4- and 5-ring PAHs were the dominant PAHs in the OC fraction of the PM samples. Particle toxicity was evaluated through three toxicological markers in human A549 cells, namely (1) acellular 2,7-dichlorofluorescein (DCFH) for oxidative potential, (2) interleukin-6 (IL-6) for inflammation, and (3) glutathione (GSH) for antioxidation after exposure. Statistical analyses revealed that vehicle sizes have statistically significant effects on the concentrations of the markers. Correlation analysis between PAHs and toxicological markers revealed that significant correlations existed between specific compounds and markers. Our results can be used as a reference by policy makers to formulate emission control strategies and as a dataset for other modeling studies.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33161716

RESUMO

Steam generation and photocatalytic degradation of organic pollutants based on solar light are regarded as two important strategies for addressing the water scarcity issues. The water evaporation efficiency was greatly inhibited by the high cost, low stability, and low efficiencies of solar light absorption and photothermal conversion of photothermal materials. Moreover, volatile organic compounds (VOCs) are easily volatilized and enriched in as-distilled water during the photothermal process. Inspired by the structure of biomass materials in nature, a bifunctional solar light-driven steam generation and VOC removal microreactor was explored by coating commercial TiO2 (P25) powders on a carbonized biomass waste Flammulina. With the 3D aligned porous carbon architectures, this microreactor exhibited both a high water evaporation rate (37.0 kg m-2 h-1) and a high energy conversion efficiency (91.2%) under simulated sunlight irradiation (light intensity = 25.5 kW m-2). A high VOC removal rate (80.9% in 40 min) was also achieved during the steam generation process via choosing phenol as the probe pollutant molecules. The nature-inspired designing concept and bifunctional microreactor in this study may open up a new strategy for producing clean distilled water from seawater with an efficient removal of VOCs.

14.
Int J Med Sci ; 17(18): 2895-2904, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33173410

RESUMO

Cancer incidence is rapidly growing, and cancer is the leading cause of death worldwide in the 21st century. Hepatocyte nuclear factor 1B (HNF1B) is a transcription factor that involves the growth and development of multiple organs. The aim of this study was to explore the significance of HNF1B in human cancer by an integrative analysis of online databases. The UALCAN database, cBio cancer genomics portal, Cancer Regulome tools, Kaplan-Meier plotter and Tumor IMmune Estimation Resource (TIMER) website were used to perform the corresponding analysis. The results showed that HNF1B is dysregulated in various cancers and associated with the differential overall survival of cancer patients. HNF1B showed many mutation forms and high mutation levels in different cancer types. In addition, we found that HNF1B interacted with different genes in multiple aspects. Moreover, HNF1B expression is associated with many immune cell infiltration levels and influences the prognostic prediction of immune cells in some kinds of cancers. In conclusion, HNF1B plays a significant role in cancer and may be a potential target for cancer immunotherapy.

15.
Postgrad Med J ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33184138

RESUMO

BACKGROUND: Early mobilisation reduces postoperative complications such as pneumonia, deep vein thrombosis and hospital length of stay. Many authors have reported poor compliance with early mobilisation within Enhanced Recovery After Surgery initiatives. OBJECTIVES: The primary objective was to increase postoperative day (POD) 2 mobilisation rate from 23% to 75% in patients undergoing elective major hepatopancreatobiliary (HPB) surgery within 6 months. METHODS: We report a multidisciplinary team clinical practice improvement project (CPIP) to improve postoperative mobilisation of patients undergoing elective major HPB surgery. We identified the common barriers to mobilisation and analysed using the fishbone or cause-and-effect diagram and Pareto chart. A series of Plan-Do-Study-Act cycles followed this. We tracked the rate of early mobilisation and mean distance walked. In the post hoc analysis, we examined the potential cost savings based on reduced hospital length of stay. RESULTS: Mobilisation rate on POD 2 following elective major HPB surgery improved from 23% to 78.9%, and this sustained at 6 months after the CPIP. Wound pain was the most common reason for failure to ambulate on POD 2. Hospital length of stay reduced from a median of 8 days to 6 days with an estimated cost saving of S$2228 per hospital stay. CONCLUSION: Multidisciplinary quality improvement intervention effort resulted in an improved POD 2 mobilisation rate for patients who underwent elective major HPB surgery. This observed outcome was sustained at 6 months after completion of the CPIP with potential cost savings.

16.
JMIR Mhealth Uhealth ; 8(11): e15978, 2020 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-33237036

RESUMO

BACKGROUND: Mobile health (mHealth) technology is an increasingly recognized and effective method for disease management and has the potential to intervene in pulmonary function, exacerbation risk, and psychological status of patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE: This study aimed to investigate the feasibility of an mHealth-based COPD management system designed for Chinese remote areas with many potential COPD patients but limited medical resources. METHODS: The system was implemented based on a tailored closed-loop care pathway that breaks the heavy management tasks into detailed pieces to be quantified and executed by computers. Low-cost COPD evaluation and questionnaire-based psychological intervention are the 2 main characteristics of the pathway. A 6-month prospective observational study at the community level was performed to evaluate the effect of the system. Primary outcomes included changes in peak expiratory flow values, quality of life measured using the COPD assessment test scale, and psychological condition. Acute exacerbations, compliance, and adverse events were also measured during the study. Compliance was defined as the ratio of the actual frequency of self-monitoring records to the prescribed number. RESULTS: A total of 56 patients was enrolled; 39 patients completed the 6-month study. There was no significant difference in the mean peak expiratory flow value before and after the 6-month period (366.1, SD 106.7 versus 313.1, SD 116.6; P=.11). Psychological condition significantly improved after 6 months, especially for depression, as measured using the Patient Health Questionnaire-9 scale (median 6.0, IQR 3.0-9.0 versus median 4.0, IQR 0.0-6.0; P=.001). The COPD assessment test score after 6 months of intervention was also lower than that at the baseline, and the difference was significant (median 4.0, IQR 1.0-6.0 versus median 3.0, IQR 0.0-6.0; P=.003). The median overall compliance was 91.1% (IQR 67%-100%). In terms of acute exacerbation, 110 exacerbations were detected and confirmed by health care providers (per 6 months, median 2.0, IQR 1.0-5.0). Moreover, 72 adverse events occurred during the study, including 1 death, 19 hospitalizations, and 52 clinic visits due to persistent respiratory symptoms. CONCLUSIONS: We designed and validated a feasible mHealth-based method to manage COPD in remote Chinese areas with limited medical resources. The proposed closed-loop care pathway was effective at the community level. Proper education and frequent communication with health care providers may encourage patients' acceptance and use of smartphones to support COPD self-management. In addition, WeChat might play an important role in improving patient compliance and psychological distress. Further research might explore the effect of such systems on a larger scale and at a higher evidence level.

17.
Cell Metab ; 32(5): 751-766.e11, 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33147485

RESUMO

The mitochondrial GTP (mtGTP)-dependent phosphoenolpyruvate (PEP) cycle couples mitochondrial PEPCK (PCK2) to pyruvate kinase (PK) in the liver and pancreatic islets to regulate glucose homeostasis. Here, small molecule PK activators accelerated the PEP cycle to improve islet function, as well as metabolic homeostasis, in preclinical rodent models of diabetes. In contrast, treatment with a PK activator did not improve insulin secretion in pck2-/- mice. Unlike other clinical secretagogues, PK activation enhanced insulin secretion but also had higher insulin content and markers of differentiation. In addition to improving insulin secretion, acute PK activation short-circuited gluconeogenesis to reduce endogenous glucose production while accelerating red blood cell glucose turnover. Four-week delivery of a PK activator in vivo remodeled PK phosphorylation, reduced liver fat, and improved hepatic and peripheral insulin sensitivity in HFD-fed rats. These data provide a preclinical rationale for PK activation to accelerate the PEP cycle to improve metabolic homeostasis and insulin sensitivity.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33205405

RESUMO

Transcatheter aortic valve replacement (TAVR) induced pathological damage in cardiac conduction system leads to symptomatic bradycardia and electric dyssynchrony such as left bundle branch block (LBBB) is associated with an increased risk for heart failure. Left bundle branch pacing (LBBP) has emerged as an alternative method for delivering physiological pacing to achieve electrical synchrony of the left ventricle. We report a case of heart failure patient with new onset LBBB (NO-LBBB) induced by TAVR, LBBP corrected the NO-LBBB and reversed the heart function with stable capture and correction threshold.

20.
Medicine (Baltimore) ; 99(44): e22886, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33126339

RESUMO

BACKGROUND: Trastuzumab emtansine (T-DM1) is an antibody-drug conjugate that retains the antitumor effects of trastuzumab while also delivering the cytotoxic antimicrotubule agent, DM1, directly to tumor cells that overexpress human epidermal growth factor receptor 2. The pharmacokinetic (PK) profile of T-DM1 has been well characterized in Western, Asian, and Japanese patients; this single-center, phase I study (NCT03153163) examined the PK of T-DM1 and safety specifically in Chinese patients. METHODS: Patients with locally advanced or metastatic breast cancer, previously treated with trastuzumab and a taxane, received open-label T-DM1 at 3.6 mg/kg every 3 weeks. Serum T-DM1 and total trastuzumab, and plasma DM1 were evaluated, and PK parameters were calculated using standard noncompartmental approaches. Adverse events (AEs) were assessed, and immunogenicity was evaluated by measuring antidrug antibodies to T-DM1. RESULTS: Among 11 Chinese patients, mean (±standard deviation) PK parameters (maximum serum concentration, 77.6 ±â€Š17.4 µg/mL; clearance 11.0 ±â€Š2.6 mL/d/kg; terminal half-life 3.8 ±â€Š1.0 days) were similar to those previously reported in Western and Japanese patients. One patient transiently developed antidrug antibodies, which did not appear to influence safety or PK. T-DM1 was generally well tolerated. Grade 3-4 AEs occurred in 7 patients (63.6%) and serious AEs occurred in 4 patients (36.4%). Platelet count decrease was the most common all-grade AE (10/11; 90.9%), grade 3-4 AE (5/11; 45.5%), and serious AE (3/11; 27.3%), but did not appear to be associated with any clinically significant bleeding events. CONCLUSIONS: T-DM1 PK in Chinese patients was consistent with those in global and Asian populations, supporting its use in patients with advanced human epidermal growth factor receptor 2-positive breast cancer following progression on trastuzumab and a taxane. The safety profile of T-DM1 was consistent with prior experience.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Receptor ErbB-2/análise , Trastuzumab , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/farmacocinética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , China , Monitoramento de Medicamentos/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos , Trastuzumab/farmacocinética , Resultado do Tratamento
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